Interest in the concept of a virtual human model that can encompass human physiology and anatomy on a biophysical (mechanistic) basis, and can assist with the clinical diagnosis and treatment of disease, appears to be growing rapidly around the globe. When such models are personalised and coupled with continual diagnostic measurements, they are called 'digital twins'. We argue here that the most useful form of virtual human model will be one that is constrained by the laws of physics, contains a comprehensive knowledge graph of all human physiology and anatomy, is multiscale in the sense of linking systems physiology down to protein function, and can to some extent be personalized and linked directly with clinical records. We discuss current progress from the IUPS Physiome Project and the requirements for a framework to achieve such a model.

Genome and transcriptome engineering have emerged as powerful tools in modern biotechnology, driving advancements in precision medicine and novel therapeutics. In this review, we provide a comprehensive overview of the current methodologies, applications, and future directions in genome and transcriptome engineering. Through this, we aim to provide a guide for tool selection, critically analyzing the strengths, weaknesses, and best use cases of these tools to provide context on their suitability for various applications. We explore standard and recent developments in genome engineering, such as base editors and prime editing, and provide insight into tool selection for change of function (knockout, deletion, insertion, substitution) and change of expression (repression, activation) contexts. Advancements in transcriptome engineering are also explored, focusing on established technologies like antisense oligonucleotides (ASOs) and RNA interference (RNAi), as well as recent developments such as CRISPR-Cas13 and adenosine deaminases acting on RNA (ADAR). This review offers a comparison of different approaches to achieve similar biological goals, and consideration of high-throughput applications that enable the probing of a variety of targets. This review elucidates the transformative impact of genome and transcriptome engineering on biological research and clinical applications that will pave the way for future innovations in the field.

Advancements in wearable sensor technologies and the digitization of medical records have contributed to the unprecedented ubiquity of biomedical time series data. Data-driven models have tremendous potential to assist clinical diagnosis and improve patient care by improving long-term monitoring capabilities, facilitating early disease detection and intervention, as well as promoting personalized healthcare delivery. However, accessing extensively labeled datasets to train data-hungry deep learning models encounters many barriers, such as long-tail distribution of rare diseases, cost of annotation, privacy and security concerns, data-sharing regulations, and ethical considerations. An emerging approach to overcome the scarcity of labeled data is to augment AI methods with human-like capabilities to leverage past experiences to learn new tasks with limited examples, called few-shot learning. This survey provides a comprehensive review and comparison of few-shot learning methods for biomedical time series applications. The clinical benefits and limitations of such methods are discussed in relation to traditional data-driven approaches. This paper aims to provide insights into the current landscape of few-shot learning for biomedical time series and its implications for future research and applications.

Large-scale Artificial General Intelligence (AGI) models, including Large Language Models (LLMs) such as ChatGPT/GPT-4, have achieved unprecedented success in a variety of general domain tasks. Yet, when applied directly to specialized domains like medical imaging, which require in-depth expertise, these models face notable challenges arising from the medical field's inherent complexities and unique characteristics. In this review, we delve into the potential applications of AGI models in medical imaging and healthcare, with a primary focus on LLMs, Large Vision Models, and Large Multimodal Models. We provide a thorough overview of the key features and enabling techniques of LLMs and AGI, and further examine the roadmaps guiding the evolution and implementation of AGI models in the medical sector, summarizing their present applications, potentialities, and associated challenges. In addition, we highlight potential future research directions, offering a holistic view on upcoming ventures. This comprehensive review aims to offer insights into the future implications of AGI in medical imaging, healthcare, and beyond.

Foundation model, trained on a diverse range of data and adaptable to a myriad of tasks, is advancing healthcare. It fosters the development of healthcare artificial intelligence (AI) models tailored to the intricacies of the medical field, bridging the gap between limited AI models and the varied nature of healthcare practices. The advancement of a healthcare foundation model (HFM) brings forth tremendous potential to augment intelligent healthcare services across a broad spectrum of scenarios. However, despite the imminent widespread deployment of HFMs, there is currently a lack of clear understanding regarding their operation in the healthcare field, their existing challenges, and their future trajectory. To answer these critical inquiries, we present a comprehensive and in-depth examination that delves into the landscape of HFMs. It begins with a comprehensive overview of HFMs, encompassing their methods, data, and applications, to provide a quick understanding of the current progress. Subsequently, it delves into a thorough exploration of the challenges associated with data, algorithms, and computing infrastructures in constructing and widely applying foundation models in healthcare. Furthermore, this survey identifies promising directions for future development in this field. We believe that this survey will enhance the community's understanding of the current progress of HFMs and serve as a valuable source of guidance for future advancements in this domain. For the latest HFM papers and related resources, please refer to our website.

