Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model

The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma.
Current management of severe dengue infection

ABSTRACT Introduction: Traditionally a disease mainly affecting the pediatric population, dengue burden has increased significantly in recent decades and adults with severe disease may become more common. There is currently no effective anti-viral agent available for the treatment of dengue and supportive care is the mainstay of management. Areas covered: We present a review of current literature on dengue severity classification systems and the management of severe dengue in adults. In particular, emphasis was placed on organ impairment in dengue and management of elderly individuals with multiple medical problems. Expert commentary: There is an urgent need to search for an effective anti-viral agent to treat infected individuals. The commercial availability of a dengue vaccine in older children has provided optimism in reducing the disease burden but long term efficacy and safety are unknown. The results from phase III trials of two new candidate vaccines are eagerly awaited.
Image-Based Localization Aided Indoor Pedestrian Trajectory Estimation Using Smartphones

Accurately determining pedestrian location in indoor environments using consumer smartphones is a significant step in the development of ubiquitous localization services. Many different map-matching methods have been combined with pedestrian dead reckoning (PDR) to achieve low-cost and bias-free pedestrian tracking. However, this works only in areas with dense map constraints and the error accumulates in open areas. In order to achieve reliable localization without map constraints, an improved image-based localization aided pedestrian trajectory estimation method is proposed in this paper. The image-based localization recovers the pose of the camera from the 2D-3D correspondences between the 2D image positions and the 3D points of the scene model, previously reconstructed by a structure-from-motion (SfM) pipeline. This enables us to determine the initial location and eliminate the accumulative error of PDR when an image is successfully registered. However, the image is not always registered since the traditional 2D-to-3D matching rejects more and more correct matches when the scene becomes large. We thus adopt a robust image registration strategy that recovers initially unregistered images by integrating 3D-to-2D search. In the process, the visibility and co-visibility information is adopted to improve the efficiency when searching for the correspondences from both sides. The performance of the proposed method was evaluated through several experiments and the results demonstrate that it can offer highly acceptable pedestrian localization results in long-term tracking, with an error of only 0.56 m, without the need for dedicated infrastructures.
Gluteal muscle damage leads to higher in vivo hip joint loads 3 months after total hip arthroplasty

Background Total hip arthroplasty (THA) is in most cases improving patients´ life quality immediately after surgery. However, a closer look at these patients, especially with modern gait analysis methods, reveals also negative consequences due to the surgical approach related injury to the pelvic muscles. We hypothesized that this damage will have a negative impact on hip joint contact forces during activities of daily living (ADL). Methods 10 patients undergoing THA received an instrumented hip joint implant enabling real time in vivo measurements of hip joint loads using a direct lateral approach. Pre- and 3 months postoperative computed tomography (CT) scans were used for evaluation of the periarticular muscle status, using muscle volume, fat ratio and lean muscle volume as parameters. An analysis of in vivo hip contact forces was made 3 months after THA during ADL (walking, stair climbing, chair rising and sitting) and correlated with the morphology of the periarticular muscles. Results We found a significant decrease of volume by 25% (-3 to -45, p = 0.005) and increase in fat ratio of the Gluteus Minimus (Gmin), resulting in a decrease in lean muscle volume of 28% (-48 to 0, p = 0.008). This was accompanied by an inverse development in the Tensor Fasciae Latae (TFL) resulting in a lean muscle volume increase of 34% (-2 to -102, p = 0.013). Changes in Gluteus Medius (Gmed) and Gluteus Maximus (Gmax) have not been observed in the short-term follow up. A decreased Gmin lean muscle volume was found to strongly correlate with high in vivo joint contact forces in all tested ADL. Conclusion The decrease of Gmin volume can be seen as a direct effect of THA surgery, whereas the increase of TFL might compensate for loss of Gmin volume. Lean muscle volume and fat ratio were better predictors for joint contact forces than total muscle volume. These effects were most pronounced during sitting down and standing up due to the higher demand on the gluteal muscles during these activities.
Cerebral hyperperfusion on arterial spin labeling MRI after reperfusion therapy is related to hemorrhagic transformation

Early detection of hemorrhagic transformation after reperfusion therapy is crucial in acute stroke treatment. Here, we evaluated the relationship between hemorrhagic transformation and post-reperfusion hyperperfusion using pulsed arterial spin labeling (ASL) perfusion MRI and 123I-iodoamphetamine single-photon emission-computed tomography. Patients who developed hemorrhagic transformation showed significantly higher cerebral blood flow in the affected lesion after thrombolysis and/or endovascular intervention. Focal hyperperfusion (ipsilateral to contralateral ratio >1.5) was associated with hemorrhagic transformation after reperfusion (odds ratio, 9.3; 95% confidence interval, 1.4–64.0). Our findings suggest that post-reperfusion hyperperfusion on ASL could represent a reliable marker of hemorrhagic transformation.
3-2008 Spatial Wage Disparities : Sorting Matters !

