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Red complex bacteria (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) have high virulence in periodontal disease. In the present study, we aimed to elucidate the detailed symbiotic relationships between the red complex and other oral bacteria in older Japanese individuals. Polymerase chain reaction was performed using dental plaque from 116 subjects and specific primers for ten periodontal pathogens. The detection rate of Prevotella intermedia and Capnocytophaga sputigena was significantly higher in P. gingivalis-positive subjects than in P. gingivalis-negative subjects (p < 0.05). The detection rate of Campylobacter rectus, Prevotella nigrescens, Capnocytophaga ochracea, and Eikenella corrodens was significantly higher in T. forsythia-positive subjects than in T. forsythia-negative subjects (p < 0.01). In a comprehensive analysis of oral microbiomes, three red complex species-positive subjects had significantly higher α-diversity than only P. gingivalis-positive subjects (p < 0.05) and had significantly lower β-diversity than only T. forsythia-positive subjects (p < 0.01). In the taxonomy analysis, Porphyromonas was significantly higher in three red complex species-positive subjects than in only P. gingivalis-positive and only T. forsythia-positive subjects (p < 0.01). These results suggest that each red complex species forms a unique oral microbiome and individuals positive for all red complex bacteria may harbor oral bacteria that confer a significant advantage in developing periodontal disease. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine whether the severity of acute Kawasaki disease (KD) can be predicted based on whether a patient remains febrile or becomes afebrile immediately after the completion of initial immunoglobulin treatment (IVIG). Methods: This retrospective cohort study at a single institution involved 306 patients with KD. They were categorized into four groups according to their fever status at two specific time points (end of the initial IVIG treatment and 24–36 h later): Group F-F, patients who remained febrile at both time points; Group F-AF, patients who were febrile at the end of the initial IVIG treatment but became afebrile 24–36 h later; Group AF-F, patients who were afebrile at the end of the initial IVIG treatment but became febrile 24–36 h later; and Group AF-AF, patients who remained afebrile at both time points. The clinical characteristics of the groups were compared. Results: Group F-F (n = 38) showed a significantly higher incidence of CAAs compared to Group AF-F (n = 37), 55.3% vs. 0.0% (p < 0.0001), although both groups were classified as resistant to the initial IVIG. Conclusions: In Japanese patients with acute KD, the presence or absence of fever at the completion of initial IVIG treatment may serve as an early predictor of the occurrence of CAAs. An earlier secondary treatment may be warranted for patients who are in a febrile state immediately after the completion of the initial IVIG treatment. Future research should include a prospective cohort study with a larger number of KD cases across multiple institutions to analyze the effects of other contributing factors related to CAL formation. [ABSTRACT FROM AUTHOR]

This paper explores the phenomenon of lapsing among young Japanese Catholics, highlighting how both local and translocal experiences of Roman Catholicism shape the ebbs and flows of faith for our interlocutors. While global Catholic events such as World Youth Day can reignite faith by fostering a sense of belonging to a larger, global Church, the contrast with the small and socially isolated Catholic community in Japan often precipitates lapsing. This study examines the influence of the New Evangelisation, which promotes active belief and translocal unity, and argues that this movement can both strengthen global Catholic identity and exacerbate feelings of alienation in local, non-Catholic societies. Ultimately, we stress, in the context of Roman Catholicism, that lapsing should not be seen as simply a rupture in faith but as part of a continuous, if turbulent, Catholic identity, mediated by translocal flows of belief and institutional authority. [ABSTRACT FROM AUTHOR]

Background: Sepiapterin is a natural precursor of tetrahydrobiopterin (BH4), a key cofactor for phenylalanine hydroxylase. It is being developed for the treatment of patients with phenylketonuria. In this study, the ethnic differences in pharmacokinetics and safety of sepiapterin in Japanese and non-Japanese participants and food effects were evaluated. Methods: Healthy participants (n = 60) received a single oral dose of sepiapterin at either 20, 40, or 60 mg/kg with a low-fat diet. The Japanese participants received two doses at 40 mg/kg, either under fasted conditions or with a low-fat diet with a 3-day washout period in between. Results: Sepiapterin was well tolerated in all participants, with no serious adverse events. Sepiapterin was quickly absorbed (Tmax 1.4–4.5 h) and rapidly and extensively converted to BH4 (Tmax ~4 h). Exposures to sepiapterin were <1% of BH4. BH4 exposures were essentially dose-independent between 20 and 60 mg/kg. A low-fat diet increased BH4 exposures in Japanese participants by 1.7-fold compared with fasted conditions. Conclusions: BH4 exposures (Cmax and AUC0–last) in Japanese participants were 10–30% higher than in non-Japanese participants, which is deemed not clinically relevant; no dose adjustment is warranted. The slightly higher BH4 exposures in Japanese participants are likely due to the higher frequency of ABCG2 c.421C>A mutation in the Japanese population. [ABSTRACT FROM AUTHOR]

Rotavirus vaccines carry a small risk of intussusception mainly 1–7 days after vaccination in the United States of America, Europe, Australia, and Latin America where the background rate of intussusception is relatively low. Such risks are undetectable in Africa and India where the background rate is the lowest. Because few studies were carried out in high-background-rate countries such as Japan, we examined how intussusception occurred in infants living in Akita prefecture, Japan, while the vaccines were sold in the private market. Between 2011 and 2018, an estimated 21,677 infants (46%) were vaccinated and 54% were not. Through a retrospective survey of medical records in 18 hospitals in the prefecture, we identified 58 infants, 28 of whom were vaccinated and 30 of whom were unvaccinated, as having intussusception that met level 1 of the Brighton criteria. Thus, the intussusception rate was 123 per 100,000 infant-years (95% confidence interval [CI]: 94–160). Despite the high rate, none developed intussusception 1–7 days after the first dose of either the monovalent human rotavirus vaccine (GSK) or the pentavalent human–bovine reassortant vaccine (MSD). The incidence rate ratio of vaccinated to unvaccinated infants between 42 and 245 days of life was estimated at 0.96 (95%CI: 0.43–2.1; p = 0.92). Given that over 95% of infants received the first dose before 15 weeks of age, the risk of intussusception associated with the rotavirus vaccines in high-incidence-rate countries can be reduced to a minimum by adhering to the recommended schedule at 2, 3, and 4 months of age. [ABSTRACT FROM AUTHOR]

