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Abstract Background It has been suggested that the association between body mass index and breast cancer risk differs between Asian women and Western women. We aimed to assess the associations between body mass index and breast cancer incidence in East Asian women. Methods Pooled analyses were performed using individual participant data of 319,189 women from 13 cohort studies in Japan, Korea, and China. Participants’ height and weight were obtained by measurement or self-reports at cohort baseline. Breast cancer was defined as code C50.0-C50.9 according to the International Classification. Using a Cox proportional hazards model, hazard ratios of breast cancer were estimated for each body mass index category, with the reference group set as the group with a body mass index of 21 to

Abstract Van der Waals (vdW) two-dimensional (2D) materials have unleashed unprecedented opportunities to probe emerging physics that could be potential candidates for various functional applications. In particular, vdW 2D magnetic materials exhibit significant potential for advanced spintronic devices. Recently, Fe3GaTe2 has been discovered to possess the room-temperature ferromagnetic property with an intrinsic perpendicular magnetic anisotropy (PMA). Furthermore, considerably large anomalous Hall and Nernst angles have been reported recently. These groundbreaking findings pave the way for significant advances in high density random-access memory as well as energy harvesting devices based on spin conversion. Enhancements in the PMA and Curie temperature contribute to improved performance with reliable operation in a wide temperature range above room temperature. Moreover, the exploration of giant anomalous Hall and Nernst angles is a crucial factor for the efficient operation of spintronic devices. In this study, we demonstrate that the application of pressure to the Fe3GaTe2 2D ferromagnetic film strengthens the interlayer coupling, resulting in an improved PMA property. In addition, the application of pressure has been found to significantly increase the anomalous Hall angle. Our findings suggest that the application of pressure effectively controls the vdW interlayer coupling, thereby manipulating the ferromagnetic and spin-conversion properties of the 2D materials.

Abstract In ferromagnetic metal (FM)/non-magnetic metal (NM) bilayer structures, dynamical spin injection is primarily attributed to spin pumping at the interface. However, thermal effects, such as the spin (dependent) Seebeck effect (S(d)SE) caused by FMR heating effect, are also expected to contribute, particularly farther from the interface within the FM layer. In this study, the detailed mechanism of dynamical spin injection in CoFeB/Pt bilayer films has been investigated. We demonstrate the proper evaluation of the CoFeB thickness dependence of inverse spin Hall voltage by subtracting the signal from single CoFeB system. The dynamical spin injection and FMR heating effect were observed to significantly depend on thickness. Additionally, we separated the contributions of SSE and SdSE by focusing on their diffusion properties and found that SSE is larger than SdSE in the CoFeB/Pt bilayer film.

Background: We prospectively examined the associations of total fat and fatty acid intake with type 2 diabetes (T2D) among Japanese adults. Methods: This study was conducted using data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC). A validated food frequency questionnaire evaluated the intake of total fat and fatty acids. Diabetes was assessed using self-reported data. Multivariable logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of incident T2D across quintiles of total fat and fatty acid intake after adjusting for potential confounders. Results: A total of 19,088 non-diabetic participants (age range, 40–79 years) enrolled in the JACC between 1988 and 1990 were included in this study. During the 5-year study period, 494 the participants developed T2D. The OR of T2D for the highest versus lowest quintiles was 0.58 (95% CI, 0.37–0.90) for total fat, 0.78 (95% CI, 0.51–1.20) for saturated fatty acid (SFA), 0.55 (95% CI, 0.35–0.86) for monounsaturated fatty acids (MUFA), 0.61 (95% CI, 0.39–0.96) for polyunsaturated fatty acids (PUFA), 0.64 (95% CI, 0.42–0.99) for n-3 PUFA, and 0.70 (95% CI, 0.45–1.09) for n-6 PUFA. Total fat and fatty acid (except SFA and n-6 PUFA) intake were inversely associated with T2D in men. Total fat and fatty acid intake were not associated with T2D in women. Conclusion: Higher intakes of total fats, MUFA, PUFA, and n-3 PUFA were inversely associated with T2D among Japanese men.

Abstract Strongly-interacting nanomagnetic arrays are ideal systems for exploring reconfigurable magnonics. They provide huge microstate spaces and integrated solutions for storage and neuromorphic computing alongside GHz functionality. These systems may be broadly assessed by their range of reliably accessible states and the strength of magnon coupling phenomena and nonlinearities. Increasingly, nanomagnetic systems are expanding into three-dimensional architectures. This has enhanced the range of available magnetic microstates and functional behaviours, but engineering control over 3D states and dynamics remains challenging. Here, we introduce a 3D magnonic metamaterial composed from multilayered artificial spin ice nanoarrays. Comprising two magnetic layers separated by a non-magnetic spacer, each nanoisland may assume four macrospin or vortex states per magnetic layer. This creates a system with a rich 16 N microstate space and intense static and dynamic dipolar magnetic coupling. The system exhibits a broad range of emergent phenomena driven by the strong inter-layer dipolar interaction, including ultrastrong magnon-magnon coupling with normalised coupling rates of $$\frac{\Delta f}{\nu }=0.57$$ Δ f ν = 0.57 , GHz mode shifts in zero applied field and chirality-control of magnetic vortex microstates with corresponding magnonic spectra.

