BigNeuron: a resource to benchmark and predict performance of algorithms for automated tracing of neurons in light microscopy datasets.

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms. The goal of generating such a hand-curated diverse dataset is to advance the development of tracing algorithms and enable generalizable benchmarking. Together with image quality features, we pooled the data in an interactive web application that enables users and developers to perform principal component analysis, t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and tracing data, and benchmarking of automatic tracing algorithms in user-defined data subsets. The image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. We observed that diverse algorithms can provide complementary information to obtain accurate results and developed a method to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms in noisy datasets. However, specific algorithms may outperform the consensus tree strategy in specific imaging conditions. Finally, to aid users in predicting the most accurate automatic tracing results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic tracings.

A Proposed Non-Destructive Method Based on Sphere Launching and Piezoelectric Diaphragm.

This work presents the study of a reproducible acoustic emission method based on the launching of a metallic sphere and low-cost piezoelectric diaphragm. For this purpose, tests were first conducted on a carbon fiber-reinforced polymer structure, and then on an aluminum structure for comparative analysis. The pencil-lead break (PLB) tests were also conducted for comparisons with the proposed method. Different launching heights and elastic deformations of the structures were investigated. The results show higher repeatability for the sphere impact method, as the PLB is more affected by human inaccuracy, and it was also effective in damage detection.

Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy-A Preliminary Study in a Brazilian Cohort Sample.

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.

Leukoreduction as a control measure in transfusion transmission of visceral leishmaniasis.

BACKGROUND: Asymptomatic visceral leishmaniasis (VL) infection is a risk for transfusion safety. Leukoreduction has been an alternative for the prevention of some blood-borne diseases, including VL. This study aimed to evaluate the role of leukoreduction of cellular blood components as a control measure for transfusional VL transmission. RESEARCH DESIGN AND METHODS: A total of 161 polytransfused patients with non-leukoreduced blood components (HNL), 95 polytransfused with leukoreduced blood components (LH), and 202 non-transfused (NT) from endemic regions for VL and with a similar epidemiological profile. The detection of antibodies against VL was performed by ELISA and the presence of the parasite was investigated by real-time PCR. Statistical significance was defined as p < .05. RESULTS: When comparing three groups, ELISA results were statistically significant (p = .0065). The residual analysis of ELISA showed statistically significant for the HNL group compared to the general group (p = .002; OR: 5.6; CI: 1.7-25.8), demonstrating that individuals who received non-leukoreduced transfusions are five times more likely to acquire Leishmania infantum infection than the general. DISCUSSION: Higher prevalence in the group with HNL and low prevalence in those who received LH, similar to NT patients, highlight the risk of transfusional VL transmission and reinforce the role of leukoreduction in its prevention.

Primary central nervous system lymphoma in a patient with multiple sclerosis using fingolimod.

Primary central nervous system lymphoma (PCNSL) is an uncommon lymphoproliferative disease associated with immunosuppression. Here, we report the case of a patient with multiple sclerosis, under treatment with fingolimod (FTY720, Gilenya) for 4 years, who developed this condition. Although the causal relationship cannot be established, there are cases in the literature that describe the appearance of lymphoma after the use of this medication. Considering the high mortality of PCNSL, epidemiological studies are necessary to establish a relationship between its arising and the use of immunosuppressants.

Preoperative scale proposal based on clinical outcome for elderly patients with ruptured intracranial aneurysms undergoing microsurgery.

INTRODUCTION: Life expectancy in individuals has increased in recent years. There is no consensus in the literature on the best treatment for a ruptured aneurysm in the elderly (> 60 years), but some places only have microsurgery as a therapeutic strategy. This work aims to develop a prognostic scale for ruptured intracranial aneurysms in the elderly. MATERIAL AND METHODS: Two thousand five hundred thirty patients with subarachnoid hemorrhage were retrospectively evaluated in the last ten years, and 550 of them were elderly. We developed a prognostic scale from the analysis of medical records, clinical and tomographic features that had statistical significance. Glasgow Coma Outcome (GOS) was the outcome of interest and p value < 0,05 was considered statistically significant. RESULTS: Five hundred fifty patients were evaluated, and the comorbidities that were independent variables for poor prognosis were smoking and arterial hypertension; clinical variables were Hunt-Hess, modified Rankin and Glasgow Coma Scale; tomographic was Fisher scale. Poor outcome was defined as GOS ≤ 3. Poor surgical outcomes were more remarkable in the high-risk factor categories, being 6.41 times higher among individuals who had 3 to 4 risk factors and 8.80 times higher among individuals with 5 to 6 risk factors. CONCLUSION: In some vascular neurosurgery services worldwide, microsurgery is the only therapeutic option. This scale aimed at the elderly patient individualizes the treatment and can predict the clinical outcome in ruptured intracranial aneurysms.

