BOD1L mediates chromatin binding and non-canonical function of H3K4 methyltransferase SETD1A.

The H3K4 methyltransferase SETD1A plays an essential role in both development and cancer. However, essential components involved in SETD1A chromatin binding remain unclear. Here, we discovered that BOD1L exhibits the highest correlated SETD1A co-dependency in human cancer cell lines. BOD1L knockout reduces leukemia cells in vitro and in vivo, and mimics the transcriptional profiles observed in SETD1A knockout cells. The loss of BOD1L immediately reduced SETD1A distribution at transcriptional start sites (TSS), induced transcriptional elongation defect, and increased the RNA polymerase II content at TSS; however, it did not reduce H3K4me3. The Shg1 domain of BOD1L has a DNA binding ability, and a tryptophan residue (W104) in the domain recruits SETD1A to chromatin through the association with SETD1A FLOS domain. In addition, the BOD1L-SETD1A complex associates with transcriptional regulators, including E2Fs. These results reveal that BOD1L mediates chromatin and SETD1A, and regulates the non-canonical function of SETD1A in transcription.

Secondary carnitine deficiency during refeeding in severely malnourished patients with eating disorders: a retrospective cohort study.

BACKGROUND: Secondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes. METHOD: In a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC). RESULTS: Upon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21-35) and a median body mass index (BMI) of 13.8 kg/m2 (IQR: 12.8-14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214-0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217-0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170-40.833, p = 0.032). CONCLUSIONS: Hypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted.

Carnitine is an amino acid derivative that plays an important role in the promotion and regulation of fatty acid metabolism, and carnitine deficiency is assumed in patients with anorexia nervosa associated with chronic starvation, but there are few reports on this issue. This study represents the inaugural documentation of hypocarnitinemia in severely malnourished patients with eating disorders, including anorexia nervosa. Hypocarnitinemia, particularly in cases of severe undernutrition (BMI < 13 kg/m²) was observed during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment was considered a potential indicator of hypocarnitinemia. Although no apparent association with adverse events other than anemia during refeeding was identified, clinical manifestations of hypocarnitinemia may occur when a sudden increase in energy demand is added to a change in the physical condition of the patient group. Further investigation is required to determine the clinical significance of hypocarnitinemia.

Healthy Japanese dietary pattern is associated with slower biological aging in older men: WASEDA'S health study.

Aging is the greatest risk factor for numerous diseases and mortality, and establishing geroprotective interventions targeting aging is required. Previous studies have suggested that healthy dietary patterns, such as the Mediterranean diet, are associated with delayed biological aging; however, these associations depend on nationality and sex. Therefore, this study aimed to investigate the relationship between dietary patterns identified through principal component analysis and biological aging in older men of Japan, one of the countries with the longest life expectancies. Principal component analysis identified two dietary patterns: a healthy Japanese dietary pattern and a Western-style dietary pattern. Eight epigenetic clocks, some of the most accurate aging biomarkers, were identified using DNA methylation data from whole-blood samples. Correlation analyses revealed that healthy Japanese dietary patterns were significantly negatively or positively correlated with multiple epigenetic age accelerations (AgeAccel), including AgeAccelGrim, FitAgeAccel, and age-adjusted DNAm-based telomere length (DNAmTLAdjAge). Conversely, the Western-style dietary pattern was observed not to correlate significantly with any of the examined AgeAccels or age-adjusted values. After adjusting for covariates, the healthy Japanese dietary pattern remained significantly positively correlated with DNAmTLAdjAge. Regression analysis showed that healthy Japanese dietary pattern contributed less to epigenetic age acceleration than smoking status. These findings suggest that a Western-style dietary pattern may not be associated with biological aging, whereas a healthy Japanese dietary pattern is associated with delayed biological aging in older Japanese men. Our findings provide evidence that healthy dietary patterns may have mild beneficial effects on delayed biological aging in older Japanese men.

Myc upregulates Ggct, γ-glutamylcyclotransferase to promote development of p53-deficient osteosarcoma.

