Machine learning and XAI approaches highlight the strong connection between O 3 and N O 2 pollutants and Alzheimer's disease.

Alzheimer's disease (AD) is the most common type of dementia with millions of affected patients worldwide. Currently, there is still no cure and AD is often diagnosed long time after onset because there is no clear diagnosis. Thus, it is essential to study the physiology and pathogenesis of AD, investigating the risk factors that could be strongly connected to the disease onset. Despite AD, like other complex diseases, is the result of the combination of several factors, there is emerging agreement that environmental pollution should play a pivotal role in the causes of disease. In this work, we implemented an Artificial Intelligence model to predict AD mortality, expressed as Standardized Mortality Ratio, at Italian provincial level over 5 years. We employed a set of publicly available variables concerning pollution, health, society and economy to feed a Random Forest algorithm. Using methods based on eXplainable Artificial Intelligence (XAI) we found that air pollution (mainly O 3 and N O 2 ) contribute the most to AD mortality prediction. These results could help to shed light on the etiology of Alzheimer's disease and to confirm the urgent need to further investigate the relationship between the environment and the disease.

Deep learning approach for denoising low-SNR correlation plenoptic images.

Correlation Plenoptic Imaging (CPI) is a novel volumetric imaging technique that uses two sensors and the spatio-temporal correlations of light to detect both the spatial distribution and the direction of light. This novel approach to plenoptic imaging enables refocusing and 3D imaging with significant enhancement of both resolution and depth of field. However, CPI is generally slower than conventional approaches due to the need to acquire sufficient statistics for measuring correlations with an acceptable signal-to-noise ratio (SNR). We address this issue by implementing a Deep Learning application to improve image quality with undersampled frame statistics. We employ a set of experimental images reconstructed by a standard CPI architecture, at three different sampling ratios, and use it to feed a CNN model pre-trained through the transfer learning paradigm U-Net architecture with VGG-19 net for the encoding part. We find that our model reaches a Structural Similarity (SSIM) index value close to 1 both for the test sample (SSIM = [Formula: see text]) and in 5-fold cross validation (SSIM = [Formula: see text]); the results are also shown to outperform classic denoising methods, in particular for images with lower SNR. The proposed work represents the first application of Artificial Intelligence in the field of CPI and demonstrates its high potential: speeding-up the acquisition by a factor 20 over the fastest CPI so far demonstrated, enabling recording potentially 200 volumetric images per second. The presented results open the way to scanning-free real-time volumetric imaging at video rate, which is expected to achieve a substantial influence in various applications scenarios, from monitoring neuronal activity to machine vision and security.

Artificial Intelligence and Complex Network Approaches Reveal Potential Gene Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the number of cases is constantly increasing. Early and accurate HCC diagnosis is crucial to improving the effectiveness of treatment. The aim of the study is to develop a supervised learning framework based on hierarchical community detection and artificial intelligence in order to classify patients and controls using publicly available microarray data. With our methodology, we identified 20 gene communities that discriminated between healthy and cancerous samples, with an accuracy exceeding 90%. We validated the performance of these communities on an independent dataset, and with two of them, we reached an accuracy exceeding 80%. Then, we focused on two communities, selected because they were enriched with relevant biological functions, and on these we applied an explainable artificial intelligence (XAI) approach to analyze the contribution of each gene to the classification task. In conclusion, the proposed framework provides an effective methodological and quantitative tool helping to find gene communities, which may uncover pivotal mechanisms responsible for HCC and thus discover new biomarkers.

An eXplainable Artificial Intelligence analysis of Raman spectra for thyroid cancer diagnosis.

Raman spectroscopy shows great potential as a diagnostic tool for thyroid cancer due to its ability to detect biochemical changes during cancer development. This technique is particularly valuable because it is non-invasive and label/dye-free. Compared to molecular tests, Raman spectroscopy analyses can more effectively discriminate malignant features, thus reducing unnecessary surgeries. However, one major hurdle to using Raman spectroscopy as a diagnostic tool is the identification of significant patterns and peaks. In this study, we propose a Machine Learning procedure to discriminate healthy/benign versus malignant nodules that produces interpretable results. We collect Raman spectra obtained from histological samples, select a set of peaks with a data-driven and label independent approach and train the algorithms with the relative prominence of the peaks in the selected set. The performance of the considered models, quantified by area under the Receiver Operating Characteristic curve, exceeds 0.9. To enhance the interpretability of the results, we employ eXplainable Artificial Intelligence and compute the contribution of each feature to the prediction of each sample.

