Miracle-dz/UniFAR-FTUs huggingface dataset:
Reactive Jumps Preserve Skeletal Muscle Structure, Phenotype, and Myofiber Oxidative Capacity in Bed Rest

Identification of countermeasures able to prevent disuse-induced muscle wasting is crucial to increase performance of crew members during space flight as well as ameliorate patient’s clinical outcome after long immobilization periods. We report on the outcome of short but high-impact reactive jumps (JUMP) as countermeasure during 60 days of 6° head-down tilt (HDT) bed rest on myofiber size, type composition, capillarization, and oxidative capacity in tissue biopsies (pre/post/recovery) from the knee extensor vastus lateralis (VL) and deep calf soleus (SOL) muscle of 22 healthy male participants (Reactive jumps in a sledge, RSL-study 2015–2016, DLR:envihab, Cologne). Bed rest induced a slow-to-fast myofiber shift (type I –>II) with an increased prevalence of hybrid fibers in SOL after bed rest without jumps (control, CTRL, p = 0.016). In SOL, JUMP countermeasure in bed rest prevented both fast and slow myofiber cross-sectional area (CSA) decrements (p = 0.005) in CTRL group. In VL, bed rest only induced capillary rarefaction, as reflected by the decrease in local capillary-to-fiber ratio (LCFR) for both type II (pre vs. post/R + 10, p = 0.028/0.028) and type I myofibers (pre vs. R + 10, p = 0.012), which was not seen in the JUMP group. VO2maxFiber (pL × mm–1 × min–1) calculated from succinate dehydrogenase (SDH)-stained cryosections (OD660 nm) showed no significant differences between groups. High-impact jump training in bed rest did not prevent disuse-induced myofiber atrophy in VL, mitigated phenotype transition (type I – >II) in SOL, and attenuated capillary rarefaction in the prime knee extensor VL however with little impact on oxidative capacity changes.
Cochlear Implant Receiver Location and Migration: Experimental Validation Pilot Study of a Clinically Applicable Screening Method

Objectives: Postoperative follow-up after cochlear implantation lacks a reliable screening method to detect cochlear implant receiver device migration. This study aims to validate a clinically applicable method to assess the position and migration of the cochlear implant receiver device. Study design: Validation study. Setting: Tertiary university medical center. Participants and method: To assess the cochlear implant receiver device location, round markers representing the external magnet were placed on both sides of the head of volunteers. Four independent clinicians took measurements of the distances between reference points on the head and the center of the marker. The reference points were: the lateral canthus (LC), tragus tip (TT), the mastoid angle (MA), and the mandibular angle (AM). Main outcome measures: The inter-clinician reliability was determined by calculating the intraclass correlation coefficient (ICC) and confidence interval (CI) with a two-way mixed model and both consistency and absolute agreement types for each distance. Results: Eight volunteers were included resulting in 16 individual cases. The consistency type ICC's for each reference point were: LC 0.90 (CI = 0.80, 0.96), TT 0.83 (CI = 0.69, 0.93), MA 0.75 (CI = 0.56, 0.89), and AM 0.29 (CI = 0.05, 0.59). The absolute agreement ICC's were: LC 0.87 (CI = 0.73, 0.95), TT 0.83 (CI = 0.68, 0.93), MA 0.68 (CI = 0.42, 0.86), and AM 0.18 (CI = 0.01, 0.46). The inter-clinician reliability was good to excellent for the lateral canthus and tragus tip reference points. Conclusions: The cochlear receiver device location can be assessed reliably by measuring the distance between the LC, TT, and the external magnet. This method can be used to registrate implant receiver location after implantation and detect implant migration postoperatively.
How Probiotics Affect the Microbiota

