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Abstract During the development of multicellular organisms and cell differentiation, the chromatin structure in the cell nucleus undergoes extensive changes, and the nucleosome structure is formed by a combination of various histone variants. Histone variants with diverse posttranslational modifications are known to play crucial roles in different regulatory functions. We have previously reported that H3t, a testis-specific histone variant, is essential for spermatogenesis. To elucidate the function of this chromatin molecule in vivo, we generated knock-in mice with a FLAG tag attached to the carboxyl terminus of H3t. In the present study, we evaluated the utility of the generated knock-in mice and comprehensively analyzed posttranslational modifications of canonical H3 and H3t using mass spectrometry. Herein, we found that H3t-FLAG was incorporated into spermatogonia and meiotic cells in the testes, as evidenced by immunostaining of testicular tissue. According to the mass spectrometry analysis, the overall pattern of H3t-FLAG posttranslational modification was comparable to that of the control H3, while the relative abundances of certain specific modifications differed between H3t-FLAG and the control bulk H3. The generated knock-in mice could be valuable for analyzing the function of histone variants in vivo.

Introduction Individuals with mental illness and their families often undergo their recovery process in their communities. This study explored the long-term outcome trajectories of individuals and families who received case management services provided by multidisciplinary outreach teams in a community setting. The primary objective of this study was to determine whether trajectories of subjective quality of life (QoL) related to personal recovery were linked to those clinical and societal outcomes and changes in outreach service frequency.Methods and analysis The protocol of this 10-year multisite cohort study was collaboratively developed with individuals with lived experience of psychiatric disorders who had received services from participating outreach teams, and with family members in Japanese family associations. The participants in the study include patients and their key family members who receive services from 23 participating multidisciplinary outreach teams. The participant recruitment period is set from 1 October 2023 to 30 September 2025. If necessary, the recruitment period may be extended and the number of participating teams may be increased. The study will annually evaluate the following outcomes after participants’ initial utilisation of services from each team: QoL related to personal recovery, personal agency, feelings of loneliness, well-being and symptom and functional assessments. The family outcomes encompass QoL, well-being, care burden and family relationships. Several meetings will be held to monitor progress and manage issues during the study. Multivariate analyses with repeated measures will be performed to investigate factors influencing changes in the patients’ QoL scores as the dependent variable.Ethics and dissemination The study protocol was approved by the ethical committee of the National Center of Neurology and Psychiatry (no. A2023-065). The study findings will be reported in peer-reviewed publications and presented at relevant scientific conferences.Trial registration number UMIN-CTR, No. UMIN000052275.

Abstract Aims This study aimed to conduct a systematic review of studies on the outcomes of long-term hospitalisation of individuals with severe mental illness, considering readmission rates as the primary outcome. Methods Studies considered were those in which participants were aged between 18 and 64 years with severe mental illness; exposure to psychiatric hospitals or wards was long-term (more than one year); primary outcomes were readmission rates; secondary outcomes were duration of readmission, employment, schooling, and social participation; and the study design was either observational or interventional with a randomised controlled trial (RCT) design. Relevant studies were searched using MEDLINE, PsycINFO, Web of Science, CINAHL, and the Japan Medical Abstract Society. The final search was conducted on 1 February 2022. The risk of bias in non-randomised studies of interventions was used to assess the methodological quality. A descriptive literature review is also conducted. Results Of the 11,999 studies initially searched, three cohort studies (2,293 participants) met the eligibility criteria. The risk of bias in these studies was rated as critical or serious. The 1–10 years readmission rate for patients with schizophrenia who had been hospitalised for more than one year ranged from 33 to 55%. The average of readmission durations described in the two studies was 70.5 ± 95.6 days per year (in the case of a 7.5-year follow-up) and 306 ± 399 days (in the case of a 3–8-year follow-up). None of the studies reported other outcomes defined in this study. Conclusions The readmission rates in the included studies varied. Differences in the follow-up period or the intensity of community services may have contributed to this variability. In countries preparing to implement de-institutionalisation, highly individualised community support should be designed to avoid relocation to residential services under supervision. The length of stay for readmissions was shorter than that for index admissions. The results also imply that discharge to the community contributes to improved clinical outcomes such as improved social functioning. The validity of retaining patients admitted because of the risk of rehospitalisation was considered low. Future research directions have also been discussed.

