Continuous Markov Models for Analyzing the Effect of Environmental Personal Exposure on Multiple Sclerosis Progression.

Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disorder of the central nervous system, leading to progressive functional impairments. Predicting disease progression with a probabilistic and time-dependent approach might help suggest interventions for a better management of the disease. Recently, there has been increasing focus on the impact of air pollutants as environmental factors influencing disease progression. This study employs a Continuous-Time Markov Model (CMM) to explore the impact of air pollution measurements on MS progression using longitudinal data from MS patients in Italy between 2013 and 2022. Preliminary findings indicate a relationship between air pollution and MS progression, with pollutants like Particulate Matter with a diameter of 10 micrometers (PM10) or 2.5 micrometers (PM2.5), Nitrogen Dioxide (NO2), and Carbon Monoxide (CO) showing potential effects on disease activity.

Bayesian Networks in the Management of Hospital Admissions: A Comparison between Explainable AI and Black Box AI during the Pandemic.

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are "black box" to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffers from poor generalization ability in the presence of dataset shifts. Here, we present a comparison between an explainable-by-design ("white box") model (Bayesian Network (BN)) versus a black box model (Random Forest), both studied with the aim of supporting clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic.

Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

BACKGROUND: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating. Knowing which tools are most effective remains unclear. To evaluate the performance of computational methods, and to encourage innovation in method development, we designed a Critical Assessment of Genome Interpretation (CAGI) community challenge to place variant prioritization models head-to-head in a real-life clinical diagnostic setting. METHODS: We utilized genome sequencing (GS) data from families sequenced in the Rare Genomes Project (RGP), a direct-to-participant research study on the utility of GS for rare disease diagnosis and gene discovery. Challenge predictors were provided with a dataset of variant calls and phenotype terms from 175 RGP individuals (65 families), including 35 solved training set families with causal variants specified, and 30 unlabeled test set families (14 solved, 16 unsolved). We tasked teams to identify causal variants in as many families as possible. Predictors submitted variant predictions with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on the rank position of causal variants, and the maximum F-measure, based on precision and recall of causal variants across all EPCR values. RESULTS: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performers recalled causal variants in up to 13 of 14 solved families within the top 5 ranked variants. Newly discovered diagnostic variants were returned to two previously unsolved families following confirmatory RNA sequencing, and two novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant in an unsolved proband with phenotypes consistent with asparagine synthetase deficiency. CONCLUSIONS: Model methodology and performance was highly variable. Models weighing call quality, allele frequency, predicted deleteriousness, segregation, and phenotype were effective in identifying causal variants, and models open to phenotype expansion and non-coding variants were able to capture more difficult diagnoses and discover new diagnoses. Overall, computational models can significantly aid variant prioritization. For use in diagnostics, detailed review and conservative assessment of prioritized variants against established criteria is needed.

Neurological diagnoses in hospitalized COVID-19 patients associated with adverse outcomes: A multinational cohort study.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19.

Diabetes Technology Meeting 2023.

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.

Forecasting dominance of SARS-CoV-2 lineages by anomaly detection using deep AutoEncoders.

The coronavirus disease of 2019 (COVID-19) pandemic is characterized by sequential emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and lineages outcompeting previously circulating ones because of, among other factors, increased transmissibility and immune escape1-3. We devised an unsupervised deep learning AutoEncoder for viral genomes anomaly detection to predict future dominant lineages (FDLs), i.e., lineages or sublineages comprising ≥10% of viral sequences added to the GISAID database on a given week4. The algorithm was trained and validated by assembling global and country-specific data sets from 16,187,950 Spike protein sequences sampled between December 24th, 2019, and November 8th, 2023. The AutoEncoder flags low frequency FDLs (0.01% - 3%), with median lead times of 4-16 weeks. Over time, positive predictive values oscillate, decreasing linearly with the number of unique sequences per data set, showing average performance up to 30 times better than baseline approaches. The B.1.617.2 vaccine reference strain was flagged as FDL when its frequency was only 0.01%, more than one year earlier of being considered for an updated COVID-19 vaccine. Our AutoEncoder, applicable in principle to any pathogen, also pinpoints specific mutations potentially linked to increased fitness, and may provide significant insights for the optimization of public health pre-emptive intervention strategies.