Reducing salt intake is a vital public health measure for combating noncommunicable diseases and mitigating rising social security expenditures in Japan. We developed a system dynamics model to analyze the potential health and cost effects of salt reduction interventions among the Japanese population aged 40 years and above from 2012 to 2040. The simulation findings derived from the model indicate that, in the base run, the disability-adjusted life years (DALYs) for cardiovascular disease (CVD) and chronic kidney disease (CKD) are projected to be approximately 55 and 9.5 per 100,000 people, respectively, contributing approximately 40 trillion yen in social security expenditures by 2040. The model predicts that implementing mandatory reformulation could decrease DALYs for CVD and CKD by 5.7% and 6.2%, respectively, resulting in an approximately 6.7% reduction in social security expenditure. Additionally, voluntary reformulation is estimated to reduce the DALYs for CVD and CKD by 4.7% and 5.2%, leading to a 5.6% decrease in social security expenditure. Finally, accelerating the adoption of a low-salt diet is expected to lower the DALYs for CVD by 2.8% and CKD by 3.2%, thereby reducing social security expenditures by 3.4%. Thus, product reformulation initiatives have a greater impact on health and economic outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is one of the most common cancers in men worldwide, and its causes are influenced by both genetic and lifestyle factors. One lifestyle factor that has shown mixed evidence is alcohol consumption. While some studies suggest that heavy drinking increases prostate cancer risk, others show little to no connection. This research aims to clarify the relationship between alcohol consumption and prostate cancer by reviewing and analyzing global studies. By exploring how different types of alcohol and drinking patterns may influence cancer risk, the goal is to provide more precise guidance for healthcare providers and patients. These findings can help inform public health recommendations and future research on cancer prevention strategies, especially for higher-risk populations. Background/Objectives: Prostate cancer (PCa) is a significant global health issue. The relationship between alcohol consumption and PCa risk has been the subject of extensive research, yet findings remain inconsistent. This review aims to clarify the association between alcohol intake and PCa risk, its aggressiveness, and the potential metabolic pathways involved in PCa onset. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed and MEDLINE, focusing on epidemiological studies, meta-analyses, cohort studies, and case–control studies. Studies evaluating alcohol consumption, prostate-specific antigen (PSA) levels, and PCa risk were included. The review also explored the roles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in alcohol metabolism. Results: The analysis reveals a complex relationship between alcohol consumption and PCa. Heavy alcohol intake is associated with an increased risk of PCa, particularly more aggressive forms, and higher mortality rates. However, studies also show weak or no association between moderate alcohol consumption and PCa. The variability in findings may be attributed to differences in alcohol types, regional factors, and study methodologies. Conclusions: The link between alcohol consumption and PCa risk is multifaceted. While heavy drinking appears to increase the risk of aggressive PCa, the overall relationship remains unclear. Further research is needed to better understand these associations and inform public health recommendations and cancer prevention strategies. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the impact of age and knee osteoarthritis (OA) on the coronal plane alignment of the lower extremity in Japanese males and females, utilizing the Coronal Plane Alignment of the Knee (CPAK) classification system. Methods: A cross-sectional analysis was conducted with 150 male and 150 female patients. Participants were divided into three groups according to age and OA progression. The mechanical lateral distal femoral angle (mLDFA) and mechanical medial proximal tibial angle (mMPTA) were measured using standard digital long-leg radiographs. Arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated, and the CPAK classification was performed to verify the distribution among the three groups. Results: The results showed increased varus alignment of the mean mLDFA correlated with OA in both genders and with aging in males. The mean mMPTA did not change in males but shifted toward varus in females with both aging and OA. Both genders demonstrated a constitutional varus alignment with the progression of osteoarthritis (males: 1.3 ± 2.4° to −3.5 ± 3.7°, p < 0.001; females: −1.2 ± 3.2° to −3.6 ± 2.9°, p < 0.001). However, this trend with aging was observed only in females (0.0 ± 2.5° to −1.2 ± 3.2°, p = 0.018). JLO maintained its apex distal position with aging and OA progression in all subjects. The study further revealed a notable transition from CPAK Type II to Type I with OA progression in both genders, additionally influenced by aging in females. Conclusions: Aging affects coronal alignment and CPAK classification differently across genders. With OA progression, there was a shift toward smaller aHKA, while JLO remained unchanged. Compared to other races, young Japanese people exhibit similar CPAK distributions, but distinct differences appear in OA-affected individuals, highlighting potential racial variations in CPAK classifications. [ABSTRACT FROM AUTHOR]

Background: Toothbrushing is important for maintaining oral health and preventing periodontal disease. However, the association between toothbrushing and systemic diseases remains unclear in adolescence. In this study, the association between dental self-care (frequency and duration of toothbrushing) and systemic diseases/disorders in adolescents was examined. Methods: We conducted a retrospective review of mandatory medical questionnaires administered during legally mandated freshman medical checkups between 2017 and 2019 at the University of Tokyo, Japan. Out of 9376 total responses, 9098 cases involving individuals under the age of 20 were included in the analysis. Respondents were classified into three groups based on their daily toothbrushing frequency: "1 time or less", "twice", and "3 times or more". For the duration of each toothbrushing session, they were classified into three groups: "1 min or less", "2–3 min", and "4 min or more". A statistical analysis was performed by Pearson's χ2 test and multinomial logistic regression analysis. Results: Regarding frequency of daily toothbrushing: The χ2 test showed no significant relationship between frequency of toothbrushing and 17 systemic diseases/disorders. A multivariate analysis found that gingival bleeding and sex were independent factors. The risk of gingival bleeding decreased dramatically with increased frequency of toothbrushing (odds ratio (OR): 0.428; 95% confidence interval (CI), 0.366–0.501; p < 0.001). Regarding the amount of time spent on toothbrushing: The χ2 test showed atopic dermatitis and arrhythmia were significantly associated with the duration of toothbrushing (p = 0.032 and p = 0.016, respectively). In the multivariate analysis, atopic dermatitis, gingival bleeding, and sex were independent factors regarding the duration of toothbrushing; longer brushing time was associated with a lower risk of atopic dermatitis (OR: 0.731, 95% CI: 0.578–0.924, p = 0.009) and a lower risk of gingival bleeding (OR: 0.643, 95% CI: 0.567–0.729, p < 0.001). Conclusions: Dental self-care was most strongly associated with gingival bleeding, while the risk of atopic dermatitis was found to increase with shorter toothbrushing times. The results suggest that dental self-care during adolescence is important not only for oral health but also for general health. [ABSTRACT FROM AUTHOR]

(1) Background: The number of patients with cancer undergoing cancer genome profiling is increasing; however, it remains unclear how accurately they understand the details of the tests and treatments. This study aimed to clarify the awareness of cancer genome profiling tests among patients with cancer who visited cancer genome medical clinics. (2) Methods: A questionnaire survey was conducted on awareness, anxiety, sources of information, and psychological states concerning cancer genome profiling tests. (3) Results: In total, 265 patients with cancer (117 men, 142 women, 6 no response, average age of 58.29 ± 11.9 years) were included in the study, of which 218 (82.3%) were aware of the term "cancer genomic medicine" and 90 (34.0%) were aware of its details. Thus, only a few respondents understood that cancer genome profiling tests facilitate the discovery of secondary findings and of genes associated with hereditary tumors. Regarding their psychological state when visiting the cancer genome clinic, the respondents were anxious about standard treatment and prognosis limits. (4) Conclusions: From the viewpoint of advance care planning, we suggest that medical professionals build a support system that links palliative care and cancer treatment and coordinates genetic counseling at an early stage. [ABSTRACT FROM AUTHOR]

Justice motivation has been considered one cause of celebrity infidelity scandals becoming flaming incidents. Nevertheless, few studies have examined how the belief in a just world (BJW), one motivation for justice, affects people's attitudes toward these incidents. This study was conducted to identify the relations among BJW, negative emotions toward infidelity (NE), and celebrity infidelity blaming (CIB). Data were collected from 1186 Japanese adults (mean age = 44.9 years, SD = 13.8; 49.4% male). The results of structural equation modeling revealed that NE positively relates to CIB and plays a mediating role between BJW and CIB. However, BJW neither facilitates NE nor positively predicts CIB; on the contrary, it suppresses both NE and CIB. The findings indicate that BJW decreases people's blame on celebrity infidelity and suggest future directions for mitigating the issues posed by casting blame on celebrities' cheating scandals. [ABSTRACT FROM AUTHOR]

In recent decades, Japanese rice wine, sake, exports to international countries have developed tremendously. Recently, in particular, sake exports are increasing in both volume and unit value due to factors such as the registration of Japanese cuisine as an intangible cultural heritage of UNESCO in 2013 and the economic situations including the rapid depreciation of Japanese yen. However, there are no studies which investigated sake exports via empirical methods as far as we know. In this study, we constructed hierarchical Bayesian models and analyzed unbalanced panel datasets on the export of Japanese sake to China, Hong Kong SAR China, Singapore, Taiwan and the US by using a Markov chain Monte Carlo (MCMC) method and an ancillary-sufficiency interweaving strategy (ASIS) as the first empirical study of Japanese sake export. As a result, it was found that the trends in export volume and unit value to China, Hong Kong SAR China, Singapore and the US were significantly positive. In addition, although Taiwan had a negative trend before UNESCO registration, the trend became positive after its registration. Based on these results, it can be concluded that Japanese sake has been booming worldwide, though the degree may vary from country to country. Especially, we found that the UNESCO registration of Japanese food, Washoku, has significant effects on booming sake exports both in terms of volume and unit value. Finally, we divided the sake export data by regional customs offices in charge and conducted a detailed analysis on regional heterogeneity in sake exports. From the results, we found there were some different trends among regions. [ABSTRACT FROM AUTHOR]

