搜索结果：Cardiovascular endocrinology & metabolism

Cardiovascular-Kidney-Metabolic (CKM) syndrome represents a growing public health crisis, yet the subclinical heterogeneity of its component systems remains underexplored. Early detection of physiological deviation is critical for preventing irreversible organ damage and mortality. Here, we characterize the prevalence and interplay of CKM impairment in a US cohort (N=841) by integrating continuous wearable data with clinical biomarkers. We assessed cardiovascular, kidney via clinical biomarkers, namely Chol/HDL, eGFR, as well as metabolic health risk through Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). We show that while metabolic and cardiovascular disruptions are significantly associated (r=0.26, p<0.001), early-stage kidney impairment manifests independently. Utilizing a normalized deviance score, we identified significant health impairments in 29.0% of the cohort. Cardiovascular deviation was the most prevalent singular phenotype (13.3%), followed by metabolic (9.1%) and renal (6.25%) deviations, with dual metabolic-cardiovascular impairment occurring in only 2.2% of participants. These findings suggest that high system-specific deviance may serve as an indi

The cardiovascular and ocular systems are intricately connected, with hemodynamic interactions playing a crucial role in both physiological regulation and pathological conditions. However, existing models often treat these systems separately, limiting the understanding of their interdependence. In this study, we present the Eye2Heart model, a novel closed-loop mathematical framework that integrates cardiovascular and ocular dynamics. Using an electricalhydraulic analogy, the model describes the interactions between the heart and retinal circulation through a system of ordinary differential equations. The model is validated against clinical and experimental data, demonstrating its ability to reproduce key cardiovascular parameters (e.g., stroke volume, cardiac output) and ocular hemodynamics (e.g., retinal blood flow). Additionally, we explore in silico the effects of intraocular pressure (IOP) and left ventricular compliance on both local ocular and global systemic circulation, revealing critical dependencies between cardiovascular and ocular health. The results highlight the model's potential for studying cardiovascular diseases with ocular manifestations, paving the way for patie

Representation of cities as organisms with metabolic processes is a useful analogy for urban design, development and sustainability. Urban metabolism can be modeled by representing urban systems as networks. The various networks included in a city's metabolism are interdependent in complex ways. Thus, understanding the interaction among these networks is essential to understanding how a healthy urban metabolism is sustained and how injuries to the metabolic system can "heal". It is particularly important to understand how disruptions to one system in an urban area affect the functioning of other systems. Using distribution-level data from a real U.S. city on the electricity distribution system and road geometry, we apply connected network modeling to two critical inter-connected urban infrastructure sectors: energy and transportation. We quantify the robustness of these interdependent networks by evaluating the connectivity disruptions that may occur due to natural or synthetic disruptive events, using both unweighted and weighted metrics.

Zero-dimensional cardiovascular models provide a computationally efficient framework for studying global hemodynamic behavior, yet the influence of model complexity on parameter sensitivity remains insufficiently understood. This work investigates two lumped-parameter cardiovascular models, a simplified single-ventricle configuration and a detailed four-chamber representation, to examine how physiological parameter sensitivities vary with model structure. Time-varying elastance functions are used to represent cardiac dynamics, and global sensitivity analysis is performed using Sobol and Morris methods to quantify the impact of key physiological parameters, including venous return, myocardial contractility, total peripheral resistance, and arterial compliance. The results demonstrate that sensitivity rankings differ substantially between the two models, highlighting the role of model granularity and parameter interactions in shaping cardiovascular responses. These findings support sensitivity-driven model reduction and provide a foundation for scalable, non-invasive cardiovascular simulation frameworks.

Background: Large language models have demonstrated strong performance on general medical examinations, but subspecialty clinical reasoning remains challenging due to rapidly evolving guidelines and nuanced evidence hierarchies. Methods: We evaluated January Mirror, an evidence-grounded clinical reasoning system, against frontier LLMs (GPT-5, GPT-5.2, Gemini-3-Pro) on a 120-question endocrinology board-style examination. Mirror integrates a curated endocrinology and cardiometabolic evidence corpus with a structured reasoning architecture to generate evidence-linked outputs. Mirror operated under a closed-evidence constraint without external retrieval. Comparator LLMs had real-time web access to guidelines and primary literature. Results: Mirror achieved 87.5% accuracy (105/120; 95% CI: 80.4-92.3%), exceeding a human reference of 62.3% and frontier LLMs including GPT-5.2 (74.6%), GPT-5 (74.0%), and Gemini-3-Pro (69.8%). On the 30 most difficult questions (human accuracy less than 50%), Mirror achieved 76.7% accuracy. Top-2 accuracy was 92.5% for Mirror versus 85.25% for GPT-5.2. Conclusions: Mirror provided evidence traceability: 74.2% of outputs cited at least one guideline-tier so

