Effects of fear of COVID-19 on older volunteers' willingness to continue their activities: REPRINTS cohort study.

AIM: This study examined the effects of fear of COVID-19 on older volunteers' willingness to continue activities that required face-to-face interactions. METHODS: From September to November 2020, a self-administered questionnaire survey was conducted with 481 older adult volunteers. A total of 423 responses were collected; 343 had no missing items and were included in the analysis. Analysis items included willingness to continue volunteer activities, fear of COVID-19, mental and physical health, and a group of items related to factors influencing the continuation of volunteer activities. RESULTS: The structural analysis of covariance indicated that volunteer orientation, which included items considered to be factors for continuing volunteer activities, had a significant positive influence on the willingness to continue activities. Fear of COVID-19 had a significant negative effect on the latent variable mental and physical health, which consisted of a subjective sense of health, but fear of COVID-19 and physical and mental health had no significant effect on the willingness to continue volunteering. CONCLUSIONS: Our results suggest that the willingness of older adults to continue volunteer activities during the COVID-19 pandemic is influenced by their volunteer orientation and is not affected by their fear of COVID-19. Geriatr Gerontol Int 2024; 24: 370-376.

Identification of target cells of human papillomavirus 18 using squamocolumnar junction organoids.

Human papillomavirus 18 (HPV18) is a highly malignant HPV genotype among high-risk HPVs, characterized by the difficulty of detecting it in precancerous lesions and its high prevalence in adenocarcinomas. The cellular targets and molecular mechanisms underlying its infection remain unclear. In this study, we aimed to identify the cells targeted by HPV18 and elucidate the molecular mechanisms underlying HPV18 replication. Initially, we established a lentiviral vector (HPV18LCR-GFP vector) containing the HPV18 long control region promoter located upstream of EGFP. Subsequently, HPV18LCR-GFP vectors were transduced into patient-derived squamocolumnar junction organoids, and the presence of GFP-positive cells was evaluated. Single-cell RNA sequencing of GFP-positive and GFP-negative cells was conducted. Differentially expressed gene analysis revealed that 169 and 484 genes were significantly upregulated in GFP-positive and GFP-negative cells, respectively. Pathway analysis showed that pathways associated with cell cycle and viral carcinogenesis were upregulated in GFP-positive cells, whereas keratinization and mitophagy/autophagy-related pathways were upregulated in GFP-negative cells. siRNA-mediated luciferase reporter assay and HPV18 genome replication assay validated that, among the upregulated genes, ADNP, FHL2, and NPM3 were significantly associated with the activation of the HPV18 early promoter and maintenance of the HPV18 genome. Among them, NPM3 showed substantially higher expression in HPV-related cervical adenocarcinomas than in squamous cell carcinomas, and NPM3 knockdown of HPV18-infected cells downregulated stem cell-related genes. Our new experimental model allows us to identify novel genes involved in HPV18 early promoter activities. These molecules might serve as therapeutic targets in HPV18-infected cervical lesions.

Influence of education and subjective financial status on dietary habits among young, middle-aged, and older adults in Japan: a cross-sectional study.

BACKGROUND: Research has suggested an association between lower socioeconomic status (SES) and unhealthy dietary habits. However, differences in the effects of different SES indicators and age remain unclear. The current study addressed this research gap by investigating the relationship between SES and unhealthy dietary habits, specifically focusing on educational attainment and subjective financial status (SFS) among varied age groups. METHODS: Data were derived from a mail survey of 8,464 people living in a suburb of Tokyo, Japan. Participants were classified into three age groups (20-39 years: young adults; 40-64 years: middle-aged adults; and 65-97 years: older adults). SES was assessed based on individual educational attainment and SFS. Unhealthy dietary habits were defined as skipping breakfast and a low frequency of balanced meal consumption. Participants were asked how often they ate breakfast, and those who did not respond "every day" were categorized as "breakfast skippers." Low frequency of balanced meal consumption was defined as eating a meal that included a staple meal, main dish, and side dishes at least twice a day for less than five days per week. Poisson regression analyses with robust variance adjusted for potential covariates were used to determine the interactive effects of educational attainment and SFS on unhealthy dietary habits. RESULTS: Individuals with lower educational attainment across all age groups skipped breakfast more frequently compared to those with higher educational attainment. For older adults, poor SFS was associated with skipping breakfast. Young adults with poor SFS and middle-aged adults with lower educational attainment tended to eat less balanced meals. In addition, an interaction effect was found in older adults, where those with lower education despite good SFS and those with poor SFS despite higher education were at a greater risk of falling into unhealthy diet. CONCLUSIONS: The findings suggested that different SES indicators affect healthy dietary habits in different generations, and therefore, health policies should consider the potential influence of different SES on promoting healthier dietary habits.

