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In this paper, we present the novel Deep-MEG approach in which image-based representations of magnetoencephalography (MEG) data are combined with ensemble classifiers based on deep convolutional neural networks. For the scope of predicting the early signs of Alzheimer’s disease (AD), functional connectivity (FC) measures between the brain bio-magnetic signals originated from spatially separated brain regions are used as MEG data representations for the analysis. After stacking the FC indicators relative to different frequency bands into multiple images, a deep transfer learning model is used to extract different sets of deep features and to derive improved classification ensembles. The proposed Deep-MEG architectures were tested on a set of resting-state MEG recordings and their corresponding magnetic resonance imaging scans, from a longitudinal study involving 87 subjects. Accuracy values of 89% and 87% were obtained, respectively, for the early prediction of AD conversion in a sample of 54 mild cognitive impairment subjects and in a sample of 87 subjects, including 33 healthy controls. These results indicate that the proposed Deep-MEG approach is a powerful tool for detecting early alterations in the spectral–temporal connectivity profiles and in their spatial relationships.

Organ-on-chip and tumor-on-chip microfluidic cell cultures represent a fast-growing research field for modelling organ functions and diseases, for drug development, and for promising applications in personalized medicine. Still, one of the bottlenecks of this technology is the analysis of the huge amount of bio-images acquired in these dynamic 3D microenvironments, a task that we propose to achieve by exploiting the interdisciplinary contributions of computer science and electronic engineering. In this work, we apply this strategy to the study of oncolytic vaccinia virus (OVV), an emerging agent in cancer immunotherapy. Infection and killing of cancer cells by OVV were recapitulated and directly imaged in tumor-on-chip. By developing and applying appropriate image analysis strategies and advanced automatic algorithms, we uncovered synergistic cooperation of OVV and immune cells to kill cancer cells. Moreover, we observed that the kinetics of immune cells were modified in presence of OVV and that these immune modulations varied during the course of infection. A correlation between cancer cell infection and cancer-immune interaction time was pointed out, strongly supporting a cause-effect relationship between infection of cancer cells and their recognition by the immune cells. These results shed new light on the mode of action of OVV, and suggest new clinical avenues for immunotherapy developments.

Pain is an alert state of the human body that can be conveyed to the external world through different modalities. A possible communication channel for human pain is represented by facial expressions, whose role in social interactions has been well established. In this work, the link between pain and transfer entropy (TE), passing through facial expressions, is investigated. A new approach to the vision-based measurement (VBM) of pain is presented, which is based on TE among the time-series of facial landmarks positions. The system is composed of three main blocks: A VBM block for the automatic landmarking and the generation of the time-series from the video-sequences; a second block for the evaluation of TE; and finally a classification model based on machine learning algorithms for pain assessment. A public database of video sequences of patients experiencing pain in a controlled scenario was used for the characterization of the system in terms of accuracy and precision. Different uncertainty contributions related to realistic signals interruptions and fluctuations were modeled and propagated to provide a comprehensive evaluation of the proposed measurement system. The obtained results indicate that TE-based approaches can provide great benefits in automatic pain assessment, opening new perspectives for remote management of patients.

The incremented uptake provided by time-lapse microscopy in Organ-on-a-Chip (OoC) devices allowed increased attention to the dynamics of the co-cultured systems. However, the amount of information stored in long-time experiments may constitute a serious bottleneck of the experimental pipeline. Forward long-term prediction of cell trajectories may reduce the spatial–temporal burden of video sequences storage. Cell trajectory prediction becomes crucial especially to increase the trustworthiness in software tools designed to conduct a massive analysis of cell behavior under chemical stimuli. To address this task, we transpose here the exploitation of the presence of “social forces” from the human to the cellular level for motion prediction at microscale by adapting the potential of Social Generative Adversarial Network predictors to cell motility. To demonstrate the effectiveness of the approach, we consider here two case studies: one related to PC-3 prostate cancer cells cultured in 2D Petri dishes under control and treated conditions and one related to an OoC experiment of tumor-immune interaction in fibrosarcoma cells. The goodness of the proposed strategy has been verified by successfully comparing the distributions of common descriptors (kinematic descriptors and mean interaction time for the two scenarios respectively) from the trajectories obtained by video analysis and the predicted counterparts.

We describe a novel method to achieve a universal, massive, and fully automated analysis of cell motility behaviours, starting from time-lapse microscopy images. The approach was inspired by the recent successes in application of machine learning for style recognition in paintings and artistic style transfer. The originality of the method relies i) on the generation of atlas from the collection of single-cell trajectories in order to visually encode the multiple descriptors of cell motility, and ii) on the application of pre-trained Deep Learning Convolutional Neural Network architecture in order to extract relevant features to be used for classification tasks from this visual atlas. Validation tests were conducted on two different cell motility scenarios: 1) a 3D biomimetic gels of immune cells, co-cultured with breast cancer cells in organ-on-chip devices, upon treatment with an immunotherapy drug; 2) Petri dishes of clustered prostate cancer cells, upon treatment with a chemotherapy drug. For each scenario, single-cell trajectories are very accurately classified according to the presence or not of the drugs. This original approach demonstrates the existence of universal features in cell motility (a so called “motility style”) which are identified by the DL approach in the rationale of discovering the unknown message in cell trajectories.

