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Household chaos, represented by high levels of disorganization and instability in the home, has been linked with suboptimal outcomes for preschoolers. The aim of this study was to examine the roles that sleep problems and executive function play in the association between household chaos and preschoolers’ aggression and prosocial behavior. The sample for the study consisted of 420 preschoolers and their mothers. The mothers provided reports on the level of chaos in the home and their preschoolers’ sleep problems, executive function, and social behavior, including aggression and prosocial behavior. The data was analyzed using structural equation modeling. When preschoolers’ sleep problems and executive function were included in the model as mediators, the results indicated that household chaos did not have direct effects on preschoolers’ aggression and prosocial behavior. Such effects were instead serially mediated by preschoolers’ sleep problems and executive function, respectively. The higher the degree of household chaos, the more preschoolers displayed sleep problems and deficits in executive function, resulting in more aggression and less prosocial behavior. The findings from this study emphasize the significance of reducing household chaos in order to reduce preschoolers’ aggression and promote prosocial behavior. They also underscore the need to identify additional variables that mediate the impact of household chaos on preschoolers’ social outcomes.

Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.

This study investigated the association between children’s perceptions of autonomy support from mothers and teachers in relation to academic procrastination. It also examined the role of self-efficacy for self-regulated learning in mediating these effects. The sample comprised 372 fifth and sixth grade elementary school students from Seoul, Korea. Each completed a questionnaire regarding mothers’ and teachers’ autonomy support, children’s self-regulated learning efficacy, and academic procrastination. The results indicated that whereas mothers’ autonomy support had a direct effect on children’s academic procrastination, teachers’ support did not. In other words, children who perceived higher levels of autonomy support from mothers tended to exhibit less academic procrastination. Regarding indirect paths, children who perceived higher levels of mothers’ and teachers’ autonomy support displayed greater efficacy for selfregulated learning, which corresponded to lower levels of academic procrastination. The discussion highlights the vital roles of autonomy support from mothers and teachers in enhancing children’s feelings of effective self-regulated learning and encouraging them to complete academic tasks. Furthermore, the present study considered not only outward behavioral factors but also the underlying cognitive and affective aspects of delaying behavior that underpin the effects of self-regulated learning efficacy and autonomy support of mothers and teachers on academic procrastination.

Objectives: Childhood trauma (ChT) is a risk factor for psychosis. Negative lifestyle factors such as rumination, negative schemas, and poor diet and exercise are common in psychosis. The present study aimed to perform a network analysis of interactions between ChT and negative lifestyle in patients and controls.Methods: We used data of patients with early-stage psychosis (n = 500) and healthy controls (n = 202). Networks were constructed using 12 nodes from five scales: the Brief Core Schema Scale (BCSS), Brooding Scale (BS), Dietary Habits Questionnaire, Physical Activity Rating, and Early Trauma Inventory Self Report-Short Form (ETI). Graph metrics were calculated.Results: The nodes with the highest predictability and expected influence in both patients and controls were cognitive (Co) and emotional domains (Em) of the BS and emotional abuse (EMO) of the ETI. The EMO was a mediator in the shortest pathway connecting the ETI and negative lifestyle for both groups. The negative other (NO) and negative self (NS) of the BCSS mediated EMO to other BCSS or BS for patients and controls, respectively.Conclusion: Our findings suggest that rumination and EMO were central symptoms in both groups and that NO and NS played important mediating roles for patients and controls, respectively.Trial Registration: ClinicalTrials.gov identifier: CUH201411002

