Interdependent culture and older adults' well-being: Health and psychological happiness in Japanese communities.

This review article examined perspectives on the well-being and health of older adults in Japan, a nation renowned for its longevity. We emphasized the impact of social capital and social relationships in local communities, considering both individual and societal factors. The prevailing values in Japanese culture tend to foster a sustained and stable form of interdependent happiness among older adults, suggesting that communal support systems play an important role. This article highlights the value of multi-level datasets, such as the Japan Gerontological Evaluation Study (JAGES) dataset, for understanding the influence of social participation on the health and well-being of older adults. A growing body of evidence underscores the central role of social relationships in the health and well-being of older adults.

Transcriptome and methylome analysis of CNS germ cell tumor finds its cell-of-origin in embryogenesis and reveals shared similarities with testicular counterparts.

BACKGROUND: CNS germ cell tumors (GCTs) predominantly develop in pediatric and young adult patients with variable responses to surgery, radiation, and chemotherapy. This study aimed to examine the complex and largely unknown pathogenesis of CNS GCTs. METHODS: We used a combined transcriptomic and methylomic approach in 84 cases and conducted an integrative analysis of the normal cells undergoing embryogenesis and testicular GCTs. RESULTS: Genome-wide transcriptome analysis in CNS GCTs indicated that germinoma had a transcriptomic profile representative of primitive cells during early embryogenesis with high meiosis/mitosis potentials, while nongerminomatous GCTs (NGGCTs) had differentiated phenotypes oriented toward tissue formation and organogenesis. Co-analysis with the transcriptome of human embryonic cells revealed that germinomas had expression profiles similar to those of primordial germ cells, while the expression profiles of NGGCTs were similar to those of embryonic stem cells. Some germinoma cases were characterized by extensive immune-cell infiltration and high expression of cancer-testis antigens. NGGCTs had significantly higher immune-cell infiltration, characterized by immune-suppression phenotype. CNS and testicular GCTs (TGCTs) had similar mutational profiles; TGCTs showed enhanced copy number alterations. Methylation analysis clustered germinoma/seminoma and nongerminoma/nonseminoma separately. Germinoma and seminoma were co-categorized based on the degree of the tumor microenvironment balance. CONCLUSIONS: These results suggested that the pathophysiology of GCTs was less dependent on their site of origin and more dependent on the state of differentiation as well as on the tumor microenvironment balance. This study revealed distinct biological properties of GCTs, which will hopefully lead to future treatment development.

12p gain is predominantly observed in non-germinomatous germ cell tumors and identifies an unfavorable subgroup of central nervous system germ cell tumors.

BACKGROUND: Central nervous system (CNS) germ cell tumors (GCTs) are neoplasms predominantly arising in pediatric and young adult populations. While germinomas generally respond to chemotherapy and radiation, non-germinomatous GCTs (NGGCTs) require more intensive treatment. This study aimed to determine whether 12p gain could predict the prognosis of CNS GCTs. METHODS: Eighty-two CNS GCTs were included in this study. The 12p gain was defined by an additional 12p in the background of potential polyploidy or polysomy. Cases were analyzed using an Illumina methylation 450K array for copy number investigations and validated by fluorescence in situ hybridization (FISH). RESULTS: A 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs (12% of germinoma cases and 50% of NGGCT cases), particularly in cases with malignant components, such as immature teratoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma. 12p gain and KIT mutation were mutually exclusive events. The presence of 12p gain correlated with shorter progression-free (PFS) and overall survival (OS) (10-year OS: 59% vs. 94%, with and without 12p gain, respectively, P = 0.0002), even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS (10-year OS: 47% vs. 90%, respectively, P = 0.02). The 12p copy number status was shared among histological components in mixed GCTs. CONCLUSIONS: 12p gain may predict the presence of malignant components of NGGCTs, and poor prognosis of the patients. It may be associated with early tumorigenesis of CNS GCT.

Change sign detection with differential MDL change statistics and its applications to COVID-19 pandemic analysis.