CAD-RADS scoring of coronary CT angiography with Multi-Axis Vision Transformer: A clinically-inspired deep learning pipeline.

BACKGROUND AND OBJECTIVE: The standard non-invasive imaging technique used to assess the severity and extent of Coronary Artery Disease (CAD) is Coronary Computed Tomography Angiography (CCTA). However, manual grading of each patient's CCTA according to the CAD-Reporting and Data System (CAD-RADS) scoring is time-consuming and operator-dependent, especially in borderline cases. This work proposes a fully automated, and visually explainable, deep learning pipeline to be used as a decision support system for the CAD screening procedure. The pipeline performs two classification tasks: firstly, identifying patients who require further clinical investigations and secondly, classifying patients into subgroups based on the degree of stenosis, according to commonly used CAD-RADS thresholds. METHODS: The pipeline pre-processes multiplanar projections of the coronary arteries, extracted from the original CCTAs, and classifies them using a fine-tuned Multi-Axis Vision Transformer architecture. With the aim of emulating the current clinical practice, the model is trained to assign a per-patient score by stacking the bi-dimensional longitudinal cross-sections of the three main coronary arteries along channel dimension. Furthermore, it generates visually interpretable maps to assess the reliability of the predictions. RESULTS: When run on a database of 1873 three-channel images of 253 patients collected at the Monzino Cardiology Center in Milan, the pipeline obtained an AUC of 0.87 and 0.93 for the two classification tasks, respectively. CONCLUSION: According to our knowledge, this is the first model trained to assign CAD-RADS scores learning solely from patient scores and not requiring finer imaging annotation steps that are not part of the clinical routine.

Advancing Italian biomedical information extraction with transformers-based models: Methodological insights and multicenter practical application.

The introduction of computerized medical records in hospitals has reduced burdensome activities like manual writing and information fetching. However, the data contained in medical records are still far underutilized, primarily because extracting data from unstructured textual medical records takes time and effort. Information Extraction, a subfield of Natural Language Processing, can help clinical practitioners overcome this limitation by using automated text-mining pipelines. In this work, we created the first Italian neuropsychiatric Named Entity Recognition dataset, PsyNIT, and used it to develop a Transformers-based model. Moreover, we collected and leveraged three external independent datasets to implement an effective multicenter model, with overall F1-score 84.77 %, Precision 83.16 %, Recall 86.44 %. The lessons learned are: (i) the crucial role of a consistent annotation process and (ii) a fine-tuning strategy that combines classical methods with a "low-resource" approach. This allowed us to establish methodological guidelines that pave the way for Natural Language Processing studies in less-resourced languages.

Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort study.

Background: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning. Methods: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes. Findings: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively. Interpretation: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems. Funding: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences.

Critical assessment of variant prioritization methods for rare disease diagnosis within the Rare Genomes Project.

Background: A major obstacle faced by rare disease families is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years, and causal variants are identified in under 50%. The Rare Genomes Project (RGP) is a direct-to-participant research study on the utility of genome sequencing (GS) for diagnosis and gene discovery. Families are consented for sharing of sequence and phenotype data with researchers, allowing development of a Critical Assessment of Genome Interpretation (CAGI) community challenge, placing variant prioritization models head-to-head in a real-life clinical diagnostic setting. Methods: Predictors were provided a dataset of phenotype terms and variant calls from GS of 175 RGP individuals (65 families), including 35 solved training set families, with causal variants specified, and 30 test set families (14 solved, 16 unsolved). The challenge tasked teams with identifying the causal variants in as many test set families as possible. Ranked variant predictions were submitted with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on rank position of true positive causal variants and maximum F-measure, based on precision and recall of causal variants across EPCR thresholds. Results: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performing teams recalled the causal variants in up to 13 of 14 solved families by prioritizing high quality variant calls that were rare, predicted deleterious, segregating correctly, and consistent with reported phenotype. In unsolved families, newly discovered diagnostic variants were returned to two families following confirmatory RNA sequencing, and two prioritized novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant, in an unsolved proband with phenotype overlap with asparagine synthetase deficiency. Conclusions: By objective assessment of variant predictions, we provide insights into current state-of-the-art algorithms and platforms for genome sequencing analysis for rare disease diagnosis and explore areas for future optimization. Identification of diagnostic variants in unsolved families promotes synergy between researchers with clinical and computational expertise as a means of advancing the field of clinical genome interpretation.