Summary Induced pluripotent stem cells (iPSCs) and cancer cells share cellular similarities and transcriptomic profiles. Here, we show that an iPSC-based cancer vaccine, comprised of autologous iPSCs and CpG, stimulated cytotoxic antitumor CD8+ T cell effector and memory responses, induced cancer-specific humoral immune responses, reduced immunosuppressive CD4+ T regulatory cells, and prevented tumor formation in 75% of pancreatic ductal adenocarcinoma (PDAC) mice. We demonstrate that shared gene expression profiles of “iPSC-cancer signature genes” and others are overexpressed in mouse and human iPSC lines, PDAC cells, and multiple human solid tumor types compared with normal tissues. These results support further studies of iPSC vaccination in PDAC in preclinical and clinical models and in other cancer types that have low mutational burdens., Graphical abstract, Highlights • The iPSC-based cancer vaccine prevents tumor growth in pancreatic cancer • The iPSC-based cancer vaccine induces cytotoxic antitumor T cell and B cell responses • The iPSC-based cancer vaccine reduces immune-suppressive Treg cells • iPSC-cancer signature genes are upregulated in mouse PDAC and human tumors, In this article, Wu and colleagues demonstrate that an iPSC-based cancer vaccine, comprised of iPSCs and CpG, stimulated cytotoxic T cell and B cell responses, reduced immune-suppressive Treg cells, and prevented tumor formation in mice injected with pancreatic ductal adenocarcinoma (PDAC) cells. The “iPSC-cancer signature genes” are overexpressed among iPSC lines, PDAC cells, and multiple human cancers. These results support further studies of iPSC-based cancer vaccine for treatment of PDAC.

In this paper, a method is presented for measurement of analyte concentration in an aqueous solution, using the magnitude change of frequency response induced by mistuned fluid-structure coupled vibration of the suggested structure immersed in the solution. Firstly, the operating principle is explained by analyzing natural characteristics and mistuned responses of the suggested structure by using finite element method (FEM). Then added mass effect induced by the fluid-structure interaction is formulated, by which variations of the analyte concentration can be manifested into the change of the added mass acting on the suggested structure. Based on the operating principle, the resonant amplitudes of the structure are investigated under different fluid densities, and it shows much higher sensitivity than the frequency changes used in previous works. Lastly, the suggested structure is optimized and simulated for detecting glucose concentration at human blood glucose level and noticeable differences are observed for different glucose concentrations.

Background: South Korea or the Republic of Korea has an area of 100,412.6 km2, and population of 52 million (51,781,000). Methods: Besides our lifetime experiences in receiving training, teaching, and practicing psychiatry, the authors collected information from the literature pertinent to the mental health care in South Korea. This review is intended to familiarize the readers of the Taiwanese Journal of Psychiatry with the information of mental health-care service as well as research and development (R and D) in South Korea. Results: Despite consistent improvement in the overall health status in Korea, the mental health status of the population is low compared with other countries in the Organization for Economic Co-operation and Development (OECD). For example, Korea has the highest suicide-related mortality and more years of life lost due to mental/behavioral diseases, compared to those of the average and a longer-than-average duration of hospital stay, respectively, of the OECD. Conversely, the government has made efforts to overhaul the mental health system. Several remarkable changes have been made in the areas of community-based service, involuntary admission, and unequal treatment. Conclusion: The mental health status is closely associated with the mental health service system, prevalence of mental disorders, health insurance system, admission system, and R and D budget for mental health. To change attitudes related to mental health, strong leadership among mental health professionals is urgently needed.

Dielectrophoresis (DEP) is an excellent tool for manipulating small particles within a liquid or gas medium. However, when the size of the particles is too small, such as with quantum dots (QDs), i...

This chapter portrays the inequalities in broadband adoption that exist across and within the nation’s largest cities, even those at the forefront of gigabit networks and smart city advances. Neighborhood maps show wide disparities in broadband subscriptions between affluent and poor zip codes, with up to 50-percentage-point differences in connectivity within cities. People in poor communities are much more likely to rely on cell phones for internet access, while residents of more affluent communities have both home broadband and smartphones. This chapter also describes local government efforts to address these inequalities and an evaluation of Chicago’s Smart Communities program. The Smart Communities initiative demonstrated a significant level of neighborhood change toward its goal of building a culture of technology use throughout the community.

