Background Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease caused by a mutation in the homogentisate 1,2-dioxygenase (HGD) gene. One of the main obstacles in studying AKU, and other ultra-rare diseases, is the lack of a standardized methodology to assess disease severity or response to treatment. Quality of Life scores (QoL) are a reliable way to monitor patients’ clinical condition and health status. QoL scores allow to monitor the evolution of diseases and assess the suitability of treatments by taking into account patients’ symptoms, general health status and care satisfaction. However, more comprehensive tools to study a complex and multi-systemic disease like AKU are needed. In this study, a Machine Learning (ML) approach was implemented with the aim to perform a prediction of QoL scores based on clinical data deposited in the ApreciseKUre, an AKU- dedicated database. Method Data derived from 129 AKU patients have been firstly examined through a preliminary statistical analysis (Pearson correlation coefficient) to measure the linear correlation between 11 QoL scores. The variable importance in QoL scores prediction of 110 ApreciseKUre biomarkers has been then calculated using XGBoost, with K-nearest neighbours algorithm (k-NN) approach. Due to the limited number of data available, this model has been validated using surrogate data analysis. Results We identified a direct correlation of 6 (age, Serum Amyloid A, Chitotriosidase, Advanced Oxidation Protein Products, S-thiolated proteins and Body Mass Index) out of 110 biomarkers with the QoL health status, in particular with the KOOS (Knee injury and Osteoarthritis Outcome Score) symptoms (Relative Absolute Error (RAE) 0.25). The error distribution of surrogate-model (RAE 0.38) was unequivocally higher than the true-model one (RAE of 0.25), confirming the consistency of our dataset. Our data showed that inflammation, oxidative stress, amyloidosis and lifestyle of patients correlates with the QoL scores for physical status, while no correlation between the biomarkers and patients’ mental health was present (RAE 1.1). Conclusions This proof of principle study for rare diseases confirms the importance of database, allowing data management and analysis, which can be used to predict more effective treatments.

Ability of adapting to different users is considered key to maximize the impact and effectiveness of Serious Games (SGs). Advances in neurosciences are making it possible to continuously monitor the player status. This paper reports the research work on the monitoring of the player flow status with a simple (4 electrode) commercial electroencephalogram (EEG). In particular, we focus on three consequential research questions: is it possible to statistically distinguish a flow from a boredom condition? For which wavelengths? Can different levels of boredom and flow be identified? Results -even if limited because of the small size of the test, are promising and enable further research. Statistically significant differences could be observed for brainwaves under various conditions. A machine learning classifier (SVM) was successful in the 2-level distinction case, in particular with personalized training.

While biological intelligence grows organically as new knowledge is gathered throughout life, Artificial Neural Networks forget catastrophically whenever they face a changing training data distribution. Rehearsal-based Continual Learning (CL) approaches have been established as a versatile and reliable solution to overcome this limitation; however, sudden input disruptions and memory constraints are known to alter the consistency of their predictions. We study this phenomenon by investigating the geometric characteristics of the learner's latent space and find that replayed data points of different classes increasingly mix up, interfering with classification. Hence, we propose a geometric regularizer that enforces weak requirements on the Laplacian spectrum of the latent space, promoting a partitioning behavior. We show that our proposal, called Continual Spectral Regularizer (CaSpeR), can be easily combined with any rehearsal-based CL approach and improves the performance of SOTA methods on standard benchmarks. Finally, we conduct additional analysis to provide insights into CaSpeR's effects and applicability.

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