The epigenetic clock evaluates human biological age based on DNA methylation patterns. It takes the form of a regression model where the methylation ratio at CpG sites serves as the predictor and age as the response variable. Due to the large number of CpG sites and their correlation, Elastic Net is commonly used to train the models. However, existing standard epigenetic clocks, trained on multiracial data, may exhibit biases due to genetic and environmental differences among specific racial groups. Developing epigenetic clocks suitable for a specific single-race population requires collecting and analyzing hundreds or thousands of samples, which costs a lot of time and money. Therefore, an efficient method to construct accurate epigenetic clocks with smaller sample sizes is needed. We propose Transfer Elastic Net, a transfer learning approach that trains a model in the target population using the information of parameters estimated by the Elastic Net in a source population. Using this method, we constructed Horvath's, Hannum's, and Levine's types of epigenetic clocks from blood samples of 143 Japanese subjects. The DNA methylation data were transformed through principal component analysis to obtain more reliable clocks. The developed clocks demonstrated the smallest prediction errors compared to both the original clocks and those trained with the Elastic Net on the same Japanese data. Transfer Elastic Net can also be applied to develop epigenetic clocks for other specific populations, and is expected to be applied in various fields. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the one-year outcomes of intravitreal ranibizumab biosimilar (RBZ-BS) injections for myopic choroidal neovascularization (mCNV) in Japanese patients. Methods: Twenty-one patients (mean age 69.0 years; 4 males, 17 females) with high myopia and mCNV were retrospectively reviewed. Twelve were treatment-naïve, and nine had previous anti-VEGF treatments. Efficacy measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: The treatment-naïve group showed significant BCVA improvement from 0.55 ± 0.34 at baseline to 0.24 ± 0.28 at 12 months. The previously treated group had no significant BCVA changes. CMT significantly decreased in both groups: from 295.3 ± 105.2 µm to 207.3 ± 63.0 µm in the treatment-naïve group, and from 196.1 ± 62.0 µm to 147.2 ± 50.1 µm in the previously treated group. Dry macula rates were high: 83% at 3 months and 83% at 12 months in the treatment-naïve group, and 67% at 3 months and 89% at 12 months in the previously treated group. No adverse events were reported. Conclusions: These findings indicate that RBZ-BS is an effective and safe treatment for mCNV, particularly in treatment-naïve patients. The use of RBZ-BS offers a cost-effective alternative to original ranibizumab, reducing financial burdens while maintaining high therapeutic efficacy. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these results and evaluate long-term outcomes and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to verify the accuracy of a new calculation formula, Barrett true axial length formula (T-AL), and the optimized lens factor (LF) for predicting postoperative refraction after cataract surgery. Methods: We included 156 Japanese patients who underwent cataract surgery using Clareon monofocal intraocular lenses at our clinic between January 2022 and June 2023. Postoperative spherical equivalent was calculated using subjective refraction values obtained 1 month post-surgery. The LFs were optimized so that the mean prediction error (PE) of each calculation formula was zero (zero optimization). We calculated the mean absolute PE (MAE) to assess accuracy and used a Friedman test for statistical comparisons. The accuracy of T-AL and the optimized LFs was compared with that of the conventional Barrett Universal II formula for ARGOS (AR-B) and OA-2000 (OA-B) with equivalent refractive index. Results: For T-AL, AR-B, and OA-B, the MAEs ± standard deviations were 0.225 ± 0.179, 0.219 ± 0.168, and 0.242 ± 0.206 D, respectively. The Friedman test showed no statistically significant differences among the three groups. The device-optimized LFs were 2.248–2.289 (T-AL), 2.236–2.246 (AR-B), and 2.07–2.08 (OA-B); the corresponding zero-optimized LFs were 2.262–2.287 (T-AL), 2.287–2.303 (AR-B), and 2.160–2.170 (OA-B). Conclusion: There were no significant differences in prediction accuracy among the formulas. However, the accuracy of LF optimization varied by device, with T-AL being closest to the value under zero optimization. This suggests that T-AL is clinically useful for predicting an accurate postoperative refraction without zero optimization. [ABSTRACT FROM AUTHOR]

To assess the effect of rice bran oil emulsified formulation (EMF) on cooked rice, a single-arm open clinical trial and in vitro testing for digestion and glycemic response were performed. Fifteen Japanese men consumed 200 g of packed rice, cooked with or without EMF. Blood samples were collected 0, 30, 60, and 120 min post-consumption and analyzed for glucose, insulin, and triglyceride levels. Continuous glucose monitoring (CGM) and sensory evaluation were also performed. A two-step in vitro digestion test, simulating gastric and small intestinal digestion was conducted. EMF-added rice group showed higher insulin response levels at 60 min than the placebo group. Stratification of participants with HbA1c ≥ 5.6 or an insulinogenic index ≤ 0.4 revealed a significant reduction in Cmax glucose levels. A significant correlation was observed between venous and CGM blood glucose levels and no significant sensory differences were observed. The in vitro test revealed significantly lower C∞, equilibrium starch concentrations, with EMF. Clinical trial suggests that EMF may stimulate insulin secretion and reduce blood glucose levels in participants with lower insulin responses. In vitro tests suggest that EMF inhibits glycemic digestion. This trial was registered at the UMIN Center (UMIN000053495; registered 31 January 2024). [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of liver dysfunction in COVID-19 patients remains unclear. In this study, we investigated the association between liver function test results and severe disease progression in COVID-19 patients. Methods: This retrospective study included consecutive Japanese COVID-19 patients admitted between February 2020 and July 2021. Predictive variables for severe disease progression were identified by multivariate logistic regression analysis. Severe disease-free survival was estimated with the Kaplan–Meier method and Cox regression analysis. Aspartate aminotransferase (AST) was divided into three grades: grade 1, AST < 30 U/L; grade 2, 30 U/L ≤ AST < 60 U/L; and grade 3, AST > 60 U/L. Results: Among 604 symptomatic patients, 141 (23.3%) developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were the significant predictive variables. Severe disease-free survival time was significantly different between the different AST grades (hazard ratio (HR): grade 2 vs. grade 1, 4.07 (95% confidential interval (CI): 2.06–8.03); grade 3 vs. grade 1, 7.66 (95% CI: 3.89–15.1)). Conclusions: The AST level at admission was an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background/Objectives: The use of food thickeners with ciprofloxacin tablets may result in a gelatinous appearance and experience delayed dissolution, which presents a challenge for the drug's efficacy, creating a healthcare economic issue. However, the pharmacokinetic impact of this compound in humans remains uncertain. Therefore, a comparative pharmacokinetic study of ciprofloxacin was conducted on healthy adult Japanese males. Methods: We compared the effects of administering tablets with water or thickened water and crushed tablets mixed with thickened water. The maximum blood concentration (Cmax) of ciprofloxacin determines the drug's efficacy. Results: There were variations in drug absorption across different administration methods. The group who took the tablets immersed in thickened water exhibited different results in the area under the blood drug concentration–time curve (AUC) and Cmax compared to the group who took the tablets in regular water. Notably, the group that consumed the crushed tablets mixed with thickened water demonstrated equivalent results for both AUC and Cmax. Conclusions: Administering crushed tablets in thickened water may yield pharmacokinetics comparable to those of tablets taken with water. However, the process of crushing tablets may result in the loss of active ingredients and compromise the formulation, necessitating a comprehensive assessment before administration. [ABSTRACT FROM AUTHOR]

Objective: To purpose of this study was to retrospectively evaluate the 1-year outcomes and factors associated with the treatment responsiveness of switching to intravitreal brolucizumab (IVBR) for neovascular age-related macular degeneration (nAMD) in Japanese patients refractory to ranibizumab or aflibercept using a treat and extend (TAE) regimen. Methods: A total of 48 eyes of 47 nAMD patients were switched to IVBR, and 36 eyes of 35 patients (27 males and 8 females) underwent 1-year treatment after the switch. Results: The rate of dry macula was significantly higher 12 months after the switch to IVBR (p < 0.001), with a significant decrease in the mean central macular thickness (CMT) and the mean central choroidal thickness (CCT) (p < 0.01 and p < 0.01, respectively). The injection interval was significantly extended from 7.0 ± 1.7 weeks to 10.3 ± 2.5 weeks 12 months after the switch (p < 0.001). In the multivariate analysis, a smaller number of prior anti-VEGF injections (p = 0.025; odds ratio: 0.947; 95% confidence interval: 0.903–0.994) and a pre-switching CCT of less than 250 µm (p = 0.023; odds ratio: 0.099; 95% confidence interval: 0.013–0.731) were associated with the good response group. Conclusions: These results suggest that IVBR may suppress disease activity and prolong the injection interval by switching for AMD patients with an insufficient response to treatment with ranibizumab and aflibercept. [ABSTRACT FROM AUTHOR]

