Health Digital Twins in Life Science and Health Care Innovation.

Health digital twins (HDTs) are virtual representations of real individuals that can be used to simulate human physiology, disease, and drug effects. HDTs can be used to improve drug discovery and development by providing a data-driven approach to inform target selection, drug delivery, and design of clinical trials. HDTs also offer new applications into precision therapies and clinical decision making. The deployment of HDTs at scale could bring a precision approach to public health monitoring and intervention. Next steps include challenges such as addressing socioeconomic barriers and ensuring the representativeness of the technology based on the training and validation data sets. Governance and regulation of HDT technology are still in the early stages.

Advances in induced pluripotent stem cell-derived cardiac myocytes: technological breakthroughs, key discoveries and new applications.

A transformation is underway in precision and patient-specific medicine. Rapid progress has been enabled by multiple new technologies including induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs). Here, we delve into these advancements and their future promise, focusing on the efficiency of reprogramming techniques, the fidelity of differentiation into the cardiac lineage, the functional characterization of the resulting cardiac myocytes, and the many applications of in silico models to understand general and patient-specific mechanisms controlling excitation-contraction coupling in health and disease. Furthermore, we explore the current and potential applications of iPSC-CMs in both research and clinical settings, underscoring the far-reaching implications of this rapidly evolving field.

Dynamic mirroring: unveiling the role of digital twins, artificial intelligence and synthetic data for personalized medicine in laboratory medicine.

In recent years, the integration of technological advancements and digitalization into healthcare has brought about a remarkable transformation in care delivery and patient management. Among these advancements, the concept of digital twins (DTs) has recently gained attention as a tool with substantial transformative potential in different clinical contexts. DTs are virtual representations of a physical entity (e.g., a patient or an organ) or systems (e.g., hospital wards, including laboratories), continuously updated with real-time data to mirror its real-world counterpart. DTs can be utilized to monitor and customize health care by simulating an individual's health status based on information from wearables, medical devices, diagnostic tests, and electronic health records. In addition, DTs can be used to define personalized treatment plans. In this study, we focused on some possible applications of DTs in laboratory medicine when used with AI and synthetic data obtained by generative AI. The first point discussed how biological variation (BV) application could be tailored to individuals, considering population-derived BV data on laboratory parameters and circadian or ultradian variations. Another application could be enhancing the interpretation of tumor markers in advanced cancer therapy and treatments. Furthermore, DTs applications might derive personalized reference intervals, also considering BV data or they can be used to improve test results interpretation. DT's widespread adoption in healthcare is not imminent, but it is not far off. This technology will likely offer innovative and definitive solutions for dynamically evaluating treatments and more precise diagnoses for personalized medicine.

Active mechanical cloaking for unsupervised damage resilience in programmable elastic metamaterials.

Owing to the architected void-filled low-density configurations, metamaterials are prone to defects during the complex manufacturing process, or damages under operational conditions. Recently mechanical cloaking has been proposed to shield the effect of such disorders in terms of homogenized mechanical responses. The major drawback in these studies are that the damage location should be known a priori, and the cloak is designed around that damaged zone before manufacturing. Such postulation does not allow unsupervised damage resilience during the manufacturing and service life of metamaterials by active reconfiguration of the stress field depending on the random and unpredictable evolution of damage. Here, we propose a radically different approach by introducing piezoelectric lattices where the effect of random appearance of any single or multiple disorders and damages with complex shapes, sizes and distributions can be shielded through active multi-physically controlled cloaks by voltage-dependent modulation of the stress fields within the cloaking region. Notably, this can be achieved without breaking periodicity and any additional material in the cloaking region unlike earlier studies concerning mechanical cloaks. The proposed active class of elastic metamaterials will bring a step-change in the on-demand mechanical performance of critically important structural components and unsupervised damage resilience for enhanced durability and sustainability.This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1)'.

Digital Twin Sensors in Cultural Heritage Ontology Applications.

This paper concerns the extension of the Heritage Digital Twin Ontology introduced in previous research to describe the reactivity of digital twins used for cultural heritage documentation by including the semantic description of sensors and activators and all of the process of interacting with the real world. After analysing previous work on the use of digital twins in cultural heritage, a summary description of the Heritage Digital Twin Ontology is provided, and the existing applications of digital twins to cultural heritage are overviewed, with references to reviews summarising the large production of scientific contributions on the topic. Then, a novel ontology named the Reactive Digital Twin Ontology is described, in which sensors, activators, and the decision processes are also semantically described, turning the previous synchronic approach to cultural heritage documentation into a diachronic one. Some case studies exemplify this theory.

