Objective This study introduces the Alzheimer's Disease Common Data Element Ontology for Clinical Trials (AD-CDO), a lightweight, semantically enriched ontology designed to represent and standardize key eligibility criteria concepts in Alzheimer's disease (AD) clinical trials. Materials and Methods We extracted high-frequency concepts from more than 1,500 AD clinical trials on ClinicalTrials.gov and organized them into seven semantic categories: Disease, Medication, Diagnostic Test, Procedure, Social Determinants of Health, Rating Criteria, and Fertility. Each concept was annotated with standard biomedical vocabularies, including the UMLS, OMOP Standardized Vocabularies, DrugBank, NDC, and NLM VSAC value sets. To balance coverage and manageability, we applied the Jenks Natural Breaks method to identify an optimal set of representative concepts. Results The optimized AD-CDO achieved over 63% coverage of extracted trial concepts while maintaining interpretability and compactness. The ontology effectively captured the most frequent and clinically meaningful entities used in AD eligibility criteria. We demonstrated AD-CDO's practical utility through two use cases: (a) an ontology-driven trial simulation system for formal modeling and virtual execution of clinical trials, and (b) an entity normalization task mapping raw clinical text to ontology-aligned terms, enabling consistency and integration with EHR data. Discussion AD-CDO bridges the gap between broad biomedical ontologies and task-specific trial modeling needs. It supports multiple downstream applications, including phenotyping algorithm development, cohort identification, and structured data integration. Conclusion By harmonizing essential eligibility entities and aligning them with standardized vocabularies, AD-CDO provides a versatile foundation for ontology-driven AD clinical trial research.

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.

The Model Context Protocol (MCP) has been proposed as a unifying standard for connecting large language models (LLMs) with external tools and resources, promising the same role for AI integration that HTTP and USB played for the Web and peripherals. Yet, despite rapid adoption and hype, its trajectory remains uncertain. Are MCP marketplaces truly growing, or merely inflated by placeholders and abandoned prototypes? Are servers secure and privacy-preserving, or do they expose users to systemic risks? And do clients converge on standardized protocols, or remain fragmented across competing designs? In this paper, we present the first large-scale empirical study of the MCP ecosystem. We design and implement MCPCrawler, a systematic measurement framework that collects and normalizes data from six major markets. Over a 14-day campaign, MCPCrawler aggregated 17,630 raw entries, of which 8,401 valid projects (8,060 servers and 341 clients) were analyzed. Our results reveal that more than half of listed projects are invalid or low-value, that servers face structural risks including dependency monocultures and uneven maintenance, and that clients exhibit a transitional phase in protocol and connection patterns. Together, these findings provide the first evidence-based view of the MCP ecosystem, its risks, and its future trajectory.

The proliferation of agent frameworks has led to fragmentation in how agents are defined, executed, and evaluated. Existing systems differ in their abstractions, data flow semantics, and tool integrations, making it difficult to share or reproduce workflows. We introduce Open Agent Specification (Agent Spec), a declarative language that defines AI agents and agentic workflows in a way that is compatible across frameworks, promoting reusability, portability and interoperability of AI agents. Agent Spec defines a common set of components, control and data flow semantics, and schemas that allow an agent to be defined once and executed across different runtimes. Agent Spec also introduces a standardized Evaluation harness to assess agent behavior and agentic workflows across runtimes - analogous to how HELM and related harnesses standardized LLM evaluation - so that performance, robustness, and efficiency can be compared consistently across frameworks. We demonstrate this using four distinct runtimes (LangGraph, CrewAI, AutoGen, and WayFlow) evaluated over three different benchmarks (SimpleQA Verified, $τ^2$-Bench and BIRD-SQL). We provide accompanying toolsets: a Python SDK (PyAgentSpec), a reference runtime (WayFlow), and adapters for popular frameworks (e.g., LangGraph, AutoGen, CrewAI). Agent Spec bridges the gap between model-centric and agent-centric standardization & evaluation, laying the groundwork for reliable, reusable, and portable agentic systems.

To foster trustworthy Artificial Intelligence (AI) within the European Union, the AI Act requires providers to mark and detect the outputs of their general-purpose models. The Article 50 and Recital 133 call for marking methods that are ''sufficiently reliable, interoperable, effective and robust''. Yet, the rapidly evolving and heterogeneous landscape of watermarks for Large Language Models (LLMs) makes it difficult to determine how these four standards can be translated into concrete and measurable evaluations. Our paper addresses this challenge, anchoring the normativity of European requirements in the multiplicity of watermarking techniques. Introducing clear and distinct concepts on LLM watermarking, our contribution is threefold. (1) Watermarking Categorisation: We propose an accessible taxonomy of watermarking methods according to the stage of the LLM lifecycle at which they are applied - before, during, or after training, and during next-token distribution or sampling. (2) Watermarking Evaluation: We interpret the EU AI Act's requirements by mapping each criterion with state-of-the-art evaluations on robustness and detectability of the watermark, and of quality of the LLM. Since interoperability remains largely untheorised in LLM watermarking research, we propose three normative dimensions to frame its assessment. (3) Watermarking Comparison: We compare current watermarking methods for LLMs against the operationalised European criteria and show that no approach yet satisfies all four standards. Encouraged by emerging empirical tests, we recommend further research into watermarking directly embedded within the low-level architecture of LLMs.

