Miracle-dz/UniFAR-FTUs huggingface dataset:
Machine phenotyping of cluster headache and its response to verapamil

Abstract Cluster headache is characterized by recurrent, unilateral attacks of excruciating pain associated with ipsilateral cranial autonomic symptoms. Although a wide array of clinical, anatomical, physiological, and genetic data have informed multiple theories about the underlying pathophysiology, the lack of a comprehensive mechanistic understanding has inhibited, on the one hand, the development of new treatments and, on the other, the identification of features predictive of response to established ones. The first-line drug, verapamil, is found to be effective in only half of all patients, and after several weeks of dose escalation, rendering therapeutic selection both uncertain and slow. Here we use high-dimensional modelling of routinely acquired phenotypic and MRI data to quantify the predictability of verapamil responsiveness and to illuminate its neural dependants, across a cohort of 708 patients evaluated for cluster headache at the National Hospital for Neurology and Neurosurgery between 2007 and 2017. We derive a succinct latent representation of cluster headache from non-linear dimensionality reduction of structured clinical features, revealing novel phenotypic clusters. In a subset of patients, we show that individually predictive models based on gradient boosting machines can predict verapamil responsiveness from clinical (410 patients) and imaging (194 patients) features. Models combining clinical and imaging data establish the first benchmark for predicting verapamil responsiveness, with an area under the receiver operating characteristic curve of 0.689 on cross-validation (95% confidence interval: 0.651 to 0.710) and 0.621 on held-out data. In the imaged patients, voxel-based morphometry revealed a grey matter cluster in lobule VI of the cerebellum (−4, −66, −20) exhibiting enhanced grey matter concentrations in verapamil non-responders compared with responders (familywise error-corrected P = 0.008, 29 voxels). We propose a mechanism for the therapeutic effect of verapamil that draws on the neuroanatomy and neurochemistry of the identified region. Our results reveal previously unrecognized high-dimensional structure within the phenotypic landscape of cluster headache that enables prediction of treatment response with modest fidelity. An analogous approach applied to larger, globally representative datasets could facilitate data-driven redefinition of diagnostic criteria and stronger, more generalizable predictive models of treatment responsiveness.
Comparison of human poly-N-acetyl-lactosamine synthase structure with GT-A fold glycosyltransferases supports a modular assembly of catalytic subsites

Poly-N-acetyl-lactosamine (poly-LacNAc) structures are composed of repeating [-Galβ(1,4)-GlcNAcβ(1,3)-]n glycan extensions. They are found on both N- and O-glycoproteins and glycolipids and play an important role in development, immune function, and human disease. The majority of mammalian poly-LacNAc is synthesized by the alternating iterative action of β1,3-N-acetylglucosaminyltransferase 2 (B3GNT2) and β1,4-galactosyltransferases. B3GNT2 is in the largest mammalian glycosyltransferase family, GT31, but little is known about the structure, substrate recognition, or catalysis by family members. Here we report the structures of human B3GNT2 in complex with UDP:Mg2+ and in complex with both UDP:Mg2+ and a glycan acceptor, lacto-N-neotetraose. The B3GNT2 structure conserves the GT-A fold and the DxD motif that coordinates a Mg2+ ion for binding the UDP-GlcNAc sugar donor. The acceptor complex shows interactions with only the terminal Galβ(1,4)-GlcNAcβ(1,3)- disaccharide unit, which likely explains the specificity for both N- and O-glycan acceptors. Modeling of the UDP-GlcNAc donor supports a direct displacement inverting catalytic mechanism. Comparative structural analysis indicates that nucleotide sugar donors for GT-A fold glycosyltransferases bind in similar positions and conformations without conserving interacting residues, even for enzymes that use the same donor substrate. In contrast, the B3GNT2 acceptor binding site is consistent with prior models suggesting that the evolution of acceptor specificity involves loops inserted into the stable GT-A fold. These observations support the hypothesis that GT-A fold glycosyltransferases employ coevolving donor, acceptor, and catalytic subsite modules as templates to achieve the complex diversity of glycan linkages in biological systems.
Fusobacterium nucleatum adheres to Clostridioides difficile via the RadD adhesin to enhance biofilm formation in intestinal mucus.