An Urban Intelligence Architecture for Heterogeneous Data and Application Integration, Deployment and Orchestration.

This paper describes a novel architecture that aims to create a template for the implementation of an IT platform, supporting the deployment and integration of the different digital twin subsystems that compose a complex urban intelligence system. In more detail, the proposed Smart City IT architecture has the following main purposes: (i) facilitating the deployment of the subsystems in a cloud environment; (ii) effectively storing, integrating, managing, and sharing the huge amount of heterogeneous data acquired and produced by each subsystem, using a data lake; (iii) supporting data exchange and sharing; (iv) managing and executing workflows, to automatically coordinate and run processes; and (v) to provide and visualize the required information. A prototype of the proposed IT solution was implemented leveraging open-source frameworks and technologies, to test its functionalities and performance. The results of the tests performed in real-world settings confirmed that the proposed architecture could efficiently and easily support the deployment and integration of heterogeneous subsystems, allowing them to share and integrate their data and to select, extract, and visualize the information required by a user, as well as promoting the integration with other external systems, and defining and executing workflows to orchestrate the various subsystems involved in complex analyses and processes.

Navigating the Evolution of Digital Twins Research through Keyword Co-Occurence Network Analysis.

Digital twin technology has become increasingly popular and has revolutionized data integration and system modeling across various industries, such as manufacturing, energy, and healthcare. This study aims to explore the evolving research landscape of digital twins using Keyword Co-occurrence Network (KCN) analysis. We analyze metadata from 9639 peer-reviewed articles published between 2000 and 2023. The results unfold in two parts. The first part examines trends and keyword interconnection over time, and the second part maps sensing technology keywords to six application areas. This study reveals that research on digital twins is rapidly diversifying, with focused themes such as predictive and decision-making functions. Additionally, there is an emphasis on real-time data and point cloud technologies. The advent of federated learning and edge computing also highlights a shift toward distributed computation, prioritizing data privacy. This study confirms that digital twins have evolved into complex systems that can conduct predictive operations through advanced sensing technologies. The discussion also identifies challenges in sensor selection and empirical knowledge integration.

Digital Twin Meets Knowledge Graph for Intelligent Manufacturing Processes.

In the highly competitive field of material manufacturing, stakeholders strive for the increased quality of the end products, reduced cost of operation, and the timely completion of their business processes. Digital twin (DT) technologies are considered major enablers that can be deployed to assist the development and effective provision of manufacturing processes. Additionally, knowledge graphs (KG) have emerged as efficient tools in the industrial domain and are able to efficiently represent data from various disciplines in a structured manner while also supporting advanced analytics. This paper proposes a solution that integrates a KG and DTs. Through this synergy, we aimed to develop highly autonomous and flexible DTs that utilize the semantic knowledge stored in the KG to better support advanced functionalities. The developed KG stores information about materials and their properties and details about the processes in which they are involved, following a flexible schema that is not domain specific. The DT comprises smaller Virtual Objects (VOs), each one acting as an abstraction of a single step of the Industrial Business Process (IBP), providing the necessary functionalities that simulate the corresponding real-world process. By executing appropriate queries to the KG, the DT can orchestrate the operation of the VOs and their physical counterparts and configure their parameters accordingly, in this way increasing its self-awareness. In this article, the architecture of such a solution is presented and its application in a real laser glass bending process is showcased.

Towards a Distributed Digital Twin Framework for Predictive Maintenance in Industrial Internet of Things (IIoT).

This study uses a wind turbine case study as a subdomain of Industrial Internet of Things (IIoT) to showcase an architecture for implementing a distributed digital twin in which all important aspects of a predictive maintenance solution in a DT use a fog computing paradigm, and the typical predictive maintenance DT is improved to offer better asset utilization and management through real-time condition monitoring, predictive analytics, and health management of selected components of wind turbines in a wind farm. Digital twin (DT) is a technology that sits at the intersection of Internet of Things, Cloud Computing, and Software Engineering to provide a suitable tool for replicating physical objects in the digital space. This can facilitate the implementation of asset management in manufacturing systems through predictive maintenance solutions leveraged by machine learning (ML). With DTs, a solution architecture can easily use data and software to implement asset management solutions such as condition monitoring and predictive maintenance using acquired sensor data from physical objects and computing capabilities in the digital space. While DT offers a good solution, it is an emerging technology that could be improved with better standards, architectural framework, and implementation methodologies. Researchers in both academia and industry have showcased DT implementations with different levels of success. However, DTs remain limited in standards and architectures that offer efficient predictive maintenance solutions with real-time sensor data and intelligent DT capabilities. An appropriate feedback mechanism is also needed to improve asset management operations.