Probiotics have been used to treat a variety of diseases for decades; however, what is the rationale for their application? Such a treatment was first proposed in the early nineteenth century based on observations of decreased bifidobacterial populations in children suffering from diarrhea, suggesting that oral intake of bifidobacteria could replete this subpopulation of the microbiota and improve health. Since then, studies have shown modifications in the gut or skin microbiota in the course of a variety of diseases and suggested positive effects of certain probiotics. Most studies failed to report any impact on the microbiota. The impact of probiotics as well as of bacteria colonizing food does not reside in their ability to graft in the microbiota but rather in sharing genes and metabolites, supporting challenged microbiota, and directly influencing epithelial and immune cells. Such observations argue that probiotics could be associated with conventional drugs for insulin resistance, infectious diseases, inflammatory diseases, and psychiatric disorders and could also interfere with drug metabolism. Nevertheless, in the context of a plethora of probiotic strains and associations produced in conditions that do not allow direct comparisons, it remains difficult to know whether a patient would benefit from taking a particular probiotic. In other words, although several mechanisms are observed when studying a single probiotic strain, not all individual strains are expected to share the same effects. To clarify the role of probiotics in the clinic, we explored the relation between probiotics and the gut and skin microbiota.
Self-Assembled 3D Actuator Using the Resilience of an Elastomeric Material

Self-folding technologies have been studied by many researchers for applications to various engineering fields. Most of the self-folding methods that use the physical properties of materials require complex preparation, and usually take time to complete. In order to solve these problems, we focus on the elasticity of a material, and propose a model for forming a 3D structure using its characteristics. Our proposed model achieves high-speed and high-precision self-folding with a simple structure, by attaching rigid frames to a stretchable elastomer. The self-folded structure is applied to introduce a self-assembled actuator by exploiting a dielectric elastomer actuator (DEA). We develop the self-assembled actuator driven with the voltage application by attaching stretchable electrodes on the both side of the elastomer. We attempt several experiments to investigate the basic characteristics of the actuator. We also propose an application of the self-assembled actuator as a gripper based on the experimental results. The gripper has three joints with the angle of 120°, and successfully grabs objects by switching the voltage.
DeepMalaria: Artificial Intelligence Driven Discovery of Potent Antiplasmodials

Antimalarial drugs are becoming less effective due to the emergence of drug resistance. Resistance has been reported for all available malaria drugs, including artemisinin, thus creating a perpetual need for alternative drug candidates. The traditional drug discovery approach of high throughput screening (HTS) of large compound libraries for identification of new drug leads is time-consuming and resource intensive. While virtual in silico screening is a solution to this problem, however, the generalization of the models is not ideal. Artificial intelligence (AI), utilizing either structure-based or ligand-based approaches, has demonstrated highly accurate performances in the field of chemical property prediction. Leveraging the existing data, AI would be a suitable alternative to blind-search HTS or fingerprint-based virtual screening. The AI model would learn patterns within the data and help to search for hit compounds efficiently. In this work, we introduce DeepMalaria, a deep-learning based process capable of predicting the anti-Plasmodium falciparum inhibitory properties of compounds using their SMILES. A graph-based model is trained on 13,446 publicly available antiplasmodial hit compounds from GlaxoSmithKline (GSK) dataset that are currently being used to find novel drug candidates for malaria. We validated this model by predicting hit compounds from a macrocyclic compound library and already approved drugs that are used for repurposing. We have chosen macrocyclic compounds as these ligand-binding structures are underexplored in malaria drug discovery. The in silico pipeline for this process also consists of additional validation of an in-house independent dataset consisting mostly of natural product compounds. Transfer learning from a large dataset was leveraged to improve the performance of the deep learning model. To validate the DeepMalaria generated hits, we used a commonly used SYBR Green I fluorescence assay based phenotypic screening. DeepMalaria was able to detect all the compounds with nanomolar activity and 87.5% of the compounds with greater than 50% inhibition. Further experiments to reveal the compounds’ mechanism of action have shown that not only does one of the hit compounds, DC-9237, inhibits all asexual stages of Plasmodium falciparum, but is a fast-acting compound which makes it a strong candidate for further optimization.
Schizophrenia Identification Using Multi-View Graph Measures of Functional Brain Networks

