The prognostic impact of variant allele frequency (VAF) in TP53 mutant patients with MDS: A systematic review and meta-analysis.

Tumor protein p53 (TP53) is frequently expressed in patients with myelodysplastic syndromes (MDS). Studies have already reported the poor prognostic impact of TP53 gene mutations in MDS patients. However, parts of this subgroup of patients with low-risk MDS still have relatively better survival and longer remission times. Therefore, we performed a meta-analysis to evaluate the prognostic difference intra-gene of variant allele frequency (VAF). The primary endpoint was overall survival (OS), and event-free survival (EFS) was selected as the secondary endpoint. We extracted the hazard ratio (HR) and 95% confidence interval (CI) for OS and EFS from univariate and multivariate Cox proportional hazard models. A total of 4003 MDS patients and 1278 TP53-mutated patients from 13 cohorts of 11 studies up to February 24, 2020, were included in our meta-analysis. Pooled HRs suggested that a high mutant VAF had an adverse impact on OS (HR = 2.11, 95% CI: 1.48-3.01, P < .0001) but no impact on EFS (HR = 15.57, 95% CI: 0.75-324.44, P = .003) in MDS patients. Twenty percent is a proper threshold to set (HR = 2.02, 95% CI: 1.31-3.13, P = .001) and is a rough line between high clone burden and low clone burden, while 40% is an exact cutoff point (HR = 2.11, 95% CI: 1.26-3.55, P < .0001) to guide diagnosis and treatment. Beyond the traditional binary classification of gene mutation, we aimed to find a way to divide mutant molecular markers more specifically by VAF to provide clinical therapeutic values. Our meta-analysis indicates that a high VAF is an independent, adverse prognostic factor for OS in TP53 mutant MDS patients. Patients with mediate/low-frequency parts who could be treated like wide-type patients have relatively better survival and may choose allogeneic hematopoietic stem cell transplantation as conditions permitting. Further prospective studies are needed in the future, and a large subgroup analysis of the same cutoff point subgroups is needed to obtain a more reliable basis for the impact of other mutant gene VAFs on the prognosis of MDS.

Prognostic significance of the EVI1 gene expression in patients with acute myeloid leukemia: a meta-analysis.

Ecotropic virus integration site-1 (EVI1) is frequently expressed in patients with acute myeloid leukemia (AML). Many studies have reported the potential poor prognostic impact of EVI1 higher expression (EVI1H) in the AML patients; however, the conclusions previously reported have not been fully assessed and are still controversial. Therefore, we performed a meta-analysis to evaluate the prognostic significance of EVI1H in patients with AML. The primary endpoint was overall survival (OS), and the event-free survival (EFS) was selected as the secondary endpoint. We extracted the hazard ratio (HR) and their 95% confidence interval (CI) for the OS and EFS from the multivariate COX proportional hazard models. A total of 4767 AML patients from 11 studies up to 23 February 2019 were subjected to our meta-analysis. Pooled HRs suggested that EVI1H had an adverse impact on OS (HR = 1.52, 95%CI 1.24-1.86) and EFS (HR = 1.41, 95%CI 1.14-1.74) in AML patients. EVI1H was also associated with a shorter OS (HR = 1.73, 95%CI 1.43-2.11) and EFS (HR = 1.17, 95%CI 1.05-1.31) in AML patients with the intermediate cytogenetic risk (ICR) according to the National Comprehensive Cancer Network (NCCN), European leukemia network (ELN), or International System for Human Cytogenetic Nomenclature (ISCN). Furthermore, EVI1H appeared to be a poor prognosis indicator in patients with normal cytogenetics (NC) (HR for OS:2.01, 95%CI 1.32-3.05; HR for EFS 1.54, 95%CI 1.09-2.17) and young patients (HR for OS 1.30, 95%CI 1.09-1.55), respectively. This meta-analysis indicates EVI1H has an independent and significantly adverse prognostic impact on AML patients in the entire population, and this conclusion same applies to some subgroups like AML patients with ICR, NC, and young AML patients.

Prognostic value of U2AF1 mutant in patients with de novo myelodysplastic syndromes: a meta-analysis.