ObjectiveChronic pancreatitis (CP) is a potentially fatal disease of the exocrine pancreas, with no specific or effective approved therapies. Due to difficulty in accessing pancreas tissues, little is known about local immune responses or pathogenesis in human CP. We sought to characterize pancreas immune responses using tissues derived from patients with different etiologies of CP and non-CP organ donors in order to identify key signaling molecules associated with human CP.DesignWe performed single-cell level cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) and T cell receptor sequencing of pancreatic immune cells isolated from organ donors, hereditary, and idiopathic CP patients who underwent total pancreatectomy. We validated gene expression data by performing flow cytometry and functional assay in the second CP patient cohort.ResultsDeep single-cell sequencing revealed distinct immune characteristics and significantly enriched CCR6+ CD4+ T cells in hereditary compared with idiopathic CP. In hereditary CP, a reduction in T cell clonality was observed due to the increased CD4+ T (Th) cells that replaced tissue-resident CD8+ T cells. Shared TCR clonotype analysis among T cell lineages also unveiled unique interactions between CCR6+ Th and Th1 subsets, and TCR clustering analysis showed unique common antigen binding motifs in hereditary CP. In addition, we observed a significant upregulation of the CCR6 ligand (CCL20) among monocytes in hereditary CP as compared with those in idiopathic CP. The functional significance of CCR6 expression in CD4+ T cells was confirmed by flow cytometry and chemotaxis assay.ConclusionSingle-cell sequencing with pancreatic immune cells in human CP highlights pancreas-specific immune crosstalk through the CCR6-CCL20 axis that might be leveraged as a potential future target in human hereditary CP.Significance of this studyWhat is already known about this subject?Chronic pancreatitis (CP) is considered an irreversible fibroinflammatory pancreatic disease and remains a major source of morbidity among gastrointestinal diseases with no active approved therapy.Inflammation is a known hallmark and contributor to CP pathogenesis. However, little is known about local immune responses in human CP especially with different etiologies.What are the new findings?Single-cell RNA sequencing of pancreatic immune cells from CP patients and organ donors revealed distinct immune transcriptomic features in CP versus non-diseased controls and hereditary versus idiopathic CP.Single-cell T cell receptor sequencing unveiled pancreas-specific clonal expansion in CD8+ T cells and CD4+ T cells-driven unique TCR repertoire changes in hereditary CP.We identified that the CCR6-CCL20 axis was significantly upregulated in hereditary CP compared with controls or idiopathic CP suggesting a potential future target for human hereditary CP.How might it impact on clinical practice in the foreseeable future?The results of this study will improve our understanding of CP heterogeneity and identify distinct immune responses in different types of human CP that could provide novel conceptual directions for therapeutic strategies in treating hereditary and idiopathic CP.The CCR6-CCL20 axis found in hereditary CP could be a potential novel targetable signaling pathways in the treatment of hereditary CP.

G protein-coupled receptor 15 (GPR15) is a chemoattractant receptor which in response to its ligand, C10orf99/GPR15L, promotes colon homing of T cells in health and colitis. The functional role of GPR15 in colon cancer is largely unexplored, motivating our current studies using murine colon cancer models and human colorectal cancer (CRC) tissues. Our initial analysis of human CRC specimen revealed significant reduction in GPR15 expression and frequency of GPR15+immune cells in tumors compared to ‘tumor-free’ surgical margins. In the AOM/DSS murine model of colitis associated colon cancer (CAC), we observed increased colonic polyps/tumor burden and lower survival rate inGpr15-deficient (KO) compared toGpr15-sufficient (Het) mice. Analysis of immune cell infiltrates in the colonic polyps showed significantly decreased CD8+T cells and increased IL-17+CD4+and IL-17+CD8+T cells inGpr15-KO than in Het mice. GPR15 deficiency thus alters the immune environment in colonic polyps to mitigate T cell-mediated anti-tumor responses resulting in severe disease. Consistent with a protective role of GPR15, administration of GPR15L to established tumors in the MC38 CRC mouse model increased CD45+cell infiltration, enhanced TNFαexpression on CD4+and CD8+T cells at the tumor site and dramatically reduced tumor burden. Our findings highlight an important, unidentified role of the GPR15-GPR15L axis in promoting a tumor-suppressive immune microenvironment and unveils a novel, colon-specific therapeutic target for CRC.