Abstract Objective Eculizumab and ravulizumab are complement protein C5 inhibitors, showing efficacy and tolerability for patients with anti‐acetylcholine receptor‐positive (AChR+) generalized myasthenia gravis (gMG) in phase 3 clinical trials and subsequent analyses. The purpose of the present study was to evaluate the clinical significance of eculizumab and switching to ravulizumab for refractory AChR+ gMG patients in the real‐world experience. Methods Among the database of Japan MG registry survey 2021, we studied AChR+ gMG patients who received eculizumab. We also evaluated these patients who switched from eculizumab to ravulizumab. Responder was defined as an improvement of at least 3 points in MG‐ADL. We performed a questionnaire of preference between eculizumab and ravulizumab. Results Among 1,106 patients with AChR+ gMG, 36 patients (3%) received eculizumab (female 78%, mean age 56.0 years). Eculizumab was preferentially used in severe and refractory MG patients. The duration of eculizumab treatment was 35 months on average. MG‐ADL improved from 9.4 ± 4.9 to 5.9 ± 5.1, and 25 (70%) of the 36 gMG patients were responders. Postintervention status was markedly improved after the eculizumab treatment. Of 13 patients who did not continue eculizumab, 6 showed insufficiencies. Early onset MG was most effective. However, 15 patients switching from eculizumab to ravulizumab kept favorable response and tolerability. Questionnaire surveys showed preference for ravulizumab over eculizumab. Interpretation Eculizumab and switching to ravulizumab showed to be effective for refractory AChR+ gMG patients in clinical settings.

Abstract Background Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. Methods We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. Results Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. Conclusion Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.

Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by the genomic expansion of CTG repeats, in which RNA-binding proteins, such as muscleblind-like protein, are sequestered in the nucleus, and abnormal splicing is observed in various genes. Although abnormal splicing occurs in the brains of patients with DM1, its relation to central nervous system symptoms is unknown. Several imaging studies have indicated substantial white matter defects in patients with DM1. Here, we performed RNA sequencing and analysis of CTG repeat lengths in the frontal lobe of patients with DM1, separating the gray matter and white matter, to investigate splicing abnormalities in the DM1 brain, especially in the white matter. Several genes showed similar levels of splicing abnormalities in both gray and white matter, with an observable trend toward an increased number of repeats in the gray matter. These findings suggest that white matter defects in DM1 stem from aberrant RNA splicing in both gray and white matter. Notably, several of the genes displaying abnormal splicing are recognized as being dominantly expressed in astrocytes and oligodendrocytes, leading us to hypothesize that splicing defects in the white matter may be attributed to abnormal RNA splicing in glial cells.

Background: For therapeutic efficacy, molnupiravir and nirmatrelvir-ritonavir must be started to treat patients within 5 days of disease onset to treat patients with novel coronavirus disease 2019 (COVID-19). However, some patients spend more than 5 days from disease onset before reporting to the Public Health Office. This study aimed to clarify the characteristics of patients with reporting delay. Methods: This study included data from 12,399 patients with COVID-19 who reported to the Public Health Office from March 3rd, 2021 to June 30th, 2021. Patients were stratified into “linked” (n = 7,814) and “unlinked” (n = 4,585) cases depending on whether they were linked to other patients. A long reporting delay was defined as the difference between the onset and reporting dates of 5 days or more. Univariate and multivariate analyses were performed using log-binomial regression to identify factors related to long reporting delay, and prevalence ratios with corresponding 95% confidence intervals were calculated. Results: The proportion of long reporting delay was 24.4% (1,904/7,814) and 29.3% (1,344/4,585) in linked and unlinked cases, respectively. Risks of long reporting delay among linked cases were living alone and onset on the day with a higher 7-day daily average confirmed cases or onset on weekends; whereas, risks for unlinked cases were age over 65 years, without occupation, and living alone. Conclusion: Our results suggest the necessity to establish a Public Health Office system that is less susceptible to the rapid increase in the number of patients, promotes educational activities for people with fewer social connections, and improves access to health care.

Artificial multiferroic heterostructures, that is to say, ferromagnetic/ferroelectric heterostructures, have been the subject of considerable research interest as a potential material basis for the creation of novel energy-efficient device applications. Given that polarization reversal occurs in ferroelectric materials when an electric field is applied, it is possible to modulate the magnetic properties of a ferromagnetic layer due to changes in the polarization charge associated with a ferroelectric material, or due to exchange coupling, ionic transport, or orbital hybridization at the interface between the ferromagnetic and ferroelectric materials. Another essential characteristic of ferroelectric materials is their inverse piezoelectricity, which induces strain through the application of an electric field. The inverse piezoelectric strain is transferred to the ferromagnetic layer, thereby modulating the magnetic properties due to the magnetoelastic effect. In comparison to the various effects, the influence of strain transfer on magnetic properties is particularly pronounced, offering promising avenues for controlling magnetic properties via an electric field without the use of an electric current. This review article aims to present an overview of recent developments in the field of electric field effects on magnetic properties, with a particular focus on the role of strain transfer in magneto-electric effects. The potential applications of artificial multiferroic heterostructures are discussed, including the control of magnetic anisotropy, as well as the manipulation of perpendicular magnetic anisotropy, magnetoresistance, interlayer exchange coupling, spin wave propagation, spin damping, magnetic phase, and superconductivity. The article concludes with a consideration of the future prospects of artificial multiferroic heterostructures for next-generation device applications.

Objectives: This study investigated the association between depressive symptoms and the instrumental activities of daily living (IADL) decline among physically and socially independent older people according to being employed or participating in social activities in a Japanese age-specific cohort. Methods: We performed a prospective cohort study including 1,508 (716 men and 792 women) aged 64/65. Depressive symptoms were assessed at baseline (2000–2005). The change in IADL status was ascertained in the secondary survey when the participants reached 70 years of age. Multivariable odds ratios (ORs) and confidence intervals (CIs) of depressive symptoms for IADL decline were calculated using a logistic regression model adjusted for enroll year, sex, employment status, marital status, education, smoking status, alcohol consumption status, body mass index, walking status, daily sleep duration, and medical histories of cancer, cardio-cerebrovascular diseases, hypertension, and diabetes mellitus. We also formally tested for potential interaction effects by employment and participation in social activities. Results: The OR of the presence of depressive symptoms and not employed was 3.25 (95% CI 1.57–6.75), compared to participants without depressive symptoms and employed, after adjusting for potential confounders. Compared to participants without depressive symptoms and with a high frequency of participation in social activities, participants with depressive symptoms and a low frequency of participation in social activities were associated with IADL decline (OR 2.45; 95% CI 1.23–4.90). However, we observed no evidence of an interaction effect by employment and participation in social activities. Conclusions: This age-specific cohort study revealed that being employed or participating in social activities may prevent IADL decline among depressed older adults.