Organ-on-chip (OOC) devices are miniaturized devices replacing animal models in drug discovery and toxicology studies. The majority of OOC devices are made from polydimethylsiloxane (PDMS), an elastomer widely used in microfluidic prototyping, but posing a number of challenges to experimentalists, including leaching of uncured oligomers and uncontrolled absorption of small compounds. Here we assess the suitability of polylactic acid (PLA) as a replacement material to PDMS for microfluidic cell culture and OOC applications. We changed the wettability of PLA substrates and demonstrated the functionalization method to be stable over a time period of at least 9 months. We successfully cultured human cells on PLA substrates and devices, without coating. We demonstrated that PLA does not absorb small molecules, is transparent (92% transparency), and has low autofluorescence. As a proof of concept of its manufacturability, biocompatibility, and transparency, we performed a cell tracking experiment of prostate cancer cells in a PLA device for advanced cell culture.

Facial expression is an important component of the pain measurement process, which can be utilized by clinicians in patients with impaired communicative or cognitive abilities. However, given the complex nature of the pain and the absence of a standard reference, accurate measurement of pain in hospital settings is a difficult practice. In this paper, we present a vision-based measurement system aimed at automatically measuring the pain intensity values through the analysis of the facial expression, based on deep-learning strategies. For the scope of providing a metrological characterization of the system, we designed a benchmark for the estimation of the measurement precision via multiexpert judgments. As a major contribution of this paper, we investigated the interobserver and intraobserver variability as sources of uncertainty at the calibration level in order to provide a robust pain estimation via an automatic framework. Reproducibility and standard reference uncertainty (due to interobserver and intraobserver variability, respectively) have been estimated, modeled, and propagated through the proposed platform using the Guide to the expression of Uncertainty in Measurement (GUM)-compliant procedures. Numerical results, provided in terms of average values and confidence intervals of the accuracy of classification, indicate that such a system can facilitate decision-making in healthcare. Moreover, the proposed benchmark offers new hints to incorporate, rationally, subjective expert judgments within automatic measurement systems.

Vision-based measurement (VBM) systems are powerful tool to extract quantitative information by acquiring video sequence or static images. When a VBM is applied to the evaluation of nominal properties, such as image characteristics, the term VBM is substituted with vision-based evaluation (VBE) by extending the framework of operation unit to a new concept of evaluation unit (EU) for the image analysis and machine learning phases. To this regard, deep learning (DL) approaches have gained an exponential interest in the research and industrial community, thanks to incredible flexibility toward visual words and the possibility to abandon subjective feature extraction procedures. From such an explosiveness of applications, it emerges the need to conduct studies on the capability of DL strategies to deal with uncertainty contributions, i.e., definitional uncertainty related to the measurand and reference uncertainty that may occur during the calibration process. In order to present a benchmark platform to analyze the effect of the major sources of uncertainties estimated, we use here an atomic force microscopy (AFM) imaging scenario for the evaluation of the effect of nanoparticles exposure on human cells in the laboratory. These studies are nowadays fundamental in toxicity analysis for monitoring the health conditions of workers and for protecting people from atherosclerosis disease. The performance of the proposed VBE-DL system to recognize cell alterations from the AFM images is related to three different sources of uncertainty and a critical analysis of the results achieved is provided.

Cell-cell interactions are an observable manifestation of underlying complex biological processes occurring in response to diversified biochemical stimuli. Recent experiments with microfluidic devices and live cell imaging show that it is possible to characterize cell kinematics via computerized algorithms and unravel the effects of targeted therapies. We study the influence of spatial and temporal resolutions of time-lapse videos on motility and interaction descriptors with computational models that mimic the interaction dynamics among cells. We show that the experimental set-up of time-lapse microscopy has a direct impact on the cell tracking algorithm and on the derived numerical descriptors. We also show that, when comparing kinematic descriptors in two diverse experimental conditions, too low resolutions may alter the descriptors’ discriminative power, and so the statistical significance of the difference between the two compared distributions. The conclusions derived from the computational models were experimentally confirmed by a series of video-microscopy acquisitions of co-cultures of unlabelled human cancer and immune cells embedded in 3D collagen gels within microfluidic devices. We argue that the experimental protocol of acquisition should be adapted to the specific kind of analysis involved and to the chosen descriptors in order to derive reliable conclusions and avoid biasing the interpretation of results.