Osteosarcoma (OS) in humans is characterized by alterations in the TP53 gene. In mice, loss of p53 triggers OS development, for which c-Myc (Myc) oncogenicity is indispensable. However, little is known about which genes are targeted by Myc to promote tumorigenesis. Here, we examined the role of γ-glutamylcyclotransferase (Ggct) which is a component enzyme of the γ-glutamyl cycle essential for glutathione homeostasis, in human and mouse OS development. We found that GGCT is a poor prognostic factor for human OS, and that deletion of Ggct suppresses p53-deficient osteosarcomagenesis in mice. Myc upregulates Ggct directly by binding to the Ggct promoter, and deletion of a Myc binding site therein by genome editing attenuated the tumorigenic potential of p53-deficient OS cells. Taken together, these results show a rationale that GGCT is widely upregulated in cancer cells and solidify its suitability as a target for anticancer drugs.

Clinical subtypes of older adults starting long-term care in Japan and their association with prognoses: a data-driven cluster analysis.

We aimed to identify the clinical subtypes in individuals starting long-term care in Japan and examined their association with prognoses. Using linked medical insurance claims data and survey data for care-need certification in a large city, we identified participants who started long-term care. Grouping them based on 22 diseases recorded in the past 6 months using fuzzy c-means clustering, we examined the longitudinal association between clusters and death or care-need level deterioration within 2 years. We analyzed 4,648 participants (median age 83 [interquartile range 78-88] years, female 60.4%) between October 2014 and March 2019 and categorized them into (i) musculoskeletal and sensory, (ii) cardiac, (iii) neurological, (iv) respiratory and cancer, (v) insulin-dependent diabetes, and (vi) unspecified subtypes. The results of clustering were replicated in another city. Compared with the musculoskeletal and sensory subtype, the adjusted hazard ratio (95% confidence interval) for death was 1.22 (1.05-1.42), 1.81 (1.54-2.13), and 1.21 (1.00-1.46) for the cardiac, respiratory and cancer, and insulin-dependent diabetes subtypes, respectively. The care-need levels more likely worsened in the cardiac, respiratory and cancer, and unspecified subtypes than in the musculoskeletal and sensory subtype. In conclusion, distinct clinical subtypes exist among individuals initiating long-term care.

Change in the Proportion of Death at Home during the COVID-19 Pandemic and Its Associated Factors in the Municipality Level: A Nationwide Study in Japan.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic may have led to an increase in home deaths due to hospital bed shortage and hospital visitation restrictions. This study aimed to examine changes in the proportion of home deaths before and after the COVID-19 pandemic and identify associated factors. Methods: We used publicly available nationwide data to describe the proportion of home deaths among total deaths from 2015 to 2021. Furthermore, we used municipal-level data to examine the factors associated with the increase in the proportion of home deaths from 2019 to 2021. The dependent variable was the absolute change in the proportion of home deaths from 2019 to 2021. The independent variables included each municipality's 2019 home death percentage, medical and long-term care (LTC) resources divided by the population of older people, population density, and cumulative number of COVID-19 cases. A multivariable linear regression analysis was conducted after the standardization of each variable. Results: The proportions of home deaths in 2015, 2019, and 2021 were 12.7%, 13.6%, and 17.2%, respectively, indicating a sharp increase in home death rate after the COVID-19 pandemic. In the multivariable linear regression analysis that included 1,696 municipalities, conventional home care support clinics and hospitals (HCSCs) (coefficient [95% confidence intervals (CIs)], 0.19 [0.01-0.37]), enhanced HCSCs (0.53 [0.34-0.71]), home-visiting nurses (0.26 [0.06-0.46]), population density (0.44 [0.21-0.67]), and cumulative COVID-19 cases (0.49 [0.27-0.70]) were positively associated with the increase in home deaths, whereas beds of LTC welfare facilities (-0.55 [-0.74--0.37]) and the proportion of home deaths in 2019 (-1.24 [-1.44--1.05]) were negatively associated with the increase. Conclusions: During the COVID-19 pandemic, home deaths significantly increased, particularly in densely populated areas with high cumulative COVID-19 cases. HCSCs, especially enhanced HCSCs, are crucial for meeting the demand for home-based end-of-life care.