Aim: This study investigated the association between participation in social activities and incident dementia among physically and socially independent older adults with or without diseases (hypertension and/or diabetes mellitus) in a Japanese age-specific cohort (the NISSIN Project). Methods: We conducted a prospective cohort study of 1,856 Japanese individuals (953 men and 903 women) aged 64/65 years. Information on medical status, demographics, and lifestyle characteristics was collected using a baseline questionnaire and health checkup (2000–2005). Incident dementia were confirmed among these received long-term care certifications using the nationally standardized dementia scale proposed by the Ministry of Health, Labor, and Welfare. A competing risk model was used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) for dementia incidence. We treated the censored cases of death as competing events. Results: During a median of 16.0 years of follow-up, incident dementia occurred in 332 participants. The presence of diseases and nonparticipation in social activities were associated with a significantly higher risk of incident dementia (HR 1.65; 95 % CI 1.21–2.26) after adjusting for potential confounders compared with participants without diseases and those who participated in social activities. Conclusions: In this age-specific cohort study, participants with diseases and those who did not participate in social activities were more likely to have incident dementia than those without diseases and those who participated in social activities. For older people with hypertension and/or diabetes mellitus, engaging in social activities could be a beneficial strategy for reducing the risk of developing dementia.

Abstract Background An elevated neutrophil‐to‐lymphocyte ratio (NLR) in peripheral blood is an independent prognostic indicator of various cancers. Aims In this study, we aimed to investigate the prognostic relevance of the intratumoral immune cell balance in gastric cancer. Methods and Results The study included 82 patients who underwent curative resection for gastric cancer. The intratumoral cluster of differentiation (CD) 15‐ and CD8‐positive cells were evaluated using immunohistochemical staining. Additionally, clinicopathological factors and prognoses were analyzed. Patients with high intratumoral CD15/CD8 ratios had significantly lower overall survival (OS) and relapse‐free survival (RFS) compared to those with low CD15/CD8 ratios (p = .0026 and p

Abstract Background Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. Methods A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow‐up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random‐effects meta‐analyses. Results Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06–1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07–1.60 vs 1.12, 1.01–1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02–1.28 vs 1.17, 0.77–1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02–1.46 vs 1.00, 0.62–1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77–5.86), and decreased with time (nonlinear p

Abstract Nanoscale soft-X-ray microscopy is a powerful analysis tool in biological, chemical, and physical sciences. To enhance its probe sensitivity and leverage multimodal soft-X-ray microscopy, precise achromatic focusing devices, which are challenging to fabricate, are essential. Here, we develop an ultracompact Kirkpatrick-Baez (ucKB) mirror, which is ideal for the high-performance nanofocusing of broadband-energy X-rays. We apply our advanced fabrication techniques and short-focal-length strategy to realize diffraction-limited focusing over the entire soft-X-ray range. We achieve a focus size of 20.4 nm at 2 keV, which represents a significant improvement in achromatic soft-X-ray focusing. The ucKB mirror extends soft-X-ray fluorescence microscopy by producing a bicolor nanoprobe with a 1- or 2-keV photon energy. We propose a subcellular chemical mapping method that allows a comprehensive analysis of specimen morphology and the distribution of light elements and metal elements. ucKB mirrors will improve soft-X-ray nanoanalyses by facilitating photon-hungry, multimodal, and polychromatic methods, even with table-top X-ray sources.

Background: While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. Methods: We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. Results: We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07–1.40), 1.22 (95% CI, 1.09–1.36), and 1.27 (95% CI, 1.08–1.49), respectively, in men and 1.21 (95% CI, 1.09–1.35), 1.23 (95% CI, 1.08–1.40), and 1.35 (95% CI, 1.003–1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. Conclusion: This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Background: The neurological prognosis of asphyxia is poor and the effect of advanced airway management (AAM) in the prehospital setting remains unclear. This study aimed to evaluate the association between AAM with adrenaline injection and prognosis in adult patients with asystole asphyxia out-of-hospital cardiac arrest (OHCA). Methods: This study assessed all-Japan Utstein cohort registry data between January 1, 2013 and December 31, 2019. We used propensity score matching analyses before logistic regression analysis to evaluate the effect of AAM on favorable neurological outcome. Results: There were 879,057 OHCA cases, including 70,299 cases of asphyxia OHCAs. We extracted the data of 13,642 cases provided with adrenaline injection by emergency medical service. We divided 7,945 asphyxia OHCA cases in asystole into 5,592 and 2,353 with and without AAM, respectively. After 1:1 propensity score matching, 2,338 asphyxia OHCA cases with AAM were matched with 2,338 cases without AAM. Favorable neurological outcome was not significantly different between the AAM and no AAM groups (adjusted odds ratio [OR] 1.1; 95% confidence interval [CI], 0.5–2.5). However, the return of spontaneous circulation (ROSC) (adjusted OR 1.7; 95% CI, 1.5–1.9) and 1-month survival (adjusted OR 1.5; 95% CI, 1.1–1.9) were improved in the AAM group. Conclusion: AAM with adrenaline injection for patients with asphyxia OHCA in asystole was associated with improved ROSC and 1-month survival rate but showed no differences in neurologically favorable outcome. Further prospective studies may comprehensively evaluate the effect of AAM for patients with asphyxia.