Linking antigen specific T-cell dynamics in a microfluidic chip to single cell transcription patterns.

A new non-invasive screening profile has been realized that can aid in determining T-cell activation state at single-cell level. Production of activated T-cells with good specificity and stable proliferation is greatly beneficial for advancing adoptive immunotherapy as innate immunological cells are not effective in recognizing and eliminating cancer as expected. The screening method is realized by relating intracellular Ca2+ intensity and motility of T-cells interacting with APC (Antigen Presenting Cells) in a microfluidic chip. The system is tested using APC pulsed with OVA257-264 peptide and its modified affinities (N4, Q4, T4 and V4), and the T-cells from OT-1 mice. In addition, single cell RNA sequencing reveals the activation states of the cells and the clusters from the derived profiles can be indicative of the T-cell activation state. The presented system here can be versatile for a comprehensive application to proceed with T-cell-based immunotherapy and screen the antigen-specific T-cells with excellent efficiency and high proliferation.

Application of organoid culture from HPV18-positive small cell carcinoma of the uterine cervix for precision medicine.

BACKGROUND: Small cell carcinoma of the uterine cervix (SCCC) is a rare and highly malignant human papillomavirus (HPV)-associated cancer in which human genes related to the integration site can serve as a target for precision medicine. The aim of our study was to establish a workflow for precision medicine of HPV-associated cancer using patient-derived organoid. METHODS: Organoid was established from the biopsy of a patient diagnosed with HPV18-positive SCCC. Therapeutic targets were identified by whole exome sequencing (WES) and RNA-seq analysis. Drug sensitivity testing was performed using organoids and organoid-derived mouse xenograft model. RESULTS: WES revealed that both the original tumor and organoid had 19 somatic variants in common, including the KRAS p.G12D pathogenic variant. Meanwhile, RNA-seq revealed that HPV18 was integrated into chromosome 8 at 8q24.21 with increased expression of the proto-oncogene MYC. Drug sensitivity testing revealed that a KRAS pathway inhibitor exerted strong anti-cancer effects on the SCCC organoid compared to a MYC inhibitor, which were also confirmed in the xenograft model. CONCLUSION: In this study, we confirmed two strategies for identifying therapeutic targets of HPV-derived SCCC, WES for identifying pathogenic variants and RNA sequencing for identifying HPV integration sites. Organoid culture is an effective tool for unveiling the oncogenic process of rare tumors and can be a breakthrough for the development of precision medicine for patients with HPV-positive SCCC.

Cells with stem-like properties are associated with the development of HPV18-positive cervical cancer.

The cellular origins of cervical cancer and the histological differentiation of human papillomavirus (HPV)-infected cells remain unexplained. To gain new insights into the carcinogenesis and histological differentiation of HPV-associated cervical cancer, we focused on cervical cancer with mixed histological types. We conducted genomic and transcriptomic analyses of cervical cancers with mixed histological types. The commonality of the cellular origins of these cancers was inferred using phylogenetic analysis and by assessing the HPV integration sites. Carcinogenesis was estimated by analyzing human gene expression profiles in different histological types. Among 42 cervical cancers with known HPV types, mixed histological types were detected in four cases, and three of them were HPV18-positive. Phylogenetic analysis of these three cases revealed that the different histological types had a common cell of origin. Moreover, the HPV-derived transcriptome and HPV integration sites were common among different histological types, suggesting that HPV integration could occur before differentiation into each histological type. Human gene expression profiles indicated that HPV18-positive cancer retained immunologically cold components with stem cell properties. Mixed cervical cancer has a common cellular origin among different histological types, and progenitor cells with stem-like properties may be associated with the development of HPV18-positive cervical cancer.