Cardiovascular events, such as heart attacks and strokes, remain a leading cause of mortality globally, necessitating meticulous monitoring and adjudication in clinical trials. This process, traditionally performed manually by clinical experts, is time-consuming, resource-intensive, and prone to inter-reviewer variability, potentially introducing bias and hindering trial progress. This study addresses these critical limitations by presenting a novel framework for automating the adjudication of cardiovascular events in clinical trials using Large Language Models (LLMs). We developed a two-stage approach: first, employing an LLM-based pipeline for event information extraction from unstructured clinical data and second, using an LLM-based adjudication process guided by a Tree of Thoughts approach and clinical endpoint committee (CEC) guidelines. Using cardiovascular event-specific clinical trial data, the framework achieved an F1-score of 0.82 for event extraction and an accuracy of 0.68 for adjudication. Furthermore, we introduce the CLEART score, a novel, automated metric specifically designed for evaluating the quality of AI-generated clinical reasoning in adjudicating cardiovascul

Smart rings offer a convenient way to continuously and unobtrusively monitor cardiovascular physiological signals. However, a gap remains between the ring hardware and reliable methods for estimating cardiovascular parameters, partly due to the lack of publicly available datasets and standardized analysis tools. In this work, we present $τ$-Ring, the first open-source ring-based dataset designed for cardiovascular physiological sensing. The dataset comprises photoplethysmography signals (infrared and red channels) and 3-axis accelerometer data collected from two rings (reflective and transmissive optical paths), with 28.21 hours of raw data from 34 subjects across seven activities. $τ$-Ring encompasses both stationary and motion scenarios, as well as stimulus-evoked abnormal physiological states, annotated with four ground-truth labels: heart rate, respiratory rate, oxygen saturation, and blood pressure. Using our proposed RingTool toolkit, we evaluated three widely-used physics-based methods and four cutting-edge deep learning approaches. Our results show superior performance compared to commercial rings, achieving best MAE values of 5.18 BPM for heart rate, 2.98 BPM for respirato

Cancer cells are often seen to prefer glycolytic metabolism over oxidative phosphorylation even in the presence of oxygen-a phenomenon termed the Warburg effect. Despite significant strides in the decades since its discovery, a clear basis is yet to be established for the Warburg effect and why cancer cells show such a preference for aerobic glycolysis. In this review, we draw on what is known about similar metabolic shifts both in normal mammalian physiology and overflow metabolism in microbes to shed new light on whether aerobic glycolysis in cancer represents some form of optimisation of cellular metabolism. From microbes to cancer, we find that metabolic shifts favouring glycolysis are sometimes driven by the need for faster growth, but the growth rate is by no means a universal goal of optimal metabolism. Instead, optimisation goals at the cellular level are often multi-faceted and any given metabolic state must be considered in the context of both its energetic costs and benefits over a range of environmental contexts. For this purpose, we identify the conceptual framework of resource allocation as a potential testbed for the investigation of the cost-benefit balance of cellu

The origin of life required the emergence of metabolism, an autocatalytic network of enzymatic reactions that synthesize amino acids, nucleotides and cofactors. At the origin of metabolism there were no enzymes--how did it start? Empirical studies addressing early metabolic evolution are lacking. Harnessing protein structures for metabolic enzymes, we identify intermediate states in primordial metabolic assembly. We show that enzymatic metabolism in the universal common ancestor was incomplete, undergoing final assembly independently in the lineages leading to Bacteria and Archaea. Native transition metals--Fe0, Co0, Ni0, Pd0--served as the catalytic forerunners of both enzymes and cofactors at metabolic origin while phosphite supplied energy, as it phosphorylates AMP to ADP and serine to phosphoserine using native metal catalysts in water. Phosphite and native metals occur in serpentinizing hydrothermal systems, identifying an energy-supplying, catalytic site of metabolic origin. Cofactors liberated nascent metabolism from native metal catalysts, engendering its autocatalytic state.

