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Suicide is a significant and rising threat to public health. In the United States, 47,500 people died from suicide in 2019, a 10-year increase of 30%. Many researchers are interested in studying the risk factors associated with suicidal ideation and suicide attempt to help inform clinical screening, intervention, and prevention efforts. Many suicide risk factor analyses draw from clinical subdomains and quantify risk factors independently. While traditional modeling approaches might assume independence between risk factors, current suicide research suggests that the development of suicidal intent is a complex, multifactorial process. Thus, it may be beneficial to how suicide risk-factors interact with one another. In this study, we used network analysis to generate visual suicidality risk relationship diagrams. We extract medical concepts from free-text clinical notes and generate cooccurrence-based risk networks for suicidal ideation and suicide attempt. In addition, we generate a network of risk factors for suicidal ideation which evolves into a suicide attempt. Our networks were able to replicate existing risk factor findings and provide additional insight into the degree to which risk factors behave as independent morbidities or as interacting comorbidities with other risk factors. These results highlight potential avenues for risk factor analyses of complex outcomes using network analysis.

BACKGROUND: Macrophages have many functions in development and homeostasis as well as innate immunity. Recent studies in mammals suggest that cells arising in the yolk sac give rise to self-renewing macrophage populations that persist in adult tissues. Macrophage proliferation and differentiation is controlled by macrophage colony-stimulating factor (CSF1) and interleukin 34 (IL34), both agonists of the CSF1 receptor (CSF1R). In the current manuscript we describe the origin, function and regulation of macrophages, and the role of CSF1R signalling during embryonic development, using the chick as a model.RESULTS: Based upon RNAseq comparison to bone marrow-derived macrophages (BMDM) grown in CSF1, we show that embryonic macrophages contribute around 2% of the total embryo RNA in day 7 chick embryos, and have similar gene expression profiles to BMDM. To explore the origins of embryonic and adult macrophages, we injected HH16 chick embryos with either yolk-sac derived blood cells, or bone marrow cells from EGFP(+) donors. In both cases, the transferred cells gave rise to large numbers of EGFP(+) tissue macrophages in the embryo. In the case of the yolk sac, these cells were not retained in hatched birds. Conversely, bone marrow EGFP(+) cells gave rise to tissue macrophages in all organs of adult birds, and regenerated CSF1-responsive marrow macrophage progenitors. Surprisingly, they did not contribute to any other hematopoietic lineage. To explore the role of CSF1 further, we injected embryonic or hatchling CSF1R-reporter transgenic birds with a novel chicken CSF1-Fc conjugate. In both cases, the treatment produced a large increase in macrophage numbers in all tissues examined. There were no apparent adverse effects of chCSF1-Fc on embryonic or post-hatch development, but there was an unexpected increase in bone density in the treated hatchlings.CONCLUSIONS: The data indicate that the yolk sac is not the major source of macrophages in adult birds, and that there is a macrophage-restricted, self-renewing progenitor cell in bone marrow. CSF1R is demonstrated to be limiting for macrophage development during development in ovo and post hatch. The chicken provides a novel and tractable model to study the development of the mononuclear phagocyte system and CSF1R signalling.