Schizophrenia (SZ) is a functional mental disorder that seriously affects the social life of patients. Therefore, accurate diagnosis of SZ has raised extensive attention of researchers. At present, study of brain network based on resting-state functional magnetic resonance imaging (rs-fMRI) has provided promising results for SZ identification by studying functional network alteration. However, previous studies based on brain network analysis are not very effective for SZ identification. Therefore, we propose an improved SZ identification method using multi-view graph measures of functional brain networks. Firstly, we construct an individual functional connectivity network based on Brainnetome atlas for each subject. Then, multi-view graph measures are calculated by the brain network analysis method as feature representations. Next, in order to consider the relationships between measures within the same brain region in feature selection, multi-view measures are grouped according to the corresponding regions and Sparse Group Lasso is applied to identify discriminative features based on this feature grouping structure. Finally, a support vector machine (SVM) classifier is employed to perform SZ identification task. To evaluate our proposed method, computational experiments are conducted on 145 subjects (71 schizophrenic patients and 74 healthy controls) using a leave-one-out cross-validation (LOOCV) scheme. The results show that our proposed method can obtain an accuracy of 93.10% for SZ identification. By comparison, our method is more effective for SZ identification than some existing methods.
Grafting of Fatty Acids on Polyvinyl Alcohol: Effects on Surface Energy and Adhesion Strength of Acrylic Pressure Sensitive Adhesives

Chemical grafting with fatty acid chlorides is known to reduce the surface energy of polymer substrates. The aim of this study was to evaluate the effect of different grafting parameters on functional properties such as the surface energy of grafted substrates and adhesion of acrylic pressure sensitive adhesives (PSA) on those substrates in dependence of storage time. Therefore, two substrates, paper and polyethylene terephthalate (PET), were coated with polyvinyl alcohol (PVOH). The PVOH showed similar degrees of hydrolysis but different molecular weights. Fatty acid chlorides (palmitoyl chloride, stearoyl chloride) were grafted on pure PET, pure paper, PVOH coated paper, and PVOH coated PET. On these samples, roughness was measured and peel strength and surface energy were determined over storage time. Peel strength was observed to increase with roughness. The chain length of fatty acid chlorides and storage time did not majorly influence peel strength.
Monitoring and Measurement of Intracranial Pressure in Pediatric Head Trauma

Purpose of Review: Monitoring of intracranial pressure (ICP) is an important and integrated part of the treatment algorithm for children with severe traumatic brain injury (TBI). Guidelines often recommend ICP monitoring with a treatment threshold of 20 mmHg. This focused review discusses; (1) different ICP technologies and how ICP should be monitored in pediatric patients with severe TBI, (2) existing evidence behind guideline recommendations, and (3) how we could move forward to increase knowledge about normal ICP in children to support treatment decisions. Summary: Current reference values for normal ICP in adults lie between 7 and 15 mmHg. Recent studies conducted in “pseudonormal” adults, however, suggest a normal range below this level where ICP is highly dependent on body posture and decreases to negative values in sitting and standing position. Despite obvious physiological differences between children and adults, no age or body size related reference values exist for normal ICP in children. Recent guidelines for treatment of severe TBI in pediatric patients recommend ICP monitoring to guide treatment of intracranial hypertension. Decision on ICP monitoring modalities are based on local standards, the individual case, and the clinician's choice. The recommended treatment threshold is 20 mmHg for a duration of 5 min. Both prospective and retrospective observational studies applying different thresholds and treatment strategies for intracranial hypertension were included to support this recommendation. While some studies suggest improved outcome related to ICP monitoring (lower rate of mortality and severe disability), most studies identify high ICP as a marker of worse outcome. Only one study applied age-differentiated thresholds, but this study did not evaluate the effect of these different thresholds on outcome. The quality of evidence behind ICP monitoring and treatment thresholds in severe pediatric TBI is low and treatment can potentially be improved by knowledge about normal ICP from observational studies in healthy children and cohorts of pediatric “pseudonormal” patients expected to have normal ICP. Acceptable levels of ICP − and thus also treatment thresholds—probably vary with age, disease and whether the patient has intact cerebral autoregulation. Future treatment algorithms should reflect these differences and be more personalized and dynamic.
Nonlinear Analysis of Eye-Tracking Information for Motor Imagery Assessments

