Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Evaluation of a Virtual Environment to Assess Cycling Hazard Perception Skills

Safe cycling requires situational awareness to identify and perceive hazards in the environment to react to and avoid dangerous situations. Concurrently, tending to external distractions leads to a failure to identify hazards or to respond appropriately in a time-constrained manner. Hazard perception training can enhance the ability to identify and react to potential dangers while cycling. Although cycling on the road in the presence of driving cars provides an excellent opportunity to develop and evaluate hazard perception skills, there are obvious ethical and practical risks, requiring extensive resources to facilitate safety, particularly when involving children. Therefore, we developed a Cycling and Hazard Perception virtual reality (VR) simulator (CHP-VR simulator) to create a safe environment where hazard perception can be evaluated and/or trained in a real-time setting. The player interacts in the virtual environment through a stationary bike, where sensors on the bike transfer the player’s position and actions (speed and road positioning) into the virtual environment. A VR headset provides a real-world experience for the player, and a procedural content generation (PCG) algorithm enables the generation of playable artifacts. Pilot data using experienced adult cyclists was collected to develop and evaluate the VR simulator through measuring gaze behavior, both in VR and in situ. A comparable scene (cycling past a parked bus) in VR and in situ was used. In this scenario, cyclists fixated 20% longer at the bus in VR compared to in situ. However, limited agreement identified that the mean differences fell within 95% confidence intervals. The observed differences were likely attributed to a lower number of concurrently appearing elements (i.e., cars) in the VR environment compared with in situ. Future work will explore feasibility testing in young children by increasing assets and incorporating a game scoring system to direct attention to overt and covert hazards.
A Systematic Review of Epstein–Barr Virus Latent Membrane Protein 1 (LMP1) Gene Variants in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is an aggressive tumor with a complex etiology. Although Epstein–Barr virus (EBV) infection is known environmental factor for NPC development, the degree to which EBV naturally infects nasopharyngeal epithelium and the moment when and why the virus actively begins to affect cell transformation remains questionable. The aim of this study was to explore the association between LMP1 gene variability and potential contribution to NPC development. A systematic review was performed through searches of PubMed, Web of Science (WoS) and SCOPUS electronic databases. Additionally, meta-analysis of the difference in the frequency of seven LMP1 gene variants in NPC and control individuals was accomplished. The results from this study give a proof of concept for the association between 30 bp deletion (OR = 3.53, 95% CI = 1.48–8.43) and Xhol loss (OR = 14.17, 95% CI = 4.99–40.20) and NPC susceptibility when comparing biopsies from NPC and healthy individuals. Otherwise, 30 bp deletion from NPC biopsies could not distinguish NPC from EBV-associated non-NPC tumors (OR = 1.74, 95% CI = 0.81–3.75). However, B95-8, China1 and North Carolina variants were uncommon for NPC individuals. Much more efforts remains to be done to verify the biological significance of the differences observed, define so-called “high-risk” EBV variants and make it available for clinical application.
Essential Oil-Loaded NLC for Potential Intranasal Administration

Complementary and alternative medicines represent an interesting field of research on which worldwide academics are focusing many efforts. In particular, the possibility to exploit pharmaceutical technology strategies, such as the nanoencapsulation, for the delivery of essential oils is emerging as a promising strategy not only in Italy but also all over the world. The aim of this work was the development of nanostructured lipid carriers (NLC) for the delivery of essential oils (Lavandula, Mentha, and Rosmarinus) by intranasal administration, an interesting topic in which Italian contributions have recently increased. Essential oil-loaded NLC, projected as a possible add-on strategy in the treatment of neurodegenerative diseases, were characterized in comparison to control formulations prepared with Tegosoft CT and Neem oil. Homogeneous (polydispersity index, PDI < 0.2) nanoparticles with a small size (<200 nm) and good stability were obtained. Morphological and physical-chemical studies showed the formation of different structures depending on the nature of the liquid oil component. In particular, NLC prepared with Lavandula or Rosmarinus showed the formation of a more ordered structure with higher cytocompatibility on two cell lines, murine and human fibroblasts. Taken together, our preliminary results show that optimized positively charged NLC containing Lavandula or Rosmarinus can be proposed as a potential add-on strategy in the treatment of neurodegenerative diseases through intranasal administration, due to the well-known beneficial effects of essential oils and the mucoadhesive properties of NLC.
Effects of a Recombinant Gonadotropin-Releasing Hormone Vaccine on Reproductive Function in Adult Male ICR Mice

