Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy.

OBJECTIVE: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. RESULTS: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. INTERPRETATION: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192.

Human versus Machine Intelligence: Assessing Natural Language Generation Models through Complex Systems Theory.

The introduction of Transformer architectures - with the self-attention mechanism - in automatic Natural Language Generation (NLG) is a breakthrough in solving general task-oriented problems, such as the simple production of long text excerpts that resemble ones written by humans. While the performance of GPT-X architectures is there for all to see, many efforts are underway to penetrate the secrets of these black-boxes in terms of intelligent information processing whose output statistical distributions resemble that of natural language. In this work, through the complexity science framework, a comparative study of the stochastic processes underlying the texts produced by the English version of GPT-2 with respect to texts produced by human beings, notably novels in English and programming codes, is offered. The investigation, of a methodological nature, consists first of all of an analysis phase in which the Multifractal Detrended Fluctuation Analysis and the Recurrence Quantification Analysis - together with Zipf's law and approximate entropy - are adopted to characterize long-term correlations, regularities and recurrences in human and machine-produced texts. Results show several peculiarities and trends in terms of long-range correlations and recurrences in the last case. The synthesis phase, on the other hand, uses the complexity measures to build synthetic text descriptors - hence a suitable text embedding - which serve to constitute the features for feeding a machine learning system designed to operate feature selection through an evolutionary technique. Using multivariate analysis, it is then shown the grouping tendency of the three analyzed text types, allowing to place GTP-2 texts in between natural language texts and computer codes. Similarly, the classification task demonstrates that, given the high accuracy obtained in the automatic discrimination of text classes, the proposed set of complexity measures is highly informative. These interesting results allow us to add another piece to the theoretical understanding of the surprising results obtained by NLG systems based on deep learning and let us to improve the design of new informetrics or text mining systems for text classification, fake news detection, or even plagiarism detection.

Brain metabolic differences between pure bulbar and pure spinal ALS: a 2-[18F]FDG-PET study.

BACKGROUND: MRI studies reported that ALS patients with bulbar and spinal onset showed focal cortical changes in corresponding regions of the motor homunculus. We evaluated the capability of brain 2-[18F]FDG-PET to disclose the metabolic features characterizing patients with pure bulbar or spinal motor impairment. METHODS: We classified as pure bulbar (PB) patients with bulbar onset and a normal score in the spinal items of the ALSFRS-R, and as pure spinal (PS) patients with spinal onset and a normal score in the bulbar items at the time of PET. Forty healthy controls (HC) were enrolled. We compared PB and PS, and each patient group with HC. Metabolic clusters showing a statistically significant difference between PB and PS were tested to evaluate their accuracy in discriminating the two groups. We performed a leave-one-out cross-validation (LOOCV) over the entire dataset. Four classifiers were considered: support vector machines (SVM), K-nearest neighbours, linear classifier, and decision tree. Then, we used a separate test set, including 10% of patients, with the remaining 90% composing the training set. RESULTS: We included 63 PB, 271 PS, and 40 HC. PB showed a relative hypometabolism compared to PS in bilateral precentral gyrus in the regions of the motor cortex involved in the control of bulbar function. SVM showed the best performance, resulting in the lowest error rate in both LOOCV (4.19%) and test set (9.09 ± 2.02%). CONCLUSIONS: Our data support the concept of the focality of ALS onset and the use of 2-[18F]FDG-PET as a biomarker for precision medicine-oriented clinical trials.

Role of brain 2-[18F]fluoro-2-deoxy-D-glucose-positron-emission tomography as survival predictor in amyotrophic lateral sclerosis.

PURPOSE: The identification of prognostic tools in amyotrophic lateral sclerosis (ALS) would improve the design of clinical trials, the management of patients, and life planning. We aimed to evaluate the accuracy of brain 2-[18F]fluoro-2-deoxy-D-glucose-positron-emission tomography (2-[18F]FDG-PET) as an independent predictor of survival in ALS. METHODS: A prospective cohort study enrolled 418 ALS patients, who underwent brain 2-[18F]FDG-PET at diagnosis and whose survival time was available. We discretized the survival time in a finite number of classes in a data-driven fashion by employing a k-means-like strategy. We identified "hot brain regions" with maximal power in discriminating survival classes, by evaluating the Laplacian scores in a class-aware fashion. We retained the top-m features for each class to train the classification systems (i.e., a support vector machine, SVM), using 10% of the ALS cohort as test set. RESULTS: Data were discretized in three survival profiles: 0-2 years, 2-5 years, and > 5 years. SVM resulted in an error rate < 20% for two out of three classes separately. As for class one, the discriminant clusters included left caudate body and anterior cingulate cortex. The most discriminant regions were bilateral cerebellar pyramid in class two, and right cerebellar dentate nucleus, and left cerebellar nodule in class three. CONCLUSION: Brain 2-[18F]FDG-PET along with artificial intelligence was able to predict with high accuracy the survival time range in our ALS cohort. Healthcare professionals can benefit from this prognostic tool for planning patients' management and follow-up. 2-[18F]FDG-PET represents a promising biomarker for individual patients' stratification in clinical trials. The lack of a multicentre external validation of the model warrants further studies to evaluate its generalization capability.

On component-wise dissimilarity measures and metric properties in pattern recognition.

