Potential therapeutic targets of gastric cancer explored under endogenous network modeling of clinical data.

Improvement in the survival rate of gastric cancer, a prevalent global malignancy and the leading cause of cancer-related mortality calls for more avenues in molecular therapy. This work aims to comprehend drug resistance and explore multiple-drug combinations for enhanced therapeutic treatment. An endogenous network modeling clinic data with core gastric cancer molecules, functional modules, and pathways is constructed, which is then transformed into dynamics equations for in-silicon studies. Principal component analysis, hierarchical clustering, and K-means clustering are utilized to map the attractor domains of the stochastic model to the normal and pathological phenotypes identified from the clinical data. The analyses demonstrate gastric cancer as a cluster of stable states emerging within the stochastic dynamics and elucidate the cause of resistance to anti-VEGF monotherapy in cancer treatment as the limitation of the single pathway in preventing cancer progression. The feasibility of multiple objectives of therapy targeting specified molecules and/or pathways is explored. This study verifies the rationality of the platform of endogenous network modeling, which contributes to the development of cross-functional multi-target combinations in clinical trials.

Radiomics Analysis of Pericoronary Adipose Tissue From Baseline Coronary Computed Tomography Angiography Enables Prediction of Coronary Plaque Progression.

PURPOSE: The relationship between plaque progression and pericoronary adipose tissue (PCAT) radiomics has not been comprehensively evaluated. We aim to predict plaque progression with PCAT radiomics features and evaluate their incremental value over quantitative plaque characteristics. PATIENTS AND METHODS: Between January 2009 and December 2020, 500 patients with suspected or known coronary artery disease who underwent serial coronary computed tomography angiography (CCTA) ≥2 years apart were retrospectively analyzed and randomly stratified into a training and testing data set with a ratio of 7:3. Plaque progression was defined with annual change in plaque burden exceeding the median value in the entire cohort. Quantitative plaque characteristics and PCAT radiomics features were extracted from baseline CCTA. Then we built 3 models including quantitative plaque characteristics (model 1), PCAT radiomics features (model 2), and the combined model (model 3) to compare the prediction performance evaluated by area under the curve. RESULTS: The quantitative plaque characteristics of the training set showed the values of noncalcified plaque volume (NCPV), fibrous plaque volume, lesion length, and PCAT attenuation were larger in the plaque progression group than in the nonprogression group ( P < 0.05 for all). In multivariable logistic analysis, NCPV and PCAT attenuation were independent predictors of coronary plaque progression. PCAT radiomics exhibited significantly superior prediction over quantitative plaque characteristics both in the training (area under the curve: 0.814 vs 0.615, P < 0.001) and testing (0.736 vs 0.594, P = 0.007) data sets. CONCLUSIONS: NCPV and PCAT attenuation were independent predictors of coronary plaque progression. PCAT radiomics derived from baseline CCTA achieved significantly better prediction than quantitative plaque characteristics.

Corrigendum: Impact of a mobile health intervention based on multi-theory model of health behavior change on self-management in patients with differentiated thyroid cancer: protocol for a randomized controlled trial.

[This corrects the article DOI: 10.3389/fpubh.2024.1327442.].

Case report: Primary pulmonary low grade fibromyxoid sarcoma progressing to dedifferentiation: probably due to TP53 driver mutation.

Low Grade Fibromyxoid Sarcoma (LGFMS), a rare entity characterized by bland histologic features, typically affects deep soft tissues of the trunk and lower extremities. Rare cases have been reported arising from the viscera and few demonstrating morphology of high-grade dedifferentiation. Here we report a 39-year-old Chinese woman presenting with primary lung LGFMS, which metastasized to the pancreas five years after diagnosis and then relapsed ten years later as a mediastinum mass. Microscopically, the lung and pancreatic lumps shared similar classical features of LGFMS, composed of bland spindle-shaped cells with low mitotic activity. However, the mediastinal mass had dedifferentiated morphology of dense sheets of round and epithelioid cells with high degree of nuclear pleomorphism and brisk mitosis. Molecular studies showed both classical and dedifferentiated areas had FUS::CREB3L2 rearrangement. However, the mediastinal dedifferentiated area presented with extra H193Y mutation of the TP53. Moreover, the mediastinal tumor displayed a strong and diffuse pattern of p53 expression immunohistochemically, but the primary lung and secondary pancreatic masses did not. Thus, we diagnosed the mediastinal mass as dedifferentiated LGFMS and proposed that TP53 mutation was probably the driver gene alteration in the process, which, to the best of our knowledge, has not been reported in the existing literature.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

