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MOTIVATION: As more behavioural assays are carried out in large-scale experiments on Drosophila larvae, the definitions of the archetypal actions of a larva are regularly refined. In addition, video recording and tracking technologies constantly evolve. Consequently, automatic tagging tools for Drosophila larval behaviour must be retrained to learn new representations from new data. However, existing tools cannot transfer knowledge from large amounts of previously accumulated data. We introduce LarvaTagger, a piece of software that combines a pre-trained deep neural network, providing a continuous latent representation of larva actions for stereotypical behaviour identification, with a graphical user interface to manually tag the behaviour and train new automatic taggers with the updated ground truth. RESULTS: We reproduced results from an automatic tagger with high accuracy, and we demonstrated that pre-training on large databases accelerates the training of a new tagger, achieving similar prediction accuracy using less data. AVAILABILITY AND IMPLEMENTATION: All the code is free and open source. Docker images are also available. See gitlab.pasteur.fr/nyx/LarvaTagger.jl.
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Conducta Animal , Drosophila , Larva , Programas Informáticos , Animales , Conducta Animal/fisiología , Grabación en Video/métodos , Redes Neurales de la ComputaciónRESUMEN
This paper addresses the exploration-exploitation dilemma inherent in decision-making, focusing on multiarmed bandit problems. These involve an agent deciding whether to exploit current knowledge for immediate gains or explore new avenues for potential long-term rewards. We here introduce a class of algorithms, approximate information maximization (AIM), which employs a carefully chosen analytical approximation to the gradient of the entropy to choose which arm to pull at each point in time. AIM matches the performance of Thompson sampling, which is known to be asymptotically optimal, as well as that of Infomax from which it derives. AIM thus retains the advantages of Infomax while also offering enhanced computational speed, tractability, and ease of implementation. In particular, we demonstrate how to apply it to a 50-armed bandit game. Its expression is tunable, which allows for specific optimization in various settings, making it possible to surpass the performance of Thompson sampling at short and intermediary times.
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The cell membrane organization has an essential functional role through the control of membrane receptor confinement in micro- or nanodomains. Several mechanisms have been proposed to account for these properties, although some features have remained controversial, notably the nature, size, and stability of cholesterol- and sphingolipid-rich domains or lipid rafts. Here, we probed the effective energy landscape acting on single-nanoparticle-labeled membrane receptors confined in raft nanodomains- epidermal growth factor receptor (EGFR), Clostridium perfringens ε-toxin receptor (CPεTR), and Clostridium septicum α-toxin receptor (CSαTR)-and compared it with hop-diffusing transferrin receptors. By establishing a new analysis pipeline combining Bayesian inference, decision trees, and clustering approaches, we systematically classified single-protein trajectories according to the type of effective confining energy landscape. This revealed the existence of only two distinct organization modalities: confinement in a quadratic energy landscape for EGFR, CPεTR, and CSαTR (A), and free diffusion in confinement domains resulting from the steric hindrance due to F-actin barriers for transferrin receptor (B). The further characterization of effective confinement energy landscapes by Bayesian inference revealed the role of interactions with the domain environment in cholesterol- and sphingolipid-rich domains with (EGFR) or without (CPεTR and CSαTR) interactions with F-actin to regulate the confinement energy depth. These two distinct mechanisms result in the same organization type (A). We revealed that the apparent domain sizes for these receptor trajectories resulted from Brownian exploration of the energy landscape in a steady-state-like regime at a common effective temperature, independently of the underlying molecular mechanisms. These results highlight that confinement domains may be adequately described as interaction hotspots rather than rafts with abrupt domain boundaries. Altogether, these results support a new model for functional receptor confinement in membrane nanodomains and pave the way to the constitution of an atlas of membrane protein organization.