Breath analysis and monitoring have emerged as pivotal components in both clinical research and daily health management, particularly in addressing the global health challenges posed by respiratory and metabolic disorders. The advancement of breath analysis strategies necessitates a multidisciplinary approach, seamlessly integrating expertise from medicine, biology, engineering, and materials science. Recent innovations in laboratory methodologies and wearable sensing technologies have ushered in an era of precise, real-time, and in situ breath analysis and monitoring. This comprehensive review elucidates the physical and chemical aspects of breath analysis, encompassing respiratory parameters and both volatile and non-volatile constituents. It emphasizes their physiological and clinical significance, while also exploring cutting-edge laboratory testing techniques and state-of-the-art wearable devices. Furthermore, the review delves into the application of sophisticated data processing technologies in the burgeoning field of breathomics and examines the potential of breath control in human-machine interaction paradigms. Additionally, it provides insights into the challenges of translating innovative laboratory and wearable concepts into mainstream clinical and daily practice. Continued innovation and interdisciplinary collaboration will drive progress in breath analysis, potentially revolutionizing personalized medicine through entirely non-invasive breath methodology.

Magnetic Resonance Imaging (MRI) is a pivotal clinical diagnostic tool, yet its extended scanning times often compromise patient comfort and image quality, especially in volumetric, temporal and quantitative scans. This review elucidates recent advances in MRI acceleration via data and physics-driven models, leveraging techniques from algorithm unrolling models, enhancement-based methods, and plug-and-play models to the emerging full spectrum of generative model-based methods. We also explore the synergistic integration of data models with physics-based insights, encompassing the advancements in multi-coil hardware accelerations like parallel imaging and simultaneous multi-slice imaging, and the optimization of sampling patterns. We then focus on domain-specific challenges and opportunities, including image redundancy exploitation, image integrity, evaluation metrics, data heterogeneity, and model generalization. This work also discusses potential solutions and future research directions, with an emphasis on the role of data harmonization and federated learning for further improving the general applicability and performance of these methods in MRI reconstruction.

Cardiac digital twins (CDTs) are personalized virtual representations used to understand complex cardiac mechanisms. A critical component of CDT development is solving the ECG inverse problem, which enables the reconstruction of cardiac sources and the estimation of patient-specific electrophysiology (EP) parameters from surface ECG data. Despite challenges from complex cardiac anatomy, noisy ECG data, and the ill-posed nature of the inverse problem, recent advances in computational methods have greatly improved the accuracy and efficiency of ECG inverse inference, strengthening the fidelity of CDTs. This paper aims to provide a comprehensive review of the methods of solving ECG inverse problem, the validation strategies, the clinical applications, and future perspectives. For the methodologies, we broadly classify state-of-the-art approaches into two categories: deterministic and probabilistic methods, including both conventional and deep learning-based techniques. Integrating physics laws with deep learning models holds promise, but challenges such as capturing dynamic electrophysiology accurately, accessing accurate domain knowledge, and quantifying prediction uncertainty persist. Integrating models into clinical workflows while ensuring interpretability and usability for healthcare professionals is essential. Overcoming these challenges will drive further research in CDTs.

Brain-computer interface (BCI) is a rapidly evolving technology that has the potential to widely influence research, clinical and recreational use. Non-invasive BCI approaches are particularly common as they can impact a large number of participants safely and at a relatively low cost. Where traditional non-invasive BCIs were used for simple computer cursor tasks, it is now increasingly common for these systems to control robotic devices for complex tasks that may be useful in daily life. In this review, we provide an overview of the general BCI framework as well as the various methods that can be used to record neural activity, extract signals of interest, and decode brain states. In this context, we summarize the current state-of-the-art of non-invasive BCI research, focusing on trends in both the application of BCIs for controlling external devices and algorithm development to optimize their use. We also discuss various open-source BCI toolboxes and software, and describe their impact on the field at large.

Searching for similar images in archives of histology and histopathology images is a crucial task that may aid in patient tissue comparison for various purposes, ranging from triaging and diagnosis to prognosis and prediction. Whole slide images (WSIs) are highly detailed digital representations of tissue specimens mounted on glass slides. Matching WSI to WSI can serve as the critical method for patient tissue comparison. In this paper, we report extensive analysis and validation of four search methods bag of visual words (BoVW), Yottixel, SISH, RetCCL, and some of their potential variants. We analyze their algorithms and structures and assess their performance. For this evaluation, we utilized four internal datasets (1269 patients) and three public datasets (1207 patients), totaling more than 200, 000 patches from 38 different classes/subtypes across five primary sites. Certain search engines, for example, BoVW, exhibit notable efficiency and speed but suffer from low accuracy. Conversely, search engines like Yottixel demonstrate efficiency and speed, providing moderately accurate results. Recent proposals, including SISH, display inefficiency and yield inconsistent outcomes, while alternatives like RetCCL prove inadequate in both accuracy and efficiency. Further research is imperative to address the dual aspects of accuracy and minimal storage requirements in histopathological image search.