A comparative study of synthetic and venous hematocrit for calculating cardiovascular magnetic resonance-derived extracellular volume.

The extracellular volume (ECV) fraction derived from cardiac magnetic resonance (CMR) can reflect various pathologies. The application of ECVs was limited by the strict requirement that hematocrit (Hct0) should be obtained within 24 hours of CMR scan. The aim of this study was to obtain accurate and convenient ECV calculated from the venous Hct and synthetic Hct in CMR. A total of 839 subjects were retrospectively enrolled. The subjects were divided into derivation cohort for local sex-specific models and validation cohort for assessing the accuracy of different ECVs. In the validation cohort, venous Hcts from 7 days before the scan (Hct1 - 7), outside 7 days (Hct> 7), the closest day (Hctclosest), and Hctsyn were compared with Hct0. The agreement and correlation of the conventional ECV (ECV0) with the corresponding ECVs were analyzed. The factors affecting the accuracy of ECVsyn were assessed. ECV1-7 and ECVclosest had the best correlation and smallest bias with ECV0 (R = 0.959 and 0.951, bias = 0.02% and - 0.03%). When using an absolute 2% error as the standard, the performance of ECV1-7 was the best, with an accuracy of 81.0%, followed by ECVclosest (78.8%), ECV> 7 (77.2%) and ECVsyn (70.7%). Abnormally low and high Hcts and decreased left ventricular ejection fractions were associated with miscalculation of ECVsyn, especially patients with dilated cardiomyopathy. We recommend extending the time interval between a Hct and a CMR scan to 7 days for ECV calculation. The synthetic ECV should be used cautiously, especially for patients with extremely low or high Hcts, decreased cardiac function, and dilated cardiomyopathy.

Single Bolus r-SAK Before Primary PCI for ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: It is uncertain whether adjunctive thrombolysis is beneficial for patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) within 120 minutes of presentation. This study was to determine whether in patients presenting with ST-segment-elevation myocardial infarction a single bolus recombinant staphylokinase (r-SAK) before timely PCI leads to improved patency of the infarct-related artery and reduces the infarct size. METHODS: This is an open-label, prospective, multicenter, randomized study. We enrolled patients aged 18 to 75 years who were within 12 hours of symptom onset of ST-segment-elevation myocardial infarction and expected to undergo PCI within 120 minutes. Patients were administered loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive 5 mg bolus of r-SAK or normal saline intravenously before PCI. The primary end point was Thrombolysis in Myocardial Infarction flow grade 2 to 3 or grade 3 in the infarct-related artery 60 minutes after thrombolysis. The infarct size was detected by cardiac magnetic resonance 5 days after randomization. The safety end point was major bleeding (Bleeding Academic Research Consortium ≥3) during 30-day follow-up. RESULTS: A total of 283 patients were screened from 8 centers and 200 were randomized (median age, 58.5 years; 14% female). The median symptom to thrombolysis time was 252.5 (interquartile range, 142.8-423.8) minutes and thrombolysis to coronary arteriography was 50.0 (interquartile range, 37.0-66.0) minutes. Patients randomized to r-SAK compared with normal saline more often had Thrombolysis in Myocardial Infarction flow grade 2 to 3 (69.0% versus 29.0%; P<0.001) and Thrombolysis in Myocardial Infarction flow grade 3 (51.0% versus 18.0%; P<0.001) and had smaller infarct size (21.91±10.84% versus 26.85±12.37%; P=0.016). There was no increase in major bleeding (r-SAK, 1.0% versus control, 3.0%; P=0.616). CONCLUSIONS: A single bolus r-SAK before primary PCI for ST-segment-elevation myocardial infarction improves infarct-related artery patency and reduces infarct size without increasing major bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05023681.

