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BMJ Open Jun 2024Despite the high prevalence of major depressive disorder (MDD) among the elderly population, the rate of treatment is low due to stigmas and barriers to medical access....
INTRODUCTION
Despite the high prevalence of major depressive disorder (MDD) among the elderly population, the rate of treatment is low due to stigmas and barriers to medical access. Wearable devices such as smartphones and smartwatches can help to screen MDD symptoms earlier in a natural setting while forgoing these concerns. However, previous research using wearable devices has mostly targeted the younger population. By collecting longitudinal data using wearable devices from the elderly population, this research aims to produce prediction algorithms for late-life depression and to develop strategies that strengthen medical access in community care systems.
METHODS AND ANALYSIS
The current cohort study recruited a subsample of 685 elderly people from the Korean Genome and Epidemiology Study-Cardiovascular Disease Association Study, a national large cohort established in 2004. The current study has been conducted over a 3-year period to explore the development patterns of late-life depression. Participants have completed three annual face-to-face interviews (baseline, the first follow-up and the second follow-up) and 2 years of app-based surveys and passive sensing data collection. All the data collection will end at the second follow-up interview. The collected self-report, observational and passive sensing data will be primarily analysed by machine learning.
ETHICS AND DISSEMINATION
This study protocol has been reviewed and approved by the Yonsei University Mirae Campus Institutional Review Board (1041849-2 02 111 SB-180-06) in South Korea. All participants provided written informed consent. The findings of this research will be disseminated by academic publications and conference presentations.
Topics: Humans; Wearable Electronic Devices; Aged; Depressive Disorder, Major; Algorithms; Republic of Korea; Male; Female; Cohort Studies; Research Design; Machine Learning; Aged, 80 and over
PubMed: 38871664
DOI: 10.1136/bmjopen-2023-073290 -
Indian Heart Journal Jun 2024Prehypertension (PHT) is a cardiovascular health risk defined by blood pressure (BP). Arterial stiffness (AS) provides beyond brachial BP inference on vascular ageing...
BACKGROUND
Prehypertension (PHT) is a cardiovascular health risk defined by blood pressure (BP). Arterial stiffness (AS) provides beyond brachial BP inference on vascular ageing and pulse wave analysis (PWA) can measure it non-invasively.We compared association between AS and PHT using age and gender matched case-controls.
METHODS
This is a sub analysis of previous PWA studies of hypertensives and non-hypertensives. Using oscillometric PWA by Mobil-o-Graph (IEM, Stolberg, Germany), parameters of AS (augmentation pressure and index, reflection magnitude, aortic pulse wave velocity, pulse pressure amplification), brachial hemodynamics (BH), and central hemodynamics (CH; aortic BP, cardiac output related parameters, stroke work) were derived. Age and gender matched case controls were compared as: 1) Nonhypertensives with BP at prehypertensive level (PHT) versus normotensives (NT) (n = 217 each), 2) Under treatment hypertensives with BP at prehypertensive level (PHT-T) versus untreated, nonhypertensives with BP at prehypertensive level (PHT-UT) (n = 74 each).
RESULTS
PHTs had higher AS, BH and CH than NTs, with statistical significance for all but few parameters. PHT-T had comparable BH but higher AS, CH than PHT-UT with significance for few parameters.
CONCLUSION
Pulse wave analysis derived arterial stiffness is associated with prehypertension compared to normal, after age and gender matching. In hypertensives, arterial stiffness is significantly higher despite being treated to prehypertension level as compared to control. It hints arterial stiffness to be better parameter than brachial BP to study prehypertension.
PubMed: 38871217
DOI: 10.1016/j.ihj.2024.06.007 -
Aging Jun 2024
PubMed: 38870314
DOI: 10.18632/aging.205914 -
Aging Jun 2024Tumor endothelial cells (TECs) are essential participants in tumorigenesis. This study is focused on elucidating the TEC traits in gastric cancer (GC) and constructing a...
BACKGROUND
Tumor endothelial cells (TECs) are essential participants in tumorigenesis. This study is focused on elucidating the TEC traits in gastric cancer (GC) and constructing a prognostic risk model to predict the clinical outcome of GC patients.