BACKGROUND Although Clostridioides difficile infection (CDI) is known to involve the disruption of the gut microbiota, little is understood regarding how mucus-associated microbes interact with C. difficile. We hypothesized that select mucus-associated bacteria would promote C. difficile colonization and biofilm formation. METHODS/RESULTS To create a model of the human intestinal mucus layer and gut microbiota, we used bioreactors inoculated with healthy human feces, treated with clindamycin and infected with C. difficile with the addition of human MUC2-coated coverslips. C. difficile was found to colonize and form biofilms on MUC2-coated coverslips and 16S rRNA sequencing revealed a unique biofilm profile with substantial co-colonization with Fusobacterium. Consistent with our bioreactor data, publicly available datasets and patient stool samples revealed that a subset of patients with C. difficile infection harbored high levels of Fusobacterium. We observed co-localization of C. difficile and F. nucleatum in an aggregation assay using adult patients and pediatric IBD patient stool and in CDI patient tissue sections. C. difficile strains were found to co-aggregate with F. nucleatum subspecies in vitro; an effect that was inhibited by blocking or mutating the adhesin RadD on Fusobacterium and removal of flagella on C. difficile. Aggregation was shown to be unique between F. nucleatum and C. difficile, as other gut commensals did not aggregate with C. difficile. Addition of F. nucleatum also enhanced C. difficile biofilm formation and extracellular polysaccharide production. CONCLUSIONS Collectively, these data demonstrate a unique interaction of between pathogenic C. difficile and F. nucleatum in the intestinal mucus layer.
Regional variation in the reliability of sweat rate measured via the ventilated capsule technique during passive heating

The ventilated capsule technique is widely used to measure time‐dependent changes in sweating in humans. However, evaluations of its reliability (consistency) have been restricted to the forearm, despite extensive regional heterogeneity in the sweating response. Given the importance of such information for experimental design, statistical analysis and interpretation, we determined the reliability of local sweat rate at nine sites during whole‐body passive (resting) heating. On three separate occasions, a water‐perfused suit was used to increase and clamp oesophageal temperature 0.6, 1.2 and 1.8°C above baseline in 14 young men [24 (SD 5) years of age], while sweat rate was measured at the forehead, chest, abdomen, biceps, forearm, hand, quadriceps, calf and foot using ventilated capsules (3.8 cm2). Absolute and relative reliability were determined via the coefficient of variation (CV) and intraclass correlation coefficient (ICC), respectively. At low heat strain (0.6°C), almost all sites had acceptable relative reliability (ICC ≥ 0.70) and moderate absolute reliability (CV < 25%). At moderate heat strain (1.2°C), only the abdomen, hand, quadriceps and foot had acceptable relative reliability, whereas the forehead, abdomen, forearm, hand and quadriceps had moderate absolute reliability. At high heat strain (1.8°C), relative reliability was acceptable at the abdomen, quadriceps, calf and foot, whereas the chest, abdomen, forearm, hand, quadriceps, calf and foot had moderate absolute reliability. Our findings indicate that the measurement site and level of heat strain impact the consistency of local sweat rate measured via the ventilated capsule technique, and we demonstrate the possible implications for research design and data interpretation.
Molecular Insights into the Multifunctional Role of Natural Compounds: Autophagy Modulation and Cancer Prevention

Autophagy is a vacuolar, lysosomal degradation pathway for injured and damaged protein molecules and organelles in eukaryotic cells, which is controlled by nutrients and stress responses. Dysregulation of cellular autophagy may lead to various diseases such as neurodegenerative disease, obesity, cardiovascular disease, diabetes, and malignancies. Recently, natural compounds have come to attention for being able to modulate the autophagy pathway in cancer prevention, although the prospective role of autophagy in cancer treatment is very complex and not yet clearly elucidated. Numerous synthetic chemicals have been identified that modulate autophagy and are favorable candidates for cancer treatment, but they have adverse side effects. Therefore, different phytochemicals, which include natural compounds and their derivatives, have attracted significant attention for use as autophagy modulators in cancer treatment with minimal side effects. In the current review, we discuss the promising role of natural compounds in modulating the autophagy pathway to control and prevent cancer, and provide possible therapeutic options.
Predicting Human Intention-Behavior Through EEG Signal Analysis Using Multi-Scale CNN