Background: High breast density found using mammographs (MGs) reduces positivity rates and is considered a risk factor for breast cancer. Research on the relationship between Volpara density grade (VDG) and compressed breast thickness (CBT) in the Japanese population is still lacking. Moreover, little attention has been paid to pseudo-dense breasts with CBT < 30 mm among high-density breasts. We investigated VDG, CBT, and apparent high breast density in patients with breast cancer. Methods: Women who underwent MG and breast cancer surgery at our institution were included. VDG and CBT were measured. VDG was divided into a non-dense group (NDG) and a dense group (DG). Results: This study included 419 patients. VDG was negatively correlated with CBT. The DG included younger patients with lower body mass index (BMI) and thinner CBT. In the DG, patients with CBT < 30 mm had lower BMI and higher VDG; however, no significant difference was noted in the positivity rate of the two groups. Conclusions: Younger women tend to have higher breast density, resulting in thinner CBT, which may pose challenges in detecting breast cancer on MGs. However, there was no significant difference in the breast cancer detection rate between CBT < 30 mm and CBT ≥ 30 mm. [ABSTRACT FROM AUTHOR]

Background and Objectives: The trends in metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic dysfunctions in Japan are unknown. Thus, we aimed to clarify these trends before the novel coronavirus disease 2019 pandemic in Japan. Materials and Methods: We included Japanese individuals aged 25–79 years who underwent health examinations at our center. We analyzed anthropometry, lifestyle-related disease, and nutritional intake in relation to MASLD trends from 2010–2019. Results: The prevalence of MASLD increased in all ages and body mass index (BMI) classes, reaching 30.3% in males and 16.1% in females, with MASLD accounting for 75% of steatotic liver cases and more than half of all type 2 diabetes mellitus (T2DM) and high waist circumference (HWC) cases. The increase in the prevalence of MASLD was thought to be largely attributable to an increase in that of the incidence of steatotic liver itself, and there was no increase in the prevalence of other factors, such as overweight, T2DM, hypertension, and dyslipidemia. The prevalence of glucose metabolic disorders (GMDs) and hypertension decreased. National nutritional data showed an increase in energy intake, total fat, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, which correlated with a decrease in GMDs. Salt intake also decreased, which correlated with hypertension. The MASLD group had a higher prevalence of all related metabolic factors than the non-MASLD group, especially HWC, T2DM, and hyperlipidemia. Conclusions: The prevalence of MASLD increased with that of steatotic liver, regardless of age or BMI. A relationship between increased dietary fat, increased steatotic liver, and decreased GMDs was suggested. [ABSTRACT FROM AUTHOR]

The critically important preoperative and intraoperative factors that affect the success of endodontic microsurgery (EMS) in Japanese patients are not defined. We conducted a retrospective study that analyzed treatment outcomes for 46 teeth in 46 Japanese patients. Treatment was provided between March 2013 and March 2015. All patients were evaluated after one year, the shortest time period over which treatment outcomes after apicoectomy could be evaluated and in which there were complete records for the recruited patient population. Healing was assessed on the basis of clinical symptoms and radiographs. With the use of a binary logistic regression model to quantify success, we estimated the effects of patient age, sex, dental arch, lesion size, lesion type, preoperative root canal treatment, the presence or absence of a post core, and the presence or absence of an isthmus on the surgically prepared dentine surface. The overall success for EMS was 93.5% after one year; failures comprised 6.5%. Successful outcomes were higher (p = 0.04) for maxillary teeth than for mandibular teeth. Success was higher (p = 0.019) for patients who received root canal instrumentation prior to EMS. Age, sex, lesion size, lesion type, the presence or absence of a post core, and the presence or absence of a root canal isthmus had no effect (p > 0.2) on success. We conclude that the percentage of successful outcomes after EMS treatment for Japanese patients presenting with periapical periodontitis is very high after one year and that success is influenced strongly by the dental arch and preoperative root canal instrumentation. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) tract harbors trillions of microorganisms known to influence human health and disease, and next-generation sequencing (NGS) now enables the in-depth analysis of their diversity and functions. Although a significant amount of research has been conducted on the GI microbiome, comprehensive metagenomic datasets covering the entire tract are scarce due to cost and technical challenges. Despite the widespread use of fecal samples, integrated datasets encompassing the entire digestive process, beginning at the mouth and ending with feces, are lacking. With this study, we aimed to fill this gap by analyzing the complete metagenome of the GI tract, providing insights into the dynamics of the microbiota and potential therapeutic avenues. In this study, we delved into the complex world of the GI microbiota, which we examined in five healthy Japanese subjects. While samples from the whole GI flora and fecal samples provided sufficient bacteria, samples obtained from the stomach and duodenum posed a challenge. Using a principal coordinate analysis (PCoA), clear clustering patterns were identified; these revealed significant diversity in the duodenum. Although this study was limited by its small sample size, the flora in the overall GI tract showed unwavering consistency, while the duodenum exhibited unprecedented phylogenetic diversity. A visual heat map illustrates the discrepancy in abundance, with Fusobacteria and Bacilli dominating the upper GI tract and Clostridia and Bacteroidia dominating the fecal samples. Negativicutes and Actinobacteria were found throughout the digestive tract. This study demonstrates that it is possible to continuously collect microbiome samples throughout the human digestive tract. These findings not only shed light on the complexity of GI microbiota but also provide a basis for future research. [ABSTRACT FROM AUTHOR]

The year 2023 marks the 12th anniversary of the Great East Japan Earthquake (GEJE). Immediately after the disaster, the number of evacuees reached approximately 470,000, but by November 2022, the number had decreased to approximately 31,000. The reconstruction of housing, disposal of debris, public infrastructure development, and overall restoration and reconstruction has progressed steadily. However, a re-examination of the status of industrial restoration and reconstruction reveals that restoration and reconstruction have not progressed in some areas. This research statistically analyzes how the Japanese public perceives the issues around the recovery process and what memories and records they would like to learn from regarding the GEJE. The purpose of this study is to ask about reconstruction issues and lessons learned from the GEJE by conducting a web-based survey with 2000 respondents in Japan. The method of estimation is the use of ordinal logistic regression analysis to statistically estimate whether there are differences in recovery issues and lessons learned depending on individual attributes. The results suggest that those who are interested in, remember, and express anxiety about the recovery issues and lessons learned tend to be men, do not have children, are highly educated, and have a higher income. In sum, many of Japan's citizens are highly interested in the reconstruction of agriculture, forestry, fisheries, housing, urban development, living environment, industry, and livelihood in the affected areas. In the future, they will play a central role in modernizing, scaling up, and integrating the agriculture, forestry, and fisheries industries, as well as in rebuilding towns and livelihoods. In the affected areas, it will be necessary to draw on the lessons learned from the GEJE and create reconstruction plans for the future, and then, policymakers will need to formulate reconstruction policies that reflect the concerns of the Japanese people. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to investigate outcomes of visual acuity (VA) and intraocular pressure (IOP) in proliferative diabetic retinopathy (PDR)-associated neovascular glaucoma (NVG) in Japanese patients treated with surgical therapies without the use of glaucoma drainage devices. Methods: A retrospective analysis of medical records was conducted for 31 consecutive PDR-associated NVG patients who underwent surgical treatments in our institution between 2013 and 2022. Patient demographics, clinical characteristics, VA, and IOP were recorded at the first and last visits, and surgical procedures, including pars plana vitrectomy with extensive panretinal and ciliary photocoagulation (PPV–PRCP), diode laser trans-scleral cyclophotocoagulation (DCPC), and trabeculectomy with mitomycin C (TLE–MMC), with or without a prior intravitreal bevacizumab (IVB) injection, were reviewed. Results: Of the thirty-one PDR patients with NVG, two patients received PPV–PRCP or DCPC alone (6.5%), respectively, three patients received TLE–MMC alone (9.7%), two patients received TLE–MMC after IVB (6.5%), six patients received PPV–PRCP and TLE–MMC (19.4%), seven patients received PPV–PRCP and TLE–MMC after IVB (22.6%), five patients received PPV–PRCP and DCPC and TLE–MMC (16.1%), and four patients received PPV–PRCP and DCPC and TLE–MMC after IVB (12.9%). The VA of two patients (6.5%) deteriorated to no light perception. In all patients, the mean logMAR VA was 1.28 ± 1.05 at the first visit and remained at 1.26 ± 1.08 at the last visit, with no significant change; the mean IOP was 33.0 ± 15.2 mmHg at the initial visit and decreased significantly to 14.0 ± 7.4 mmHg at the last visit. The number of eyes with IOP ≥ 21 decreased from twenty-eight (90.3%) to three (9.7%). Although IOP in patients with IOP > 30 mmHg at the initial visit reduced to a level comparable to that of patients with IOP ≤ 30 mmHg, the IOP > 30 mmHg group received IVB more frequently and had significantly higher logMAR VA at the last visit compared to the IOP ≤ 30 mmHg group. Hypotony (<6 mmHg) was observed in four eyes (12.9%). Conclusions: In PDR patients with NVG, various combinations of PPV–PRCP, DCPC, and TLE–MMC after adjunctive IVB without the use of glaucoma drainage devices lowered IOP sufficiently; for these patients, neovascular regression was observed, with no further deterioration of VA. However, surgical procedures should be performed for PDR patients with NVG before visual impairment occurs. On the other hand, approximately less than 15% of patients developed blindness or low IOP. [ABSTRACT FROM AUTHOR]