Comparison of Point Cloud Registration Techniques on Scanned Physical Objects.

This paper presents a comparative analysis of six prominent registration techniques for solving CAD model alignment problems. Unlike the typical approach of assessing registration algorithms with synthetic datasets, our study utilizes point clouds generated from the Cranfield benchmark. Point clouds are sampled from existing CAD models and 3D scans of physical objects, introducing real-world complexities such as noise and outliers. The acquired point cloud scans, including ground-truth transformations, are made publicly available. This dataset includes several cleaned-up scans of nine 3D-printed objects. Our main contribution lies in assessing the performance of three classical (GO-ICP, RANSAC, FGR) and three learning-based (PointNetLK, RPMNet, ROPNet) methods on real-world scans, using a wide range of metrics. These include recall, accuracy and computation time. Our comparison shows a high accuracy for GO-ICP, as well as PointNetLK, RANSAC and RPMNet combined with ICP refinement. However, apart from GO-ICP, all methods show a significant number of failure cases when applied to scans containing more noise or requiring larger transformations. FGR and RANSAC are among the quickest methods, while GO-ICP takes several seconds to solve. Finally, while learning-based methods demonstrate good performance and low computation times, they have difficulties in training and generalizing. Our results can aid novice researchers in the field in selecting a suitable registration method for their application, based on quantitative metrics. Furthermore, our code can be used by others to evaluate novel methods.

Leveraging LiDAR-Based Simulations to Quantify the Complexity of the Static Environment for Autonomous Vehicles in Rural Settings.

This paper uses virtual simulations to examine the interaction between autonomous vehicles (AVs) and their surrounding environment. A framework was developed to estimate the environment's complexity by calculating the real-time data processing requirements for AVs to navigate effectively. The VISTA simulator was used to synthesize viewpoints to replicate the captured environment accurately. With an emphasis on static physical features, roadways were dissected into relevant road features (RRFs) and full environment (FE) to study the impact of roadside features on the scene complexity and demonstrate the gravity of wildlife-vehicle collisions (WVCs) on AVs. The results indicate that roadside features substantially increase environmental complexity by up to 400%. Increasing a single lane to the road was observed to increase the processing requirements by 12.3-16.5%. Crest vertical curves decrease data rates due to occlusion challenges, with a reported average of 4.2% data loss, while sag curves can increase the complexity by 7%. In horizontal curves, roadside occlusion contributed to severe loss in road information, leading to a decrease in data rate requirements by as much as 19%. As for weather conditions, heavy rain increased the AV's processing demands by a staggering 240% when compared to normal weather conditions. AV developers and government agencies can exploit the findings of this study to better tailor AV designs and meet the necessary infrastructure requirements.

Realistic 3D Phantoms for Validation of Microwave Sensing in Health Monitoring Applications.

The development of new medical-monitoring applications requires precise modeling of effects on the human body as well as the simulation and the emulation of realistic scenarios and conditions. The first aim of this paper is to develop realistic and adjustable 3D human-body emulation platforms that could be used for evaluating emerging microwave-based medical monitoring/sensing applications such as the detection of brain tumors, strokes, and breast cancers, as well as for capsule endoscopy studies. New phantom recipes are developed for microwave ranges for phantom molds with realistic shapes. The second aim is to validate the feasibility and reliability of using the phantoms for practical scenarios with electromagnetic simulations using tissue-layer models and biomedical antennas. The third aim is to investigate the impact of the water temperature in the phantom-cooking phase on the dielectric properties of the stabilized phantom. The evaluations show that the dielectric properties of the developed phantoms correspond closely to those of real human tissue. The error in dielectric properties varies between 0.5-8%. In the practical-scenario simulations, the differences obtained with phantoms-based simulations in S21 parameters are 0.1-13 dB. However, the differences are smaller in the frequency ranges used for medical applications.

RGB Color Model: Effect of Color Change on a User in a VR Art Gallery Using Polygraph.