This study investigates the assessment of motor imagery (MI) ability in humans. Commonly, MI ability is measured through two methodologies: a self-administered questionnaire (MIQ-3) and the mental chronometry (MC), which measures the temporal discrepancy between the actual and the imagined motor tasks. However, both measures rely on subjects' self-assessment and do not use physiological measures. In this study, we propose a novel set of features extracted from the nonlinear dynamics of the eye gaze signal to discriminate between good and bad imagers. To this aim, we designed an experiment where twenty volunteers, categorized as good or bad imagers according to MC, performed three tasks: a motor task (MT), a visual Imagery task (VI), and a kinaesthetic Imagery task (KI). Throughout the experiment, the subjects' eye gaze was continuously monitored using an eye-tracking system. Eye gaze time series were analyzed through recurrence quantification analysis of the reconstructed phase space and compared between the two groups. Statistical results have shown how nonlinear eye behavior can express an inner dynamics of imagery mental process and may be used as a more objective and physiological-based measure of MI ability.
The Law of Recency: An Episodic Stimulus-Response Retrieval Account of Habit Acquisition

A habit is a regularity in automatic responding to a specific situation. Classical learning psychology explains the emergence of habits by an extended learning history during which the response becomes associated to the situation (learning of stimulus-response associations) as a function of practice (“law of exercise”) and/or reinforcement (“law of effect”). In this paper, we propose the “law of recency” as another route to habit acquisition that draws on episodic memory models of automatic response regulation. According to this account, habitual responding results from (a) storing stimulus-response episodes in memory, and (b) retrieving these episodes when encountering the stimulus again. This leads to a reactivation of the response that was bound to the stimulus (c) even in the absence of extended practice and reinforcement. As a measure of habit formation, we used a modified color-word contingency learning (CL) paradigm, in which irrelevant stimulus features (i.e., word meaning) were predictive of the to-be-executed color categorization response. The paradigm we developed allowed us to assess effects of global CL and of an instance-based episodic response retrieval simultaneously within the same experiment. Two experiments revealed robust CL as well as episodic response retrieval effects. Importantly, these effects were not independent: Controlling for response retrieval effects eliminated effects of CL, which supports the claim that habit formation can be mediated by episodic retrieval processes, and that short-term binding effects are not fundamentally separate from long-term learning processes. Our findings have theoretical and practical implications regarding (a) models of long-term learning, and (b) the emergence and change of habitual responding.
Nimble Cloning: A Simple, Versatile, and Efficient System for Standardized Molecular Cloning

Molecular cloning is one of the most fundamental technologies in molecular biology, and has been critical for driving biotechnological advances. In this study, we have developed a novel method for standardized molecular cloning. The cloning technique known as “Nimble Cloning” uses the restriction enzyme, SfiI, in combination with the T5 exonuclease, to linearize the vector and generate 3′-overhangs simultaneously. Both PCR products and plasmids can be used for the cloning reaction in the Nimble Cloning system. The cloning system is highly efficient, suitable for gene expression in both prokaryotic and eukaryotic expression systems, and enables the reuse of DNA fragments or plasmid entry clones. Nimble Cloning is applicable for the cloning of single or multiple fragments, as well as multi-site cloning. Due also to its simplicity and versatility, the cloning method has great potential for the modular assembly of DNA constructs.
Endoplasmic Reticulum Stress and Mitochondrial Function in Airway Smooth Muscle