We are concerned with the issue of detecting changes and their signs from a data stream. For example, when given time series of COVID-19 cases in a region, we may raise early warning signals of an epidemic by detecting signs of changes in the data. We propose a novel methodology to address this issue. The key idea is to employ a new information-theoretic notion, which we call the differential minimum description length change statistics (D-MDL), for measuring the scores of change sign. We first give a fundamental theory for D-MDL. We then demonstrate its effectiveness using synthetic datasets. We apply it to detecting early warning signals of the COVID-19 epidemic using time series of the cases for individual countries. We empirically demonstrate that D-MDL is able to raise early warning signals of events such as significant increase/decrease of cases. Remarkably, for about [Formula: see text] of the events of significant increase of cases in studied countries, our method can detect warning signals as early as nearly six days on average before the events, buying considerably long time for making responses. We further relate the warning signals to the dynamics of the basic reproduction number R0 and the timing of social distancing. The results show that our method is a promising approach to the epidemic analysis from a data science viewpoint.

Low tumor cell content predicts favorable prognosis in germinoma patients.

BACKGROUND: Germinoma preferentially occurs in pediatric and young adult age groups. Although they are responsive to treatment with chemotherapy and radiation, the treatment may cause long-term sequelae in their later lives. Here, we searched for clinical and histopathological features to predict the prognosis of germinoma and affect treatment response. METHODS: A total of 114 germinoma cases were included in the analysis. We investigated the association between clinical factors, tumor cell content, and progression-free survival (PFS). RESULTS: The tumor cell content was widely distributed from <5% to 90% in the specimens, with a median value of 50%. Female patients showed higher tumor cell content in the specimens (P = .002). Cases with lesions at atypical sites showed shorter PFS than those with lesions at other sites (P = .03). Patients with a higher tumor cell content (≥50%) showed shorter PFS than those with a lower tumor cell content (<50%) (P = .03). In multivariate analysis, tumor cell content was the only statistically significant prognostic factor (P = .04). Among the 7 cases treated with local radiation and chemotherapy, all 3 cases that recurred (2 outside of the radiation field, 1 unknown) had tumor cell content of ≥50% in the original specimen, whereas all 4 cases without recurrence had tumor cell contents of <50%. CONCLUSIONS: We found that tumor cell content significantly affected the prognosis of germinomas. Although validation of these results using an independent and larger cohort is necessary, this potentially opens the possibility of leveraging this pathological factor in future clinical trials when stratifying the treatment intensity.

Do you feel happy when other members look happy? Moderating effect of community-level social capital on interconnection of happiness.

One's happiness is expected to be affected by the happiness of surrounding others. This socio-psychological nature of happiness, however, has not been fully examined in the literature of social psychology. The current study examined if this "psychological interconnection of happiness" occurs when (i) individuals have strong personal social capital and/or (ii) individuals belong to a community where other members have strong social capital. We analysed a large social survey dataset sampled from 408 communities in Japan (N = 7295). The psychological interconnection of happiness was measured by calculating the correlation between individual happiness and perceived community happiness. The multilevel analyses revealed that the psychological interconnection of happiness was moderated by community-level social capital above and beyond individual-level social capital, while individual-level social capital did not have a significant moderation effect.

How do socio-ecological factors shape culture? Understanding the process of micro-macro interactions.

Socio-ecological environments produce certain psychological functions. that are adaptive for survival in each environment. Past evidence suggests that interdependence-related psychological features are prevalent in East Asian cultures partly due to the history of 'rice-crop farming' (versus herding) in those areas. However, it is unclear how and why certain functional behaviors required by the socio-ecological environment are sublimated to become cultural values, which are then transmitted and shared among people. In this paper, we conceptually review the works examining various macro sharing processes for cultural values, and focus on the use of multilevel analysis in elucidating the effect of both macro and individual level factors. Uchida et al.'s study (2019) suggests that collective activities at the macro level (community-level), which is required by a certain socio-ecological environment, promote interdependence not only among farmers but also non-farmers. The multilevel processes of how psychological characteristics are construed by macro factors will be discussed.

Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium.

BACKGROUND: We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. METHODS: Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews. RESULTS: All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. CONCLUSIONS: The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

Farming cultivates a community-level shared culture through collective activities: Examining contextual effects with multilevel analyses.

It has been suggested that the well-known cultural differences in interdependence across cultures are linked to economic activities, such as farming. However, the underlying processes of how such psychological tendencies are shared among people in a society has not been sufficiently investigated. This article addresses the multilevel processes of how psychological characteristics are shared among people. We focus on collective activities that go beyond the individual's personal economic activities. Multilevel analyses on a large-scale survey (residents of Japanese communities, N = 7,295) of 408 communities, along with a follow-up survey (N = 1,714) of 86 communities, suggested that "concern for reputation" (one aspect of interdependence) was more prevalent in farming communities than in nonfarming communities, not only for farmers, but also for nonfarmers. Furthermore, multilevel mediational analyses suggested that, (a) the proportion of farmers in a community was positively associated with participation in collective activities (e.g., maintenance of community infrastructure) by both farmers and nonfarmers, and (b) this is in turn associated with increased levels of concern for reputation at the community level. Community-level longitudinal analyses revealed that collective activities promoted residents' concern for reputation about two years later. These findings support our "collective activity" hypothesis, and demonstrate that interdependence can be constructed through social interaction via community activities. Fishing was associated with high levels of self-esteem and risk avoidance, and these effects were found only at the individual level. We conclude that economic activities affect social interaction, which in turn affects the multilevel processes of cultural emergence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Significance of molecular classification of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogeneous group of tumors.

Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category.

Cross-cultural invariances in the architecture of shame.

Human foragers are obligately group-living, and their high dependence on mutual aid is believed to have characterized our species' social evolution. It was therefore a central adaptive problem for our ancestors to avoid damaging the willingness of other group members to render them assistance. Cognitively, this requires a predictive map of the degree to which others would devalue the individual based on each of various possible acts. With such a map, an individual can avoid socially costly behaviors by anticipating how much audience devaluation a potential action (e.g., stealing) would cause and weigh this against the action's direct payoff (e.g., acquiring). The shame system manifests all of the functional properties required to solve this adaptive problem, with the aversive intensity of shame encoding the social cost. Previous data from three Western(ized) societies indicated that the shame evoked when the individual anticipates committing various acts closely tracks the magnitude of devaluation expressed by audiences in response to those acts. Here we report data supporting the broader claim that shame is a basic part of human biology. We conducted an experiment among 899 participants in 15 small-scale communities scattered around the world. Despite widely varying languages, cultures, and subsistence modes, shame in each community closely tracked the devaluation of local audiences (mean r = +0.84). The fact that the same pattern is encountered in such mutually remote communities suggests that shame's match to audience devaluation is a design feature crafted by selection and not a product of cultural contact or convergent cultural evolution.

Invariances in the architecture of pride across small-scale societies.

Becoming valuable to fellow group members so that one would attract assistance in times of need is a major adaptive problem. To solve it, the individual needs a predictive map of the degree to which others value different acts so that, in choosing how to act, the payoff arising from others' valuation of a potential action (e.g., showing bandmates that one is a skilled forager by pursuing a hard-to-acquire prey item) can be added to the direct payoff of the action (e.g., gaining the nutrients of the prey captured). The pride system seems to incorporate all of the elements necessary to solve this adaptive problem. Importantly, data from western(-ized), educated, industrialized, rich, and democratic (WEIRD) societies indicate close quantitative correspondences between pride and the valuations of audiences. Do those results generalize beyond industrial mass societies? To find out, we conducted an experiment among 567 participants in 10 small-scale societies scattered across Central and South America, Africa, and Asia: (i) Bosawás Reserve, Nicaragua; (ii) Cotopaxi, Ecuador; (iii) Drâa-Tafilalet, Morocco; (iv) Enugu, Nigeria; (v) Le Morne, Mauritius; (vi) La Gaulette, Mauritius; (vii) Tuva, Russia; (viii) Shaanxi and Henan, China; (ix) farming communities in Japan; and (x) fishing communities in Japan. Despite widely varying languages, cultures, and subsistence modes, pride in each community closely tracked the valuation of audiences locally (mean r = +0.66) and even across communities (mean r = +0.29). This suggests that the pride system not only develops the same functional architecture everywhere but also operates with a substantial degree of universality in its content.

Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas.

Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling. We showed that pure germinomas are characterized by global low DNA methylation, a unique epigenetic feature making them distinct from all other iGCTs subtypes. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, possibly indicating the cell of origin for these tumors. Unlike PGC, however, hypomethylation extends to long interspersed nuclear element retrotransposons. Histologically and epigenetically distinct microdissected components of mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell.

Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy.

Germ cell tumors constitute a heterogeneous group that displays a broad spectrum of morphology. They often arise in testes; however, extragonadal occurrence, in particular brain, is not uncommon, and whether they share a common pathogenesis is unknown. We performed whole exome sequencing in 41 pairs of central nervous system germ cell tumors (CNS GCTs) of various histology and their matched normal tissues. We then performed targeted sequencing of 41 selected genes in a total of 124 CNS GCTs, 65 testicular germ cell tumors (tGCTs) and 8 metastatic GCTs to the CNS. The results showed that mutually exclusive mutations of genes involved in the MAPK pathway were most common (48.4 %), typically in KIT (27.4 %), followed by those in the PI3K pathway (12.9 %), particularly in MTOR (6.5 %), among the 124 CNS GCTs. Pure germinomas and non-germinomatous germ cell tumors (NGGCTs), as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting that GCTs share a common molecular pathogenesis. Mutated MTOR identified in CNS GCTs upregulated phosphorylation of the AKT pathway proteins including AKT and 4EBP1 in nutrient-deprived conditions and enhanced soft-agar colony formation; both events were suppressed in a dose-dependent manner by addition of the MTOR inhibitor pp242. Our findings indicate that the dominant genetic drivers of GCTs regardless of the site of origin are activation of the MAPK and/or PI3K pathways by somatic point mutations. Mutated MTOR represents a potential target for novel targeted therapies for refractory GCTs.

Glioblastomas with IDH1/2 mutations have a short clinical history and have a favorable clinical outcome.

OBJECTIVE: Glioblastomas with isocitrate dehydrogenase 1/2 mutations comprise a biologically distinct subgroup of glioblastomas. We studied isocitrate dehydrogenase 1/2 mutant glioblastomas at the clinical, molecular and radiological levels to define their clinical features, including the prognostic value of isocitrate dehydrogenase 1/2 mutations compared with isocitrate dehydrogenase 1/2 wild-type glioblastomas. METHODS: We investigated 128 newly diagnosed glioblastoma patients who were treated at our institute between January 2005 and May 2013. Isocitrate dehydrogenase 1/2 mutation status was determined using pyrosequencing. O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation and 1p/19q co-deletions were also analyzed using pyrosequencing and multiplex ligation-dependent probe amplification, respectively. RESULTS: Isocitrate dehydrogenase 1/2 mutations were detected in 10 of 128 patients (7.8%). Isocitrate dehydrogenase 1/2 mutations were correlated with a younger age, the presence of an oligodendroglial component and 1p/19q co-deletions and a longer survival time. The interval from initial symptom to initial operation did not differ according to isocitrate dehydrogenase 1/2 mutation status (median interval: 2.3 versus 1.2 months; P = 0.13). Two of three isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions had an oligodendroglial component and were associated with a prolonged survival time. Multivariate analysis of 90 patients treated with temozolomide-based chemoradiotherapy indicated that age, extent of resection, postoperative Karnofsky performance score and O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation were correlated with better survival. Isocitrate dehydrogenase 1/2 mutations showed a trend for improved survival (P = 0.068). CONCLUSIONS: Most isocitrate dehydrogenase 1/2 mutant glioblastomas have a short clinical history, and some isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions behave like oligodendroglial tumors. Isocitrate dehydrogenase 1/2 mutations may have a positive prognostic impact on the Japanese population.