Abstract Aims This study investigated outcomes in community mental health research that were important to caregivers of people with schizophrenia. Methods Using an online survey conducted from August 1 to 31, 2020, data were collected from caregivers belonging to the LINE Schizophrenia Family Association. Caregivers identified outcomes important in community mental health research. Two researchers categorized caregivers' statements into research outcomes. Results A total of 132 caregivers completed the online selfreported questionnaire, and 296 caregiver statements were identified. Qualitative analysis identified 17 outcome categories. The caregivers tended to value having more free time, maintaining an appropriate relationship with people with schizophrenia, and being able to cope with their symptoms. Conclusions This exploratory study newly demonstrates the outcomes that caregivers of people with schizophrenia consider important in community mental health research. The findings may be useful in selecting outcomes for future studies of caregivers.

Abstract Background Patient and public involvement (PPI) has become essential in health research. However, little is known about multiple stakeholders' perspectives on the implementation of PPI in community mental health research settings. The present study aimed to qualitatively analyse multiple stakeholders' views on PPI, including potential concerns, barriers and approaches. Methods This study involved conducting focus group interviews and collecting qualitative data from 37 participants in multiple stakeholder groups (patients = 6, caregivers = 5, service providers = 7, government staff = 5 and researchers = 14) in the community mental health field. The data were qualitatively analysed using a data‐driven approach that derived domains, themes and subthemes related to perspectives on PPI and to specific challenges and approaches for implementing PPI. Results The qualitative analysis identified four domains. The ‘Positive views and expectations regarding PPI’ domain consisted of themes related to supportive views of PPI in a mental health service research setting and improvements in the quality of research and service. The ‘General concerns about PPI’ domain included themes concerning the need for non‐PPI research and tokenism, excessive expectations concerning social changes and use of evidence from PPI research, and heavy burdens resulting from PPI. The ‘Specific issues regarding the implementation of PPI’ domain consisted of four themes, including academic systems, selection methods (e.g., representativeness and conflict of interest issues), relationship building, and ambiguous PPI criteria. In particular, all stakeholder groups expressed concerns about relational equality during PPI implementation in Japan. The ‘Approaches to PPI implementation’ domain included themes such as facilitating mutual understanding, creating a tolerant atmosphere, establishing PPI support systems (e.g., training, ethics and human resource matching) and empowering patient organizations. Conclusion The study replicated most of the barriers and approaches to PPI reported by qualitative research in Western counties. However, utilization of evidence produced by PPI research and partnership in the PPI process may be particularly serious issues in Japan. Future PPI studies should carefully address solutions that fit each culture. Patient or Public Contribution A patient‐researcher was involved in all stages of this project, from development of the research topic and the protocol to manuscript preparation.

Abstract Background Outcome selection in intervention studies is a critical issue for synthesizing evidence. This study is aimed to investigate outcomes used in Cochrane reviews assessing community‐based psychosocial interventions for adults with severe mental illness. Methods Cochrane reviews that evaluated a community‐based psychosocial intervention for adults with severe mental illness were searched electronically and manually. We extracted all outcomes specified in the Methods section in each Cochrane review. Outcomes that represent the same concept and context were synthesized into an outcome term. Outcome terms were categorized according to the existing taxonomy. Results We included 33 Cochrane reviews. Of the 216 outcome terms identified, 13 were used in more than half of the reviews: quality of life, mental state, admission to hospital, economic outcome, leaving the study early, social functioning, satisfaction, global state, relapse, adverse events/effects, carer satisfaction, employment, and duration of admission. Most outcome terms were categorized into the life impact core area (55%), followed by the resource use area (21%). Conclusions Our study provides a candidate outcome list for developing a core outcome set for severe mental illness and offers a basis for comparison for future outcome investigation on mental health research.

Abstract Background Treatment goals for mental illness have expanded from hospital discharge and improved functioning to employment, living alone, and personal realization. These changes in treatment goals have also influenced mental health research. Recent studies have addressed the development of core outcome sets focusing on clinical aspects of mental illness such as depression and anxiety. However, a well‐developed framework of essential outcomes for people with mental illness (service users) who live in the community is lacking. In addition, recent worldwide trends suggest more patient and public involvement and the importance of considering multiple stakeholders’ views in the area of mental health research. Purpose of this study is to explore consensus on high‐priority outcome domains among multiple stakeholders in community mental healthcare fields in Japan. Methods A three‐step approach to developing an outcome list will be used. First, we developed a long list of outcomes for community mental health through a literature review, focus group interviews with key stakeholders, and online questionnaire surveys of service users and caregivers. Second, the long list was checked and revised in a pilot study. Third, the long list will be shortened to the outcome list through the Delphi methodology with participation from multiple stakeholders. Discussion Identifying important common outcome domains through collaboration with multiple stakeholders appears to contribute to the development of evidence for community mental health research in Japan. In addition, the study process itself may help promote patient and public involvement in education, practice, and research in the field of community mental health.