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Microdominios de Membrana , Microdominios de Membrana/metabolismo , Receptores de Transferrina/metabolismo , Receptores de Transferrina/química , Teorema de Bayes , Receptores ErbB/metabolismo , Receptores ErbB/química , Termodinámica , DifusiónRESUMEN
To coordinate cellular physiology, eukaryotic cells rely on the rapid exchange of molecules at specialized organelle-organelle contact sites1,2. Endoplasmic reticulum-mitochondrial contact sites (ERMCSs) are particularly vital communication hubs, playing key roles in the exchange of signalling molecules, lipids and metabolites3,4. ERMCSs are maintained by interactions between complementary tethering molecules on the surface of each organelle5,6. However, due to the extreme sensitivity of these membrane interfaces to experimental perturbation7,8, a clear understanding of their nanoscale organization and regulation is still lacking. Here we combine three-dimensional electron microscopy with high-speed molecular tracking of a model organelle tether, Vesicle-associated membrane protein (VAMP)-associated protein B (VAPB), to map the structure and diffusion landscape of ERMCSs. We uncovered dynamic subdomains within VAPB contact sites that correlate with ER membrane curvature and undergo rapid remodelling. We show that VAPB molecules enter and leave ERMCSs within seconds, despite the contact site itself remaining stable over much longer time scales. This metastability allows ERMCSs to remodel with changes in the physiological environment to accommodate metabolic needs of the cell. An amyotrophic lateral sclerosis-associated mutation in VAPB perturbs these subdomains, likely impairing their remodelling capacity and resulting in impaired interorganelle communication. These results establish high-speed single-molecule imaging as a new tool for mapping the structure of contact site interfaces and reveal that the diffusion landscape of VAPB at contact sites is a crucial component of ERMCS homeostasis.
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Retículo Endoplásmico , Mitocondrias , Membranas Mitocondriales , Movimiento , Proteínas de Transporte Vesicular , Humanos , Esclerosis Amiotrófica Lateral/genética , Retículo Endoplásmico/química , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/ultraestructura , Mitocondrias/química , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Membranas Mitocondriales/química , Membranas Mitocondriales/metabolismo , Membranas Mitocondriales/ultraestructura , Transducción de Señal , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Transporte Vesicular/ultraestructura , Microscopía Electrónica , Imagenología Tridimensional , Sitios de Unión , Difusión , Factores de Tiempo , Mutación , HomeostasisRESUMEN
INTRODUCTION: In patients with haemophilia, repeated bleeding in large joints leads to chronic haemophilic arthropathy, a rare disease that can be managed surgically with ankle arthrodesis or with total ankle replacement (TAR). TAR has been reported to provide good surgical results in the medium/long-term and allow preservation of joint mobility but the medical therapeutic management of the patients has not been described. AIM: To describe the medical therapeutic management of TAR. METHODS: All patients with haemophilia A/B, with haemophilic ankle arthropathy, and who underwent TAR between April 2006 and October 2019 were retrospectively included. Factor consumption, perioperative and early complications, volume of blood lost, and orthopaedic data were collected. RESULTS: A total of 25 patients underwent 29 TAR (mean age was 44.7 years [range: 26-65]). In the 17 patients with HA without history of anti-FVIII inhibitor, the mean ± SD consumption the day of surgery was 116 ± 16 UI/kg when clotting factors were administered by continuous infusion, 106 ± 13 UI/kg when SHL factors were administered by bolus infusion, and 75 ± 22 UI/kg when EHL factors were administered by bolus infusion. During hospitalisation, the mean factor cost was 38,073 (83.7% of the total cost of surgery). Mean blood loss was significantly lower in patients treated with tranexamic acid (164 mL, range: 40-300) than in those not (300 mL, range: 70-800; p = .01). Six patients had haematoma. The 10-year survival free of any prosthesis removal/arthrodesis was estimated to be 92.2% (95% CI [83; 100]). CONCLUSION: The medical therapeutic management of TAR is complex, carried out by a multidisciplinary team but effective in avoiding the occurrence of complications.