Impact of a mobile health intervention based on multi-theory model of health behavior change on self-management in patients with differentiated thyroid cancer: protocol for a randomized controlled trial.

Introduction: Theoretical models of health behavior are important guides for disease prevention and detection, treatment and rehabilitation, and promotion and maintenance of physical and mental health, but there are no intervention studies related to differentiated thyroid cancer (DTC) that use theoretical models of health as a guide. In this study, we used a microblogging platform as an intervention vehicle and mobile patient-doctor interactive health education as a means of intervention, with the aim of improving the health behaviors of DTC patients as well as the corresponding clinical outcomes. Methods: This research project is a quantitative methodological study, and the trial will be a single-blind, single-center randomized controlled trial conducted at the Fourth Hospital of Harbin Medical University in Harbin, Heilongjiang Province. The study subjects are patients over 18 years of age with differentiated thyroid cancer who were given radioactive iodine-131 therapy as well as endocrine therapy after radical surgery for thyroid cancer. The intervention group will receive MTM-mhealth, and the realization of health education will rely on the smart terminal WeChat platform. Routine discharge education will be given to the control group at discharge. The primary outcome will be change in thyroid-stimulating hormone (TSH) from baseline and at 3 and 6 months of follow-up, and secondary outcomes will include change in self-management behavior, social cognitive and psychological, and metabolic control. Discussion: This study will explore a feasible mHealth intervention program applied to a population of DTC patients using the Multi-theory model of health behavior change (MTM) as a guide, with the aim of evaluating the MTM-based intervention program for clinical outcome improvement in DTC patients, as well as determining the effectiveness of the MTM-based intervention program in improving self-management skills in DTC patients. The results of this study will indicate the feasibility as well as the effectiveness of the application of health theoretical modeling combined with mHealth applications in disease prognostic health management models, and provide policy recommendations and technological translations for the development of mobility-based health management applications in the field of health management.

Extracellular contrast agent-enhanced MRI is as effective as gadoxetate disodium-enhanced MRI for predicting microvascular invasion in HCC.

PURPOSE: To compare the performances of gadoxetate disodium-enhanced MRI (EOB-MRI) and extracellular contrast agent-enhanced MRI (ECA-MRI) for predicting microvascular invasion (MVI) in HCC. MATERIALS AND METHODS: From November 2009 to December 2021, consecutive HCC patients who underwent preoperative contrast-enhanced MRI were retrospectively enrolled into either an ECA-MRI or EOB-MRI cohort. In the ECA-MRI cohort, a preoperative MVI score was constructed in the training dataset using a logistic regression model that evaluated pathological type. In a propensity score-matched testing dataset of the ECA-MRI cohort, the MVI score was validated and compared with a previously proposed EOB-MRI-based MVI score calculated in the EOB-MRI cohort. Time-to-early recurrence survival was evaluated by the Kaplan-Meier method with the log-rank test. RESULTS: A total of 536 patients were included (478 men; 53 years, interquartile range, 46-62 years), 322 (60.1 %) with pathologically confirmed MVI. Based on the training dataset, independent variables associated with MVI included serum alpha-fetoprotein > 400 ng/ml (odds ratio [OR] = 2.3), infiltrative appearance (OR = 4.9), internal artery (OR = 2.5) and nodule-in-nodule architecture (OR = 2.4), which were incorporated into the ECA-MRI-based MVI score. The testing dataset AUC of the ECA-MRI score was 0.720, which was comparable to that of the EOB-MRI-based MVI score (AUC = 0.721; P =.99). Patients from either the ECA-MRI or the EOB-MRI cohort with model-predicted MVI had significantly shorter time-to-early recurrence than those without MVI (P <.001). CONCLUSION: Based on the preoperative serum alpha-fetoprotein and three MRI features, ECA-MRI demonstrated comparable performance to EOB-MRI for predicting MVI in HCC.

