Miracle-dz/UniFAR-FTUs huggingface dataset:
Skeletal Biology and Disease Modeling in Zebrafish

Zebrafish are teleosts (bony fish) that share with mammals a common ancestor belonging to the phylum Osteichthyes, from which their endoskeletal systems have been inherited. Indeed, teleosts and mammals have numerous genetically conserved features in terms of skeletal elements, ossification mechanisms, and bone matrix components in common. Yet differences related to bone morphology and function need to be considered when investigating zebrafish in skeletal research. In this review, we focus on zebrafish skeletal architecture with emphasis on the morphology of the vertebral column and associated anatomical structures. We provide an overview of the different ossification types and osseous cells in zebrafish and describe bone matrix composition at the microscopic tissue level with a focus on assessing mineralization. Processes of bone formation also strongly depend on loading in zebrafish, as we elaborate here. Furthermore, we illustrate the high regenerative capacity of zebrafish bones and present some of the technological advantages of using zebrafish as a model. We highlight zebrafish axial and fin skeleton patterning mechanisms, metabolic bone disease such as after immunosuppressive glucocorticoid treatment, as well as osteogenesis imperfecta (OI) and osteopetrosis research in zebrafish. We conclude with a view of why larval zebrafish xenografts are a powerful tool to study bone metastasis. © 2021 American Society for Bone and Mineral Research (ASBMR).
Competitive Microtubule Binding of PEX14 Coordinates Peroxisomal Protein Import and Motility

PEX14 functions as peroxisomal docking protein for the import receptor PEX5. For docking, the conserved N-terminal domain of PEX14 (PEX14-NTD) binds amphipathic alpha-helical ligands, typically comprising one or two aromatic residues, of which human PEX5 possesses eight. Here, we show that the PEX14-NTD also binds to microtubular filaments in vitro with a dissociation constant in nanomolar range. PEX14 interacts with two motifs in the C-terminal region of human ß-tubulin. At least one of the binding motifs is in spatial proximity to the binding site of microtubules (MT) for kinesin. Both PEX14 and kinesin can bind to MT simultaneously. Notably, binding of PEX14 to tubulin can be prevented by its association with PEX5. The data suggest that PEX5 competes peroxisome anchoring to MT by occupying the ß-tubulin-binding site of PEX14. The competitive correlation of matrix protein import and motility may facilitate the homogeneous dispersion of peroxisomes in mammalian cells.
Telemedicine in the management of hypertension: Evolving technological platforms for blood pressure telemonitoring

The prevalence of hypertension is high and still increasing in almost all communities regardless of high, middle, or low income. The control rate remains low in most countries. Telemedicine offers possibilities to improve blood pressure control. The past two decades witnessed the fast evolving telecommunication from telephone transmission to smart mobile phone technology for telemedicine. There is some evidence from randomized controlled trials that telemonitoring improves blood pressure control. However, it requires co‐interventions. The emerging new technology may offer even more possibilities in telemonitoring and co‐interventions, for instance, an interactive platform between patients and health professionals for the management of hypertension. Telemedicine might ultimately change the situation of the unsatisfactory management of hypertension in many communities. It helps fully utilize antihypertensive treatment, the most effective cardiovascular prevention, to achieve the goal of ending atherosclerosis and arteriosclerosis in humans.
Estimation of Kinematics from Inertial Measurement Units Using a Combined Deep Learning and Optimization Framework

The difficulty of estimating joint kinematics remains a critical barrier toward widespread use of inertial measurement units in biomechanics. Traditional sensor-fusion filters are largely reliant on magnetometer readings, which may be disturbed in uncontrolled environments. Careful sensor-to-segment alignment and calibration strategies are also necessary, which may burden users and lead to further error in uncontrolled settings. We introduce a new framework that combines deep learning and top-down optimization to accurately predict lower extremity joint angles directly from inertial data, without relying on magnetometer readings. We trained deep neural networks on a large set of synthetic inertial data derived from a clinical marker-based motion-tracking database of hundreds of subjects. We used data augmentation techniques and an automated calibration approach to reduce error due to variability in sensor placement and limb alignment. On left-out subjects, lower extremity kinematics could be predicted with a mean (± STD) root mean squared error of less than 1.27 ° (± 0.38 °) in flexion/extension, less than 2.52 ° (± 0.98 °) in ad/abduction, and less than 3.34 ° (± 1.02 °) internal/external rotation, across walking and running trials. Errors decreased exponentially with the amount of training data, confirming the need for large datasets when training deep neural networks. While this framework remains to be validated with true inertial measurement unit (IMU) data, the results presented here are a promising advance toward convenient estimation of gait kinematics in natural environments. Progress in this direction could enable large-scale studies and offer an unprecedented view into disease progression, patient recovery, and sports biomechanics.
Désordre linéaire dans les cristaux (cas du silicium, du quartz, et des pérovskites ferroélectriques)