Background: Constipation causes substantial morbidity worldwide. Methods: This survey assessed constipation-related factors in Japan using the Japanese version of the Irritable Bowel Syndrome Quality of Life (IBS-QOL-J) instrument. We also examined the relationship among laxative type, Bristol Stool Form Scale (BSFS) scores, and treatment cost. Finally, we examined differences in satisfaction scores according to laxative type, treatment type, treatment cost, and BSFS score. Results: IBS-QOL-J was higher among those taking salt and/or irritation laxatives. Those paying >JPY 5000 (USD 50.00) had the lowest IBS-QOL-J. IBS-QOL-J was significantly lower among those with a BSFS score of 1 or 2 (severe constipation). Conclusions: This study's findings suggest that a variety of factors, including treatment type and cost, are associated with defecation satisfaction. Those who had hard stools, used multiple laxatives, or spent more on treatment were less satisfied. Future strategies should target therapies that do not require multiple laxatives with lower treatment costs. Adequate defecation with a small number of appropriate laxatives at minimal cost appears to improve defecation satisfaction. It is desirable to identify appropriate laxatives and improve dietary habits and exercise routines. It is also necessary to stop blindly increasing laxative usage and properly diagnose constipation disorders such as anatomical abnormalities other than functional constipation. [ABSTRACT FROM AUTHOR]

Background: Repetitive episodes of apnea and hypopnea during sleep in patients with obstructive sleep apnea (OSA) are known to increase the risk of atherosclerosis. Underlying obesity and related disorders, such as insulin resistance, are indirectly related to the development of atherosclerosis. In addition, OSA is independently associated with insulin resistance; however, data regarding this relationship are scarce in Japanese populations. Methods: This study aimed to examine the relationship between the severity of OSA and insulin resistance in a Japanese population. We analyzed the data of consecutive patients who were referred for polysomnography under clinical suspicion of developing OSA and who did not have diabetes mellitus or any cardiovascular disease. Multiple regression analyses were performed to determine the relationship between the severity of OSA and insulin resistance. Results: The data from a total of 483 consecutive patients were analyzed. The median apnea-hypopnea index (AHI) was 40.9/h (interquartile range: 26.5, 59.1) and the median homeostasis model assessment for insulin resistance (HOMA-IR) was 2.00 (interquartile range: 1.25, 3.50). Multiple regression analyses revealed that the AHI, the lowest oxyhemoglobin saturation (SO2), and the percentage of time spent on SO2 < 90% were independently correlated with HOMA-IR (an adjusted R-squared value of 0.01278821, p = 0.014; an adjusted R-squared value of −0.01481952, p = 0.009; and an adjusted R-squared value of 0.018456581, p = 0.003, respectively). Conclusions: The severity of OSA is associated with insulin resistance assessed by HOMA-IR in a Japanese population. [ABSTRACT FROM AUTHOR]

Background: Psoriatic arthritis (PsA) is characterized by enthesitis. As persistent inflammation around joints results in bone and cartilage destruction and physical impairment, a detailed assessment of inflammation is essential. We previously reported the difference between clinical assessment (tenderness) and ultrasound (US) assessment (inflammation) of entheses. Herein, we investigated whether clinical or US assessment of joints and entheses can predict the progression of joint destruction in Japanese patients with PsA. Methods: Thirty joints and 14 entheses in 47 patients were assessed using US and clinical examination. The US greyscale (GS) and power Doppler (PD) scores at the ultrasonographic synovitis, the US active enthesitis count, and the clinical tender joint/entheses count were assessed. Additionally, the yearly radiographic progression of the Sharp–van der Heijde scoring method for PsA was assessed. Their correlations were investigated. Results: About half of the patients with PsA experienced joint destruction during a follow-up period of 20.4 months. Progression of joint destruction in patients with PsA only correlated with joint GS and PD scores, reflecting the severity of ultrasonographic synovitis, not with the tender joint/entheses count. Conclusions: US examinations are essential for preventing joint destruction and physical impairment in patients with PsA. [ABSTRACT FROM AUTHOR]

Background: A decrease in populations could affect healthcare access and systems, particularly in medically underserved areas (MUAs) where depopulation is becoming more prevalent. This study aimed to simulate the future population and land areas of MUAs in Japan. Methods: This study covered 380,948 1 km meshes, 87,942 clinics, and 8354 hospitals throughout Japan as of 2020. The areas outside a 4 km radius of medical institutions were considered as MUAs, based on the measure of areas in the current Japanese Medical Care Act. Based on the population estimate for a 1 km mesh, the population of mesh numbers of MUAs was predicted for every 10 years from 2020 to 2050 using geographic information system analysis. If the population within a 4 km radius from a medical institution fell below 1000, the institution was operationally assumed to be closed. Results: The number of MUAs was predicted to decrease from 964,310 (0.77% of the total Japanese population) in 2020 to 763,410 (0.75%) by 2050. By 2050, 48,105 meshes (13% of the total meshes in Japan) were predicted to be new MUAs, indicating a 31% increase in MUAs from 2020 to 2050. By 2050, 1601 medical institutions were tentatively estimated to be in close proximity. Conclusions: In Japan, the population of MUAs will decrease, while the land area of MUAs will increase. Such changes may reform rural healthcare policy and systems. [ABSTRACT FROM AUTHOR]

In the lives of those who are the target of community health nursing, it is important to collaborate with individuals and communities to improve their quality of life. Herein, we aimed to determine the association between Internet use among older individuals and locomotive syndrome (LS), frailty, and sarcopenia. In this cross-sectional study conducted between July 2022 and March 2023, we recruited 105 community-dwelling older Japanese adults who participated in a care prevention project called "Kayoi-no-ba". All participants were divided into Internet and non-Internet user groups according to the classification of a previous study. We assessed LS (standing test, two-step test, and five-question Geriatric Locomotive Function Scale), frailty (through the Questionnaire for Medical Checkup of Old-Old), and sarcopenia (grip strength, normal walking speed, and skeletal muscle mass index) and made group comparisons between Internet users and non-users. Binomial logistic regression analyses were performed with Internet use as the independent variable and sarcopenia or LS as the dependent variables. The Internet and non-Internet user groups had 69 and 36 participants, respectively. The Internet user group comprised 65.7% of all participants, which was similar to that reported in a previous study of the same age group. Between-group comparisons showed significant differences in sarcopenia and LS items, whereas adjusted binomial logistic analysis showed a significant association between sarcopenia and Internet use. In summary, among LS, frailty, and sarcopenia, sarcopenia showed the highest association with Internet use. Older adults without sarcopenia having good physical functions, such as grip strength, walking speed, and skeletal muscle index, more likely used the Internet; while older adults with sarcopenia were less likely to use the Internet. This implied that Internet use may be associated with physical function. [ABSTRACT FROM AUTHOR]

