In the literature: February 2026 highlights

Corti, Anna, et al. “Advancing Coronary Risk Assessment Through Combined Radiomic, Mechanical, and Hemodynamic Analysis.” Annals of biomedical engineering.

Detecting vulnerable coronary plaques through coronary computed tomography angiography (CCTA) is a crucial, yet challenging task. To date, most of the proposed vulnerability markers have been studied in isolation. This study introduces the first integrated analysis combining radiomic, mechanical, and hemodynamic factors to explore their synergistic contribution to plaque vulnerability.

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Goldring, Christopher E., et al. “Quantitative systems toxicology: modelling to mechanistically understand and predict drug safety.” Nature Reviews Drug Discovery 25.2 (2026): 138-153.

Reliable prediction and prevention of adverse drug reactions (ADRs) remains a key challenge in the development of new medicines. Advanced mathematical and computational modelling approaches, which incorporate cutting-edge mechanistic understanding of ADRs in concert with systematically collected data addressing knowledge gaps, are integral components of model-informed drug discovery and development (MID3). These approaches provide a precise, quantitative framework for predicting and mitigating safety risks in the earliest phases of drug development. Here, we highlight recent developments in the burgeoning field of quantitative systems toxicology (QST), including insights into the current state-of-the-art, as well as outcomes from the Innovative Medicines Initiative (IMI) 2 TransQST project. QST models that describe the disruption of cardiovascular, gastrointestinal, hepatic and renal physiological functions following drug exposure are presented, along with recommendations for their application in drug discovery and development.

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Berg, Lucas Arantes, et al. “Toward cardiac electrophysiology digital twins with an efficient open source scalable solver on GPU clusters.” Scientific Reports (2026).

Modelling and simulation are essential in biomedicine, and specifically in computational cardiology. Reliable, efficient and accurate solvers are critical. This study presents an open-source, GPU-based cardiac electrophysiology solver for scalable multiscale simulations (monoalg3d), incorporating conduction system calibration and performance optimization. The solver employs the monodomain equation coupled with the Purkinje network, solved via the finite volume method, featuring a GPU-based linear solver and concurrent simulation dispatch with MPI. We demonstrate a  speedup over a CPU-based solution and scalability by running 512 simulations on 128 compute nodes. Coarse and fine biventricular mesh simulations with 855, 670 and 6, 845, 360 control volumes are completed in less than 24 min and 303 min, respectively, considering a single beat and a human-based ventricular cellular model with 43 state variables. The proposed open-source solver enhances computational efficiency and physiological fidelity through Purkinje-muscle-junction calibration, enabling large-scale, high-speed cardiac simulations including the conduction system. This work marks a significant step toward fast and scalable cardiac simulations on GPU architectures by providing execution of concurrent simulations with the novel MPI batch feature and calibration of Purkinje coupling parameters, paving the way for integration into a Digital Twin personalisation pipeline, including the conduction system.

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Russo, Giulia, et al. “NX210c Demonstrates Therapeutic Potential to Restore Blood–Brain Barrier in a QSP Model of Relapsing–Remitting Multiple Sclerosis.” International Journal of Molecular Sciences 27.3 (2026): 1349.