Many crystals produce a diffuse scattering of X-rays which is localized in a series of relplanes. It is shown that the corresponding linear disorder in the crystal may have various origins. In silicon, the scattering is due to thermal vibrations and is well explained by the elastic properties of the crystal. In neutron irradiated quartz the radiation damage is responsible for the major part of the scattering. The case of BaTiO3 and KNbO3 is discussed in detail. A linear disorder is proposed which accounts better for the different distributions of the scattering in the 4 allotropic phases than the alternative explanation of the soft mode. In spite of some neutron inelastic scattering results it is not yet possible to distinguish between static and dynamic disorder.
Salt-induced changes in the growth of polyelectrolyte layers of poly(diallyl-dimethylammonium chloride) and poly(4-styrene sulfonate of sodium)

Multilayers formed by the sodium salt of poly(4-styrene sulfonate), PSS, and poly(diallyldimethylammonium) chloride, PDADMAC, have been built by electrostatic self-assembly from polyelectrolyte aqueous solutions of different ionic strengths. The growth of the multilayers has been followed using dissipative quartz crystal microbalance and ellipsometry. Neutron reflectometry and XPS data indicate that the PSS and PDADMAC layers interpenetrate leading to an almost homogeneous polymer film. The results show that on increasing [NaCl] the growing process changes from a linear to a non-linear regime. The comparison of the thickness values obtained from QCM and ellipsometry has allowed us to calculate the water content of the polymer film. The results agree with those obtained by neutron reflectometry. The analysis of the QCM data has provided values of the complex shear modulus, which are typical of a rubber-like polymer system. The analysis of the mass adsorbed calculated by the ellipsometry measurements indicated that the charge compensation mechanism changes from intrinsic at low ionic strengths to mainly extrinsic at high ionic strengths. Finally, it was found that the response of a polymer film to a change in [NaCl] is rather different for films grown at low or at high ionic strengths.
Diagnosing pulmonary tuberculosis using sequence-specific purification of urine cell-free DNA

Transrenal urine cell-free DNA (cfDNA) is a promising tuberculosis (TB) biomarker, but is challenging to detect because of the short length (<100 bp) and low concentration of TB-specific fragments. We aimed to improve the diagnostic sensitivity of TB urine cfDNA by increasing recovery of short fragments during sample preparation. We developed a highly sensitive sequence-specific purification method that uses hybridization probes immobilized on magnetic beads to capture short TB cfDNA (50 bp) with 91.8% average efficiency. Combined with short-target PCR, the assay limit of detection was [≤]5 copies of cfDNA in 10 mL urine. In a clinical cohort study in South Africa, our urine cfDNA assay had 83.7% sensitivity (95% CI: 71.0-91.5%) and 100% specificity (95% CI: 86.2-100%) for diagnosis of active pulmonary TB when using sputum Xpert MTB/RIF as the reference standard. The detected cfDNA concentration was 0.14-2804 copies/mL (median 14.6 copies/mL) and was inversely correlated with CD4 count and days to culture positivity. Sensitivity was non-significantly higher in HIV-positive (88.2%) compared to HIV-negative patients (73.3%), and was not dependent on CD4 count. Sensitivity remained high in sputum smear-negative (76.0%) and urine LAM-negative (76.5%) patients. With improved sample preparation, urine cfDNA is a viable biomarker for TB diagnosis. Our assay has the highest reported accuracy of any TB urine cfDNA test to date and has the potential to enable rapid non-sputum-based TB diagnosis across key underserved patient populations.
Deagglomeration of cohesive particles by turbulence

Abstract We present a numerical study analysing the breakup of a single cohesive particle aggregate in turbulence. Solid particles with diameters smaller than the Kolmogorov length scale ($d_p<\eta$) are initially aggregated into a spherical ‘clump’ of diameter $D>\eta$ and placed in homogeneous isotropic turbulence. Parameters are chosen relevant to dust or powder suspended in air such that cohesion due to van der Waals is important. Simulations are performed using an Eulerian–Lagrangian framework that models two-way coupling between the fluid and solid phases and resolves particle–particle interactions. Aggregate breakup is investigated for different adhesion numbers ${Ad}$, Taylor microscale Reynolds numbers ${Re}_\lambda$ and non-dimensional clump sizes $D/d_p$. The intermittency of turbulence is found to play a key role on the early stage breakup process, which can be characterized by a turbulent adhesion number ${Ad}_\eta$ that relates the potential energy of the van der Waals force to turbulent shear stresses. A scaling analysis shows that the time rate of breakup for each case collapses when scaled by ${Ad}_\eta$ and an aggregate Reynolds number proportional to $D$. A phenomenological model of the breakup process is proposed that acts as a granular counterpart to the Taylor analogy breakup (TAB) model commonly used for droplet breakup. Such a model is useful for predicting particle breakup in coarse-grained simulation frameworks, such as Reynolds-averaged Navier–Stokes, where relevant spatial and temporal scales are not resolved.
Ubiquity of particle–vortex interactions in turbulent counterflow of superfluid helium

