There is a pressing need to assess user-dependent reproducibility of multi-fibre probabilistic tractography in order to encourage clinical implementation of these advanced and relevant approaches. The goal of this study was to evaluate both intrinsic and inter-user reproducibility of corticospinal tract estimation.
Materials and methods
Six clinical datasets including motor functional and diffusion MRI were used. Three users performed an independent tractography analysis following identical instructions. Dice indices were calculated to quantify the reproducibility of seed region, fMRI-based end region, and streamline maps.
Results
The inter-user reproducibility ranged 41–93%, 29–94%, and 50–92%, for seed regions, end regions, and streamline maps, respectively. Differences in streamline maps correlated with differences in seed and end regions. Good inter-user agreement in seed and end regions, yielded inter-user reproducibility close to the intrinsic reproducibility (92–97%) and in most cases higher than 80%.
Discussion
Uncertainties related to user-dependent decisions and the probabilistic nature of the analysis should be considered when interpreting probabilistic tractography data. The standardization of the methods used to define seed and end regions is a necessary step to improve the accuracy and robustness of multi-fiber probabilistic tractography in a clinical setting. Clinical users should choose a feasible compromise between reproducibility and analysis duration.
The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific. 相似文献
The modulation of protein-protein interactions (PPIs) by small molecules represents a valuable strategy for pharmacological intervention in several human diseases. In this context, computer-aided drug discovery techniques offer useful resources to predict the network of interactions governing the recognition process between protein partners, thus furnishing relevant information for the design of novel PPI modulators. In this work, we focused our attention on the MUC1-CIN85 complex as a crucial PPI controlling cancer progression and metastasis. MUC1 is a transmembrane glycoprotein whose extracellular domain contains a variable number of tandem repeats (VNTRs) regions that are highly glycosylated in normal cells and under-glycosylated in cancer. The hypo-glycosylation fosters the exposure of the backbone to new interactions with other proteins, such as CIN85, that alter the intracellular signalling in tumour cells. Herein, different computational approaches were combined to investigate the molecular recognition pattern of MUC1-CIN85 PPI thus unveiling new structural information useful for the design of MUC1-CIN85 PPI inhibitors as potential anti-metastatic agents. 相似文献
Femtosecond pulses from a Ti:Sapphire laser were used to irradiate specimens of yttria-stabilised (35% mol) tetragonal zirconia (Y-TZP) with the purpose of studying the effects of the irradiations on their surface properties and morphology after ageing. Zirconia disks were divided into eight groups (n = 32) according to their surface treatment and subsequent ageing: Control: no treatment; sandblasting: Al2O3 sandblasting 50 μm; and ultrashort laser pulses irradiation with 25 μJ pulses, considering two different scanning steps based on the width between two grooves. These groups were duplicated and submitted to ageing. The surfaces were analysed using scanning electron microscopy (SEM), and X-ray diffraction. A finite element analysis, a biaxial flexure test, as well as fractographic and Weibull analyses, were performed. The strengths of the disks were statistically different for the treatment factor, and the principal stresses seemed to be concentrated at the centre of the specimens, as predicted by the computer simulations. Ageing decreased the strengths for all groups and increased the Weibull modulus for the laser group with the 40 μm-width between two grooves. The sandblasting group presented the highest monoclinic phase peak. Although the most significant strength was found within the sandblasting group, the phase transformation was favourable to the laser groups. The Weibull modulus was higher for the laser group with the 60 μm-width between two grooves, confirming the highest homogeneity of its failure distribution. Regardless of the surface treatment, strength was decreased with ageing in all groups. The femtosecond Ti:Sa ultra-short pulse laser irradiation can be suggested as an alternative to the gold standard sandblasting in long-term Y-TZP zirconia rehabilitations, such as crowns and veneers. 相似文献