A Symbolic AI Approach to Medical Training

: In traditional medical education, learners are mostly trained to diagnose and treat patients through supervised practice. Artificial Intelligence and simulation techniques can complement such an educational practice. In this paper, we present GLARE-Edu, an innovative system in which AI knowledge-based methodologies and simulation are exploited to train learners "how to act" on patients based on the evidence-based best practices provided by clinical practice guidelines. GLARE-Edu is being developed by a multi-disciplinary team involving physicians and AI experts, within the AI-LEAP (LEArning Personalization of AI and with AI) Italian project. GLARE-Edu is domain-independent: it supports the acquisition of clinical guidelines and case studies in a computer format. Based on acquired guidelines (and case studies), it provides a series of educational facilities: (i) navigation, to navigate the structured representation of the guidelines provided by GLARE-Edu, (ii) automated simulation, to show learners how a guideline would suggest to act, step-by-step, on a specific case, and (iii) (self)verification, asking learners how they would treat a case, and comparing step-by-step the learner's proposal with the suggestions of the proper guideline. In this paper, we describe GLARE-Edu architecture and general features, and we demonstrate our approach through a concrete application to the melanoma guideline and we propose a preliminary evaluation

Durable complete response in a patient with BRAF-mutated advanced melanoma with ocular and skin toxicities from BRAF/MEK targeted therapy after immune checkpoint inhibitor treatment: a case report

Here we report the case of a woman suffering from advanced melanoma who developed severe toxicities with BRAF and MEK inhibitors (BRAFis, MEKis), given as second-line therapy after failure of immunotherapy, who achieved a complete and durable response lasting for over 5 years. Significant progress has been achieved in the treatment of advanced melanoma with immune checkpoint inhibitors (ICIs) and targeted therapies using BRAFis and MEKis. While these treatments improve survival, they also pose risks of severe toxicities. Notably, when targeted therapy follows immunotherapy, immune-mediated toxicities may emerge months later due to tumor microenvironment modulation. Despite these risks, both approaches offer a durable response in eligible patients. Further understanding is needed to determine how prior immunotherapy may influence subsequent toxicity risks of target therapy. Understanding these factors could optimize treatment strategies and improve patient outcomes

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Surgical Treatment of Stage Four Knee Pressure Injury with Pedicled Fasciocutaneous Flap in Patient Affected by Spina Bifida – Case Report

Introduction:Patients affected by spina bifida (SB) can present varying degrees of paralysis, limited mobility, impaired sensation, orthopedic problems and bowel, bladder, and renal impairments. Skin wounds are reported as one of the primary diagnosis associated with hospitalizations in SB affected patients. In young patients, pressure injuries can occur more frequently at the lower limb. A multidisciplinary approach and a proper surgical technique are mandatory to obtain favorable long-term outcomes, in terms of adequate coverage and risk of recurrence. Case Presentation:A Caucasian male 21-year-old wheelchair-bound patient with history of SB was admitted to our department with stage four pressure injury on the medial aspect of knee joint and osteomyelitis. After antibiotic therapy wound preparation and debridement, we covered the pressure sore with a pedicled fasciocutaneous flap harvested from the medial compartment of the thigh. In the distal part, we splitted the fascia from the flap and used it to reconstruct the exposed knee joint. We did not report any complications and no recurrence was observed at 1-year follow-up examination. Conclusion:In this reported case, the multidisciplinary approach and the surgical technique allowed us to cover the soft-tissue defect around knee joint, reducing morbidity, surgical time, and cost with good long-term outcomes. Keywords:Spina bifida, pressure injuries, fasciocutaneous flap.</jats:p