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Current research in nephrology is increasingly focused on elucidating the complexity inherent in tightly interwoven molecular systems and their correlation with pathology and related therapeutics, including dialysis and renal transplantation. Rapid advances in the omics sciences, medical device sensorization, and networked digital medical devices have made such research increasingly data centered. Data-centric science requires the support of computationally powerful and sophisticated tools able to handle the overflow of novel biomarkers and therapeutic targets. This is a context in which artificial intelligence (AI) and, more specifically, machine learning (ML) can provide a clear analytical advantage, given the rapid advances in their ability to harness multimodal data, from genomic information to signal, image and even heterogeneous electronic health records (EHR). However, paradoxically, only a small fraction of ML-based medical decision support systems undergo validation and demonstrate clinical usefulness. To effectively translate all this new knowledge into clinical practice, the development of clinically compliant support systems based on interpretable and explainable ML-based methods and clear analytical strategies for personalized medicine are imperative. Intelligent nephrology, that is, the design and development of AI-based strategies for a data-centric approach to nephrology, is just taking its first steps and is by no means yet close to its coming of age. These first steps are not even homogeneously taken, as a digital divide in access to technology has become evident between developed and developing countries, also affecting underrepresented minorities. With all this in mind, this editorial aim to provide a selective overview of the current use of AI technologies in nephrology and heralds the "Artificial Intelligence in Nephrology" special issue launched by BMC Nephrology. [ABSTRACT FROM AUTHOR]

G-protein coupled receptors (GPCRs) are transmembrane proteins that transmit signals from the extracellular environment to the inside of the cells. Their ability to adopt various conformational states, which influence their function, makes them crucial in pharmacoproteomic studies. While many drugs target specific GPCR states to exert their effects—thereby regulating the protein's activity—unraveling the activation pathway remains challenging due to the multitude of intermediate transformations occurring throughout this process, and intrinsically influencing the dynamics of the receptors. In this context, computational modeling, particularly molecular dynamics (MD) simulations, may offer valuable insights into the dynamics and energetics of GPCR transformations, especially when combined with machine learning (ML) methods and techniques for achieving model interpretability for knowledge generation. The current study builds upon previous work in which the layer relevance propagation (LRP) technique was employed to interpret the predictions in a multi-class classification problem concerning the conformational states of the β 2 -adrenergic ( β 2 AR) receptor from MD simulations. Here, we address the challenges posed by class imbalance and extend previous analyses by evaluating the robustness and stability of deep learning (DL)-based predictions under different imbalance mitigation techniques. By meticulously evaluating explainability and imbalance strategies, we aim to produce reliable and robust insights. [ABSTRACT FROM AUTHOR]

The standard treatment in glioblastoma includes maximal safe resection followed by concomitant radiotherapy plus chemotherapy and adjuvant temozolomide. The first follow‐up study to evaluate treatment response is performed 1 month after concomitant treatment, when contrast‐enhancing regions may appear that can correspond to true progression or pseudoprogression. We retrospectively evaluated 31 consecutive patients at the first follow‐up after concomitant treatment to check whether the metabolic pattern assessed with multivoxel MRS was predictive of treatment response 2 months later. We extracted the underlying metabolic patterns of the contrast‐enhancing regions with a blind‐source separation method and mapped them over the reference images. Pattern heterogeneity was calculated using entropy, and association between patterns and outcomes was measured with Cramér's V. We identified three distinct metabolic patterns—proliferative, necrotic, and responsive, which were associated with status 2 months later. Individually, 70% of the patients showed metabolically heterogeneous patterns in the contrast‐enhancing regions. Metabolic heterogeneity was not related to the regions' size and only stable patients were less heterogeneous than the rest. Contrast‐enhancing regions are also metabolically heterogeneous 1 month after concomitant treatment. This could explain the reported difficulty in finding robust pseudoprogression biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: Within the rapidly evolving landscape of Machine Learning in the medical field, this paper focuses on the forefront advancements in neuro-oncological radiology. More specifically, it aims to provide the reader with an in-depth exploration of the latest advancements in employing Deep Learning methodologies for the classification of brain tumor radiological images. This review meticulously scrutinizes papers published from 2018 to 2023, unveiling ongoing topics of research while underscoring the main remaining challenges and potential avenues for future research identified by those studies. Beyond the review itself, the paper also underscores the importance of placing the image data modelling provided by Deep Learning techniques within the framework of analytical pipeline research. This means that data quality control and pre-processing should be correctly coupled with modelling itself, in a way that emphasizes the importance of responsible data utilization, as well as the critical need for transparency in data disclosure to ensure trustworthiness and reproducibility of findings. Machine Learning is entering a phase of maturity, but its medical applications still lag behind in terms of practical use. The field of oncological radiology (and neuro-oncology in particular) is at the forefront of these developments, now boosted by the success of Deep-Learning methods for the analysis of medical images. This paper reviews in detail some of the most recent advances in the use of Deep Learning in this field, from the broader topic of the development of Machine-Learning-based analytical pipelines to specific instantiations of the use of Deep Learning in neuro-oncology; the latter including its use in the groundbreaking field of ultra-low field magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy (MRS) is an MR technique that provides information about the biochemistry of tissues in a noninvasive way. MRS has been widely used for the study of brain tumors, both preoperatively and during follow‐up. In this study, we investigated the performance of a range of variants of unsupervised matrix factorization methods of the non‐negative matrix underapproximation (NMU) family, namely, sparse NMU, global NMU, and recursive NMU, and compared them with convex non‐negative matrix factorization (C‐NMF), which has previously shown a good performance on brain tumor diagnostic support problems using MRS data. The purpose of the investigation was 2‐fold: first, to ascertain the differences among the sources extracted by these methods; and second, to compare the influence of each method in the diagnostic accuracy of the classification of brain tumors, using them as feature extractors. We discovered that, first, NMU variants found meaningful sources in terms of biological interpretability, but representing parts of the spectrum, in contrast to C‐NMF; and second, that NMU methods achieved better classification accuracy than C‐NMF for the classification tasks when one class was not meningioma. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs) are a large and heterogeneous superfamily of receptors that are key cell players for their role as extracellular signal transmitters. Class C GPCRs, in particular, are of great interest in pharmacology. The lack of knowledge about their full 3-D structure prompts the use of their primary amino acid sequences for the construction of robust classifiers, capable of discriminating their different subtypes. In this paper, we investigate the use of feature selection techniques to build Support Vector Machine (SVM)-based classification models from selected receptor subsequences described as n-grams. We show that this approach to classification is useful for finding class C GPCR subtype-specific motifs.