Callosotomy vs Vagus Nerve Stimulation in the Treatment of Lennox-Gastaut Syndrome: A Systematic Review With Meta-Analysis.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe drug-resistant epileptic syndrome. Palliative treatments such as corpus callosotomy (CC) and vagus nerve stimulation (VNS) have emerged as treatments to reduce the number of seizures in patients. The aim of this study is to compare the effectiveness of CC and VNS in patients with LGS studied in the last 30 years. MATERIALS AND METHODS: We conducted a systematic review with meta-analysis and collected papers from PubMed (MEDLINE), Ovidsp, Web of Science, and Cochrane Library data bases. The articles analyzed were published between January 1990 and December 2020. Keywords were chosen based on internal and external validation in the PubMed data base (the analysis is available in the Supplementary Data Supplementary Appendix). Prospective or retrospective case reports (n ≥ 2), case series, cohort studies, or case-control studies involving patients with LGS were included in the analysis. We selected studies that had no age or sex restriction and that provided data on seizures before and after treatments. Studies not written in English, published without peer review, or not indexed in the data bases were excluded. Other exclusion criteria were the absence of seizure data and the impossibility of extracting this information from the studies. To analyze the results, we used the random-effects model based on the assessment of heterogeneity (I2 statistics) in two scenarios. In scenario 1, we assessed the incidence of patients with a seizure reduction ≥ 50%; in scenario 2, we assessed the incidence of patients with a seizure reduction > 0%. RESULTS: Of the 7418 articles found using the keywords, 32 were considered eligible. Of these, 18 articles were on VNS (175 patients) and 14 on CC (107 patients). For scenario 1 (seizure reduction ≥ 50%), CC had an incidence of 65% (95% CI, 37%-94%), with an I2 value of 82.7%; VNS had an incidence of 34% (95% CI, 11%-57%), with an I2 value of 80.7%. For scenario 2 (seizure reduction > 0%), CC had an incidence of 80% (95% CI, 58%-100%), with an I2 value of 84.7%; VNS had an incidence of 64% (95% CI, 38%-89%), with an I2 value of 90.8%. There was an overlap of confidence intervals, with no statistical difference between the treatments in both scenarios. DISCUSSION: Our analysis of LGS showed that the CC and VNS treatments are significantly beneficial to reducing seizures, without superiority between them.

Trackosome: a computational toolbox to study the spatiotemporal dynamics of centrosomes, nuclear envelope and cellular membrane.

During the initial stages of mitosis, multiple mechanisms drive centrosome separation and positioning. How they are coordinated to promote centrosome migration to opposite sides of the nucleus remains unclear. Here, we present Trackosome, an open-source image analysis software for tracking centrosomes and reconstructing nuclear and cellular membranes, based on volumetric live-imaging data. The toolbox runs in MATLAB and provides a graphical user interface for easy access to the tracking and analysis algorithms. It provides detailed quantification of the spatiotemporal relationships between centrosomes, nuclear envelope and cellular membrane, and can also be used to measure the dynamic fluctuations of the nuclear envelope. These fluctuations are important because they are related to the mechanical forces exerted on the nucleus by its adjacent cytoskeletal structures. Unlike previous algorithms based on circular or elliptical approximations, Trackosome measures membrane movement in a model-free condition, making it viable for irregularly shaped nuclei. Using Trackosome, we demonstrate significant correlations between the movements of the centrosomes, and identify specific oscillation modes of the nuclear envelope. Overall, Trackosome is a powerful tool that can be used to help unravel new elements in the spatiotemporal dynamics of subcellular structures.

Single-Nucleotide Variants in microRNAs Sequences or in their Target Genes Might Influence the Risk of Epilepsy: A Review.