Protective Role of Endothelial Fibulin-4 in Valvulo-Arterial Integrity.

Background Homeostasis of the vessel wall is cooperatively maintained by endothelial cells (ECs), smooth muscle cells, and adventitial fibroblasts. The genetic deletion of fibulin-4 (Fbln4) in smooth muscle cells (SMKO) leads to the formation of thoracic aortic aneurysms with the disruption of elastic fibers. Although Fbln4 is expressed in the entire vessel wall, its function in ECs and relevance to the maintenance of valvulo-arterial integrity are not fully understood. Methods and Results Gene silencing of FBLN4 was conducted on human aortic ECs to evaluate morphological changes and gene expression profile. Fbln4 double knockout (DKO) mice in ECs and smooth muscle cells were generated and subjected to histological analysis, echocardiography, Western blotting, RNA sequencing, and immunostaining. An evaluation of the thoracic aortic aneurysm phenotype and screening of altered signaling pathways were performed. Knockdown of FBLN4 in human aortic ECs induced mesenchymal cell-like changes with the upregulation of mesenchymal genes, including TAGLN and MYL9. DKO mice showed the exacerbation of thoracic aortic aneurysms when compared with those of SMKO and upregulated Thbs1, a mechanical stress-responsive molecule, throughout the aorta. DKO mice also showed progressive aortic valve thickening with collagen deposition from postnatal day 14, as well as turbulent flow in the ascending aorta. Furthermore, RNA sequencing and immunostaining of the aortic valve revealed the upregulation of genes involved in endothelial-to-mesenchymal transition, inflammatory response, and tissue fibrosis in DKO valves and the presence of activated valve interstitial cells. Conclusions The current study uncovers the pivotal role of endothelial fibulin-4 in the maintenance of valvulo-arterial integrity, which influences thoracic aortic aneurysm progression.

Integrated spatial analysis of gene mutation and gene expression for understanding tumor diversity in formalin-fixed paraffin-embedded lung adenocarcinoma.

Introduction: A deeper understanding of intratumoral heterogeneity is essential for prognosis prediction or accurate treatment plan decisions in clinical practice. However, due to the cross-links and degradation of biomolecules within formalin-fixed paraffin-embedded (FFPE) specimens, it is challenging to analyze them. In this study, we aimed to optimize the simultaneous extraction of mRNA and DNA from microdissected FFPE tissues (φ = 100 µm) and apply the method to analyze tumor diversity in lung adenocarcinoma before and after erlotinib administration. Method: Two magnetic beads were used for the simultaneous extraction of mRNA and DNA. The decross-linking conditions were evaluated for gene mutation and gene expression analyses of microdissected FFPE tissues. Lung lymph nodes before treatment and lung adenocarcinoma after erlotinib administration were collected from the same patient and were preserved as FFPE specimens for 4 years. Gene expression and gene mutations between histologically classified regions of lung adenocarcinoma (pre-treatment tumor in lung lymph node biopsies and post-treatment tumor, normal lung, tumor stroma, and remission stroma, in resected lung tissue) were compared in a microdissection-based approach. Results: Using the optimized simultaneous extraction of DNA and mRNA and whole-genome amplification, we detected approximately 4,000-10,000 expressed genes and the epidermal growth factor receptor (EGFR) driver gene mutations from microdissected FFPE tissues. We found the differences in the highly expressed cancer-associated genes and the positive rate of EGFR exon 19 deletions among the tumor before and after treatment and tumor stroma, even though they were collected from tumors of the same patient or close regions of the same specimen. Conclusion: Our integrated spatial analysis method would be applied to various FFPE pathology specimens providing area-specific gene expression and gene mutation information.

Reproducible and sensitive micro-tissue RNA sequencing from formalin-fixed paraffin-embedded tissues for spatial gene expression analysis.