ObjectiveChronic pancreatitis (CP) is a potentially fatal disease of the exocrine pancreas, with no specific or effective approved therapies. Due to difficulty in accessing pancreas tissues, little is known about local immune responses or pathogenesis in human CP. We sought to characterise pancreatic immune responses using tissues derived from patients with different aetiologies of CP and non-CP organ donors in order to identify key signalling molecules associated with human CP.DesignWe performed single-cell level cellular indexing of transcriptomes and epitopes by sequencing and T-cell receptor (TCR) sequencing of pancreatic immune cells isolated from organ donors, hereditary and idiopathic patients with CP who underwent total pancreatectomy. We validated gene expression data by performing flow cytometry and functional assays in a second patient with CP cohort.ResultsDeep single-cell sequencing revealed distinct immune characteristics and significantly enriched CCR6+ CD4+ T cells in hereditary compared with idiopathic CP. In hereditary CP, a reduction in T-cell clonality was observed due to the increased CD4+ T (Th) cells that replaced tissue-resident CD8+ T cells. Shared TCR clonotype analysis among T-cell lineages also unveiled unique interactions between CCR6+ Th and Th1 subsets, and TCR clustering analysis showed unique common antigen binding motifs in hereditary CP. In addition, we observed a significant upregulation of the CCR6 ligand (CCL20) expression among monocytes in hereditary CP as compared with those in idiopathic CP. The functional significance of CCR6 expression in CD4+ T cells was confirmed by flow cytometry and chemotaxis assay.ConclusionSingle-cell sequencing with pancreatic immune cells in human CP highlights pancreas-specific immune crosstalk through the CCR6-CCL20 axis, a signalling pathway that might be leveraged as a potential future target in human hereditary CP.

10021 Background: Asparaginase is a key component of treatment of acute lymphoblastic leukemia (ALL), which is the most common cancer in the pediatric population. However, asparaginase is associated with many toxicities, including pancreatitis, which is observed in up to 10% of patients and can lead to severe sequelae. Methods: We performed analysis of (1) transcriptomic data from (a) asparaginase-treated leukemic cells, and (b) the pancreas of mice that were induced with a chemical form of pancreatitis; (2) the US FDA Adverse Reporting System (FAERS) and electronic health records (TriNetX); (3) global plasma metabolomic screen and dietary intake evaluation from ALL patients; and (4) experimental animal studies to identify factors that impact asparaginase-associated pancreatitis (AAP). Results: Connectivity map analysis showed that asparaginase-induced gene signatures are potentially reversed by the retinoids (vitamin A and its natural and synthetic analogs). Analysis of TriNetX and FAERES demonstrated a 2-fold reduction in AAP risk with concomitant exposure to vitamin A. Further, we performed a case-control metabolomic study of 50 subjects with ALL enrolled in the Dana-Farber Cancer Institute DFCI ALL clinical trial protocols 05-001 (NCT00400946) and 11-001 (NCT01574274). All subjects were given a single dose of pegylated E. Coli asparaginase during induction therapy. Twenty-four subjects developed pancreatitis within 9 months from the start of induction therapy and were considered cases. The median time to develop pancreatitis among cases was 3.68 months (interquartile range: 3.58 months). Twenty-six control subjects were identified among patients who did not develop pancreatitis within the same evaluation period. The controls were matched for age, sex, and initial ALL risk. The screening revealed that the plasma levels of carotene diol isomers, from the start of induction to its end, were reduced by about 60% in the cases compared to the controls. A detailed 30-day dietary recall showed that the cases had received less dietary vitamin A than the controls during induction therapy. Notably, the median value for the composite intake of vitamin A constituents, termed the RAE (retinol activity equivalents) was 656.92 mcg per day among the controls, but was 34.6% lower among in the cases (median of 429.40 mcg per day, which is just above the recommended dietary allowance level of 400 mcg per day for the 4–8 year-old age group). In mice, asparaginase administration as a single agent was sufficient to reduce circulating and hepatic retinol levels. Conclusions: Based on these data, we propose that circulating retinoids maintain pancreatic health, that asparaginase reduces circulating retinoids, and AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach provides the impetus to examine the role of dietary vitamin A supplementation for preventing or treating AAP.