Transcriptional regulation, which involves a complex interplay between regulatory sequences and proteins, directs all biological processes. Computational models of transcription lack generalizability to accurately extrapolate to unseen cell types and conditions. Here we introduce GET (general expression transformer), an interpretable foundation model designed to uncover regulatory grammars across 213 human fetal and adult cell types.
View Article and Find Full Text PDFDisenfranchised grief is a form of grief that remains unacknowledged and unsupported. Building on Doka's foundational concept of disenfranchised grief, the guiding framework for this pilot project was the Knowledge to Action framework. This study is a quantitative cross-sectional web-based survey, which included a validated questionnaire: the Witnessing Disenfranchised Grief Scale.
View Article and Find Full Text PDFIn recognition of accelerating health care spending and alignment with the American College of Physicians (ACP) principles of promoting high-value care, the ACP Clinical Guidelines Committee (CGC) developed a framework to standardize its approach to identifying, appraising, and considering economic evidence in the development of ACP clinical guidelines. This article presents the CGC's process for incorporating economic evidence, which encompasses cost-effectiveness analyses, economic outcomes in randomized controlled trials, and resource utilization (intervention cost) data. Economic evidence is one component of ACP recommendations.
View Article and Find Full Text PDFStem cells reside in specialized microenvironments, termed niches, at several different locations in tissues. The differential functions of heterogeneous stem cells and niches are important given the increasing clinical applications of stem-cell transplantation and immunotherapy. Whether hierarchical structures among stem cells at distinct niches exist and further control aspects of immune tolerance is unknown.
View Article and Find Full Text PDFBackground And Aims: Ulcerative colitis (UC) can be treated with infliximab (IFX). Therapeutic drug monitoring (TDM) can yield superior outcomes, but its cost-effectiveness is unknown.
Methods: We used a decision analytic Markov model to conduct a cost-effectiveness analysis comparing proactive TDM, reactive TDM, no TDM, and combinations of proactive and reactive TDM in 25-year-old patients with UC started on IFX.