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BackgroundAs an innovative approach to providing web-based health care services from physical hospitals to patients at a distance, e-hospitals (ie, extended care hospitals through the internet) have been extensively developed in China. This closed health care delivery chain was developed by combining e-hospitals with physical hospitals; treatment begins with web-based consultation and registration, and then, patients are diagnosed and treated in a physical hospital. This approach is promising in its ability to improve accessibility, efficiency, and quality of health care. However, there is limited research on end users’ acceptance of e-hospitals and the effectiveness of strategies aimed to prompt the adoption of e-hospitals in China. ObjectiveThis study aimed to provide insights regarding the adoption of e-hospitals by investigating patients’ willingness to use e-hospitals and analyzing the barriers and facilitators to the adoption of this technology. MethodsWe used a pretested self-administered questionnaire and performed a cross-sectional analysis in 1032 patients across three hierarchical hospitals in West China from June to August 2019. Patients’ sociodemographic characteristics, medical history, current disease status, proficiency with electronic devices, previous experience with web-based health services, willingness to use e-hospitals, and perceived facilitators and barriers were surveyed. Multiple significance tests were employed to examine disparities across four age groups, as well as those between patients who were willing to use e-hospitals and those who were not. Multivariate logistic regression was also performed to identify the potential predictors of willingness to use e-hospitals. ResultsOverall, it was found that 65.6% (677/1032) of participants were willing to use e-hospitals. The significant predictors of willingness to use e-hospitals were employment status (P=.02), living with children (P

The mechanisms underlying stimuli-induced dynamic structural remodeling of RNAs for the maintenance of cellular physiological function and survival remain unclear. Here, we showed that in MGMT promoter–methylated glioblastoma (GBM), the RNA helicase DEAD-box helicase 46 (DDX46) is phosphorylated by temozolomide (TMZ)–activated checkpoint kinase 1 (CHK1), resulting in a dense-to-loose conformational change and an increase in DDX46 helicase activity. DDX46-mediated tertiary structural remodeling of LINC01956 exposes the binding motifs of LINC01956 to the 3′ untranslated region of O6-methylguanine DNA methyltransferase (MGMT). This accelerates recruitment of MGMT mRNA to the RNA export machinery and transportation of MGMT mRNA from the nucleus to the cytoplasm, leading to increased MGMT abundance and TMZ resistance. Using patient-derived xenograft (PDX) and tumor organoid models, we found that treatment with the CHK1 inhibitor SRA737abolishes TMZ-induced structural remodeling of LINC01956 and subsequent MGMT up-regulation, resensitizing TMZ-resistant MGMT promoter–methylated GBM to TMZ. In conclusion, these findings highlight a mechanism underlying temozolomide-induced RNA structural remodeling and may represent a potential therapeutic strategy for patients with TMZ-resistant MGMT promoter–methylated GBM. Editor's summary: Glioblastomas are usually treated with temozolomide (TMZ), but up-regulation of O6-methylguanine DNA methyltransferase (MGMT) leads to resistance. MGMT promoter–methylated glioblastomas show reduced MGMT expression and increased sensitivity to TMZ, although resistance can occur through unclear mechanisms. Here, Liao and colleagues showed that in resistant MGMT promoter–methylated glioblastoma, TMZ activates checkpoint kinase 1 (CHK1), which then activates an RNA helicase that alters the tertiary structure of the long noncoding RNA LINC01956. LINC01956 can then bind to MGMT, resulting in increased MGMT export from the nucleus and ultimately TMZ resistance. Administration of a CHK1 inhibitor prevents the structural remodeling of LINC01956, thereby blocking up-regulation of MGMT and restoring sensitivity to TMZ in vitro and in mouse models of disease, suggesting a potential treatment option to resensitize resistant MGMT promoter–methylated glioblastoma to TMZ. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Functionally graded ceramics (FGCs), which combine the properties of various composite ceramics, have been widely used in the aerospace, armament, and other industries. One of the newest melt‐growth ceramic additive manufacturing techniques, laser directed energy deposition (LDED), enables the creation of gradient materials by controlling the ratio of powder delivery. Ceramic–ceramic type gradient materials are the subject of fewer studies, and the majority of LDED gradient material systems now in research are metal–metal type and metal–ceramic type gradient materials. In this paper, LDED is used to create TiCp reinforced Al2O3 FGCs with three different transition paths. The results indicate that the longitudinal section of the gradient samples distinctly exhibits characteristics of gradient distribution. Furthermore, as the proportion of TiCp increases, there is a corresponding increase in the proportion of TiCp particles in the samples. The microstructure of Al2O3 transforms from columnar crystals to irregular shapes. Regarding the mechanical properties of the gradient samples, the area containing 30 wt.% of TiCp shows a significant improvement in wear resistance, with a 48.13% increase compared to the Al2O3 region. Additionally, this region demonstrates a 12.62% rise in hardness and a 9.48% increase in fracture toughness. [ABSTRACT FROM AUTHOR]