In many real-world applications concerning pattern recognition techniques, it is of utmost importance the automatic learning of the most appropriate dissimilarity measure to be used in object comparison. Real-world objects are often complex entities and need a specific representation grounded on a composition of different heterogeneous features, leading to a non-metric starting space where Machine Learning algorithms operate. However, in the so-called unconventional spaces a family of dissimilarity measures can be still exploited, that is, the set of component-wise dissimilarity measures, in which each component is treated with a specific sub-dissimilarity that depends on the nature of the data at hand. These dissimilarities are likely to be non-Euclidean, hence the underlying dissimilarity matrix is not isometrically embeddable in a standard Euclidean space because it may not be structurally rich enough. On the other hand, in many metric learning problems, a component-wise dissimilarity measure can be defined as a weighted linear convex combination and weights can be suitably learned. This article, after introducing some hints on the relation between distances and the metric learning paradigm, provides a discussion along with some experiments on how weights, intended as mathematical operators, interact with the Euclidean behavior of dissimilarity matrices.

Modelling and Recognition of Protein Contact Networks by Multiple Kernel Learning and Dissimilarity Representations.

Multiple kernel learning is a paradigm which employs a properly constructed chain of kernel functions able to simultaneously analyse different data or different representations of the same data. In this paper, we propose an hybrid classification system based on a linear combination of multiple kernels defined over multiple dissimilarity spaces. The core of the training procedure is the joint optimisation of kernel weights and representatives selection in the dissimilarity spaces. This equips the system with a two-fold knowledge discovery phase: by analysing the weights, it is possible to check which representations are more suitable for solving the classification problem, whereas the pivotal patterns selected as representatives can give further insights on the modelled system, possibly with the help of field-experts. The proposed classification system is tested on real proteomic data in order to predict proteins' functional role starting from their folded structure: specifically, a set of eight representations are drawn from the graph-based protein folded description. The proposed multiple kernel-based system has also been benchmarked against a clustering-based classification system also able to exploit multiple dissimilarities simultaneously. Computational results show remarkable classification capabilities and the knowledge discovery analysis is in line with current biological knowledge, suggesting the reliability of the proposed system.

(Hyper)graph Kernels over Simplicial Complexes.

Graph kernels are one of the mainstream approaches when dealing with measuring similarity between graphs, especially for pattern recognition and machine learning tasks. In turn, graphs gained a lot of attention due to their modeling capabilities for several real-world phenomena ranging from bioinformatics to social network analysis. However, the attention has been recently moved towards hypergraphs, generalization of plain graphs where multi-way relations (other than pairwise relations) can be considered. In this paper, four (hyper)graph kernels are proposed and their efficiency and effectiveness are compared in a twofold fashion. First, by inferring the simplicial complexes on the top of underlying graphs and by performing a comparison among 18 benchmark datasets against state-of-the-art approaches; second, by facing a real-world case study (i.e., metabolic pathways classification) where input data are natively represented by hypergraphs. With this work, we aim at fostering the extension of graph kernels towards hypergraphs and, more in general, bridging the gap between structural pattern recognition and the domain of hypergraphs.

Metabolic networks classification and knowledge discovery by information granulation.

Graphs are powerful structures able to capture topological and semantic information from data, hence suitable for modelling a plethora of real-world (complex) systems. For this reason, graph-based pattern recognition gained a lot of attention in recent years. In this paper, a general-purpose classification system in the graphs domain is presented. When most of the information of the available patterns can be encoded in edge labels, an information granulation-based approach is highly discriminant and allows for the identification of semantically meaningful edges. The proposed classification system has been tested on the entire set of organisms (5299) for which metabolic networks are known, allowing for both a perfect mirroring of the underlying taxonomy and the identification of most discriminant metabolic reactions and pathways. The widespread diffusion of graph (network) structures in biology makes the proposed pattern recognition approach potentially very useful in many different fields of application. More specifically, the possibility to have a reliable metric to compare different metabolic systems is instrumental in emerging fields like microbiome analysis and, more in general, for proposing metabolic networks as a universal phenotype spanning the entire tree of life and in direct contact with environmental cues.

An Infoveillance System for Detecting and Tracking Relevant Topics From Italian Tweets During the COVID-19 Event.

The year 2020 opened with a dramatic epidemic caused by a new species of coronavirus that soon has been declared a pandemic by the WHO due to the high number of deaths and the critical mass of worldwide hospitalized patients, of order of millions. The COVID-19 pandemic has forced the governments of hundreds of countries to apply several heavy restrictions in the citizens' socio-economic life. Italy was one of the most affected countries with long-term restrictions, impacting the socio-economic tissue. During this lockdown period, people got informed mostly on Online Social Media, where a heated debate followed all main ongoing events. In this scenario, the following study presents an in-depth analysis of the main emergent topics discussed during the lockdown phase within the Italian Twitter community. The analysis has been conducted through a general purpose methodological framework, grounded on a biological metaphor and on a chain of NLP and graph analysis techniques, in charge of detecting and tracking emerging topics in Online Social Media, e.g. streams of Twitter data. A term-frequency analysis in subsequent time slots is pipelined with nutrition and energy metrics for computing hot terms by also exploiting the tweets quality information, such as the social influence of the users. Finally, a co-occurrence analysis is adopted for building a topic graph where emerging topics are suitably selected. We demonstrate via a careful parameter setting the effectiveness of the topic tracking system, tailored to the current Twitter standard API restrictions, in capturing the main sociopolitical events that occurred during this dramatic phase.