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ObjectiveUnbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.DesignLiterature review, pooling analysis and correlation analysis.Data sourcesPubMed, from 1 January 2010 to 30 June 2017.Eligibility criteria for selecting studiesEligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments.ResultsOf 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29).ConclusionsNo systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.

Rapid industrialization and economic development have caused a tremendous increase in municipal solid waste (MSW) generation in China. China began implementing a policy of MSW disposal fees for household waste management at the end of last century. Three charging methods were implemented throughout the country: a fixed disposal fee, a potable water-based disposal fee, and a plastic bag-based disposal fee. To date, there has been little qualitative or quantitative analysis on the effectiveness of this relatively new policy. This paper provides a general overview of MSW fee policy in China, attempts to verify whether the policy is successful in reducing general waste collected, and proposes an improved charging system to address current problems. The paper presents an empirical statistical analysis of policy effectiveness derived from an environmental Kuznets curve (EKC) test on panel data of China. EKC tests on different kinds of MSW charge systems were then examined for individual provinces or cities. A comparison of existing charging systems was conducted using environmental and economic criteria. The results indicate the following: (1) the MSW policies implemented over the study period were effective in the reduction of waste generation, (2) the household waste discharge fee policy did not act as a strong driver in terms of waste prevention and reduction, and (3) the plastic bag-based disposal fee appeared to be performing well according to qualitative and quantitative analysis. Based on current situation of waste discharging management in China, a three-stage transitional charging scheme is proposed and both advantages and drawbacks discussed. Evidence suggests that a transition from a fixed disposal fee to a plastic bag-based disposal fee involving various stakeholders should be the next objective of waste reduction efforts.

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Background The effect of dairy products intake on breast cancer (BC) is highly controversial. This study aims to investigate the relationship between dairy intake and BC incidence. Methods A search was carried out in PubMed, EBSCO, Web of Science, and Cochrane Library databases before January 2021. The primary objective was the risk of BC and intake of dairy products were exposure variables. Results The meta-analysis comprised 36 articles with 1,019,232 participants. Total dairy products have a protective effect on female population (hazard ratio (HR) =0.95, 95% confidence interval (CI) =0.91–0.99, p = 0.019), especially for estrogen receptor-positive (ER+) (HR = 0.79, p = 0.002) and progesterone receptor-positive (PR+) BC (HR = 0.75, p = 0.027). For ER+/PR+ BC, there is a trend of protection, but it has not reached statistical significance (HR = 0.92, p = 0.075). Fermented dairy products can reduce BC risk in postmenopausal population (HR = 0.96, 95%CI = 0.93–0.99, p = 0.021), but have no protective effect on premenopausal population (HR = 0.98, 95%CI = 0.94–1.03, p = 0.52). Non-fermented dairy products have no significant effect on BC occurrence (p > 0.05). High-fat dairy products are harmful to women, without statistical difference (HR = 1.06, 95%CI = 1.00–1.13, p = 0.066). On the contrary, low-fat dairy products can protect the premenopausal population (HR = 0.94, 95%CI = 0.89–1.00, p = 0.048). Conclusion The intake of dairy products can overall reduce BC risk in the female population, but different dairy products have varying effects on different BC subtypes and menopausal status.

Objective: This study aims to comprehensively analyze the influence of spontaneous tumor rupture on the prognosis of hepatocellular carcinoma patients following hepatic resection.Methods: We systematically searched four online electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, for eligible studies published from inception to March 2021. The main endpoints were overall survival (OS) and disease-free survival (DFS).Results: This meta-analysis included 21 observational articles with 57,241 cases. The results revealed that spontaneous tumor rupture was associated with worse OS (hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.33–2.05) and DFS (HR, 1.42; 95% CI, 1.12–1.80) in resectable hepatocellular carcinoma patients. This phenomenon was observed in most subgroups, which were classified by recorded survival time, age, country, alpha-fetoprotein (AFP) concentration, liver cirrhosis, and microvascular invasion. However, in subgroups of macrovascular invasion positive, spontaneous tumor rupture was not a risk factor for OS (HR, 1.55; 95% CI, 0.99–2.42) and DFS (HR, 1.23; 95% CI, 0.91–1.65) in hepatocellular carcinoma patients after hepatectomy. For macrovascular invasion negative, compared with non-ruptured hepatocellular carcinoma patients, ruptured hepatocellular carcinoma patients exhibited worse prognosis for OS (HR, 1.55; 95% CI, 0.99–2.42) and DFS (HR, 1.23; 95% CI, 0.91–1.65) following hepatectomy.Conclusions: Spontaneous tumor rupture was a prognostic risk factor for hepatocellular carcinoma patients after hepatic resection. However, in macrovascular invasion patients, spontaneous tumor rupture was not a prognostic risk factor.

A total of 16 OsS40 genes of Oryza sativa were identified in our previous work, but their functions remain unclear. In this study, 13 OsS40 members were knocked out using the CRISPR/cas9 gene-editing technology. After screening phenotype characterization of CRISPR/Cas9 mutants compared to WT, five oss40s mutants exhibited a stay-green phenotype at 30 days after heading. Moreover, increased grain size and grain weight occurred in the oss40-1, oss40-12, and oss40-14 lines, while declined grain weight appeared in the oss40-7 and oss40-13 mutants. The transcript levels of several senescence-associated genes (SAGs), chlorophyll degradation-related genes (CDGs), as well as WRKY members were differentially decreased in the five stay-green oss40s mutants compared to WT. Five oss40 mutants also exhibited a stay-green phenotype when the detached leaves were incubated under darkness for 4 days. OsSWEET4 and OsSWEET1b were significantly upregulated, while OsSWEET1a and OsSWEET13 were significantly downregulated in both oss40-7 and oss40-14 compared to WT. Furthermore, these five OsS40 displayed strong transcriptional activation activity and were located in the nucleus. Most of the OsS40 genes were downregulated in the oss40-1, oss40-7, and oss40-12 mutants, but upregulated in the oss40-13 and oss40-14 mutants, indicating coordinated regulation among OsS40 members. These results suggest that OsS40-1, OsS40-7, OsS40-12, OsS40-13, and OsS40-14 are senescence-associated genes, involved in the senescence and carbon allocation network by modulating other OsS40 members, SWEET member genes, and senescence-related gene expression.