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Artritis , Artroplastia de Reemplazo de Tobillo , Hemofilia A , Artropatías , Humanos , Adulto , Artroplastia de Reemplazo de Tobillo/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Articulación del Tobillo/cirugía , Hemofilia A/complicaciones , Hemofilia A/cirugía , Artropatías/complicaciones , Artritis/complicaciones , ArtrodesisRESUMEN
The energy consumption of a building is significantly influenced by the habits of its occupants. These habits not only pertain to occupancy states, such as presence or absence, but also extend to more detailed aspects of occupant behavior. To accurately capture this information, it is essential to use tools that can monitor occupant habits without altering them. Invasive methods such as body sensors or cameras could potentially disrupt the natural habits of the occupants. In our study, we primarily focus on occupancy states as a representation of occupant habits. We have created a model based on artificial neural networks (ANNs) to ascertain the occupancy state of a building using environmental data such as CO2 concentration and noise level. These data are collected through non-intrusive sensors. Our approach involves rule-based a priori labeling and the use of a long short-term memory (LSTM) network for predictive purposes. The model is designed to predict four distinct states in a residential building. Although we lack data on actual occupancy states, the model has shown promising results with an overall prediction accuracy ranging between 78% and 92%.
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BACKGROUND: When performing total hip arthroplasty in patients with severe developmental dysplasia, shortening the femur facilitates reduction while also preventing sciatic or crural nerve injury and excessive length of the operated limb. No consensus exists about the optimal type of implant and best internal fixation procedure, two parameters that directly govern the risk of the most common intraoperative and postoperative complications (diaphyseal fractures, dislocation, non-union). To minimise these risks, we developed a technique combining a transverse subtrochanteric shortening osteotomy, a long ovoid-profiled, cementless stem anchored in the metaphysis, and double tension-band wiring for internal fixation. The primary objective of this study was to evaluate the outcomes of this technique with emphasis on (i) complications and femoral implant survival, (ii) clinical outcomes (functional scores and lower-limb length inequality [LLLI]), and time to healing. HYPOTHESIS: Our technique is associated with low rates of intraoperative and postoperative complications. MATERIAL AND METHODS: This single-centre retrospective cohort study included patients who underwent THA with a transverse subtrochanteric shortening osteotomy and fixation using double tension-band wiring to treat severe (Crowe III or IV) developmental hip dysplasia. The femoral implant was a long, ovoid, cementless stem fully coated with hydroxyapatite. We collected the intraoperative and postoperative complications, survival, LLLI, functional scores (Harris Hip Score [HHS] and Forgotten Joint Score [FJS]), patient satisfaction, and radiographic outcomes. RESULTS: The study included 31 hips in 25 patients. Two patients (2/31 hips, 6.5%) were lost to follow-up, leaving 29 hips for the analysis of postoperative outcomes. Mean follow-up was 13.7±4.2 years (range, 5.8-18.3 years). The four intraoperative complications (4/31, 12.9%) consisted fracture of the diaphysis (2/31, 6.5%), fracture of the greater trochanter (1/31, 3.2%), and sciatic nerve injury followed by a full recovery (1/29, 3.4%). The 8 (8/29, 27.5%) postoperative complications consisted of dislocation (2/29, 6.9%), stem subsidence (2/29, 6.9%), and non-union (4/29, 13.8%). Femoral implant survival at last follow-up was 87.1% (95% CI, 76.1-99.7). The mean HHS increased from 39.6±12.0 (range, 14-61) before surgery to 81.7±13.2 (range, 48-100) at last follow-up (p<0.01). The FJS at last follow-up indicated that the joint was forgotten in 14/29 (48.2%) cases and caused only acceptable symptoms in 9/29 (31.0%) of cases. Clinically significant (≥ 1cm) LLLI was present in 8/29 (27.6%) patients postoperatively compared to 19/29 (65.5%) preoperatively. The mean LLLI decreased from 20.8±19.7mm (range, 0-60mm) to 5.0±7.3mm (range, 0-30mm). Mean time to healing was 4.3±2.4 months (range, 2-11 months). CONCLUSION: Regarding these complex procedures, this technique was associated with low rates of intraoperative fractures and early postoperative complications. However, femoral stem survival was shorter than in earlier studies and the non-union rate was high, despite satisfactory functional and clinical outcomes.