Objectives Identifying social policies that can promote cognitive health is crucial for reducing the global burden of dementia. We evaluated the importance of educational attainment for later-life cognitive function in various social and geographic settings. Methods Using harmonized data for individuals aged ≥65 years from the United States Health and Retirement Study (HRS) and its international partner studies in England, Mexico, China, and India, and each study's respective Harmonized Cognitive Assessment Protocol (HCAP), we conducted a cross-national comparative study to examine the role of educational attainment in later-life cognitive function across countries (n = 14,980, 2016–2019). We used multivariable-adjusted regression to estimate associations between educational attainment and harmonized global cognitive function scores. Results In Mexico, China, and India, the general cognitive function scores on average are approximately one standard deviation of the HRS-HCAP cognitive function score distribution lower compared to the United States and England, paralleling patterns of educational attainment across countries. In all countries, higher educational attainment was associated with progressively higher later-life cognitive function scores. Population-level differences in educational attainment explained about 50%–90% of the observed differences in cognitive function scores across countries. Discussion The relationship between education and later-life cognitive function across social and geographic contexts underscores the crucial role of education to promote cognitive health and reduce dementia risk. Continual improvement of educational attainment in low- and middle-income settings may yield a significant pay-off in later-life cognitive health. [ABSTRACT FROM AUTHOR]

Aim To investigate mid-life employment trajectories in relation to later-life memory function and rate of decline in rural South Africa. Methods Data from the Agincourt Health and Socio-Demographic Surveillance System were linked to the 'Health and Ageing in Africa: A Longitudinal Study of an INDEPTH Community in South Africa' (HAALSI) in rural Agincourt, South Africa (N  =   3133). Employment was assessed every 4 years over 2000–12 as being employed (0, 1, 2 and ≥3 time points), being employed in a higher-skill occupation (0, 1, 2 and ≥3 time points) and dynamic employment trajectories identified using sequence analysis. Latent memory z-scores were assessed over 2014–22. Mixed-effects linear regression models were fitted to examine the associations of interest. Results Sustained mid-life employment from 2000–12 (β = 0.052, 95% CI: -0.028 to 0.132, 1 vs 0 time points; β = 0.163, 95% CI: 0.077 to 0.250, 2 vs 0 time points; β = 0.212, 95% CI: 0.128 to 0.296, ≥3 vs 0 time points) and greater time spent in a higher-skill occupation (β = 0.077, 95% CI: -0.020 to 0.175, 1 vs 0 time points; β = 0.241, 95% CI: 0.070 to 0.412, 2 vs 0 time points; β = 0.361, 95% CI: 0.201 to 0.520, ≥3 vs 0 time points) were associated with higher memory scores in 2014/15, but not subsequent rate of memory decline. Moving from a lower-skill to higher-skill occupation was associated with higher memory function, but a faster rate of decline over 2014–22. Conclusions Sustained mid-life employment, particularly in higher-skill occupations, may contribute to later-life memory function in this post-Apartheid South African setting. [ABSTRACT FROM AUTHOR]

Introduction: The study objective was to investigate the association between loneliness duration and memory function over a 20‐year period. Methods: Data were from 9032 adults aged ≥50 in the Health and Retirement Study. Loneliness status (yes vs. no) was assessed biennially from 1996 to 2004 and its duration was categorized as never, 1 time point, 2 time points, and ≥3 time points. Episodic memory was assessed from 2004 to 2016 as a composite of immediate and delayed recall trials combined with proxy‐reported memory. Mixed‐effects linear regression models were fitted. Results: A longer duration of loneliness was associated with lower memory scores (P < 0.001) and a faster rate of decline (P < 0.001). The association was stronger among adults aged ≥65 than those aged <65 (three‐way interaction P = 0.013) and was stronger among women than men (three‐way interaction P = 0.002). Discussion: Cumulative loneliness may be a salient risk factor for accelerated memory aging, especially among women aged ≥65. Highlight: A longer duration of loneliness was associated with accelerated memory aging.The association was stronger among women than men and among older adults than the younger.Reducing loneliness in mid‐ to late life may help maintain memory function. [ABSTRACT FROM AUTHOR]