A Dementia mortality rates dataset in Italy (2012-2019).

Dementia is on the rise in the world population and has been defined by the World Health Organization as a global public health priority. In Italy, according to demographic projections, in 2051 there will be 280 elderly people for every 100 young people, with an increase in all age-related chronic diseases, including dementia. Currently the total number of patients with dementia is estimated to be over 1 million (mainly with Alzheimer's disease (AD) and Parkinson's disease (PD)). In-depth studies of the etiology and physiology of dementia are complicated due to the complexity of these diseases and their long duration. In this work we present a dataset on mortality rates (in the form of Standardized Mortality Ratios, SMR) for AD e PD in Italy at provincial level over a period of 8 years (2012-2019). Access to long-term, spatially detailed and ready-to-use data could favor both health monitoring and the research of new treatments and new drugs as well as innovative methodologies for early diagnosis of dementia.

Consensus molecular environment of schizophrenia risk genes in coexpression networks shifting across age and brain regions.

Schizophrenia is a neurodevelopmental brain disorder whose genetic risk is associated with shifting clinical phenomena across the life span. We investigated the convergence of putative schizophrenia risk genes in brain coexpression networks in postmortem human prefrontal cortex (DLPFC), hippocampus, caudate nucleus, and dentate gyrus granule cells, parsed by specific age periods (total N = 833). The results support an early prefrontal involvement in the biology underlying schizophrenia and reveal a dynamic interplay of regions in which age parsing explains more variance in schizophrenia risk compared to lumping all age periods together. Across multiple data sources and publications, we identify 28 genes that are the most consistently found partners in modules enriched for schizophrenia risk genes in DLPFC; twenty-three are previously unidentified associations with schizophrenia. In iPSC-derived neurons, the relationship of these genes with schizophrenia risk genes is maintained. The genetic architecture of schizophrenia is embedded in shifting coexpression patterns across brain regions and time, potentially underwriting its shifting clinical presentation.

Haemorrhage and Survival Times: Medical-Legal Evaluation of the Time of Death and Relative Evidence.

Haemorrhage is the name used to describe the loss of blood from damaged blood vessels (arteries, veins, capillaries). Identifying the time of haemorrhage remains a clinical challenge, knowing that blood perfusion of systemic tissues is poorly correlated with the perfusion of specific tissues. In forensic science, one of the most discussed elements is the time of death. This study aims to provide the forensic scientist with a valid model to establish a precise time-of-death interval in cases of exsanguination following trauma with vascular injury, which can be useful as a technical aid in the investigation of criminal cases. To calculate the calibre and resistance of the vessels, we used an extensive literature review of distributed one-dimensional models of the systemic arterial tree as a reference. We then arrived at a formula that allows us to estimate, based on a subject's total blood volume and the calibre of the injured vessel, a time interval within which a subject's death from haemorrhage from vascular injury falls. We applied the formula to four cases in which death had been caused by the injury of a single arterial vessel and obtained comforting results. The study model we have offered is only a good prospect for future work. In fact, we intend to improve the study by expanding the case and statistical analysis with particular regard to the interference factors to confirm its actual usability in practical cases; in this way, useful corrective factors can be identified.

Detecting the socio-economic drivers of confidence in government with eXplainable Artificial Intelligence.

The European Quality of Government Index (EQI) measures the perceived level of government quality by European Union citizens, combining surveys on corruption, impartiality and quality of provided services. It is, thus, an index based on individual subjective evaluations. Understanding the most relevant objective factors affecting the EQI outcomes is important for both evaluators and policy makers, especially in view of the fact that perception of government integrity contributes to determine the level of civic engagement. In our research, we employ methods of Artificial Intelligence and complex systems physics to measure the impact on the perceived government quality of multifaceted variables, describing territorial development and citizen well-being, from an economic, social and environmental viewpoint. Our study, focused on a set of regions in European Union at a subnational scale, leads to identifying the territorial and demographic drivers of citizens' confidence in government institutions. In particular, we find that the 2021 EQI values are significantly related to two indicators: the first one is the difference between female and male labour participation rates, and the second one is a proxy of wealth and welfare such as the average number of rooms per inhabitant. This result corroborates the idea of a central role played by labour gender equity and housing policies in government confidence building. In particular, the relevance of the former indicator in EQI prediction results from a combination of positive conditions such as equal job opportunities, vital labour market, welfare and availability of income sources, while the role of the latter is possibly amplified by the lockdown policies related to the COVID-19 pandemics. The analysis is based on combining regression, to predict EQI from a set of publicly available indicators, with the eXplainable Artificial Intelligence approach, that quantifies the impact of each indicator on the prediction. Such a procedure does not require any ad-hoc hypotheses on the functional dependence of EQI on the indicators used to predict it. Finally, using network science methods concerning community detection, we investigate how the impact of relevant indicators on EQI prediction changes throughout European regions. Thus, the proposed approach enables to identify the objective factors at the basis of government quality perception by citizens in different territorial contexts, providing the methodological basis for the development of a quantitative tool for policy design.

