Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80-93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93-98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89-98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
The development of solution-processed photovoltaic (PV) devices for indoor applications has recently attracted widespread attention owing to their outstanding potential in harvesting energy efficiently for low-power-consumption electronic devices, such as...
The Big-fish-little-Pond effect is well acknowledged as the negative effect of class/school average achievement on student academic self-concept, which profoundly impacts student academic performance and mental development. Although a few studies have been done with regard to this effect, inconsistence exists in the effect size with little success in finding moderators. Here, we present a meta-analysis to synthesize related literatures to reach a summary conclusion on the BFLPE. Furthermore, student age, comparison target, academic self-concept domain, student location, sample size, and publication year were examined as potential moderators. Thirty-three studies with fifty-six effect sizes (total N = 1,276,838) were finally included. The random effects model led to a mean of the BFLPE at β = −0.28 (p < 0.001). Moreover, moderator analyses revealed that the Big-Fish-Little-Pond effect is an age-based process and an intercultural phenomenon, which is stronger among high school students, in Asia and when verbal self-concept is considered. This meta-analysis is the first quantitative systematic overview of BFLPE, whose results are valuable to the understanding of BFLPE and reveal the necessity for educators from all countries to learn about operative means to help students avoid the potential negative effect. Future research expectations are offered subsequently.
EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both “on target” and “off target” mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.
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