Digital Twins (DTs) are computational models that simulate the states and temporal dynamics of real-world systems, playing a crucial role in prediction, understanding, and decision-making across diverse domains. However, existing approaches to DTs often struggle to generalize to unseen conditions in data-scarce settings, a crucial requirement for such models. To address these limitations, our work begins by establishing the essential desiderata for effective DTs.

A digital twin is a virtual replica of a real-world physical phenomena that uses mathematical modeling to characterize and simulate its defining features. By constructing digital twins for disease processes, we can perform in-silico simulations that mimic patients' health conditions and counterfactual outcomes under hypothetical interventions in a virtual setting. This eliminates the need for invasive procedures or uncertain treatment decisions. In this paper, we propose a method to identify digital twin model parameters using only noninvasive patient health data. We approach the digital twin modeling as a composite inverse problem, and observe that its structure resembles pretraining and finetuning in self-supervised learning (SSL). Leveraging this, we introduce a physics-informed SSL algorithm that initially pretrains a neural network on the pretext task of learning a differentiable simulator of a physiological process. Subsequently, the model is trained to reconstruct physiological measurements from noninvasive modalities while being constrained by the physical equations learned in pretraining. We apply our method to identify digital twins of cardiac hemodynamics using noninvasive echocardiogram videos, and demonstrate its utility in unsupervised disease detection and in-silico clinical trials.

Serving as an emerging and powerful tool, Large Language Model (LLM) - driven Human Digital Twins are showing great potential in healthcare system research. However, its actual simulation ability for complex human psychological traits, such as distrust in the healthcare system, remains unclear. This research gap particularly impacts health professionals' trust and usage of LLM - based Artificial Intelligence (AI) systems in assisting their routine work. In this study, based on the Twin-2K-500 dataset, we systematically evaluated the simulation results of the LLM-driven human digital twin using the Health Care System Distrust Scale (HCSDS) with an established human-subject sample, analyzing item-level distributions, summary statistics, and demographic subgroup patterns. Results show ed that the simulated responses by the digital twin were significantly more centralized with lower variance and had fewer selections of extreme options (all p<0.001) . While the digital twin broa dly reproduces human results in major demographic patterns, such as age and gender, it exhibits relatively low sensitivity in capturing minor differences in education levels. The LLMbased digital twin simulation has the potential to simulate population trends, but it also presents challenges in making detailed, specific distinction s in subgroups of human beings. This study suggests that the current LLM - driven Digital Twins have limitations in modeling complex human attitudes, which require careful calibration and validation before applying them in inferential analyses or policy simulations in health systems engineering. Future studies are necessary to examine the emotional reasonin g mechanism of LLMs before their use, particularly for studies that involve simulations sensitive to social topics, such as human-automation trust.

Virtual representations of physical critical infrastructures, such as water or energy plants, are used for simulations and digital twins to ensure resilience and continuity of their services. These models usually require 3D point clouds from laser scanners that are expensive to acquire and require specialist knowledge to use. In this article, we present a graph generation pipeline based on photogrammetry. The pipeline detects relevant objects and predicts their relation using RGB images and depth data generated by a stereo camera. This more cost-effective approach uses deep learning for object detection and instance segmentation of the objects, and employs user-defined heuristics or rules to infer their relations. Results of two hydraulic systems show that this strategy can produce graphs close to the ground truth while its flexibility allows the method to be tailored to specific applications and its transparency qualifies it to be used in the high stakes decision-making that is required for critical infrastructures.

Cardiovascular disease is the leading global cause of mortality, with coronary artery disease (CAD) as its most prevalent form, necessitating early risk prediction. While 3D coronary artery digital twins reconstructed from imaging offer detailed anatomy for personalized assessment, their analysis relies on computationally intensive computational fluid dynamics (CFD), limiting scalability. Data-driven approaches are hindered by scarce labeled data and lack of physiological priors. To address this, we present PINS-CAD, a physics-informed self-supervised learning framework. It pre-trains graph neural networks on 200,000 synthetic coronary digital twins to predict pressure and flow, guided by 1D Navier-Stokes equations and pressure-drop laws, eliminating the need for CFD or labeled data. When fine-tuned on clinical data from 635 patients in the multicenter FAME2 study, PINS-CAD predicts future cardiovascular events with an AUC of 0.73, outperforming clinical risk scores and data-driven baselines. This demonstrates that physics-informed pretraining boosts sample efficiency and yields physiologically meaningful representations. Furthermore, PINS-CAD generates spatially resolved pressure and fractional flow reserve curves, providing interpretable biomarkers. By embedding physical priors into geometric deep learning, PINS-CAD transforms routine angiography into a simulation-free, physiology-aware framework for scalable, preventive cardiology.

Such models are integral to the development of context-aware surgical training systems and process monitoring platforms [11], [19] as well as for encoding adaptive robotic control policies in teleoperated environments [13], [20], [78]. However, their limited capacity to capture continuous biophysical dynamics can constrain their utility in applications where physiological fidelity is essential. Recognizing the limitations inherent in purely continuous or discrete approaches, hybrid modeling strategies have emerged as a state-of-the-art solution for surgical digital twins. These frameworks integrate continuous dynamic models with discrete state machines, enabling the simultaneous tracking of physiological changes and procedural events [8], [7], [19], [37]. For example, hybrid automata have been deployed to synchronize real-time updates of tissue deformation with the sequencing of surgical tool actions [7], [19]. This integration allows digital twins to provide context-sensitive support, adapting to abrupt workflow transitions and physiological perturbations alike--a critical requirement in both routine and emergent surgical scenarios [8], [11], [7]. B. Mutual Information and Information-Theoretic Approaches With the proliferation of multi-modal surgical data, information-theoretic concepts have become indispensable for quantifying uncertainty, relevance, and redundancy across heterogeneous information streams. Mutual information I(X; Y) has been adopted as a rigorous metric for selecting the most informative sensors, imaging modalities, or clinical parameters, thereby enhancing the efficiency and robustness of digital twin-enabled decision support [2], [3], [13], [34], [11], [51], [48], [26], [29]. This is formally captured as Eq.