Single-nucleotide variant (SNV) is a single base mutation at a specific location in the genome and may play an import role in epilepsy pathophysiology. The aim of this study was to review case-control studies that have investigated the relationship between SNVs within microRNAs (miRs) sequences or in their target genes and epilepsy susceptibility from January 1, 2010 to October 31, 2020. Nine case-control studies were included in the present review. The mainly observed SNVs associated with drug-resistant epilepsy (DRE) risk were SNVs n.60G > C (rs2910164) and n.-411A > G (rs57095329), both located at miR-146a mature sequence and promoter region, respectively. In addition, the CC haplotype (rs987195-rs969885) and the AA genotype at rs4817027 in the MIR155HG/miR-155 tagSNV were also genetic susceptibility markers for early-onset epilepsy. MiR-146a has been observed as upregulated in human astrocytes in epileptogenesis and it regulates inflammatory process through NF-κB signaling by targeting tumor necrosis factor-associated factor 6 (TRAF6) gene. The SNVs rs2910164 and rs57095329 may modify the expression level of mature miR-146a and the risk for epilepsy and SNVs located at rs987195-rs969885 haplotype and at rs4817027 in the MIR155HG/miR-155 tagSNV could interfere in the miR-155 expression modulating inflammatory pathway genes involved in the development of early-onset epilepsy. In addition, SNVs rs662702, rs3208684, and rs35163679 at 3'untranslated region impairs the ability of miR-328, let-7b, and miR-200c binding affinity with paired box protein PAX-6 (PAX6), BCL2 like 1 (BCL2L1), and DNA methyltransferase 3 alpha (DNMT3A) target genes. The SNV rs57095329 might be correlated with DRE when a larger number of patients are evaluated. Thus, we concluded that the main drawback of most of studies is the small number of individuals enrolled, which lacks sample power.

Dravet syndrome and Dravet syndrome-like phenotype: a systematic review of the SCN1A and PCDH19 variants.

Dravet syndrome (DS) is a rare and severe epileptic syndrome of childhood with prevalence between 1/22,000 and 1/49,900 of live births. Approximately 80% of patients with this syndrome present SCN1A pathogenic variants, which encodes an alpha subunit of a neural voltage-dependent sodium channel. There is a correlation between PCDH19 pathogenic variants, encodes the protocadherin 19, and a similar disease to DS known as DS-like phenotype. The present review aims to clarify the differences between DS and DS-like phenotype according to the SCN1A and PCDH19 variants. A systematic review was conducted in PubMed and Virtual Health Library (VHL) databases, using "Dravet Syndrome" and "Severe Myoclonic Epilepsy in Infancy (SMEI)" search words, selecting cohort of studies published in journal with impact factor of two or greater. The systematic review was according to the Preferred Reporting Items for Systematic Review and Meta-Analysis recommendations. Nineteen studies were included in the present review, and a significant proportion of patients with DS-carrying SCN1A was greater than patients with DS-like phenotype-harboring PCDH19 variants (76.6% versus 23.4%). When clinical and genetic data were correlated, autism was predominantly observed in patients with DS-like-carrying PCDH19 variants compared to SCN1A variant carriers (62.5% versus 37.5%, respectively, P-value = 0.044, P-value corrected = 0.198). In addition, it was noticed a significant predisposition to hyperthermia during epilepsy crisis in individuals carrying PCDH19 variants (P-value = 0.003; P-value corrected = 0.027). The present review is the first to point out differences between the DS and DS-like phenotype according to the SCN1A and PCDH19 variants.

Bone marrow cell response after injury and during early stage of regeneration is independent of the tissue-of-injury in 2 injury models.

Selectively recruiting bone marrow (BM)-derived stem and progenitor cells to injury sites is a promising therapeutic approach. The coordinated action of soluble factors is thought to trigger the mobilization of stem cells from the BM and recruit them to lesions to contribute to tissue regeneration. Nevertheless, the temporal response profile of the major cellular players and soluble factors involved in priming the BM and recruiting BM-derived cells to promote regeneration is unknown. We show that injury alters the BM cellular composition, introducing population-specific fluctuations during tissue regeneration. We demonstrate that injury causes an immediate, transient response of mesenchymal stromal cells and endothelial cells followed by a nonoverlapping increase in hematopoietic stem and progenitor cells. Moreover, BM reaction is identical whether the injury is inflicted on skin and muscle or also involves a bone defect, but these 2 injury paradigms trigger distinct systemic cytokine responses. Together, our results indicate that the BM response to injury in the early stages of regeneration is independent of the tissue-of-injury based on the 2 models used, but the injured tissue dictates the systemic cytokine response.-Leitão, L., Alves, C. J., Alencastre, I. S., Sousa, D. M., Neto, E., Conceição, F., Leitão, C., Aguiar, P., Almeida-Porada, G., Lamghari, M. Bone marrow cell response after injury and during early stage of regeneration is independent of the tissue-of-injury in 2 injury models.