Abstract Thermal counterflow of superfluid $^4$He is investigated experimentally, by employing the particle tracking velocimetry technique. A flat heater, located at the bottom of a vertical channel of square cross-section, is used to generate this unique type of thermally driven flow. Micronic solid particles, made in situ, probe this quantum flow and their time-dependent positions are collected by a digital camera, in a plane perpendicular to the heat source, away from the channel walls. The experiments are performed at relatively large heating powers, resulting in fluid velocities exceeding $10\ \textrm {mm}\,\textrm {s}^{-1}$, to ensure the existence of sufficiently dense tangles of quantized vortices. Within the investigated parameter range, we observe that the particles intermittently switch between two distinct motion regimes, along their trajectories, that is, a single particle can experience both regimes while travelling upward. The regimes can be loosely associated with fast particles, which are moving away from the heat source along almost straight tracks, and to slow particles, whose erratic upward motion can be said to be significantly influenced by quantized vortices. We propose a separation scheme to study the properties of these regimes and of the corresponding transients between them. We find that particles in both regimes display non-classical, broad distributions of velocity, which indicate the relevance of particle–vortex interactions in both cases. At the same time, we observe that the fast particles move along straighter trajectories than the slow ones, suggesting that the strength of particle–vortex interactions in the two regimes is notably different.
Low-calorie sweeteners in the human diet: scientific evidence, recommendations, challenges and future needs. A symposium report from the FENS 2019 conference

Abstract Abstract Overconsumption of free sugars, particularly from sugar-sweetened beverages (SSB), has potential negative health impacts. Implementation of a range of public health strategies is needed to reduce intakes of free sugars, including reducing portion sizes, promoting healthier dietary choices and reformulating foods and beverages. Although low-calorie sweeteners (LCS) are a useful tool for reducing energy intake and control glucose response when consuming sweet foods and drinks, several opinions persist about the adverse health effects of LCS, many of which are based on poor, little or no scientific evidence. This symposium report summarises key messages of the presentations and related discussions delivered at a scientific symposium at the 13th European Nutrition Conference (FENS 2019). These presentations considered the scientific evidence and current recommendations about the use and potential benefits of LCS for human health, with a particular focus on current evidence in relation to body weight and glycaemic control. Many of the studies to date on LCS have focused on low-calorie sweetened beverages (LCSB); however, the psychological and behavioural factors influencing consumer beliefs and consumption of LCSB need to be further explored. Current recommendations for LCS use are described, including the conclusions from a recent expert consensus report identifying the challenges that remain with LCS research. Finally, existing knowledge gaps and future actions are described, as well as two large ongoing research projects: SWITCH and SWEET.
Topical Review

Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this ‘respiratory gating’ is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R–R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R–R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.
Electrical Source Imaging in Freely Moving Rats: Evaluation of a 12-Electrode Cortical Electroencephalography System

This work presents and evaluates a 12-electrode intracranial electroencephalography system developed at the National Institute of Mental Health (Klecany, Czech Republic) in terms of an electrical source imaging (ESI) technique in rats. The electrode system was originally designed for translational research purposes. This study demonstrates that it is also possible to use this well-established system for ESI, and estimates its precision, accuracy, and limitations. Furthermore, this paper sets a methodological basis for future implants. Source localization quality is evaluated using three approaches based on surrogate data, physical phantom measurements, and in vivo experiments. The forward model for source localization is obtained from the FieldTrip-SimBio pipeline using the finite-element method. Rat brain tissue extracted from a magnetic resonance imaging template is approximated by a single-compartment homogeneous tetrahedral head model. Four inverse solvers were tested: standardized low-resolution brain electromagnetic tomography, exact low-resolution brain electromagnetic tomography (eLORETA), linear constrained minimum variance (LCMV), and dynamic imaging of coherent sources. Based on surrogate data, this paper evaluates the accuracy and precision of all solvers within the brain volume using error distance and reliability maps. The mean error distance over the whole brain was found to be the lowest in the eLORETA solution through signal to noise ratios (SNRs) (0.2 mm for 25 dB SNR). The LCMV outperformed eLORETA under higher SNR conditions, and exhibiting higher spatial precision. Both of these inverse solvers provided accurate results in a phantom experiment (1.6 mm mean error distance across shallow and 2.6 mm across subcortical testing dipoles). Utilizing the developed technique in freely moving rats, an auditory steady-state response experiment provided results in line with previously reported findings. The obtained results support the idea of utilizing a 12-electrode system for ESI and using it as a solid basis for the development of future ESI dedicated implants.
Tryptamine Attenuates Experimental Multiple Sclerosis Through Activation of Aryl Hydrocarbon Receptor