Background and Objective: Excellent generalizability is the precondition for the widespread practical implementation of machine learning models. In our previous study, we developed the schizophrenia classification model (SZ classifier) to identify potential schizophrenia patients in the Japanese population. The SZ classifier has exhibited impressive performance during internal validation. However, ensuring the robustness and generalizability of the SZ classifier requires external validation across independent sample sets. In this study, we aimed to present an external validation of the SZ classifier using outpatient data. Methods: The SZ classifier was trained by using online survey data, which incorporate demographic, health-related, and social comorbidity features. External validation was conducted using an outpatient sample set which is independent from the sample set during the model development phase. The model performance was assessed based on the sensitivity and misclassification rates for schizophrenia, bipolar disorder, and major depression patients. Results: The SZ classifier demonstrated a sensitivity of 0.75 when applied to schizophrenia patients. The misclassification rates were 59% and 55% for bipolar disorder and major depression patients, respectively. Conclusions: The SZ classifier currently encounters challenges in accurately determining the presence or absence of schizophrenia at the individual level. Prior to widespread practical implementation, enhancements are necessary to bolster the accuracy and diminish the misclassification rates. Despite the current limitations of the model, such as poor specificity for certain psychiatric disorders, there is potential for improvement if including multiple types of psychiatric disorders during model development. [ABSTRACT FROM AUTHOR]

Background: Chronic spontaneous urticaria (CSU), characterized by the recurrence of pruritic hives and/or angioedema for >6 weeks with no identifiable trigger, has a negative impact on health-related quality of life (HRQoL). Methods: The objective of this web-based cross-sectional study was to evaluate disease control, disease burden, and treatment satisfaction in Japanese adults with CSU using the Urticaria Control Test (UCT), HRQoL outcomes, and the Treatment Satisfaction Questionnaire for Medication–9 items (TSQM-9). Results: In total, 529 adults were included in the analysis (59.9% female), with a mean ± standard deviation (SD) in CSU duration of 13.2 ± 13.0 years. Based on UCT scores, two-thirds of patients had poor (score of 0–7; 23.6%) or insufficient (score of 8–11; 43.3%) symptom control, and one-third had good control (score of 12–16; 33.1%). Overall treatment satisfaction was not high, with mean ± SD TSQM-9 scores of 55.5 ± 17.6% for effectiveness, 68.2 ± 18.8% for convenience, and 59.2 ± 18.4% for global satisfaction. No apparent differences in TSQM-9 scores were observed between patients receiving different medications. HRQoL outcomes were worse among patients with poor/insufficient symptom control. Conclusions: Japanese adults with CSU have a high disease burden, and better treatment options are needed to increase treatment satisfaction. [ABSTRACT FROM AUTHOR]

Background: This retrospective cross-sectional study investigated the cutoff values (COVs) for developmental dysplasia of the hip (DDH) using a three-dimensional (3D) pelvic model reconstructed using computed tomography (CT). We included 107 healthy Japanese participants and 73 patients who had undergone curved periacetabular osteotomy (CPO) for DDH between 2012 and 2017. Methods: The hip CT images were adjusted to the anterior pelvic plane (APP), functional pelvic plane (FPP), sagittal anterior center-edge angle (ACEA), and sagittal posterior center-edge angle (PCEA). The lateral center-edge angle (LCEA), acetabular roof obliquity (ARO), anterior acetabular sector angle (AASA), and posterior acetabular sector angle (PASA) were measured. Receiver operating characteristic (ROC) curves were used to calculate the COVs, and the association between the parameters was analyzed using multiple logistic regression. Results: The ARO (≥10.2°) and LCEA (≤22.2°) were independent influencing factors for the APP, whereas the AASA (≤53.1°) and LCEA (≤24.5°) were independent influencing factors for the FPP. Conclusions: The 3D criteria for the diagnosis of DDH in Japanese individuals can identify DDH with insufficient anterior coverage, which anteroposterior plain radiographs cannot visualize, and can help determine indications for acetabular osteotomy. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) ranks as the second most common cancer in Japanese males, while bladder cancer (BC) holds the tenth spot. Among double urological cancers, the incidence of synchronous or metachronous BC and PCa is the highest. Reports on upper urinary tract (UUT) urothelial cancer (UC) in PCa patients are limited. Here, we present three cases of metachronous PCa and BC, with subsequent diagnosis of ureteral and renal pelvic cancer during the course of the disease. In the follow-up of patients with urological cancers, it is important to be aware not only of the progression of the initial cancer but also the potential development of a second cancer. [ABSTRACT FROM AUTHOR]

The role of metabolic traits in ischemic stroke (IS) has been explored through observational studies and a few Mendelian randomization (MR) studies employing limited methods in European populations. This study aimed to investigate the causal effects of metabolic traits on IS in both East Asian and European populations utilizing multiple MR methods based on genetic insights. Two-sample and multivariable MR were performed, and MR estimates were calculated as inverse-variance weighted (IVW), weighted median, and penalized weighted median. Pleiotropy was assessed by MR–Egger and Mendelian randomization pleiotropy residual sum and outlier tests. Systolic blood pressure (SBP) was associated with an increased risk of IS by IVW in both European (ORIVW: 1.032, 95% CI: 1.026–1.038, p < 0.001) and Japanese populations (ORIVW: 1.870, 95% CI: 1.122–3.116, p = 0.016), which was further confirmed by other methods. Unlike the European population, the evidence for the association of diastolic blood pressure (DBP) with IS in the Japanese population was not stable. No evidence supported an association between the other traits and IS (all Ps > 0.05) in both races. A positive association was found between SBP and IS in two races, while the results of DBP were only robust in Europeans. [ABSTRACT FROM AUTHOR]

Once-weekly semaglutide is a widely used glucagon-like peptide-1 receptor agonist (GLP-1RA) used for the treatment of type 2 diabetes (T2D). In clinical trials, semaglutide improved glycemic control and obesity, and reduced major cardiovascular events. However, the reports are limited on its real-world efficacy relating to various metabolic factors such as dyslipidemia or metabolic dysfunction-associated steatotic liver disease (MASLD) in Asian patients with T2D. In our retrospective longitudinal study, we selected patients with T2D who were given once-weekly semaglutide and compared metabolic parameters before and after the start of semaglutide. Seventy-five patients were eligible. HbA1c decreased significantly, by 0.7–0.9%, and body weight by 1.4–1.7 kg during the semaglutide treatment. Non-HDL cholesterol decreased significantly at 3, 6 and 12 months after the initiation of semaglutide; LDL cholesterol decreased at 3 and 6 months; and HDL cholesterol increased at 12 months. The effects on body weight, HbA1c and lipid profile were pronounced in patients who were given semaglutide as a first GLP-1RA (GLP-1R naïve), whereas improvements in HbA1c were also observed in patients who were given semaglutide after being switched from other GLP-1RAs. During a 12-month semaglutide treatment, the hepatic steatosis index (HSI) tended to decrease. Moreover, a significant decrease in the AST-to-platelet ratio index (APRI) was observed in GLP-1RA naïve patients. Our real-world study confirmed the beneficial effects of once-weekly semaglutide, namely, improved body weight, glycemic control and atherogenic lipid profile. The beneficial effects on MASLD were also suggested. [ABSTRACT FROM AUTHOR]

Whilst study abroad (SA) periods hold much promise for foreign language development, increasing research suggests sojourners' experiences are unique, and language development does not always follow a linear trajectory. For some learners, SA has little impact on their language performance despite the affordances of L2 immersion (the Survivors). Other learners maximise the potential of SA, and this has a positive impact on their language development (the Thrivers). This paper examines the selected cases of four Japanese learners of English and their request language performance during a 10-month SA in the UK. Changes in pragmatic knowledge (based on appropriateness ratings) were documented at three equidistant time points. Language contact profile data also provided quantitative insights into the learners' extracurricular language use and qualitative personal reflections. The selected cases illustrate two learners surviving the SA experience, showing minimal change in their request performance. The other two learners thrived during SA, showing accelerated performance in terms of lexical variation at the production level. This paper reports on the case histories of these learners to better understand these unique experiences and pragmatic discrepancies. Suggestions for how learners might be more pragmatically successful during SA are also offered. [ABSTRACT FROM AUTHOR]