Spatial transcriptome analysis of formalin-fixed paraffin-embedded (FFPE) tissues using RNA-sequencing (RNA-seq) provides interactive information on morphology and gene expression, which is useful for clinical applications. However, despite the advantages of long-term storage at room temperature, FFPE tissues may be severely damaged by methylene crosslinking and provide less gene information than fresh-frozen tissues. In this study, we proposed a sensitive FFPE micro-tissue RNA-seq method that combines the punching of tissue sections (diameter: 100 µm) and the direct construction of RNA-seq libraries. We evaluated a method using mouse liver tissues at two years after fixation and embedding and detected approximately 7000 genes in micro-punched tissue-spots (thickness: 10 µm), similar to that detected with purified total RNA (2.5 ng) equivalent to the several dozen cells in the spot. We applied this method to clinical FFPE specimens of lung cancer that had been fixed and embedded 6 years prior, and found that it was possible to determine characteristic gene expression in the microenvironment containing tumor and non-tumor cells of different morphologies. This result indicates that spatial gene expression analysis of the tumor microenvironment is feasible using FFPE tissue sections stored for extensive periods in medical facilities.

Effects of intergenerational contact on social capital in community-dwelling adults aged 25-84 years: a non-randomized community-based intervention.

BACKGROUND: Accumulating social capital in urban areas is essential to improve community health. Previous studies suggested that intergenerational contact may be effective for enhancing social capital. However, no study has examined the effect of intergenerational contact on social capital through a population-based evaluation. This study aimed to investigate the effects of a community-based intervention to increase the frequency of intergenerational contact on social capital among adults aged 25-84 years. METHODS: This study used a non-randomized controlled trial design to conduct a community-based intervention (from March 2016 to March 2019). The study area was Tama ward, Kawasaki city, Kanagawa, Japan. The area comprises five districts; one district was assigned as the intervention group and the other four districts as the control group. We provided the intervention to residents in the intervention group. The intervention comprised three phases: Phase 1 was the preparation term (organizing the project committee); Phase 2 was the implementation term (trained volunteer staff members, conducted the intergenerational greeting campaign, and held intergenerational contact events); and Phase 3 was the transition term (surrendering the lead role of the project to the city hall field workers). In the control group, field workers provided public health services as usual. We conducted mail surveys in September 2016 and November 2018 to assess the effects of the intervention on social capital during Phase 2. Eligible participants were randomly selected from community-dwelling adults aged 25-84 years according to age (10,620 control group individuals and 4479 intervention group individuals). We evaluated social trust, norm of reciprocity, and social support as outcome variables. RESULTS: In total, 2518 participants completed both surveys and were analyzed (control group: 1727; intervention group: 791). We found that social trust (coefficient = 0.065; 95% confidence interval [CI]: 0.006, 0.125) and norm of reciprocity (coefficient = 0.084; 95% CI: 0.020, 0.149) positively changed in the intervention group compared with the control group. CONCLUSIONS: This community-based intervention may contribute to sustaining and improving social capital among community-dwelling adults. TRIAL REGISTRATION: UMIN000046769 (UMIN-CTR); first registered on January 28, 2022 (retrospectively registered).

Examining health risk behaviors of self-employed and employed workers in Japan: a cross-sectional study.

OBJECTIVES: Self-employed workers have a higher risk for adverse health outcomes than employed workers. However, the differences in health risk behaviors by employment status are largely unknown. This study examined differences in health risk behaviors between self-employed and employed (permanent/non-permanent) workers by sex and age (20-59 years, 60-79 years). STUDY DESIGN: This was a cross-sectional study involving community-dwelling adults living in urban cities in Japan. METHODS: In 2019, we conducted a mail survey in Wako city, Saitama, and Fuchu city, Tokyo. In total, 30,315 adults aged ≥18 years were randomly selected, and 14,185 completed the survey (response rate: 46.8%). The participants for analysis were 8538 workers. Health risk behaviors included physical inactivity (<150 min/wk of moderate-to-vigorous physical activity), prolonged sitting (>480 min/d), high-frequency drinking (≥3 d/wk), tobacco use (current smoker), and overweight (body mass index ≥ 25 kg/m2). We also calculated the total number of health risk behaviors. RESULTS: Self-employed workers had more health risk behaviors than permanent and non-permanent employees, with this difference more significant among younger males. In younger males, compared with self-employment, permanent employment was associated with less tobacco use, and non-permanent employment was associated with less physical inactivity, prolonged sitting, high-frequency drinking, and overweight. In younger females, non-permanent employment was associated with less prolonged sitting and overweight than self-employment. In older males and females, the prevalence of physical inactivity was lower in non-permanent employed than in self-employed workers. CONCLUSIONS: Promoting health behaviors among self-employed may be beneficial for reducing health inequalities between self-employed and employed workers.

