Do the benefits of homeownership on mental health vary by race and poverty status? An application of doubly robust estimation for causal inference.

While empirical studies have observed that homeownership is associated with improved mental health conditions, research indicates that this relationship might vary by race. Moreover, such a White-Black disparity in the impacts of homeownership on mental health could be complexed by poverty status, as maintaining one's homeownership could be a financial burden for people living in poverty status, defined by the US official poverty threshold. We add to the existing literature by analyzing the impacts of homeownership on psychological distress, simultaneously disaggregating by race and poverty status using survey data from the Panel Study on Income Dynamics from the 2017 and 2019 waves (N = 7059). Propensity score weighting and doubly robust estimation are applied to estimate causal inference for the impact of 2017 homeownership on 2019 psychological distress using negative binomial models. First, we found the impacts of homeownership on reducing psychological distress are significant for White Americans, not for Black Americans. Second, we found such a White-Black disparity is only observable for populations not living in poverty. On the other hand, for populations living in poverty, homeownership no longer lowers psychological distress for either race. Findings suggest that financial support and mental health support are needy to address inequality in the impacts of homeownership on mental health, which could simultaneously vary by poverty status and race. Implications are discussed.

Clinicopathological role of Cyclin A2 in uterine corpus endometrial carcinoma: Integration of tissue microarrays and ScRNA-Seq.

BACKGROUND: The comprehensive expression level and potential molecular role of Cyclin A2 (CCNA2) in uterine corpus endometrial carcinoma (UCEC) remains undiscovered. METHODS: UCEC and normal endometrium tissues from in-house and public databases were collected for investigating protein and messenger RNA expression of CCNA2. The transcription factors of CCNA2 were identified by the Cistrome database. The prognostic significance of CCNA2 in UCEC was evaluated through univariate and multivariate Cox regression as well as Kaplan-Meier curve analysis. Single-cell RNA-sequencing (scRNA-seq) analysis was performed to explore cell types in UCEC, and the AUCell algorithm was used to investigate the activity of CCNA2 in different cell types. RESULTS: A total of 32 in-house UCEC and 30 normal endometrial tissues as well as 720 UCEC and 165 control samples from public databases were eligible and collected. Integrated calculation showed that the CCNA2 expression was up-regulated in the UCEC tissues (SMD = 2.43, 95% confidence interval 2.23∼2.64). E2F1 and FOXM1 were identified as transcription factors due to the presence of binding peaks on transcription site of CCNA2. CCNA2 predicted worse prognosis in UCEC. However, CCNA2 was not an independent prognostic factor in UCEC. The scRNA-seq analysis disclosed five cell types: B cells, T cells, monocytes, natural killer cells, and epithelial cells in UCEC. The expression of CCNA2 was mainly located in B cells and T cells. Moreover, CCNA2 was active in T cells and B cells using the AUCell algorithm. CONCLUSION: CCNA2 was up-regulated and mainly located in T cells and B cells in UCEC. Overexpression of CCNA2 predicted unfavorable prognosis of UCEC.

Tumor-infiltrating immune cells and survival in head and neck squamous cell carcinoma: a retrospective computational study.

The immune infiltration profiles of the tumor microenvironment have effects on the prognosis of head and neck squamous cell carcinoma (HNSCC). Whereas, HNSCC is a heterogeneous group of tumors, but past work has not taken this into consideration. Herein, we investigate the associations between survival and the function of immune cells in different tumorigenic sites of HNSCC. 1149 samples of HNSCC were collected from publicly accessible databases. Based on gene expression data, CIBERSORTx was applied to determine the proportion of 22 immune cell subpopulations. In the Cox regression model, the associations between overall survival, disease-free survival, and immune cells were examined, modeling gene expression and immune cell proportion as quartiles. Consensus cluster analysis was utilized to uncover immune infiltration profiles. Regardless of tumor sites, CD8+ T cells and activated CD4 memory T cells were associated with favorable survival, while eosinophils were the opposite. The survival of the hypopharynx, oral cavity, and larynx subsites was somewhat affected by immune cells, while the survival of the oropharynx subsite potentially was the most impacted. High expression of TIGIT, CIITA, and CXCR6 was linked to better survival, mainly in the oropharynx subsite. Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy.

Risk and Protective Factors for Parental Involvement and Early Indicators of School Achievement in Alaska.