This paper presents computer and color vision research focusing on human color perception in VR environments. A VR art gallery with digital twins of original artworks is created for this experiment. In this research, the field of colorimetry and the application of the L*a*b* and RGB color models are applied. The inter-relationships of the two color models are applied to create a color modification of the VR art gallery environment using C# Script procedures. This color-edited VR environment works with a smooth change in color tone in a given time interval. At the same time, a sudden change in the color of the RGB environment is defined in this interval. This experiment aims to record a user's reaction embedded in a VR environment and the effect of color changes on human perception in a VR environment. This research uses lie detector sensors that record the physiological changes of the user embedded in VR. Five sensors are used to record the signal. An experiment on the influence of the user's color perception in a VR environment using lie detector sensors has never been conducted. This research defines the basic methodology for analyzing and evaluating the recorded signals from the lie detector. The presented text thus provides a basis for further research in the field of colors and human color vision in a VR environment and lays an objective basis for use in many scientific and commercial areas.

The Triumph of the Spin Chemistry of Fullerene C60 in the Light of Its Free Radical Copolymerization with Vinyl Monomers.

The spin theory of fullerenes is taken as a basis concept to virtually exhibit a peculiar role of C60 fullerene in the free radical polymerization of vinyl monomers. Virtual reaction solutions are filled with the initial ingredients (monomers, free radicals, and C60 fullerene) as well as with the final products of a set of elementary reactions, which occurred in the course of the polymerization. The above objects, converted to the rank of digital twins, are considered simultaneously under the same conditions and at the same level of the theory. In terms of the polymerization passports of the reaction solutions, a complete virtual picture of the processes considered is presented.

[Generative artificial intelligence and large language models in healthcare]. / La médecine du futur Intelligence artificielle générative et modèle linguistique large en soins de santé. Du battage médiatique à la réalité.

Generative artificial intelligence (GAI) and large language models (LLM) made their fulgurant irruption in our society at all levels, inclusive in health care. Possible applications and proofs of concept are everywhere. There is without any reasonable doubt an enormous potential, especially nowadays as we are facing an ever-growing imbalance between the flux of data and the availability of human resources. The creativity of GAI will be highlighted in the quest of defining protein structures and search for new medications, as well as for the development and use of digital twins in clinical research. As far as LLM's are concerned, we need to make a distinction between general models and models dedicated specifically to healthcare. Again, making an extensive overview of used cases is becoming impossible today, facing the numerous publications in the field.

Les mots intelligence artificielle générative (GAI) et modèles linguistiques larges (LLM) sont devenus ubiquitaires et incontournables en un temps record. En médecine aussi, le nombre d'applications possibles et preuves de concept foisonnent. Le potentiel est effectivement énorme, en particulier aujourd'hui, dans un monde de soins en déséquilibre, caractérisé par un flux énorme de données et un manque de moyens humains. La force créative de la GAI est illustrée par un exemple issu de la recherche protéomique et le développement de nouveaux médicaments, ainsi que dans le monde de la recherche clinique avec le développement des jumeaux digitaux. Pour le LLM, il faut faire la distinction entre modèles généralistes et spécialisés (adaptés au monde des soins). Là aussi, il devient de plus en plus difficile aujourd'hui d'en faire une revue exhaustive, car la littérature abonde de cas d'usage.

A multiscale predictive digital twin for neurocardiac modulation.

Cardiac function is tightly regulated by the autonomic nervous system (ANS). Activation of the sympathetic nervous system increases cardiac output by increasing heart rate and stroke volume, while parasympathetic nerve stimulation instantly slows heart rate. Importantly, imbalance in autonomic control of the heart has been implicated in the development of arrhythmias and heart failure. Understanding of the mechanisms and effects of autonomic stimulation is a major challenge because synapses in different regions of the heart result in multiple changes to heart function. For example, nerve synapses on the sinoatrial node (SAN) impact pacemaking, while synapses on contractile cells alter contraction and arrhythmia vulnerability. Here, we present a multiscale neurocardiac modelling and simulator tool that predicts the effect of efferent stimulation of the sympathetic and parasympathetic branches of the ANS on the cardiac SAN and ventricular myocardium. The model includes a layered representation of the ANS and reproduces firing properties measured experimentally. Model parameters are derived from experiments and atomistic simulations. The model is a first prototype of a digital twin that is applied to make predictions across all system scales, from subcellular signalling to pacemaker frequency to tissue level responses. We predict conditions under which autonomic imbalance induces proarrhythmia and can be modified to prevent or inhibit arrhythmia. In summary, the multiscale model constitutes a predictive digital twin framework to test and guide high-throughput prediction of novel neuromodulatory therapy. KEY POINTS: A multi-layered model representation of the autonomic nervous system that includes sympathetic and parasympathetic branches, each with sparse random intralayer connectivity, synaptic dynamics and conductance based integrate-and-fire neurons generates firing patterns in close agreement with experiment. A key feature of the neurocardiac computational model is the connection between the autonomic nervous system and both pacemaker and contractile cells, where modification to pacemaker frequency drives initiation of electrical signals in the contractile cells. We utilized atomic-scale molecular dynamics simulations to predict the association and dissociation rates of noradrenaline with the ß-adrenergic receptor. Multiscale predictions demonstrate how autonomic imbalance may increase proclivity to arrhythmias or be used to terminate arrhythmias. The model serves as a first step towards a digital twin for predicting neuromodulation to prevent or reduce disease.

