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Methods to Adjust for Confounding in Test-Negative Design COVID-19 Effectiveness Studies: Simulation Study.
JMIR Form Res
January 2025
Vaccine Study Center, Northern California Division of Research, Kaiser Permanente, Oakland, CA, United States.
Background: Real-world COVID-19 vaccine effectiveness (VE) studies are investigating exposures of increasing complexity accounting for time since vaccination. These studies require methods that adjust for the confounding that arises when morbidities and demographics are associated with vaccination and the risk of outcome events. Methods based on propensity scores (PS) are well-suited to this when the exposure is dichotomous, but present challenges when the exposure is multinomial.
View Article and Find Full Text PDFInternet-Based Dementia Prevention Intervention (DementiaRisk): Protocol for a Randomized Controlled Trial and Knowledge Translation.
JMIR Res Protoc
January 2025
McMaster University, Hamilton, ON, Canada.
Background: Research has shown that engaging in a range of healthy lifestyles or behavioral factors can help reduce the risk of developing dementia. Improved knowledge of modifiable risk factors for dementia may help engage people to reduce their risk, with beneficial impacts on individual and public health. Moreover, many guidelines emphasize the importance of providing education and web-based resources for dementia prevention.
View Article and Find Full Text PDFHow can we make sound replication decisions?
Proc Natl Acad Sci U S A
February 2025
Department of Computer Science, Faculty of Information Technology and Electrical Engineering, Norwegian University of Science and Technology, Trondheim 7030, Norway.
Replication and the reported crises impacting many fields of research have become a focal point for the sciences. This has led to reforms in publishing, methodological design and reporting, and increased numbers of experimental replications coordinated across many laboratories. While replication is rightly considered an indispensable tool of science, financial resources and researchers' time are quite limited.
View Article and Find Full Text PDFRational Design of Nanozymes for Engineered Cascade Catalytic Cancer Therapy.
Chem Rev
January 2025
Center for Theoretical Interdisciplinary Sciences Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, P. R. China.
Nanozymes have shown significant potential in cancer catalytic therapy by strategically catalyzing tumor-associated substances and metabolites into toxic reactive oxygen species (ROS) , thereby inducing oxidative stress and promoting cancer cell death. However, within the complex tumor microenvironment (TME), the rational design of nanozymes and factors like activity, reaction substrates, and the TME itself significantly influence the efficiency of ROS generation. To address these limitations, recent research has focused on exploring the factors that affect activity and developing nanozyme-based cascade catalytic systems, which can trigger two or more cascade catalytic processes within tumors, thereby producing more therapeutic substances and achieving efficient and stable cancer therapy with minimal side effects.
View Article and Find Full Text PDFHighly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.
J Med Chem
January 2025
Pharmaron Beijing Co., Ltd., 6 Taihe Road, BDA, Beijing 100176, P. R. China.
Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.
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