Motivation In fluorescence microscopy, single-molecule localization microscopy (SMLM) techniques aim at localizing with high-precision high-density fluorescent molecules by stochastically activating and imaging small subsets of blinking emitters. Super resolution plays an important role in this field since it allows to go beyond the intrinsic light diffraction limit. Results In this work, we propose a deep learning-based algorithm for precise molecule localization of high-density frames acquired by SMLM techniques whose ℓ2-based loss function is regularized by non-negative and ℓ0-based constraints. The ℓ0 is relaxed through its continuous exact ℓ0 (CEL0) counterpart. The arising approach, named DeepCEL0, is parameter-free, more flexible, faster and provides more precise molecule localization maps if compared to the other state-of-the-art methods. We validate our approach on both simulated and real fluorescence microscopy data. Availability and implementation DeepCEL0 code is freely accessible at https://github.com/sedaboni/DeepCEL0.

The dynamic contrast-enhanced MR imaging plays a crucial role in evaluating the effectiveness of neoadjuvant chemotherapy (NAC) even since its early stage through the prediction of the final pathological complete response (pCR). In this study, we proposed a transfer learning approach to predict if a patient achieved pCR (pCR) or did not (non-pCR) by exploiting, separately or in combination, pre-treatment and early-treatment exams from I-SPY1 TRIAL public database. First, low-level features, i.e., related to local structure of the image, were automatically extracted by a pre-trained convolutional neural network (CNN) overcoming manual feature extraction. Next, an optimal set of most stable features was detected and then used to design an SVM classifier. A first subset of patients, called fine-tuning dataset (30 pCR; 78 non-pCR), was used to perform the optimal choice of features. A second subset not involved in the feature selection process was employed as an independent test (7 pCR; 19 non-pCR) to validate the model. By combining the optimal features extracted from both pre-treatment and early-treatment exams with some clinical features, i.e., ER, PgR, HER2 and molecular subtype, an accuracy of 91.4% and 92.3%, and an AUC value of 0.93 and 0.90, were returned on the fine-tuning dataset and the independent test, respectively. Overall, the low-level CNN features have an important role in the early evaluation of the NAC efficacy by predicting pCR. The proposed model represents a first effort towards the development of a clinical support tool for an early prediction of pCR to NAC.

Anemia; Microfluídica; Enfermedad de células falciformes Anèmia; Microfluídica; Malaltia de cèl·lules falciformes Anaemia; Microfluidics; Sickle cell disease Combining microfluidics technology with machine learning represents an innovative approach to conduct massive quantitative cell behavior study and implement smart decision-making systems in support of clinical diagnostics. The spleen plays a key-role in rare hereditary hemolytic anemia (RHHA), being the organ responsible for the premature removal of defective red blood cells (RBCs). The goal is to adapt the physiological spleen filtering strategy for in vitro study and monitoring of blood diseases through RBCs shape analysis. Then, a microfluidic device mimicking the slits of the spleen red pulp area and video data analysis are combined for the characterization of RBCs in RHHA. This microfluidic unit is designed to evaluate RBC deformability by maintaining them fixed in planar orientation, allowing the visual inspection of RBC’s capacity to restore their original shape after crossing microconstrictions. Then, two cooperative learning approaches are used for the analysis: the majority voting scheme, in which the most voted label for all the cell images is the class assigned to the entire video; and the maximum sum of scores to decide the maximally scored class to assign. The proposed platform shows the capability to discriminate healthy controls and patients with an average efficiency of 91%, but also to distinguish between RHHA subtypes, with an efficiency of 82%. This work was supported by Networking Biomedical Research Center (CIBER), Spain. CIBER is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund. This work was funded by the European Commission H2020-MSCA-ITN-2019, Grant Agreement N860436, “EVIDENCE” and by the CERCA Programme and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017 SGR 1079), it has been developed in the context of AdvanceCat with the support of ACCIÓ (Catalonia Trade and Investment; Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund) 2014–2020.

Summary One of the most challenging frontiers in biological systems understanding is fluorescent label-free imaging. We present here the NeuriTES platform that revisits the standard paradigms of video analysis to detect unlabeled objects and adapt to the dynamic evolution of the phenomenon under observation. Object segmentation is reformulated using robust algorithms to assure regular cell detection and transfer entropy measures are used to study the inter-relationship among the parameters related to the evolving system. We applied the NeuriTES platform to the automatic analysis of neurites degeneration in presence of amyotrophic lateral sclerosis (ALS) and to the study of the effects of a chemotherapy drug on living prostate cancer cells (PC3) cultures. Control cells have been considered in both the two cases study. Accuracy values of 93% and of 92% are achieved, respectively. NeuriTES not only represents a tool for investigation in fluorescent label-free images but demonstrates to be adaptable to individual needs., Highlights • Monitoring of cell phenotype changes by fluorescence label-free time-lapse microscopy • Adaptive semantic segmentation for the robust detection of cell shape • TE to correlate morphological and textural soma descriptors along time • Directed TE graph for the representation of mutual relationship among descriptors, The bigger picture One of the most challenging frontiers for the automatic understanding of biological systems is fluorescent label-free imaging in which the behavior changes of living being are characterized without cell staining. To this aim, we present here the NeuriTES platform that revisits standard paradigms of video analysis to detect unlabeled objects and correlate the analysis to phenotype evolution of the mechanisms under observation. Through the exploitation of adaptive algorithms and of transfer entropy measures, the platform assures regular cell detection and the possibility to extract reliable parameters related to the evolving cell system. As a proof-of-concept, NeuriTES is applied to two fascinating phenotype investigation scenarios, amyotrophic lateral sclerosis (ALS) disease mechanism and the study of the effects of a chemotherapy drug on living prostate cancer cells (PC3) cultures. Directed graphs assist the biologists with a visual understanding of the mechanisms identified., Nowadays, observational traits (phenotype) of biological entities complement with genomics offering the possibility to monitor phenomenon evolutions and underlying mechanism (neurodegeneration, cancer cell replication, etc.). By complementing video, data analysis, and machine learning approaches with label-free time-lapse microscopy, NeuriTES tool allows automatically analyzing such traits and extracting as outcomes proof of concepts and visual graph-based representation of the phenotypical rationale behind.