Polygenic Risk Score, Cardiorespiratory Fitness, and Cardiometabolic Risk Factors: WASEDA'S Health Study.

PURPOSE: This study estimated an individual's genetic liability to cardiometabolic risk factors by polygenic risk score (PRS) construction and examined whether high cardiorespiratory fitness (CRF) modifies the association between PRS and cardiometabolic risk factors. METHODS: This cross-sectional study enrolled 1,296 Japanese adults aged ≥40 years. The PRS for each cardiometabolic trait (blood lipids, glucose, hypertension, and obesity) was calculated using the LDpred2 and clumping and thresholding methods. Participants were divided into low-, intermediate-, and high-PRS groups according to PRS tertiles for each trait. CRF was quantified as peak oxygen uptake (VO 2 peak) per kg body weight. Participants were divided into low-, intermediate-, and high-CRF groups according to the tertile VO 2 peak value. RESULTS: Linear regression analysis revealed a significant interaction between PRS for triglyceride (PRS TG ) and CRF groups on serum TG levels regardless of the PRS calculation method, and attenuated the association between PRS TG and TG levels in the high-CRF group. Logistic regression analysis revealed a significant sub-additive interaction between LDpred2 PRS TG and CRF on the prevalence of high TG, indicating that high CRF attenuated the genetic predisposition to high TG. Furthermore, a significant sub-additive interaction between PRS for body mass index and CRF on obesity was detected regardless of the PRS calculation method. These significant interaction effects on high TG and obesity were diminished in the sensitivity analysis using VO 2 peak per kg fat-free mass as the CRF index. Effects of PRSs for other cardiometabolic traits were not significantly attenuated in the high-CRF group regardless of PRS calculation methods. CONCLUSIONS: The findings of the present study suggest that individuals with high CRF overcome the genetic predisposition to high TG levels and obesity.

Changes in long-term care insurance revenue among service providers during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has impacted peoples' health-related behaviors, especially those of older adults, who have restricted their activities in order to avoid contact with others. Moreover, the pandemic has caused concerns in long-term care insurance (LTCI) providers regarding management and financial issues. This study aimed to examine the changes in revenues among LTCI service providers in Japan during the pandemic and analyze its impact on different types of services. METHODS: In this study, we used anonymized data from "Kaipoke," a management support platform for older adult care operators provided by SMS Co., Ltd. Kaipoke provides management support services to more than 27,400 care service offices nationwide and has been introduced in many home-care support offices. The data used in this study were extracted from care plans created by care managers on the Kaipoke platform. To examine the impact of the pandemic, an interrupted time-series analysis was conducted in which the date of the beginning of the pandemic was set as the prior independent variable. RESULTS: The participating providers were care management providers (n = 5,767), home-visit care providers (n = 3,506), home-visit nursing providers (n = 971), and adult day care providers (n = 4,650). The results revealed that LTCI revenues decreased significantly for care management providers, home-visit nursing providers, and adult day care providers after the COVID-19 pandemic began. The largest decrease was an average base of USD - 1668.8 in adult day care. CONCLUSION: The decrease in revenue among adult day care providers was particularly concerning in terms of the sustainability of their business. This decrease in revenue may have made it difficult to retain personnel, and staff may have needed to be laid off as a result. Although this study has limitations, it may provide useful suggestions for countermeasures in such scenarios, in addition to support conducted measures.

Relationship between health checkups and cancer screenings of wives and health checkups of their husbands: A cross-sectional study in Japan.