Gonadotropin-releasing hormone (GnRH) regulates the reproductive endocrine system in mammals. The GnRH immunocontraception vaccine can aid animal population control and management. We evaluated a recombinant GnRH fusion protein with the adjuvant MONTANIDE ISA 206 VG as a GnRH vaccine in adult male ICR mice by evaluating anti-GnRH antibodies; concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone; testis size and histomorphology; and semen quality. Response was assessed after intramuscular administration of the vaccine to mice in weeks 0, 4, and 8. The vaccine induced specific antibody response by week 5, with peak of antibody levels observed by week 13 and a declining level thereafter until the end of the study at week 24. Furthermore, it reduced serum FSH, LH, and testosterone concentrations. The vaccinated mice exhibited testicular atrophy and reduced sperm quality, concentration, morphology, and viability compared to control males. The outcomes of pairings of treated males with untreated females revealed reduced mating, pregnancy rates and number of litters compared to control pairings. Assessment of this GnRH vaccine in different species could assist its development for future applications.
Consideration of Metabolite Efflux in Radiolabelled Choline Kinetics

Hypoxia is a complex microenvironmental condition known to regulate choline kinase α (CHKA) activity and choline transport through transcription factor hypoxia-inducible factor-1α (HIF-1α) and, therefore, may confound the uptake of choline radiotracer [18F]fluoromethyl-[1,2-2H4]-choline ([18F]-D4-FCH). The aim of this study was to investigate how hypoxia affects the choline radiotracer dynamics. Three underlying mechanisms by which hypoxia could potentially alter the uptake of the choline radiotracer, [18F]-D4-FCH, were investigated: 18F-D4-FCH import, CHKA phosphorylation activity, and the efflux of [18F]-D4-FCH and its phosphorylated product [18F]-D4-FCHP. The effects of hypoxia on [18F]-D4-FCH uptake were studied in CHKA-overexpressing cell lines of prostate cancer, PC-3, and breast cancer MDA-MB-231 cells. The mechanisms of radiotracer efflux were assessed by the cell uptake and immunofluorescence in vitro and examined in vivo (n = 24). The mathematical modelling methodology was further developed to verify the efflux hypothesis using [18F]-D4-FCH dynamic PET scans from non-small cell lung cancer (NSCLC) patients (n = 17). We report a novel finding involving the export of phosphorylated [18F]-D4-FCH and [18F]-D4-FCHP via HIF-1α-responsive efflux transporters, including ABCB4, when the HIF-1α level is augmented. This is supported by a graphical analysis of human data with a compartmental model (M2T6k + k5) that accounts for the efflux. Hypoxia/HIF-1α increases the efflux of phosphorylated radiolabelled choline species, thus supporting the consideration of efflux in the modelling of radiotracer dynamics.
Metformin Prevents Hyperglycemia-Associated, Oxidative Stress-Induced Vascular Endothelial Dysfunction: Essential Role for the Orphan Nuclear Receptor Human Nuclear Receptor 4A1 (Nur77)