Background: The purpose of this study was to clarify the structural relationship of quality of life (QOL) in survivors of breast cancer, including difficulty in daily life and negative experiences in daily activities, as health-related indicators. Methods: Participants were survivors of breast cancer for more than 2 years after primary breast cancer surgery and belonged to self-help groups. The assessment used FACT-B (QOL), HADS (anxiety and depression), SOC (sense of coherence), WHODAS 2.0 (difficulties in daily life), and CAOD (negative experiences in daily activities). Bayesian structural equation modeling (BSEM) was performed to analyze the hypothesized model. If the causal model was significant, multiplication of the path coefficient from emotional distress (anxiety and depression) to QOL, and from SOC to emotional distress, was considered a direct effect on QOL, and from SOC to difficulty in daily life, from difficulty in daily life to negative experiences in daily activities, and from negative experiences in daily activities to anxiety and depression were considered indirect effects on QOL. Results: The participants comprised 73 survivors of breast cancer. The goodness of fit of the model in the BSEM was satisfactory. The direct effect was 0.274, and the indirect effect was 0.164. Conclusions: An additional finding of this study is that coping with difficulty in daily life and negative experiences in daily activities related to QOL may improve QOL.

In this study,field surveys were carried out at the damaged area of slope stabilization works,where the main cause was presumed to be the frost heaving of the rock mass.Field measurements of the freezing depth and the amount of frost heave were also conducted.In addition, the effectiveness of the slope stabilization work with the frost heave measures was verified based on the investigation results.The findings are summarized as follows. (1) From the results of the field survey and the field measurements,it was found that even if frost heaving occurred in the extreme surface layer, the rock mass would be degraded and the slope stabilization work would be affected.(2)From the results of the frost heaving tests, it is clear that the frost susceptibility of the damaged rock slope is extremely high, and there was wide agreement between the results of the frost heaving tests and the results of determining the frost susceptibility of the damaged rock slope using a simple strength test method. Therefore, the validity of the simple method proposed by Nakamura et al. for determining the frost susceptibility of rocks by using the strength test was also verified. (3)It was confirmed that both the gabion and the continuous fiber reinforced soil work were effective in preventing the freezing front from advancing into the rock mass.The method of covering the rock slope with non-frost susceptible material to prevent the penetration of the freezing front was found to be effective as a countermeasure against frost heaving.

Abstract Aims The purpose of this study was to retrospectively investigate care difficulties experienced by caregivers of people with schizophrenia during COVID‐19 pandemic lockdowns in Japan (April 7‐May 25, 2020) and examine associations between these care difficulties during lockdowns and daily caregiver burden. Methods Data were collected from 132 participants of the LINE Schizophrenia Family Association using an online survey. Results Caregivers were mostly concerned about who would care for people with schizophrenia if caregivers become infected with COVID‐19. A significant association was found between higher daily caregiver burden and more difficult care experiences during COVID‐19 pandemic lockdowns (B = 0.58, 95% confidence interval, 0.40‐0.75, P

Background. This study is aimed at verifying a hypothetical model of the structural relationship between the recovery process and difficulties in daily life mediated by occupational dysfunction in severe and persistent mental illness (SPMI). Methods. Community-dwelling participants with SPMI were enrolled in this multicenter cross-sectional study. The Recovery Assessment Scale (RAS), the World Health Organization Disability Assessment Schedule second edition (WHODAS 2.0), and the Classification and Assessment of Occupational Dysfunction (CAOD) were used for assessment. Confirmatory factor analysis, multiple regression analysis, and Bayesian structural equation modelling (BSEM) were determined to analyze the hypothesized model. If the mediation model was significant, the path coefficient from difficulty in daily life to recovery and the multiplication of the path coefficients mediated by occupational dysfunction were considered as each the direct effect and the indirect effect. The goodness of fit in the model was determined by the posterior predictive P value (PPP). Each path coefficient was validated with median and 95% confidence interval (CI). Results. The participants comprised 98 individuals with SPMI. The factor structures of RAS, WHODAS 2.0, and CAOD were confirmed by confirmatory factor analysis to be similar to those of their original studies. Multiple regression analysis showed that the independent variables of RAS were WHODAS 2.0 and CAOD, and that of CAOD was WHODAS 2.0. The goodness of fit of the model in the BSEM was satisfactory with a PPP=0.27. The standardized path coefficients were, respectively, significant at −0.372 (95% CI: −0.586, −0.141) from “difficulty in daily life” to “recovery” as the direct effect and at −0.322 (95% CI: −0.477, −0.171) mediated by “occupational dysfunction” as the indirect effect. Conclusions. An approach for reducing not only difficulty in daily life but also occupational dysfunction may be an additional strategy of person-centered, recovery-oriented practice in SPMI.