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Artroplastia de Reemplazo de Cadera , Luxación Congénita de la Cadera , Luxaciones Articulares , Humanos , Artroplastia de Reemplazo de Cadera/métodos , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/cirugía , Luxación Congénita de la Cadera/complicaciones , Estudios Retrospectivos , Fémur/cirugía , Complicaciones Posoperatorias/cirugía , Luxaciones Articulares/cirugía , Osteotomía/métodos , Extremidad Inferior/cirugía , Complicaciones Intraoperatorias , Estudios de SeguimientoRESUMEN
OBJECTIVES: Two limitations of the clinical use of 3-dimensional (3D) reconstruction and virtual reality systems are the relatively high cost and the amount of experience required to use hardware and software to effectively explore medical images. We have tried to simplify the process and validate a new tool developed for this purpose with a novel software package. METHODS: Five patients with right partial anomalous pulmonary venous return with adequate preoperative images acquired with magnetic resonance imaging were enrolled. Five volunteers with no previous experience in the field of 3D reconstruction were instructed to use the software after viewing a short video tutorial. Users were then asked to create a 3D model of each patient's heart using DIVA software. Their results were compared quantitatively and qualitatively with a benchmark reconstruction performed by an experienced user. RESULTS: All our participants recreated 3D models in a relatively short time, maintaining a good overall quality (average quality score ≥ 3 on a scale of 1-5). The overall trend of all the parameters analysed showed a statistical improvement between case 1 and case 5, as users became more and more experienced. CONCLUSIONS: DIVA is a simple software program that allows accurate 3D reconstruction in a relatively short time ("fast-track" virtual reality). In this study, we demonstrated the potential use of DIVA by inexperienced users, with a significant improvement in quality and time after a few cases were performed. Further studies are needed to confirm the potential application of this technology on a larger scale.
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INTRODUCTION: The Extreme™ modular stem was developed for implant revision with metaphyseal-diaphyseal defect. Due to the high breakage rate, a new "reduced modularity" design has been introduced, but without reported results. We therefore conducted a retrospective assessment of (1) overall stem survival, (2) functional results, (3) osseointegration, and (4) the rate of complications, and notably of mechanical failure. HYPOTHESIS: Reduced modularity reduces the risk of revision surgery for mechanical failure. MATERIAL AND METHODS: Forty-five prostheses were implanted between January 2007 and December 2010 in 42 patients with severe bone defect (Paprosky≥III) or periprosthetic shaft fracture. Mean age was 69.6years (range: 44-91years). Minimum follow-up was 5years, for a mean 115.4months (range: 60-156months). The main study endpoint was femoral stem survival, counting all-cause explantation as event. Functional assessment comprised subjective rating of satisfaction, Postel Merle d'Aubigné (PMA) and Harris Hip scores, and Forgotten Joint Score (FJS). Whether the revision assembly was carried out in situ, in the patient's hip, or outside, on the operating table, was not known in 2 cases; in the other 43, assembly was in situ in 15 cases (35%) and on the operating table in 28 (65%). RESULTS: Five-year stem survival was 75.7% (95% CI: 61.9-89.5%), taking all causes of change together. Seventeen patients (45.9%) had complications, 13 (35.1%) requiring revision surgery, including 10 (27.0%) for stem replacement. Five patients (13.5%) had steam breakage at the junction between the metaphysis and the diaphyseal stem, 4 of which occurred within 2 years of implantation or of fixation of a periprosthetic fracture. Mean preoperative Harris score was 48.4 [IQR (25-75% interquartile range): 37-58] and PMA score 11.1 (IQR: 10-12), compared to respectively 74 (IQR: 67-89) and 13.6 (IQR: 12.5-16) at follow-up. Mean FJS at follow-up was 71.5 (IQR: 61-94.5). In the 15 in situ assemblies, there were 3 breakages (20%), compared to 2 (7.1%) in the 28 table assemblies (p=0.21). DISCUSSION: The stem breakage rate was high despite the reduced modularity, which concentrated all stress on a single junction but without reducing the risk of mechanical failure. Surgical technique was faulty in some cases, with in situ assembly of the metaphysis after implanting the diaphyseal stem, which does not respect the manufacturer's recommendations. LEVEL OF EVIDENCE: IV; retrospective study.