At present, the application of Electroencephalogram (EEG) signal classification to human intention-behavior prediction has become a hot topic in the brain computer interface (BCI) research field. In recent studies, the introduction of convolutional neural networks (CNN) has contributed to substantial improvements in the EEG signal classification performance. However, there is still a key challenge with the existing CNN-based EEG signal classification methods, the accuracy of them is not very satisfying. This is because most of the existing methods only utilize the feature maps in the last layer of CNN for EEG signal classification, which might miss some local and detailed information for accurate classification. To address this challenge, this paper proposes a multi-scale CNN model-based EEG signal classification method. In this method, first, the EEG signals are preprocessed and converted to time-frequency images using the short-time Fourier Transform (STFT) technique. Then, a multi-scale CNN model is designed for EEG signal classification, which takes the converted time-frequency image as the input. Especially, in the designed multi-scale CNN model, both the local and global information is taken into consideration. The performance of the proposed method is verified on the benchmark data set 2b used in the BCI contest IV. The experimental results show that the average accuracy of the proposed method is 73.9 percent, which improves the classification accuracy of 10.4, 5.5, 16.2 percent compared with the traditional methods including artificial neural network, support vector machine, and stacked auto-encoder.
Gene‐specific facial dysmorphism in Axenfeld‐Rieger syndrome caused by FOXC1 and PITX2 variants

Axenfeld‐Rieger syndrome is a genetic condition characterized by ocular and systemic features and is most commonly caused by variants in the FOXC1 or PITX2 genes. Facial dysmorphism is part of the syndrome but the differences between both genes have never been systematically assessed. Here, 11 facial traits commonly reported in Axenfeld‐Rieger syndrome were assessed by five clinical geneticists blinded to the molecular diagnosis. Individuals were drawn from the Australian and New Zealand Registry of Advanced Glaucoma in Australia or recruited through the Genetic and Ophthalmology Unit of l'Azienda Socio‐Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda in Italy. Thirty‐four individuals from 18 families were included. FOXC1 variants were present in 64.7% of individuals and PITX2 variants in 35.3% of individuals. A thin upper lip (55.9%) and a prominent forehead (41.2%) were common facial features shared between both genes. Hypertelorism/telecanthus (81.8% vs 25.0%, p = 0.002) and low‐set ears (31.8% vs 0.0%, p = 0.036) were significantly more prevalent in individuals with FOXC1 variants compared with PITX2 variants. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling.
Discovery of Marburg virus neutralizing antibodies from virus-naïve human antibody repertoires using large-scale structural predictions

Significance Marburg virus (MARV) is a member of the Filoviridae family that causes severe hemorrhagic fevers with high fatality rates in humans. Despite the major efforts made to develop an effective vaccine after the most recent filovirus outbreak, still no Food and Drug Administration-licensed MARV disease vaccines exist. A good vaccine should be capable of eliciting neutralizing antibodies in MARV-naïve humans. This requires preexistence of antibodies with some affinity to the antigen. Here we used a large-scale computational antibody structure prediction approach to identify whether the epitope of the human anti-MARV monoclonal antibody MR78 can be recognized by antibodies from MARV-naïve humans and thus whether it is a promising candidate for vaccine design. Marburg virus (MARV) disease is lethal, with fatality rates up to 90%. Neutralizing antibodies (Abs) are promising drug candidates to prevent or treat the disease. Current efforts are focused in part on vaccine development to induce such MARV-neutralizing Abs. We analyzed the antibody repertoire from healthy unexposed and previously MARV-infected individuals to assess if naïve repertoires contain suitable precursor antibodies that could become neutralizing with a limited set of somatic mutations. We computationally searched the human Ab variable gene repertoire for predicted structural homologs of the neutralizing Ab MR78 that is specific to the receptor binding site (RBS) of MARV glycoprotein (GP). Eight Ab heavy-chain complementarity determining region 3 (HCDR3) loops from MARV-naïve individuals and one from a previously MARV-infected individual were selected for testing as HCDR3 loop chimeras on the MR78 Ab framework. Three of these chimerized antibodies bound to MARV GP. We then tested a full-length native Ab heavy chain encoding the same 17-residue-long HCDR3 loop that bound to the MARV GP the best among the chimeric Abs tested. Despite only 57% amino acid sequence identity, the Ab from a MARV-naïve donor recognized MARV GP and possessed neutralizing activity against the virus. Crystallization of both chimeric and full-length native heavy chain-containing Abs provided structural insights into the mechanism of binding for these types of Abs. Our work suggests that the MARV GP RBS is a promising candidate for epitope-focused vaccine design to induce neutralizing Abs against MARV.
Composite C/C à matrice nanochargée en alumine et en nitrure d'aluminium