A comparative analysis of the effects of containment policies on the epidemiological manifestation of the COVID-19 pandemic across nine European countries.

The COVID-19 pandemic has been a catastrophic event that has seriously endangered the world's population. Governments have largely been unprepared to deal with such an unprecedented calamity, partially due to the lack of sufficient or adequately fine-grained data necessary for forecasting the pandemic's evolution. To fill this gap, researchers worldwide have been collecting data about different aspects of COVID-19's evolution and government responses to them so as to provide the foundation for informative models and tools that can be used to mitigate the current pandemic and possibly prevent future ones. Indeed, since the early stages of the pandemic, a number of research initiatives were launched with this goal, including the PERISCOPE (Pan-European Response to the ImpactS of COVID-19 and future Pandemics and Epidemics) Project, funded by the European Commission. PERISCOPE aims to investigate the broad socio-economic and behavioral impacts of the COVID-19 pandemic, with the goal of making Europe more resilient and prepared for future large-scale risks. The purpose of this study, carried out as part of the PERISCOPE project, is to provide a first European-level analysis of the effect of government policies on the spread of the virus. To do so, we assessed the relationship between a novel index, the Policy Intensity Index, and four epidemiological variables collected by the European Centre for Disease Control and Prevention, and then applied a comprehensive Pan-European population model based on Multilevel Vector Autoregression. This model aims at identifying effects that are common to some European countries while treating country-specific policies as covariates, explaining the different evolution of the pandemic in nine selected countries due to data availability: Spain, France, Netherlands, Latvia, Slovenia, Greece, Ireland, Cyprus, Estonia. Results show that specific policies' effectiveness tend to vary consistently within the different countries, although in general policies related to Health Monitoring and Health Resources are the most effective for all countries.

Performance of an AI algorithm during the different phases of the COVID pandemics: what can we learn from the AI and vice versa.

Background: Artificial intelligence (AI) has proved to be of great value in diagnosing and managing Sars-Cov-2 infection. ALFABETO (ALL-FAster-BEtter-TOgether) is a tool created to support healthcare professionals in the triage, mainly in optimizing hospital admissions. Methods: The AI was trained during the pandemic's "first wave" (February-April 2020). Our aim was to assess the performance during the "third wave" of the pandemics (February-April 2021) and evaluate its evolution. The neural network proposed behavior (hospitalization vs home care) was compared with what was actually done. If there were discrepancies between ALFABETO's predictions and clinicians' decisions, the disease's progression was monitored. Clinical course was defined as "favorable/mild" if patients could be managed at home or in spoke centers and "unfavorable/severe" if patients need to be managed in a hub center. Results: ALFABETO showed accuracy of 76%, AUROC of 83%; specificity was 78% and recall 74%. ALFABETO also showed high precision (88%). 81 hospitalized patients were incorrectly predicted to be in "home care" class. Among those "home-cared" by the AI and "hospitalized" by the clinicians, 3 out of 4 misclassified patients (76.5%) showed a favorable/mild clinical course. ALFABETO's performance matched the reports in literature. Conclusions: The discrepancies mostly occurred when the AI predicted patients could stay at home but clinicians hospitalized them; these cases could be handled in spoke centers rather than hubs, and the discrepancies may aid clinicians in patient selection. The interaction between AI and human experience has the potential to improve both AI performance and our comprehension of pandemic management.

The Role of Native T1 and T2 Mapping Times in Identifying PD-L1 Expression and the Histological Subtype of NSCLCs.