Interleukin-33/serum stimulation-2 pathway: Regulatory mechanisms and emerging implications in immune and inflammatory diseases.

Interleukin (IL)- 33, a nuclear factor and pleiotropic cytokine of the IL-1 family, is gaining attention owing to its important role in chronic inflammatory and autoimmune diseases. This review extends our knowledge of the effects exerted by IL-33 on target cells by binding to its specific receptor serum stimulation-2 (ST2). Depending on the tissue context, IL-33 performs multiple functions encompassing host defence, immune response, initiation and amplification of inflammation, tissue repair, and homeostasis. The levels and activity of IL-33 in the body are controlled by complex IL-33-targeting regulatory pathways. The unique temporal and spatial expression patterns of IL-33 are associated with host homeostasis and the development of immune and inflammatory disorders. Therefore, understanding the origin, function, and processes of IL-33 under various conditions is crucial. This review summarises the regulatory mechanisms underlying the IL-33/ST2 signalling axis and its potential role and clinical significance in immune and inflammatory diseases, and discusses the current complex and conflicting findings related to IL-33 in host responses.

Unveiling the Occurrence and Non-Negligible Role of Amino Sugars in Waste Activated Sludge Fermentation by an Enriched Chitin-Degradation Consortium.

Polysaccharides in extracellular polymeric substances (EPS) can form a hybrid matrix network with proteins, impeding waste-activated sludge (WAS) fermentation. Amino sugars, such as N-acetyl-d-glucosamine (GlcNAc) polymers and sialic acid, are the non-negligible components in the EPS of aerobic granules or biofilm. However, the occurrence of amino sugars in WAS and their degradation remains unclear. Thus, amino sugars (∼6.0%) in WAS were revealed, and the genera of Lactococcus and Zoogloea were identified for the first time. Chitin was used as the substrate to enrich a chitin-degrading consortium (CDC). The COD balances for methane production ranged from 83.3 and 95.1%. Chitin was gradually converted to oligosaccharides and GlcNAc after dosing with the extracellular enzyme. After doing enriched CDC in WAS, the final methane production markedly increased to 60.4 ± 0.6 mL, reflecting an increase of ∼62%. Four model substrates of amino sugars (GlcNAc and sialic acid) and polysaccharides (cellulose and dextran) could be used by CDC. Treponema (34.3%) was identified as the core bacterium via excreting chitinases (EC 3.2.1.14) and N-acetyl-glucosaminidases (EC 3.2.1.52), especially the genetic abundance of chitinases in CDC was 2.5 times higher than that of WAS. Thus, this study provides an elegant method for the utilization of amino sugar-enriched organics.

Enhancing production and purity of 9-OH-AD from phytosterols by balancing metabolic flux of the side-chain degradation and 9-position hydroxylation in Mycobacterium neoaurum.

9α-Hydroxyandroster-4-ene-3,17-dione (9-OH-AD) is a representative steroid drug intermediate that can be prepared by phytosterols (PS) biotransformation with mycobacteria in a resting cell-cyclodextrin system. In this study, over-expression of 17ß-hydroxysteroid dehydrogenase (Hsd4A) was testified to enhance the side-chain degradation of PS and to reduce the incomplete degradation by-products. Meanwhile, the complete degradation product 4-androstene-3,17-dione (AD) was increased due to the lack of 3-Ketosteroid 9α-Hydroxylase (KshA1) activities. To increase the production and purity of 9-OH-AD, the metabolic pathway of the side-chain degradation of PS and 9-position hydroxylation was modulated by balancing the over-expression of Hsd4A and KshA1 in mycobacteria and reducing the bioconversion rate via lowering the ratio of PS and cyclodextrin. The production and purity of 9-OH-AD in broth were improved from 22.18 g L-1 and 77.13% to 28.27 g L-1 and 87.84%, with a molar yield of 78.32%.