Natural history of intraventricular meningiomas: systematic review.

Review the data published on the subject to create a more comprehensive natural history of intraventricular meningiomas (IVMs). A Medline search up to March 2018 using "intraventricular meningioma" returned 98 papers. As a first selection step, we adopted the following inclusion criteria: series and case reports about IVMs, as well as papers written in other languages, but abstracts written in English were evaluated. Six hundred eighty-one tumors were evaluated from 98 papers. The majority of the tumors were located in the lateral ventricles (602-88.4%), fourth ventricle (59-8.7%), and third ventricle (20-2.9%). These tumors accounted for a mortality rate of 4.0% (25 deaths) and a recurrence rate of 5.3% (26 recurrences). The majority of the tumors were grade I (89.8%) and consisted of the following subtypes: fibrous, 39.7% (n = 171); transitional, 22.0% (n = 95); meningothelial, 18.6% (n = 80); angiomatosus, 3.2% (n = 14); psammomatous, 2.6% (n = 11); and others, 13.9% (n = 60). Forty-five patients (7.4%) presented with grade II (GII) tumors, and 17 patients (2.8%) presented with grade III (GIII) tumors. These tumors follow the histopathological distribution of meningiomas in general, with the exception of the higher prevalence of the fibrous subtype, possibly due to its embryonic origin. Recurrence and mortality were lower than in other localizations likely due to a complete surgical resection rate than in the convexity and skull base, which suggests that GTR is the gold standard for the management of IVMs.

Erratum: Aulestia Viera, M., et al. A Time-Frequency Acoustic Emission-Based Technique to Assess Workpiece Surface Quality in Ceramic Grinding with PZT Transducer. Sensors 2019, 19, 3913.

The authors wish to make the following erratum to this paper [...].

Improved 3D tracking and automated classification of rodents' behavioral activity using depth-sensing cameras.

Analysis of rodents' behavior/activity is of fundamental importance in many research fields. However, many behavioral experiments still rely on manual scoring, with obvious problems in reproducibility. Despite important advances in video-analysis systems and computational ethology, automated behavior quantification is still a challenge. The need for large training datasets, background stability requirements, and reduction to two-dimensional analysis (impairing full posture characterization), limit their use. Here we present a novel integrated solution for behavioral analysis of individual rats, combining video segmentation, tracking of body parts, and automated classification of behaviors, using machine learning and computer vision methods. Low-cost depth cameras (RGB-D) are used to enable three-dimensional tracking and classification in dark conditions and absence of color contrast. Our solution automatically tracks five anatomical landmarks in dynamic environments and recognizes seven distinct behaviors, within the accuracy range of human annotations. The developed free software was validated in experiments where behavioral differences between Wistar Kyoto and Wistar rats were automatically quantified. The results reveal the capability for effective automated phenotyping. An extended annotated RGB-D dataset is also made publicly available. The proposed solution is an easy-to-use tool, with low-cost setup and powerful 3D segmentation methods (in static/dynamic environments). The ability to work in dark conditions means that natural animal behavior is not affected by recording lights. Furthermore, automated classification is possible with only ~30 minutes of annotated videos. By creating conditions for high-throughput analysis and reproducible quantitative measurements of animal behavior experiments, we believe this contribution can greatly improve behavioral analysis research.

A Novel Ultrasound Technique Based on Piezoelectric Diaphragms Applied to Material Removal Monitoring in the Grinding Process.

The interest of the scientific community for ultrasound techniques has increased in recent years due to its wide range of applications. A continuous effort of researchers and industries has been made in order to improve and increase the applicability of non-destructive evaluations (NDE). In this context, the monitoring of manufacturing processes, such as the grinding process, arises. This work proposes a novel technique of ultrasound monitoring (chirp-through-transmission) through low-cost piezoelectric diaphragms and digital signal processing. The proposed technique was applied to the monitoring of material removal during the grinding process. The technique is based on changes in ultrasonic waves when propagated through the material under study, with the difference that this technique does not use traditional parameters of ultrasonic techniques but digital signal processing (RMS and Counts). Furthermore, the novelty of the proposed technique is also the use of low-cost piezoelectric diaphragms in the emission and reception of ultrasonic waves, enabling the implementation of a low-cost monitoring system. The results show that the monitoring technique proposed in this work, when used in conjunction with the frequency band selection, is sensitive to the material removal in the grinding process and therefore presents an advance for monitoring the grinding processes.