Spatial wage disparities can result from spatial differences in the skill composition of the workforce, in nonhuman endowments, and in local interactions. To distinguish between these explanations, we estimate a model of wage determination across local labour markets using a very large panel of French workers. We control for worker characteristics, worker fixed effects, industry fixed effects, and the characteristics of the local labour market. Our findings suggest that individual skills account for a large fraction of existing spatial wage disparities with strong evidence of spatial sorting by skills. Interaction effects are mostly driven by the local density of employment. Not controlling for worker heterogeneity leads to very biased estimates of interaction effects. Endowments only appear to play a small role.
Preparation and properties of calcium-silicate filled resins for dental restoration. Part II: Micro-mechanical behaviour to primed mineral-depleted dentine

Abstract Objective. Evaluating microtensile bond strength (μTBS) and Knoop micro-hardness (KHN) of resin bonded-dentine interfaces created with two methacrylate-based systems either incorporating Bioglass® 45S5 (3-E&RA/BG) or MTA (3-E&RA/WMTA). Materials and methods. Solvated resins (50% ethanol/50% co-monomers) were used as primers while their neat counterparts were filled with the two calcium-silicate compounds. Application of neat resin adhesive with no filler served as control (3-E&RA). μTBS, KHN analysis and confocal tandem scanning microscopy (TSM) micropermeability were carried out after 24 h and 10 months of storage in phosphate buffer solution (DPBS). Scanning electron microscopy (SEM) was also performed after debonding. Results. High μTBS values were achieved in all groups after 24 h of DPBS storage. On the contrary, solely the specimens created using 3-E&RA/BG and 3-E&RA/WMTA agents showed no significant reduction in terms of μTBS even after 10 months in DPBS; similarly, they did not restore the average superficial micro-hardness to the level of sound dentine, but maintained unchanged KHN values, and no statistical decrease was found following 10 months of DPBS storage. The only statistically significant changes occurred in the resin–dentine interfaces bonded with 3-E&RA that were subjected to a reduction of both μTBS and KHN values with ageing. In terms of micropermeability, adverse results were obtained with 3-E&RA while 3-E&RA/BG and 3-E&RA/WMTA demonstrated a beneficial effect after prolonged DPBS storage. Conclusion. Calcium-silicate filled composite resins performed better than a current etch-and-rinse adhesive and had a therapeutic/protective effect on the micro-mechanical properties of mineral-depleted resin–dentine interfaces. Clinical significance. The incorporation of calcium-silicates into dental restorative and bonding agents can create more biomimetic (life-like) restorations. This will not only enable these materials to mimic the physical characteristics of the tooth structure, but will also stabilize and protect the remaining dental hard tissues.
A Framework for Pedagogical Feedback in the Motor Skill Domain

With increasingly rapid development in Computer-based Sport Training (CBST), feedback plays an important role in both coaching and learning. A good CBST system includes not only good training strategies but also effective feedback design. Feedback in the motor skill domain via CBST may be synthetically designed to allow athletes to practise in a more effective way, and enhance their skill acquisition. Existing designs lack pedagogical elements. To bridge the gap, we propose a framework for the design of pedagogically-informed feedback based on learning transactions, competence, cybernetics, and behaviourism.
Spectrum of cystic fibrosis mutations in Syrian patients.

BACKGROUND Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. However, it is considered to be rare in Arabs. Reports of the cystic fibrosis transmembrane regulator (CFTR) mutations from Syrians are limited. The main aim of this study was to identify the frequency of CFTR mutations in 25 CF patients. To the best of our knowledge, this is the first comprehensive report about CF in Syrian patients. METHODS The main clinical presentations were respiratory system symptoms (recurrent pneumonia and chronic cough) in 16 (64%) patients, failure to thrive in 15 (60%), GI system symptoms (diarrhea, steatorrhea) in 15 (60%) and nasal polyps in 1 (4%). RESULTS A total of 36 known mutations in the CFTR gene were screened among 25 CF Syrian patients. However, 13 different CFTR mutations were identified. These mutations in order of frequency were: ΔF508 (18%), W1282X (12%), I148T (6%), CFTRdel 2.3 (6%), 2182AA→G (6%), G542X (6%), N1303K (6%), G551D (4%), G85E (4%), R117H (4%), G85E (4%), R347P (2%), M.2183AA>G (2%) and 3199del6 (2%). However, 22% of the total mutations could not be detected in this study. Moreover, 142 healthy Syrian individuals were tested for ΔF508 and G551D mutations in an attempt to determine the carrier rate in the Syrian population. These two mutations were not detected in this cohort of healthy Syrians. CONCLUSIONS These results provide important tools for adapting a molecular diagnostic test and prenatal diagnosis for the Syrian population.
A global sensitivity analysis for African sleeping sickness

