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.

Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research.

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB; <37 weeks) or (2) early preterm birth (ePTB; <32 weeks) from 9 vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from public raw data via phylogenetic harmonization. The predictive models are validated on two independent unpublished datasets representing 331 samples from 148 pregnant individuals. The top-performing models (among 148 and 121 submissions from 318 teams) achieve area under the receiver operator characteristic (AUROC) curve scores of 0.69 and 0.87 predicting PTB and ePTB, respectively. Alpha diversity, VALENCIA community state types, and composition are important features in the top-performing models, most of which are tree-based methods. This work is a model for translation of microbiome data into clinically relevant predictive models and to better understand preterm birth.

Making sense of chemical space network shows signs of criticality.

Chemical space modelling has great importance in unveiling and visualising latent information, which is critical in predictive toxicology related to drug discovery process. While the use of traditional molecular descriptors and fingerprints may suffer from the so-called curse of dimensionality, complex networks are devoid of the typical drawbacks of coordinate-based representations. Herein, we use chemical space networks (CSNs) to analyse the case of the developmental toxicity (Dev Tox), which remains a challenging endpoint for the difficulty of gathering enough reliable data despite very important for the protection of the maternal and child health. Our study proved that the Dev Tox CSN has a complex non-random organisation and can thus provide a wealth of meaningful information also for predictive purposes. At a phase transition, chemical similarities highlight well-established toxicophores, such as aryl derivatives, mostly neurotoxic hydantoins, barbiturates and amino alcohols, steroids, and volatile organic compounds ether-like chemicals, which are strongly suspected of the Dev Tox onset and can thus be employed as effective alerts for prioritising chemicals before testing.

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.

Microbiome Preterm Birth DREAM Challenge: Crowdsourcing Machine Learning Approaches to Advance Preterm Birth Research.

Globally, every year about 11% of infants are born preterm, defined as a birth prior to 37 weeks of gestation, with significant and lingering health consequences. Multiple studies have related the vaginal microbiome to preterm birth. We present a crowdsourcing approach to predict: (a) preterm or (b) early preterm birth from 9 publicly available vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from raw sequences via an open-source tool, MaLiAmPi. We validated the crowdsourced models on novel datasets representing 331 samples from 148 pregnant individuals. From 318 DREAM challenge participants we received 148 and 121 submissions for our two separate prediction sub-challenges with top-ranking submissions achieving bootstrapped AUROC scores of 0.69 and 0.87, respectively. Alpha diversity, VALENCIA community state types, and composition (via phylotype relative abundance) were important features in the top performing models, most of which were tree based methods. This work serves as the foundation for subsequent efforts to translate predictive tests into clinical practice, and to better understand and prevent preterm birth.

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.

The impact of harmonization on radiomic features in Parkinson's disease and healthy controls: A multicenter study.

Radiomics is a challenging development area in imaging field that is greatly capturing interest of radiologists and neuroscientists. However, radiomics features show a strong non-biological variability determined by different facilities and imaging protocols, limiting the reproducibility and generalizability of analysis frameworks. Our study aimed to investigate the usefulness of harmonization to reduce site-effects on radiomics features over specific brain regions. We selected T1-weighted magnetic resonance imaging (MRI) by using the MRI dataset Parkinson's Progression Markers Initiative (PPMI) from different sites with healthy controls (HC) and Parkinson's disease (PD) patients. First, the investigation of radiomics measure discrepancies were assessed on healthy brain regions-of-interest (ROIs) via a classification pipeline based on LASSO feature selection and support vector machine (SVM) model. Then, a ComBat-based harmonization approach was applied to correct site-effects. Finally, a validation step on PD subjects evaluated diagnostic accuracy before and after harmonization of radiomics data. Results on healthy subjects demonstrated a dependence from site-effects that could be corrected with ComBat harmonization. LASSO regressor after harmonization was unable to select any feature to distinguish controls by site. Moreover, harmonized radiomics features achieved an area under the receiving operating characteristic curve (AUC) of 0.77 (compared to AUC of 0.71 for raw radiomics measures) in distinguish Parkinson's patients from HC. We found a not-negligible site-effect studying radiomics of HC pre- and post-harmonization of features. Our validation study on PD patients demonstrated a significant influence of non-biological noise source in diagnostic performances. Finally, harmonization of multicenter radiomic data represent a necessary step to make analysis pipelines reliable and replicable for multisite neuroimaging studies.