Objectives: This study investigated the relationship between health checkups, cervical cancer screenings, and breast cancer screenings (collectively referred to as wellness examinations) of wives and health checkups of their husbands. We aimed to develop strategies to encourage wellness examinations among married individuals in Japan. Methods: This study used the 2019 Comprehensive Survey of Living Conditions, focusing on married couples aged 40-64. We analyzed the percentage of wives undergoing wellness examinations, grouped based on whether their husbands had undergone health checkups. Subsequently, multivariable modified Poisson regression analysis was performed considering sociodemographic and health-related factors. All analyses considered medical insurance of wives because wellness examination methods varied depending on medical insurance type. Results: The sample comprised 40,560 couples undergoing health checkups, 39,870 undergoing cervical cancer screening, and 39,895 undergoing breast cancer screening. Regardless of the medical insurance type of the wife, a significant positive association was observed between the wellness examination of wives and the health checkup of husbands across all age groups. After adjusting for covariates, prevalence ratios (95% confidence intervals) for wives whose husbands underwent health checkups were 2.24 (2.09-2.40) for national health insurance, 1.18 (1.16-1.21) for employee insurance (employee), and 1.53 (1.44-1.63) for employee insurance (family) for health checkups. Similar trends were observed in cervical and breast cancer screening. Conclusions: Wellness examinations of wives were associated with those of their husbands, suggesting that couples often share similar health-seeking behaviors. Hence, targeted interventions are important for couples who do not undergo wellness examinations.

Associations between cardiorespiratory fitness and lifestyle-related factors with DNA methylation-based ageing clocks in older men: WASEDA'S Health Study.

DNA methylation-based age estimators (DNAm ageing clocks) are currently one of the most promising biomarkers for predicting biological age. However, the relationships between cardiorespiratory fitness (CRF), measured directly by expiratory gas analysis, and DNAm ageing clocks are largely unknown. We investigated the relationships between CRF and the age-adjusted value from the residuals of the regression of DNAm ageing clock to chronological age (DNAmAgeAcceleration: DNAmAgeAccel) and attempted to determine the relative contribution of CRF to DNAmAgeAccel in the presence of other lifestyle factors. DNA samples from 144 Japanese men aged 65-72 years were used to appraise first- (i.e., DNAmHorvath and DNAmHannum) and second- (i.e., DNAmPhenoAge, DNAmGrimAge, and DNAmFitAge) generation DNAm ageing clocks. Various surveys and measurements were conducted, including physical fitness, body composition, blood biochemical parameters, nutrient intake, smoking, alcohol consumption, disease status, sleep status, and chronotype. Both oxygen uptake at ventilatory threshold (VO2 /kg at VT) and peak oxygen uptake (VO2 /kg at Peak) showed a significant negative correlation with GrimAgeAccel, even after adjustments for chronological age and smoking and drinking status. Notably, VO2 /kg at VT and VO2 /kg at Peak above the reference value were also associated with delayed GrimAgeAccel. Multiple regression analysis showed that calf circumference, serum triglyceride, carbohydrate intake, and smoking status, rather than CRF, contributed more to GrimAgeAccel and FitAgeAccel. In conclusion, although the contribution of CRF to GrimAgeAccel and FitAgeAccel is relatively low compared to lifestyle-related factors such as smoking, the results suggest that the maintenance of CRF is associated with delayed biological ageing in older men.

Safety and stable survival of stem-cell-derived retinal organoid for 2 years in patients with retinitis pigmentosa.

Transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into retinal disease animal models has yielded promising results, and several clinical trials on iPSC-derived retinal pigment epithelial cell transplantation have confirmed its safety. In this study, we performed allogeneic iPSC-derived retinal organoid sheet transplantation in two subjects with advanced retinitis pigmentosa (jRCTa050200027). The primary endpoint was the survival and safety of the transplanted retinal organoid sheets in the first year post-transplantation. The secondary endpoints were the safety of the transplantation procedure and visual function evaluation. The grafts survived in a stable condition for 2 years, and the retinal thickness increased at the transplant site without serious adverse events in both subjects. Changes in visual function were less progressive than those of the untreated eye during the follow-up. Allogeneic iPSC-derived retinal organoid sheet transplantation is a potential therapeutic approach, and the treatment's safety and efficacy for visual function should be investigated further.

Cryo-EM structures of RNA polymerase II-nucleosome complexes rewrapping transcribed DNA.