People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese PLWH. NAb titers were assessed in polyclonal IgG fractions by lentiviral-based pseudovirus assays. Overall, NAb titers against Wuhan, following two-dose vaccination, were assessed in 82 PLWH on treatment, whereby 17/82 (20.73%) were classified as low-NAb participants. Within the low-NAb participants, the third booster vaccination enhanced NAb titers against Wuhan and VOCs, albeit to a significantly lower magnitude than the rest. In the multivariate analysis, NAb titers against Wuhan after two-dose vaccination correlated with age and days since vaccination, but not with CD4+ count, CD4+/CD8+ ratio, and plasma high-sensitivity C-Reactive protein (hsCRP). Interestingly, an extended analysis within age subgroups revealed NAb titers to correlate positively with the CD4+ count and negatively with plasma hsCRP in younger, but not older, participants. In conclusion, a third booster vaccination substantially enhances NAb titers, but the benefit may be suboptimal in subpopulations of PLWH exhibiting low titers at baseline. Considering clinical and immune parameters could provide a nuanced understanding of factors associated with vaccine responses in PLWH. [ABSTRACT FROM AUTHOR]

As a highly urbanized country, Japan is facing the phenomenon of a continuous migration of young people from rural areas to cities, leading to an aging and decreasing population in rural communities. Influenced by the pandemic, people began to reconsider the issue of population concentration in large cities, causing urban residents to become interested in returning to rural areas. The focus of this study is on the perceptions and relocation intentions of Japanese youth towards rural areas, particularly in Hanyu-shi, Saitama Prefecture. Through semi-structured interviews with 26 urban university students who live in urban areas, this study explores the factors that attract or hinder them from having rural lives. The survey results show that childhood experiences and current lifestyle preferences have influenced their views on rural areas. The main hindering factors include backwards infrastructure, communication difficulties, and limited job prospects. This study reveals a significant cognitive gap in urban youth's attitudes towards rural life in Japan. The study emphasizes the need to eliminate these hindrances and enhance the attractiveness of rural areas to promote reverse urban migration. This study provides important insights for policymakers and urban planners, highlighting the necessity of formulating development strategies that meet the needs of urban youth residents, which is crucial for the sustainable revitalization of rural Japan. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) has been associated with increased prostate cancer (PCa) risk. However, the mechanisms underlying UC and increased PCa risk remain unclear, and research on this topic is scarce in Japan. We have investigated whether UC is associated with PCa risk in the Japanese population and the risk factors related to PCa among older UC patients. This retrospective single-center cohort study was conducted between January 2010 and April 2022. A total of 68 cases were analyzed, and 9 cases of PCa were observed (13.2%). PCa occurred more frequently in the adult-onset group (8/40, 20.0%) than in the older-onset group with UC (1/28; 3.57%). No significant differences were observed between immunosuppressive therapies and PCa in patients, excluding those with pancolitis-type UC. PCa occurred more frequently in the pancolitis type, and the biologics group had no PCa cases, but the difference was not statistically significant (p = 0.07). This study suggests that pancolitis type and UC onset in middle-aged patients may be risk factors and found that biologics potentially suppress PCa development. [ABSTRACT FROM AUTHOR]

The present study examined the effects of foods containing lipopolysaccharides from Pantoea agglomerans (LPSp) on eye–nose allergic symptoms using a double-blind, placebo-controlled, randomized, parallel-group comparative research design. Sixty-three Japanese individuals aged 20–65 years with eye–nose allergic symptoms were included in this study and assigned to the LPS (480 μg/day)-containing food and placebo groups. Data on the subjective eye–nose allergic symptoms and antiallergic medication during the 8-week period were evaluated. The immunoglobulin E (IgE) and eosinophil counts were measured as indicators that may be correlated with allergy. No significant group differences were found in the change in eye–nose allergic symptoms from baseline. However, the LPS group showed a significantly shorter duration of antiallergic medication use and lower total antiallergic drug score than the placebo group. The corrected nasal allergy score calculated by taking into account the antiallergic drug score at week 8 was predominantly lower in the LPS group. The IgE to house dust and cedar pollen and eosinophil counts tended to be lower in the LPS group, and the total IgE and eosinophil counts were significantly lower in the LPS group at week 4. In conclusion, our results indicate that LPS-containing foods alleviate eye–nose allergic symptoms and consequently lower the use of antiallergic drugs (UMIN000049974). [ABSTRACT FROM AUTHOR]

Portal vein thrombosis (PVT), one of the most prevalent hepatic vascular conditions in patients with liver cirrhosis (LC), is associated with high mortality rates. An imbalance between a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) enzyme and von Willebrand factor (VWF) is responsible for hypercoagulability, including spontaneous thrombus formation in blood vessels. Herein, we aimed to identify potential prognostic and diagnostic biomarkers in Japanese patients with LC and PVT. In total, 345 patients were divided into two groups: 40 patients who developed PVT (PVT group) and 305 who did not develop PVT (NPVT group). Among the 345 patients with LC, 81% (279/345) were deemed ineligible due to the presence of preventive comorbidities, active or recent malignancies, and organ dysfunction. The remaining 66 patients were divided into two groups: the PVT group (n = 33) and the NPVT group (n = 33). Plasma ADAMTS-13 activity (ADAMTS-13:AC) and the vWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. Contrast-enhanced, three-dimensional helical computed tomography (CT) was used to detect and characterize PVT. ADAMTS-13:AC was significantly lower in the PVT group than in the NPVT group. No significant differences in plasma vWF:Ag or liver stiffness were observed between the two groups. ADAMTS-13:AC of <18.8 was an independent risk factor for PVT on multivariate analyses (odds ratio: 1.67, 95% confidence interval: 1.21–3.00, p < 0.002). The receiver operating characteristic analysis of ADAMTS-13:AC revealed an area under the curve of 0.913 in PVT detection. Patients with PVT having ADAMTS-13:AC ≥18.8 (n = 17) had higher albumin levels and better prognoses than those with ADAMTS-13:AC <18.8 (n = 16). No significant correlations of ADAMTS-13:AC levels with either fibrin degradation product or D-dimer levels were observed. ADAMTS-13:AC levels could be potential diagnostic and prognostic biomarkers for PVT in Japanese patients with LC. [ABSTRACT FROM AUTHOR]

Visits to the palace of the sea god are a recurring theme in premodern Japanese narratives, and comparing these stories across time periods reveals shifting perceptions of the supernatural world. The earliest sources for narratives of travel to the palace of the sea god in Japan date from the eighth century, most notably in the stories of Luck of the Mountain and Urashima Tarō. In these stories, the descriptions of the sea god's palace, the relationship of the sea god to the natural world, and even the location of the palace were tied to eighth-century understandings of kingship, weather, and geography. Later adaptations of these stories incorporate features of Buddhist geography, Chinese architecture, Buddhist narrative motifs, and even an alternative vision of supernatural time. These alterations occurred because the eighth-century narratives required adaptation to fit a new political, social, and religious reality. This comparison demonstrates that our vision of the supernatural world is inextricably tied to our understanding of the natural. When our fundamental grasp of the nature of reality changes, our imagination of the supernatural transforms in turn. [ABSTRACT FROM AUTHOR]

Introduction: Candida dubliniensis was reclassified from the C. albicans genotype D, and reports show its frequent detection in HIV-positive individuals and easy acquisition of antifungal drug resistance. However, the oral carriage rate in healthy people and contribution to candidiasis in Japan is unclear. Methods: We conducted a cross-sectional survey of the C. dubliniensis carriage rate, performed genotyping and tested antifungal drug susceptibility and protease productivity. Specimens from 2432 Japanese subjects in six regions (1902 healthy individuals, 423 with candidiasis individuals, 107 HIV-positive individuals) were cultured using CHROMagarTMCandida, and the species was confirmed via 25S rDNA amplification and ITS sequences analyzed for genotyping. Results: The C. dubliniensis carriage rate in healthy Japanese was low in the central mainland (0–15%) but high in the most northerly and southerly areas (30–40%). The distribution of these frequencies did not differ depending on age or disease (HIV-infection, candidiasis). Genotype I, previously identified in other countries, was most frequent in Japan, but novel genotypes were also observed. Six antifungal drugs showed higher susceptibility against C. albicans, but protease productivity was low. Conclusions: Oral C. dubliniensis has low pathogenicity with distribution properties attributed to geography and not dependent on age or disease status. [ABSTRACT FROM AUTHOR]