TIRESIA: An eXplainable Artificial Intelligence Platform for Predicting Developmental Toxicity.

Herein, a robust and reproducible eXplainable Artificial Intelligence (XAI) approach is presented, which allows prediction of developmental toxicity, a challenging human-health endpoint in toxicology. The application of XAI as an alternative method is of the utmost importance with developmental toxicity being one of the most animal-intensive areas of regulatory toxicology. In this work, the established CAESAR (Computer Assisted Evaluation of industrial chemical Substances According to Regulations) training set made of 234 chemicals for model learning is employed. Two test sets, including as a whole 585 chemicals, were instead used for validation and generalization purposes. The proposed framework favorably compares with the state-of-the-art approaches in terms of accuracy, sensitivity, and specificity, thus resulting in a reliable support system for developmental toxicity ensuring informativeness, uncertainty estimation, generalization, and transparency. Based on the eXtreme Gradient Boosting (XGB) algorithm, our predictive model provides easy interpretative keys based on specific molecular descriptors and structural alerts enabling one to distinguish toxic and nontoxic chemicals. Inspired by the Organisation for Economic Co-operation and Development (OECD) principles for the validation of Quantitative Structure-Activity Relationships (QSARs) for regulatory purposes, the results are summarized in a standard report in portable document format, enclosing also details concerned with a density-based model applicability domain and SHAP (SHapley Additive exPlanations) explainability, the latter particularly useful to better understand the effective roles played by molecular features. Notably, our model has been implemented in TIRESIA (Toxicology Intelligence and Regulatory Evaluations for Scientific and Industry Applications), a free of charge web platform available at http://tiresia.uniba.it.

The harmonium model and its unified system view of psychopathology: a validation study by means of a convolutional neural network.

The harmonium model (HM) is a recent conceptualization of the unifying view of psychopathology, namely the idea of a general mechanism underpinning all mental disorders (the p factor). According to HM, psychopathology consists of a low dimensional Phase Space of Meaning (PSM), where each dimension of meaning maps a component of the environmental variability. Accordingly, the lower thenumber of independent dimensions in the PSM, and hence its intrinsic complexity, the more limited the way of interpreting the environment. The current simulation study, based on a Convolutional Neural Network (CNN) framework, aims at validating the HM low-dimensionality hypothesis. CNN-based classifiers were employed to simulate normotypical and pathological cognitive processes. Results revealed that normotypical and pathological CNNs were different in terms of both classification performance and layer activation patterns. Using Principal Component Analysis to characterize the PSM associated with the two algorithms, we found that the performance of the normotypical CNN relies on a larger and more evenly distributed number of components, compared with the pathological one. This finding might be indicative of the fact that psychopathology can be modelled as a low-dimensional, poorly modulable PSM, which means the environment is detected through few components of meaning, preventing complex information patterns from being taken into account.

Worldwide impact of lifestyle predictors of dementia prevalence: An eXplainable Artificial Intelligence analysis.

Introduction: Dementia is an umbrella term indicating a group of diseases that affect the cognitive sphere. Dementia is not a mere individual health issue, since its interference with the ability to carry out daily activities entails a series of collateral problems, comprising exclusion of patients from civil rights and welfare, unpaid caregiving work, mostly performed by women, and an additional burden on the public healthcare systems. Thus, gender and wealth inequalities (both among individuals and among countries) tend to amplify the social impact of such a disease. Since at present there is no cure for dementia but only drug treatments to slow down its progress and mitigate the symptoms, it is essential to work on prevention and early diagnosis, identifying the risk factors that increase the probability of its onset. The complex and multifactorial etiology of dementia, resulting from an interplay between genetics and environmental factors, can benefit from a multidisciplinary approach that follows the "One Health" guidelines of the World Health Organization. Methods: In this work, we apply methods of Artificial Intelligence and complex systems physics to investigate the possibility to predict dementia prevalence throughout world countries from a set of variables concerning individual health, food consumption, substance use and abuse, healthcare system efficiency. The analysis uses publicly available indicator values at a country level, referred to a time window of 26 years. Results: Employing methods based on eXplainable Artificial Intelligence (XAI) and complex networks, we identify a group of lifestyle factors, mostly concerning nutrition, that contribute the most to dementia incidence prediction. Discussion: The proposed approach provides a methodological basis to develop quantitative tools for action patterns against such a disease, which involves issues deeply related with sustainable, such as good health and resposible food consumption.