Background: Systems of systems are becoming increasingly dynamic and heterogeneous, and this adds pressure on the long-standing challenge of interoperability. Besides its technical aspect, interoperability has also an economic side, as development time efforts are required to build the interoperability artifacts. Objectives: With the recent advances in the field of large language models (LLMs), we aim at analyzing the effectiveness of LLM-based strategies to make systems interoperate autonomously, at runtime, without human intervention. Method: We selected 13 open source LLMs and curated four versions of a dataset in the agricultural interoperability use case. We performed three runs of each model with each version of the dataset, using two different strategies. Then we compared the effectiveness of the models and the consistency of their results across multiple runs. Results: qwen2.5-coder:32b was the most effective model using both strategies DIRECT (average pass@1 >= 0.99) and CODEGEN (average pass@1 >= 0.89) in three out of four dataset versions. In the fourth dataset version, which included an unit conversion, all models using the strategy DIRECT failed, whereas using CODEGEN qwen2.5-coder:32b succeeded with an average pass@1 = 0.75. Conclusion: Some LLMs can make systems interoperate autonomously. Further evaluation in different domains is recommended, and further research on reliability strategies should be conducted.

Abstract--Autonomous AI agents now operate across cloud, enterprise, and decentralized domains, creating demand for registry infrastructures that enable trustworthy discovery, capability negotiation, and identity assurance. We analyze five prominent approaches: (1) MCP Registry (centralized publication of mcp.json descriptors), (2) A2A Agent Cards (decentralized self-describing JSON capability manifests), (3) AGNTCY Agent Directory Service (IPFS Kademlia DHT content routing extended for semantic taxonomy-based content discovery, OCI artifact storage, and Sigstore-backed integrity), (4) Microsoft Entra Agent ID (enterprise SaaS directory with policy and zero-trust integration), and (5) NANDA Index AgentFacts (cryptographically verifiable, privacy-preserving fact model with credentialed assertions). Using four evaluation dimensions--security, authentication, scalability, and maintainability--we surface architectural trade-offs between centralized control, enterprise governance, and distributed resilience. We conclude with design recommendations for an emerging Internet of AI Agents requiring verifiable identity, adaptive discovery flows, and interoperable capability semantics. Autonomous AI agents are rapidly becoming foundational across domains from cloud-native assistants and robotics to decentralized systems and edge-based IoT controllers. These agents act independently, make decisions, and collaborate at scale. As agent populations grow into the billions across heterogeneous platforms and administrative boundaries, the ability to identify, discover, and trust agents in real time has emerged as a critical infrastructure challenge. Traditional mechanisms like DNS and static service catalogs are poorly suited to agent ecosystems, which demand dynamic discovery, verifiable metadata, and privacy-preserving interactions [1]. Legacy systems assume fixed endpoints and ownership-based trust models, lacking the flexibility and cryptographic assurances needed for agents that rotate capabilities, change locations, and form ephemeral collaborations. To address these limitations, several agent frameworks have introduced discovery metadata models.

Context: Modern Systems of Systems (SoSs) increasingly operate in dynamic environments (e.g., smart cities, autonomous vehicles) where runtime composition -- the on-the-fly discovery, integration, and coordination of constituent systems (CSs)--is crucial for adaptability. Despite growing interest, the literature lacks a cohesive synthesis of runtime composition in dynamic SoSs. Objective: This study synthesizes research on runtime composition in dynamic SoSs and identifies core challenges, solution strategies, supporting tools, and evaluation methods. Methods: We conducted a Systematic Literature Review (SLR), screening 1,774 studies published between 2019 and 2024 and selecting 80 primary studies for thematic analysis (TA). Results: Challenges fall into four categories: modeling and analysis, resilient operations, system orchestration, and heterogeneity of CSs. Solutions span seven areas: co-simulation and digital twins, semantic ontologies, integration frameworks, adaptive architectures, middleware, formal methods, and AI-driven resilience. Service-oriented frameworks for composition and integration dominate tooling, while simulation platforms support evaluation. Interoperability across tools, limited cross-toolchain workflows, and the absence of standardized benchmarks remain key gaps. Evaluation approaches include simulation-based, implementation-driven, and human-centered studies, which have been applied in domains such as smart cities, healthcare, defense, and industrial automation. Conclusions: The synthesis reveals tensions, including autonomy versus coordination, the modeling-reality gap, and socio-technical integration. It calls for standardized evaluation metrics, scalable decentralized architectures, and cross-domain frameworks. The analysis aims to guide researchers and practitioners in developing and implementing dynamically composable SoSs.

Connected health is a multidisciplinary approach focused on health management, prioritizing pa-tient needs in the creation of tools, services, and treatments. This paradigm ensures proactive and efficient care by facilitating the timely exchange of accurate patient information among all stake-holders in the care continuum. The rise of digital technologies and process innovations promises to enhance connected health by integrating various healthcare data sources. This integration aims to personalize care, predict health outcomes, and streamline patient management, though challeng-es remain, particularly in data architecture, application interoperability, and security. Data analytics can provide critical insights for informed decision-making and health co-creation, but solutions must prioritize end-users, including patients and healthcare professionals. This perspective was explored through an agile System Development Lifecycle in an EU-funded project aimed at developing an integrated AI-generated solution for managing cancer patients undergoing immunotherapy. This paper contributes with a collaborative digital framework integrating stakeholders across the care continuum, leveraging federated big data analytics and artificial intelligence for improved decision-making while ensuring privacy. Analytical capabilities, such as treatment recommendations and adverse event predictions, were validated using real-life data, achieving 70%-90% accuracy in a pilot study with the medical partners, demonstrating the framework's effectiveness.