Simple Summary An early prediction of Breast Cancer Recurrence (BCR) for patients undergoing neoadjuvant chemotherapy (NACT) could better guide clinicians in the identification of the most suitable combination treatments for individual patient scenarios. We proposed a transfer learning approach to give an early prediction of three-year BCR for patients undergoing NACT, using DCE-MRI exams from I-SPY1 TRIAL and BREAST-MRI-NACT-Pilot public databases. Because no technical expertise is required in the extraction of meaningful features from images, the predictive model qualifies as a user-friendly tool for any medical expert in support of therapeutic choices. Only pre-treatment and early-treatment MRI examinations were analyzed to allow for potential therapy changes at a very early stage of treatment. We tested the strength of the model on an independent test. The best predictive performances (accuracy of 85.2%, sensitivity of 84.6%, and AUC of 0.83) were achieved by combining the extracted features with some clinical factors: age, ER, PgR, HER2+. Abstract Cancer treatment planning benefits from an accurate early prediction of the treatment efficacy. The goal of this study is to give an early prediction of three-year Breast Cancer Recurrence (BCR) for patients who underwent neoadjuvant chemotherapy. We addressed the task from a new perspective based on transfer learning applied to pre-treatment and early-treatment DCE-MRI scans. Firstly, low-level features were automatically extracted from MR images using a pre-trained Convolutional Neural Network (CNN) architecture without human intervention. Subsequently, the prediction model was built with an optimal subset of CNN features and evaluated on two sets of patients from I-SPY1 TRIAL and BREAST-MRI-NACT-Pilot public databases: a fine-tuning dataset (70 not recurrent and 26 recurrent cases), which was primarily used to find the optimal subset of CNN features, and an independent test (45 not recurrent and 17 recurrent cases), whose patients had not been involved in the feature selection process. The best results were achieved when the optimal CNN features were augmented by four clinical variables (age, ER, PgR, HER2+), reaching an accuracy of 91.7% and 85.2%, a sensitivity of 80.8% and 84.6%, a specificity of 95.7% and 85.4%, and an AUC value of 0.93 and 0.83 on the fine-tuning dataset and the independent test, respectively. Finally, the CNN features extracted from pre-treatment and early-treatment exams were revealed to be strong predictors of BCR.

Combining microfluidics technology with machine learning represents an innovative approach to conduct massive quantitative cell behavior study and implement smart decision-making systems in support of clinical diagnostics. The spleen plays a key-role in rare hereditary hemolytic anemia (RHHA), being the organ responsible for the premature removal of defective red blood cells (RBCs). The goal is to adapt the physiological spleen filtering strategy for in vitro study and monitoring of blood diseases through RBCs shape analysis. Then, a microfluidic spleen-like filtering unit and video data analysis are combined for the characterization of RBCs in RHHA. A filtering unit is designed to measure deformability by maintaining fixed the RBC orientation to study its capacity of restoring the original shape after crossing microconstrictions. Two cooperative learning approaches are used for the analysis: the majority voting scheme, in which the most voted label for all the cell images is the class assigned to the entire video; and the maximum sum of scores to decide the maximally scored class to assign. The proposed platform shows the capability to discriminate healthy controls and patients with an average efficiency of 91%, but also to distinguish between RHHA subtypes, with an efficiency of 82%.