Identification of two cancer stem cell-like populations in triple-negative breast cancer xenografts.

Gene expression analysis at the single-cell level by next-generation sequencing has revealed the existence of clonal dissemination and microheterogeneity in cancer metastasis. The current spatial analysis technologies can elucidate the heterogeneity of cell-cell interactions in situ. To reveal the regional and expressional heterogeneity in primary tumors and metastases, we performed transcriptomic analysis of microtissues dissected from a triple-negative breast cancer (TNBC) cell line MDA-MB-231 xenograft model with our automated tissue microdissection punching technology. This multiple-microtissue transcriptome analysis revealed three cancer cell-type clusters in the primary tumor and axillary lymph node metastasis, two of which were cancer stem cell (CSC)-like clusters (CD44/MYC-high, HMGA1-high). Reanalysis of public single-cell RNA-sequencing datasets confirmed that the two CSC-like populations existed in TNBC xenograft models and in TNBC patients. The diversity of these multiple CSC-like populations could cause differential anticancer drug resistance, increasing the difficulty of curing this cancer.

Suicide Prevention Program with Cooperation from Senior Volunteers, Governments, and Schools: A Study of the Intervention Effects of "Educational Lessons Regarding SOS Output" Focusing on Junior High School Students.

As a suicide countermeasure for young people, implementing "SOS output education" that provides young people with opportunities and approaches to seeking support with community cooperation can be expected to reduce lifelong suicide risk. We implemented an "SOS output education" for junior high school students with cooperation from educators, government staff, and older people working as community volunteers. A total of 188 students were allocated to an intervention group and a waiting group. Outcome assessments were implemented at three points in time: before the program (Time 1), after the program (Time 2), and three months after the program (Time 3). Results showed that the number of people with worries increased in the intervention group compared with the waiting group between Time 1 and Time 2. There was also an increase in people with "reliable adults" between Time 1 and Time 3, and people with "adults who you can talk to at any time" increased between Time 2 and Time 3 in the intervention group. By implementing the SOS output education program with community cooperation, an increase was observed in the intervention group in terms of support-seeking awareness and the number of people with reliable adults and with adults who they can talk to at any time.

Influence of "Face-to-Face Contact" and "Non-Face-to-Face Contact" on the Subsequent Decline in Self-Rated Health and Mental Health Status of Young, Middle-Aged, and Older Japanese Adults: A Two-Year Prospective Study.

This study aims to identify the independent influence of face-to-face contact (FFC) and non-face-to-face contact (NFFC) on the subsequent decline in self-rated health and mental health status by age. A total of 12,000 participants were randomly selected among residents in the study area, and 1751 of them responded to both the 2016 and 2018 mail surveys. The participants were subsequently classified into three age groups (25-49: Young adults; 50-64: Mid-aged adults; and 65-84: Older adults). Social contact was assessed by computing the frequencies of FFC and NFFC. Multiple logistic regression analysis showed the risk of social contact on the decline in self-rated health and World Health Organization-Five Well-Being Index. Both FFC and NFFC were significantly associated with maintaining mental health; however, the impacts of FFC on mental health were more significant than that of NFFC among older adults and young adults. Compared with the no contact group, FFC was significantly associated with maintaining self-rated health in mid-aged adults. The influence of FFC and NFFC on health differed by age group.