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Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Fracturas Periprotésicas , Humanos , Anciano , Artroplastia de Reemplazo de Cadera/métodos , Prótesis de Cadera/efectos adversos , Estudios Retrospectivos , Estudios de Seguimiento , Falla de Prótesis , Fracturas Periprotésicas/cirugía , Fracturas Periprotésicas/etiología , Reoperación/efectos adversos , Diseño de Prótesis , Resultado del TratamientoRESUMEN
Numerous models have been developed to account for the complex properties of the random walks of biomolecules. However, when analysing experimental data, conditions are rarely met to ensure model identification. The dynamics may simultaneously be influenced by spatial and temporal heterogeneities of the environment, out-of-equilibrium fluxes and conformal changes of the tracked molecules. Recorded trajectories are often too short to reliably discern such multi-scale dynamics, which precludes unambiguous assessment of the type of random walk and its parameters. Furthermore, the motion of biomolecules may not be well described by a single, canonical random walk model. Here, we develop a two-step statistical testing scheme for comparing biomolecule dynamics observed in different experimental conditions without having to identify or make strong prior assumptions about the model generating the recorded random walks. We first train a graph neural network to perform simulation-based inference and thus learn a rich summary statistics vector describing individual trajectories. We then compare trajectories obtained in different biological conditions using a non-parametric maximum mean discrepancy (MMD) statistical test on their so-obtained summary statistics. This procedure allows us to characterise sets of random walks regardless of their generating models, without resorting to model-specific physical quantities or estimators. We first validate the relevance of our approach on numerically simulated trajectories. This demonstrates both the statistical power of the MMD test and the descriptive power of the learnt summary statistics compared to estimates of physical quantities. We then illustrate the ability of our framework to detect changes in α-synuclein dynamics at synapses in cultured cortical neurons, in response to membrane depolarisation, and show that detected differences are largely driven by increased protein mobility in the depolarised state, in agreement with previous findings. The method provides a means of interpreting the differences it detects in terms of single trajectory characteristics. Finally, we emphasise the interest of performing various comparisons to probe the heterogeneity of experimentally acquired datasets at different levels of granularity (e.g., biological replicates, fields of view, and organelles).
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Redes Neurales de la Computación , Proteínas , Simulación por Computador , Movimiento (Física) , Proteínas/químicaRESUMEN
We introduce a simulation-based, amortized Bayesian inference scheme to infer the parameters of random walks. Our approach learns the posterior distribution of the walks' parameters with a likelihood-free method. In the first step a graph neural network is trained on simulated data to learn optimized low-dimensional summary statistics of the random walk. In the second step an invertible neural network generates the posterior distribution of the parameters from the learned summary statistics using variational inference. We apply our method to infer the parameters of the fractional Brownian motion model from single trajectories. The computational complexity of the amortized inference procedure scales linearly with trajectory length, and its precision scales similarly to the Cramér-Rao bound over a wide range of lengths. The approach is robust to positional noise, and generalizes to trajectories longer than those seen during training. Finally, we adapt this scheme to show that a finite decorrelation time in the environment can furthermore be inferred from individual trajectories.
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Microscopy image observation is commonly performed on 2D screens, which limits human capacities to grasp volumetric, complex, and discrete biological dynamics. With the massive production of multidimensional images (3D + time, multi-channels) and derived images (e.g., restored images, segmentation maps, and object tracks), scientists need appropriate visualization and navigation methods to better apprehend the amount of information in their content. New modes of visualization have emerged, including virtual reality (VR)/augmented reality (AR) approaches which should allow more accurate analysis and exploration of large time series of volumetric images, such as those produced by the latest 3D + time fluorescence microscopy. They include integrated algorithms that allow researchers to interactively explore complex spatiotemporal objects at the scale of single cells or multicellular systems, almost in a real time manner. In practice, however, immersion of the user within 3D + time microscopy data represents both a paradigm shift in human-image interaction and an acculturation challenge, for the concerned community. To promote a broader adoption of these approaches by biologists, further dialogue is needed between the bioimaging community and the VR&AR developers.
