Click here to read some interesting recently published papers from our community. If you have published an article in the field of in silico medicine, send it to us: we will include it in this section of the newsletter!
Cell report medicine: Multi-organ single-cell analysis reveals an on/off switch system with potential for personalized treatment of immunological diseases
Sandra Lilja et al
Abstract
Prioritization of disease mechanisms, biomarkers, and drug targets in immune-mediated inflammatory diseases (IMIDs) is complicated by altered interactions between thousands of genes. Our multi-organ single-cell RNA sequencing of a mouse IMID model, namely collagen-induced arthritis, shows highly complex and heterogeneous expression changes in all analyzed organs, even though only joints showed signs of inflammation. We organized those into a multi-organ multicellular disease model, which shows predicted molecular interactions within and between organs. That model supports that inflammation is switched on or off by altered balance between pro- and anti-inflammatory upstream regulators (URs) and downstream pathways. Meta-analyses of human IMIDs show a similar, but graded, on/off switch system. This system has the potential to prioritize, diagnose, and treat optimal combinations of URs on the levels of IMIDs, subgroups, and individual patients. That potential is supported by UR analyses in more than 600 sera from patients with systemic lupus erythematosus.
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eLife Cancer Biology: A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation
Jeffrey West et al
Abstract
Adaptive therapy is a dynamic cancer treatment protocol that updates (or āadaptsā) treatment decisions in anticipation of evolving tumor dynamics. This broad term encompasses many possible dynamic treatment protocols of patient-specific dose modulation or dose timing. Adaptive therapy maintains high levels of tumor burden to benefit from the competitive suppression of treatment-sensitive subpopulations on treatment-resistant subpopulations. This evolution-based approach to cancer treatment has been integrated into several ongoing or planned clinical trials, including treatment of metastatic castrate resistant prostate cancer, ovarian cancer, and BRAF-mutant melanoma. In the previous few decades, experimental and clinical investigation of adaptive therapy has progressed synergistically with mathematical and computational modeling. In this work, we discuss 11 open questions in cancer adaptive therapy mathematical modeling. The questions are split into three sections: (1) integrating the appropriate components into mathematical models (2) design and validation of dosing protocols, and (3) challenges and opportunities in clinical translation.
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SageJournals: Acceptability of wearable devices for measuring mobility remotely: Observations from the Mobilise-D technical validation study
Alison Keogh et al
Abstract
This study aimed to explore the acceptability of a wearable device for remotely measuring mobility in the Mobilise-D technical validation study (TVS), and to explore the acceptability of using digital tools to monitor health.
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Biomechanics and Modeling in Mechanobiology:Effects of geometric individualisation of a human spine model on load sharing: neuro-musculoskeletal simulation reveals significant differences in ligament and muscle contribution
Laura Meszaros-Beller et al
Abstract
In spine research, two possibilities to generate models exist: generic (population-based) models representing the average human and subject-specific representations of individuals. Despite the increasing interest in subject specificity, individualisation of spine models remains challenging. Neuro-musculoskeletal (NMS) models enable the analysis and prediction of dynamic motions by incorporating active muscles attaching to bones that are connected using articulating joints under the assumption of rigid body dynamics. In this study, we used forward-dynamic simulations to compare a generic NMS multibody model of the thoracolumbar spine including fully articulated vertebrae, detailed musculature, passive ligaments and linear intervertebral disc (IVD) models with an individualised model to assess the contribution of individual biological structures. Individualisation was achieved by integrating skeletal geometry from computed tomography and custom-selected muscle and ligament paths. Both models underwent a gravitational settling process and a forward flexion-to-extension movement. The model-specific load distribution in an equilibrated upright position and local stiffness in the L4/5 functional spinal unit (FSU) is compared. Load sharing between occurring internal forces generated by individual biological structures and their contribution to the FSU stiffness was computed. The main finding of our simulations is an apparent shift in load sharing with individualisation from an equally distributed element contribution of IVD, ligaments and muscles in the generic spine model to a predominant muscle contribution in the individualised model depending on the analysed spine level.
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Nature: ChatGPT: five priorities for research
Eva A M van Dis et al
(no abstract available)
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Journal of Cardiovascular Electrophysiology: In silico experiments explain the nonāconsistent benefit of conduction system pacing over cardiac resynchronization therapy. The need to personalize therapy
MarĆa S Guillem et al
Abstract
The study by Strocchi et al. adds evidence that choosing the cardiac resynchronization therapy (CRT) according to the cardiac substrate of each patient could be beneficial. Perhaps the most appropriate approach in CRT would be to find the appropriate niche for each pacing method. It may be less about demonstrating the superiority of conduction system pacing (CSP) and more about personalizing the therapy for each particular patient. That is, a patient with septal scarring or diffuse conduction system disease could benefit more from biventricular CRT. On the other hand, someone with lateral myocardial scar or localized pathology (focal or proximal disease) within the conduction system would benefit more from CSP. In this context, ECGI could eventually play a main role in selecting the best therapy for each patient.
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Journal of Cardiovascular Electrophysiology: Effect of scar and His-Purkinje and myocardium conduction on response to conduction system pacing
Marina Strocchi et al
Abstract
Conduction system pacing (CSP), in the form of His bundle pacing (HBP) or left bundle branch pacing (LBBP), is emerging as a valuable cardiac resynchronization therapy (CRT) delivery method. However, patient selection and therapy personalization for CSP delivery remain poorly characterized. We aim to compare pacing-induced electrical synchrony during CRT, HBP, LBBP, HBP with left ventricular (LV) epicardial lead (His-optimized CRT [HOT-CRT]), and LBBP with LV epicardial lead (LBBP-optimized CRT [LOT-CRT]) in patients with different conduction disease presentations using computational modeling.