Abstract Background The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. Methods This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. Results Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66–1.13] compared to 0.60 [0.49–0.73], 0.46 [0.38–0.56] and 0.62 [0.51–0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14–1.84] compared to 1.25 [0.99–1.58], 1.06 [0.85–1.32] and 0.86 [0.69–1.08]) and alcohol consumption (1.22 [1.01–1.48] compared to 1.10 [0.90–1.33], 1.15 [0.96–1.38], and 1.07 [0.91–1.26]). Conclusion We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

AbstractYKL-40 is implicated in inflammation and tissue repair, but no reports have investigated its involvement in myositis in polymyositis (PM) and dermatomyositis (DM). Therefore, we aimed to investigate the relationship between YKL-40 and PM/DM. We retrospectively enrolled 35 patients diagnosed with PM/DM along with 26 healthy controls (HCs). Both PM and DM were diagnosed according to Bohan and Peter’s criteria. Serum YKL-40 levels were measured, age-corrected to YKL-40 percentile values, and compared to HCs. Patients with myositis without interstitial lung disease were also enrolled and compared to HCs. Immunofluorescence staining was performed to identify YKL-40-positive inflammatory cells in muscle biopsy samples from two patients each with PM and DM. Age-corrected serum YKL-40 levels were significantly higher in patients with PM/DM compared to HCs with and without lung disease; however, these levels decreased significantly after treatment. Immunohistochemical analysis showed infiltration of YKL-40-positive inflammatory cells into the intramuscular sheath and perimuscular membrane. Immunofluorescence staining showed CD68 expression in YKL-40-positive inflammatory cells, suggesting that these cells were macrophages. To the best of our knowledge, this is the first study to demonstrate that YKL-40-positive macrophages are present in PM and DM, indicating that YKL-40 may be involved in PM/DM.

The relationship between participation in extracurricular school club activities in adolescence and subsequent depressive state experiences in adulthood, after joining the workforce, is unclear. The present study aimed to explore this relationship in new recruits of the Japan Ground Self-Defense Force (JGSDF). In April 2013, 925 recruits of the JGSDF, all of whom were male and aged 18–27 years, were enrolled. Club activity status during high school was categorized as follows: participated in sports club, participated in nonsport club, or no club participation. Depressive symptoms were assessed with the 20-item version of the Center for Epidemiologic Studies Depression Scale (CES-D), at the baseline survey and a second survey conducted 2 months later, in June 2013. Analysis of covariance was used for association between club activity status and changes in CES-D scores. After a 2-month period, results showed a significantly higher average of CES-D score changes for participants in nonsport club activities (β = 3.90, 95% confidence interval = 2.22–6.71) or those with no club activities (β = 2.24, 95% confidence interval = 0.20–2.94), compared to those who participated in a sports club. These findings were adjusted for age, baseline CES-D score, regular exercise, smoking status, alcohol consumption, sleep duration, and breakfast habits. Recruits without a history of sports club participation may be at higher risk of developing depressive symptoms than those who participated in a sports club. Our results may be useful for the early detection of people who are susceptible to depression engaged in occupations such as the JDSF.

Most adult cases of hen's egg allergy are carried over from childhood, and new-onset adult cases are rare. Such cases may result from cross-reactivity or sensitization by inhalation. Here we present a rare case of adult-onset egg allergy due to monosensitization to ovalbumin (Gal d 2) with an unclear sensitization pathway. A 27-year-old woman developed recurrent gastrointestinal symptoms after ingestion of raw and under-cooked eggs. She had never suffered from atopic dermatitis or food allergies. She had never kept birds as pets and had no history of exposure to egg allergens. Prick to prick testing was positive only with raw egg white. Specific IgE testing revealed monosensitization to Gal d 2. She was advised to avoid raw and undercooked eggs and her symptoms resolved. In the management of adult-onset egg allergy, evaluation of allergen components will lead to appropriate elimination guidelines, and investigation of sensitization pathways may help identify the cause of this disease.

Background: Although cigarette smoking is an established risk factor for bladder cancer, assessment of smoking impact on bladder cancer in Asian populations has been hindered by few cohort studies conducted in Asian populations. Therefore, we investigated the risk of bladder cancer associated with smoking status, cumulative smoking intensity, and smoking cessation in Japan. Methods: We analyzed data for 157,295 men and 183,202 women in 10 population-based cohort studies in Japan. The risk associated with smoking behaviors was estimated using Cox regression models within each study, and pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for the incidence of bladder cancer were calculated. Results: During 4,729,073 person-years of follow-up, 936 men and 325 women developed bladder cancer. In men, former smokers (HR 1.47; 95% CI, 1.18–1.82) and current smokers (HR 1.96; 95% CI, 1.62–2.38) had higher risk than never smokers. In women, current smokers had higher risk than never smokers (HR 2.35; 95% CI, 1.67–3.32). HRs in men linearly increased with increasing pack-years. Risk decreased with increasing years of smoking cessation in men, with a significant dose-response trend. Former smokers with a duration of more than 10 years after smoking cessation had no significantly increased risk compared with never smokers (HR 1.26; 95% CI, 0.97–1.63). Conclusion: Data from a pooled analysis of 10 population-based cohort studies in Japan clearly show an association between cigarette smoking and bladder cancer risk. The risk of smokers may approximate that of never smokers following cessation for many years.

Equine herpesvirus-1 (EHV-1) causes respiratory diseases, abortion, and encephalomyelitis in horses. The EHV-1 immediate-early (IE) protein, essential for viral replication, is transactivated by the binding of a multiprotein complex including the open reading frame 12 (ORF12) and some host factors to the IE promoter region. Promoter-associated non-coding RNAs (pancRNAs), which are transcribed from bidirectional promoters, regulate the transcription of neighboring genes in mammals and pathogens. In this study, we identified a novel pancRNA transcribed from across the areas of the 5′-untranslated region and a promoter of EHV-1 IE and named it IE pancRNA. IE pancRNA and mRNA were simultaneously expressed in EHV-1-infected RN33B-A68B2M cells. This pancRNA was also transcribed in RK13 and E. Derm cells, which are highly susceptible to EHV-1 infection. Furthermore, IE pancRNA upregulated IE gene expression in the presence of ORF12, and stable expression of IE pancRNA increased the number of EHV-1-infected RN33B-A68B2M cells. These results suggest that IE pancRNAs facilitate EHV-1 proliferation by promoting IE gene expression.