Autophagy-related 7 proteindependent autophagy mediates resveratrol-caused upregulation of mitochondrial biogenesis and steroidogenesis in aged Leydig cell.

BACKGROUND: Mitochondrial dysfunction may contribute to decreased testosterone synthesis in aged Leydig cells. Resveratrol (RSV) as an antioxidant has been shown to exhibit multiple positive effects on mitochondrion, where steroidogenesis takes place. Whether RSV can improve steroidogenesis in aged testis is still unknown. This study investigates the effect of RSV on testosterone production during aging and corresponding changes in mitochondrial biogenesis and autophagy activity, which are closely associated with steroidogenesis. Whether ATG7, an important autophagy-related protein, functions in RSV-treated aged Leydig cells will also be explored. METHODS AND RESULTS: Two-month-old male C57BL/6 mice were fed for 16 months by customized regular diet with or without RSV as diet supplement. Leydig cell line TM3 cells were treated with D-galactose to induce senescence, followed with or without RSV treatment. Results found that RSV supplement increased testosterone production in both aged mice and D-galactose-induced senescent Leydig cells. Western blot results revealed that RSV treatment elevated levels of steroidogenic rate-limiting enzymes StAR and 3ß-HSD, as well as autophagy-related proteins LC3II, Beclin1, ATG5 and ATG7 and mitochondrial function-related proteins mtTFA and COXIV. However, after Atg7 was knocked down in senescent Leydig cells, even though RSV was added, levels of these proteins declined significantly, accompanied by decreased levels of mitochondrial transcript factors PGC-1α, mtTFA and NRF-1 and more fragmented mitochondria, demonstrating that Atg7 knockdown wrecked the protective effects of RSV on steroidogenesis in senescent Leydig cells. CONCLUSION: ATG7-dependent autophagy plays a key role in RSV-brought testosterone production increase through regulating mitochondrial biogenesis in senescent Leydig cells.

Interfacial Engineering of Ru Nanocluster-Modified TiO2 Nanotube-Assisted Regulation of Lithium Polysulfide Reactions.

The inhibition of lithium polysulfide (LiPS) diffusion and the acceleration of reaction kinetics are two major challenges for the practical application of lithium-sulfur (Li-S) batteries. Herein, through an interface engineering strategy, a multifunctional sulfur host based on Ru nanocluster-modified TiO2 nanotubes (TiO2-Ru) was designed. The TiO2-Ru interface field effect, combined with the hollow nanotube structure and the strong chemical action of TiO2, enhanced the LiPS trapping ability and inhibited the "shuttle effect". Furthermore, the high catalytic activity of Ru nanoclusters reduced the energy barrier of multistep LiPS reactions, thus speeding up the electrode kinetics. As a result, the TiO2-Ru-based composite sulfur cathode delivered excellent electrochemical performance, including an extremely low capacity loss of ∼0.015% per cycle and an increased areal capacity of ∼6.1 mAh cm-2 at 4.8 mg cm-2. This work contributes to a better sulfur cathode design from insights into morphology and phase interface engineering.

The neuroprotective effect of dl-3-n-butylphthalide on the brain with experimental intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, nevertheless specific treatments with conclusive clinical benefit in improving outcomes of ICH remain lacking. The present study applied dl-3-n-butylphthalide (NBP), a compound approved for the treatment of ischemic stroke and rarely studied in ICH, to an experimental animal model of ICH, aiming to evaluate the therapeutic effects of NBP on ICH and the potential mechanisms. The results showed that rats receiving NBP administration exhibited a structural and functional restoration of brain after ICH mainly manifested as alleviation of neuronal apoptosis, suppression of neuroinflammation and oxidative stress, neurovascular remodeling, and eventually improvement of neurological deficits. In addition, several protein targets of NBP were revealed, which mainly play molecular functions of ribonucleoside triphosphate phosphatase activity, pyrophosphatase activity, hydrolase activity and GTPase activity, and participate in the biological process of brain development by regulating the formation of cellular components such as spindles, polymeric cytoskeletal fibers, microtubules and synapses, through mediating pathways such as VEGF signaling pathway, Fc epsilon RI signaling pathway, ECM-receptor interaction, Fc gamma R-mediated phagocytosis, peroxisome and so on, guiding the mechanism exploration of NBP therapy to some extent. Taken together, the study added some new evidence to the application of NBP in ICH treatment.