RNA polymerase II (RNAPII) transcribes DNA wrapped in the nucleosome by stepwise pausing, especially at nucleosomal superhelical locations -5 and -1 [SHL(-5) and SHL(-1), respectively]. In the present study, we performed cryo-electron microscopy analyses of RNAPII-nucleosome complexes paused at a major nucleosomal pausing site, SHL(-1). We determined two previously undetected structures, in which the transcribed DNA behind RNAPII is sharply kinked at the RNAPII exit tunnel and rewrapped around the nucleosomal histones in front of RNAPII by DNA looping. This DNA kink shifts the DNA orientation toward the nucleosome, and the transcribed DNA region interacts with basic amino acid residues of histones H2A, H2B, and H3 exposed by the RNAPII-mediated nucleosomal DNA peeling. The DNA loop structure was not observed in the presence of the transcription elongation factors Spt4/5 and Elf1. These RNAPII-nucleosome structures provide important information for understanding the functional relevance of DNA looping during transcription elongation in the nucleosome.

Association between circadian clock gene expressions and meal timing in young and older adults.

Ageing is associated with a decline in circadian clock systems, which correlates with the development of ageing-associated diseases. Chrononutrition is a field of chronobiology that examines the relationship between the timing of meal/nutrition and circadian clock systems. Although there is growing evidence regarding the role of chrononutrition in the prevention of lifestyle and ageing-related diseases, the optimal timing of meal intake to regulate the circadian clock in humans remains unknown. In this study, we investigated the relationship between clock gene expression and meal timing in young and older adults. In this cross-sectional study, we enrolled 51 healthy young men and 35 healthy older men (age, mean±standard deviation: 24 ± 4 and 70 ± 4 y, respectively). Under daily living conditions, beard follicle cells were collected at 4-h intervals over a 24-h period to evaluate clock gene expression. Participants were asked to record the timing of habitual sleep and wake-up, breakfast, lunch, and dinner. From these data, we calculated "From bedtime to breakfast time," "From wake up to first meal time," and "From dinner to bed time." NR1D1 and PER3 expressions in older adults at 06:00 h were significantly higher than those in young adults (P = 0.001). There were significant differences in the peak time for NR1D2 (P = 0.003) and PER3 (P = 0.049) expression between young and older adults. "From bedtime to breakfast time" was significantly longer in older adults than in young adults. In contrast, "From dinner to bed time" was significantly shorter in older adults than in young adults. Moreover, higher rhythmicity of NR1D1 correlated with longer "From bedtime to breakfast time" (r = -0.470, P = 0.002) and shorter "From wake up to first meal time" in young adults (r = 0.302, P = 0.032). Higher rhythmicity of PER3 correlated with longer "From bedtime to breakfast time" in older adults (r = -0.342, P = 0.045). These results suggest that the peak time of clock gene expression in older adults may be phase-advanced compared to that in young adults. In addition, a longer fasting duration from bedtime to breakfast in both young and older adults and earlier intake of meals after waking up in young adults may correlate with robust clock gene expression rhythms.

The combined effect of rowing exercise and the intake of functional foods containing inulin on muscle mass and bone mineral density in older Japanese women.

AIM: Aging decreases muscle mass and bone mineral density (BMD), especially in older women. It has been reported that rowing and inulin intake positively affect muscle and bone, respectively. We examined the synergistic effect of rowing and functional food intake, including inulin, on lean body mass, BMD, and physical function parameters in older Japanese women. METHODS: Fifty women aged 65-79 years were divided into four groups with or without inulin intake and rowing. The interventions were carried out for 12 weeks in each group. We assessed lean body mass and BMD using dual-energy X-ray absorptiometry at baseline and after the intervention and examined the changes in the values in each group. RESULTS: Lean body mass in all groups decreased, and the change in lean body mass in the group with rowing and inulin intake was significantly smaller than that in the group without them (-0.05 ± 0.61; -0.83 ± 0.59 kg; P = 0.030). The BMD in the three intervention groups increased after the 12-week intervention. The change in BMD in each of the three intervention groups showed significant differences compared with the control group (Rowing + Inulin: P = 0.03; Rowing + No inulin: P = 0.01; No rowing + Inulin: P < 0.01). CONCLUSIONS: Rowing and the intake of functional foods, including inulin, synergistically prevented a decrease in lean body mass. These factors, individually and additively, might increase BMD in older Japanese women. Geriatr Gerontol Int 2023; 23: 779-787.