Human chorionic gonadotropin is expressed virtually in all intracranial germ cell tumors.

Human chorionic gonadotropin (hCG) production has been utilized as a diagnostic marker for germinoma with syncytiotrophoblastic giant cells (STGC) and choriocarcinoma. Elevated hCG in germinoma is considered to predict less favorable prognosis, and an intensive treatment strategy may accordingly be applied. However, there is some evidence that any germinoma may produce hCG to varying extent. We investigated mRNA expression of the hCG ß subunit (hCGß) using real time quantitative polymerase chain reaction in 94 germ cell tumors (GCTs). Most (93.3 %) GCTs showed higher expression levels compared with that of normal brain tissue (1.09 × 10(0)-1.40 × 10(5) fold). The expression was the highest in GCTs which harbor choriocarcinoma or STGC components. The expression level of hCGß in germinoma was highly variable (1.09 × 10(0)-5.88 × 10(4) fold) in linear but not bimodal distribution. hCG concentrations in serum and CSF correlated with gene expression, especially when GCTs with single histological component were analyzed separately. The expression was not significantly associated with recurrence in pure germinoma. These results suggest that the serum/CSF hCG levels may need to be interpreted with caution as most GCTs appear to have the capacity of producing hCG irrespective of their histology. The clinical significance of ubiquitous hCG expression in GCTs needs further investigation.

Revisiting TP53 Mutations and Immunohistochemistry--A Comparative Study in 157 Diffuse Gliomas.

The association between p53 immunohistochemistry and TP53 mutation status has been controversial. The present study aims to re-evaluate the efficacy of p53 immunohistochemistry to predict the mutational status of TP53. A total of 157 diffuse gliomas (World Health Organization grades II-IV) were assessed by exon-by-exon DNA sequencing from exon 4 through 10 of TP53 using frozen tissue samples. Immunohistochemistry with a p53 antibody (DO-7) on paired formalin-fixed paraffin-embedded materials was assessed for the extent and intensity of reactivity in all cases. A total of 72 mutations were detected in 66 samples. They included 60 missense mutations, five nonsense mutations, four deletions and three alterations in the splicing sites. A receiver operating characteristic curve analysis revealed that strong p53 immunoreactivity in more than 10% of cells provided the most accurate prediction of mutation. Using this cutoff value, 52 of 55 immunopositive cases harbored a mutation, whereas only 14 of 102 immunonegative cases showed mutations, sensitivity and specificity being 78.8% and 96.7%. Tumors with frameshift mutations frequently showed negative immunostaining. Staining interpretation by an independent observer yielded comparable accuracy. We thus propose p53 immunohistochemistry as a moderately sensitive and highly specific marker to predict TP53 mutation.

Development of a robust and sensitive pyrosequencing assay for the detection of IDH1/2 mutations in gliomas.

Assessment of the mutational status of the isocitrate dehydrogenase 1/2 (IDH1/2) gene has become an integral part of the standard diagnostic procedure and, therefore, needs to be accurate. This may, however, be compromised by various factors including the method of analysis and a low tumor cell content. We have developed a rapid, sensitive and robust assay to detect all types of mutation in either IDH1 or IDH2 using pyrosequencing. The efficacy of detecting mutation was evaluated using a panel of control plasmids representing all the different types of IDH1/2 mutation and a set of 160 tumor specimens. The sensitivity of the assays was examined by a serial dilution analysis performed on samples containing various ratios of wild-type and mutant alleles. The pyrosequencing assay detected as little as 5 % of mutant alleles for most mutation types, while conventional Sanger sequencing required the presence of at least 20 % of mutant alleles for identifying mutations. The pyrosequencing assay detected IDH1/2 mutations in three samples which were missed by Sanger sequencing due to their low tumor cell contents. Our assay is particularly useful for the analysis of a large number of specimens as in a retrospective clinical study for example.