We conducted a cross-sectional survey among SARS-CoV-2–positive persons and negative controls in Sapporo, Japan, to clarify symptoms of long COVID. We collected responses from 8,018 participants, 3,694 case-patients and 3,672 controls. We calculated symptom prevalence for case-patients at 2–3, 4–6, 7–9, 10–12, and 13–18 months after illness onset. We used logistic regression, adjusted for age and sex, to estimate the odds ratio (OR) for each symptom and control reference. We calculated symptom prevalence by stratifying for disease severity, age, and sex. At 4–18 months from illness onset, ORs for anosmia, ageusia, dyspnea, alopecia, and brain fog were consistently >1, whereas ORs for common cold–like, gastrointestinal, and dermatologic symptoms were

Abstract The aim of cross-sectional study was to investigate whether the presence of autistic traits in pregnant women was positively associated with the prevalence and severity of antenatal pain. We analyzed 89,068 pregnant women from a Japanese national birth cohort cross-sectionally. Autistic traits were assessed using the Japanese version of the Autism-Spectrum Quotient short form (AQ-10-J). Antenatal pain was measured using the SF-8 bodily pain item (SF-8-Pain). Antenatal pain in the second to third trimester during pregnancy was categorized into three groups: without pain, mild pain, and moderate-to-severe pain. Participants were divided into eight groups by AQ-10-J score: seven consecutive scoring groups (scores 0–6), and those above the cut-off (≥ 7) for probable autistic spectrum disorders. Odds ratios (OR) for the prevalence of mild and moderate-to-severe pain were calculated for each AQ-10-J scoring group (reference: without pain group) using multinominal logistic regression analysis. Autistic traits were positively associated with mild and moderate-to-severe pain in a dose–response manner, but the association with moderate-to-severe pain was strongest. Fully-adjusted ORs (95% confidence intervals) for moderate-to-severe pain were: 1.01 (0.91–1.13) for 1 point, 1.13 (1.02–1.25) for 2 points, 1.16 (1.04–1.29) for 3 points, 1.20 (1.07–1.34) for 4 points, 1.23 (1.09–1.40) for 5 points, 1.27 (1.10–1.47) for 6 points, and 1.24 (1.05–1.46) for ≥ 7 points (AQ-10-J cut-off). We identified an association between maternal autistic traits and antenatal pain. Maternal autistic traits may need to be considered when addressing antenatal pain during healthcare for expectant mothers.

Abstract In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review and meta-analysis of published studies evaluating patient response to antiviral therapy for chronic hepatitis C on the risk of HCC occurrence in Japan. Articles were searched using terms determined a priori through PubMed, screened by title and abstract, and selected by full-text assessment according to criteria determined a priori, including HCC occurrence in response to interferon (IFN)-based or IFN-free therapy, Japanese study, and 2 or more years of follow-up. We excluded studies on HCC recurrence. We calculated the pooled estimate of the crude incidence rate ratio with data from the selected studies using the person-years method with Poisson regression model and pooled estimate of the hazard ratio adjusted for potential confounders reported by the studies using a random effects model. A total of 26 studies were identified, all of which examined only IFN-based therapy as a result of the selection process. The pooled estimate (95% confidence interval [CI]) of 25 studies was 0.37 (0.33–0.43) for sustained virologic response (SVR) and 1.70 (1.61–1.80) for non-SVR for the HCC incidence rate per 100 person-years, and 0.22 (0.19–0.26) for the incidence rate ratio (SVR vs. non-SVR). The pooled estimate of the hazard ratio (95% CI) of HCC incidence adjusted for potential confounders of 8 studies was 0.25 (0.19–0.34). SVR to interferon therapy for chronic hepatitis C reduces the risk of HCC occurrence.

Background: Prenatal exposure to metallic elements may adversely affect early childhood health. However, more evidence is needed as population-based cohort studies are currently limited. Objectives: We aimed to examine the associations between prenatal metallic (mercury, selenium, and manganese) exposure and the risk of allergic diseases in early childhood until three years of age. Methods: The data from 94,794 mother-infant pairs, who participated in the Japan Environment and Children’s study, were used in this study. Prenatal metallic element exposure was measured in maternal blood collected during mid-pregnancy. The incidence of atopic dermatitis, food allergies, asthma, and allergic rhinitis during the first three years of life was prospectively investigated using self-reports of physician-diagnosed allergies. A multivariable modified Poisson regression model was used to estimate the cumulative incidence ratio and their 95% confidence intervals of allergic diseases associated with prenatal exposure to mercury, selenium, and manganese. We further evaluated the interaction between mercury and selenium exposures in this association. Results: We confirmed 26,238 cases of childhood allergic diseases: atopic dermatitis, food allergies, asthma, and allergic rhinitis in 9,715 (10.3%), 10,897 (11.5%), and 9,857 (10.4%), 4,630 (4.9%), respectively. No association was found between prenatal mercury or manganese exposure and the risk of allergic diseases. Prenatal selenium exposure was inversely associated with atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases, but not with asthma. These inverse associations were more pronounced for lower mercury exposures than for higher exposures. Conclusions: Our findings suggest that prenatal exposure to selenium may be beneficial for reducing the risk of atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases in early childhood, especially with lower prenatal mercury exposure.

Abstract Background The Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related northern hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious diseases, notably infectious diseases from which Australia has been largely shielded. Unlike mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to highly pathogenic avian influenza. Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information. Results Here, we generate the first chromosome-length black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We use these genomes and transcriptomes to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to highly pathogenic avian influenza. We also implicate genetic differences in SLC45A2 gene in the iconic plumage of the black swan. Conclusion Together, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat, the black swan would be in a significant peril.