Tryptamine is a naturally occurring monoamine alkaloid which has been shown to act as an aryl hydrocarbon receptor (AHR) agonist. It is produced in large quantities from the catabolism of the essential amino acid tryptophan by commensal microorganisms within the gastrointestinal (GI) tract of homeothermic organisms. Previous studies have established microbiota derived AHR ligands as potent regulators of neuroinflammation, further defining the role the gut-brain axis plays in the complex etiology in multiple sclerosis (MS) progression. In the current study, we tested the ability of tryptamine to ameliorate symptoms of experimental autoimmune encephalomyelitis (EAE), a murine model of MS. We found that tryptamine administration attenuated clinical signs of paralysis in EAE mice, decreased the number of infiltrating CD4+ T cells in the CNS, Th17 cells, and RORγ T cells while increasing FoxP3+Tregs. To test if tryptamine acts through AHR, myelin oligodendrocyte glycoprotein (MOG)-sensitized T cells from wild-type or Lck-Cre AHRflox/flox mice that lacked AHR expression in T cells, and cultured with tryptamine, were transferred into wild-type mice to induce passive EAE. It was noted that in these experiments, while cells from wild-type mice treated with tryptamine caused marked decrease in paralysis and attenuated neuroinflammation in passive EAE, similar cells from Lck-Cre AHRflox/flox mice treated with tryptamine, induced significant paralysis symptoms and heightened neuroinflammation. Tryptamine treatment also caused alterations in the gut microbiota and promoted butyrate production. Together, the current study demonstrates for the first time that tryptamine administration attenuates EAE by activating AHR and suppressing neuroinflammation.
Functional Neurological Disorders as Seen by a Cohort of General Practitioners in Northern Italy: Evidence From an Online Survey

General practitioners (GPs) provide primary care and advise their patients on which diagnostic and therapeutic pathways they judge most appropriate. For patients with functional neurological disorders (FND), receiving a proper explanation of diagnosis by their GP from the very beginning may drastically improve prognosis. Novel approaches to the diagnosis and treatment of FND have important implications for effective management. The aim of this study was to investigate Italian GP opinion and knowledge about FND in light of new approaches to the illness. To do this, we evaluated the responses to a 13-item web-based survey completed by 133 GPs practicing in northern Italy. Psychological terms to describe FND were more frequently used than functional neurological disorder and mental illness was considered an important predictor of diagnosis. Referral to a neurologist rather than to a psychiatrist was largely preferred, while physiotherapy consultation was seldom recognized as a valuable approach to treating FND. Overall, the survey findings suggest that knowledge about novel approaches to FND is somewhat lacking. Currently, GPs appear to be transitioning from a classical psychological view of the disorder toward a more modern conceptualization, in which neurobiological, psychological, and social factors all play an important role. Professional education during this transition would be an advantageous way to optimize physician management of FND and to enhance diagnosis, explanation, and management across primary and secondary care pathways.
Multilocus Sequence Typing of Leuconostoc mesenteroides Strains From the Qinghai-Tibet Plateau

Leuconostoc mesenteroides strains were a type of epiphytic bacterium widely used in fermented foods and products in the biochemical and pharmaceutical industries but data on its presence in foods from Qinghai-Tibet Plateau in China was scarce. In this study, molecular analysis based on multilocus sequence typing (MLST) with eight housekeeping genes (pyrG, groeL, rpoB, recA, uvrC, murC, carB, and pheS) was carried out on 45 L. mesenteroides strains isolated from different plants and dairy products from Qinghai-Tibet Plateau in China. The objective of this study was to perform genetic diversity analysis and explore the relationship between strains and isolate samples or separate regions. A total of 25 sequence types (STs) were identified with a diversity of up to 55.6%, which were grouped into one clonal complexes (CCs), 3 doublets and 17 singletons by eBURST. The results of minimum spanning tree and clustering analysis indicated these L. mesenteroides strains from the Qinghai-Tibet Plateau were relatively weakly related to the isolated region. However, there was a close relationship between the genotypes of L. mesenteroides strains and the type of the isolated sample, which was consistent with the results of API 50CH. The MLST scheme presented in this study provides a shareable and comparable sequence database and enhances our knowledge of the population diversity of L. mesenteroides strains which will be further used for the selection of industrial strains.