Blood–brain barrier (BBB) breakdown is a hallmark of several neurological disorders, including multiple sclerosis (MS). NX210c, a novel therapeutic peptide, has shown promise in restoring BBB integrity, in both preclinical and clinical settings, offering potential for use in MS populations and across various central nervous system conditions with overlapping mechanisms. In this study, we evaluated the therapeutic potential of NX210c in patients with relapsing–remitting MS (RRMS) using a previous quantitative systems pharmacology (QSP) model currently redesigned to capture the dynamic interplay between BBB integrity and immune system activity. We validated the QSP model using both preclinical and clinical datasets, and generated virtual populations representing healthy individuals and RRMS patients for in silico testing. NX210c was assessed as both a monotherapy and in combination with established MS treatments. Simulations predicted time course changes in key BBB integrity markers, including tight junction protein (TJP) expression and transendothelial electrical resistance (TEER), under various dosing regimens. NX210c treatment was associated with a significant attenuation of BBB degradation compared to untreated controls (~7–8% higher TJP expression and BBB electrical resistance). Furthermore, we investigated the long-term impact of NX210c on clinical outcomes such as relapse rates. Both 5 and 10 mg/kg doses (single cycle [thrice-weekly for 4 weeks]) induced improvement in disease activity in RRMS patients, as well as a 10 mg/kg dose (single or repeated 4-week cycles every 6 months) in highly active patients. Particularly when administered alongside one of five commonly used MS therapies (interferon β-1a, teriflunomide, cladribine, natalizumab, ocrelizumab), in the highly active subpopulation, the model on average predicted a reduction in relapse frequency in the 10 mg NX210c-treated group versus untreated group from four to no relapses over two years. These findings suggest that NX210c may enhance therapeutic efficacy in RRMS by promoting BBB restoration and modulating immune responses, offering a promising avenue for combination treatment strategies.

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Iulini, Martina, et al. “An integrated in vitro and in silico testing strategy applied to PFAS inhibition of antibody production to define a tolerable daily intake.” Toxicology Letters (2026): 111817.

Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals known for their persistence, bioaccumulation, and adverse health effects, particularly on the immune system. Epidemiological studies link PFAS exposure to immunosuppression, with increased infection susceptibility and reduced vaccine efficacy. In this paper, we describe the workflow we used to establish an integrated testing strategy (ITS) combining in vitro and in silico methods to model PFAS inhibition of antibody production and to define a tolerable daily intake. This strategy was based on data generated within an EFSA-sponsored project. Using human peripheral blood mononuclear cells, the effects of PFAS on antibody production were assessed. Mathematical models were then applied to determine PFAS free concentrations in vitro, while Physiologically Based Kinetics (PBK) modeling enabled quantitative in vitro to in vivo extrapolation (QIVIVE) to translate in vitro effects into external doses. In addition, the Universal Immune System Simulator was used to predict immune-related outcomes and threshold doses for sensitive populations. Following this strategy, we were able to demonstrate that the oral equivalent effect doses derived through QIVIVE were similar to, or lower than, the tolerable weekly intake established by EFSA for PFAS, indicating that our approach is conservative. We demonstrate the possibility of using alternative methods for studying PFAS toxicity, offering insights into their dynamics and kinetics without animal testing. The strategy provides a promising framework for assessing other chemicals, advancing toxicology toward more human-relevant and ethical practices.

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Vanmechelen, Anna, et al. “Gait pathomechanics in early-stage knee osteoarthritis: do non-traumatic and post-traumatic patients walk differently?.” Journal of Electromyography and Kinesiology (2026): 103113.

Altered knee joint loading in early-stage osteoarthritis may accelerate cartilage degeneration and symptom progression. This cross-sectional observational study investigates differences in knee joint pathomechanics between 22 patients with early-stage post-traumatic knee osteoarthritis (PTOA), 26 patients with early-stage non-traumatic knee osteoarthritis (NTOA) and 20 age-/gender-matched healthy controls. Participants walked barefoot at self-selected speeds while marker data (100 Hz), ground reaction forces (1000 Hz), and surface electromyography (1000 Hz) were recorded. electromyography-informed musculoskeletal simulations estimated knee contact forces (KCF) and joint mechanics. Group differences in these outcomes and measured muscle activations were assessed via Statistical Parametric Mapping t-tests. Analysis of Covariance investigated the influence of covariates (age, gender, gait speed, alignment, strength). Early-stage NTOA and PTOA patients exhibit similar KCF and joint mechanics. Both patient groups exhibited significantly reduced second KCF peaks compared to controls (p = 0.019, Δmean NTOA – controls = 1.07 BW, Δmean PTOA – controls = 0.98 BW), suggesting knee underloading, in contrast to the joint overload typically seen in established OA. Additionally, gait speed significantly influenced KCF peaks. These findings suggest that early OA may be characterized by cartilage underloading. Longitudinal studies and more demanding tasks may reveal phenotype-specific biomechanical distinctions and also confirm continuous cartilage underloading in disease progression.