A Time-Frequency Acoustic Emission-Based Technique to Assess Workpiece Surface Quality in Ceramic Grinding with PZT Transducer.

Innovative monitoring systems based on sensor signals have emerged in recent years in view of their potential for diagnosing machining process conditions. In this context, preliminary applications of fast-response and low-cost piezoelectric diaphragms (PZT) have recently emerged in the grinding monitoring field. However, there is a lack of application regarding the grinding of ceramic materials. Thus, this work presents an analysis of the feasibility of using the acoustic emission signals obtained through the PZT diaphragm, together with digital signal processing in the time-frequency domain, in the monitoring of the surface quality of ceramic components during the surface grinding process. For comparative purpose, an acoustic emission (AE) sensor, commonly used in industry, was used as a baseline. The results obtained by the PZT diaphragm were similar to the results obtained using the AE sensor. The time-frequency analysis allowed to identify irregularities throughout the monitored process.

Dressing Tool Condition Monitoring through Impedance-Based Sensors: Part 2-Neural Networks and K-Nearest Neighbor Classifier Approach.

This paper presents an approach for impedance-based sensor monitoring of dressing tool condition in grinding by using the electromechanical impedance (EMI) technique. This method was introduced in Part 1 of this work and the purpose of this paper (Part 2) is to achieve an optimal selection of the excitation frequency band based on multi-layer neural networks (MLNN) and k-nearest neighbor classifier (k-NN). The proposed approach was validated on the basis of dressing tool condition information obtained from the monitoring of experimental dressing tests with two industrial stationary single-point dressing tools. Moreover, representative damage indices for diverse damage cases, obtained from impedance signatures at different frequency bands, were taken into account for MLNN data processing. The intelligent system was able to select the most damage-sensitive features based on optimal frequency band. The best models showed a general overall error lower than 2%, thus robustly contributing to the efficient automation of grinding and dressing operations. The promising results of this study foster the EMI-based sensor monitoring approach to fault diagnosis in dressing operations and its effective implementation for industrial grinding process automation.

Dressing Tool Condition Monitoring through Impedance-Based Sensors: Part 1-PZT Diaphragm Transducer Response and EMI Sensing Technique.

Low-cost piezoelectric lead zirconate titanate (PZT) diaphragm transducers have attracted increasing attention as effective sensing devices, based on the electromechanical impedance (EMI) principle, for applications in many engineering sectors. Due to the considerable potential of PZT diaphragm transducers in terms of excellent electromechanical coupling properties, low implementation cost and wide-band frequency response, this technique provides a new alternative approach for tool condition monitoring in grinding processes competing with the conventional and expensive indirect sensor monitoring methods. This paper aims at assessing the structural changes caused by wear in single-point dressers during their lifetime, in order to ensure the reliable monitoring of the tool condition during dressing operations. Experimental dressing tests were conducted on aluminum oxide grinding wheels, which are highly relevant for industrial grinding processes. From the results obtained, it was verified that the dresser tip diamond material and the position of the PZT diaphragm transducer mounted on the dressing tool holder have a significant effect on the sensitivity of damage detection. This paper contributes to the realization of an effective monitoring system of dressing operations capable to avoid catastrophic tool failures as the proposed sensing approach can identify different stages of the dressing tool lifetime based on representative damage indices.

Compartmentalized Microfluidic Platforms: The Unrivaled Breakthrough of In Vitro Tools for Neurobiological Research.

Microfluidic technology has become a valuable tool to the scientific community, allowing researchers to study fine cellular mechanisms with higher variable control compared with conventional systems. It has evolved tremendously, and its applicability and flexibility made its usage grow exponentially and transversely to several research fields. This has been particularly noticeable in neuroscience research, where microfluidic platforms made it possible to address specific questions extending from axonal guidance, synapse formation, or axonal transport to the development of 3D models of the CNS to allow pharmacological testing and drug screening. Furthermore, the continuous upgrade of microfluidic platforms has allowed a deeper study of the communication occurring between different neuronal and glial cells or between neurons and other peripheral tissues, both in physiological and pathological conditions. Importantly, the evolution of microfluidic technology has always been accompanied by the development of new computational tools addressing data acquisition, analysis, and modeling.