Skeletal myogenesis in the embryo is regulated by the coordinated expression of the MyoD family of muscle regulatory factors (MRFs). MyoD and Myf-5, which are the primary muscle lineage-determining factors, function in a partially redundant manner to establish muscle progenitor cell identity. Previous diphtheria toxin (DTA)-mediated ablation studies showed that MyoD+ progenitors rescue myogenesis in embryos in which Myf-5-expressing cells were targeted for ablation, raising the possibility that the regulative behavior of distinct, MRF-expressing populations explains the functional compensatory activities of these MRFs. Using MyoDiCre mice, we show that DTA-mediated ablation of MyoD-expressing cells results in the cessation of myogenesis by embryonic day 12.5 (E12.5), as assayed by myosin heavy chain (MyHC) and Myogenin staining. Importantly, MyoDiCre/+;R26DTA/+ embryos exhibited a concomitant loss of Myf-5+ progenitors, indicating that the vast majority of Myf-5+ progenitors express MyoD, a conclusion consistent with immunofluorescence analysis of Myf-5 protein expression in MyoDiCre lineage-labeled embryos. Surprisingly, staining for the paired box transcription factor, Pax7, which functions genetically upstream of MyoD in the trunk and is a marker for fetal myoblasts and satellite cell progenitors, was also lost by E12.5. Specific ablation of differentiating skeletal muscle in ACTA1Cre;R26DTA/+ embryos resulted in comparatively minor effects on MyoD+, Myf-5+ and Pax7+ progenitors, indicating that cell non-autonomous effects are unlikely to explain the rapid loss of myogenic progenitors in MyoDiCre/+;R26DTA/+ embryos. We conclude that the vast majority of myogenic populations transit through a MyoD+ state, and that MyoD+ progenitors are essential for myogenesis and stem cell development.

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the process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal). Within the decidua, the maternal immune system undergoes continued changes, as the pregnancy progress, in terms of the cell population, phenotype and production of immune factors, cytokines and chemokines. Human chorionic gonadotropin (hCG) is one of the earliest hormones produced by the blastocyst and has potent immune modulatory effects, especially in relation to T cells. We hypothesized that trophoblastderived hcG modulates the immune population present at the maternal fetal interface by modifying the cytokine profile produced by the stromal/decidual cells. Using in vitro models from decidual samples we demonstrate that hcG inhibits CXCL10 expression by inducing H3K27me3 histone methylation, which binds to Region 4 of the CXCL10 promoter, thereby suppressing its expression. hCG-induced histone methylation is mediated through EZH2, a functional member of the PRC2 complex. Regulation of CXCL10 expression has a major impact on the capacity of endometrial stromal cells to recruit CD8 cells. We demonstrate the existence of a cross talk between the placenta (hCG) and the decidua (CXCL10) in the control of immune cell recruitment. Alterations in this immune regulatory function, such as during infection, will have detrimental effects on the success of the pregnancy. The coordinated balance between the invading trophoblast and a receptive maternal decidua is critical for the success of pregnancy 1,2. The process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal) 3-5. Within the decidua, the maternal immune system undergoes continued modifications, as the pregnancy progresses, in terms of the cell population, phenotype and production of immune factors, cytokines and chemokines 6. These adaptation processes are essential for the normal progression of the pregnancy. The decidua, the pregnant uterine endometrium, has long been considered as a supportive environment for the immune cells and the trophoblast present at the implantation site. However, growing evidence suggest that decidual stromal cells (DSCs) may play a more active role in the regulation of differentiation, migration and function of uterine immune cells 7 as well as in the protection against infections 8. Immune cells are a major cellular component of the human and rodents' pregnant uterus, and their specific role has been an area of active research. During the first trimester of the human pregnancy, 70% of the leukocytes found in the decidua are Natural Killer (NK) cells, 20% to 25% are macrophages, and approximately 1.7% are dendritic cells (DCs) 9-11. In addition, the uterine T cell population expands across gestation, and are mostly regulatory in nature 12. The recruitment of immune cells into the uterus is cell specific and their function is locally controlled 7 .

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IMPORTANCE There is growing consensus that reliance on P values, particularly a cutoff level of .05 for statistical significance, is a factor in the challenges in scientific reproducibility. Despite this consensus, publications describing clinical trial results with P values near .05 anecdotally use declarative statements that do not express uncertainty. OBJECTIVES To quantify uncertainty expression in abstracts describing the results of cancer randomized clinical trials (RCTs) with P values between .01 and .10 and examine whether trial features are associated with uncertainty expression. DATA SOURCES A total of 5777 prospective trials indexed on HemOnc.org, as of September 15, 2019. STUDY SELECTION Two-arm RCTs with a superiority end point with P values between .01 and .10. DATA EXTRACTION AND SYNTHESIS Abstracts were evaluated based on an uncertainty expression algorithm. Ordinal logistic regression modeling with multiple imputation was performed to identify whether characteristics of study design, results, trial authors, and context were associated with uncertainty expression. P values were normalized by dividing by prespecified α value. MAIN OUTCOMES AND MEASURES Uncertainty expression in abstracts as determined by the algorithm and its association with trial and publication characteristics. RESULTS Of 5777 trials screened, 556 met analysis criteria. Of these, 222 trials (39.9%) did not express uncertainty, 161 trials (29.0%) expressed some uncertainty, and 173 trials (31.1%) expressed full uncertainty. In ordinal logistic regression with multiple imputation, trial features with statistically significant associations with uncertainty expression included later year of publication (odds ratio [