METHODS
Single-cell RNA sequencing (scRNA-seq) data were obtained from the GEO database. Using specific markers, the Seurat R package aided in processing scRNA-seq data and identifying TEC clusters. Based on TEC cluster-associated genes identified by Pearson correlation analysis, TEC-related prognostic genes were screened by lasso-Cox regression analysis, thereby constructing a risk signature. A nomogram was created by combining the risk signature with clinicopathological features.
RESULTS
Based on the scRNA-seq data, 5 TEC clusters were discovered in GC, with 3 of them showing prognostic associations in GC. A total of 163 genes were pinpointed among 3302 DEGs as significantly linked to TEC clusters, leading to the formulation of a risk signature comprising 8 genes. Furthermore, there was a notable correlation between the risk signature and the immune cell infiltration. Multivariate analysis findings indicated that the risk signature served as an independent prognostic factor for GC. Moreover, its efficacy in forecasting immune response was validated.
CONCLUSION
TEC-based risk model is highly effective in predicting the survival outcomes of GC patients and can forecast the immune response. Targeting TECs may significantly inhibit tumor progression and enhance the efficacy of immunotherapy.
PubMed: 38870270
DOI: 10.18632/aging.205928 -
Aging Jun 2024Gastric carcinoma (GC) is one of the most fatal human malignancies globally, with a median survival time less than 1 year. E-cadherin exerts a crucial role in the...
BACKGROUNDS
Gastric carcinoma (GC) is one of the most fatal human malignancies globally, with a median survival time less than 1 year. E-cadherin exerts a crucial role in the development and progression of GC as an adhesive, invasive suppressor gene. Whether reduced E-cadherin has an impact on prognosis, clinicopathological features for GC has been well studied, but no conclusive results has been obtained.
METHODS
Eligible studies and relevant data were obtained from PubMed, Elsevier, Embase, Cochrane Library and Web of Science databases until June 30, 2023. A fixed- or random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Correlation of E-cadherin expression with overall survival (OS), clinicopathological features and risk factors were evaluated.
RESULTS
36 studies fulfilled the selected criteria. 9048 cases were included. This meta-analysis showed that patients with GC with reduced E-cadherin had unfavourable clinicopathological features and poor OS. The pooled ORs of one-, three- and five-year OS were 0.38 ( = 25 studies, 95%CI: 0.25-0.57, Z = 4.61, < 0.00001), 0.33 ( = 25 studies, 95% CI: 0.23-0.47, Z = 6.22, < 0.00001), 0.27 ( = 22 studies, 95% CI: 0.18-0.41, Z = 6.23, < 0.00001), respectively. Moreover, reduced E-cadherin expression significantly correlated with differentiation grade (OR = 0.29, 95% CI: 0.22-0.39, Z = 8.58, < 0.00001), depth of invasion (OR = 0.49, 95% CI: 0.36-0.66, Z = 4.58, < 0.00001), lymphatic node metastasis (OR = 0.49, 95% CI: 0.38-0.64, Z = 5.38, < 0.00001), distant metastasis (OR = 2.24, 95% CI: 1.62-3.09, Z = 4.88, < 0.00001), peritoneal metastasis (OR = 2.17, 95% CI: 1.39-3.39, Z = 3.40, = 0.0007), TNM stage (OR = 0.41, 95% CI: 0.28-0.61, Z = 4.44, < 0.00001), lymphatic vessel invasion (OR = 1.77, 95% CI: 1.11-2.82, Z = 2.39, = 0.02), vascular invasion (OR = 1.55, 95% CI: 1.22-1.96, Z = 3.58, = 0.0003), Lauren type (OR = 0.35, 95% CI: 0.21-0.57, Z = 4.14, < 0.0001), Borrmann classification (OR = 0.50, 95% CI: 0.25-0.99, Z = 1.97, = 0.048) and tumor size (≥5 cm vs. <5 cm: OR = 1.73, 95% CI: 1.34-2.23, Z = 4.19, < 0.0001; ≥6 cm vs. <6 cm: OR = 2.29, 95% CI: 1.51-3.49, Z = 3.87, = 0.0001). No significant association was observed between reduced E-cadherin expression and liver metastasis, perineural invasion, alcohol consumption, smoking status, familial history, Helicobacter pylori (HP) infection.