OBJECTIVES: Parental involvement can affect child school readiness, which in turn influences subsequent child learning outcomes. While social support, stress, caregiver psychological distress, and drinking could affect parental involvement, it is unknown whether and how these factors influence downstream child learning outcomes through parental involvement and child school readiness. This study tests those associations. METHODS: Using de-identified data provided by the Alaska Longitudinal Child Abuse and Neglect Linkage project (N = 683), we use Structural Equation Modeling to assess direct and indirect effects of paths embedded in the proposed model. RESULTS: This study found statistically significant indirect effects: (1) path linking stress faced by caregivers to child reading proficiency through caregiver psychological distress, parental involvement, and child school readiness, (2) path linking stress faced by caregivers to child reading proficiency through caregiver drinking, parental involvement, and child school readiness, and (3) path linking social support for caregivers to child reading proficiency through caregiver psychological distress, parental involvement, and child school readiness. Post-estimation showed that the sum of the magnitude of total effects of stress and the magnitude of total effects of support is significantly larger than either alone. CONCLUSIONS FOR PRACTICE: Findings suggest that reducing caregiver stress and offering social support could not only benefit caregivers but learning outcomes of their children as well. For child learning outcomes, simultaneously reducing stress and offering social support for caregivers, rather than just one of them alone, is suggested. These results are important for children, particularly for those raised by caregivers experiencing psychological distress or drinking issues.

Gut microbial structural variation associates with immune checkpoint inhibitor response.

The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.

Using the matrixed multiple case study methodology to understand site differences in the outcomes of a Hybrid Type 1 trial of a peer-led healthy lifestyle intervention for people with serious mental illness.

Site differences in implementation trial outcomes are common but often not examined. In a Hybrid Type 1 trial examining the effectiveness-implementation of a peer-led group life-style balance (PGLB) intervention for people with serious mental illness (SMI) in three supportive housing agencies, we found that PGLB recipients' physical health outcomes differed by study sites. The matrixed multiple case study methodology was used to explore how implementation outcomes and changes in context of usual care (UC) services contributed to these site differences. Two implementation outcomes (i.e. PGLB fidelity ratings and intervention recipients' acceptability of PGLB and UC) and changes in healthcare services integration at the study sites were examined. ANOVAs were used to examine site differences in fidelity ratings and client satisfaction. Directed content analysis was used to analyze leadership interviews to identify changes in the context of UC services. Site 3 showed a trend approaching significance (P = .05) towards higher fidelity ratings. High levels of satisfaction with PGLB were reported at all sites. Significant differences in PGLB recipients' satisfaction with UC were found, with Site 3 reporting the lowest levels of satisfaction. Agency leaders reported an increase in prioritizing client's health throughout the trial with sites differing in how these priorities were put into action. Differences in PGLB recipients' satisfaction with UC, and changes in healthcare service integration seemed to have contributed to the site differences in our trial. The matrixed multiple case study methodology is a useful approach to identify implementation outcomes contributing to the heterogeneity of multisite implementation trial results.

A healthy lifestyle intervention delivered by people with lived experience of serious mental illness (SMI) led to improved health outcomes among participants living with SMI in three supportive housing agencies, but these outcomes differed by study sites. This study aimed to identify which factors influenced these site differences in study outcomes by examining if the intervention was delivered as intended, intervention recipients' satisfaction with the intervention and the pre-existing health care services delivered at each study site, and what changes occurred in health care services offered at each of the supportive housing agencies throughout the study. The intervention was found to have high levels of satisfaction across all three agencies but the agency which had the best outcomes also had the highest levels of intervention delivery adherence and the lowest levels of intervention recipients' satisfaction with existing health care services. Additionally, during the study period, the same agency described minimal changes in their existing health care services while the other two agencies were found to have made more significant changes integrating health care services to their day-to-day operations. As a result, findings from this study emphasize the importance of understanding the context in which interventions are delivered in routine practice settings to ensure their overall success.

The Application of Family Stress Model to Investigating Adolescent Problematic Behaviors: The Moderating Role of Assets.