Disrupting the infectious disease ecosystem in the digital precision health era innovations and converging emerging technologies.

This commentary explores the convergence of precision health and evolving technologies, including the critical role of artificial intelligence (AI) and emerging technologies in infectious diseases (ID) and microbiology. We discuss their disruptive impact on the ID ecosystem and examine the transformative potential of frontier technologies in precision health, public health, and global health when deployed with robust ethical and data governance guardrails in place.

A new door to a different world: opportunities from the metaverse and the raise of meta-medical laboratories.

OBJECTIVES: In the digital age, the metaverse has emerged with impressive potential for many segments of society. The metaverse could be presented as a parallel dimension able to enhance the physical world as well as our actions and decisions in it with the objective to use a coalition between the natural and virtual worlds for value creation. Our aim was to elaborate on the impact of the metaverse on laboratory medicine. METHODS: Based on the available evidence, literature and reports, we analyzed the different perspectives of the metaverse on laboratory medicine and the needs for an efficient transition. RESULTS: The convergence and integration of technologies in the metaverse will participate to the reimagination of laboratory medicine services with augmented services, users' experiences, efficiency, and personalized care. The revolution around the metaverse offers different opportunities for laboratory medicine but also open multiple related challenges that are presented in this article. CONCLUSIONS: Scientific societies, multidisciplinary teams and specialists in laboratory medicine must prepare the integration metaverse and meta-medical laboratories, raise the awareness, educate, set guidance to obtain a maximum of value and mitigate potential adverse consequences.

Children's views on artificial intelligence and digital twins for the daily management of their asthma: a mixed-method study.

New technologies enable the creation of digital twin systems (DTS) combining continuous data collection from children's home and artificial intelligence (AI)-based recommendations to adapt their care in real time. The objective was to assess whether children and adolescents with asthma would be ready to use such DTS. A mixed-method study was conducted with 104 asthma patients aged 8 to 17 years. The potential advantages and disadvantages associated with AI and the use of DTS were collected in semi-structured interviews. Children were then asked whether they would agree to use a DTS for the daily management of their asthma. The strength of their decision was assessed as well as the factors determining their choice. The main advantages of DTS identified by children were the possibility to be (i) supported in managing their asthma (ii) from home and (iii) in real time. Technical issues and the risk of loss of humanity were the main drawbacks reported. Half of the children (56%) were willing to use a DTS for the daily management of their asthma if it was as effective as current care, and up to 93% if it was more effective. Those with the best computer skills were more likely to choose the DTS, while those who placed a high value on the physician-patient relationship were less likely to do so.   Conclusions: The majority of children were ready to use a DTS for the management of their asthma, particularly if it was more effective than current care. The results of this study support the development of DTS for childhood asthma and the evaluation of their effectiveness in clinical trials. What is Known: • New technologies enable the creation of digital twin systems (DTS) for children with asthma. • Acceptance of these DTSs by children with asthma is unknown. What is New: • Half of the children (56%) were willing to use a DTS for the daily management of their asthma if it was as effective as current care, and up to 93% if it was more effective. •Children identified the ability to be supported from home and in real time as the main benefits of DTS.

Epistemic Rights and Responsibilities of Digital Simulacra for Biomedicine.

Big data and AI have enabled digital simulation for prediction of future health states or behaviors of specific individuals, populations or humans in general. "Digital simulacra" use multimodal datasets to develop computational models that are virtual representations of people or groups, generating predictions of how systems evolve and react to interventions over time. These include digital twins and virtual patients for in silico clinical trials, both of which seek to transform research and health care by speeding innovation and bridging the epistemic gap between population-based research findings and their application to the individual. Nevertheless, digital simulacra mark a major milestone on a trajectory to embrace the epistemic culture of data science and a potential abandonment of medical epistemological concepts of causality and representation. In doing so, "data first" approaches potentially shift moral attention from actual patients and principles, such as equity, to simulated patients and patient data.