Factors associated with non-participation in breast cancer screening: analysis of the 2016 and 2019 comprehensive survey of living conditions in Japan.

BACKGROUND: The participation rate for breast cancer screening remains to be suboptimal in Japan. Therefore, it is important to identify factors associated with non-participation and identify people at high risk for non-participation. METHODS: We carried out a cross-sectional study using the data of women aged 40-74 years from the 2016 and 2019 Comprehensive Survey of Living Conditions. We selected candidate predictor variables from the survey sheets and conducted a multivariable logistic regression for non-participation in breast cancer screening for the past 2 years. In addition, using data from 2016, we created an integer risk score for non-participation and tested its predictive performance in 2019. RESULTS: The proportion of participants in breast cancer screening in 2016 and 2019 were 46.7% (50,177/107,513) and 48.7% (49,498/101,716), respectively. In multivariable logistic regression analysis, age over 50 years, single/divorced/widowed, lower education level, lower household expenditure, being insured for National Health Insurance, employed to small/middle scale company, non-regularly employed, current smoker, never/quit drinking or middle/high-risk drinking, lower self-rated health status, higher Kessler Psychological Distress Scale score, non-participation in the annual health checkups for diseases other than cancer, not constantly visiting hospitals/clinics showed a positive association with non-participation. The 9-item risk score (age, marital status, education, health insurance plan, employment, smoking, drinking, non-participation in the annual health checkups for diseases other than cancer, and not constantly visiting hospitals/clinics) and 3-item risk score (age, health insurance plan, non-participation in the annual health checkups for diseases other than cancer) showed the area under the receiver operating characteristic curve of 0.744 and 0.720, respectively. CONCLUSION: We identified factors associated with non-participation in breast cancer screening. The simple risk score would be useful for public health sectors to identify people at risk for non-participation.

C/ebpα represses the oncogenic Runx3-Myc axis in p53-deficient osteosarcoma development.

Osteosarcoma (OS) is characterized by TP53 mutations in humans. In mice, loss of p53 triggers OS development, and osteoprogenitor-specific p53-deleted mice are widely used to study the process of osteosarcomagenesis. However, the molecular mechanisms underlying the initiation or progression of OS following or parallel to p53 inactivation remain largely unknown. Here, we examined the role of transcription factors involved in adipogenesis (adipo-TFs) in p53-deficient OS and identified a novel tumor suppressive molecular mechanism mediated by C/ebpα. C/ebpα specifically interacts with Runx3, a p53 deficiency-dependent oncogene, and, in the same manner as p53, decreases the activity of the oncogenic axis of OS, Runx3-Myc, by inhibiting Runx3 DNA binding. The identification of a novel molecular role for C/ebpα in p53-deficient osteosarcomagenesis underscores the importance of the Runx-Myc oncogenic axis as a therapeutic target for OS.

High Cathode Loading and Low-Temperature Operating Garnet-Based All-Solid-State Lithium Batteries - Material/Process/Architecture Optimization and Understanding of Cell Failure.

All-solid-state lithium batteries (ASSLBs) are prepared using garnet-type solid electrolytes by quick liquid phase sintering (Q-LPS) without applying high pressure during the sintering. The cathode layers are quickly sintered with a heating rate of 50-100 K min-1 and a dwell time of 10 min. The battery performance is dramatically improved by simultaneously optimizing materials, processes, and architectures, and the initial discharge capacity of the cell with a LiCoO2 -loading of 8.1 mg reaches 1 mAh cm-2 and 130 mAh g-1 at 25 °C. The all-solid-state cell exhibits capacity at a reduced temperature (10 °C) or a relatively high rate (0.1 C) compared to the previous reports. The Q-LPS would be suitable for large-scale manufacturing of ASSLBs. The multiphysics analyses indicate that the internal stress reaches 1 GPa during charge/discharge, which would induce several mechanical failures of the cells: broken electron networks, broken ion networks, separation of interfaces, and delamination of layers. The experimental results also support these failures.