CONCLUSIONS
The reduced expression of E-cadherin is significantly correlated with poor OS and unfavourable clinicopathological features in GC. The expression level of E-cadherin not only serves as a predictor for disease progression and prognosis in GC but also emerges as a novel therapeutic target.
PubMed: 38870263
DOI: 10.18632/aging.205929 -
The causal role of immune cells on lung cancer: a bi-directional Mendelian randomization (MR) study.Aging Jun 2024Immune cells play a vital role in the development and progression of lung cancer (LC). We aimed to explore the causal role of immune cells in LC with Mendelian...
Immune cells play a vital role in the development and progression of lung cancer (LC). We aimed to explore the causal role of immune cells in LC with Mendelian randomization (MR) study. Summary statistic data used in the study were obtained from genome-wide association studies (GWAS). A comprehensive two-sample MR was carried out to explore the causal role of 731 immune cell traits (ICTs) in LC, Non-small cell lung cancer (NSCLC), and Small cell lung cancer (SCLC). An inverse-variance weighted (IVW) approach was applied to present the MR estimates. The heterogeneity test was performed using Cochran's Q statistic. MR-Egger intercept test and MR-PRESSO were utilized for the pleiotropy test. MR showed that 15, 31, and 11 ICTs had protective effects on LC, NSCLC, and SCLC, respectively, and 12, 31, and 11 ICTs had adverse effects on LC, NSCLC, and SCLC, respectively. Of note, CD3 on CD28 CD4 in the Treg panel could significantly increase the risk of LC, as well as NSCLC and SCLC. Moreover, the MR results revealed that LC was vital in IgD on IgD in the B cell panel and NSCLC on CCR2 on CD14- CD16- in the Monocyte panel. Our study revealed multiple close connections between immune cells and LC.
PubMed: 38870262
DOI: 10.18632/aging.205917 -
Aging Jun 2024In all mammals, the basement membrane serves as a pivotal extracellular matrix. Hepatocellular carcinoma (HCC) is a challenge among numerous cancer types shaped by...
In all mammals, the basement membrane serves as a pivotal extracellular matrix. Hepatocellular carcinoma (HCC) is a challenge among numerous cancer types shaped by basement membrane-related genes (BMGs). Our research established an innovative prognostic model that is highly accurate in its prediction of HCC prognoses and immunotherapy efficacy to summarize the crucial role of BMGs in HCC. We obtained HCC transcriptome analysis data and corresponding clinical data from The Cancer Genome Atlas (TCGA). To augment our dataset, we incorporated 222 differentially expressed BMGs identified from relevant literature. A weighted gene coexpression network analysis (WGCNA) of 10158 genes demonstrated four modules that were connected to HCC. Additionally, 66 genes that are found at the intersection of BMGs and HCC-related genes were designated as hub HCC-related BMGs. MMP1, ITGA2, P3H1, and CTSA comprise the novel model that was engineered using univariate and multivariate Cox regression analysis. Furthermore, the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) datasets encouraged the BMs model's validity. The overall survival (OS) of individuals with HCC may be precisely predicted in the TCGA and ICGC databases utilizing the BMs model. A nomogram based on the model was created in the TCGA database at similar time, and displayed a favorable discriminating ability for HCC. Particularly, when compared to the patients at an elevated risk, the patients with a low-risk profile presented different tumor microenvironment (TME) and hallmark pathways. Moreover, we discovered that a lower risk score of HCC patients would display a greater response to immunotherapy. Finally, quantitative real-time PCR (qRT-PCR) experiments were used to verify the expression patterns of BMs model. In summary, BMs model demonstrated efficacy in prognosticating the survival probability of HCC patients and their immunotherapeutic responsiveness.
PubMed: 38870261
DOI: 10.18632/aging.205923 -
Aging Jun 2024HCC, also known as hepatocellular carcinoma, is a frequently occurring form of cancer with an unfavorable prognosis. This research constructed a prognostic signature...