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Learning which stimuli (classical conditioning) or which actions (operant conditioning) predict rewards or punishments can improve chances of survival. However, the circuit mechanisms that underlie distinct types of associative learning are still not fully understood. Automated, high-throughput paradigms for studying different types of associative learning, combined with manipulation of specific neurons in freely behaving animals, can help advance this field. The Drosophila melanogaster larva is a tractable model system for studying the circuit basis of behaviour, but many forms of associative learning have not yet been demonstrated in this animal. Here, we developed a high-throughput (i.e. multi-larva) training system that combines real-time behaviour detection of freely moving larvae with targeted opto- and thermogenetic stimulation of tracked animals. Both stimuli are controlled in either open- or closed-loop, and delivered with high temporal and spatial precision. Using this tracker, we show for the first time that Drosophila larvae can perform classical conditioning with no overlap between sensory stimuli (i.e. trace conditioning). We also demonstrate that larvae are capable of operant conditioning by inducing a bend direction preference through optogenetic activation of reward-encoding serotonergic neurons. Our results extend the known associative learning capacities of Drosophila larvae. Our automated training rig will facilitate the study of many different forms of associative learning and the identification of the neural circuits that underpin them.
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Condicionamiento Operante , Drosophila , Animales , Condicionamiento Operante/fisiología , Drosophila/fisiología , Larva/fisiología , Drosophila melanogaster/fisiología , Condicionamiento Clásico/fisiologíaRESUMEN
MOTIVATION: Single-molecule localization microscopy allows studying the dynamics of biomolecules in cells and resolving the biophysical properties of the molecules and their environment underlying cellular function. With the continuously growing amount of data produced by individual experiments, the computational cost of quantifying these properties is increasingly becoming the bottleneck of single-molecule analysis. Mining these data requires an integrated and efficient analysis toolbox. RESULTS: We introduce TRamWAy, a modular Python library that features: (i) a conservative tracking procedure for localization data, (ii) a range of sampling techniques for meshing the spatio-temporal support of the data, (iii) computationally efficient solvers for inverse models, with the option of plugging in user-defined functions and (iv) a collection of analysis tools and a simple web-based interface. AVAILABILITY AND IMPLEMENTATION: TRamWAy is a Python library and can be installed with pip and conda. The source code is available at https://github.com/DecBayComp/TRamWAy.
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Programas Informáticos , Movimiento (Física)RESUMEN
Hematopoietic stem cell transplantation (HSCT) is a therapy used for multiple malignant and nonmalignant diseases, with chemotherapy used for pretransplantation myeloablation. The post-HSCT brain contains peripheral engrafted parenchymal macrophages, despite their absence in the normal brain, with the engraftment mechanism still undefined. Here we show that HSCT chemotherapy broadly disrupts mouse brain regenerative populations, including a permanent loss of adult neurogenesis. Microglial density was halved, causing microglial process expansion, coinciding with indicators of broad senescence. Although microglia expressed cell proliferation markers, they underwent cell cycle arrest in S phase with a majority expressing the senescence and antiapoptotic marker p21. In vivo single-cell tracking of microglia after recovery from chemical depletion showed loss of their regenerative capacity, subsequently replaced with donor macrophages. We propose that HSCT chemotherapy causes microglial senescence with a gradual decrease to a critical microglial density, providing a permissive niche for peripheral macrophage engraftment of the brain.
