A modular computational framework for medical digital twins.

This paper presents a modular software design for the construction of computational modeling technology that will help implement precision medicine. In analogy to a common industrial strategy used for preventive maintenance of engineered products, medical digital twins are computational models of disease processes calibrated to individual patients using multiple heterogeneous data streams. They have the potential to help improve diagnosis, prognosis, and personalized treatment for a wide range of medical conditions. Their large-scale development relies on both mechanistic and data-driven techniques and requires the integration and ongoing update of multiple component models developed across many different laboratories. Distributed model building and integration requires an open-source modular software platform for the integration and simulation of models that is scalable and supports a decentralized, community-based model building process. This paper presents such a platform, including a case study in an animal model of a respiratory fungal infection.

Activation of innate immunity accelerates sialoadenitis in a mouse model for Sjögren's syndrome-like disease.

OBJECTIVE: Sjögren's syndrome is a chronic autoimmune disorder characterized by progressive lymphocytic infiltration within the salivary and lacrimal glands. This study was undertaken to investigate the effects of innate immunity activation on sialoadenitis in a mouse strain genetically susceptible for development of SS-like disease. METHODS: Female New Zealand Black X New Zealand White F1 mice were repeatedly treated with toll-like 3 receptor agonist poly(I:C). Submandibular glands were investigated at different time points for sialoadenitis by immunohistochemistry and for gene expression of different chemokines by quantitative PCR. Submandibular gland-infiltrating cells were characterized by flow cytometry. RESULTS: Poly(I:C) treatment significantly upregulated the expression of multiple chemokines within the submandibular glands. The severity and incidence of sialoadenitis was considerably higher in poly(I:C)-treated mice. There was a preponderance of dendritic cells and NK cells in the initial inflammatory cell infiltrates, and these were followed by CD4+ T cells. CONCLUSIONS: Our data clearly demonstrate that systemic activation of innate immunity accelerates sialoadenitis in a mouse model for SS-like disease. These findings suggest that chronic activation of innate immunity can influence certain features of SS.

Selective preconcentration and determination of chromium(VI) using a flat sheet polymer inclusion sorbent: potential application for Cr(VI) determination in real samples.

A method for sorption preconcentration of Cr(VI) from aqueous samples was developed using a polymer inclusion sorbent (PIS). The PIS used in this method was prepared by physical inclusion of Aliquat-336 in the matrix formed by cellulose triacetate and 2-nitrophenyl octyl ether. This sorbent was found to be stable, cost-effective, efficient for preconcentration of Cr(VI) present in the aqueous samples, and amenable to direct quantitative analysis of Cr(VI) held in it by neutron activation analysis and spectrophotometry. The quantifying of Cr(VI) in PIS by spectrophotometry was carried out by developing color directly on the PIS after reacting it with 1,5-diphenylcarbazide. The distinct color developed on the PIS even at very low concentrations of Cr(VI) suggests its possible use for field determination of Cr(VI). The composition of PIS was optimized to obtain maximum uptake of Cr(VI) without sacrificing uniformity in terms of thickness and distribution of ion-exchange sites, stability, and time required for quantitative sorption of Cr(VI) from aqueous samples. The Cr(VI) species held in the PIS, mainly HCrO4- and CrO4(2-), were found to vary as a function of pH of the aqueous samples from which Cr(VI) was preconcentrated. A close agreement was found in the abundances of Cr(VI) species held in the PIS with those reported in the literature for aqueous solutions at different pH. The variation of Cr(VI) species as a function of pH was found to have a significant impact on the tolerance to anions on the uptake of Cr(VI) in the PIS. The high selectivity of PIS toward Cr(VI) from aqueous solution at pH = 2 was explained on the basis of hydration of anions. The uptake of Cr(VI) was found to be fairly constant (88 +/- 3%) up to nearly complete exchange of counterions present in the PIS. The method developed in the present work was successfully used for the preconcentration of Cr(VI) from tap water and seawater samples containing low levels of Cr(VI).