Evaluation of enhanced home care support clinics regarding emergency home visits, hospitalization, and end-of-life care: a retrospective cohort study in a city of Japan.

BACKGROUND: To meet the increasing demand for home healthcare in Japan as the population ages, home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in 2006 and 2012, respectively. This study aimed to evaluate whether enhanced HCSCs fulfilled the expected role in home healthcare. METHODS: We conducted a retrospective cohort study using linked medical and long-term care claims data from a municipality in Japan. Participants were ≥ 65 years of age, had newly started regular home visits between July 2014 and March 2018, and used either conventional or enhanced HCSCs. Patients were followed up for one year after they started regular home visits or until the month following the end of the regular home visits if they ended within one year. The outcome measures were (i) emergency home visits at all hours and on nights and holidays at least once, respectively, (ii) hospitalization at least once, and (iii) end-of-life care, which was evaluated based on the place of death and whether a physician was present at the time of in-home death. Multivariable logistic regression analyses were conducted for the outcomes of emergency home visits and hospitalizations. RESULTS: The analysis included 802 patients, including 405 patients in enhanced HCSCs and 397 patients in conventional HCSCs. Enhanced HCSCs had more emergency home visits at all hours than conventional HCSCs (65.7% vs. 49.1%; adjusted odds ratio 1.70, 95% CI [1.26-2.28]), more emergency home visits on nights and holidays (33.6% vs. 16.7%; 2.20 [1.55-3.13]), and fewer hospitalizations (21.5% vs. 32.2%; 0.55 [0.39-0.76]). During the follow-up period, 229 patients (152 patients in enhanced HCSCs and 77 patients in HCSCs) died. Deaths at home were significantly more common in enhanced HCSCs than in conventional HCSCs (80.9% vs. 64.9%; p < .001), and physician-attended deaths among those who died at home were also significantly more common in enhanced HCSCs (99.2% vs. 78.0%; p < .001). CONCLUSIONS: This study confirms that enhanced HCSCs are more likely to be able to handle emergency home visits and end-of-life care at home, which are important medical functions in home healthcare. Further promotion of enhanced HCSCs would be advantageous.

Association between types of home healthcare and emergency house calls, hospitalization, and end-of-life care in Japan.

BACKGROUND: To meet the increasing demand for home healthcare in Japan, as part of the national healthcare system, home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in 2006 and 2012 respectively. This study aimed to evaluate whether HCSCs has succeeded in providing 24-h home care services through the end of life. METHODS: A retrospective cohort study was conducted using the national database in Japan. Participants were ≥ 65 years of age, had newly started regular home visits between July 2014 and September 2015, and used general clinics, conventional HCSCs, or enhanced HCSCs. Each patient was followed up for 6 months after the first visit. The outcome measures were (i) emergency house call(s), (ii) hospitalization(s), and (iii) end-of-life care defined as in-home death. Multivariable logistic regression analyses were performed for statistical analysis. RESULTS: The analysis included 160,674 patients, including 13,477, 64,616, and 82,581 patients receiving regular home visits by general clinics, conventional HCSCs, and enhanced HCSCs respectively. Compared to general clinics, the use of conventional and enhanced HCSCs was associated with an increased likelihood of emergency house calls (adjusted odds ratio [aOR] and 95% confidence intervals [CIs] of 1.62 [1.56-1.69] and 1.86 [1.79-1.93], respectively) and a decreased likelihood of hospitalizations (aOR [95% CIs] of 0.86 [0.82-0.90] and 0.88 [0.84-0.92] respectively). Among 39,082 patients who died during the follow-up period, conventional and enhanced HCSCs had more in-home deaths (aOR [95% CIs] of 1.46 [1.33-1.59] and 1.60 [1.46-1.74], respectively) compared to general clinics. CONCLUSIONS: HCSCs (especially enhanced HCSCs) provided more emergency house calls, reduced hospitalization, and enabled expected deaths at home, suggesting that further promotion of HCSCs (especially enhanced HSCSs) would be advantageous.