The effects of reciprocal support on mental health among intergenerational non-relatives-A comparison by age group.

PURPOSE: This study aimed to verify the direction of providing and receiving intergenerational support and examine its effects on mental health among intergenerational non-relatives. MATERIALS AND METHODS: In the initial survey (Time1), approximately 65,000 residents of Wako City in Saitama Prefecture, Japan, were considered, from which, a sample of 7,000 people was obtained. A total of 2,982 valid responses was received, and a follow-up survey was conducted two years later (Time2). RESULTS: Structural equation modeling with a cross-lagged effect model and a synchronous effect model showed that the direction of giving and receiving intergenerational support had changed with age; while the young and middle-aged groups shifted their direction from receiving support to giving support, the older adults shifted their direction from giving support to receiving support. Furthermore, in the young-adults group, receiving support from older adults positively influenced their mental health two years later. For the middle-aged group, giving support positively influenced their mental health at Time2. For the old-old group, receiving support from young and middle-aged people positively influenced the mental health at Time2. CONCLUSIONS: To facilitate intergenerational mutual help in the local community, it is necessary to create opportunities for older adults to provide support to young and middle-aged people and, in return, create a mechanism to prompt support from young and middle-aged people for older adults.

[A Case of Diffuse Large B Cell Lymphoma of the Extrahepatic Bile Duct Cholangiocarcinoma].

The patient was an 81-year-old man who was hospitalized with poor appetite and obstructive jaundice. An abdominal CT scan showed remarkable thickening of the wall from the cystic duct to extrahepatic bile duct. Endoscopic retrograde cholangiopancreatography( ERCP)revealed stricture at the extrahepatic bile duct. Cholangiocarcinoma was diagnosed and pancreaticoduodenectomy was performed. The histopathological diagnosis was diffuse large B cell lymphoma (DLBCL). The patient was stable after the operation. We present a case report describing the resection of DLBCL of the extrahepatic bile duct along with a review of the literature.

[Information tools commonly used during a natural disaster among information and communication technology device users].

Objective　During a natural disaster, accessing appropriate information is essential to reduce damage to health. Information and community technology (ICT) devices can help in obtaining information. This study aimed to identify the characteristics of information tools commonly used by ICT device users during a natural disaster, and identify associations between sociodemographic factors and Internet-based information tools.Methods　In 2019, 21,300 adults aged 18 years and above living in Fuchu city, Tokyo, were enrolled in our survey. Participants were asked which ICT devices (computer, smartphone, tablet, or mobile phone) they used. Those who used at least one device were classified as ICT device users. To evaluate the information tools commonly used during a natural disaster, participants were asked to select information resources they would use from a list provided (television, radio, Internet search, alert mail, administrative radio system, local government website, neighborhood, family, and friends). We classified Internet search, alert mail, and local government website as Internet-based tools. A Poisson regression model with robust variance was used to assess sex and age differences among ICT device users and clarify associations between sociodemographic factors and the use of Internet-based information tools.Results　The respondents were 9,201 adults (response rate: 43.2%). Among the ICT device users, more than 95% were below 70 years. Moreover, 66.7% of women and 70.6% of men were 80 years or above. More than 80% preferred television to get information during a natural disaster. Over 70% of women below 60 years and men below 70 years preferred to use an Internet search, compared with 7.8% of women aged 80 years or above. Those who selected Internet search were more likely to be women, have a high household income and high educational attainment, be widowed/divorced/single, and be less likely to live alone or be older adults (especially older women). Participants who selected alert mail were more likely to be women and have high educational attainment, and less likely to be widowed/divorced/single and older adults. Those who selected government websites were more likely to be women, have high educational attainment and be widowed/divorced/single, and less likely to live alone, be widowed/divorced/single, and be older adults (especially older women).Conclusion　There were differences by sex and age in information tools selected for use during a natural disaster among ICT device users. Sociodemographic factors were associated with Internet-based tools, and use differed by type of information tool.

Distinctive Regulation of Emotional Behaviors and Fear-Related Gene Expression Responses in Two Extended Amygdala Subnuclei With Similar Molecular Profiles.