A robust framework to investigate the reliability and stability of explainable artificial intelligence markers of Mild Cognitive Impairment and Alzheimer's Disease.

In clinical practice, several standardized neuropsychological tests have been designed to assess and monitor the neurocognitive status of patients with neurodegenerative diseases such as Alzheimer's disease. Important research efforts have been devoted so far to the development of multivariate machine learning models that combine the different test indexes to predict the diagnosis and prognosis of cognitive decline with remarkable results. However, less attention has been devoted to the explainability of these models. In this work, we present a robust framework to (i) perform a threefold classification between healthy control subjects, individuals with cognitive impairment, and subjects with dementia using different cognitive indexes and (ii) analyze the variability of the explainability SHAP values associated with the decisions taken by the predictive models. We demonstrate that the SHAP values can accurately characterize how each index affects a patient's cognitive status. Furthermore, we show that a longitudinal analysis of SHAP values can provide effective information on Alzheimer's disease progression.

A Machine Learning Approach to Parkinson's Disease Blood Transcriptomics.

The increased incidence and the significant health burden associated with Parkinson's disease (PD) have stimulated substantial research efforts towards the identification of effective treatments and diagnostic procedures. Despite technological advancements, a cure is still not available and PD is often diagnosed a long time after onset when irreversible damage has already occurred. Blood transcriptomics represents a potentially disruptive technology for the early diagnosis of PD. We used transcriptome data from the PPMI study, a large cohort study with early PD subjects and age matched controls (HC), to perform the classification of PD vs. HC in around 550 samples. Using a nested feature selection procedure based on Random Forests and XGBoost we reached an AUC of 72% and found 493 candidate genes. We further discussed the importance of the selected genes through a functional analysis based on GOs and KEGG pathways.

Territorial bias in university rankings: a complex network approach.

University rankings are increasingly adopted for academic comparison and success quantification, even to establish performance-based criteria for funding assignment. However, rankings are not neutral tools, and their use frequently overlooks disparities in the starting conditions of institutions. In this research, we detect and measure structural biases that affect in inhomogeneous ways the ranking outcomes of universities from diversified territorial and educational contexts. Moreover, we develop a fairer rating system based on a fully data-driven debiasing strategy that returns an equity-oriented redefinition of the achieved scores. The key idea consists in partitioning universities in similarity groups, determined from multifaceted data using complex network analysis, and referring the performance of each institution to an expectation based on its peers. Significant evidence of territorial biases emerges for official rankings concerning both the OECD and Italian university systems, hence debiasing provides relevant insights suggesting the design of fairer strategies for performance-based funding allocations.

Sustainable development goals: conceptualization, communication and achievement synergies in a complex network framework.

In this work we use a network-based approach to investigate the complex system of interactions among the 17 Sustainable Development Goals (SDGs), that constitute the structure of the United Nations 2030 Agenda for a sustainable future. We construct a three-layer multiplex, in which SDGs represent nodes, and their connections in each layer are determined by similarity definitions based on conceptualization, communication, and achievement, respectively. In each layer of the multiplex, we investigate the presence of nodes with high centrality, corresponding to strategic SDGs. We then compare the networks to establish whether and to which extent similar patterns emerge. Interestingly, we observe a significant relation between the SDG similarity patterns determined by their achievement and their communication and perception, revealed by social network data. The proposed framework represents an instrument to unveil new and nontrivial aspects of sustainability, laying the foundation of a decision support system to define and implement SDG achievement strategies.

Characterization of real-world networks through quantum potentials.

Network connectivity has been thoroughly investigated in several domains, including physics, neuroscience, and social sciences. This work tackles the possibility of characterizing the topological properties of real-world networks from a quantum-inspired perspective. Starting from the normalized Laplacian of a network, we use a well-defined procedure, based on the dressing transformations, to derive a 1-dimensional Schrödinger-like equation characterized by the same eigenvalues. We investigate the shape and properties of the potential appearing in this equation in simulated small-world and scale-free network ensembles, using measures of fractality. Besides, we employ the proposed framework to compare real-world networks with the Erdos-Rényi, Watts-Strogatz and Barabási-Albert benchmark models. Reconstructed potentials allow to assess to which extent real-world networks approach these models, providing further insight on their formation mechanisms and connectivity properties.

