Estimating the Post-Mortem Interval Under Extreme Heat Environments: A Climate-Adaptive Case Series Based on Artificial Intelligence-Supported Diagnostics Francesco Sessa, Clelia Grippaldi, Massimiliano Esposito, Carlos A. Gutierrez, Emina Dervišević, Efehan Ulas, Federica Ministeri, Lucio Di Mauro, Matteo Bolcato, Cristoforo Pomara, Monica Salerno Diagnostics, 2026 Background/Objectives: Accurate post-mortem interval (PMI) estimation becomes increasingly difficult when bodies decompose under extreme heat. Hyperthermal Mediterranean environments accelerate soft-tissue degradation, induce early mummification, and distort classical thanatological indicators, often resulting in substantial PMI overestimation. This study analyzes three forensic cases affected by climate-driven decomposition anomalies and presents a climate-adaptive, AI-assisted diagnostic framework applied uniformly across all cases to improve PMI interpretation. Methods: A retrospective case series analysis was conducted on three individuals recovered during summer heatwaves. Crime scene investigation, post-mortem computed tomography (PMCT), autopsy, and genetic identification were integrated with 5–15-year meteorological datasets. Classical PMI estimations were compared with circumstantial data. A multimodal AI model, incorporating environmental features, decomposition morphology, and microenvironmental modifiers, was operationalized for each case using a hybrid Random Forest–LSTM architecture. Engineered indices included Accumulated Degree Days (ADD), a Decomposition Index, and climate-stress metrics (Thermal Load Index, Desiccation Pressure Factor, Microenvironmental Distortion Coefficient). Quantile regression provided calibrated prediction intervals. Results: Morphological assessments overestimated PMI in every case, suggesting intervals of 1–6 months despite true PMIs of approximately 20 days (Cases 1–2) or 36–48 h (Case 3). The AI model yielded conceptual outputs more consistent with verified PMIs, ~21 days (Case 1), ~23 days (Case 2), and ~42 h (Case 3), each accompanied by 50% and 90% prediction intervals. Explainability analyses identified thermal load, desiccation pressure, and microenvironmental distortion, particularly insulation in Case 3, as dominant drivers. Conclusions: Extreme heat fundamentally alters decomposition trajectories, rendering classical PMI methods unreliable. Applying a climate-aware, AI-assisted diagnostic framework across all three cases improved interpretability, providing uncertainty-aware estimates aligned with true PMIs. The AI framework is presented as a conceptual, non-trained, proof-of-concept system, and reported outputs represent operational demonstrations rather than validated predictions, offering a promising foundation for next-generation PMI diagnostics in hyperthermal forensic settings.
AI-Assisted Diagnostic Evaluation of IHC in Forensic Pathology: A Comparative Study with Human Scoring Francesco Sessa, Mara Ragusa, Massimiliano Esposito, Mario Chisari, Cristoforo Pomara, Monica Salerno Diagnostics, 2026 Background/Objectives: Immunohistochemistry (IHC) is a critical diagnostic tool in forensic pathology, enabling molecular-level assessment of wound vitality, post-mortem interval, and cause of death. However, IHC interpretation is subject to variability due to its reliance on human expertise. This study investigates whether artificial intelligence (AI), specifically a generative model, can assist in the diagnostic evaluation of IHC slides and replicate expert-level scoring, thereby improving consistency and reproducibility. Methods: A total of 225 high-resolution IHC images were classified into five immunoreactivity categories. The AI model (ChatGPT-4V) was trained on 150 labeled images and tested blindly on 75 unseen slides. Performance was assessed using confusion matrices, per-class precision/recall/F1, overall accuracy, Cohen’s κ (unweighted and weighted), and binary metrics (sensitivity, specificity, MCC). Results: Overall accuracy was 81.3% (95% CI: 71.1–88.5%), with substantial agreement (κ = 0.767 unweighted; 0.805 linear-weighted; 0.848 quadratic-weighted). Binary classification achieved a sensitivity of 98.3%, specificity of 93.3%, MCC of 0.92. Accuracy was highest in extreme categories (− and +++, 93.3%), while intermediate classes (+ and ++) showed reduced performance (error rates up to 33%). Evaluation was rapid and consistent but lacked interpretative reasoning and struggled with borderline cases. Conclusions: AI-assisted diagnostic evaluation of IHC slides demonstrates promising accuracy and consistency, particularly in well-defined staining patterns. While not a replacement for human expertise, AI can serve as a valuable adjunct in forensic pathology, supporting rapid and standardized assessments. Ethical and legal considerations must guide its implementation in medico-legal contexts.