Background: Fermented soybean (natto)-induced hypersensitivity reactions (natto allergy) are rare and can result in late-onset anaphylaxis. The allergen in natto is considered to be poly-γ-glutamic acid (PGA), and marine sports are a risk factor for natto allergy due to epicutaneous sensitization to PGA from cnidarian stings. However, no research on natto allergy in fishery workers has yet been performed. Methods: We conducted a chart review of inpatients diagnosed with anaphylaxis due to natto at Hokkaido Prefectural Haboro Hospital between April 1, 2009, and August 31, 2020. We also administered self-report questionnaires about food hypersensitivity reactions to Japanese fishery workers, including members of the Kitarumoi Fishery Cooperative Association and part-time workers in this area, from February 1 to May 31, 2021. Results: We found six inpatients (29 inpatients with food-induced anaphylaxis among approximately 11,000 community-dwelling residents) with late-onset anaphylaxis due to natto; all were involved in scallop aquaculture. The questionnaires revealed that 27 participants had natto allergy. We divided the fishery workers into a scallop aquaculture (Scallop) group (n = 211) and other fishery group (n = 106). The Scallop group was significantly associated with natto allergy after adjustments for confounders (OR: 5.73, 95% CI: 1.46–22.56) by logistic regression analysis. In the Scallop group, older age, experience in repairing nets, and a longer length of work experience were significantly related to participants with natto allergy (n = 23), but not participants without natto allergy (n = 181). Conclusions: Our results indicated an association between scallop aquaculture and natto allergy.

Abstract This study examined the association between coronavirus disease 2019 (COVID-19)-related stress, exercise habits, and oral health-related quality of life (OHRQoL) in a sample of 215 community-dwelling older adults in Japan (57 men, 158 women; M age = 74.2 years, SD = 6.0). Data were collected during wellness checkups in October 2020 and included participants’ demographic characteristics, measures of instrumental activities of daily living and depressive tendencies, number of teeth, oral hypofunction, OHRQoL, COVID-19-related stress, and exercise habits. Four mutually exclusive groups were created, using the presence or absence of COVID-19-related stress and lack of exercise habits as risk factors for poor OHRQoL (no COVID-19-related stress and no lack of exercise, COVID-19-related stress only, lack of exercise habits only, and both COVID-19-related stress and lack of exercise habits). Poisson regression with robust standard errors provided the prevalence ratio for poor OHRQoL. The presence of both COVID-19-related stress and lack of exercise habits (adjusted prevalence ratio: 2.20, 95% CI: 1.31– 3.69) was associated with poor OHRQoL. The results indicate that COVID-19-related stress and exercise habits should be considered when designing oral health and public health initiatives.

This study investigated the size–frequency distribution of 512 landslides triggered by heavy rain in July 2018 on Omishima Island, western Japan. Since the island has undergone rapid land use and land cover changes in recent decades, this study statistically examined the impact of past land cover changes on the shape of, and local variability in, the size–frequency distribution using the inverse gamma model. The possible influence of rainfall conditions was also examined. The landslides were classified based on the severity of anthropogenic disturbance and rainfall using a 56-year (1962–2018) land cover trajectory map and hourly rainfall distribution data. The results indicated that the land cover change (mainly forest conversion into farmland and its abandonment) affected the size and frequency of landslides that occurred decades after the disturbance. Although all landslide groups had similar small rollovers (location of probability peak; 0.042–0.075 × 10−3 km2), the scaling exponents of the negative power-law decay were lower for landslides in secondary forest and newly developed farmland (ρ = 1.084–1.231) than in old forest and farmland (ρ = 2.504–2.611). This difference is considered significant compared to general exponent values (ρ = 2.30 ± 0.56), suggesting that farmland development after 1962 caused widespread slope instability, leading to an increase in the proportion of large landslides. By contrast, no clear correlations with rainfall intensity were found, primarily due to complex localised variations in rainfall conditions.

The timely and cost-effective identification of the onset of corrosion and its progress would be critical for effectively maintaining structural integrity. Consequently, a series of fundamental experiments were conducted to capture the corrosion process on a steel plate using a new type of plastic optical fiber (POF) sensor. Electrolytic corrosion experiments were performed on a 5 mm thick steel plate immersed in an aqueous solution. The POF sensor installed on the upper side of the plate and directed downward detected the upward progression of the corrosion zone that formed on the underside of the plate. The results showed that the POF sensors could detect the onset of the upward-progressing corrosion front as it passed the 1 and 2 mm marks related to the thickness of the corroded zone. The POF sensors were designed to optically identify corrosion; therefore, the data obtained by these sensors could be processed using a newly developed graphic application software for smartphones and also identified by the naked eye. This method offered an easy and cost-effective solution for verifying the corrosion state of structural components.

Abstract Aims/Introduction We investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre‐pregnancy body mass index (BMI) and/or gestational weight gain (GWG). Materials and Methods Data from the national birth cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM. Results The OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre‐pregnancy BMI of ≥25.0 kg/m2 and insufficient GWG (7.25 kg) was 2.04 (1.56–2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m2 in the GDM group than in the non‐GDM group. Conclusions Large for gestational age and hypertensive disorders of pregnancy were associated with pre‐pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m2 are at risk of having small for gestational age and large for gestational age infants depending on GWG.

Abstract A dynamical spin injection based on the ferromagnetic resonance in a ferromagnetic/nonmagnetic bi-layered structure, is a powerful mean for generating and manipulating the spin current. Although the mechanism of the dynamical spin injection is mainly attributed to the spin pumping, the detailed mechanism and the quantitative understanding for related phenomena are still controversial. As an another important contribution to the dynamical spin injection, the heating effect due to the resonant precessional motion of the magnetization is pointed out recently. In order to quantify the contribution from the heating effect, we here investigate the dynamical spin injection in a CoFeB/Pt/CoFeB trilayer. Although the contribution from the spin pumping diminishes because of the symmetric spin injection from the upper and lower interfaces, a significant inverse spin Hall voltage has been clearly observed. We show that the observed voltage can be quantitatively understood by the thermal spin injection due to a heating effect during the ferromagnetic resonance. A proper combination between the spin pumping and the heat-flow control in the multi-layered system is a key for the efficient dynamical spin injection.