The Family Stress Model framework proposes that household income can influence child and youth development through caregiver psychological distress. While prior studies have observed stronger associations among households with lower income, the role of assets has been ignored. This is unfortunate, as many existing policies and practices that intend to improve child and family well-being are focused on assets. The purpose of this study is to clarify whether asset poverty moderates the direct and indirect effects of paths linking household income, caregiver psychological distress, and adolescent problematic behaviors. Using the 2017 and 2019 Panel Study of Income Dynamic Main Study and 2019 and 2020 Child Development Supplements, we find that the family stress processes consisting of household income, caregiver psychological distress, and adolescent problematic behaviors are less intensive for families with more assets. These findings not only add our knowledge of FSM by taking account the moderating role of assets but also advance our understanding that assets can benefit child and family well-being through alleviating family stress processes.

Establishment of extensive artificial intelligence models for kinase inhibitor prediction: Identification of novel PDGFRB inhibitors.

Identifying hit compounds is an important step in drug development. Unfortunately, this process continues to be a challenging task. Several machine learning models have been generated to aid in simplifying and improving the prediction of candidate compounds. Models tuned for predicting kinase inhibitors have been established. However, an effective model can be limited by the size of the chosen training dataset. In this study, we tested several machine learning models to predict potential kinase inhibitors. A dataset was curated from a number of publicly available repositories. This resulted in a comprehensive dataset covering more than half of the human kinome. More than 2,000 kinase models were established using different model approaches. The performances of the models were compared, and the Keras-MLP model was determined to be the best performing model. The model was then used to screen a chemical library for potential inhibitors targeting platelet-derived growth factor receptor-ß (PDGFRB). Several PDGFRB candidates were selected, and in vitro assays confirmed four compounds with PDGFRB inhibitory activity and IC50 values in the nanomolar range. These results show the effectiveness of machine learning models trained on the reported dataset. This report would aid in the establishment of machine learning models as well as in the discovery of novel kinase inhibitors.

The effectiveness of an egg-based intervention on improving the nutrition of poor school-age children in China: A quasi-experimental assessment.

OBJECTIVES: Although egg-based interventions are effective in alleviating undernutrition for infants and toddlers, little is known regarding their effectiveness for children in remote and poor areas of China. For policy and intervention implications, the aim of this study was to examine the effects of offering one hard-boiled egg per school day to school-age children in less-developed areas of China. METHODS: This analytical sample included 346 school-age children. Children in the treatment group received one egg per school day. Applying propensity score weighting to the difference-in-difference models, this study examined the effects of the egg intervention on child nutrition status measured in height-for-age Z score (HAZ), weight-for-age Z score (WAZ), and body-mass-index-for-age Z score (BMIZ). RESULTS: After applying propensity score weighting, the average treatment effect (ATE) and the average treatment effects on the treated (ATT) estimations showed that the increase in HAZ scores from wave 1 to wave 3 for the program participants was 0.28 points higher compared with the increase in HAZ scores from wave 1 to wave 3 for the control group (P < 0.05). The ATE and the ATT estimations showed that the increase in WAZ scores from wave 1 to wave 3 for the program participants was 0.50 and 0.49 points higher compared with the increase in WAZ scores from wave 1 to wave 3 for the control group (P < 0.001). Regarding BMIZ score improvement from wave 1 to wave 3, the program participation had relatively larger effects by 0.57 and 0.55 points based on the ATE and ATT estimations (P < 0.001), respectively. CONCLUSIONS: The egg intervention can be an effective intervention to improve child development in less-developed areas of China.

Discovering a trans-omics biomarker signature that predisposes high risk diabetic patients to diabetic kidney disease.

Diabetic kidney disease is the leading cause of end-stage kidney disease worldwide; however, the integration of high-dimensional trans-omics data to predict this diabetic complication is rare. We develop artificial intelligence (AI)-assisted models using machine learning algorithms to identify a biomarker signature that predisposes high risk patients with diabetes mellitus (DM) to diabetic kidney disease based on clinical information, untargeted metabolomics, targeted lipidomics and genome-wide single nucleotide polymorphism (SNP) datasets. This involves 618 individuals who are split into training and testing cohorts of 557 and 61 subjects, respectively. Three models are developed. In model 1, the top 20 features selected by AI give an accuracy rate of 0.83 and an area under curve (AUC) of 0.89 when differentiating DM and non-DM individuals. In model 2, among DM patients, a biomarker signature of 10 AI-selected features gives an accuracy rate of 0.70 and an AUC of 0.76 when identifying subjects at high risk of renal impairment. In model 3, among non-DM patients, a biomarker signature of 25 AI-selected features gives an accuracy rate of 0.82 and an AUC of 0.76 when pinpointing subjects at high risk of chronic kidney disease. In addition, the performance of the three models is rigorously verified using an independent validation cohort. Intriguingly, analysis of the protein-protein interaction network of the genes containing the identified SNPs (RPTOR, CLPTM1L, ALDH1L1, LY6D, PCDH9, B3GNTL1, CDS1, ADCYAP and FAM53A) reveals that, at the molecular level, there seems to be interconnected factors that have an effect on the progression of renal impairment among DM patients. In conclusion, our findings reveal the potential of employing machine learning algorithms to augment traditional methods and our findings suggest what molecular mechanisms may underlie the complex interaction between DM and chronic kidney disease. Moreover, the development of our AI-assisted models will improve precision when diagnosing renal impairment in predisposed patients, both DM and non-DM. Finally, a large prospective cohort study is needed to validate the clinical utility and mechanistic implications of these biomarker signatures.