Simple Summary: One of the main applications of in vivo magnetic resonance spectroscopy (MRS) is in the non-invasive monitoring of the metabolic pattern of brain tumors. MRS comes in two basic modalities, single-voxel (SV), from which the signal is obtained, and multivoxel (MV), in which one or more contiguous grids of SVs are acquired. The purpose of our proof-of-concept study was to test whether it would be possible to train machine learning models using SV data at 1.5T, and test them with MV 3T data from independent patients, obtaining color-coded images of pathology (nosological images) to help radiologists in their preoperative evaluation of patients. With sequential forward feature selection followed by linear discriminant analysis, we obtained AUCs = 0.95 (meningioma), 0.89 (aggressive), 0.82 (low-grade glioma), and 0.82 (normal brain) in the MV test set. In vivo magnetic resonance spectroscopy (MRS) has two modalities, single-voxel (SV) and multivoxel (MV), in which one or more contiguous grids of SVs are acquired. Purpose: To test whether MV grids can be classified with models trained with SV. Methods: Retrospective study. Training dataset: Multicenter multiformat SV INTERPRET, 1.5T. Testing dataset: MV eTumour, 3T. Two classification tasks were completed: 3-class (meningioma vs. aggressive vs. normal) and 4-class (meningioma vs. low-grade glioma vs. aggressive vs. normal). Five different methods were tested for feature selection. The classification was implemented using linear discriminant analysis (LDA), random forest, and support vector machines. The evaluation was completed with balanced error rate (BER) and area under the curve (AUC) on both sets. The accuracy in class prediction was calculated by developing a solid tumor index (STI) and segmentation accuracy with the Dice score. Results: The best method was sequential forward feature selection combined with LDA, with AUCs = 0.95 (meningioma), 0.89 (aggressive), 0.82 (low-grade glioma), and 0.82 (normal). STI was 66% (4-class task) and 71% (3-class task) because two cases failed completely and two more had suboptimal STI as defined by us. Discussion: The reasons for failure in the classification of the MV test set were related to the presence of artifacts. [ABSTRACT FROM AUTHOR]