Predicting Physical Appearance from Low Template: State of the Art and Future Perspectives Francesco Sessa, Emina Dervišević, Massimiliano Esposito, Martina Francaviglia, Mario Chisari, Cristoforo Pomara, Monica Salerno Genes, 2026 Background/Objectives: Forensic DNA phenotyping (FDP) enables the prediction of externally visible characteristics (EVCs) such as eye, hair, and skin color, ancestry, and age from biological traces. However, low template DNA (LT-DNA), often derived from degraded or trace samples, poses significant challenges due to allelic dropout, contamination, and incomplete profiles. This review evaluates recent advances in FDP from LT-DNA, focusing on the integration of machine learning (ML) models to improve predictive accuracy and operational readiness, while addressing ethical and population-related considerations. Methods: A comprehensive literature review was conducted on FDP and ML applications in forensic genomics. Key areas examined include SNP-based trait modeling, genotype imputation, epigenetic age estimation, and probabilistic inference. Comparative performance of ML algorithms (Random Forests, Support Vector Machines, Gradient Boosting, and deep learning) was assessed using datasets such as the 1000 Genomes Project, UK Biobank, and forensic casework samples. Ethical frameworks and validation standards were also analyzed. Results: ML approaches significantly enhance phenotype prediction from LT-DNA, achieving AUC > 0.9 for eye color and improving SNP recovery by up to 15% through imputation. Tools like HIrisPlex-S and VISAGE panels remain robust for eye and hair color, with moderate accuracy for skin tone and emerging capabilities for age and facial morphology. Limitations persist in admixed populations and traits with polygenic complexity. Interpretability and bias mitigation remain critical for forensic admissibility. Conclusions: L integration strengthens FDP from LT-DNA, offering valuable investigative leads in challenging scenarios. Future directions include multi-omics integration, portable sequencing platforms, inclusive reference datasets, and explainable AI to ensure accuracy, transparency, and ethical compliance in forensic applications.
Genetic and epigenetic determinants of fetal alcohol spectrum disorders: Toward a precision medicine approach Francesco Sessa, Marco Carotenuto, Davide Ferorelli, Massimiliano Esposito, Cristoforo Pomara, Monica Salerno Experimental and Molecular Pathology, 2025 Fetal Alcohol Spectrum Disorders (FASD) encompass a continuum of neurodevelopmental and physical impairments resulting from prenatal alcohol exposure (PAE). Despite widespread recognition of ethanol's teratogenic effects, the clinical variability observed in FASD suggests a multifactorial etiology involving genetic, biochemical, epigenetic, and environmental influences. This review provides an integrative analysis of how genetic polymorphisms in key alcohol-metabolizing enzymes (ADH1B, ADH1C, ALDH2, CYP2E1, and CAT) modulate maternal and fetal susceptibility to ethanol and its toxic metabolite, acetaldehyde. These polymorphisms influence enzymatic activity, oxidative stress responses, and detoxification efficiency, thereby shaping fetal exposure and risk. The review further explores maternal-fetal genotype interactions, gene-environment dynamics, and the timing of exposure as critical modulators of FASD outcomes. Epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA regulation, are examined as mediators of long-term gene expression changes and neurodevelopmental disruption. Novel insights are provided into the roles of the 5-HTTLPR and orexin systems in neuropsychiatric vulnerability. By synthesizing molecular, genetic, and clinical perspectives, this review advocates for a precision medicine approach to FASD prevention and management. It discusses the potential of genetic screening, predictive modeling, and theranoMiRNAs for risk stratification and early intervention. Importantly, it also addresses the translational challenges, including cost, feasibility, and the risk of false positives/negatives, that must be overcome to move from theory to clinical practice. These insights support the development of personalized, ethically grounded strategies to reduce fetal harm and improve outcomes in genetically and environmentally susceptible populations.
Fatal Dog Attacks in Italy (2009–2025): The Urgent Need for a National Risk Registry Fabrizio Iarussi, Francesco Sessa, Serena Piccirillo, Martina Francaviglia, Alessandra Recchia, Antonella Colella, Matteo Bolcato, Monica Salerno, Angelo Peli, Cristoforo Pomara Animals, 2025 Fatal dog attacks are rare but devastating events with significant public health, forensic, and legal implications. Italy lacks a centralized registry for such incidents, limiting the ability to monitor trends and implement preventive strategies. This retrospective study analyzes all verified fatal dog attacks in Italy from 2009 to 2025. Data were collected from national and regional media, cross-verified, and organized into a comprehensive database. Descriptive statistics, chi-square tests, logistic and Poisson regressions, and interaction analyses were performed to identify patterns in victim demographics, breed involvement, ownership status, and environmental context. A total of 54 fatal attacks were recorded, with an increasing trend observed in the last five years. Elderly individuals (≥65) and preschool-aged children (≤4) were the most affected groups. Molosser and bull-type breeds were implicated in 69% of cases, and 92.6% of attacks involved owned dogs—more than half belonging to the victim. Private settings accounted for 66.7% of incidents. Comparative analysis with U.S. data revealed similar demographic and breed-related patterns, but also highlighted Italy’s lack of a centralized behavioral risk registry. Fatal dog attacks in Italy follow recurring and preventable patterns. The absence of a national database severely limits surveillance and intervention. A centralized behavioral risk registry, modeled on international systems, should be established to support early detection, policy development, and multidisciplinary collaboration.
Applying the WHO ICF Framework to Fetal Alcohol Spectrum Disorder (FASD): A Forensic and Clinical Perspective on Disability Assessment and Patient Support Davide Ferorelli, Francesco Calò, Gianmarco Sirago, Dania Comparcini, Filippo Gibelli, Francesco Sessa, Marco Carotenuto, Biagio Solarino, Monica Salerno Healthcare Switzerland, 2025 Background/Objectives: This article aims to investigate the multifaceted effects of alcohol on neurophysiopathological development from gestational stages through adult life and the consequent dynamic-relational challenges in individuals with Fetal Alcohol Spectrum Disorder (FASD). FASD, resulting from prenatal alcohol exposure (PAE), is characterized by a range of neurological, cognitive, behavioral, and sometimes physical impairments. This article explores how alcohol and its toxic metabolites cross the placenta, inducing direct cellular toxicity and epigenetic alterations that disrupt critical neurodevelopmental processes such as neurogenesis and brain circuit formation. Clinically, individuals with FASD exhibit diverse deficits in executive functioning, learning, memory, social skills, and sensory-motor abilities, leading to significant lifelong disabilities. A central focus is the application of the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) criteria to comprehensively frame these disabilities. The ICF’s biopsychosocial model allows for a multidimensional assessment of impairments in body functions and structures, limitations in activities, and restrictions in participation, while also considering the crucial role of environmental factors. Methods: PubMed and Semantic Scholar databases were searched for relevant papers published in English. Results: This article highlights the utility of the ICF in creating individualized functioning profiles to guide interventions and support services, addressing the limitations of traditional assessment methods. Conclusions: While the ICF framework offers a robust approach for understanding and managing FASD, further research is essential to develop and validate FASD-specific ICF-based assessment tools to enhance support and social participation for affected individuals.
A nationwide forensic case-series of femicides in Italy – Part 1: Clues to the motives of the murder Rossana Cecchi, Anna Laura Santunione, Jessika Camatti, Alice Buzzelli, Alessandra De Martina, Alessandra Sannella, Marco Vinceti, Graziamaria Corbi, Carlo Pietro Campobasso, Matilde Sassani, Giovanna Laura De Fazio, Paolo Fais, Susi Pelotti, Arianna Giorgetti, Elena Lacchè, Andrea Verzeletti, Bianca Beltrame, Riccardo Zoia, Lorenzo Franceschetti, Giulia Vignali, Carlo Moreschi, Lorenzo Desinan, Ugo Da Broi, Georgia Zara, Sarah Gino, Valentina Bugelli, Simone Balduini, Debora Ginocchio, Elisabetta Lubian, Antonietta Porzio, Federica Cascone, Guido Viel, Francesco Angiola, Francesco Introna, Sara Sablone, Mariagrazia Calvano, Francesco Ausania, Luca-Maria Solari, Alessio Asmundo, Elvira Ventura Spagnolo, Gennaro Baldino, Silvia Damiana Visonà, Sofia Bodini, Emanuela Turillazzi, Mario Gabbrielli, Alice Bacchio, Antonina Argo, Ginevra Malta, Ernesto D’Aloja, Roberto Demontis, Camilla Gozzelino, Jessica Sanna, Raffaele Giorgetti, Federica Bora, Francesco Ventura, Isabella Caristo, Antonio Oliva, Giulia Mercuri, Cristoforo Pomara, Monica Salerno, Luigi Cipolloni, Vilma Pinchi, Martina Focardi, Luigi Tonino Marsella, Michele Treglia, Isabella Aquila, Matteo Antonio Sacco, Rosamaria Gaudio, Margherita Neri, Raffaella Marino Legal Medicine, 2025 Understanding the motives behind femicides is crucial to design effective prevention strategies and to support women's self-determination, free from threats to their mental and physical integrity. We conducted a retrospective, multicenter forensic study involving 27 Italian Institutes of Legal Medicine, analyzing 1238 female homicides (1950-2023). Cases were classified as femicide or non-femicide female homicide according to the medico-legal definition of femicide as the murder due to the failure to recognize women's right to self-determination. Motives were categorized into 12 groups, and relevant anamnestic and circumstantial data were collected. Of the 1238 cases, 410 were identified as femicides, 395 as non-femicides, and 433 were excluded for insufficient information. Femicides were most frequently driven by jealousy/rejection (n = 185; 45.1 %) and separation/divorce (n = 144; 35.1 %), often in the context of intimate partner violence or inability to accept the end of a relationship. Non-femicides were predominantly associated with the perpetrator's psychiatric disorder and/or drug addiction (n = 126; 31.9 %), violent aggression without gender-related motive (n = 69; 17.5 %), victim's illness (n = 63; 15.9 %), or economic reasons (n = 58; 14.7 %). In the Italian context, most femicides stem from relational dynamics - particularly jealousy, rejection, and separation - whereas non-femicides are more often linked to psychiatric illness, substance abuse, or non-gender-related aggression. Incorporating these findings into clinical risk assessment protocols, especially in emergency and primary care settings, may help identify women at high risk and guide targeted prevention strategies.
A nationwide forensic case-series of femicides in Italy – Part 2: Clues to its epidemiology, prediction and prevention Rossana Cecchi, Jessika Camatti, Anna Laura Santunione, Marco Vinceti, Tommaso Filippini, Riccardo Mazzoli, Alice Buzzelli, Alessandra De Martina, Graziamaria Corbi, Carlo Pietro Campobasso, Alessandra Sannella, Paolo Fais, Susi Pelotti, Arianna Giorgetti, Elena Lacchè, Andrea Verzeletti, Bianca Beltrame, Riccardo Zoia, Lorenzo Franceschetti, Giulia Vignali, Carlo Moreschi, Lorenzo Desinan, Ugo Da Broi, Georgia Zara, Sarah Gino, Valentina Bugelli, Simone Balduini, Silvia Pascari, Virginia Tordoni, Antonietta Porzio, Federica Cascone, Guido Viel, Giorgia Franchetti, Francesco Introna, Sara Sablone, Mariagrazia Calvano, Francesco Ausania, Luca-Maria Solari, Alessio Asmundo, Elvira Ventura Spagnolo, Gennaro Baldino, Giovanni Cecchetto, Chiara Franzetti, Emanuela Turillazzi, Mario Gabbrielli, Francesco Baldari, Flavio Pertosa, Antonina Argo, Ginevra Malta, Ernesto D’Aloja, Roberto Demontis, Matteo Nioi, Jessica Sanna, Raffaele Giorgetti, Loredana Buscemi, Mariasole Fede, Francesco Ventura, Isabella Caristo, Antonio Oliva, Giulia Mercuri, Giorgia Guarnieri, Cristoforo Pomara, Monica Salerno, Francesco Sessa, Luigi Cipolloni, Vilma Pinchi, Martina Focardi, Luigi Tonino Marsella, Michele Treglia, Isabella Aquila, Matteo Antonio Sacco, Rosamaria Gaudio, Margherita Neri, Raffaella Marino Legal Medicine, 2025 • Femicide is a growing medico-legal and public health concern. • Overkilling and injury to identity/erogenous zones common in femicide. • Dose response link found between lesion count and femicide likelihood. • Results highlight patterns relevant for forensic classification and prevention. • Standardization of medico-legal indicators is needed for comparability. Femicides are grievous, but little is known about risk factors and preventive measures. We present the results of a study conducted across 27 Italian Forensic Institutes. We analyzed 1,238 cases of female homicide and, adopting the definition of femicide as the murder due to the failure to recognize women’s right to self-determination, we identified 410 cases as femicides and 395 as non-femicides Current partners were identified as aggressors in a much larger proportion of femicide cases (241 femicides vs. 145 non-femicides; odds ratio (OR) of femicide 2.46, 95 % CI 1.85–3.27), such association being more pronounced for ex-partners (102 vs. 11; OR 11.56, 95 % CI 6.10–21.92). Sharp weapons showed a higher frequency in femicides (168 vs. 140; OR 1.26, 95 % CI 0.95–1.68). Femicides were more often associated with bodies found in vehicles (31 vs. 9; OR 3.50, 95 % CI 1.64–7.45) and outdoor (68 vs. 43; OR 1.62, 95 % CI 1.08–2.45). There was an indication of femicides being more frequently associated with overkilling (87/323 vs. 71/324; OR 1.24, 95 % CI 0.88–1.76) and even more with lesions located in erogenous zones (94/316 vs. 70/325; OR 1.38, 95 % CI: 0.97–1.95). However, the strongest (though statistically imprecise) association emerged for overkilling in erogenous zones (12/398 vs. 6/389; OR 1.95, 95 % CI: 0.72–5.25). The number of lesions showed a nonlinear association with femicide likelihood. These findings offer forensic indicators that could contribute in predicting and potentially prevent femicide occurrence in a Western population such as the Italian one.
Toxicological Advancements in Cocaine Detection: A Review Massimiliano Esposito, Francesco Sessa, Federico Giuseppe Patanè, Andreana Nicoletta Maria Maglitto, Giuseppe Cocimano, Nunzio Di Nunno, Monica Salerno Current Medicinal Chemistry, 2023
Covid-19 vaccine and death: Causality algorithm according to the who eligibility diagnosis Cristoforo Pomara, Francesco Sessa, Marcello Ciaccio, Francesco Dieli, Massimiliano Esposito, Giovanni Maurizio Giammanco, Sebastiano Fabio Garozzo, Antonino Giarratano, Daniele Prati, Francesca Rappa, Monica Salerno, Claudio Tripodo, Pier Mannuccio Mannucci, Paolo Zamboni Diagnostics, 2021
Transcranial magnetic stimulation as a tool to investigate motor cortex excitability in sport Fiorenzo Moscatelli, Antonietta Messina, Anna Valenzano, Vincenzo Monda, Monica Salerno, Francesco Sessa, Ester La Torre, Domenico Tafuri, Alessia Scarinci, Michela Perrella, Gabriella Marsala, Marcellino Monda, Giuseppe Cibelli, Chiara Porro, Giovanni Messina Brain Sciences, 2021
Anaphylactic death: A new forensic workflow for diagnosis Massimiliano Esposito, Angelo Montana, Aldo Liberto, Veronica Filetti, Nunzio Di Nunno, Francesco Amico, Monica Salerno, Carla Loreto, Francesco Sessa Healthcare Switzerland, 2021
Dog-bite-related attacks: A new forensic approach Fabrizio Iarussi, Luigi Cipolloni, Giuseppe Bertozzi, Luigi Sasso, Michela Ferrara, Monica Salerno, Giuseppe Tommaso Roberto Rubino, Francesca Maglietta, Armida Dinisi, Davide Albano, Valerio Iarussi, Cristoforo Pomara, Francesco Sessa Forensic Science International, 2020
The Important Role of Adiponectin and Orexin-A, Two Key Proteins Improving Healthy Status: Focus on Physical Activity Rita Polito, Vincenzo Monda, Ersilia Nigro, Antonietta Messina, Girolamo Di Maio, Maria Teresa Giuliano, Stefania Orrù, Esther Imperlini, Giuseppe Calcagno, Laura Mosca, Maria Pina Mollica, Giovanna Trinchese, Alessia Scarinci, Francesco Sessa, Monica Salerno, Gabriella Marsala, Pasqualina Buono, Annamaria Mancini, Marcellino Monda, Aurora Daniele, Giovanni Messina Frontiers in Physiology, 2020
Neuropeptides’ hypothalamic regulation of sleep control in children affected by functional non‐retentive fecal incontinence Vincenzo Monda, Marco Carotenuto, Francesco Precenzano, Diego Iacono, Antonietta Messina, Monica Salerno, Francesco Sessa, Valentina Lanzara, Giovanni Messina, Giuseppe Quatrosi, Rosaria Nardello, Francesca Felicia Operto, Claudia Santoro, Fiorenzo Moscatelli, Chiara Porro, Christian Zammit, Marcellino Monda, Grazia Maria Giovanna Pastorino, Luigi Vetri, Lucia Parisi, Maria Ruberto, Michele Roccella Brain Sciences, 2020
Ketogenic diet and sport performance F. Moscatelli, Anna Valenzano, Rita Polito, Sessa Francesco, A. Montana, M. Salerno, Antonietta Messina, M. Monda, G. Cibelli, V. Monda, G. Messina Sport Mont, 2020
Homicide or car accident: The case of the ‘guilty’ fibre Stefania De Simone, Francesca Maglietta, Michela Ferrara, Lorenzo Spagnolo, Pietrantonio Ricci, Dania De Carlo, Monica Salerno, Francesco Sessa, Giuseppe Bertozzi Medico Legal Journal, 2019
25-hydroxy vitamin D detection using different analytic methods in patients with migraine Luca Gallelli, Andzelika Michniewicz, Erika Cione, Aida Squillace, Manuela Colosimo, Corrado Pelaia, Alessia Fazio, Stefania Zampogna, Francesco Peltrone, Rosario Iannacchero, Giovambattista De Sarro, G&SP Working Group, Monica Salerno, Giulio Di Mizio Journal of Clinical Medicine, 2019
Human brain injury and mirnas: An experimental study Francesco Sessa, Francesca Maglietta, Giuseppe Bertozzi, Monica Salerno, Giulio Di Mizio, Giovanni Messina, Angelo Montana, Pietrantonio Ricci, Cristoforo Pomara International Journal of Molecular Sciences, 2019
Aerobic exercise and orexin A: Role of sympathetic activity and redox system Journal of Biological Regulators and Homeostatic Agents, 2019
Sports training and adaptive changes Francesco Sessa, Giovanni Messina, Anna Valenzano, Antonietta Messina, Monica Salerno, et al. Sport Sciences for Health, 2018