Cardiovascular signals such as photoplethysmography (PPG), electrocardiography (ECG), and blood pressure (BP) are inherently correlated and complementary, together reflecting the health of cardiovascular system. However, their joint utilization in real-time monitoring is severely limited by diverse acquisition challenges from noisy wearable recordings to burdened invasive procedures. Here we propose UniCardio, a multi-modal diffusion transformer that reconstructs low-quality signals and synthesizes unrecorded signals in a unified generative framework. Its key innovations include a specialized model architecture to manage the signal modalities involved in generation tasks and a continual learning paradigm to incorporate varying modality combinations. By exploiting the complementary nature of cardiovascular signals, UniCardio clearly outperforms recent task-specific baselines in signal denoising, imputation, and translation. The generated signals match the performance of ground-truth signals in detecting abnormal health conditions and estimating vital signs, even in unseen domains, while ensuring interpretability for human experts. These advantages position UniCardio as a promising a

Background: Photoplethysmography (PPG), increasingly available through wearable devices, provides a non-invasive means of monitoring human hemodynamics. In this study, we introduce artificial intelligence-derived photoplethysmography (AI-PPG) age, a deep learning-based estimate of biological age from raw PPG signals, and evaluate its potential as a digital biomarker for cardiovascular health. Methods: We developed a deep learning model with a distribution-aware loss function to reduce bias from imbalanced data. The model was trained and evaluated on the UK Biobank cohort (N = 212,231). We analyzed the association between the AI-PPG age gap (AI-PPG age minus calendar age) and multiple cardiovascular and metabolic outcomes, assessed its longitudinal value using serial PPG measurements, and externally validated its generalizability in an independent MIMIC-III-derived cohort (N = 2,343). Results: After adjusting for key confounders, participants with an AI-PPG age gap greater than 9 years have a significantly higher risk of major adverse cardiovascular and cerebrovascular events (hazard ratio of 2.37, p = 8.46x10$^{-80}$), as well as seven secondary outcomes including coronary heart di

Cardiovascular diseases are the leading cause of death. Increased levels of plasma cholesterol are consistently associated with an increased risk of cardiovascular disease. As a result, it is imperative that studies are conducted to determine the best course of action to reduce whole-body cholesterol levels. A whole-body mathematical model for cholesterol metabolism and transport is proposed. The model can simulate the effects of lipid-lowering drugs like statins and anti-PCSK9. The model is based on ordinary differential equations and kinetic functions. It has been validated against literature data. It offers a versatile platform for designing personalized interventions for cardiovascular health management.

Cardiovascular disease (CVD) remains the leading global cause of mortality, yet current risk stratification methods often fail to detect early, subclinical changes. Previous studies have generally not integrated retinal microvasculature characteristics with comprehensive serum lipidomic profiles as potential indicators of CVD risk. In this study, an innovative imaging omics framework was introduced, combining retinal microvascular traits derived through deep learning based image processing with serum lipidomic data to highlight asymptomatic biomarkers of cardiovascular risk beyond the conventional lipid panel. This represents the first large scale, covariate adjusted and stratified correlation analysis conducted in a healthy population, which is essential for identifying early indicators of disease. Retinal phenotypes were quantified using automated image analysis tools, while serum lipid profiling was performed by Ultra High Performance Liquid Chromatography Electrospray ionization High resolution mass spectrometry (UHPLC ESI HRMS). Strong, age- and sex-independent correlations were established, particularly between average artery width, vessel density, and lipid subclasses such a

Metabolism plays a crucial role in sleep regulation, yet its effects are challenging to track in real time. This study introduces a machine learning-based framework to analyze sleep patterns and identify how metabolic changes influence sleep at specific time points. We first established that sleep periods in Drosophila melanogaster function independently, with no causal relationship between different sleep episodes. Using gradient boosting models and explainable artificial intelligence techniques, we quantified the influence of time-dependent sleep features. Causal inference and autocorrelation analyses further confirmed that sleep states at different times are statistically independent, providing a robust foundation for exploring metabolic effects on sleep. Applying this framework to flies with altered monocarboxylate transporter 2 expression, we found that changes in ketone transport modified sleep stability and disrupted transitions between day and night sleep. In an Alzheimers disease model, metabolic interventions such as beta hydroxybutyrate supplementation and intermittent fasting selectively influenced the timing of day to night transitions rather than uniformly altering sl