The blood-brain barrier (BBB) is a dynamic cellular barrier that regulates brain nutrient supply, waste efflux, and paracellular diffusion through specialized junctional complexes. Finding a system to mimic and monitor BBB integrity (i.e., to be able to assess the effect of certain compounds on opening or closing the barrier) is of vital importance in several pathologies. This work aims to overcome some limitations of current barrier integrity measuring techniques thanks to a multi-layer microfluidic platform with integrated electrodes and Multi-frequency Trans-Endothelial Electrical Resistance (MTEER) in synergy with machine learning algorithms. MTEER measurements are performed across the barrier in a range of frequencies up to 10 MHz highlighting the presence of information on different frequency ranges. Results show that the proposed platform can detect barrier formation, opening, and regeneration afterwards, correlating with the results obtained from immunostaining of junctional complexes. This model presents novel techniques for a future biological barrier in-vitro studies that could potentially help on elucidating barrier opening or sealing on treatments with different drugs., This work was supported by Networking Biomedical Research Center (CIBER), Spain. CIBER is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund. This work was funded by the CERCA Programme and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017 SGR 1079). This work has been developed in the context of AdvanceCat with the support of ACCIÓ (Catalonia Trade and Investment; Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund) 2014–2020. This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the projects MINDS (Proyectos I + D Excelencia + FEDER) TEC2015-70104-P, CTQ2016-75870-P, BIOBOT (Programa Explora Ciencia / Tecnología), TEC2015- 72718-EXP and RTI2018-097038-B-C21.

Background Optical technologies, relying on spectral analysis, are more and more implemented in portable devices for food analysis. Thereby, each food safety, quality or authenticity provision as well as each technology requires the generation of a dedicated spectral database with reference data. Currently, knowledge on how these databases might be connected or transferred across food commodities, targeted compounds or devices are very limited. Hence, repetitive work is conducted and technologies are not optimally used. Scope and approach This perspective focuses on the currently available technologies and approaches for data handling and database transfer across miniaturized devices and technologies for food safety, quality and authenticity assessments. Key findings and conclusions For almost every food commodity or target compound a miniaturized spectroscopic device can be applied with the respective database to compare findings. Recent developments in optical spectroscopy allow more possibilities for their use as well as facilitate the production of portable devices. A multifunctional device hyphenating several sensors and broadening the application range is still not marketed. Newly developed software architecture, accessing and extracting data, helps to overcome sample heterogenicity or spurious measured data. In addition, several data fusion approaches using machine learning and deep learning strategies are available to fuse spectroscopic data with itself or other non-spectroscopic data. Following the research results presented in this field, spectral data can possibly be re-used and shared across instruments and locations, highly increasing the applicability of data sets. Thereby, obstacles such as policy or confidentiality are taken into account.

Background: A Critical Shoulder Angle (CSA), evaluated on plain radiographs, greater than 35&deg, is considered predictive of rotator cuff tears. The present prospective comparative study aimed, firstly, to develop a formula to calculate the amount of acromion that should be resected performing a lateral acromioplasty and, secondly, verify whether lateral acromioplasty to reduce the CSA associated with arthroscopic cuff repair decreased the rate of recurrence of the tears, and impacted favorably on clinical postoperative outcomes. Methods: Patients undergoing arthroscopic rotator cuff repair (RCR) for rotator cuff tears with a CSA greater than 35&deg, were included in this study and divided into two groups, based on whether the CSA had been reduced by arthroscopic resection of the lateral portion of the acromion. A new mathematical formula was developed in order to quantify the amount of bone to be resected while performing the lateral acromioplasty. Patients with traumatic tears, previous surgery, osteoarthritis or plain radiographs, not classified as A1 according to Suter-Henninger, were excluded. Clinical and radiographic outcomes were assessed at a minimum of 2 years of follow-up considering the tear size. Results: 289 patients were included in this study. Thirty-seven were lost to follow-up. Group A (Lateral acromioplasty) patients included: 38 small tears, 30 medium tears, 28 large tears and 22 massive tears, Group B (control group) was composed of 40 small tears, 30 medium tears, 30 large tears and 23 massive tears. The Constants Score value and retear Rate were, respectively, significant higher (p = 0.007 and p = 0.004) and lower (p = 0.029 and p = 0.028) in Group A, both in the Small-and Medium-size subgroups. No complications were outlined. The mediolateral width of the acromion was reduced, according to the preoperatively calculated measure. Conclusion: Arthroscopic lateral acromioplasty decreased the CSA within the favorable range (30&deg, &ndash, 35&deg, ) in all patients treated, resecting the amount of bone predicted by the mathematical formula. Lateral acromioplasty is a safe and reproducible technique which may prevent recurrence of rotator cuff tears in patients with small and medium lesions. Level of evidence: II.

Cell motility is the brilliant result of cell status and its interaction with close environments. Its detection is now possible, thanks to the synergy of high-resolution camera sensors, time-lapse microscopy devices, and dedicated software tools for video and data analysis. In this scenario, we formulated a novel paradigm in which we considered the individual cells as a sort of sensitive element of a sensor, which exploits the camera as a transducer returning the movement of the cell as an output signal. In this way, cell movement allows us to retrieve information about the chemical composition of the close environment. To optimally exploit this information, in this work, we introduce a new setting, in which a cell trajectory is divided into sub-tracks, each one characterized by a specific motion kind. Hence, we considered all the sub-tracks of the single-cell trajectory as the signals of a virtual array of cell motility-based sensors. The kinematics of each sub-track is quantified and used for a classification task. To investigate the potential of the proposed approach, we have compared the achieved performances with those obtained by using a single-trajectory paradigm with the scope to evaluate the chemotherapy treatment effects on prostate cancer cells. Novel pattern recognition algorithms have been applied to the descriptors extracted at a sub-track level by implementing features, as well as samples selection (a good teacher learning approach) for model construction. The experimental results have put in evidence that the performances are higher when a further cluster majority role has been considered, by emulating a sort of sensor fusion procedure. All of these results highlighted the high strength of the proposed approach, and straightforwardly prefigure its use in lab-on-chip or organ-on-chip applications, where the cell motility analysis can be massively applied using time-lapse microscopy images.