Detection of Complement C1q B Chain Overexpression and Its Latent Molecular Mechanisms in Cervical Cancer Tissues Using Multiple Methods.

Aim: The aim of this study is to demonstrate the expression and clinicopathological significance of complement C1q B chain (C1QB) in cervical cancer. Methods: In total, 120 cervical cancer tissues, as well as 20 samples each of high-grade squamous intraepithelial lesions (HSILs), low-grade squamous intraepithelial lesions (LSILs), and benign cervical tissue, were collected to evaluate the expression of C1QB protein via immunohistochemical staining. We conducted an integrated analysis of C1QB mRNA expression in cervical cancer using public microarrays and RNA-seq data sets by calculating standard mean differences (SMDs). Simultaneously, we explored the relations of C1QB with clinicopathological parameters and the expression of P16, Ki-67, and P53. Results: The expression of C1QB protein was higher in cervical cancer samples than that in benign cervical tissue, LSIL, and HSIL samples (p < 0.05). A combined SMD of 0.65 (95% CI: [0.52, 0.79], p < 0.001) revealed upregulation of C1QB mRNA in cervical cancer. C1QB expression may also be related to the depth of infiltration, lymphovascular invasion, and perineural invasion in cervical cancer (p < 0.05). We also found that C1QB protein expression was positively correlated with P16 and Ki-67 expression in cervical cancer (p < 0.05). The gene set enrichment analysis showed that C1QB may participate in apoptosis and autophagy. A relationship was predicted between C1QB expression and drug sensitivity to cisplatin, paclitaxel, and docetaxel. Conclusion: We confirmed the overexpression of C1QB in cervical cancer at both mRNA and protein levels for the first time. C1QB may serve as an oncogene in the tumorigenesis of cervical cancer, but this possibility requires further study.

Downregulated Dual-Specificity Protein Phosphatase 1 in Ovarian Carcinoma: A Comprehensive Study With Multiple Methods.

Introduction: We aimed to explore the abnormal expression of dual-specificity protein phosphatase 1 (DUSP1) and its latent molecular mechanisms in ovarian carcinoma (OVCA). Materials and Methods: Two clinical cohorts collected from two different hospitals were used to evaluate the expression of DUSP1 protein in OVCA tissues. RNA-sequencing and microarray datasets were utilised to verify DUSP1 expression at mRNA levels in both OVCA tissues and in the peripheral blood of OVCA patients. Furthermore, an integrated calculation was performed to pool the standard mean difference (SMD) from each cohort in order to comprehensively assess the expression of DUSP1 in OVCA. Furthermore, we examined the relationship among DUSP1, tumour microenvironment (TME), and chemotherapy resistance in OVCA. Moreover, we used pathway enrichment analysis to explore the underlying mechanisms of DUSP1 in OVCA. Results: A pooled SMD of -1.19 (95% CI [-2.00, -0.38], p = 0.004) with 1,240 samples revealed that DUSP1 was downregulated in OVCA at both mRNA and protein levels. The area under the receiver operating characteristic curve of 0.9235 indicated the downregulated DUSP1 in peripheral blood may have a non-invasive diagnostic value in OVCA. Through six algorithms, we identified that DUSP1 may related to tumour-infiltrating T cells and cancer associated fibroblasts (CAFs) in OVCA. Pathway enrichment demonstrated that DUSP1 might participate in the mitogen-activated protein kinase (MAPK) signalling pathway. Furthermore, DUSP1 may have relations with chemotherapy resistance, and a favourable combining affinity was observed in the paclitaxel-DUSP1 docking model. Conclusion: DUSP1 was downregulated in OVCA, and this decreasing trend may affect the infiltration of CAFs. Finally, DUSP1 may have a targeting relation with paclitaxel and participate in MAPK signaling pathways.

