| 1. |
- Korenblik, R., et al.
(author)
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Dragon 1 Protocol Manuscript : Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy
- 2022
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In: Cardiovascular and Interventional Radiology. - : Springer. - 0174-1551 .- 1432-086X. ; 45, s. 1391-1398
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Journal article (peer-reviewed)abstract
- Study Purpose The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. Methods The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Results Not applicable. Conclusion DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR.
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| 2. |
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| 3. |
- Coy, R., et al.
(author)
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Combining in silico and in vitro models to inform cell seeding strategies in tissue engineering
- 2020
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In: Journal of the Royal Society Interface. - : The Royal Society Publishing. - 1742-5689 .- 1742-5662. ; 17:164
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Journal article (peer-reviewed)abstract
- The seeding density of therapeutic cells in engineered tissue impacts both cell survival and vascularization. Excessively high seeded cell densities can result in increased death and thus waste of valuable cells, whereas lower seeded cell densities may not provide sufficient support for the tissue in vivo, reducing efficacy. Additionally, the production of growth factors by therapeutic cells in low oxygen environments offers a way of generating growth factor gradients, which are important for vascularization, but hypoxia can also induce unwanted levels of cell death. This is a complex problem that lends itself to a combination of computational modelling and experimentation. Here, we present a spatio-temporal mathematical model parametrized using in vitro data capable of simulating the interactions between a therapeutic cell population, oxygen concentrations and vascular endothelial growth factor (VEGF) concentrations in engineered tissues. Simulations of collagen nerve repair constructs suggest that specific seeded cell densities and non-uniform spatial distributions of seeded cells could enhance cell survival and the generation of VEGF gradients. These predictions can now be tested using targeted experiments.
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| 4. |
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| 5. |
- Brodrick, J. P., et al.
(author)
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Testing nonlocal models of electron thermal conduction for magnetic and inertial confinement fusion applications
- 2017
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In: Physics of Plasmas. - : AIP Publishing. - 1089-7674 .- 1070-664X. ; 24:9
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Journal article (peer-reviewed)abstract
- Three models for nonlocal electron thermal transport are here compared against Vlasov-Fokker-Planck (VFP) codes to assess their accuracy in situations relevant to both inertial fusion hohlraums and tokamak scrape-off layers. The models tested are (i) a moment-based approach using an eigenvector integral closure (EIC) originally developed by Ji, Held, and Sovinec [Phys. Plasmas 16, 022312 (2009)]; (ii) the non-Fourier Landau-fluid (NFLF) model of Dimits, Joseph, and Umansky [Phys. Plasmas 21, 055907 (2014)]; and (iii) Schurtz, Nicolaï, and Busquet's [Phys. Plasmas 7, 4238 (2000)] multigroup diffusion model (SNB). We find that while the EIC and NFLF models accurately predict the damping rate of a small-amplitude temperature perturbation (within 10% at moderate collisionalities), they overestimate the peak heat flow by as much as 35% and do not predict preheat in the more relevant case where there is a large temperature difference. The SNB model, however, agrees better with VFP results for the latter problem if care is taken with the definition of the mean free path. Additionally, we present for the first time a comparison of the SNB model against a VFP code for a hohlraum-relevant problem with inhomogeneous ionisation and show that the model overestimates the heat flow in the helium gas-fill by a factor of ?2 despite predicting the peak heat flux to within 16%.
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| 6. |
- Bojmar, Linda, et al.
(author)
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Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer
- 2024
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In: Nature Medicine. - : NATURE PORTFOLIO. - 1078-8956 .- 1546-170X.
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Journal article (peer-reviewed)abstract
- Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B(+) natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B(+) NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.<br />
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| 7. |
- Thornton, Martin R, et al.
(author)
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Neurotrophins 3 and 4 differentially regulate NCAM, L1 and N-cadherin expression during peripheral nerve regeneration.
- 2008
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In: Biotechnology and applied biochemistry. - 0885-4513 .- 1470-8744. ; 49:Pt 2, s. 165-74
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Journal article (peer-reviewed)abstract
- The addition of NT-3 (neurotrophin 3) or NT-4 to injured nerves improves their regeneration potential and may aid axon guidance. It is not well defined whether NTs (neurotrophins) influence other elements, such as the cell-adhesion molecules, which promote nerve guidance and regeneration. Using poly-3-hydroxybutyrate conduits, we applied either NT-3 or NT-4 to axotomized rat sciatic nerves and monitored nerve regeneration and cell-adhesion molecule expression. Regenerating nerves were stained with antibodies against NCAM (neural cell-adhesion molecule) and N-cadherin 2 weeks after injury and staining intensity was quantified. NCAM, N-cadherin and L1 (L1 cell-adhesion molecule) transcription was measured in the proximal and distal stumps and ipsilateral DRG (dorsal root ganglia) (fourth and fifth DRG) using RT (reverse transcriptase)-PCR. Both NT-3 and NT-4 increased NCAM and L1 transcript levels in the DRG of axotomized nerves. This is reflected in the increased NCAM expression at the proximal stump and regeneration front. Increased levels of NCAM were also observed in the distal stump. NT-4 administration increased N-cadherin levels proximal to the injury, but not distally. Following NT-3 administration, N-cadherin expression decreased in proximal and distal stumps compared with the control. In conclusion, NTs differentially alter adhesion molecule expression in regenerating nerves and transcription in the corresponding DRG, although these changes in expression do not alter NT-enhanced regeneration. Thus we propose that retrograde transport of the NTs to the DRG affects adhesion molecule transcription, reflected by protein expression in peripheral nerve axons.
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