Vascular pathology is increased in diabetes because of reactive-oxygen-species (ROS)-induced endothelial cell damage. We found that in vitro and in a streptozotocin diabetes model in vivo, metformin at diabetes-therapeutic concentrations (1–50 µM) protects tissue-intact and cultured vascular endothelial cells from hyperglycemia/ROS-induced dysfunction typified by reduced agonist-stimulated endothelium-dependent, nitric oxide–mediated vasorelaxation in response to muscarinic or proteinase-activated-receptor 2 agonists. Metformin not only attenuated hyperglycemia-induced ROS production in aorta-derived endothelial cell cultures but also prevented hyperglycemia-induced endothelial mitochondrial dysfunction (reduced oxygen consumption rate). These endothelium-protective effects of metformin were absent in orphan-nuclear-receptor Nr4a1-null murine aorta tissues in accord with our observing a direct metformin-Nr4a1 interaction. Using in silico modeling of metformin-NR4A1 interactions, Nr4a1-mutagenesis, and a transfected human embryonic kidney 293T cell functional assay for metformin-activated Nr4a1, we identified two Nr4a1 prolines, P505/P549 (mouse sequences corresponding to human P501/P546), as key residues for enabling metformin to affect mitochondrial function. Our data indicate a critical role for Nr4a1 in metformin’s endothelial-protective effects observed at micromolar concentrations, which activate AMPKinase but do not affect mitochondrial complex-I or complex-III oxygen consumption rates, as does 0.5 mM metformin. Thus, therapeutic metformin concentrations requiring the expression of Nr4a1 protect the vasculature from hyperglycemia-induced dysfunction in addition to metformin’s action to enhance insulin action in patients with diabetes. SIGNIFICANCE STATEMENT Metformin improves diabetic vasodilator function, having cardioprotective effects beyond glycemic control, but its mechanism to do so is unknown. We found that metformin at therapeutic concentrations (1–50µM) prevents hyperglycemia-induced endothelial dysfunction by attenuating reactive oxygen species–induced damage, whereas high metformin (>250 µM) impairs vascular function. However, metformin’s action requires the expression of the orphan nuclear receptor NR4A1/Nur77. Our data reveal a novel mechanism whereby metformin preserves diabetic vascular endothelial function, with implications for developing new metformin-related therapeutic agents.
The Algerian Chapter of SARS-CoV-2 Pandemic: An Evolutionary, Genetic, and Epidemiological Prospect

To explore the SARS-CoV-2 pandemic in Algeria, a dataset comprising ninety-five genomes originating from SARS-CoV-2 sampled from Algeria and other countries worldwide, from 24 December 2019, through 4 March 2021, was thoroughly examined. While performing a multi-component analysis regarding the Algerian outbreak, the toolkit of phylogenetic, phylogeographic, haplotype, and genomic analysis were effectively implemented. We estimated the Time to the Most Recent Common Ancestor (TMRCA) in reference to the Algerian pandemic and highlighted the multiple introductions of the disease and the missing data depicted in the transmission loop. In addition, we emphasized the significant role played by local and international travels in disease dissemination. Most importantly, we unveiled mutational patterns, the effect of unique mutations on corresponding proteins, and the relatedness regarding the Algerian sequences to other sequences worldwide. Our results revealed individual amino-acid replacements such as the deleterious replacement A23T in the orf3a gene in Algeria_EPI_ISL_418241. Additionally, a connection between Algeria_EPI_ISL_420037 and sequences originating from the USA was observed through a USA characteristic amino-acid replacement T1004I in the nsp3 gene, found in the aforementioned Algerian sequence. Similarly, successful tracing could be established, such as Algeria/G37318-8849/2020|EPI_ISL_766863, which was imported from Saudi Arabia during the pilgrimage. Lastly, we assessed the Algerian mitigation measures regarding disease containment using statistical analyses.
Active Circulation of Madariaga Virus, a Member of the Eastern Equine Encephalitis Virus Complex, in Northeast Brazil

Madariaga virus (MADV) is a member of the eastern equine encephalitis virus (EEEV) complex that circulates in Central and South America. It is a zoonotic, mosquito-borne pathogen, belonging to the family Togaviridae. Disturbances in the natural transmission cycle of this virus result in outbreaks in equines and humans, leading to high case fatality in the former and acute febrile illness or neurological disease in the latter. Although a considerable amount of knowledge exists on the eco-epidemiology of North American EEEV strains, little is known about MADV. In Brazil, the most recent isolations of MADV occurred in 2009 in the States of Paraíba and Ceará, northeast Brazil. Because of that, health authorities have recommended vaccination of animals in these regions. However, in 2019 an equine encephalitis outbreak was reported in a municipality in Ceará. Here, we present the isolation of MADV from two horses that died in this outbreak. The full-length genome of these viruses was sequenced, and phylogenetic analyses performed. Pathological findings from postmortem examination are also discussed. We conclude that MADV is actively circulating in northeast Brazil despite vaccination programs, and call attention to this arbovirus that likely represents an emerging pathogen in Latin America.
The Effectiveness of Specific Collagen Peptides on Osteoarthritis in Dogs-Impact on Metabolic Processes in Canine Chondrocytes