Abstract Hemangiosarcoma (HSA) is a malignant tumor derived from endothelial cells. Tumor-associated macrophages are one of the major components of tumor microenvironment and crucial for cancer development. The presence and function of macrophages in HSA have not been studied because there is no syngeneic model for HSA. In this study, we evaluated two mouse HSA cell lines and one immortalized mouse endothelial cell line for their usefulness as syngeneic models for canine HSA. Our results showed that the ISOS-1 cell line developed tumors with similar morphology to canine HSA. ISOS-1 cells highly expressed KDM2B and had similar KDM2B target expression patterns with canine HSA. Moreover, we determined that in both ISOS-1 and canine HSA tumors, macrophages were present as a major constituent of the tumor microenvironment. These macrophages were positive for CD204, an M2 macrophage marker, and express PD-L1, an immune checkpoint molecule. Canine HSA with macrophages expressing PD-L1 had a smaller number of T-cells in tumor tissues than tumors with PD-L1 negative macrophages. ISOS-1-conditioned medium could induce M2 polarization and PD-L1 expression in RAW264.7 mouse macrophage cell line and mouse peritoneal macrophages. These results show that ISOS-1 can be used as a syngenic model for canine HSA and suggest that macrophages play an important role in immune evasion in HSA. Using the syngeneic mouse model for canine HSA, we can further study the role of immune cells in the pathology of HSA.

Abstract Background Sedentary behavior and decreased physical activity are associated with reduced kidney function, yet most evidence is based on self-reported physical activity. This study investigated the association between accelerometer-based physical activity level and kidney function in a general Japanese population. Methods A cross-sectional study was conducted in 440 community-dwelling Japanese participants, aged 35–79 years. Time (min/d) was assessed for the following types of physical activity: sedentary behavior, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Kidney function was assessed using estimated glomerular filtration rate (eGFR). A linear regression model was employed to calculate the β coefficient of eGFR for a 60-min/d increase in sedentary behavior and LPA and a 10-min/d increase in MVPA. A logistic regression model was used to calculate the odds ratio for low eGFR (

We prospectively examined the association between low-carbohydrate diet (LCD) score and incidence of type 2 diabetes (T2D) in Japanese adults using Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) data. A total of 19 084 (7052 men and 12 032 women) Japanese non-diabetic participants aged 40–79 years, who enrolled in the JACC study between 1988 and 1990, were included in our analysis. Dietary intake was evaluated using a validated food-frequency questionnaire. The overall, animal and vegetable LCD scores were calculated by dividing the study participants into eleven categories based on the percentages of energy from carbohydrates, protein and fat. The incidence of T2D was assessed using a self-administered questionnaire. We used multivariable logistic regression analysis to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) of incident T2D across the quintile of each LCD score, with adjustment for potential confounders. During the 5-year study period, 490 adults (247 men and 243 women) developed T2D. The multivariable-adjusted OR of incident T2D for the highest v. lowest quintiles of overall and animal LCD scores, respectively, were 0·64 (95 % CI 0·42, 0·99) and 0·83 (95 % CI 0·55, 1·27) for men, 0·78 (95 % CI 0·51, 1·18) and 0·84 (95 % CI 0·57, 1·24) for women. The vegetable LCD score was associated with a lower risk of T2D in men (OR 0·51; 95 % CI 0·33, 0·77). Our results suggest that diets lower in carbohydrates and higher in fat and protein are unlikely to higher the T2D risk among Japanese individuals.

Abstract Background Previous studies have demonstrated that some patients have spontaneous right atrium (RA)‐superior vena cava (SVC) conduction block, which could be utilized to isolate the SVC effectively by using the Rhythmia mapping system (Boston Scientific). However, employing this approach for SVC isolation using the CARTO electroanatomical mapping system (Biosense Webster) has not yet been clarified. This study aimed to evaluate the safety and efficacy of SVC isolation using the extended early meets late (EEML) tool with the CARTO system. Methods The patients who underwent SVC isolation using the CARTO system were enrolled in this study. The RA‐SVC conduction block was visualized with an EEML tool. We prospectively assessed the safety and efficacy of SVC isolation using this system. Results We analyzed 54 patients, and all SVCs were successfully isolated with no complications. Altogether, 44 patients (81.5%) had spontaneous RA‐SVC conduction block, and the remaining 10 patients (18.5%) did not. The block group required fewer radiofrequency deliveries for the SVC isolation than the nonblock group (10.7 ± 5.0 vs 15.5 ± 4.8, P = .009). The size of the isolated area in the block group was larger than that in the nonblock group (15.2 ± 5.1 cm2 vs 12.4 ± 2.5 cm2, P = .017). Conclusions Approximately 80% of the patients in this study developed a spontaneous RA‐SVC conduction block, which might contribute to shortening the time of ablation and avoiding complications.

Abstract Background Gait was proved to be strongly associated with global cognitive function and multiple cognitive domains; however, previous research usually concentrated on individual gait parameters. This study used wearable sensors to measure gait parameters in different aspects and comprehensively explored the association of gait with global cognitive function and cognitive domains. Methods The data of this cross-sectional study were obtained from 236 community-dwelling Japanese older adults (125 men and 111 women) aged 70–81 years. Gait was measured by asking participants to walk a 6-m course and back using the Physilog® sensors (GaiUp®, Switzerland). Global cognitive function and cognitive domains were evaluated by face-to-face interviews using the Japanese version of the Montreal Cognitive Assessment. Twenty gait parameters were summarized as independent gait factors using factor analysis. A generalized linear model and linear regression model were used to explore the relationship of gait with global cognitive function and cognitive domains adjusted for several confounding factors. Results Factor analysis yielded four gait factors: general cycle, initial contact, propulsion, and mid-swing. Among them, general cycle factor was significantly associated with global cognitive function (β = − 0.487, [− 0.890, − 0.085]) and executive function (P = 0.049); initial contact was associated with executive function (P = 0.017). Conclusion General cycle of gait might be the better marker of global cognitive function and gait is most strongly associated with executive function. The longitudinal relationships should be examined in future cohort studies.