Expression Profile and Molecular Basis of Cyclin-Dependent Kinases Regulatory Subunit 2 in Endometrial Carcinoma Detected by Diversified Methods.

Purpose: Our purpose was to systematically appraise the clinicopathological significance and explore the molecular bases of CKS2 in endometrial carcinoma. Patients and Methods: We measured the clinicopathological significance of CKS2 using diverse methods of public RNA-seq, microarrays, and in-house tissue microarrays to investigate the molecular basis of CKS2 in endometrial carcinoma through upstream transcriptional analysis, immune infiltration correlation analysis, and co-expression analysis. Results: Both the analysis for public RNA-seq plus the microarray data and in-house tissue microarray confirmed the significant overexpression of CKS2 in a total of 1,021 endometrial carcinoma samples compared with 279 non-cancer endometrium samples (SMD = 2.10, 95% CI = 0.72-3.48). The upregulated CKS2 was significantly related to the lymph node metastasis and advanced clinical grade of endometrial carcinoma patients (p < 0.001). Mutation types such as amplification and mRNA occurred with high frequency in the CKS2 gene in endometrial carcinoma patients. A series of miRNAs and transcription factors, such as hsa-miR-26a, hsa-miR-130a, hsa-miR-30, E2F4, MAX, and GABPA, were predicted to regulate the transcription and expression of CKS2. Significant links were found between CKS2 expression and the infiltration level of B cells, CD4+ T cells, and neutrophils in endometrial carcinoma. CKS2-coexpressed genes were actively involved in pathways such as the mitotic cell cycle process, PID aurora B pathway, and prolactin signaling pathway. Conclusion: The overexpressed CKS2 showed positive correlations with the clinical progression of endometrial carcinoma and was associated with various cancer-related biological processes and pathways, showing potential as a promising clinical biomarker for endometrial carcinoma.

[Effect of Connexin on Cochlear Blood-Labyrinth Barrier in a Mouse Model of Endolymphatic Hydrops].

Objective: To examine the expression of tight-junction connexin ZO-1 in the stria vascularis tissue of the cochlea by using spontaneous endolymphatic hydrops animal model constructed with PHEX gene mutant mice, and to analyze the dynamic changes of the gene mutant mice in pathology, imaging, and hearing function. Methods: Male Hyp-Duk/Y mice with PHEX gene mutation were selected as the experimental group at three time points, 21 days post birth (P21), 90 days post birth (P90) and 120 days post birth (P120), and wild-type male mice of the same ages were selected as the control groups. The cochlear sections were HE-stained in order to observe whether endolymphatic hydrops was present or absent and to assess its severity. The expression of connexin ZO-1 in both groups was evaluated through immunohistochemical staining of cochlear sections. Auditory-evoked brainstem response (ABR) was induced in both groups at P90 and gadolinium-enhanced MRI was conducted in vivo to observe the middle-order endolymphatic dilatation of cochlea in experimental and control mice aged P21, P90 and P120. Results: HE staining of pathological sections of PHEX Hyp-Duk/Y mice aged P90 and P120 showed increased endolymphatic hydronephrosis. The level of striae ZO-1 in PHEX Hyp-Duk/Y mice aged P90 and P120 was significantly lower than that of the controls of the same age (P<0.05). The expression level of ZO-1 was significantly negatively correlated with the degree of endolymphatic hydronephrosis (r=-0.939, P<0.01). The bilateral ABR threshold of PHEX Hyp-Duk/Y mice aged P90 was higher than that of the wild-type mice of the same age, and the mutant mice showed asymmetric hearing loss on both sides. Severe endolymphatic hydronephrosis was observed in PHEX Hyp-Duk/Y mice aged P90 and P120 through in vivo MRI gadolinium imaging. Conclusion: PHEX Hyp-Duk/Y can be used as a sound model for basic research of Ménière's disease. Compared with wild-type mice, PHEX Hyp-Duk/Y mice showed decreased expression of connexin protein ZO-1, which damaged the function of the blood-labyrinth barrier in stria vascularis, and was involved in the formation of endolymphatic hydrops. 7.0 T MRI gadolinium imaging can be used to observe the changes of severe endolymphatic hydrops in mice in vivo, providing imaging basis for the diagnosis of Ménière's disease.