We investigated the association of T1/T2 mapping values with programmed death-ligand 1 protein (PD-L1) expression in lung cancer and their potential in distinguishing between different histological subtypes of non-small cell lung cancers (NSCLCs). Thirty-five patients diagnosed with stage III NSCLC from April 2021 to December 2022 were included. Conventional MRI sequences were acquired with a 1.5 T system. Mean T1 and T2 mapping values were computed for six manually traced ROIs on different areas of the tumor. Data were analyzed through RStudio. Correlation between T1/T2 mapping values and PD-L1 expression was studied with a Wilcoxon-Mann-Whitney test. A Kruskal-Wallis test with a post-hoc Dunn test was used to study the correlation between T1/T2 mapping values and the histological subtypes: squamocellular carcinoma (SCC), adenocarcinoma (ADK), and poorly differentiated NSCLC (PD). There was no statistically significant correlation between T1/T2 mapping values and PD-L1 expression in NSCLC. We found statistically significant differences in T1 mapping values between ADK and SCC for the periphery ROI (p-value 0.004), the core ROI (p-value 0.01), and the whole tumor ROI (p-value 0.02). No differences were found concerning the PD NSCLCs.

Artificial intelligence and statistical methods for stratification and prediction of progression in amyotrophic lateral sclerosis: A systematic review.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord. The fact that ALS's disease course is highly heterogeneous, and its determinants not fully known, combined with ALS's relatively low prevalence, renders the successful application of artificial intelligence (AI) techniques particularly arduous. OBJECTIVE: This systematic review aims at identifying areas of agreement and unanswered questions regarding two notable applications of AI in ALS, namely the automatic, data-driven stratification of patients according to their phenotype, and the prediction of ALS progression. Differently from previous works, this review is focused on the methodological landscape of AI in ALS. METHODS: We conducted a systematic search of the Scopus and PubMed databases, looking for studies on data-driven stratification methods based on unsupervised techniques resulting in (A) automatic group discovery or (B) a transformation of the feature space allowing patient subgroups to be identified; and for studies on internally or externally validated methods for the prediction of ALS progression. We described the selected studies according to the following characteristics, when applicable: variables used, methodology, splitting criteria and number of groups, prediction outcomes, validation schemes, and metrics. RESULTS: Of the starting 1604 unique reports (2837 combined hits between Scopus and PubMed), 239 were selected for thorough screening, leading to the inclusion of 15 studies on patient stratification, 28 on prediction of ALS progression, and 6 on both stratification and prediction. In terms of variables used, most stratification and prediction studies included demographics and features derived from the ALSFRS or ALSFRS-R scores, which were also the main prediction targets. The most represented stratification methods were K-means, and hierarchical and expectation-maximisation clustering; while random forests, logistic regression, the Cox proportional hazard model, and various flavours of deep learning were the most widely used prediction methods. Predictive model validation was, albeit unexpectedly, quite rarely performed in absolute terms (leading to the exclusion of 78 eligible studies), with the overwhelming majority of included studies resorting to internal validation only. CONCLUSION: This systematic review highlighted a general agreement in terms of input variable selection for both stratification and prediction of ALS progression, and in terms of prediction targets. A striking lack of validated models emerged, as well as a general difficulty in reproducing many published studies, mainly due to the absence of the corresponding parameter lists. While deep learning seems promising for prediction applications, its superiority with respect to traditional methods has not been established; there is, instead, ample room for its application in the subfield of patient stratification. Finally, an open question remains on the role of new environmental and behavioural variables collected via novel, real-time sensors.

Localizing in-domain adaptation of transformer-based biomedical language models.

In the era of digital healthcare, the huge volumes of textual information generated every day in hospitals constitute an essential but underused asset that could be exploited with task-specific, fine-tuned biomedical language representation models, improving patient care and management. For such specialized domains, previous research has shown that fine-tuning models stemming from broad-coverage checkpoints can largely benefit additional training rounds over large-scale in-domain resources. However, these resources are often unreachable for less-resourced languages like Italian, preventing local medical institutions to employ in-domain adaptation. In order to reduce this gap, our work investigates two accessible approaches to derive biomedical language models in languages other than English, taking Italian as a concrete use-case: one based on neural machine translation of English resources, favoring quantity over quality; the other based on a high-grade, narrow-scoped corpus natively written in Italian, thus preferring quality over quantity. Our study shows that data quantity is a harder constraint than data quality for biomedical adaptation, but the concatenation of high-quality data can improve model performance even when dealing with relatively size-limited corpora. The models published from our investigations have the potential to unlock important research opportunities for Italian hospitals and academia. Finally, the set of lessons learned from the study constitutes valuable insights towards a solution to build biomedical language models that are generalizable to other less-resourced languages and different domain settings.