Increasing demands on medical imaging departments are taking a toll on the radiologist's ability to deliver timely and accurate reports. Recent technological advances in artificial intelligence have demonstrated great potential for automatic radiology report generation (ARRG), sparking an explosion of research. This survey paper conducts a methodological review of contemporary ARRG approaches by way of (i) assessing datasets based on characteristics, such as availability, size, and adoption rate, (ii) examining deep learning training methods, such as contrastive learning and reinforcement learning, (iii) exploring state-of-the-art model architectures, including variations of CNN and transformer models, (iv) outlining techniques integrating clinical knowledge through multimodal inputs and knowledge graphs, and (v) scrutinising current model evaluation techniques, including commonly applied NLP metrics and qualitative clinical reviews. Furthermore, the quantitative results of the reviewed models are analysed, where the top performing models are examined to seek further insights. Finally, potential new directions are highlighted, with the adoption of additional datasets from other radiological modalities and improved evaluation methods predicted as important areas of future development.

The advent of flexible, compact, energy-efficient, robust, and user-friendly wearables has significantly impacted the market growth, with an estimated value of 61.30 billion USD in 2022. Wearable sensors have revolutionized in-home health monitoring by warranting continuous measurements of vital parameters. Ultrasound is used to non-invasively, safely, and continuously record vital parameters. The next generation of smart ultrasonic devices for healthcare integrates microelectronics with flexible, stretchable patches and body-conformable devices. They offer not only wearability, and user comfort, but also higher tracking accuracy of immediate changes of cardiovascular parameters. Moreover, due to the fixed adhesion to the skin, errors derived from probe placement or patient movement are mitigated, even though placement at the correct anatomical location is still critical and requires a user's skill and knowledge. In this review, the steps required to bring wearable ultrasonic systems into the medical market (technologies, device development, signal-processing, in-lab validation, and, finally, clinical validation) are discussed. The next generation of vascular ultrasound and its future research directions offer many possibilities for modernizing vascular health assessment and the quality of personalized care for home and clinical monitoring.

Alzheimer's disease (AD) progressively impairs the memory and thinking skills of patients, resulting in a significant global economic and social burden each year. However, diagnosis of this neurodegenerative disorder can be challenging, particularly in the early stages of developing cognitive decline. Current clinical techniques are expensive, laborious, and invasive, which hinders comprehensive studies on Alzheimer's biomarkers and the development of efficient devices for Point-of-Care testing (POCT) applications. To address these limitations, researchers have been investigating various biosensing techniques. Unfortunately, these methods have not been commercialized due to several drawbacks, such as low efficiency, reproducibility, and the lack of accurate identification of AD markers. In this review, we present diverse promising hallmarks of Alzheimer's disease identified in various biofluids and body behaviors. Additionally, we thoroughly discuss different biosensing mechanisms and the associated challenges in disease diagnosis. In each context, we highlight the potential of realizing new biosensors to study various features of the disease, facilitating its early diagnosis in POCT. This comprehensive study, focusing on recent efforts for different aspects of the disease and representing promising opportunities, aims to conduct the future trend toward developing a new generation of compact multipurpose devices that can address the challenges in the early detection of AD.

Harvesting energy from the human body is an area of growing interest. While several techniques have been explored, the focus in the field is converging on using Glucose Fuel Cells (GFCs) that use glucose oxidation reactions at an anode and oxygen reduction reactions (ORRs) at a cathode to create a voltage gradient that can be stored as power. To facilitate these reactions, catalysts are immobilized at an anode and cathode that result in electrochemistry that typically produces two electrons, a water molecule, and gluconic acid. There are two competing classes of these catalysts: enzymes, which use organic proteins, and abiotic options, which use reactive metals. Enzymatic catalysts show better specificity towards glucose, whereas abiotic options show superior operational stability. The most advanced enzymatic test showed a maximum power density of 119 μW/cm and an efficiency loss of 4% over 15 hours of operation. The best abiotic experiment resulted in 43 μW/cm and exhibited no signs of performance loss after 140 hours. Given the range of existing implantable devices' power budget from 10μW to 100mW and expected operational duration of 10 years or more, GFCs hold promise, but considerable advances need to be made to translate this technology to practical applications.