Background: Previous research has established that women accumulate less moderate-to-vigorous physical activity (MVPA) than men. To date, however, little is known about the gender differences in device-based activity patterns of sedentary behavior (SB) and light-intensity physical activity (LPA). We aimed to compare time spent in SB and different intensities of physical activity taking into account of co-dependence of time use domains. Methods: This cross-sectional study was conducted in Suttu town, Hokkaido, Japan. Data were analyzed from 634 Japanese adults (278 men, aged 19–92 years) who provided valid accelerometer (HJA-750C) data. Gender differences in activity behavior patterns were tested using multivariate analysis of covariance (MANCOVA) based on isometric log-ratio transformations of time use, adjusting for age. We also developed bootstrap percentile confidence intervals (CI) to support the interpretation of which behavior differed between genders. Results: Overall, participants had percent time spent in SB, LPA, MVPA during wearing time (mean, 14.8 hours) corresponding to 53.9%, 41.7%, and 4.4% of wearing time, respectively. Activity behavior patterns differed significantly between genders after controlling for time spent in all activities. Women spent relatively 13.3% (95% CI, 9.9–15.9%) less time in SB and 19.8% (95% CI, 14.9–24.6%) more time in LPA compared to men. The difference of time spent in MVPA was not statistically significant. Conclusions: In contrast with previous studies, our findings suggest that Japanese women are more physically active than men when all intensities of activities are considered. Given the health benefits of LPA, evaluating only MVPA may disproportionately underestimate the level of physical activity of women.

Objectives To investigate whether having a purpose in life (Ikigai) is associated with risk of cardiovascular disease (CVD) mortality and whether the association varies by employment status.Design Prospective cohort study.Setting Residents in 45 municipalities, Japan.Participants 29 517 men and 41 984 women aged 40–79 years, free of CVD and cancer at baseline from 1988 to 1990.Primary outcome measures CVD mortality.Results During the median follow-up of 19.1 years, 4680 deaths (2393 men and 2287 women) from total CVD were observed. Greater Ikigai was associated with a lower risk of CVD mortality, and the result was stronger for men than for women. Stratified by employment status, the inverse association was confined to unemployed persons. Among unemployed persons, the multivariable HRs of total CVD were higher for moderate and high versus low levels of Ikigai. Multivariable HRs (95% CIs) were 0.74 (0.57 to 0.97) and 0.69 (0.52 to 0.93), P for trend

Maintaining physical and mental health of older people is one of the important issues to be addressed in the aging society. Social capital, defined as the resources available to members of social groups, has recently attracted attention as a factor influencing public health. Most of the previous studies targeted various communities having different aging rates or population densities at once to examine the associations of social capital and health outcomes. However, the results of those studies are not always consistent. Moreover, because few studies have targeted a particular advanced aging society, associations of social capital and health at such societies have remained unknown. This study examined how social capital associates with health at a particular city having a very high aging rate and low population density. We targeted Iwamizawa city, Hokkaido, Japan, which is one of the most advanced aging areas, with an aging rate of 36.6% and a population density of 165/km2. We analyzed self-administered questionnaire data obtained from “HELLO (HEalth, Lifestyle, and LOcal community of Iwamizawa citizen) Study” in 2018. The sample comprised 1237 individuals aged 65 and older. Following previous studies, we regarded three items—social cohesion, reciprocity, and civic participation—as social capital indices, and targeted two health outcomes: self-rated health (SRH) and degree of depression. Multilevel Poisson regression analyses were used to calculate prevalence ratios (PRs). We found that at the individual-level, the PR (95% confidence interval) of having poor SRH among those with more civic participation was 0.81 (0.71–0.93), and that of being depressed among those with more social cohesion was 0.32 (0.21–0.51), even after adjusting for compositional factors. We also found that the community-level civic participation significantly correlated with aging rate. Our findings indicate that social capital positively associates with older people's health at the advanced aging city.

Background: Reproductive history has been addressed as a risk factor for cardiovascular disease (CVD). We examined the relationship between reproductive history and CVD mortality in Japanese women. Methods: We followed 53,836 women without previous CVD or cancer history from 1988–1990 to 2009 in a prospective cohort study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of CVD mortality were estimated according to the number of deliveries and maternal age at first delivery. Results: During the follow-up, 2,982 CVD-related deaths were identified. There was U-shaped association between the number of deliveries and risk of CVD mortality with reference to three deliveries, although the excess risk of CVD mortality associated with ≥5 deliveries was of borderline statistical significance. The corresponding multivariable HRs were 1.33 (95% CI, 1.12–1.58) and 1.11 (95% CI, 0.99–1.24). In addition, higher CVD mortality was associated with maternal age ≥28 years at first delivery than maternal age of 24–27 years at first delivery. The multivariable HRs were 1.22 (95% CI, 1.10–1.36) for 28–31 years at first delivery and 1.26 (95% CI, 1.04–1.52) for ≥32 years at first delivery. Moreover, among women with ≥3 deliveries, maternal age ≥28 years at first delivery was associated with 1.2- to 1.5-fold increased CVD mortality. Conclusion: The number of deliveries showed a U-shaped association with risk of CVD mortality. Higher maternal age at first delivery was associated with an increased risk of CVD mortality, and excessive risk in women aged ≥28 years at first delivery was noted in those with ≥3 deliveries.