In clinical trials over the past decade, the beneficial effect of orally administered collagen peptides in osteoarthritic dogs has been clearly demonstrated [1] [2] [3]. Although a statistically significant improvement in the lameness and vitality of dogs in general has been documented, the mode of action of the collagen peptide treatment is still under discussion. A previous study [3] indicated that the reduction in lameness and increased mobility in dogs after collagen peptide treatment were associated with a statistically significantly lowered plasma content of MMP-3, which is involved in collagen degradation. In addition, the content of the MMP-antagonist TIMP-1 increased slightly after collagen peptide supplementation, suggesting a direct impact on the cartilage metabolism, particularly on the decrease of extracellular matrix degradation. Based on these findings, the impact of specific collagen peptides (PETA-GILE? ) on cartilage metabolism was tested in canine chondrocytes in the current investigation. In addition to the biosynthesis of various matrix molecules (type II collagen, aggrecan and elastin), the RNA profile of inflammatory cytokines and degenerative matrix molecules was investigated. The results showed clearly that the supplementation of specific collagen peptides reduced catabolic processes, as indicated by a statistically significant decrease in inflammatory cytokines and proteases in canine chondrocytes compared with untreated control experiments. In addition, a statistically significantly enhanced biosynthesis of type II collagen, elastin, and aggrecan was observed. Hence, the current data supports the suggested anti-inflammatory effect of specific collagen peptides, but also clearly demonstrates a pronounced stimulatory impact on matrix molecule synthesis. A combination of both observed effects might help to explain the previously reported clinical improvements after collagen peptide supplementation. Furthermore, the beneficial effect of the specific collagen peptides was also confirmed in case reports on osteoarthritic dogs that demonstrated decreased lameness and increased vitality in the affected animals after PETAGILE treatment.
Steady-State Visual Evoked Potential Classification Using Complex Valued Convolutional Neural Networks

The steady-state visual evoked potential (SSVEP), which is a kind of event-related potential in electroencephalograms (EEGs), has been applied to brain–computer interfaces (BCIs). SSVEP-based BCIs currently perform the best in terms of information transfer rate (ITR) among various BCI implementation methods. Canonical component analysis (CCA) or spectrum estimation, such as the Fourier transform, and their extensions have been used to extract features of SSVEPs. However, these signal extraction methods have a limitation in the available stimulation frequency; thus, the number of commands is limited. In this paper, we propose a complex valued convolutional neural network (CVCNN) to overcome the limitation of SSVEP-based BCIs. The experimental results demonstrate that the proposed method overcomes the limitation of the stimulation frequency, and it outperforms conventional SSVEP feature extraction methods.
Cytomegalovirus Infection Impairs the Mobilization of Tissue-Resident Innate Lymphoid Cells into the Peripheral Blood Compartment in Response to Acute Exercise

Circulating immune cell numbers and phenotypes are impacted by high-intensity acute bouts of exercise and infection history with the latent herpesviruses cytomegalovirus (CMV). In particular, CMV infection history impairs the exercise-induced mobilization of cytotoxic innate lymphoid cells 1 (ILC1) cells, also known as NK cells, in the blood. However, it remains unknown whether exercise and CMV infection modulate the mobilization of traditionally tissue-resident non-cytotoxic ILCs into the peripheral blood compartment. To address this question, 22 healthy individuals with or without CMV (20–35 years—45% CMVpos) completed 30 min of cycling at 70% VO2 max, and detailed phenotypic analysis of circulating ILCs was performed at rest and immediately post-exercise. We show for the first time that a bout of high-intensity exercise is associated with an influx of ILCs that are traditionally regarded as tissue-resident. In addition, this is the first study to highlight that latent CMV infection blunts the exercise-response of total ILCs and progenitor ILCs (ILCPs). These promising data suggest that acute exercise facilitates the circulation of certain ILC subsets, further advocating for the improvements in health seen with exercise by enhancing cellular mobilization and immunosurveillance, while also highlighting the indirect deleterious effects of CMV infection in healthy adults.
In Vitro Biodegradation Pattern of Collagen Matrices for Soft Tissue Augmentation