H3K9me3 and H3K27me3 chromatin silencing marks are usually deposited by different SET-domain proteins. Here the authors show that the Enhancer-of-zeste-like protein Ezl1, from the unicellular eukaryote Paramecium tetraurelia, catalyzes methylation of histone H3 in vitro and in vivo with an apparent specificity toward K9 and K27, and controls the repression of transposable elements.

Recently it has been found that frost heave phenomena can be seen not also in soil but also in rock. It is obvious, however, that the number of researches on frost heaving in rock is much less than that of researches on frost heaving in soil. In the present research, we newly developed test equipment in which a pressure transducer is incorporated into a device for testing frost heave in rock. Frost heaving tests were performed using three types of rocks (Ohya tuff, which is soft rock with high frost susceptibility; Kimachi sandstone, which is medium-hard rock with low frost susceptibility; and Sapporo soft rock, which is non-frost-heaving soft rock) to measure the suction pressure generated in the process of frost heaving. In these tests, we obtained fairly large negative pressures for Ohya tuff and Kimachi sandstone. In mediumhard Kimachi sandstone, negative pressure was generated before frost heaving displacement started. On the other hand, negative pressure was not generated in non-frost-heaving Sapporo soft rock. Therefore we considered that frost heaving in rock might be caused by negative pressure generated in the process of frost heaving.

Background/Objective Few studies have addressed the type of time course regression that can predict changes in functional ability in inpatients with schizophrenia. This study investigated the possibility of predicting changes in functional ability by logarithmic and linear regression modelling when treating schizophrenia. Methods This longitudinal study included two analysis rounds. Analysis 1 comprised 40 inpatients (male/female: 16/24, mean age: 39.7 ± 13.5 years) for the identification of the time course of changes in functional ability based on the Activity Profile Scale for Patients with Psychiatric Disorders score from the group data. Analysis 2 comprised 17 inpatients (male/female: 9/8, mean age: 38.5 ± 9.4 years) to ensure correlation of the group data with the prediction of each individual’s degree of functional ability. Results In Analysis 1, Activity Profile Scale for Patients with Psychiatric Disorders score was assessed at the initial occupational therapy visit, one week and one month thereafter, and at discharge; logarithmic modelling using the scores at the initial visit, one month later and at discharge was more suitable (R 2 = .506, p

In this study, we conducted a follow-up survey of brick cracking on a brick wall in the parking space of JR Kitami Station and installed temperature sensors on the surface of the brick wall in order to measure changes in the brick wall temperature during late winter. In addition, we attempted to reproduce the brick cracking observed on the brick wall by conducting an indoor freeze-thaw experiment. The field investigation confirmed that the brick cracking on the brick wall occurred on the south-facing wall in the period from the coldest season to late winter. It was also confirmed from the records of the measured surface temperatures of the brick wall that, even in winter, the bricks could thaw in daytime and re-freeze at night, depending on the weather, solar radiation, and depth of snow coverage. Furthermore, we were successful in reproducing the brick cracking observed on the brick wall in the parking space of JR Kitami Station in the indoor freeze-thaw experiment. Our experience outlined above has demonstrated that frost damage can occur on the brick wall at JR Kitami station by a mechanism caused by the phenomenon of closed-system freeze-thaw, which the authors propose.