Generation IV (Gen-IV) nuclear power plants are envisioned to replace the current reactor fleet, bringing improvements in performance, safety, reliability, and sustainability. However, large cost investments currently inhibit the deployment of these advanced reactor concepts. Digital twins bridge real-world systems with digital tools to reduce costs, enhance decision-making, and boost operational efficiency. In this work, a digital twin framework is designed to operate the Gen-IV Fluoride-salt-cooled High-temperature Reactor, utilizing data-enhanced methods to optimize operational and maintenance policies while adhering to system constraints. The closed-loop framework integrates surrogate modeling, reinforcement learning, and Bayesian inference to streamline end-to-end communication for online regulation and self-adjustment. Reinforcement learning is used to consider component health and degradation to drive the target power generations, with constraints enforced through a Reference Governor control algorithm that ensures compliance with pump flow rate and temperature limits. These input driving modules benefit from detailed online simulations that are assimilated to measurement data with Bayesian filtering. The digital twin is demonstrated in three case studies: a one-year long-term operational period showcasing maintenance planning capabilities, short-term accuracy refinement with high-frequency measurements, and system shock capturing that demonstrates real-time recalibration capabilities when change in boundary conditions. These demonstrations validate robustness for health-aware and constraint-informed nuclear plant operation, with general applicability to other advanced reactor concepts and complex engineering systems.

Reinforcement learning (RL) is a powerful framework for optimizing decision-making in complex systems under uncertainty, an essential challenge in real-world settings, particularly in the context of the energy transition. A representative example is remote microgrids that supply power to communities disconnected from the main grid. Enabling the energy transition in such systems requires coordinated control of renewable sources like wind turbines, alongside fuel generators and batteries, to meet demand while minimizing fuel consumption and battery degradation under exogenous and intermittent load and wind conditions. These systems must often conform to extensive regulations and complex operational constraints. To ensure that RL agents respect these constraints, it is crucial to provide interpretable guarantees. In this paper, we introduce Shielded Controller Units (SCUs), a systematic and interpretable approach that leverages prior knowledge of system dynamics to ensure constraint satisfaction. Our shield synthesis methodology, designed for real-world deployment, decomposes the environment into a hierarchical structure where each SCU explicitly manages a subset of constraints. We demonstrate the effectiveness of SCUs on a remote microgrid optimization task with strict operational requirements. The RL agent, equipped with SCUs, achieves a 24% reduction in fuel consumption without increasing battery degradation, outperforming other baselines while satisfying all constraints. We hope SCUs contribute to the safe application of RL to the many decision-making challenges linked to the energy transition.

Emerging from NASA's spacecraft simulations in the 1960s, digital twin technology has advanced through industrial adoption to spark a healthcare transformation. A digital twin is a dynamic, data-driven virtual counterpart of a physical system, continuously updated through real-time data streams and capable of bidirectional interaction. In medicine, digital twin integrates imaging, biosensors, and computational models to generate patient-specific simulations that support diagnosis, treatment planning, and drug development. Representative applications include cardiac digital twin for predicting arrhythmia treatment outcomes, oncology digital twin for tracking tumor progression and optimizing radiotherapy, and pharmacological digital twin for accelerating drug discovery. Despite rapid progress, major challenges, including interoperability, data privacy, and model fidelity, continue to limit widespread clinical integration. Emerging solutions such as explainable AI, federated learning, and harmonized regulatory frameworks offer promising pathways forward. Looking ahead, advances in multi-organ digital twin, genomics integration, and ethical governance will be essential to ensure that digital twin shifts healthcare from reactive treatment to predictive, preventive, and truly personalized medicine.

A critical barrier to the trustworthiness of sixth-generation (6G) agentic autonomous networks is the uncertainty neglect bias; a cognitive tendency for large language model (LLM)-powered agents to make high-stakes decisions based on simple averages while ignoring the tail risk of extreme events. This paper proposes an unbiased, risk-aware framework for agentic negotiation, designed to ensure robust resource allocation in 6G network slicing. Specifically, agents leverage Digital Twins (DTs) to predict full latency distributions, which are then evaluated using a formal framework from extreme value theory, namely, Conditional Value-at-Risk (CVaR). This approach fundamentally shifts the agent's objective from reasoning over the mean to reasoning over the tail, thereby building a statistically-grounded buffer against worst-case outcomes. Furthermore, our framework ensures full uncertainty awareness by requiring agents to quantify epistemic uncertainty -- confidence in their own DTs predictions -- and propagate this meta-verification to make robust decisions, preventing them from acting on unreliable data. We validate this framework in a 6G inter-slice negotiation use-case between an eMBB and a URLLC agent. The results demonstrate the profound failure of the biased, mean-based baseline, which consistently fails its SLAs with a 25\% rate. Our unbiased, CVaR-aware agent successfully mitigates this bias, eliminating SLA violations and reducing the URLLC and eMBB p99.999 latencies by around 11\%. We show this reliability comes at the rational and quantifiable cost of slightly reduced energy savings to 17\%, exposing the false economy of the biased approach. This work provides a concrete methodology for building the trustworthy autonomous systems required for 6G.