Collagen matrices have become a great alternative to the use of connective tissue grafts for soft tissue augmentation procedures. One of the main problems with these matrices is their volume instability and rapid degradation. This study has been designed with the objective of examining the degradation of three matrices over time. For this purpose, pieces of 10 × 10 mm2 of Fibro-Gide, Mucograft and Mucoderm were submitted to three different degradation tests—(1) hydrolytic degradation in phosphate buffer solution (PBS); (2) enzyme resistance, using a 0.25% porcine trypsin solution; and (3) bacterial collagenase resistance (Clostridium histolyticum)—over different immersion periods of up to 50 days. Weight measurements were performed with an analytic microbalance. Thickness was measured with a digital caliper. A stereomicroscope was used to obtain the matrices’ images. ANOVA and Student–Newman–Keuls tests were used for mean comparisons (p < 0.05), except when analyzing differences between time-points within the same matrix and solution, where pair-wise comparisons were applied (p < 0.001). Fibro-Gide attained the highest resistance to all degradation challenges. The bacterial collagenase solution was shown to constitute the most aggressive test as all matrices presented 100% degradation before 14 days of storage.
Testing Off-the-Shelf Optical Wireless LANs for Smart City Environments

Optical wireless LANs (OWLs) constitute an emerging networking paradigm for indoor scenarios’ fit to different smart cities’ fields of applications. Commercial products employing this technology have been made available on the market in recent years. In this work, we investigate, through a set of indoor communication experiments based on commercially available products, how different environmental and usage modes affect the performance of the system, addressing the presence of multiple users, the position and mobility of the mobile devices, the handover among adjacent cells and the effect of background lighting. Our finding shows that the system is quite robust with respect to the variation of operational conditions. We show that, in most conditions, the links can reliably sustain a stable throughput, achieving at least 50% of the throughput achieved with using the maximum light intensity of the transmitting lamp, while they are affected in a very mild way by factors like position and height of the mobile device, and virtually unaffected by variations in the background light.
Palliation of malignant dysphagia with a segmented self-expanding metal stent

Abstract Self-expanding metal stents (SEMSs) in different geometric shapes are an established palliative treatment for malignant tumors of the esophagus. Mechanical properties and stent design have an impact on patient comfort, migration rate, and removability. SEMS with a segmented design (segSEMS) have recently become available on the market, promising new biomechanical properties for stent placement in benign and malignant esophageal diseases. In this study, we evaluated recurrent dysphagia, quality of life as well as technical success and complications for segmented SEMS-implantation in a retrospective study in palliative patients with dysphagia caused by malignant tumors of the esophagus. Between May 2017 and December 2018, patients presented to the interdisciplinary department of endoscopy of the University Hospital Cologne underwent segmented SEMS placement for malignant dysphagia. Patient follow-up was evaluated, and complications were monitored. Quality of life and functional improvement were monitored using the EORTC QLQ-C30 and QLQ-OE18. A total of 20 consecutive patients (16 men, 4 women; mean age: 65.5, range: 46–82) participated in the study and were treated with 20 segSEMS in total. The success rate of stent placement was 100%. Stent migration occurred in 3 patients (15.0%). Insertion of segSEMS immediately lead to a 48.0% reduction of dysphagia in the first 2 months (P < .001). Pain while eating (odynophagia) could also be significantly reduced by 39.6% over the first 2 months (P < .001). Implantation of segSEMS is a feasible and effective treatment for dysphagia in palliative patients with malignant tumors of the esophagus, offering immediate relief of symptoms and gain of physical functions.