The binding of heterochromatin protein 1 (HP1) to lysine 9-methylated histone H3 (H3K9me) is an essential step in heterochromatin assembly. Chp2, an HP1-family protein in the fission yeast Schizosaccharomyces pombe, is required for heterochromatic silencing. Chp2 recruits SHREC, a multifunctional protein complex containing the nucleosome remodeler Mit1 and the histone deacetylase Clr3. Although the targeting of SHREC to chromatin is thought to occur via two distinct modules regulated by the SHREC components Chp2 and Clr2, it is not clear how Chp2's chromatin binding regulates SHREC function. Here, we show that H3K9me binding by Chp2's chromodomain (CD) is essential for Chp2's silencing function and for SHREC's targeting to chromatin. Cells expressing a Chp2 mutant with defective H3K9me binding (Chp2-W199A) have a silencing defect, with a phenotype similar to that of chp2-null cells. Genetic analysis using a synthetic silencing system revealed that a Chp2 mutant and SHREC-component mutants had similar phenotypes, suggesting that Chp2's function also affects SHREC's chromatin binding. Size-exclusion chromatography of native protein complexes showed that Chp2-CD's binding of H3K9me3 ensures Clr3's chromatin binding, and suggested that SHREC's chromatin binding is mediated by separable functional modules. Interestingly, we found that the stability of the Chp2 protein depended on the Clr3 protein's histone deacetylase activity. Our findings demonstrate that Chp2's H3K9me binding is critical for SHREC function and that the two modules within the SHREC complex are interdependent.

SUV39H is the major histone H3 lysine 9 (H3K9)-specific methyltransferase that targets pericentric regions and is crucial for assembling silent heterochromatin. SUV39H recognizes trimethylated H3K9 (H3K9me3) via its chromodomain (CD), and enriched H3K9me3 allows SUV39H to target specific chromosomal regions. However, the detailed targeting mechanisms, especially for naïve chromatin without preexisting H3K9me3, are poorly understood. Here we show that Suv39h1’s CD (Suv39h1-CD) binds nucleic acids, and this binding is important for its function in heterochromatin assembly. Suv39h1-CD had higher binding affinity for RNA than DNA, and its ability to bind nucleic acids was independent of its H3K9me3 recognition. Suv39h1 bound major satellite RNAs in vivo, and knockdown of major satellite RNAs lowered Suv39h1 retention on pericentromere. Suv39h1 mutational studies indicated that both the nucleic acid–binding and H3K9me–binding activities of Suv39h1-CD were crucial for its pericentric heterochromatin assembly. These results suggest that chromatin-bound RNAs contribute to creating SUV39H’s target specificity.

In recent years, earthquakes have caused several types of damage to residential embankments. To assess the integrity of residential embankments and ascertain necessary countermeasures following ground disasters, it is crucial to accurately define the boundary of cutting and filling. Although surface wave methods nondestructively unveil the S-wave velocity VS across a broad spectrum, there are currently no methods available to predict the boundary of cutting and filling based on VS. In this investigation, surface wave measurements were conducted in an area thought to be an embankment, according to aerial topographic interpretation. The acquired VS data were used to ascertain the soil characteristics of the unaffected residential embankment. Furthermore, the applicability of a method for predicting the boundary of cutting and fillings was examined. When the mode value of VS within the embankment was selected as the threshold for the boundary of cutting and filling, some agreement was confirmed with the outcomes calculated through aerial topographic interpretation. In addition, a straightforward technique for calculating ground subsidence based on VS was considered. It was found that it may be feasible to determine the estimated seismic settlement of residential levees swiftly and nondestructively throughout a sizable region. These results indicate that the use of the surface wave method has the potential to advance residential embankment health assessment systems. [ABSTRACT FROM AUTHOR]

Background/Aim: To evaluate retrospectively whether bland embolization using microspheres is safe and useful for relieving pain in patients with painful malignant musculoskeletal (MSK) tumors. Patients and Methods: Bland embolization using microspheres was performed for 20 patients (11 women/9 men) with a median age of 69 years (range=40-89 years) who had 22 painful malignant MSK tumors. The maximum tumor diameters were 2.4-13.8 cm (median, 7.5 cm). Pain was evaluated using the visual analog scale. A decrease of this score by 2 or more after embolization was defined as clinically effective pain relief. Adverse events (AEs) were evaluated using CTCAE v5.0. Objective response, disease control rates, and overall survival were also evaluated. Results: Effective pain relief was achieved in 18 patients (90.0%, 18/20). Grade-3 AEs developed in four patients (20.0%, 4/20): skin ulcer (n=2), skin ulcer and pain (n=1), and muscle weakness with dysesthesia (n=1). No grade-4 or grade-5 AEs developed. Objective response and disease control rates were 26.7% (4/15) and 86.7% (13/15), respectively. The 1-year survival rate was 43.8%, with median survival of 9.2 months (range=0.5-41.0 months). Conclusion: Although the survival benefit is equivocal, bland embolization is acceptably safe and useful for relieving pain by controlling tumor growth in patients with painful malignant MSK tumors. [ABSTRACT FROM AUTHOR]