Reproducibility of MRI-based white matter tract estimation using multi-fiber probabilistic tractography: effect of user-defined parameters and regions

Objective

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.

     

Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

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.     

The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.     

Exploring Molecular Contacts of MUC1 at CIN85 Binding Interface to Address Future Drug Design Efforts

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.     

Enriched multi-agent middleware for building rule-based distributed security solutions for IoT environments

The Journal of Supercomputing - The increasing number of connected devices and the complexity of Internet of Things (IoT) ecosystems are demanding new architectures for managing and securing these...     

Femtosecond Ti: Sa ultra short-pulse laser irradiation effects on the properties and morphology of the zirconia surface after ageing

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.     

Microwave hybrid fast sintering of red clay ceramics

This work aimed to examine the performance of the hybrid sintering of clay ceramic in a microwave furnace, compared to the sintering process in a conventional furnace. The raw materials were subjected to X-ray fluorescence, loss on ignition (LOI), X-ray diffraction, particle size distribution, real specific mass, and thermogravimetric analyses. The red clay ceramic mass was prepared, extruded, pre-sintered in a conventional furnace at 600°C/60 min, and sintered at temperatures between 700 °C and 1100 °C. The sintering conventional (resistive oven) was carried out for 60 min with a heating rate of 10°C/min. In the microwave furnace, the sintering times were 5, 10, and 15 min, with a heating rate of 50°C/min, with a sintering chamber coated with silicon carbide (susceptor). The sintered specimens were characterized according to linear shrinkage, water absorption, apparent porosity, apparent specific mass, X-ray diffraction, Raman spectroscopy analysis, spectroscopy analysis in the ultraviolet and visible regions, microhardness, and scanning electron microscopy. The results showed that microwave sintering promoted an increase in the microhardness and apparent specific mass, and reduction in water absorption and apparent porosity values, due to greater densification in the microstructure. The best results occurred for specimens sintered at 1100°C.     

Effect of metallurgical evolution during post-weld aging treatment on localised corrosion of resistance spot welding joints of A286 superalloy

The combined effect of resistance spot welding and precipitation hardening on the localised corrosion of A286 superalloy is studied. The specimens tested by double loop electrochemical potentiokinetic reactivation were welded in the solution treated condition, and then subjected to different precipitation hardening treatments. For both base metal and weld nugget, the maximum localised corrosion is reached when η phase is clearly observable. The fact that the localised corrosion resistance of weld nugget is different from that shown by base metal may be explained by the segregation of Ni and Ti towards the interdendritic region of weld nugget (studied by using scanning electron microscope/energy dispersive X-ray analysis).