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Trasplante de Células Madre Hematopoyéticas , Microglía , Animales , Encéfalo , Macrófagos , Ratones , Acondicionamiento PretrasplanteRESUMEN
PURPOSE: The treatment of breast cancer, the leading cause of cancer and cancer mortality among women worldwide, is mainly on the basis of surgery. In this study, we describe the use of a medical image visualization tool on the basis of virtual reality (VR), entitled DIVA, in the context of breast cancer tumor localization among surgeons. The aim of this study was to evaluate the speed and accuracy of surgeons using DIVA for medical image analysis of breast magnetic resonance image (MRI) scans relative to standard image slice-based visualization tools. MATERIALS AND METHODS: In our study, residents and practicing surgeons used two breast MRI reading modalities: the common slice-based radiology interface and the DIVA system in its VR mode. Metrics measured were compared in relation to postoperative anatomical-pathologic reports. RESULTS: Eighteen breast surgeons from the Institut Curie performed all the analysis presented. The MRI analysis time was significantly lower with the DIVA system than with the slice-based visualization for residents, practitioners, and subsequently the entire group (P < .001). The accuracy of determination of which breast contained the lesion significantly increased with DIVA for residents (P = .003) and practitioners (P = .04). There was little difference between the DIVA and slice-based visualization for the determination of the number of lesions. The accuracy of quadrant determination was significantly improved by DIVA for practicing surgeons (P = .01) but not significantly for residents (P = .49). CONCLUSION: This study indicates that the VR visualization of medical images systematically improves surgeons' analysis of preoperative breast MRI scans across several different metrics irrespective of surgeon seniority.
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Neoplasias de la Mama , Cirujanos , Realidad Virtual , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Deviations from Brownian motion leading to anomalous diffusion are found in transport dynamics from quantum physics to life sciences. The characterization of anomalous diffusion from the measurement of an individual trajectory is a challenging task, which traditionally relies on calculating the trajectory mean squared displacement. However, this approach breaks down for cases of practical interest, e.g., short or noisy trajectories, heterogeneous behaviour, or non-ergodic processes. Recently, several new approaches have been proposed, mostly building on the ongoing machine-learning revolution. To perform an objective comparison of methods, we gathered the community and organized an open competition, the Anomalous Diffusion challenge (AnDi). Participating teams applied their algorithms to a commonly-defined dataset including diverse conditions. Although no single method performed best across all scenarios, machine-learning-based approaches achieved superior performance for all tasks. The discussion of the challenge results provides practical advice for users and a benchmark for developers.
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Neural stem cell (NSC) populations persist in the adult vertebrate brain over a lifetime, and their homeostasis is controlled at the population level through unknown mechanisms. Here, we combine dynamic imaging of entire NSC populations in their in vivo niche over several weeks with pharmacological manipulations, mathematical modeling, and spatial statistics and demonstrate that NSCs use spatiotemporally resolved local feedback signals to coordinate their decision to divide in adult zebrafish brains. These involve Notch-mediated short-range inhibition from transient neural progenitors and a dispersion effect from the dividing NSCs themselves exerted with a delay of 9-12 days. Simulations from a stochastic NSC lattice model capturing these interactions demonstrate that these signals are linked by lineage progression and control the spatiotemporal distribution of output neurons. These results highlight how local and temporally delayed interactions occurring between brain germinal cells generate self-propagating dynamics that maintain NSC population homeostasis and coordinate specific spatiotemporal correlations.
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Células-Madre Neurales , Neurogénesis , Animales , Encéfalo , Proliferación Celular , Retroalimentación , Pez CebraRESUMEN
BACKGROUND AND AIM OF THE STUDY: We sought to evaluate the appropriateness of cardiac anatomy renderings by a new virtual reality (VR) technology, entitled DIVA, directly applicable to raw magnetic resonance imaging (MRI) data without intermediate segmentation steps in comparison to standard three-dimensional (3D) rendering techniques (3D PDF and 3D printing). Differences in post-processing times were also evaluated. METHODS: We reconstructed 3D (STL, 3D-PDF, and 3D printed ones) and VR models of three patients with different types of complex congenital heart disease (CHD). We then asked a senior pediatric heart surgeon to compare and grade the results obtained. RESULTS: All anatomical structures were well visualized in both VR and 3D PDF/printed models. Ventricular-arterial connections and their relationship with the great vessels were better visualized with the VR model (Case 2); aortic arch anatomy and details were also better visualized by the VR model (Case 3). The median post-processing time to get VR models using DIVA was 5 min in comparison to 8 h (range 8-12 h including printing time) for 3D models (PDF/printed). CONCLUSIONS: VR directly applied to non-segmented 3D-MRI data set is a promising technique for 3D advanced modeling in CHD. It is systematically more consistent and faster when compared to standard 3D-modeling techniques.