U2 small nuclear RNA auxiliary factor 1 (U2AF1) mutant is the most common molecular biological abnormality in patients with myelodysplastic syndromes. Some studies have reported the prognostic impact of U2AF1 mutant in patients with de novo MDS, with discrepant results, so we do a meta-analysis about the relevant literatures to further investigate their prognostic impact on patients with de novo MDS. We conducted a literature search on databases such as PubMed, Embase, and the Cochrane Library to obtain studies on the prognosis of U2AF1 mutant in patients with de novo MDS published up to August 9, 2018. The primary endpoint was overall survival (OS), and the secondary endpoint was acute myeloid leukemia (AML) transformation. We extracted the hazard ratios (HRs) of OS and AML transformation and their 95% confidence intervals (CIs). Meta-analysis was performed by selecting a fixed-effect model or a random-effects model based on the heterogeneity between studies. A total of 14 cohort studies were included in the final meta-analysis, including 3322 patients with de no MDS, in which 390 patients were associated with U2AF1 mutant. The results showed that U2AF1 mutant had an adverse prognostic impact on OS (HR = 1.84, 95% CI: 1.45-2.33, P < 0.00001) and AML transformation (HR = 2.47, 95% CI: 1.50-4.06, P = 0.0004). U2AF1 mutant was associated with shorter OS in subgroup analyses of low- or intermediate-1-IPSS, U2AF1S34 and U2AF1Q157/R156. Out meta-analysis indicates that U2AF1 mutants are independent, detrimental prognostic factors for OS and AML transformation in patients with de novo MDS, as well as associating with shorter OS in subgroups of low- or intermediate-1-IPSS, U2AF1S34 and U2AF1Q157/R156. Further prospective studies are needed in the future, and subgroup analysis of U2AF1 subgroups is needed to obtain a more reliable basis for the impact of U2AF1 mutant on the prognosis of de novo MDS.

Development of a composite regional vulnerability index and its relationship with the impacts of the COVID-19 pandemic.

The interactions between vulnerability and human activities have largely been regarded in terms of the level of risk they pose, both internally and externally, for certain groups of disadvantaged individuals and regions/areas. However, to date, very few studies have attempted to develop a comprehensive composite regional vulnerability index, in relation to travel, housing, and social deprivation, which can be used to measure vulnerability at an aggregated level in the social sciences. Therefore, this research aims to develop a composite regional vulnerability index with which to examine the combined issues of travel, housing and socio-economic vulnerability (THASV index). It also explores the index's relationship with the impacts of the COVID-19 pandemic, reflecting both social and spatial inequality, using Greater London as a case study, with data analysed at the level of Middle Layer Super Output Areas (MSOAs). The findings show that most of the areas with high levels of composite vulnerability are distributed in Outer London, particularly in suburban areas. In addition, it is also found that there is a spatial correlation between the THASV index and the risk of COVID-19 deaths, which further exacerbates the potential implications of social deprivation and spatial inequality. Moreover, the results of the multiscale geographically weighted regression (MGWR) show that the travel and socio-economic indicators in a neighbouring district and the related vulnerability indices are strongly associated with the risk of dying from COVID-19. In terms of policy implications, the findings can be used to inform sustainable city planning and urban development strategies designed to resolve urban socio-spatial inequalities and the potential related impacts of COVID-19, as well as guiding future policy evaluation of urban structural patterns in relation to vulnerable areas.

Aging-friendly cities: Investigating the effects of street usage on the psychological satisfaction of older adults in megacities.

The psychological satisfaction of older adults is an important evaluation standard for the construction of elder-friendly cities. Meanwhile, as important space carriers carrying the travel activities and social participation of older adults, streets are also of great significance to improve psychological wellbeing. However, few studies pay attention to the street usage of aging population, especially in the context of megacities. Moreover, the previous literature rarely distinguishes the types of streets. Thus, employing a mixed approach, we investigate the relationships between street usage and psychological satisfaction for older adults. Based on the survey in Shanghai, we find that a clear role for different usage indicators in the determination of subjective psychological satisfaction of older adults. More specially, the street usage and psychological satisfaction for older adults are strongly correlated, especially for living streets. Psychological satisfaction for older adults in different types of streets is not always positively related to the positive perception of street usage. The psychological satisfaction of different streets depends on different factors. By focusing on the case of a megacity, our study emphasizes the differences between different types of streets, which will be conducive to the proposal of practical planning policies. In addition, employing mixed research methods not only explains how different street usage affects the psychological welfare of older adults on a macro scale, but also emphasizes the inner world of respondents.

Dealing with an aging China-Delaying retirement or the second-child policy?

To tackle China's rapidly aging population, a policy was framed by using overlapping generations (OLG) model and computable general equilibrium (CGE) model; the main objective was to successfully implement "second-child policy" and "delayed retirement age" for female or male workers. The 2012 census data was obtained from National Bureau of Statistics of China. Our research findings suggest that the economy can be improved in the short-term by delaying retirement age; however, Chinese economy would improve tremendously in the long run by implementing second-child policy. Compared to delayed retirement age, second-child policy would be more effective in improving the economy in China. In terms of industrial output, the three policies have a greater influence on labor-intensive industries, such as agriculture, light industry, finance, and service sector; the impact is less significant on construction and heavy industry. In terms of industrial import and export, these three policies have greatly influenced following industries: finance, electric power, and fossil energy. From a monetary perspective, these three policies can significantly improve household income; these three policies did not significantly impact both government and corporate incomes.