Machine learning of treadmill exercise test to improve selection for testing for coronary artery disease.

BACKGROUND AND AIMS: The high false-positive rate of the treadmill exercise test (TET) may lead to unnecessary invasive coronary angiography. We aimed to develop a machine learning-based algorithm to improve the diagnostic performance of TET. METHODS: Study included 2325 patients who underwent TET and subsequent coronary angiography within one-year interval. The mean age was 58.7 (48.1-69.3) years, 1731 (74.5%) were male, 1858 (79.9%) had positive TET result, and 812 (34.9%) had obstructive coronary artery disease (≥70% stenosis in at least one vessel). The study population were randomly divided into training (70%) and testing (30%) groups for algorithm development. A total of 93 features, including exercise performance, hemodynamics and ST-segment changes were extracted from the TET results. Clinical features included comorbidity, smoking, height, weight, and Framingham risk score. Support vector machine, logistic regression, random forest, k-nearest neighbor and extreme gradient boosting machine learning algorithms were used to build the predictive models. The performance of each model was compared with that of conventional TET. RESULTS: Four of the five models exhibited comparable diagnostic performance and were better than conventional TET. The random forest algorithm had an area under the curve (AUC) of 0.73. When used with clinical features, the AUC improved to 0.74. The major advantage of the algorithm is the reduction of the false-positive rate compared with conventional TET (55% vs. 76.3%, respectively), while maintaining comparable sensitivity (85%). CONCLUSIONS: Using the information obtained from conventional TET, a more accurate diagnosis can be made by incorporating an artificial intelligence-based model.

Clinicopathological significance and underlying molecular mechanism of downregulation of basonuclin 1 expression in ovarian carcinoma.

In this study, we aim to identify the clinical significance of basonuclin 1 (BNC1) expression in ovarian carcinoma (OV) and to explore its latent mechanisms. Via integrating in-house tissue microarrays, gene chips, and RNA-sequencing data, we explored the expression and clinical value of BNC1 in OV. Immunohistochemical staining was utilized to confirm the protein expression status of BNC1. A combined SMD of -2.339 (95% CI: -3.649 to -1.028, P < 0.001) identified that BNC1 was downregulated based on 1346 samples, and the sROC (AUC = 0.93) showed a favorable discriminatory ability of BNC1 in OV patients. We used univariate and multivariate Cox regulation to evaluate the prognostic role of BNC1 for OV patients, and a combined hazard ratio of 0.717 (95% CI: 0.445-0.989, P < 0.001) revealed that BNC1 was a protective factor for OV. Furthermore, the fraction of infiltrating naive B cells, memory B cells, and other immune cells showed statistical differences between the high- and low-BNC1 expression groups through cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Enrichment analysis showed that BNC1 may have a relationship with immune-related items in OV. By predicting the potential regulatory transcription factors (TFs) of BNC1, friend leukemia virus integration 1 (FLI1) may be a potential upstream TF of BNC1. Corporately, a decreasing trend of BNC1 may serve as a tumor suppressor and prognostic biomarker in OV patients. Moreover, BNC1 may take part in immune-related pathways and influence the fraction of tumor-infiltrating immune cells.

Impact of Moderating Demographic Variables on a Health Intervention for People with Serious Mental Illness.

Purpose: Healthy lifestyle interventions can improve the health of people with serious mental illness (SMI). Little is known whether demographic variables moderate the effectiveness of these interventions on health outcomes. Method: Data from an effectiveness trial of a peer-led healthy lifestyle intervention (PGLB) for people with SMI examine whether age, racial/ethnic minoritized status, and gender moderated the effectiveness of PGLB compared to usual care (UC) in achieving clinically significant improvements in weight, cardiorespiratory fitness, and cardiovascular disease (CVD) risk reduction. Results: Compared to UC, PGLB was most beneficial for participants age 49 and younger for achieving clinically significant weight loss and from racial/ethnic minoritized communities for achieving clinically significant weight loss and reductions in CVD risk. Conclusions: These findings suggest the impact of healthy lifestyle interventions for people with SMI may not be uniform and adaptations may be needed to make these interventions responsive to the needs of diverse populations.