Simple Summary: Accurately grading gliomas, which are the most common and aggressive malignant brain tumors in adults, poses a significant challenge for radiologists. This study explores the application of Deep Learning techniques in assisting tumor grading using Magnetic Resonance Images (MRIs). By analyzing a glioma database sourced from multiple public datasets and comparing different settings, the aim of this study is to develop a robust and reliable grading system. The study demonstrates that by focusing on the tumor region of interest and augmenting the available data, there is a significant improvement in both the accuracy and confidence of tumor grade classifications. While successful in differentiating low-grade gliomas from high-grade gliomas, the accurate classification of grades 2, 3, and 4 remains challenging. The research findings have significant implications for advancing the development of a non-invasive, robust, and trustworthy data-driven system to support clinicians in the diagnosis and therapy planning of glioma patients. Glioma is the most common type of tumor in humans originating in the brain. According to the World Health Organization, gliomas can be graded on a four-stage scale, ranging from the most benign to the most malignant. The grading of these tumors from image information is a far from trivial task for radiologists and one in which they could be assisted by machine-learning-based decision support. However, the machine learning analytical pipeline is also fraught with perils stemming from different sources, such as inadvertent data leakage, adequacy of 2D image sampling, or classifier assessment biases. In this paper, we analyze a glioma database sourced from multiple datasets using a simple classifier, aiming to obtain a reliable tumor grading and, on the way, we provide a few guidelines to ensure such reliability. Our results reveal that by focusing on the tumor region of interest and using data augmentation techniques we significantly enhanced the accuracy and confidence in tumor classifications. Evaluation on an independent test set resulted in an AUC-ROC of 0.932 in the discrimination of low-grade gliomas from high-grade gliomas, and an AUC-ROC of 0.893 in the classification of grades 2, 3, and 4. The study also highlights the importance of providing, beyond generic classification performance, measures of how reliable and trustworthy the model's output is, thus assessing the model's certainty and robustness. [ABSTRACT FROM AUTHOR]

G-protein-coupled receptors (GPCRs) are cell membrane proteins of relevance as therapeutic targets, and are associated to the development of treatments for illnesses such as diabetes, Alzheimer's, or even cancer. Therefore, comprehending the underlying mechanisms of the receptor functional properties is of particular interest in pharmacoproteomics and in disease therapy at large. Their interaction with ligands elicits multiple molecular rearrangements all along their structure, inducing activation pathways that distinctly influence the cell response. In this work, we studied GPCR signaling pathways from molecular dynamics simulations as they provide rich information about the dynamic nature of the receptors. We focused on studying the molecular properties of the receptors using deep-learning-based methods. In particular, we designed and trained a one-dimensional convolution neural network and illustrated its use in a classification of conformational states: active, intermediate, or inactive, of the β 2 -adrenergic receptor when bound to the full agonist BI-167107. Through a novel explainability-oriented investigation of the prediction results, we were able to identify and assess the contribution of individual motifs (residues) influencing a particular activation pathway. Consequently, we contribute a methodology that assists in the elucidation of the underlying mechanisms of receptor activation–deactivation. [ABSTRACT FROM AUTHOR]

Generative topographic mapping is a nonlinear latent variable model introduced by Bishop et al. as a probabilistic reformulation of self-organizing maps. The complexity of this model is mostly determined by the number and form of basis functions generating the nonlinear mapping from latent space to data space, but it can be further controlled by adding a regularization term to increase the stiffness of the mapping and avoid data over-fitting. In this paper, we improve the map smoothing by introducing multiple regularization terms, one associated with each of the basis functions. A similar technique to that of automatic relevance determination, our selective map smoothing locally controls the stiffness of the mapping depending on length scales of the underlying manifold, while optimizing the effective number of active basis functions. Index Terms--Automatic relevance determination (ARD), Bayesian probability theory, generative topographic mapping (GTM), regularization, self-organizing map (SOM).

Despite the success of automated pattern recognition methods in problems of human brain tumor diagnostic classification, limited attention has been paid to the issue of automated data quality assessment in the field of MRS for neuro‐oncology. Beyond some early attempts to address this issue, the current standard in practice is MRS quality control through human (expert‐based) assessment. One aspect of automatic quality control is the problem of detecting artefacts in MRS data. Artefacts, whose variety has already been reviewed in some detail and some of which may even escape human quality control, have a negative influence in pattern recognition methods attempting to assist tumor characterization. The automatic detection of MRS artefacts should be beneficial for radiology as it guarantees more reliable tumor characterizations, as well as the development of more robust pattern recognition‐based tumor classifiers and more trustable MRS data processing and analysis pipelines. Feature extraction methods have previously been used to help distinguishing between good and bad quality spectra to apply subsequent supervised pattern recognition techniques. In this study, we apply feature extraction differently and use a variant of a method for blind source separation, namely Convex Non‐Negative Matrix Factorization, to unveil MRS signal sources in a completely unsupervised way. We hypothesize that, while most sources will correspond to the different tumor patterns, some of them will reflect signal artefacts. The experimental work reported in this paper, analyzing a combined short and long echo time 1H‐MRS database of more than 2000 spectra acquired at 1.5T and corresponding to different tumor types and other anomalous masses, provides a first proof of concept that points to the possible validity of this approach. [ABSTRACT FROM AUTHOR]