Country-level factors dynamics and ABO/Rh blood groups contribution to COVID-19 mortality.

The identification of factors associated to COVID-19 mortality is important to design effective containment measures and safeguard at-risk categories. In the last year, several investigations have tried to ascertain key features to predict the COVID-19 mortality tolls in relation to country-specific dynamics and population structure. Most studies focused on the first wave of the COVID-19 pandemic observed in the first half of 2020. Numerous studies have reported significant associations between COVID-19 mortality and relevant variables, for instance obesity, healthcare system indicators such as hospital beds density, and bacillus Calmette-Guerin immunization. In this work, we investigated the role of ABO/Rh blood groups at three different stages of the pandemic while accounting for demographic, economic, and health system related confounding factors. Using a machine learning approach, we found that the "B+" blood group frequency is an important factor at all stages of the pandemic, confirming previous findings that blood groups are linked to COVID-19 severity and fatal outcome.

Predicting brain age with complex networks: From adolescence to adulthood.

In recent years, several studies have demonstrated that machine learning and deep learning systems can be very useful to accurately predict brain age. In this work, we propose a novel approach based on complex networks using 1016 T1-weighted MRI brain scans (in the age range 7-64years). We introduce a structural connectivity model of the human brain: MRI scans are divided in rectangular boxes and Pearson's correlation is measured among them in order to obtain a complex network model. Brain connectivity is then characterized through few and easy-to-interpret centrality measures; finally, brain age is predicted by feeding a compact deep neural network. The proposed approach is accurate, robust and computationally efficient, despite the large and heterogeneous dataset used. Age prediction accuracy, in terms of correlation between predicted and actual age r=0.89and Mean Absolute Error MAE =2.19years, compares favorably with results from state-of-the-art approaches. On an independent test set including 262 subjects, whose scans were acquired with different scanners and protocols we found MAE =2.52. The only imaging analysis steps required in the proposed framework are brain extraction and linear registration, hence robust results are obtained with a low computational cost. In addition, the network model provides a novel insight on aging patterns within the brain and specific information about anatomical districts displaying relevant changes with aging.

Potential energy of complex networks: a quantum mechanical perspective.

We propose a characterization of complex networks, based on the potential of an associated Schrödinger equation. The potential is designed so that the energy spectrum of the Schrödinger equation coincides with the graph spectrum of the normalized Laplacian. Crucial information is retained in the reconstructed potential, which provides a compact representation of the properties of the network structure. The median potential over several random network realizations, which we call ensemble potential, is fitted via a Landau-like function, and its length scale is found to diverge as the critical connection probability is approached from above. The ruggedness of the ensemble potential profile is quantified by using the Higuchi fractal dimension, which displays a maximum at the critical connection probability. This demonstrates that this technique can be successfully employed in the study of random networks, as an alternative indicator of the percolation phase transition. We apply the proposed approach to the investigation of real-world networks describing infrastructures (US power grid). Curiously, although no notion of phase transition can be given for such networks, the fractality of the ensemble potential displays signatures of criticality. We also show that standard techniques (such as the scaling features of the largest connected component) do not detect any signature or remnant of criticality.

An equity-oriented rethink of global rankings with complex networks mapping development.

Nowadays, world rankings are promoted and used by international agencies, governments and corporations to evaluate country performances in a specific domain, often providing a guideline for decision makers. Although rankings allow a direct and quantitative comparison of countries, sometimes they provide a rather oversimplified representation, in which relevant aspects related to socio-economic development are either not properly considered or still analyzed in silos. In an increasingly data-driven society, a new generation of cutting-edge technologies is breaking data silos, enabling new use of public indicators to generate value for multiple stakeholders. We propose a complex network framework based on publicly available indicators to extract important insight underlying global rankings, thus adding value and significance to knowledge provided by these rankings. This approach enables the unsupervised identification of communities of countries, establishing a more targeted, fair and meaningful criterion to detect similarities. Hence, the performance of states in global rankings can be assessed based on their development level. We believe that these evaluations can be crucial in the interpretation of global rankings, making comparison between countries more significant and useful for citizens and governments and creating ecosystems for new opportunities for development.