Down-Regulation of Activating Transcription Factor 3 (ATF3) in Hepatoblastoma and Its Relationship with Ferroptosis.

PURPOSE: The molecular mechanisms and signal pathways of ferroptosis in hepatoblastoma (HB) have not yet been clarified. In previous studies, activating transcription factor 3 (ATF3) was reported to be correlated with several tumors, but the clinical significance of ATF3 has never been determined. Herein, we investigated the clinicopathological value and mechanisms of ATF3 in regulating ferroptosis in HB. METHODS: The mRNA microarray and RNA-sequencing data of 402 samples from our hospital and public databases were used to estimate ATF3 expression and assess its clinical role in HB. The standard mean difference (SMD) and summary receiver operating characteristic curves were utilized to judge the discrimination ability of ATF3 between HB and non-HB liver tissues. We examined the expression variation of ATF3 in HB cells after the treatment with erastin. We also predicted the target genes of ATF3 as a transcriptional factor from public Chromatin Immunoprecipitation-sequencing data and selected the ferroptosis-related genes for a signaling pathway analysis. RESULTS: In ten series, the pooled SMD for ATF3 was -0.91, demonstrating that ATF3 expression was predominantly lower in HB than in non-HB liver tissues. ATF3 down-regulation showed moderate potential to distinguish HB from non-HB liver tissues (area under curves = 0.83, 95% confidence interval = 0.79-0.86). Altogether, 4855 putative targets of ATF3 as a transcriptional factor were collected, among which, 60 genes were ferroptosis-related. CONCLUSION: The down-regulated ATF3 expression may play a vital role in the occurrence of HB possible partially by regulating ferroptosis.

Downregulation of the Coiled-Coil Domain Containing 80 and Its Perspective Mechanisms in Ovarian Carcinoma: A Comprehensive Study.

INTRODUCTION: We aimed to explore the downregulation of the coiled-coil domain containing 80 (CCDC80) and its underlying molecular mechanisms in ovarian carcinoma (OVCA). Materials/Methods. Immunohistochemical staining was performed to confirm the expression status of CCDC80 protein. Combining the data from in-house tissue microarrays and high-throughput datasets, we identified the expression level of CCDC80 in OVCA. We utilized cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm and single-sample gene set enrichment analysis (ssGSEA) to explore the relationship between CCDC80 and the tumor microenvironment (TME) landscape in OVCA. Pathway enrichment, function annotation, and transcription factor (TFs) exploration were conducted to study the latent molecular mechanisms. Moreover, the cell line data in the Genomics of Drug Sensitivity in Cancer (GDSC) database was used to discover the relationship between CCDC80 and drug sensitivity. RESULTS: An integrated standard mean difference (SMD) of -0.919 (95% CI: -1.515-0.324, P = 0.002) identified the downregulation of CCDC80 in OVCA based on 1048 samples, and the sROC (AUC = 0.76) showed a moderate discriminatory ability of CCDC80 in OVCA. The fraction of infiltrating naive B cells showed significant differences between the high- and low-CCDC80 expression groups. Also, CCDC80-related genes are enriched in the Ras signaling pathway and metabolic of lipid. Nuclear receptor subfamily three group C member 1 (NR3C1) may be an upstream TF of CCDC80, and CCDC80 may be related to the sensitivity of mitocycin C and nilotinib. CONCLUSION: CCDC80 was downregulated in OVCA and may play a role as a tumor suppressor in OVCA.

Kidcope and the COVID-19 Pandemic: Understanding High School Students' Coping and Emotional Well-Being.

The COVID-19 pandemic has resulted in social isolation, grief, and loss among many adolescents. As the pandemic continues to impact individuals and communities across the globe, it is critical to address the psychological well-being of youths. More studies are needed to understand the effective ways adolescents cope with pandemic-related psychological distress. In this study, 146 students from 1 high school in a U.S. midwestern state completed an adapted version of Kidcope, a widely used coping instrument in disaster research, and measures were taken on generalized distress and COVID-19-related worries. Findings indicated that most students experienced COVID-19-related fears and general emotional distress. Additionally, we found that disengagement coping strategies were associated with lower general distress (p ≤ 0.05) and COVID-19 worries (p ≤ 0.10). Active coping was not associated with general distress and COVID-19 worries. Overall, our findings highlight the need to develop tailored interventions targeting youth coping strategies to reduce and prevent emotional distress and amplify healthy coping skills as the pandemic persists.