Danielsen Lundgaard (skirtblock6)

Phen2Gene outperforms existing gene prioritization tools in speed and acts as a real-time phenotype-driven gene prioritization tool to aid the clinical diagnosis of rare undiagnosed diseases. In addition to a command line tool released under the MIT license (https//github.com/WGLab/Phen2Gene), we also developed a web server and web service (https//phen2gene.wglab.org/) for running the tool via web interface or RESTful API queries. Finally, we have curated a large amount of benchmarking data for phenotype-to-gene tools involving 197 patients across 76 scientific articles and 85 patients' de-identified HPO term data from the Children's Hospital of Philadelphia.An unresolved issue in autoimmunity is the lack of surrogate biomarkers of immunological self-tolerance for disease monitoring. Here, we show that peripheral frequency of a regulatory T cell population, characterized by the co-expression of CD3 and CD56 molecules (TR3-56), is reduced in subjects with new-onset type 1 diabetes (T1D). In three independent T1D cohorts, we find that low frequency of circulating TR3-56 cells is associated with reduced β-cell function and with the presence of diabetic ketoacidosis. As autoreactive CD8+ T cells mediate disruption of insulin-producing β-cells1-3, we demonstrate that TR3-56 cells can suppress CD8+ T cell functions in vitro by reducing levels of intracellular reactive oxygen species. The suppressive function, phenotype and transcriptional signature of TR3-56 cells are also altered in T1D children. Together, our findings indicate that TR3-56 cells constitute a regulatory cell population that controls CD8+ effector functions, whose peripheral frequency may represent a traceable biomarker for monitoring immunological self-tolerance in T1D.The emergence of SARS-CoV-2 in China and transmission to more than 80 territories worldwide, including nine countries in Africa, presents a delicate situation for low-resource settings. Countries in Eastern and Central Africa have been on high alert since mid-2018 in anticipation of regional spread of the Ebola virus from the Democratic Republic of Congo. Significant investment has been made to support enhanced surveillance at point of entry and hospitals, infection control practices, clinical case management, and clinical research. With a new threat on the horizon, African countries have an opportunity to leverage the existing capacities for Ebola preparedness to brace for the imminent threat.Purpose The purpose of this report is to quantify how pressure applied to the human cornea, either physiological or intentional, affects its curvature. In particular, how pneumatic procedures flatten the central cornea and keep it flat over time, thereby decreasing the patient's myopia. Methods A viscoelastic model is developed for plastic deformation which gives us the basic governing equations of the elastic and plastic strain of corneal stroma. The model is applied to data from corneas of six patients who underwent pneumatic keratology (NEumatica Keratologia) to reduce their myopia. Results The model shows corneal dimensional stability for long periods of time after NEumatica Keratologia that decay with an exponential time constant. Separate equations are developed that relate corneal plastic strain to the pressure applied and its duration ε = σ 0 t 1/η 1, to change in refraction ε = 2 × ΔRefr, to keratometry radius increase ε = ΔR/R, and to corneal thinning ε = sqr (Δh/h). The average values obtained for ε from the patients' data are 3%, 3.2%, 3%, and 2.6%, respectively, all in remarkable agreement. The average refraction change is found to remain stable at ΔRefr = +1.67D ± 5.2%. Clinical data yield good agreement of theory and treatment results. Conclusions The model proposed is a good description of NEumatica Keratologia outcomes. Practical applications include the long-term stable correction of myopia with refractive procedures. High myopia subjects can benefit from this procedure because NEumatica Kera