Quantifying cardiovascular parameters like ejection fraction in zebrafish as a host of biological investigations has been extensively studied. Since current manual monitoring techniques are time-consuming and fallible, several image processing frameworks have been proposed to automate the process. Most of these works rely on supervised deep-learning architectures. However, supervised methods tend to be overfitted on their training dataset. This means that applying the same framework to new data with different imaging setups and mutant types can severely decrease performance. We have developed a Zebrafish Automatic Cardiovascular Assessment Framework (ZACAF) to quantify the cardiac function in zebrafish. In this work, we further applied data augmentation, Transfer Learning (TL), and Test Time Augmentation (TTA) to ZACAF to improve the performance for the quantification of cardiovascular function quantification in zebrafish. This strategy can be integrated with the available frameworks to aid other researchers. We demonstrate that using TL, even with a constrained dataset, the model can be refined to accommodate a novel microscope setup, encompassing diverse mutant types and accommod

Molecular chirality is critical to biochemical function, but it is unknown when chiral selectivity first became important in the evolutionary transition from geochemistry to biochemistry during the emergence of life. Here, we identify key transitions in the selection of chiral molecules in metabolic evolution, showing how achiral molecules (lacking chiral centers) may have given rise to specific and abundant chiral molecules in the elaboration of metabolic networks from geochemically available precursor molecules. Simulated expansions of biosphere-scale metabolism suggest new hypotheses about the evolution of chiral molecules within biochemistry, including a prominent role for both achiral and chiral compounds as nucleation sites of early metabolic network growth, an increasing enrichment of molecules with more chiral centers as these networks expand, and conservation of broken chiral symmetries along reaction pathways as a general organizing principle. We also find an unexpected enrichment in large, non-polymeric achiral molecules. Leveraging metabolic data of 40,023 genomes and metagenomes, we analyzed the statistics of chiral and achiral molecules in the large-scale organization

What makes living things special is how they manage matter, energy, and entropy. A general theory of organismal metabolism should therefore be quantified in these three currencies while capturing the unique way they flow between individuals and their environments. We argue that such a theory has quietly arrived -- 'Dynamic Energy Budget' (DEB) theory -- which conceptualises organisms as a series of macrochemical reactions that use energy to transform food into structured biomass and bioproducts while producing entropy. We show that such conceptualisation is deeply rooted in thermodynamic principles and that, with the help of a small set of biological assumptions, it underpins the emergence of fundamental ecophysiological phenomena, most notably the three-quarter power scaling of metabolism. Building on the subcellular nature of the theory, we unveil the eco-evolutionary relevance of coarse-graining biomass into qualitatively distinct, stoichiometricially fixed pools with implicitly regulated dynamics based on surface area-volume relations. We also show how generalised enzymes called 'synthesising units' and an information-based state variable called 'maturity' capture transitions b

Metabolic models condense biochemical knowledge about organisms in a structured and standardised way. As large-scale network reconstructions are readily available for many organisms, genome-scale models are being widely used among modellers and engineers. However, these large models can be difficult to analyse and visualise and occasionally generate predictions that are hard to interpret or even biologically unrealistic. Of the thousands of enzymatic reactions in a typical bacterial metabolism, only a few hundred form the metabolic pathways essential to produce energy carriers and biosynthetic precursors. These pathways carry relatively high flux, are central to maintaining and reproducing the cell, and provide precursors and energy to engineered metabolic pathways. Focusing on these central metabolic subsystems, we present iCH360, a manually curated medium-scale model of energy and biosynthesis metabolism for the well-studied bacterium Escherichia coli K-12 MG1655. The model is a sub-network of the most recent genome-scale reconstruction, iML1515, and comes with an updated layer of database annotations and with a range of metabolic maps for visualisation. We enriched the stoichiom

Biological systems are governed by coupled interactions between intracellular metabolism and bioreactor operation that span multiple time scales. Constraint-based metabolic models are widely used to describe intracellular metabolism, but repeatedly solving the optimization problem at each time step in dynamic models introduces numerical challenges related to infeasibility and computational efficiency. This work presents a multi-scale modeling framework that integrates genome-scale, constraint-based metabolic models with dynamic bioreactor simulations. Intracellular metabolism is described using positive flux variables in a parsimonious flux balance analysis, and the resulting embedded optimization problem is replaced by a neural network surrogate. The surrogate provides a smooth approximation of the embedded optimization mapping and eliminates repeated linear program solves during simulation. The approach is demonstrated for fed-batch fermentation of Escherichia coli, in which the surrogate model yields intracellular fluxes under substrate-limited conditions, whereas the underlying linear program would otherwise be infeasible. The framework provides a continuous representation of i