An Analysis of the Interpretability of Neural Networks trained on Magnetic Resonance Imaging for Stroke Outcome Prediction

Applying deep learning models to MRI scans of acute stroke patients to extract features that are indicative of short-term outcome could assist a clinician’s treatment decisions. Deep learning models are usually accurate but are not easily interpretable. Here, we trained a convolutional neural network on ADC maps from hyperacute ischaemic stroke patients for prediction of short-term functional outcome and used an interpretability technique to highlight regions in the ADC maps that were most important in the prediction of a bad outcome. Although highly accurate, the model’s predictions were not based on aspects of the ADC maps related to stroke pathophysiology

Receptor Ubiquitination Regulates Il-5rα Function

Eosinophils are multifunctional leukocytes implicated in the pathogenesis of inflammatory processes including hypereosinophilic syndrome, eosinophilic esophagitis, and allergic asthma. Due to its role in the initiation and propagation of inflammatory responses, and as modulators between innate and adaptive immunity, eosinophils are emerging as critical cells in both health and disease. Eosinophil activation and inflammatory signaling are dependent on interleukin-5 (IL-5) and signaling by its receptor, IL-5R, comprised of a ligand specific alpha chain (IL-5Rα) and a shared signaling component, βc. Previously, our laboratory demonstrated the critical role of three membrane proximal lysine residues in the cytoplasmic domain of βc for Janus kinase (JAK) binding and optimal receptor ubiquitination, and such binding is responsible for receptor signaling and endocytosis following IL-5 stimulation. However, little is known about whether or not IL-5Rα itself is ubiquitinated or what the molecular determinants are. Since βc and IL-5Rα are both members of the Type I cytokine receptor family, with similar structural features, we hypothesized that IL-5Rα is also ubiquitinated and that lysine residues in homologous regions were important for this process. To test this hypothesis, we performed site directed mutagenesis on four membrane proximal lysine residues within the cytoplasmic domain of IL-5Rα, generating six mutant receptors expressed in HEK293 cell lines with wild-type βc. Our data revealed that IL-5Rα is ubiquitinated under steady state conditions, highlighting a novel role of ubiquitin in stabilizing cell surface expression of receptors prior to cytokine stimulation. In addition, the binding of JAKs to IL-5Rα depended on the presence of all four lysine residues, and such binding resulted in optimal ubiquitination under basal conditions. Our most striking finding was the IL-5-induced deubiquitination of IL-5Rα that triggers receptor internalization, with this deubiquitination event being dependent on the presence of the third and fourth lysine residues (Lys^370 and Lys^379). In sum, these findings reveal a unique regulatory role for ubiquitin in IL-5Rα biology, particularly the significance of receptor deubiquitination following cytokine stimulation. Due to the specific role of IL-5Rα within eosinophil biology, results from this study may provide more insight into IL-5Rα regulation and perhaps help identify novel molecular targets for controlling inappropriate signaling associated with eosinophilic inflammation

Isolation and optimization of the production of Staphylococcus epidermidis bacteriophage from environmental samples

Staphylococcus epidermidis is now among the most important nosocomial pathogenic agents owing its virulence to the adhesion and biofilm-forming abilities on medical surfaces, such as catheters. Biofilm control by antibiotics is often innefective and new strategies of biofilm control are being sought. One promising strategy is the use of bacteria-specific virus, known as bacteriophages, to control infections by pathogenic bacteria. Bacteriophages, also know as phages, have been suggested to be one of the most abundant biological agents on the planet. Phages are currently suggested as possible alternatives to antibiotics for the treatment of bacterial diseases in humans to minimize the pathogen loads in medical devices . The goal of this study was to isolate new phages with potential bactericidal activity against S. epidermidis clinical isolates. Bacteriophages were isolated from an effluent from Waste Water Treatment Plants or from Hospital efluents, using a set of 40 bacterial strains as background. Five phages were isolated but when determining the phage titer the achieved concentration was around 10E5 pfu/ml and this titer was reduced 1 fold in two week‘s time. In order to increase the concentration of bacteriophages, since the obtained concentration was not sufficient to use in biofilm assays, severall optimization steps were performed, using previous described isolation protocols, namelly: using different concentrations of CaCl2, using different concentrations of top agar, using different buffers, and using different phage filtration systems. For the optimization protocols we selected the bacteriophage with the higher titters and found that an optimized protocol was achieved by using Tris Buffer, Top Agar at 0.4%, and purification with CsCl2 gradient (q = 1.3, 1.5, and 1.7) with ultracentrifugation at 100,000g for 1 h at 4⁰C. This phage titter was determined to be around 10E8-10E9 pfu/ml. The optimized produced phage was then characterized by determining the lytic spectrum. The phage was able to lyse 13 strains, and of these strains 10 had the biofilms genes present. Finally, the 10 selected strains were tested for biofilm formation, using the microtiter assay, and it was confirmed that they formed biofilms in TSB supplemented with 1% glucose. For future work; we need to determine if we have lytic or temperate phages with DNA sequence analyses and to test the Phage against to the Biofilm formation of relevant bacterial strains