Aflatoxins are fungal metabolites extensively produced by many different fungal species that may contaminate a wide range of agricultural food products. They have been studied extensively because of being associated with various chronic and acute diseases, especially immunosuppression and cancer, and their presence in food is strictly monitored and regulated worldwide. Aflatoxin detection and measurement relies mainly on chemical methods usually based on chromatography approaches, and recently developed immunochemical based assays that have advantages but also limitations, since these are expensive and destructive techniques. Nondestructive, optical approaches are recently being developed to assess presence of contamination in a cost and time effective way, maintaining acceptable accuracy and reproducibility. In this paper are presented the results obtained with a simple portable device for nondestructive detection of aflatoxins in almonds. The presented approach is based on the analysis of fluorescence spectra of slurried almonds under 375 nm wavelength excitation. Experiments were conducted with almonds contaminated in the range of 2.7–320.2 ng/g total aflatoxins B (AFB1 + AFB2) as determined by High Performance Liquid Chromatography with Fluorescence Detection (HPLC/FLD). After applying pre-processing steps, spectral analysis was carried out using a binary classification model based on Support Vector Machine (SVM) algorithm. A majority vote procedure was then performed on the classification results. In this way we could achieve, as best result, a classification accuracy of 94% (and false negative rate 5%) with a threshold set at 6.4 ng/g. These results illustrate the feasibility of such approach in the great challenge of aflatoxin detection for food and feed safety.

International audience; Time-continuous emotion estimation (e. g., arousal and valence) from spontaneous speech expressions has recently drawn increasing commercial attention. However, real-life applications of emotion recognition technology require challenging conditions, such as noise from recording devices and background environments. In this work, we introduce a novel personalized emotion prediction model validated in different noisy environments. It is performed by a three-level noise reduction algorithm: (i) data downsampling, (ii) feature synchronization, and (iii) a modified version of graph total variation. The approach has been validated on the broadly used RECOLA database with different types of noises, including convolutive and additive noise with different SNRs. The process of feature synchronization improves the concordance correlation coefficient (CCC) absolute values by 0.271 on average for arousal and 0.137 for valence. The proposed denoising approach further improves the values by 0.101 for arousal and 0.086 for valence. Finally, the proposed model considerably improves the CCC values on raw data and all types of noisy data and outperforms the standard denoising methods

Biological experiments based on organ-on-chips (OOCs) exploit light Time-Lapse Microscopy (TLM) for a direct observation of cell movement that is an observable signature of underlying biological processes. A high spatial resolution is essential to capture cell dynamics and interactions from recorded experiments by TLM. Unfortunately, due to physical and cost limitations, acquiring high resolution videos is not always possible. To overcome the problem, we present here a new deep learning-based algorithm that extends the well known Deep Image Prior (DIP) to TLM Video Super Resolution (SR) without requiring any training. The proposed Recursive Deep Prior Video (RDPV) method introduces some novelties. The weights of the DIP network architecture are initialized for each of the frames according to a new recursive updating rule combined with an efficient early stopping criterion. Moreover, the DIP loss function is penalized by two different Total Variation (TV) based terms. The method has been validated on synthetic, i.e., artificially generated, as well as real videos from OOC experiments related to tumor-immune interaction. Achieved results are compared with several state-of-the-art trained deep learning SR algorithms showing outstanding performances., Paper submitted to a peer-reviewed journal

Several studies demonstrate that since emotions are spontaneously manifested through different measurable quantities (e.g. vocal and facial expressions), this makes possible a sort of automatic estimation of emotion from objective measurements. However, the reliability of such estimations is strongly influenced by the availability of the different sensor modalities used to monitor the affective status of a subject, and furthermore the extraction of objective parameters is sometime thwarted in a noisy and disturbed environment. This paper introduces a personalized emotion estimation based on a heterogeneous array of physical sensors for the measurement of vocal, facial, and physiological (electro-cardiogram and electro-dermal) activities. As a proof of concept, changes in the levels of both emotion reactiveness and pleasantness are estimated under critical operative conditions. The estimator model takes advantage from the time-varying selection of the most relevant non-spurious sensors features and the adaptation of the k-nearest neighbour paradigm to the continuous identification of the most affine model templates. The model, once trained, demonstrated to autonomously embed new sensorial input and adapt to unwanted/unpredicted sensor noise or emotion alteration. The proposed approach has been successfully tested on the RECOLA database, a multi-sensorial corpus of spontaneous emotional interactions in French.