DeepMiCa: Automatic segmentation and classification of breast MIcroCAlcifications from mammograms.

BACKGROUND AND OBJECTIVE: Breast cancer is the world's most prevalent form of cancer. The survival rates have increased in the last years mainly due to factors such as screening programs for early detection, new insights on the disease mechanisms as well as personalised treatments. Microcalcifications are the only first detectable sign of breast cancer and diagnosis timing is strongly related to the chances of survival. Nevertheless microcalcifications detection and classification as benign or malignant lesions is still a challenging clinical task and their malignancy can only be proven after a biopsy procedure. We propose DeepMiCa, a fully automated and visually explainable deep-learning based pipeline for the analysis of raw mammograms with microcalcifications. Our aim is to propose a reliable decision support system able to guide the diagnosis and help the clinicians to better inspect borderline difficult cases. METHODS: DeepMiCa is composed by three main steps: (1) Preprocessing of the raw scans (2) Automatic patch-based Semantic Segmentation using a UNet based network with a custom loss function appositely designed to deal with extremely small lesions (3) Classification of the detected lesions with a deep transfer-learning approach. Finally, state-of-the-art explainable AI methods are used to produce maps for a visual interpretation of the classification results. Each step of DeepMiCa is designed to address the main limitations of the previous proposed works resulting in a novel automated and accurate pipeline easily customisable to meet radiologists' needs. RESULTS: The proposed segmentation and classification algorithms achieve an area under the ROC curve of 0.95 and 0.89 respectively. Compared to previously proposed works, this method does not require high performance computational resources and provides a visual explanation of the final classification results. CONCLUSION: To conclude, we designed a novel fully automated pipeline for detection and classification of breast microcalcifications. We believe that the proposed system has the potential to provide a second opinion in the diagnosis process giving the clinicians the opportunity to quickly visualise and inspect relevant imaging characteristics. In the clinical practice the proposed decision support system could help reduce the rate of misclassified lesions and consequently the number of unnecessary biopsies.

A comparative study of the definitions of intradialytic hypotension correlated with increased mortality to identify universal predictors.

Intradialytic hypotension (IDH) is a common complication in patients undergoing hemodialysis therapy. No consensus on the definition of intradialytic hypotension has been established so far. As a result, coherent and consistent evaluation of its effects and causes is difficult. Some studies have highlighted existing correlations between certain definitions of IDH and the risk of mortality for the patients. This work is mainly focused on these definitions. Our aim is to understand if different IDH definitions, all correlated with increased mortality risk, catch the same onset mechanisms or dynamics. To check whether the dynamics captured by these definitions are similar, we performed analyses of the incidence, of the IDH event onset timing, and checked whether there were similarities between the definitions in those aspects. We evaluated how these definitions overlap with each other and we evaluated which common factors could allow identifying patients at risk of IDH at the beginning of a dialysis session. The definitions of IDH we analyzed through statistical and machine learning approaches, showed a variable incidence on the HD sessions and had different onset time. We found that the set of parameters relevant for the prediction of the IDH was not always the same for the definitions considered. However, it can be observed that some predictors, such as the presence of comorbidities such as diabetes or heart disease, and a low pre-dialysis diastolic blood pressure, have shown universal relevance in highlighting an increased risk of IDH during the treatment. Among those parameters, the one that showed a major importance is the diabetes status of the patients. Diabetes or heart disease presence are permanent risk factors pointing out an increased IDH risk during the treatments, while, pre-dialysis diastolic blood pressure is instead a parameter that can change at every session and should be used to evaluate the specific risk to develop IDH for each session. The identified parameters could be used in the future to train more complex prediction models.

MALDI mass spectrometry imaging shows a gradual change in the proteome landscape during mouse ovarian folliculogenesis.

