Platelet rich plasma (PRP) is a suspension of bioactive factors and chemokine enriched plasma. Platelets are a distinctive source of membrane bound and soluble proteins that are released upon their activation. The higher count of platelets renders PRP with an array of tissue regenerative abilities. PRP can be employed in the form of platelet containing plasma, platelet lysate plasma, or in the form of a pre-gelled fibrin matrix. PRP has been an essential alternative source of growth factors in the healing and regeneration of various tissues, such as musculoskeletal, cardiovascular, and dermal tissue, with additional applications in other tissues, such as hepatic and neural. A wide range of preparative and isolation strategies have been developed for various forms of PRP at laboratory and commercial scales. Concomitantly, PRP has found its applicability as an active component in several tissue regenerative approaches, including 3D printed/bioprinted constructs, injectable hydrogels, and crosslinked scaffolds. This review focuses on the various forms of PRP and their preparation methods, the latest tissue engineering applications of PRP, and the various tissue-specific clinical trials and findings conducted using PRP. We have further discussed the optimizations required in the methods of preparation, delivery, and long-term storage of PRP. Therefore, this review seeks to benefit the scope of research on PRP-based therapeutic agents in tissue engineering by providing comprehensive insights into the widespread application. We envisage PRP could be instrumental in future patient-specific tissue engineering applications in both pre-clinical and clinical settings.

Simulation models and artificial intelligence (AI) are largely used to address healthcare and biomedical engineering problems. Both approaches showed promising results in the analysis and optimization of healthcare processes. Therefore, the combination of simulation models and AI could provide a strategy to further boost the quality of health services. In this work, a systematic review of studies applying a hybrid simulation models and AI approach to address healthcare management challenges was carried out. Scopus, Web of Science, and PubMed databases were screened by independent reviewers. The main strategies to combine simulation and AI as well as the major healthcare application scenarios were identified and discussed. Moreover, tools and algorithms to implement the proposed approaches were described. Results showed that machine learning appears to be the most employed AI strategy in combination with simulation models, which mainly rely on agent-based and discrete-event systems. The scarcity and heterogeneity of the included studies suggested that a standardized framework to implement hybrid machine learning-simulation approaches in healthcare management is yet to be defined. Future efforts should aim to use these approaches to design novel intelligent in-silico models of healthcare processes and to provide effective translation to the clinics.

Objective. The EPHNOGRAM project aimed to develop a low-cost, low-power device for simultaneous electrocardiogram (ECG) and phonocardiogram (PCG) recording, with additional channels for environmental audio to enhance PCG through active noise cancellation. The objective was to study multimodal electro-mechanical activities of the heart, offering insights into the differences and synergies between these modalities during various cardiac activity levels. Approach. We developed and tested several hardware prototypes of a simultaneous ECG-PCG acquisition device. Using this technology, we collected simultaneous ECG and PCG data from 24 healthy adults during different physical activities, including resting, walking, running, and stationary biking, in an indoor fitness center. The data were annotated using a robust software that we developed for detecting ECG R-peaks and PCG S1 and S2 components, and overseen by a human expert. We also developed machine learning models using ECG-based, PCG-based, and joint ECG-PCG features, like R�VR and S1�VS2 intervals, to classify physical activities and analyze electro-mechanical dynamics. Main results. The results show a significant coupling between ECG and PCG components, especially during high-intensity exercise. Notable micro-variations in S2-based heart rate show differences in the heart's electrical and mechanical functions. The Lomb-Scargle periodogram and approximate entropy analyses confirm the higher volatility of S2-based heart rate compared to ECG-based heart rate. Correlation analysis shows stronger coupling between R�VR and R-S1 intervals during high-intensity activities. Hybrid ECG-PCG features, like the R-S2 interval, were identified as more informative for physical activity classification through mRMR feature selection and SHAP value analysis. Significance. The EPHNOGRAM database, is available on PhysioNet. The database enhances our understanding of cardiac function, enabling future studies on the heart's mechanical and electrical interrelationships. The results of this study can contribute to improved cardiac condition diagnoses. Additionally, the designed hardware has the potential for integration into wearable devices and the development of multimodal stress test technologies.

Objective. This study aims to automate the segmentation of retinal arterioles and venules (A/V) from digital fundus images (DFI), as changes in the spatial distribution of retinal microvasculature are indicative of cardiovascular diseases, positioning the eyes as windows to cardiovascular health. Approach. We utilized active learning to create a new DFI dataset with 240 crowd-sourced manual A/V segmentations performed by 15 medical students and reviewed by an ophthalmologist. We then developed LUNet, a novel deep learning architecture optimized for high-resolution A/V segmentation. The LUNet model features a double dilated convolutional block to widen the receptive field and reduce parameter count, alongside a high-resolution tail to refine segmentation details. A custom loss function was designed to prioritize the continuity of blood vessel segmentation. Main Results. LUNet significantly outperformed three benchmark A/V segmentation algorithms both on a local test set and on four external test sets that simulated variations in ethnicity, comorbidities and annotators. Significance. The release of the new datasets and the LUNet model (www.aimlab-technion.com/lirot-ai) provides a valuable resource for the advancement of retinal microvasculature analysis. The improvements in A/V segmentation accuracy highlight LUNet's potential as a robust tool for diagnosing and understanding cardiovascular diseases through retinal imaging.

Background and Objective. Sleep-disordered breathing (SDB) poses health risks linked to hypertension, cardiovascular disease, and diabetes. However, the time-consuming and costly standard diagnostic method, polysomnography (PSG), limits its wide adoption and leads to underdiagnosis. To tackle this, cost-effective algorithms using single-lead signals (like respiratory, blood oxygen, and electrocardiogram) have emerged. Despite respiratory signals being preferred for SDB assessment, a lack of comprehensive reviews addressing their algorithmic scope and performance persists. This paper systematically reviews 2012�V2022 literature, covering signal sources, processing, feature extraction, classification, and application, aiming to bridge this gap and provide future research references. Methods. This systematic review followed the registered PROSPERO protocol (CRD42022385130), initially screening 342 papers, with 32 studies meeting data extraction criteria. Results. Respiratory signal sources include nasal airflow (NAF), oronasal airflow (OAF), and respiratory movement-related signals such as thoracic respiratory effort (TRE) and abdominal respiratory effort (ARE). Classification techniques include threshold rule-based methods (8), machine learning models (13), and deep learning models (11). The NAF-based algorithm achieved the highest average accuracy at 94.11%, surpassing 78.19% for other signals. Hypopnea detection sensitivity with single-source respiratory signals remained modest, peaking at 73.34%. The TRE and ARE signals proved to be reliable in identifying different types of SDB because distinct respiratory disorders exhibited different patterns of chest and abdominal motion. Conclusions. Multiple detection algorithms have been widely applied for SDB detection, and their accuracy is closely related to factors such as signal source, signal processing, feature selection, and model selection..