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- Qin, F., et al.
(författare)
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Frailty and risk of adverse outcomes among community-dwelling older adults in China: a comparison of four different frailty scales
- 2023
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Ingår i: Frontiers In Public Health. - 2296-2565. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundData on which frailty scales are most suitable for estimating risk in Chinese community populations remain limited. Herein we examined and compared four commonly used frailty scales in predicting adverse outcomes in a large population-based cohort of Chinese older adults. MethodsA total of 5402 subjects (mean age 66.3 +/- 9.6 years, 46.6% male) from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Frailty was measured using a 35-item frailty index (FI), the frailty phenotype (FP), FRAIL, and Tilburg Frailty Indicator (TFI). Multivariate logistic regression models were performed to evaluate the independent association between frailty and outcomes including 4-year disability, hospitalization, and 4- and 7-year all-cause mortality. The accuracy for predicting these outcomes was determined by evaluating the area under the curve (AUC). The prevalence of frailty, sensitivity, and specificity were calculated using our proposed cut-off points and other different values. ResultsPrevalence of frailty ranged from 4.2% (FRAIL) to 16.9% (FI). FI, FRAIL and TFI were comparably associated with 4-year hospitalization, and 4- and 7-year mortality (adjusted odds ratios [aORs] 1.44-1.69, 1.91-2.22 and 1.85-2.88, respectively). FRAIL conferred the greatest risk of 4-year disability, followed by FI and TFI (aOR 5.55, 3.50, and 1.91, respectively). FP only independently predicted 4- and 7-year mortality (aOR 1.57 and 2.21, respectively). AUC comparisons showed that FI, followed by TFI and FRAIL, exhibited acceptable predictive accuracy for 4-year disability, 4- and 7-year mortality (AUCs 0.76-0.78, 0.71-0.71, 0.65-0.72, respectively), whereas all scales poorly predicted 4-year hospitalization (AUCs 0.53-0.57). For each scale, while specificity estimates (85.3-97.3%) were high and similar across all outcomes, their sensitivity estimates (6.3-56.8%) were not sufficient yet. Prevalence of frailty, sensitivity, and specificity varied considerably when different cut-off points were used. ConclusionFrailty defined using any of the four scales was associated with an increased risk of adverse outcomes. Although FI, FRAIL and TFI exhibited fair-to-moderate predictive accuracy and high specificity estimates, their sensitivity estimates were not sufficient yet. Overall, FI performed best in estimating risk, while TFI and FRAIL were additionally useful, the latter perhaps being more applicable to Chinese community-dwelling older adults.
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| 2. |
- Wei, Yanfei, et al.
(författare)
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Stalled oligodendrocyte differentiation in IDH-mutant gliomas.
- 2023
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Ingår i: Genome medicine. - 1756-994X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Roughly 50% of adult gliomas harbor isocitrate dehydrogenase (IDH) mutations. According to the 2021 WHO classification guideline, these gliomas are diagnosed as astrocytomas, harboring no 1p19q co-deletion, or oligodendrogliomas, harboring 1p19q co-deletion. Recent studies report that IDH-mutant gliomas share a common developmental hierarchy. However, the neural lineages and differentiation stages in IDH-mutant gliomas remain inadequately characterized.Using bulk transcriptomes and single-cell transcriptomes, we identified genes enriched in IDH-mutant gliomas with or without 1p19q co-deletion, we also assessed the expression pattern of stage-specific signatures and key regulators of oligodendrocyte lineage differentiation. We compared the expression of oligodendrocyte lineage stage-specific markers between quiescent and proliferating malignant single cells. The gene expression profiles were validated using RNAscope analysis and myelin staining and were further substantiated using data of DNA methylation and single-cell ATAC-seq. As a control, we assessed the expression pattern of astrocyte lineage markers.Genes concordantly enriched in both subtypes of IDH-mutant gliomas are upregulated in oligodendrocyte progenitor cells (OPC). Signatures of early stages of oligodendrocyte lineage and key regulators of OPC specification and maintenance are enriched in all IDH-mutant gliomas. In contrast, signature of myelin-forming oligodendrocytes, myelination regulators, and myelin components are significantly down-regulated or absent in IDH-mutant gliomas. Further, single-cell transcriptomes of IDH-mutant gliomas are similar to OPC and differentiation-committed oligodendrocyte progenitors, but not to myelinating oligodendrocyte. Most IDH-mutant glioma cells are quiescent; quiescent cells and proliferating cells resemble the same differentiation stage of oligodendrocyte lineage. Mirroring the gene expression profiles along the oligodendrocyte lineage, analyses of DNA methylation and single-cell ATAC-seq data demonstrate that genes of myelination regulators and myelin components are hypermethylated and show inaccessible chromatin status, whereas regulators of OPC specification and maintenance are hypomethylated and show open chromatin status. Markers of astrocyte precursors are not enriched in IDH-mutant gliomas.Our studies show that despite differences in clinical manifestation and genomic alterations, all IDH-mutant gliomas resemble early stages of oligodendrocyte lineage and are stalled in oligodendrocyte differentiation due to blocked myelination program. These findings provide a framework to accommodate biological features and therapy development for IDH-mutant gliomas.
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