This cross-sectional study examined the prevalence and characteristics of steatotic liver disease (SLD) based on a recently introduced nomenclature in the Japanese health checkup population. SLD was evaluated using liver ultrasonography, and participants were categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol associated steatotic liver disease (MetALD), alcohol-associated/related liver disease (ALD), and cryptogenic SLD groups. The prevalence and characteristics of the SLD subclasses were assessed, and subgroup analyses were conducted for the non-obese (body mass index [BMI] ≤ 25 kg/m2) and lean (BMI ≤ 23 kg/m2) populations. Among the 694 participants, with a median age of 47 years and comprising 54% males, the prevalence of MASLD, MetALD, ALD, and cryptogenic SLD was 26%, 2%, 1%, and 2%, respectively. A remarkable difference was observed in the prevalence of SLD subclasses according to age, sex, and BMI. Subgroup analyses revealed heterogeneous demographic, clinical, and biochemical parameters between the SLD categories. Individuals with MetALD had higher gamma-glutamyl transferase levels, lower platelet counts, and higher fibrosis-4 index than did those with MASLD. Furthermore, the prevalence of non-obese and lean MASLD was 13% and 6%, respectively. This study provides preliminary information on the prevalence of SLD based on a new nomenclature in the Japanese population. [ABSTRACT FROM AUTHOR]

Rapid eye movement (REM) sleep behavior disorder (RBD) is generally common among males and is an established risk factor for neurodegenerative diseases. As the population ages, the prevalence of α-synucleinopathy (such as Parkinson's disease) is increasing. Additionally, the number of female patients is increasing in Japan. Therefore, we aimed to clarify the clinical characteristics of RBD from the perspective of gender differences in the Japanese population. The proportion of male RBD patients (65.2%) was significantly higher than that of female patients (34.8%). Additionally, female patients (70.5 ± 8.2 years) were significantly older than male patients (67.9 ± 8.0 years, p < 0.05). The mean score on the RBD Screening Questionnaire was significantly higher in male patients than in female (8.6 ± 2.9 vs. 7.7 ± 3.1, p < 0.05), while the mean score on the Pittsburgh Sleep Quality Index was significantly higher in males (5.9 ± 3.8 vs. 7.2 ± 3.600, p < 0.001). The Self-rating Depression Scale in females was 41.7 ± 8.5, and they were more likely to show depressive tendencies than males. In polysomnography, higher rates of obstructive sleep apnea and longer duration of stage N1 sleep were detected in males. After adjusting for age, BMI, and polysomnographic parameters, we found that female RBD patients had significantly worse sleep quality and rates of depression compared to male patients. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a heterogeneous and debilitating psychiatric disorder with a strong genetic component. To elucidate functional networks perturbed in schizophrenia, we analysed a large dataset of whole-genome studies that identified SNVs, CNVs, and a multi-stage schizophrenia genome-wide association study. Our analysis identified three subclusters that are interrelated and with small overlaps: GO:0007017~Microtubule-Based Process, GO:00015629~Actin Cytoskeleton, and GO:0007268~SynapticTransmission. We next analysed three distinct trio cohorts of 75 SZ Algerian, 45 SZ French, and 61 SZ Japanese patients. We performed Illumina HiSeq whole-exome sequencing and identified de novo mutations using a Bayesian approach. We validated 88 de novo mutations by Sanger sequencing: 35 in French, 21 in Algerian, and 32 in Japanese SZ patients. These 88 de novo mutations exhibited an enrichment in genes encoding proteins related to GO:0051015~actin filament binding (p = 0.0011) using David, and enrichments in GO: 0003774~transport (p = 0.019) and GO:0003729~mRNA binding (p = 0.010) using Amigo. One of these de novo variant was found in CORO1C coding sequence. We studied Coro1c haploinsufficiency in a Coro1c+/− mouse and found defects in the corpus callosum. These results could motivate future studies of the mechanisms surrounding genes encoding proteins involved in transport and the cytoskeleton, with the goal of developing therapeutic intervention strategies for a subset of SZ cases. [ABSTRACT FROM AUTHOR]

This study presents the enfortumab vedotin (EV) treatment analysis at our institution. We retrospectively analyzed patients with metastatic urothelial cancer (mUC) treated with EV between January 2021 and October 2023. EV was administered at 1.25 mg/kg on days 1, 8, and 15 in a 28-day cycle. Whole-body computed tomography scans were performed to assess the treatment response. Patient characteristics, treatment histories, response rates, progression-free survival, and adverse events were evaluated. Response rates were determined, and adverse events were recorded. Among the 20 patients, 70% were male and 65% had bladder tumors. Most patients had lung (65%) or lymph node (65%) metastases. The median follow-up was 11.2 months, with 45% of the patients succumbing to the disease. The overall response rate was 55%. The median progression-free and median overall survivals were 10.5 and 12.9 months, respectively. Severe adverse events occurred in 35% of patients. In this real-world study, EV demonstrated promising efficacy and manageable safety profiles in Japanese patients with mUC. The study's results were consistent with previous clinical trials, although a longer follow-up was required. Our findings support EV use as a treatment option for patients with mUC who exhibit disease progression after platinum-based chemotherapy and immune-checkpoint inhibitor therapy. [ABSTRACT FROM AUTHOR]

Strabismus, a neuro-ophthalmological condition characterized by misalignment of the eyes, is a common ophthalmic disorder affecting both children and adults. In our previous study, we identified the microsomal glutathione S-transferase 2 (MGST2) gene as one of the potential candidates for comitant strabismus susceptibility in a Japanese population. The MGST2 gene belongs to the membrane-associated protein involved in the generation of pro-inflammatory mediators, and it is also found in the protection against oxidative stress by decreasing the reactivity of oxidized lipids. To look for the roles of the MGST2 gene in the development, eye alignment, and overall morphology of the eye as the possible background of strabismus, MGST2 gene knockout (KO) mice were generated by CRISPR/Cas9-mediated gene editing with guide RNAs targeting the MGST2 exon 2. The ocular morphology of the KO mice was analyzed through high-resolution images obtained by a magnetic resonance imaging (MRI) machine for small animals. The morphometric analyses showed that the height, width, and volume of the eyeballs in MGST2 KO homozygous mice were significantly greater than those of wild-type mice, indicating that the eyes of MGST2 KO homozygous mice were significantly enlarged. There were no significant differences in the axis length and axis angle. These morphological changes may potentially contribute to the development of a subgroup of strabismus. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer increases the risk of venous thrombosis (VTE) and anticoagulant therapy is often used to treat this condition. Therefore, it is essential to identify risk factors for bleeding events in these patients. In our study, we used data from the Rising-VTE/NEJ037 study, which involved Japanese patients with advanced lung cancer, to calculate these risk factors. We found that complications with VTE were the most significant risk factor. This finding underscores the importance of carefully assessing the risks and benefits before starting anticoagulant therapy in patients with cancer. Our research aims to inform safer treatment strategies for patients with advanced lung cancer, which could have meaningful implications for their care and treatment approaches in the research community. Despite the occurrence of various hemorrhagic events during advanced lung cancer treatment, few researchers have reported on their risk factors. Moreover, the development of cancer-related thromboembolism indicates anticoagulant use. However, adverse events such as bleeding should be monitored. In this study, we aimed to identify factors that influence the onset of hemorrhagic events in patients with lung cancer. The Rising-VTE/NEJ037 study was a multicenter, prospective, observational study. A total of 1008 patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Multivariate analysis using a Cox proportional hazard model was performed to compare the outcomes of the time to the onset of hemorrhagic events for 2 years after registration. Hemorrhagic events occurred in 115 patients (11.4%), with 35 (30.4%) experiencing major bleeding. Significant risk factors included venous thromboembolism (VTE) (hazard ratio [HR]: 4.003, p < 0.001) and an Eastern Cooperative Oncology Group Performance Status score of 1 (HR: 2.476, p < 0.001). Factors that significantly reduced hemorrhagic event risk were female sex (HR: 0.454, p = 0.002) and M1a status (HR: 0.542, p = 0.038). VTE is a risk factor for hemorrhagic events in patients with advanced lung cancer, and risks associated with anticoagulant therapy should be considered. [ABSTRACT FROM AUTHOR]