The central nucleus of the amygdala (CeA) and the lateral division of the bed nucleus of the stria terminalis (BNST) are the two major nuclei of the central extended amygdala that plays essential roles in threat processing, responsible for emotional states such as fear and anxiety. While some studies suggested functional differences between these nuclei, others showed anatomical and neurochemical similarities. Despite their complex subnuclear organization, subnuclei-specific functional impact on behavior and their underlying molecular profiles remain obscure. We here constitutively inhibited neurotransmission of protein kinase C-δ-positive (PKCδ+) neurons-a major cell type of the lateral subdivision of the CeA (CeL) and the oval nucleus of the BNST (BNSTov)-and found striking subnuclei-specific effects on fear- and anxiety-related behaviors, respectively. To obtain molecular clues for this dissociation, we conducted RNA sequencing in subnuclei-targeted micropunch samples. The CeL and the BNSTov displayed similar gene expression profiles at the basal level; however, both displayed differential gene expression when animals were exposed to fear-related stimuli, with a more robust expression change in the CeL. These findings provide novel insights into the molecular makeup and differential engagement of distinct subnuclei of the extended amygdala, critical for regulation of threat processing.

Development of an Inflammatory CD14+ Dendritic Cell Subset in Humanized Mice.

Humanized mouse models are attractive experimental models for analyzing the development and functions of human dendritic cells (DCs) in vivo. Although various types of DC subsets, including DC type 3 (DC3s), have been identified in humans, it remains unclear whether humanized mice can reproduce heterogeneous DC subsets. CD14, classically known as a monocyte/macrophage marker, is reported as an indicator of DC3s. We previously observed that some CD14+ myeloid cells expressed CD1c, a pan marker for bona fide conventional DC2 (cDC2s), in humanized mouse models in which human FLT3L and GM-CSF genes were transiently expressed using in vivo transfection (IVT). Here, we aimed to elucidate the identity of CD14+CD1c+ DC-like cells in humanized mouse models. We found that CD14+CD1c+ cells were phenotypically different from cDC2s; CD14+CD1c+ cells expressed CD163 but not CD5, whereas cDC2s expressed CD5 but not CD163. Furthermore, CD14+CD1c+ cells primed and polarized naïve CD4+ T cells toward IFN-γ+ Th1 cells more profoundly than cDC2s. Transcriptional analysis revealed that CD14+CD1c+ cells expressed several DC3-specific transcripts, such as CD163, S100A8, and S100A9, and were clearly segregated from cDC2s and monocytes. When lipopolysaccharide was administered to the humanized mice, the frequency of CD14+CD1c+ cells producing IL-6 and TNF-α was elevated, indicating a pro-inflammatory signature. Thus, humanized mice are able to sustain development of functional CD14+CD1c+ DCs, which are equivalent to DC3 subset observed in humans, and they could be useful for analyzing the development and function of DC3s in vivo.

Social Contact with Family and Non-Family Members Differentially Affects Physical Activity: A Parallel Latent Growth Curve Modeling Approach.

BACKGROUND: Social contact leads to an increased likelihood of engaging in physical activity (PA). However, the influence of social contact on PA would be different depending on the social contact source. This study aimed to identify the association of changes in social contact with family and non-family members with the change in PA using a parallel latent growth curve modeling. METHODS: Participants were randomly selected from among residents in the study area age ≥ 20 years (n = 7000). We conducted mail surveys in 2014, 2016, and 2019. The 1365 participants completed all surveys. PA was assessed with validated single-item physical activity measure. Social contact was assessed by summing frequencies of face-to-face and non-face-to-face contacts with family/relatives not living with the participant and friends/neighbors. Parallel latent growth curve modeling was used to assess the cross-sectional, prospective, and parallel associations of social contact with PA change. RESULTS: There was a positive cross-sectional association between contact with friends/neighbors and PA, whereas prospective and parallel associations between contact with family/relatives and PA. CONCLUSION: Contacting friends/neighbors did not predict the change in PA, and a high frequency of contact with family/relatives at baseline and increasing contact with family/relatives was associated with increased PA over 5-year.