Our knowledge regarding the role proteins play in the mutual relationship among oocytes, surrounding follicle cells, stroma, and the vascular network inside the ovary is still poor and obtaining insights into this context would significantly aid our understanding of folliculogenesis. Here, we describe a spatial proteomics approach to characterize the proteome of individual follicles at different growth stages in a whole prepubertal 25-day-old mouse ovary. A total of 401 proteins were identified by nano-scale liquid chromatography-electrospray ionization-tandem mass spectrometry (nLC-ESI-MS/MS), 69 with a known function in ovary biology, as demonstrated by earlier proteomics studies. Enrichment analysis highlighted significant KEGG and Reactome pathways, with apoptosis, developmental biology, PI3K-Akt, epigenetic regulation of gene expression, and extracellular matrix organization being well represented. Then, correlating these data with the spatial information provided by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) on 276 follicles enabled the protein profiles of single follicle types to be mapped within their native context, highlighting 94 proteins that were detected throughout the secondary to the pre-ovulatory transition. Statistical analyses identified a group of 37 proteins that showed a gradual quantitative change during follicle differentiation, comprising 10 with a known role in follicle growth (NUMA1, TPM2), oocyte germinal vesicle-to-metaphase II transition (SFPQ, ACTBL, MARCS, NUCL), ovulation (GELS, CO1A2), and preimplantation development (TIF1B, KHDC3). The proteome landscape identified includes molecules of known function in the ovary, but also those whose specific role is emerging. Altogether, this work demonstrates the utility of performing spatial proteomics in the context of the ovary and offers sound bases for more in-depth investigations that aim to further unravel its spatial proteome.

Bioengineering and medical informatics education in MD programs: perspectives from three Italian experiences.

BACKGROUND: Given the impact of bioengineering and medical informatics technologies in health care, the design and implementation of education programs able to combine medical curricula with a proper teaching on engineering and informatics is now of paramount importance. In Italy, this goal has to fit in with the existing higher education system, which is structured into Bachelor programs and Master programs. Medicine and Surgery programs, instead, are designed as a six-year single-cycle Degree Program in Medicine and Surgery which comprises both class attendance and hospital internship and training. This program allows students to become Medical Doctors (MD). The different organization of this University program makes it not easy to introduce further contents, namely hard science courses, in the educational program. Notwithstanding this, we present here some recent innovative programs aimed at widening MD curriculum by including biomedical engineering and informatics subjects. In particular, we will introduce three of them. Two are joint-degree programs, the first between Humanitas University and Politecnico di Milano (MEDTEC School), and the second between University of Calabria and University Magna Graecia of Catanzaro (Medicina e Chirurgia TD). The Third one is a Professional Master coupled with an MD degree, based on a joint program among Pavia University, Pisa University, the Institute of Advanced studies in Pavia and the Scuola Superiore S. Anna in Pisa (MEET). CONTRIBUTION: The paper provides a description of the fundamental design principles of the three above mentioned programs, and explores some aspects of the teaching modules, highlighting their positive aspects. In particular, we show how the three different programs allow students to enrich their knowledge by studying engineering subjects and innovative methods and technologies, as well as their applications to patient care. CONCLUSIONS: The MEDTEC program is the first degree program at Italian and international scale which integrates medical and engineering subjects. In the following years, other programs were issued in Italy, defining similar education programs to couple a degree in medicine education with bioengineering and medical informatics, among which Medicina e Chirurgia TD and MEET. We believe the experiences described here in this paper represent the possibility of bridging the gap between medical and technological competencies.

Why did AI get this one wrong? - Tree-based explanations of machine learning model predictions.

Increasingly complex learning methods such as boosting, bagging and deep learning have made ML models more accurate, but harder to interpret and explain, culminating in black-box machine learning models. Model developers and users alike are often presented with a trade-off between performance and intelligibility, especially in high-stakes applications like medicine. In the present article we propose a novel methodological approach for generating explanations for the predictions of a generic machine learning model, given a specific instance for which the prediction has been made. The method, named AraucanaXAI, is based on surrogate, locally-fitted classification and regression trees that are used to provide post-hoc explanations of the prediction of a generic machine learning model. Advantages of the proposed XAI approach include superior fidelity to the original model, ability to deal with non-linear decision boundaries, and native support to both classification and regression problems. We provide a packaged, open-source implementation of the AraucanaXAI method and evaluate its behaviour in a number of different settings that are commonly encountered in medical applications of AI. These include potential disagreement between the model prediction and physician's expert opinion and low reliability of the prediction due to data scarcity.