HCC, also known as hepatocellular carcinoma, is a frequently occurring form of cancer with an unfavorable prognosis. This research constructed a prognostic signature related to ubiquitination and investigated its correlation with the response to immunotherapy in HCC. The Molecular Signatures Database provided a compilation of genes associated with ubiquitination. A gene signature related to ubiquitination was obtained through Cox regression using the Least Absolute Shrinkage and Selection Operator method. The genetic factors CPY26B1, MCM10, SPINK4, and TRIM54 notably impacted the outcomes of HCC. The patients were divided into two groups: one group had a high risk of poor survival while the other had a low risk but a greater chance of controlling HCC progression. Both univariate and multivariate analyses using Cox regression found the risk score to be an independent predictor of HCC prognosis. Gene set enrichment analysis (GSEA) indicated enrichment in cell cycle and cancer-related microRNAs in high-risk groups. The tumor microenvironment (TME), response to immunotherapy, and effectiveness of chemotherapy medications positively correlated with the risk score. In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC.
PubMed: 38870259
DOI: 10.18632/aging.205926 -
PloS One 2024Family caregivers often play a key role in medical decision-making for patients with cancer. Adult-children account for nearly half of caregivers, but often have less... (Comparative Study)
Comparative Study
BACKGROUND
Family caregivers often play a key role in medical decision-making for patients with cancer. Adult-children account for nearly half of caregivers, but often have less experience with serious illness care and decision-making and face unique relational challenges as the patient's child. Yet little research explores the potentially distinctive decision-making, involvement in decisions, and support needs of adult-child caregivers.
METHODS
Analysis of survey data of U.S. cancer caregivers conducted by CancerCare® in 2021. Chi-square tests and multivariable regression models assessed whether adult-child and spousal caregivers differed on the type of medical decisions they participated in (e.g., treatment planning, medication management), who made the decision (e.g., caregiver or joint decision), and the resources that informed decisions (e.g., friends and family, education materials).
RESULTS
Adult-children (N = 892) were less likely than spouses (N = 314) to participate in treatment planning (beta = -0.41; 95%CI = -0.81,-0.01), but more likely to be involved in decisions about whether to challenge medical authority (e.g., seeking alternative treatment, second opinion) (beta = 0.50; 95%CI = 0.22,0.78). Compared to spouses, adult-children made joint decisions with patients less often (-13.2-percentage points; 95%CI = -19.64,-6.67) and acted as primary decision-maker more frequently (5.60-percentage points; 95%CI = 0.01,10.43). More adult-children than spouses sought help and information regarding decisions from the oncology team (8.42-percentage points; 95%CI = 1.98,14.87) and friends and family (7.91-percentage points; 95%CI = 1.34,14.48).
CONCLUSIONS
How cancer caregivers and patients are related to each other shapes caregivers' medical decision-making. Adult-children's and spouses' probabilities of participating in and influencing decisions differed for certain types of decisions while adult-children were more likely to seek information and social support regarding decisions. These findings highlight the importance of the patient's and caregiver's relationship type in medical decision-making, suggesting that decision support programs may be more effective if they tailor programs by relationship type.
Topics: Humans; Caregivers; Female; Male; Middle Aged; Neoplasms; Adult; Spouses; Adult Children; Aged; Decision Making; Surveys and Questionnaires
PubMed: 38870142
DOI: 10.1371/journal.pone.0300450 -
The Journal of Clinical Investigation Jun 2024The identification of genes that confer either extension of lifespan or accelerate age-related decline was a step forward in understanding the mechanisms of ageing and...
The identification of genes that confer either extension of lifespan or accelerate age-related decline was a step forward in understanding the mechanisms of ageing and revealed that it is partially controlled by genetics and transcriptional programs. Here we discovered that the human DNA sequence C16ORF70 encoded for a protein, named MYTHO (Macroautophagy and YouTH Optimizer), which controls life- and health-span. MYTHO protein is conserved from C. elegans to humans and its mRNA was upregulated in aged mice and elderly people. Deletion of the ortholog myt-1 gene in C. elegans dramatically shortened lifespan and decreased animal survival upon exposure to oxidative stress. Mechanistically, MYTHO is required for autophagy likely because it acts as a scaffold that binds WIPI2 and BCAS3 to recruit and assemble the conjugation system at the phagophore, the nascent autophagosome. We conclude that MYTHO is a transcriptionally regulated initiator of autophagy that is central in promoting stress resistance and healthy ageing.
PubMed: 38869949
DOI: 10.1172/JCI165814