Abstract Background In-vivo single voxel proton magnetic resonance spectroscopy (SV 1H-MRS), coupled with supervised pattern recognition (PR) methods, has been widely used in clinical studies of discrimination of brain tumour types and follow-up of patients bearing abnormal brain masses. SV 1H-MRS provides useful biochemical information about the metabolic state of tumours and can be performed at short (< 45 ms) or long (> 45 ms) echo time (TE), each with particular advantages. Short-TE spectra are more adequate for detecting lipids, while the long-TE provides a much flatter signal baseline in between peaks but also negative signals for metabolites such as lactate. Both, lipids and lactate, are respectively indicative of specific metabolic processes taking place. Ideally, the information provided by both TE should be of use for clinical purposes. In this study, we characterise the performance of a range of Non-negative Matrix Factorisation (NMF) methods in two respects: first, to derive sources correlated with the mean spectra of known tissue types (tumours and normal tissue); second, taking the best performing NMF method for source separation, we compare its accuracy for class assignment when using the mixing matrix directly as a basis for classification, as against using the method for dimensionality reduction (DR). For this, we used SV 1H-MRS data with positive and negative peaks, from a widely tested SV 1H-MRS human brain tumour database. Results The results reported in this paper reveal the advantage of using a recently described variant of NMF, namely Convex-NMF, as an unsupervised method of source extraction from SV1H-MRS. Most of the sources extracted in our experiments closely correspond to the mean spectra of some of the analysed tumour types. This similarity allows accurate diagnostic predictions to be made both in fully unsupervised mode and using Convex-NMF as a DR step previous to standard supervised classification. The obtained results are comparable to, or more accurate than those obtained with supervised techniques. Conclusions The unsupervised properties of Convex-NMF place this approach one step ahead of classical label-requiring supervised methods for the discrimination of brain tumour types, as it accounts for their increasingly recognised molecular subtype heterogeneity. The application of Convex-NMF in computer assisted decision support systems is expected to facilitate further improvements in the uptake of MRS-derived information by clinicians.

The vibrant Mediterranean city of Barcelona, in Spain, welcomed the 13th edition of WSOM + 2019, the Workshop on Self-Organizing Maps and Learning Vector Quantization, Clustering and Data Visualization. A self-organizing world: special issue of the 13th edition of the workshop on self-organizing maps and learning vector quantization, clustering and data visualization, WSOM + 2019 Passive concept drift handling via variations of learning vector quantization. [Extracted from the article]

Circulatory shock is a life-threatening disease that accounts for around one-third of all admissions to intensive care units (ICU). It requires immediate treatment, which is why the development of tools for planning therapeutic interventions is required to deal with shock in the critical care environment. In this study, the ShockOmics European project original database is used to extract attributes capable of predicting mortality due to shock in the ICU. Missing data imputation techniques and machine learning models were used, followed by feature selection from different data subsets. Selected features were later used to build Bayesian Networks, revealing causal relationships between features and ICU outcome. The main result is a subset of predictive features that includes well-known indicators such as the SOFA and APACHE II scores, but also less commonly considered ones related to cardiovascular function assessed through echocardiograpy or shock treatment with pressors. Importantly, certain selected features are shown to be most predictive at certain time-steps. This means that, as shock progresses, different attributes could be prioritized. Clinical traits obtained at 24h. from ICU admission are shown to accurately predict cardiogenic and septic shock mortality, suggesting that relevant life-saving decisions could be made shortly after ICU admission. [ABSTRACT FROM AUTHOR]

Background: Biology is experiencing a gradual but fast transformation from a laboratory-centred science towards a data-centred one. As such, it requires robust data engineering and the use of quantitative data analysis methods as part of database curation. This paper focuses on G protein-coupled receptors, a large and heterogeneous super-family of cell membrane proteins of interest to biology in general. One of its families, Class C, is of particular interest to pharmacology and drug design. This family is quite heterogeneous on its own, and the discrimination of its several sub-families is a challenging problem. In the absence of known crystal structure, such discrimination must rely on their primary amino acid sequences.Methods: We are interested not as much in achieving maximum sub-family discrimination accuracy using quantitative methods, but in exploring sequence misclassification behavior. Specifically, we are interested in isolating those sequences showing consistent misclassification, that is, sequences that are very often misclassified and almost always to the same wrong sub-family. Random forests are used for this analysis due to their ensemble nature, which makes them naturally suited to gauge the consistency of misclassification. This consistency is here defined through the voting scheme of their base tree classifiers.Results: Detailed consistency results for the random forest ensemble classification were obtained for all receptors and for all data transformations of their unaligned primary sequences. Shortlists of the most consistently misclassified receptors for each subfamily and transformation, as well as an overall shortlist including those cases that were consistently misclassified across transformations, were obtained. The latter should be referred to experts for further investigation as a data curation task.Conclusion: The automatic discrimination of the Class C sub-families of G protein-coupled receptors from their unaligned primary sequences shows clear limits. This study has investigated in some detail the consistency of their misclassification using random forest ensemble classifiers. Different sub-families have been shown to display very different discrimination consistency behaviors. The individual identification of consistently misclassified sequences should provide a tool for quality control to GPCR database curators. [ABSTRACT FROM AUTHOR]