Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute’s Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.
Part of clinically applicable bone graft substitutes are developed by using mechanical stimulation of flow-perfusion into cell-seeded scaffolds. The role of fluid flow is crucial in driving the nutrient to seeded cells and in stimulating cell colonization. A common numerical approach is to use a multiscale model to link some physical quantities (wall shear stress and inlet flow rate) that act at different scales. In this study, a multiscale model is developed in order to determine the optimal inlet flow rate to cultivate osteoblast-like cells seeded in a controlled macroporous biomaterial inside a perfusion bioreactor system. We focus particularly on the influence of Wall Shear Stress on cell colonization to predict cell colonization at the macroscale. Results obtained at the microscale are interpolated at the macroscale to determine the optimal flow rate. For a macroporous scaffold made of interconnected pores with pore diameters of above 350 μm and interconnection diameters of 150 μm, the model predicts a cell colonization of 325% after a 7-day-cell culture with a constant inlet flow rate of 0.69 mL·min-1. Furthermore, the strength of this protocol is the possibility to adapt it to most porous biomaterials and dynamic cell culture systems.
Growing in the field of construction, 3D printing allows to build non-standard shapes and to optimise the use of resources. The development of printable materials requires good control of the fresh state of the material—between mixing and printing, a printable material has to evolve from fluid matter to be pumpable (extrudability) up to a matter supporting its own weight and those of superior layers (buildability). Our researches are focused on printable materials used in large printers, i.e., printers able to build structural pieces for buildings. As many pumps and printers can be used to achieve a wide range of parts, this paper presents a simple method to provide valuable guidance to users when a decision needs to be made about printable materials. In this context, our researches both try to maximise the use of industrial by-products to reduce the environmental cost of printed material and to propose tests easy to carry out in the field. Consequently, on the one hand, some printable materials that mainly include quarry washing fines have been developed and, on the other hand, Fall cone and Vicat tests have been used to determine the printability limit. By not focusing on a single formula, the novelty of this paper is to present to readers some parametric models, i.e., a methodology that can be used according to their own devices and applications. Based on a design of experiments, 20 formulas have been tested. Parameters that influence the quality of printing are highlighted. Mechanical tests results at hardened state and shrinkage measurements are also shown to demonstrate the ability of some formulas to be structural materials: compressive strengths at 28 days between 7.50 MPa and 18.40 MPa.
This work is based on the production of a bioprobe that is compatible with magnetic resonance imaging (MRI) for laser-induced thermotherapy (LITT) in liver cancer laser therapy. This probe is made of an alumina tube (3-mm diameter) in which an optical fibre is centred and fixed. A shooting window (20mm) is created using a mechanical rectifier. The device is then consolidated by the injection of a transparent and heat-resistant resin. Through numerical modelling, the thermal power damping of the laser source is evaluated as well as the propagation of the heat in the ex vivo liver tissue according to different heating scenarios. These analyses allow for an estimation of the irradiated volume. Ex vivo tests were performed on bovine liver to confirm the adequacy of the bioprobe for LITT and of the irradiated volumes predicted by the numerical model. There was a difference of 8% between the simulations and ex vivo experiments. The pulsed mode heating scenario was the most effective under the experimental conditions.