The performance of an Unsupervised Online feature Selection (UOS) algorithm was investigated for the selection of training features of multispectral images acquired from a dairy product (vanilla cream) stored under isothermal conditions. The selected features were further used as input in a support vector machine (SVM) model with linear kernel for the determination of the microbiological quality of vanilla cream. Model training (n = 65) was based on two batches of cream samples provided directly by the manufacturer and stored at different isothermal conditions (4, 8, 12, and 15 &deg, C), whereas model testing (n = 132) and validation (n = 48) were based on real life conditions by analyzing samples from different retail outlets as well as expired samples from the market. Qualitative analysis was performed for the discrimination of cream samples in two microbiological quality classes based on the values of total viable counts [TVC &le, 2.0 log CFU/g (fresh samples) and TVC &ge, 6.0 log CFU/g (spoiled samples)]. Results exhibited good performance with an overall accuracy of classification for the two classes of 91.7% for model validation. Further on, the model was extended to include the samples in the TVC range 2&ndash, 6 log CFU/g, using 1 log step to define the microbiological quality of classes in order to assess the potential of the model to estimate increasing microbial populations. Results demonstrated that high rates of correct classification could be obtained in the range of 2&ndash, 5 log CFU/g, whereas the percentage of erroneous classification increased in the TVC class (5,6) that was close to the spoilage level of the product. Overall, the results of this study demonstrated that the UOS algorithm in tandem with spectral data acquired from multispectral imaging could be a promising method for real-time assessment of the microbiological quality of vanilla cream samples.

The increasing interest for microfluidic devices in medicine and biology has opened the way to new time-lapse microscopy era where the amount of images and their acquisition time will become crucial. In this optic, new data analysis algorithms have to be developed in order to extract novel features of cell behavior and cell–cell interactions. In this brief article, we emphasize the potential strength of a new paradigm arising in the integration of microfluidic devices (i.e., organ on chip), time-lapse microscopy analysis, and machine learning approaches. Some snapshots of previous case studies in the context of immunotherapy are included as proof of concepts of the proposed strategies while a visionary description concludes the work foreseeing future research and applicative scenarios.

In recent years, applications like Apple’s Siri or Microsoft’s Cortana have created the illusion that one can actually “chat” with a machine. However, a perfectly natural human-machine interaction is far from real as none of these tools can empathize. This issue has raised an increasing interest in speech emotion recognition systems, as the possibility to detect the emotional state of the speaker. This possibility seems relevant to a broad number of domains, ranging from man-machine interfaces to those of diagnostics. With this in mind, in the present work, we explored the possibility of applying a precision approach to the development of a statistical learning algorithm aimed at classifying samples of speech produced by children with developmental disorders(DD) and typically developing(TD) children. Under the assumption that acoustic features of vocal production could not be efficiently used as a direct marker of DD, we propose to apply the Emotional Modulation function(EMF) concept, rather than running analyses on acoustic features per se to identify the different classes. The novel paradigm was applied to the French Child Pathological & Emotional Speech Database obtaining a final accuracy of 0.79, with maximum performance reached in recognizing language impairment (0.92) and autism disorder (0.82).

A major challenge in cancer research is the complexity of the tumor microenvironment and the necessity to take into account the host immunological setting. An innovative way to address these problems is to exploit the emerging technology of organ-on-chip to achieve co-cultures in microfluidic devises that recapitulate ex vivo the tumor ecosystem. We generated tumors-on-chip integrating four cell populations (cancer, immune, endothelial cells and fibroblasts) in a 3D collagen matrix, reconstituting HER2 breast cancer ecosystem. By time-lapse microscopy, differential live staining and a novel automated analysis method, we visualized, and quantified the complex dynamics of this ecosystem, in absence or in presence of the drug trastuzumab (Herceptin), a targeted antibody therapy directed against the HER2 receptor. We uncovered the capacity of the drug trastuzumab to specifically promote long cancer-immune interactions (≳ 60 min), recapitulating an anti-tumoral ADCC (antibody-dependent cell-mediated cytotoxicity) immune response. Cancer-associated fibroblasts (CAFs) on the contrary inhibited cancer-immune interactions, antagonizing the action of the trastuzumab. These observations constitute a proof-of-concept that tumors-on-chip are novel powerful platforms that can be exploited to study ex vivo immunocompetent tumor microenvironments, to characterize ecosystem-level responses to anti-cancer drugs, and to dissect the roles of the various cellular components of the stroma.