Ethnopharmacological Approaches to Wound Repair

Wound is breaking of the skin by a physical injury. Wound healing is a connective tissue response along with the repair process which immediately comes after the injury. It occurs as a sequence of phases such as haemostasis, inflammation, proliferation, and remodelling and causes series of interactions between the extracellular matrix, cytokine mediators, and different cell types. For rapid healing several medicinal plants were reported in ethnobotanical studies. Traditional remedies which claimed to have wound healing potential are widely used in developing countries due to their accessibility and low cost. However, these remedies should be evaluated for their efficacy and safety before their utilization. In this context, the papers selected for this special issue include scientifically evaluated information and lead to development of novel drugs for rapid healing of wounds.We would like to thank the authors for their contributions for this special issue. This special issue contains twelve papers. T. Lin et al. investigated the wound healing effect of tocopherol in diabetic rats.This study has proven thewound healing potential of tocopherol cream by increasing the rate of wound closure and total protein content significantly in diabetic condition

Acquired Generalized Lipodystrophy Associated with Autoimmune Hepatitis and Low Serum C4 Level

Lipodystrophies are a group of diseases characterized by loss of fat tissue and are associated with insulin resistance. A six-year- old girl followed with the diagnosis of autoimmune hepatitis showed a severe loss of fat tissue, hyperinsulinemia, impaired glucose tolerance, hypertriglyceridemia and low serum complement 4 (C4) levels. She had coarse facial features with generalized loss of subcutaneous fat and prominent muscularity. Remarkable acanthosis nigricans was present over the neck, axilla, and umbilicus. Two hours after glucose loading, the glucose tolerance test revealed a glucose level of 258 mg/dL, a HbA1c value of 6.8%, and an insulin level of 642.9 mIU/mL, documenting a state of insulin resistance and type 2 diabetes mellitus. Acquired generalized lipodystrophy was diagnosed and metformin with dietary intervention was initiated. Low serum complement levels proved the autoimmune nature of the process. We conclude that the serum complement levels must be investigated in patients with acquired lipodystrophy, particularly when it is associated with autoimmune hepatitis

A Rare Cause of Precocious Puberty: Hepatoblastoma

Hepatoblastoma, an embryonal tumor, is one of the most common primary liver tumors in childhood. It secretes human chorionic gonadotropin (hCG), which can cause precocious puberty (PP). Herein, we present a case with PP who had enlarged penile size noticed during a diagnosis of hepatoblastoma. Laboratory examination revealed increased testosterone, alpha-fetoprotein (AFP), and hCG levels. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were within prepubertal ranges. The diagnosis of hepatoblastoma was made by liver biopsy. Chemotherapy was administered, and the patient was referred to surgery. Ten months later, testis volumes were below 4 ml bilaterally, and penile length was 5.5 cm. Serum testosterone, AFP, and hCG levels decreased. Resection of the tumor and chemotherapy are essential for the treatment of hepatoblastoma and they can eliminate the symptoms of PP

Multimodal Fusion Strategies for Outcome Prediction in Stroke

Data driven methods are increasingly being adopted in the medical domain for clinical predictive modeling. Prediction of stroke outcome using machine learning could provide a decision support system for physicians to assist them in patient-oriented diagnosis and treatment. While patient-specific clinical parameters play an important role in outcome prediction, a multimodal fusion approach that integrates neuroimaging with clinical data has the potential to improve accuracy. This paper addresses two research questions: (a) does multimodal fusion aid in the prediction of stroke outcome, and (b) what fusion strategy is more suitable for the task at hand. The baselines for our experimental work are two unimodal neural architectures: a 3D Convolutional Neural Network for processing neuroimaging data, and a Multilayer Perceptron for processing clinical data. Using these unimodal architectures as building blocks we propose two feature-level multimodal fusion strategies: 1) extracted features , where the unimodal architectures are trained separately and then fused, and 2) end-to-end, where the unimodal architectures are trained together. We show that integration of neuroimaging information with clinical metadata can potentially improve stroke outcome prediction. Additionally, experimental results indicate that the end-to-end fusion approach proves to be more robust