SUMMARY African sleeping sickness is a parasitic disease transmitted through the bites of tsetse flies of the genus Glossina. We constructed mechanistic models for the basic reproduction number, R0, of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively the causative agents of West and East African human sleeping sickness. We present global sensitivity analyses of these models that rank the importance of the biological parameters that may explain variation in R0, using parameter ranges based on literature, field data and expertize out of Uganda. For West African sleeping sickness, our results indicate that the proportion of bloodmeals taken from humans by Glossina fuscipes fuscipes is the most important factor, suggesting that differences in the exposure of humans to tsetse are fundamental to the distribution of T. b. gambiense. The second ranked parameter for T. b. gambiense and the highest ranked for T. b. rhodesiense was the proportion of Glossina refractory to infection. This finding underlines the possible implications of recent work showing that nutritionally stressed tsetse are more susceptible to trypanosome infection, and provides broad support for control strategies in development that are aimed at increasing refractoriness in tsetse flies. We note though that for T. b. rhodesiense the population parameters for tsetse – species composition, survival and abundance – were ranked almost as highly as the proportion refractory, and that the model assumed regular treatment of livestock with trypanocides as an established practice in the areas of Uganda experiencing East African sleeping sickness.
A fast and energy efficient FPGA-based system for real-time object tracking

Visual object tracking has achieved great advances in the past decades and has been widely applied in vision-based applications. Due to the popularization of the power-sensitive mobile platform, robust and low power real-time tracking solution is strongly required. An energy efficient real-time object tracking system on both static and moving camera is proposed in this paper. The system reduces the computational cost and explores data reuse by optimizing the tracking algorithm, the data flow, and the parallelism strategies. The architecture is implemented on a Xilinx ZC706 FPGA, and the experimental data shows that the system obtains 41 frame/s throughput for the 640×480 video and achieves higher energy efficiency comparing to other similar works.
Canalization Leads to Similar Whole Bone Mechanical Function at Maturity in Two Inbred Strains of Mice

Previously, we showed that cortical mineralization is coordinately adjusted to mechanically offset external bone size differences between A/J (narrow) and C57BL/6J (wide) mouse femora to achieve whole bone strength equivalence at adulthood. The identity of the genes and their interactions that are responsible for establishing this homeostatic state (ie, canalization) remain unknown. We hypothesize that these inbred strains, whose interindividual differences in bone structure and material properties mimic that observed among humans, achieve functional homeostasis by differentially adjusting key molecular pathways regulating external bone size and mineralization throughout growth. The cortices of A/J and C57BL/6J male mouse femora were phenotyped and gene expression levels were assessed across growth (ie, ages 2, 4, 6, 8, 12, 16 weeks). A difference in total cross‐sectional area (p < 0.01) and cortical tissue mineral density were apparent between mouse strains by age 2 weeks and maintained at adulthood (p < 0.01). These phenotypic dissimilarities corresponded to gene expression level differences among key regulatory pathways throughout growth. A/J mice had a 1.55‐ to 7.65‐fold greater expression among genes inhibitory to Wnt pathway induction, whereas genes involved in cortical mineralization were largely upregulated 1.50‐ to 3.77‐fold to compensate for their narrow diaphysis. Additionally, both mouse strains showed an upregulation among Wnt pathway antagonists corresponding to the onset of adult ambulation (ie, increased physiological loads). This contrasts with other studies showing an increase in Wnt pathway activation after functionally isolated, experimental in vivo loading regimens. A/J and C57BL/6J long bones provide a model to develop a systems‐based approach to identify individual genes and the gene‐gene interactions that contribute to trait differences between the strains while being involved in the process by which these traits are coordinately adjusted to establish similar levels of mechanical function, thus providing insight into the process of canalization. © 2017 American Society for Bone and Mineral Research.
Reoxidation during ladle treatment

