New insights on the cardiac safety factor: Unraveling the relationship between conduction velocity and robustness of propagation.

Cardiac conduction disturbances are linked with arrhythmia development. The concept of safety factor (SF) has been derived to describe the robustness of conduction, but the usefulness of this metric has been constrained by several limitations. For example, due to the difficulty of measuring the necessary input variables, SF calculations have only been applied to synthetic data. Moreover, quantitative validation of SF is lacking; specifically, the practical meaning of particular SF values is unclear, aside from the fact that propagation failure (i.e., conduction block) is characterized by SF < 1. This study aims to resolve these limitations for our previously published SF formulation and explore its relationship to relevant electrophysiological properties of cardiac tissue. First, HL-1 cardiomyocyte monolayers were grown on multi-electrode arrays and the robustness of propagation was estimated using extracellular potential recordings. SF values reconstructed purely from experimental data were largely between 1 and 5 (up to 89.1% of sites characterized). This range is consistent with values derived from synthetic data, proving that the formulation is sound and its applicability is not limited to analysis of computational models. Second, for simulations conducted in 1-, 2-, and 3-dimensional tissue blocks, we calculated true SF values at locations surrounding the site of current injection for sub- and supra-threshold stimuli and found that they differed from values estimated by our SF formulation by <10%. Finally, we examined SF dynamics under conditions relevant to arrhythmia development in order to provide physiological insight. Our analysis shows that reduced conduction velocity (Θ) caused by impaired intrinsic cell-scale excitability (e.g., due to sodium current a loss-of-function mutation) is associated with less robust conduction (i.e., lower SF); however, intriguingly, Θ variability resulting from modulation of tissue scale conductivity has no effect on SF. These findings are supported by analytic derivation of the relevant relationships from first principles. We conclude that our SF formulation, which can be applied to both experimental and synthetic data, produces values that vary linearly with the excess charge needed for propagation. SF calculations can provide insights helpful in understanding the initiation and perpetuation of cardiac arrhythmia.

Patient-Centric Interoperability and Cybersecurity for Cross-Border Healthcare.

In Web 3.0 the user owns the information. Decentralized Identity Documents (DID documents) allow users to create their own digital identity and decentralized cryptographic material resistant to quantum computing. A patient's DID document also contains a unique identifier for cross-border healthcare, endpoints for receiving DIDComm messages and for SOS services, and additional identifiers (passport, etc.). We propose a blockchain for cross-border healthcare to store the evidence of different electronic, physical identities, and identifiers, but also the rules approved by the patient or legal guardians to access patient data. The International Patient Summary (IPS) is the de facto standard for cross-border healthcare and includes an index of information classified into sections (HL7 FHIR Composition) that healthcare professionals and services can update and read on the patient's SOS service, then retrieving all the necessary patient information from the different FHIR API endpoints of different healthcare providers according to the approved rules.

Interoperable Universal Resource Identifier for Selective Disclosure of Data.

All the information stored in the different information systems is issued in a format that allows the holder (the information owner) to disclose only certain information to a third party, which will act as a requester, receiver and verifier of the information disclosed by the holder. We define the Interoperable Universal Resource Identifier (iURI) as a harmonized method of representing a claim (minimum piece of verifiable information) using disparate encoding systems, agnostic to the original encoding system and data format. Encoding systems are represented in Reverse Domain Name Resolution (Reverse-DNS) format for HL7 FHIR, OpenEHR, and other data formats. The iURI can then be used in JSON Web Token for Selective Disclosure (SD-JWT) and Verifiable Credential (VC), among others. The method enables a person to demonstrate data that already exists in different information systems in disparate data formats, and even an information system, to verify certain claims, in a harmonized way.

Quality and Traceability of Starting Materials from Supplier to Recipient.

Quality of processes and products is based on traceability and review of both components, material processing and product flow throughout the manufacturing and supply chain. Blockchain technology enables cross-border audit trail and traceability while reducing costs. Donors are the providers of biological raw material (starting material). They can share their health records when donating by using an IPS document or a FHIR Questionnaire-response resource. It allows health personnel to retrieve and verify relevant clinical information when donating. Additionally, health personnel can generate an anonymized and de-identified digital twin of the donor for research purposes, and it can be updated over time. The starting material can include a reference to a digital twin of an unknown supplier, which improves the data quality and enhances research possibilities. Adverse reactions and events can be also recorded on blockchain to improve safety, transparency, traceability, medical research and product quality.

Unified Identification Protocol for Cross-Border Healthcare.

The Unified Identification Protocol (UIP) is an innovation which empowers patients and legal guardians to generate their unique digital identity for cross-border healthcare. This digital identity seamlessly links to local identifiers across different territories and organizations, bridging the gap between disparate systems. Combined with the International Patient Summary (IPS) - endorsed by the G7 and the EU - UIP is pioneering a new paradigm in telehealth services. Championing a user-centric approach in line with Web 3.0 principles, UIP places data control directly in the hands of patients and their legal guardians. This ensures accurate identification, streamlined access to health data, and robust privacy protection. When harmonized with tools like the SMART-On-FHIR API, FHIR Contract, DID Documents, and blockchain certification, UIP lays down transparent, user-approved guidelines for sharing healthcare data across borders. This framework guarantees that data is securely exchanged, encrypted specifically for the intended recipients upon user consent, adhering to international standards, and in full compliance with prevailing regulations. Furthermore, UIP facilitates certification of health courses and competences for patients, caregivers, and practitioners, enhancing healthcare understanding and management.