Automatic detection of the nipple in mammograms is an important step in computerized systems that combine multiview information for accurate detection and diagnosis of breast cancer. Locating the nipple is a difficult task owing to variations in image quality, presence of noise, and distortion and displacement of the breast tissue due to compression. In this work, we propose a novel Hessian-based method to locate automatically the nipple in screen-film and full-field digital mammograms (FFDMs). The method includes detection of a plausible nipple/retroareolar area in a mammogram using geometrical constraints, analysis of the gradient vector field by mean and Gaussian curvature measurements, and local shape-based conditions. The proposed procedure was tested on 566 mammographic images consisting of 372 randomly selected scanned films from two public databases (mini-MIAS and DDSM), and 194 digital mammograms acquired with a GE Senographe 2000D FFDM system. A radiologist independently marked the centers of the nipples for evaluation of the results. The average error obtained was 6.7 mm (22 pixels) with reference to the center of the nipple as identified by the radiologist. Only two out of the 566 detected nipples (0.35 %) had an error larger than 50 mm. The method was also directly compared with two other techniques for the detection of the nipple. The results indicate that the proposed method outperforms other algorithms presented in the literature and can be used to identify accurately the nipple on various types of mammographic images.

In clinical practice, the constructive consultation among experts improves the reliability of the diagnosis and leads to the definition of the treatment plan for the patient. Aggregation of the different opinions collected by many experts can be performed at the level of patient information, abnormality delineation, or final assessment. In this study, we present a novel cooperative strategy that exploits the dynamic contribution of the classification models composing the ensemble to make the final class assignment. As a proof of concept, we applied the proposed approach to the assessment of malignant infiltration in 103 vertebral compression fractures in magnetic resonance images. The results obtained with repeated random subsampling and receiver operating characteristic analysis indicate that the cooperative system statistically improved ( $$p

In this paper we discuss the applicability of numerical descriptors and statistical physics concepts to characterize complex biological systems observed at microscopic level through organ on chip approach. To this end, we employ data collected on a microfluidic platform in which leukocytes can move through suitably built channels toward their target. Leukocyte behavior is recorded by standard time lapse imaging. In particular, we analyze three groups of human peripheral blood mononuclear cells (PBMC): heterozygous mutants (in which only one copy of the FPR1 gene is normal), homozygous mutants (in which both alleles encoding FPR1 are loss-of-function variants) and cells from ‘wild type’ donors (with normal expression of FPR1). We characterize the migration of these cells providing a quantitative confirmation of the essential role of FPR1 in cancer chemotherapy response. Indeed wild type PBMC perform biased random walks toward chemotherapy-treated cancer cells establishing persistent interactions with them. Conversely, heterozygous mutants present a weaker bias in their motion and homozygous mutants perform rather uncorrelated random walks, both failing to engage with their targets. We next focus on wild type cells and study the interactions of leukocytes with cancerous cells developing a novel heuristic procedure, inspired by Lyapunov stability in dynamical systems.

At present, mammography is the most effective examination for an early diagnosis of breast cancer. Nevertheless, the detection of cancer signs in mammograms is a difficult procedure owing to the great number of non-pathological structures which are also present in the image. Recent statistics show that in current breast cancer screenings 10%-25% of the tumors are missed by the radiologists. For this reason, a lot of research is currently being done to develop systems for Computer Aided Detection (CADe). Probably, some causes of the false-negative screening examinations are that tumoral masses have varying dimension and irregular shape, their borders are often ill-defined and their contrast is very low, thus making difficult the discrimination from parenchymal structures. Therefore, in a CADe system a preliminary segmentation procedure has to be implemented in order to separate the mass from the background tissue. In this way, various characteristics of the segmented mass can be evaluated and used in a classification step to discriminate benign and malignant cases. In this paper, we describe an effective algorithm for massive lesions segmentation based on a region-growing technique and we provide full details the performance evaluation procedure used in this specific context.

Summary: A major challenge in cancer research is the complexity of the tumor microenvironment, which includes the host immunological setting. Inspired by the emerging technology of organ-on-chip, we achieved 3D co-cultures in microfluidic devices (integrating four cell populations: cancer, immune, endothelial, and fibroblasts) to reconstitute ex vivo a human tumor ecosystem (HER2+ breast cancer). We visualized and quantified the complex dynamics of this tumor-on-chip, in the absence or in the presence of the drug trastuzumab (Herceptin), a targeted antibody therapy directed against the HER2 receptor. We uncovered the capacity of the drug trastuzumab to specifically promote long cancer-immune interactions (>50 min), recapitulating an anti-tumoral ADCC (antibody-dependent cell-mediated cytotoxicity) immune response. Cancer-associated fibroblasts (CAFs) antagonized the effects of trastuzumab. These observations constitute a proof of concept that tumors-on-chip are powerful platforms to study ex vivo immunocompetent tumor microenvironments, to characterize ecosystem-level drug responses, and to dissect the roles of stromal components. : Inspired by the emerging technology of tumor-on-chip, Nguyen et al. reconstituted ex vivo a human tumor microenvironment (HER2+ breast cancer), characterized the ecosystem-level responses to the drug trastuzumab (Herceptin), and dissected the roles of stromal components (immune cells and fibroblasts), demonstrating the power of immunocompetent tumors-on-chip for preclinical drug studies. Keywords: tumor microenvironment, organ-on-chip, tumor-on-chip, trastuzumab, HER2+ breast cancer, cancer-associated fibroblasts, live cell imaging, microfluidics, pre-clinical models, immunotherapy