Marital status, gender, and depression: Analysis of the baseline survey of the Korean Longitudinal Study of Ageing (KLoSA)

Marital status is a robust predictor of health outcomes in Western populations. However, data from Asian cultures remain sparse, and some studies suggest marked gender differences in the health benefits of marriage among Asian populations. We investigated the influence of marital status on depressive symptoms in older adult Koreans. Data were obtained from a sample of adults aged 45 to 85 years (4016 men, 5003 women) who participated in the 2006 cross-sectional baseline survey of the Korean Longitudinal Study of Ageing. Depressive symptoms were measured by the 10-item Center for Epidemiological Studies-Depression scale. A multiple regression model was used to examine the association between marital status and depressive symptoms, controlling for socioeconomic status, living arrangement, disability, and number of chronic diseases. In women aged 75 to 85 years, no significant differences were found between women who were married versus those who were widowed, divorced, or separated with regard to depressive symptoms. These findings were driven by increasing depressive symptoms among married women with age. Whereas divorced and widowed men in the sample reported higher rates of depressive symptoms than did married men, the difference between married vs. widowed/divorced women converged as they aged. This pattern of depressive symptoms by gender and life stage may reflect the distinctive influence of the Asian context on relations between men and women, such as traditional gender roles and patriarchal norms for older generation.Depressive symptoms Marital status Korea Ageing Gender

HIF-1 alpha activation in myeloid cells accelerates dextran sodium sulfate-induced colitis progression in mice

Inflammatory bowel disease (IBD) is a chronic inflammatory disease, in which the intestinal epithelium loses its barrier function. Given the existence of the oxygen gradient in the intestinal epithelium and that inflammation further contributes to the tissue hypoxia, we investigated the role of hypoxia-inducible factor (HIF), a transcription factor activated under hypoxic conditions in myeloid cells, in the progression of IBD. To do this, we utilized myeloid-specific knockout (KO) mice targeting HIF pathways, created by a Cre-loxP system with human MRP8 (hMRP8), an intracellular calcium-binding protein, as the myeloid promoter. By feeding 5% dextran sodium sulfate (DSS) to hMRP8 von Hippel Lindau (Vhl) KO mice, in which HIF-1 alpha and HIF-2 alpha are constitutively activated in myeloid cells, we found that these mice were highly susceptible to DSS-induced colitis, demonstrating greater body weight loss, increased mortality, faster onset of rectal bleeding, shortened colon length, and increased CD11b- or Gr-1-positive myeloid cells in the colon compared with wild-type (WT) mice. These parameters were restored to, if not better than, the WT levels when we examined hMRP8 Hif-1a KO mice upon 5% DSS feeding. hMRP8 Hif-2a KO mice, on the other hand, exhibited a similar degree of DSS-induced colitis to that of WT mice. Lastly, when DSS was given together with azoxymethane to induce tumorigenesis in the colon, we found that hMRP8 Hif-1a KO mice exhibited comparable levels of colorectal tumors to those of WT mice, indicating that HIF-1 alpha in myeloid cells is dispensable for tumorigenesis. Collectively, our results suggest that HIF-1 alpha activation in myeloid cells critically regulates IBD progressio

HIF-1α activation in myeloid cells accelerates dextran sodium sulfate-induced colitis progression in mice

Inflammatory bowel disease (IBD) is a chronic inflammatory disease, in which the intestinal epithelium loses its barrier function. Given the existence of the oxygen gradient in the intestinal epithelium and that inflammation further contributes to the tissue hypoxia, we investigated the role of hypoxia-inducible factor (HIF), a transcription factor activated under hypoxic conditions in myeloid cells, in the progression of IBD. To do this, we utilized myeloid-specific knockout (KO) mice targeting HIF pathways, created by a Cre-loxP system with human MRP8 (hMRP8), an intracellular calcium-binding protein, as the myeloid promoter. By feeding 5% dextran sodium sulfate (DSS) to hMRP8 von Hippel Lindau (Vhl) KO mice, in which HIF-1α and HIF-2α are constitutively activated in myeloid cells, we found that these mice were highly susceptible to DSS-induced colitis, demonstrating greater body weight loss, increased mortality, faster onset of rectal bleeding, shortened colon length, and increased CD11b- or Gr-1-positive myeloid cells in the colon compared with wild-type (WT) mice. These parameters were restored to, if not better than, the WT levels when we examined hMRP8 Hif-1a KO mice upon 5% DSS feeding. hMRP8 Hif-2a KO mice, on the other hand, exhibited a similar degree of DSS-induced colitis to that of WT mice. Lastly, when DSS was given together with azoxymethane to induce tumorigenesis in the colon, we found that hMRP8 Hif-1a KO mice exhibited comparable levels of colorectal tumors to those of WT mice, indicating that HIF-1α in myeloid cells is dispensable for tumorigenesis. Collectively, our results suggest that HIF-1α activation in myeloid cells critically regulates IBD progression

Hypoxia-inducible factor-1 (HIF-1) activation in myeloid cells accelerates DSS-induced colitis progression in mice

nflammatory bowel disease (IBD) is a chronic inflammatory disease where the intestinal epithelium loses its barrier function. Given the existence of the oxygen gradient in the intestinal epithelium and that inflammation further contributes to the tissue hypoxia, we investigated a role of hypoxia-inducible factor (HIF), a transcription factor activated under hypoxic conditions in myeloid cells in the progression of IBD. To do this, we utilized myeloid-specific knockout (KO) mice targeting HIF pathways created by Cre-loxP system with human MRP8 (hMRP8), an intracellular calcium binding protein as the myeloid promoter. By feeding 5% dextran sodium sulfate (DSS) to hMRP8 von Hippel Lindau (Vhl) KO mice where HIF-1α and HIF-2α are constitutively activated in myeloid cells, we found that these mice were highly susceptible to DSS-induced colitis, demonstrating greater body weight loss, increased mortality, faster onset of rectal bleeding, shortened colon length, and increased CD11b- or Gr-1-positive myeloid cells in the colon compared to wild-type (WT) mice. These parameters were restored to, if not better than the WT levels when we examined hMRP8 Hif-1α KO mice upon 5% DSS feeding. hMRP8 Hif-2α KO mice on the other hand exhibited similar degree of DSS-induced colitis to WT mice. Lastly, when DSS was given together with azoxymethane to induce tumorigenesis in the colon, we found that hMRP8 Hif-1α KO mice exhibited comparable levels of colorectal tumors to WT mice, indicating that HIF-1α in myeloid cells is dispensable for tumorigenesis. Collectively, our results suggest that HIF-1 activation in myeloid cells critically regulates IBD progression.112sciescopu

Comprehensive functional genomic resource and integrative model for the human brain.

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders

Assessment of deep learning-based auto-contouring on interobserver consistency in target volume and organs-at-risk delineation for breast cancer: Implications for RTQA program in a multi-institutional study

Purpose: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. Methods and materials: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. Results: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5–19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. Conclusion: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation