Background and Objective: Hepatoblastoma is the most common pediatric liver cancer and represents a serious clinical challenge as no effective therapies have yet been found for advanced states and relapses of the disease. Methods: In this work, we use a well-established agent-based model of the immune response now equipped with anti-cancer therapy response to study the evolution of the disease and the role of the immune system in its containment. Results: We simulate the course of hepatoblastoma over three years in a population of virtual patients, successfully mimicking clinical mortality and symptom onset rates, as well as observations on the main tumor transcriptomic subtypes. Conclusions: The capacity of the introduced framework to reproduce clinical data and the heterogeneity of hepatoblastoma, combined with the possibility of observing the dynamics of cellular entities at the microscopic scale and the key chemical signals involved in disease progression, makes the model a promising resource for future research on in silico trials.

Addressing complexity in the study of life sciences through Systems Biology and Systems Medicine has been transformative, making Systems Pharmacology the next logical step. In this review, we focus on physical stimuli, whose potential in pharmacology has been neglected, despite demonstrated therapeutic properties. To address this overlooked aspect of pharmacology, we aim to (i), highlight how physical stimuli (mechanical, optical, magnetic, electrical) influence inflammation; (ii) identify known overlaps among transduction mechanisms of physical stimuli and highlight the need for deeper understanding of these mechanisms; (iii) promote advanced network approaches as tools to understand this complexity and enhance the potential of anti-inflammatory physical therapies; and (iv), integrate physical stimuli into the mindset of pharmacologists. The overall purpose of this review is to spark questions rather than provide answers, and to drive research in this critically underexplored area.

Personalized medicine strategies are gaining momentum nowadays, enabling the introduction of targeted treatments based on individual differences that can lead to greater therapeutic efficacy by reducing adverse effects. Despite its crucial role, studying the contribution of the immune system (IS) in this context is difficult because of the intricate interplay between host, pathogen, therapy, and other external stimuli. To address this problem, a multidisciplinary approach involving in silico models can be of great help. In this perspective, we will discuss the use of a well-established agent-based model of the immune response, C-ImmSim, to study the relationship between long-lasting diseases and the combined effects of IS, drug therapies and exogenous factors such as physical activity and dietary habits.

Early detection of prediabetes is crucial to preventing its progression to diabetes. Providing individuals with a personalized sense of their risk could improve prevention efforts. While complex mathematical models that simulate metabolic and inflammatory processes offer detailed and patient-specific insights, their computational cost usually makes them impractical for real-time prediction on mobile platforms. This work introduces a long short-term memory (LSTM) surrogate for the MT2D model, that simulates the main metabolic and inflammatory processes undergoing the transition to prediabetes. The model is developed using a dataset of 43 669 simulated subjects, each with lifestyle inputs and biomarker outputs over six months. Using 8 time series inputs, the surrogate predicts the dynamics of 11 key metabolic and inflammatory outputs, closely replicating the behaviour of the MT2D model. After training, the proposed LSTM model reduces computational time from an average of 8.4 hours to 0.1 seconds per simulation, making it suitable for mobile device deployment. The model achieves root mean squared errors on the order of 10-2 on scaled data, and shows promise for prediabetes risk assessment by capturing trends in inflammatory biomarkers. This surrogate model can provide real-time and patient-specific insights into the metabolic health, potentially improving the understanding of prediabetes risk.

The importance of the immune system (IS) in tuberculosis (TB) drug development is often underestimated because of the intricate nature of experiments and the specialized knowledge needed. In vitro and animal studies fall short in replicating the intricate reactions of the human IS to drugs and infections. In this study, we present our initial efforts in employing an in silico approach to comprehend how an individual’s IS impacts the efficacy of therapy, particularly in managing mycobacterium tuberculosis (Mtb) infection and minimizing the risk of relapse. We employed a well-established agent-based IS simulator called C-IMMSIM. We conducted simulations to investigate the long-term outcomes of TB disease in a virtual cohort infected with Mtb over a 50-year period. Our simulations revealed that individuals with competent IS showed a high success rate in containing Mtb infection. Furthermore, to better understand the dynamic interactions between Mtb and the IS, we deliberately introduced specific IS deficiencies, thus successfully inducing short-term relapses and mortality. These results confirm the model’s ability to elucidate the mechanisms underlying the interactions between Mtb and the IS.