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These data also fundamentally change our understanding of the progressive, site-specific nature of CLN1 disease pathogenesis, and highlight the importance of the neuroimmune response. This should greatly impact our approach to the timing and targeting of future therapeutic trials for this and similar disorders.Pleural effusion is very common, but an etiologic diagnosis is often difficult. We used three unconventional diagnostic techniques (voltammetric analysis, protein electrophoresis and pH measurement) performed on pleural effusion to do a preliminary distinction between a neoplastic and a non-neoplastic origin. Pleural fluid samples were collected through thoracentesis, thoracoscopy, or post-surgery pleural drainage of 116 patients admitted to acute care wards. Samples were analyzed with the three unconventional techniques voltammetric analysis using the BIONOTE system, capillary electrophoresis and pH measurement using a potentiometric method. The BIONOTE system is an innovative system that performs a cyclic voltammetric analysis of a biological liquid sample. The final output of the electrochemical analysis is an electrical pattern that represents a fingerprint of the analyzed sample and each sample has a different fingerprint. Data from the three unconventional diagnostic techniques were analyzed using partial least squares discriminant analysis to discriminate neoplastic from non-neoplastic effusions; we also evaluated sensitivity, specificity and percentage of correct classification. The mean age was 68 years (SD 12); 78 (67.24%) participants were men. Results obtained from all the unconventional techniques employed showed that neoplastic and non-neoplastic pleural effusions were correctly classified in 80.2% of cases, with a sensitivity of 77% and specificity of 83%. The combined use of voltammetric analysis, protein electrophoresis and pH measurement of pleural fluid can easily and quickly distinguish a neoplastic from a non-neoplastic pleural effusion with reliable accuracy and represents an innovative diagnostic approach. In fact, this protocol can be executed in just few minutes directly in the patient's bed and it holds great promise to improve the prognosis and therapeutic chances.A coherent anti-Stokes Raman scattering (CARS) rigid endoscope was developed to visualize peripheral nerves without labeling for nerve-sparing endoscopic surgery. The developed CARS endoscope had a problem with low imaging speed, i.e. low imaging rate. In this study, we demonstrate that noise reduction with deep learning boosts the nerve imaging speed with CARS endoscopy. We employ fine-tuning and ensemble learning and compare deep learning models with three different architectures. In the fine-tuning strategy, deep learning models are pre-trained with CARS microscopy nerve images and retrained with CARS endoscopy nerve images to compensate for the small dataset of CARS endoscopy images. read more We propose using the equivalent imaging rate (EIR) as a new evaluation metric for quantitatively and directly assessing the imaging rate improvement by deep learning models. The highest EIR of the deep learning model was 7.0 images/min, which was 5 times higher than that of the raw endoscopic image of 1.4 images/min. We believe that the improvement of the nerve imaging speed will open up the possibility of reducing postoperative dysfunction by intraoperative nerve identification.The gut microbiome is known to be sensitive to changes in the immune system, especially during autoimmune diseases such as Multiple Sclerosis (MS). Our study examines the changes to the gut microbiome that occur during experimental autoimmune encephalomyelitis (EAE), an animal model for MS. We collected fecal samples at key stages of EAE progression and quantified microbial abundances with 16S V3-V4 amplicon sequencing. Our analysis of the data suggests that the abundance of commensal Lactobacillaceae decreases during EAE while other commensal populations belonging to the Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae families expand. Community analysis with microbial co-occurrence networks points to these three expanding taxa as potential mediators of gut microbiome dysbiosis. We also employed PICRUSt2 to impute MetaCyc Enzyme Consortium (EC) pathway abundances from the original microbial abundance data. From this analysis, we found that a number of imputed EC pathways responsible for the production of immunomodulatory compounds appear to be enriched in mice undergoing EAE. Our analysis and interpretation of results provides a detailed picture of the changes to the gut microbiome that are occurring throughout the course of EAE disease progression and helps to evaluate EAE as a viable model for gut dysbiosis in MS patients.Historical variation in food resources is expected to be a major driver of cetacean evolution, especially for the smallest species like porpoises. Despite major conservation issues among porpoise species (e.g., vaquita and finless), their evolutionary history remains understudied. Here, we reconstructed their evolutionary history across the speciation continuum. Phylogenetic analyses of 63 mitochondrial genomes suggest that porpoises radiated during the deep environmental changes of the Pliocene. However, all intra-specific subdivisions were shaped during the Quaternary glaciations. We observed analogous evolutionary patterns in both hemispheres associated with convergent evolution to coastal versus oceanic environments. This suggests that similar mechanisms are driving species diversification in northern (harbor and Dall's) and southern species (spectacled and Burmeister's). In contrast to previous studies, spectacled and Burmeister's porpoises shared a more recent common ancestor than with the vaquita that diverged from southern species during the Pliocene. The low genetic diversity observed in the vaquita carried signatures of a very low population size since the last 5,000 years. Cryptic lineages within Dall's, spectacled and Pacific harbor porpoises suggest a richer evolutionary history than previously suspected. These results provide a new perspective on the mechanisms driving diversification in porpoises and an evolutionary framework for their conservation.