The shortened radio frequency wavelength in high field MRI makes it challenging to create a uniform excitation pattern over a large field of view, or to achieve satisfactory transmission efficiency at a local area. Transmit arrays are one tool that can be used to create a desired excitation pattern. To be effective, it is important to be able to control the current amplitude and phase at the array elements. The control of the current may get complicated by the coil coupling in many applications. Various methods have been proposed to achieve current control, either in the presence of coupling, or by effectively decouple the array elements. These methods are applied in different subsystems in the RF transmission chain: coil; coil-amplifier interface; amplifier, etc. In this review paper, we provide an overview of the various approaches and aspects of transmit current control and decoupling.

Techniques to resolve images beyond the diffraction limit of light with a large field of view (FOV) are necessary to foster progress in various fields such as cell and molecular biology, biophysics, and nanotechnology, where nanoscale resolution is crucial for understanding the intricate details of large-scale molecular interactions. Although several means of achieving super-resolutions exist, they are often hindered by factors such as high costs, significant complexity, lengthy processing times, and the classical tradeoff between image resolution and FOV. Microsphere-based super-resolution imaging has emerged as a promising approach to address these limitations. In this review, we delve into the theoretical underpinnings of microsphere-based imaging and the associated photonic nanojet. This is followed by a comprehensive exploration of various microsphere-based imaging techniques, encompassing static imaging, mechanical scanning, optical scanning, and acoustofluidic scanning methodologies. This review concludes with a forward-looking perspective on the potential applications and future scientific directions of this innovative technology.

Breast cancer has reached the highest incidence rate worldwide among all malignancies since 2020. Breast imaging plays a significant role in early diagnosis and intervention to improve the outcome of breast cancer patients. In the past decade, deep learning has shown remarkable progress in breast cancer imaging analysis, holding great promise in interpreting the rich information and complex context of breast imaging modalities. Considering the rapid improvement in deep learning technology and the increasing severity of breast cancer, it is critical to summarize past progress and identify future challenges to be addressed. This paper provides an extensive review of deep learning-based breast cancer imaging research, covering studies on mammograms, ultrasound, magnetic resonance imaging, and digital pathology images over the past decade. The major deep learning methods and applications on imaging-based screening, diagnosis, treatment response prediction, and prognosis are elaborated and discussed. Drawn from the findings of this survey, we present a comprehensive discussion of the challenges and potential avenues for future research in deep learning-based breast cancer imaging.

The last few years witnessed radical improvements in lower-limb prostheses. Researchers have presented innovative solutions to overcome the limits of the first generation of prostheses, refining specific aspects which could be implemented in future prostheses designs. Each aspect of lower-limb prostheses has been upgraded, but despite these advances, a number of deficiencies remain and the most capable limb prostheses fall far short of the capabilities of the healthy limb. This article describes the current state of prosthesis technology; identifies a number of deficiencies across the spectrum of lower limb prosthetic components with respect to users' needs; and discusses research opportunities in design and control that would substantially improve functionality concerning each deficiency. In doing so, the authors present a roadmap of patients related issues that should be addressed in order to fulfill the vision of a next-generation, neurally-integrated, highly-functional lower limb prosthesis.

With the recent advancement of novel biomedical technologies such as high-throughput sequencing and wearable devices, multi-modal biomedical data ranging from multi-omics molecular data to real-time continuous bio-signals are generated at an unprecedented speed and scale every day. For the first time, these multi-modal biomedical data are able to make precision medicine close to a reality. However, due to data volume and the complexity, making good use of these multi-modal biomedical data requires major effort. Researchers and clinicians are actively developing artificial intelligence (AI) approaches for data-driven knowledge discovery and causal inference using a variety of biomedical data modalities. These AI-based approaches have demonstrated promising results in various biomedical and healthcare applications. In this review paper, we summarize the state-of-the-art AI models for integrating multi-omics data and electronic health records (EHRs) for precision medicine. We discuss the challenges and opportunities in integrating multi-omics data with EHRs and future directions. We hope this review can inspire future research and developing in integrating multi-omics data with EHRs for precision medicine.

Artificial intelligence and machine learning are transforming many fields including medicine. In diabetes, robust biosensing technologies and automated insulin delivery therapies have created a substantial opportunity to improve health. While the number of manuscripts addressing the topic of applying machine learning to diabetes has grown in recent years, there has been a lack of consistency in the methods, metrics, and data used to train and evaluate these algorithms. This manuscript provides consensus guidelines for machine learning practitioners in the field of diabetes, including best practice recommended approaches and warnings about pitfalls to avoid.