Explainable artificial intelligence (XAI) detects wildfire occurrence in the Mediterranean countries of Southern Europe.

The impacts and threats posed by wildfires are dramatically increasing due to climate change. In recent years, the wildfire community has attempted to estimate wildfire occurrence with machine learning models. However, to fully exploit the potential of these models, it is of paramount importance to make their predictions interpretable and intelligible. This study is a first attempt to provide an eXplainable artificial intelligence (XAI) framework for estimating wildfire occurrence using a Random Forest model with Shapley values for interpretation. Our findings accurately detected regions with a high presence of wildfires (area under the curve 81.3%) and outlined the drivers empowering occurrence, such as the Fire Weather Index and Normalized Difference Vegetation Index. Furthermore, our analysis suggests the presence of anomalous hotspots. In contexts where human and natural spheres constantly intermingle and interact, the XAI framework, suitably integrated into decision support systems, could support forest managers to prevent and mitigate future wildfire disasters and develop strategies for effective fire management, response, recovery, and resilience.

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.

Psychological counseling in the Italian academic context: Expected needs, activities, and target population in a large sample of students.

University psychological counseling (UPC) is receiving growing attention as a means to promote mental health and academic success among young adults and prevent irregular attendance and dropout. However, thus far, little effort has been directed towards the implementation of services attuned to students' expectations and needs. This work intends to contribute to the existing literature on this topic, by exploring the perceptions of UPC among a population of 39,277 students attending one of the largest universities in the South of Italy. Almost half of the total population correctly identified the UPC target population as university students, and about one third correctly expected personal distress to be the main need that UPC should target. However, a large percentage did not have a clear idea about UPC target needs, activities, and population. When two specific student subsamples were analyzed using a person-centered analysis, namely (i) those who expressed their intention to use the counseling service but had not yet done so and (ii) those who had already used it, the first subsample clustered into two groups, characterized by an "emotional" and a "psychopathological" focus, respectively, while the second subsample clustered into three groups with a "clinical", "socioemotional", and "learning" focus, respectively. This result shows a somewhat more "superficial" and "common" representation of UPC in the first subsample and a more "articulated" and "flexible" vision in the second subsample. Taken together, these findings suggest that UPC services could adopt "student-centered" strategies to both identify and reach wider audiences and specific student subgroups. Recommended strategies include robust communication campaigns to help students develop a differentiated perception of the available and diverse academic services, and the involvement of active students to remove the barriers of embarrassment and shame often linked to the stigma of using mental health services.

A primer on machine learning techniques for genomic applications.

High throughput sequencing technologies have enabled the study of complex biological aspects at single nucleotide resolution, opening the big data era. The analysis of large volumes of heterogeneous "omic" data, however, requires novel and efficient computational algorithms based on the paradigm of Artificial Intelligence. In the present review, we introduce and describe the most common machine learning methodologies, and lately deep learning, applied to a variety of genomics tasks, trying to emphasize capabilities, strengths and limitations through a simple and intuitive language. We highlight the power of the machine learning approach in handling big data by means of a real life example, and underline how described methods could be relevant in all cases in which large amounts of multimodal genomic data are available.

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.

Hausdorff clustering.

A clustering algorithm based on the Hausdorff distance is analyzed and compared to the single, complete, and average linkage algorithms. The four clustering procedures are applied to a toy example and to the time series of financial data. The dendrograms are scrutinized and their features compared. The Hausdorff linkage relies on firm mathematical grounds and turns out to be very effective when one has to discriminate among complex structures.