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A Real-World Evidence (RWE) Scientific Working Group (SWG) of the American Statistical Association Biopharmaceutical Section (ASA BIOP) has been reviewing statistical considerations for the generation of RWE to support regulatory decision-making. As part of the effort, the working group is addressing estimands in RWE studies. Constructing the right estimand--the target of estimation--which reflects the research question and the study objective, is one of the key components in formulating a clinical study. ICH E9(R1) describes statistical principles for constructing estimands in clinical trials with a focus on five attributes--population, treatment, endpoints, intercurrent events, and population-level summary. However, defining estimands for clinical studies using real-world data (RWD), that is, RWE studies, requires additional considerations due to, for example, heterogeneity of study population, complexity of treatment regimes, different types and patterns of intercurrent events, and complexities in choosing study endpoints. This article reviews the essential components of estimands and causal inference framework, discusses considerations in constructing estimands for RWE studies, highlights similarities and differences in traditional clinical trial and RWE study estimands, and provides a roadmap for choosing appropriate estimands for RWE studies. [ABSTRACT FROM AUTHOR]

In recent years, breast cancer attracts more and more attention because of its high incidence. To explore the molecular functions and mechanisms, we performed RNA sequencing on the tumor tissues and their paired normal tissues from three breast cancer patients. By differential expression analysis, we found 3764 differentially expressed (DE) mRNAs, 5416 DE lncRNAs, and 148 DE circRNAs. Enrichment analysis suggested that the DE lncRNAs and DE circRNAs were enriched in mitochondria and nucleus, which indicated that they may participate in the vital metabolism directly or indirectly, such as fatty acid metabolism. Subsequently, the protein-protein interaction (PPI) network was constructed and we got 8 key proteins, of which the matrix metalloproteinase-9 (MMP9; degree 5) draws our attention. Based on the 38 up-regulated circRNAs and 14 down-regulated circRNAs, we constructed competing endogenous RNA (ceRNA) networks, from which the has-miR-6794-5p has been identified to enriched in the up-regulated network and correlated with the circNFIX directly. At this point, we presented that the circNFIX and MMP9 may play a significant role by regulating fatty acid metabolism in breast cancer. [ABSTRACT FROM AUTHOR]

This paper investigates the maximum genus and upper embeddability of connected 4-regular graphs. We obtain lower bounds on the maximum genus of connected 4-regular simple graphs and connected 4-regular graphs without loops in terms of the Betti number. The definition of the Betti number is referred to [Gross and Tucker, Topological Graph Theory, New York, 1987]. Furthermore, we give examples that show that these lower bounds are tight. [ABSTRACT FROM AUTHOR]