Inflammatory airway diseases such as asthma affect more than 300 million people world-wide. Inflammation triggers pathophysiology via such as tumor necrosis factor α (TNFα) and interleukins (e.g., IL-13). Hypercontraction of airway smooth muscle (ASM) and ASM cell proliferation are major contributors to the exaggerated airway narrowing that occurs during agonist stimulation. An emergent theme in this context is the role of inflammation-induced endoplasmic reticulum (ER) stress and altered mitochondrial function including an increase in the formation of reactive oxygen species (ROS). This may establish a vicious cycle as excess ROS generation leads to further ER stress. Yet, it is unclear whether inflammation-induced ROS is the major mechanism leading to ER stress or the consequence of ER stress. In various diseases, inflammation leads to an increase in mitochondrial fission (fragmentation), associated with reduced levels of mitochondrial fusion proteins, such as mitofusin 2 (Mfn2). Mitochondrial fragmentation may be a homeostatic response since it is generally coupled with mitochondrial biogenesis and mitochondrial volume density thereby reducing demand on individual mitochondrion. ER stress is triggered by the accumulation of unfolded proteins, which induces a homeostatic response to alter protein balance via effects on protein synthesis and degradation. In addition, the ER stress response promotes protein folding via increased expression of molecular chaperone proteins. Reduced Mfn2 and altered mitochondrial dynamics may not only be downstream to ER stress but also upstream such that a reduction in Mfn2 triggers further ER stress. In this review, we summarize the current understanding of the link between inflammation-induced ER stress and mitochondrial function and the role played in the pathophysiology of inflammatory airway diseases.
Effects of Vitamin D2 (Ergocalciferol) and D3 (Cholecalciferol) on Atlantic Salmon (Salmo salar) Primary Macrophage Immune Response to Aeromonas salmonicida subsp. salmonicida Infection

Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are fat-soluble secosteroid hormones obtained from plant and animal sources, respectively. Fish incorporates vitamin D2 and D3 through the diet. In mammals, vitamin D forms are involved in mineral metabolism, cell growth, tissue differentiation, and antibacterial immune response. Vitamin D is an essential nutrient in aquafeeds for finfish. However, the influence of vitamin D on fish cell immunity has not yet been explored. Here, we examined the effects of vitamin D2 and vitamin D3 on Salmo salar primary macrophage immune response to A. salmonicida subspecies salmonicida infection under in vitro conditions. We determined that high concentrations of vitamin D2 (100,000 ng/ml) and D3 (10,000 ng/ml) affect the growth of A. salmonicida and decrease the viability of S. salar primary macrophages. In addition, we determined that primary macrophages pre-treated with a biologically relevant concentration of vitamin D3 for 24 h showed a decrease of A. salmonicida infection. In contrast, vitamin D2 did not influence the antibacterial activity of the S. salar macrophages infected with A. salmonicida. Vitamin D2 and D3 did not influence the expression of canonical genes related to innate immune response. On the other hand, we found that A. salmonicida up-regulated the expression of several canonical genes and suppressed the expression of leukocyte-derived chemotaxin 2 (lect-2) gene, involved in neutrophil recruitment. Primary macrophages pre-treated for 24 h with vitamin D3 counteracted this immune suppression and up-regulated the transcription of lect-2. Our results suggest that vitamin D3 affects A. salmonicida attachment to the S. salar primary macrophages, and as a consequence, the A. salmonicida invasion decreased. Moreover, our study shows that the positive effects of vitamin D3 on fish cell immunity seem to be related to the lect-2 innate immunity mechanisms. We did not identify positive effects of vitamin D2 on fish cell immunity. In conclusion, we determined that the inactive form of vitamin D3, cholecalciferol, induced anti-bacterial innate immunity pathways in Atlantic salmon primary macrophages, suggesting that its utilization as a component of a healthy aquafeed diet in Atlantic salmon could enhance the immune response against A. salmonicida.