Un procede de synthese de depots nanostructures de ceramiques a bases d’aluminium au sein de composites carbone/carbone (C/C) est developpe. Il consiste a synthetiser a partir de precurseurs dissout en solution aqueuse des nano-particules de morphologies variees. La maitrise du procede se deroule en deux etapes. Dans un premier temps une etude sur substrat plan permet de saisir les points cles du procede, puis l’adaptation de la synthese au sein d’un echantillon massif permet le changement d’echelle a des echantillons fibreux. Quatre gammes d’eprouvettes de materiaux densifies sont ainsi elaborees. La caracterisation des materiaux permet de prouver la bonne cohesion de ceux-ci et de mesurer plusieurs proprietes mecaniques et structurales.En complement plusieurs interfaces carbone|alumine ou nitrure d’aluminium sont simulees par une approche de dynamique moleculaire ab initio. La methode choisie pour generer les modeles consiste a simuler la trempe d’un carbone amorphe a haute temperature sur une surface ceramique immobile, puis de relaxer les contraintes.Des disparites sur l’organisation structurale des nano-structures et en particulier sur l’orientation des plans de graphene generes vis-a-vis de la surface sont observees en fonction des modeles. Lorsque les plans sont plutot perpendiculaires a la surface, l’interface est constituee de nombreuses liaisons fortes et le comportement en simulation de traction est bon, tandis que des plans paralleles entrainent une interface et un comportement faible.Enfin, la caracterisation HRTEM de certains materiaux elabores permet d’identifier experimentalement des interfaces semblables a celles obtenus par les modeles.
Sleep Management within Skilled Nursing Facilities: A Practice Survey

Abstract A cross-sectional descriptive survey of 105 occupational therapy practitioners examined the practice patterns in sleep management within skilled nursing facilities. All participants viewed sleep as essential to address in their settings, since clients frequently reported inadequate sleep, daytime sleepiness, difficulty staying asleep, and situational interruption. Majority of the practitioners reported not screening, assessing, treating, or documenting sleep issues and lack the use of standardized assessments and evidence-based interventions for sleep. Results suggest that practitioners need more training, education, and advocacy skills to promote the role of occupational therapy in addressing sleep management in skilled nursing facilities.
NMR APPLIED TO FLOW MEASUREMENT

NUCLEAR MAGNETIC RESONANCE (NMR) PRINCIPLES FORM THE BASIS FOR A NEW INDUSTRIAL FLOWMETER. THE NMR FLOWMETER WAS DEVELOPED TO PROVIDE A HIGH-PERFORMANCE, UNIVERSAL, VELOCITY FLOWMETER, INDEPENDENT OF SUCH FLUID PROPERTIES AS CONDUCTIVITY, TEMPERATURE, VISCOSITY, DENSITY, GAS OR SOLIDS ENTRAINMENT AND OPACITY. IT HAS NO MOVING PARTS, MECHANICAL CONTACT WITH THE FLUID, OR ELECTRICAL CONTACT WITH THE FLUID. NUCLEAR MAGNETIZATION OF THE FLUID PERMITS FLOW MEASUREMENT FROM THE OUTSIDE OF A STRAIGHT PIPE. THE FLOW IS NOT CONTACTED IN ANY WAY. THE OUTPUT OF THE FLOWMETER IS A SIGNAL WHOSE FREQUENCY IS PROPORTIONAL TO THE FLOW VELOCITY. IF THE ATOMIC NUCLEUS OF A CONSTITUENT ELEMENT IN A FLUID HAS MAGNETIC DIPOLE MOMENT, THE FLUID CAN BE METERED SINCE NMR CAN BE GENERATED. TESTS DEMONSTRATE THAT THE METER CAN OPERATE OVER A RANGE OF ORTHO CONCENTRATIONS OF ONE HALF TO THREE PERCENT, AND RELAXATION TIMES BETWEEN 4.5 AND 9.5 MILLISECONDS.
Personalized attention control therapy for PTSD: effectiveness and moderators of outcome in a randomized controlled trial