Abstract Cleanliness of steel is mainly determined by the presence of oxide inclusions. The reoxidation of liquid steel before, during and after ladle treatment at the Sidmar steel plant was quantified for three steel grades, as it is a potential source of inclusions. A mass balance calculation was performed to compare the expected and measured steel composition. The total reoxidation was calculated from the reactions of the dissolved elements. A dissimilarity in behaviour of the steel grades was found. The resultant compositions of the slags were calculated and compared with measured compositions. Some differences between computed slag compositions and average measured values are explained. Finally, the relation between the reoxidation and internal cleanliness at the end of ladle treatment was examined.
Using satellite data to improve the leaf phenology of a global terrestrial biosphere model

Abstract. Correct representation of seasonal leaf dynamics is crucial for terrestrial biosphere models (TBMs), but many such models cannot accurately reproduce observations of leaf onset and senescence. Here we optimised the phenology-related parameters of the ORCHIDEE TBM using satellite-derived Normalized Difference Vegetation Index data (MODIS NDVI v5) that are linearly related to the model fAPAR. We found the misfit between the observations and the model decreased after optimisation for all boreal and temperate deciduous plant functional types, primarily due to an earlier onset of leaf senescence. The model bias was only partially reduced for tropical deciduous trees and no improvement was seen for natural C4 grasses. Spatial validation demonstrated the generality of the posterior parameters for use in global simulations, with an increase in global median correlation of 0.56 to 0.67. The simulated global mean annual gross primary productivity (GPP) decreased by ~ 10 PgC yr−1 over the 1990–2010 period due to the substantially shortened growing season length (GSL – by up to 30 days in the Northern Hemisphere), thus reducing the positive bias and improving the seasonal dynamics of ORCHIDEE compared to independent data-based estimates. Finally, the optimisations led to changes in the strength and location of the trends in the simulated vegetation productivity as represented by the GSL and mean annual fraction of absorbed photosynthetically active radiation (fAPAR), suggesting care should be taken when using un-calibrated models in attribution studies. We suggest that the framework presented here can be applied for improving the phenology of all global TBMs.
Structural abnormalities in the primary somatosensory cortex and a normal behavioral profile in Contactin-5 deficient mice

ABSTRACT Contactin-5 (Cntn5) is an immunoglobulin cell adhesion molecule that is exclusively expressed in the central nervous system. In view of its association with neurodevelopmental disorders, particularly autism spectrum disorder (ASD), this study focused on Cntn5-positive areas in the forebrain and aimed to explore the morphological and behavioral phenotypes of the Cntn5 null mutant (Cntn5−/−) mouse in relation to these areas and ASD symptomatology. A newly generated antibody enabled us to elaborately describe the spatial expression pattern of Cntn5 in P7 wild type (Cntn5+/+) mice. The Cntn5 expression pattern included strong expression in the cerebral cortex, hippocampus and mammillary bodies in addition to described previously brain nuclei of the auditory pathway and the dorsal thalamus. Thinning of the primary somatosensory (S1) cortex was found in Cntn5−/− mice and ascribed to a misplacement of Cntn5-ablated cells. This phenotype was accompanied by a reduction in the barrel/septa ratio of the S1 barrel field. The structure and morphology of the hippocampus was intact in Cntn5−/− mice. A set of behavioral experiments including social, exploratory and repetitive behaviors showed that these were unaffected in Cntn5−/− mice. Taken together, these data demonstrate a selective role of Cntn5 in development of the cerebral cortex without overt behavioral phenotypes.
In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial

In animal models, the incretin hormone GLP-1 affects Alzheimer’s disease (AD). We hypothesized that treatment with GLP-1 or an analog of GLP-1 would prevent accumulation of Aβ and raise, or prevent decline of, glucose metabolism (CMRglc) in AD. In this 26-week trial, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [11C]PIB (PIB), CMRglc with [18F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe in placebo and treatment patients (both P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMRglc declined in all regions, significantly so by the following means in precuneus (P = 0.009, 3.2 μmol/hg/min, 95% CI: 5.45; 0.92), and in parietal (P = 0.04, 2.1 μmol/hg/min, 95% CI: 4.21; 0.081), temporal (P = 0.046, 1.54 μmol/hg/min, 95% CI: 3.05; 0.030), and occipital (P = 0.009, 2.10 μmol/hg/min, 95% CI: 3.61; 0.59) lobes, and in cerebellum (P = 0.04, 1.54 μmol/hg/min, 95% CI: 3.01; 0.064). In contrast, the GLP-1 analog treatment caused a numerical but insignificant increase of CMRglc after 6 months. Cognitive scores did not change. We conclude that the GLP-1 analog treatment prevented the decline of CMRglc that signifies cognitive impairment, synaptic dysfunction, and disease evolution. We draw no firm conclusions from the Aβ load or cognition measures, for which the study was underpowered.