With the recent explosion in high-resolution protein structures, one of the next frontiers in biology is elucidating the mechanisms by which conformational rearrangements in proteins are regulated to meet the needs of cells under changing conditions. Rigorously measuring protein energetics and dynamics requires the development of new methods that can resolve structural heterogeneity and conformational distributions. We have previously developed steady-state transition metal ion fluorescence resonance energy transfer (tmFRET) approaches using a fluorescent noncanonical amino acid donor (Anap) and transition metal ion acceptor to probe conformational rearrangements in soluble and membrane proteins. Here, we show that the fluorescent noncanonical amino acid Acd has superior photophysical properties that extend its utility as a donor for tmFRET. Using maltose-binding protein (MBP) expressed in mammalian cells as a model system, we show that Acd is comparable to Anap in steady-state tmFRET experiments and that its long, single-exponential lifetime is better suited for probing conformational distributions using time-resolved FRET. These experiments reveal differences in heterogeneity in the apo and holo conformational states of MBP and produce accurate quantification of the distributions among apo and holo conformational states at subsaturating maltose concentrations. Our new approach using Acd for time-resolved tmFRET sets the stage for measuring the energetics of conformational rearrangements in soluble and membrane proteins in near-native conditions.

Health digital twins are defined as virtual representations (“digital twin”) of patients (“physical twin”) that are generated from multimodal patient data, population data, and real-time updates on patient and environmental variables. With appropriate use, HDTs can model random perturbations on the digital twin to gain insight into the expected behavior of the physical twin—offering groundbreaking applications in precision medicine, clinical trials, and public health. Main considerations for translating HDT research into clinical practice include computational requirements, clinical implementation, as well as data governance, and product oversight.

Artificial intelligence systems are increasingly being applied to healthcare. In surgery, AI applications hold promise as tools to predict surgical outcomes, assess technical skills, or guide surgeons intraoperatively via computer vision. On the other hand, AI systems can also suffer from bias, compounding existing inequities in socioeconomic status, race, ethnicity, religion, gender, disability, or sexual orientation. Bias particularly impacts disadvantaged populations, which can be subject to algorithmic predictions that are less accurate or underestimate the need for care. Thus, strategies for detecting and mitigating bias are pivotal for creating AI technology that is generalizable and fair. Here, we discuss a recent study that developed a new strategy to mitigate bias in surgical AI systems.

Even as innovation occurs within digital medicine, challenges around equity and racial health disparities remain. Golden et al. evaluate structural racism in their recent paper focused on reproductive health. They recommend a framework to Remove, Repair, Restructure, and Remediate. We propose applying the framework to three areas within digital medicine: artificial intelligence (AI) applications, wearable devices, and telehealth. With this approach, we can continue to work towards an equitable future for digital medicine.

Rapid advances in digital technology and artificial intelligence in recent years have already begun to transform many industries, and are beginning to make headway into healthcare. There is tremendous potential for new digital technologies to improve the care of surgical patients. In this piece, we highlight work being done to advance surgical care using machine learning, computer vision, wearable devices, remote patient monitoring, and virtual and augmented reality. We describe ways these technologies can be used to improve the practice of surgery, and discuss opportunities and challenges to their widespread adoption and use in operating rooms and at the bedside.

The importance of infection risk prediction as a key public health measure has only been underscored by the COVID-19 pandemic. In a recent study, researchers use machine learning to develop an algorithm that predicts the risk of COVID-19 infection, by combining biometric data from wearable devices like Fitbit, with electronic symptom surveys. In doing so, they aim to increase the efficiency of test allocation when tracking disease spread in resource-limited settings. But the implications of technology that applies data from wearables stretch far beyond infection monitoring into healthcare delivery and research. The adoption and implementation of this type of technology will depend on regulation, impact on patient outcomes, and cost savings.

Due to its enormous capacity for benefit, harm, and cost, health care is among the most tightly regulated industries in the world. But with the rise of smartphones, an explosion of direct-to-consumer mobile health applications has challenged the role of centralized gatekeepers. As interest in health apps continue to climb, national regulatory bodies have turned their attention toward strategies to protect consumers from apps that mine and sell health data, recommend unsafe practices, or simply do not work as advertised. To characterize the current state and outlook of these efforts, Essén and colleagues map the nascent landscape of national health app policies and raise several considerations for cross-border collaboration. Strategies to increase transparency, organize app marketplaces, and monitor existing apps are needed to ensure that the global wave of new digital health tools fulfills its promise to improve health at scale.

Innovations in robotics, virtual and augmented reality, and artificial intelligence are being rapidly adopted as tools of “digital surgery”. Despite its quickly emerging role, digital surgery is not well understood. A recent study defines the term itself, and then specifies ethical issues specific to the field. These include privacy and public trust, consent, and litigation.