Abstract Background Previous randomized controlled trials (RCTs) suggest that attention control therapy (ACT), targeting aberrant fluctuations of attention toward and away from threats in patients with PTSD, may be effective in reducing symptoms. The current RCT examined whether the use of personalized-trauma stimuli enhances ACT efficacy in patients with PTSD. Additional moderators of treatment outcome were tested on an exploratory basis. Methods Sixty patients with PTSD were randomly assigned to either personalized ACT, non-personalized ACT, or a control condition. Changes in symptoms were examined across pre-treatment, post-treatment, and a 3-month follow-up. Attentional interference was examined pre- and post-treatment. Baseline clinical and cognitive indices as well as the time elapsed since the trauma were tested as potential moderators of treatment outcome. Results A significant reduction in clinical symptoms was noted for all three conditions with no between-group differences. Attention bias variability decreased following ACT treatment. Personalized ACT was more effective relative to the control condition when less time had elapsed since the trauma. Baseline clinical and cognitive indices did not moderate treatment outcome. Conclusions In this RCT of patients with PTSD, ACT was no more effective in reducing PTSD symptoms than a control condition. The data also suggest a potential benefit of personalized ACT for patients who experienced their trauma more recently.
A Decentralized Framework for Biostatistics and Privacy Concerns

Biostatistics and machine learning have been the cornerstone of a variety of recent developments in medicine. In order to gather large enough datasets, it is often necessary to set up multi-centric studies; yet, centralization of measurements can be difficult, either for practical, legal or ethical reasons. As an alternative, federated learning enables leveraging multiple centers' data without actually collating them. While existing works generally require a center to act as a leader and coordinate computations, we propose a fully decentralized framework where each center plays the same role. In this paper, we apply this framework to logistic regression, including confidence intervals computation. We test our algorithm on two distinct clinical datasets split among different centers, and show that it matches results from the centralized framework. In addition, we discuss possible privacy leaks and potential protection mechanisms, paving the way towards further research.
FXYD protein isoforms differentially modulate human Na/K pump function

Regulation of the Na/K pump is essential to maintain cells’ electrochemical gradients. Meyer et al. coexpressed the human α1β1 pump with five different FXYD proteins in Xenopus oocytes and show that FXYD isoforms have distinct effects on the pump’s ion affinity and membrane abundance.
The cGMP system in normal and degenerating mouse neuroretina: New proteins with cGMP interaction potential identified by a proteomics approach

The hereditary disease Retinitis pigmentosa results in severe vision loss due to photoreceptor degeneration by unclear mechanisms. In several disease models, the second messenger cGMP accumulates in the degenerating photoreceptors, where it may over‐activate specific cGMP‐interacting proteins, like cGMP‐dependent protein kinase. Moreover, interventions that counteract the activity of these proteins lead to reduced photoreceptor cell death. Yet there is little or no information whether other than such regular cGMP‐interactors are present in the retina, which we, therefore, investigated in wild‐type and retinal degeneration (rd1, rd10, and rd2) mouse models. An affinity chromatography based proteomics approach that utilized immobilized cGMP analogs was applied to enrich and select for regular and potentially new cGMP‐interacting proteins as identified by mass spectrometry. This approach revealed 12 regular and 10 potentially new retinal cGMP‐interacting proteins (e.g., EPAC2 and CaMKIIα). Several of the latter were found to be expressed in the photoreceptors and to have proximity to cGMP and may thus be of interest when defining prospective therapeutic targets or biomarkers for retinal degeneration.
Biological aerated filters: assessment of the process based on 12 sewage treatment plants

Biological aerated filtration is a recent and intensive process which has been greatly developed over the last few years. It is a technology based on biological processes with certain advantages, in particular the absence of secondary clarifiers, the modular nature and the wide variety of treatment applications. The monitoring of a dozen medium capacity (7,500 to 150,000 p.e.) plants designed to treat organic pollution, has enabled us to evaluate the process and its performance. The results obtained show that at applied loads of less than 7 kg of COD, the effluent is of satisfactory quality (< 90 mg / 1 of COD) and that the process has a high efficiency to remove suspended solids. Numerous other aspects have been studied and the data collected confirm the potential of this process, which nevertheless requires a careful and regular system operation procedure.