Machine learning-based prediction model of acute kidney injury in patients with acute respiratory distress syndrome.

BACKGROUND: Acute kidney injury (AKI) can make cases of acute respiratory distress syndrome (ARDS) more complex, and the combination of the two can significantly worsen the prognosis. Our objective is to utilize machine learning (ML) techniques to construct models that can promptly identify the risk of AKI in ARDS patients. METHOD: We obtained data regarding ARDS patients from the Medical Information Mart for Intensive Care III (MIMIC-III) and MIMIC-IV databases. Within the MIMIC-III dataset, we developed 11 ML prediction models. By evaluating various metrics, we visualized the importance of its features using Shapley additive explanations (SHAP). We then created a more concise model using fewer variables, and optimized it using hyperparameter optimization (HPO). The model was validated using the MIMIC-IV dataset. RESULT: A total of 928 ARDS patients without AKI were included in the analysis from the MIMIC-III dataset, and among them, 179 (19.3%) developed AKI after admission to the intensive care unit (ICU). In the MIMIC-IV dataset, there were 653 ARDS patients included in the analysis, and among them, 237 (36.3%) developed AKI. A total of 43 features were used to build the model. Among all models, eXtreme gradient boosting (XGBoost) performed the best. We used the top 10 features to build a compact model with an area under the curve (AUC) of 0.850, which improved to an AUC of 0.865 after the HPO. In extra validation set, XGBoost_HPO achieved an AUC of 0.854. The accuracy, sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and F1 score of the XGBoost_HPO model on the test set are 0.865, 0.813, 0.877, 0.578, 0.957 and 0.675, respectively. On extra validation set, they are 0.724, 0.789, 0.688, 0.590, 0.851, and 0.675, respectively. CONCLUSION: ML algorithms, especially XGBoost, are reliable for predicting AKI in ARDS patients. The compact model maintains excellent predictive ability, and the web-based calculator improves clinical convenience. This provides valuable guidance in identifying AKI in ARDS, leading to improved patient outcomes.

Modular synthesis of clickable peptides via late-stage maleimidation on C(7)-H tryptophan.

Cyclic peptides have attracted tremendous attention in the pharmaceutical industry owing to their excellent cell penetrability, stability, thermostability, and drug-like properties. However, the currently available facile methodologies for creating such peptides are rather limited. Herein, we report an efficient and direct peptide cyclization via rhodium(III)-catalyzed C(7)-H maleimidation. Notably, this catalytical system has excellent regioselectivity and high tolerance of functional groups which enable late-stage cyclization of peptides. This architecture of cyclic peptides exhibits higher bioactivity than its parent linear peptides. Moreover, the Trp-substituted maleimide displays excellent reactivity toward Michael addition, indicating its potential as a click functional group for applications in chemical biology and medicinal chemistry. As a proof of principle, RGD-GFLG-DOX, which is a peptide-drug-conjugate, is constructed and it displays a strong binding affinity and high antiproliferative activity toward integrin-αvß3 overexpressed cancer cell lines. The proposed strategy for rapid preparation of stapled peptides would be a robust tool for creating peptide-drug conjugates.

Predicting coronary plaque progression with conventional plaque parameters and radiomics features derived from coronary CT angiography.

OBJECTIVES: To determine the value of combining conventional plaque parameters and radiomics features derived from coronary computed tomography angiography (CCTA) for predicting coronary plaque progression. MATERIALS AND METHODS: Clinical data and CCTA images of 400 patients who underwent at least two CCTA examinations between January 2009 and August 2020 were analyzed retrospectively. Diameter stenosis, total plaque volume and burden, calcified plaque volume and burden, noncalcified plaque volume and burden (NCPB), pericoronary fat attenuation index (FAI), and other conventional plaque parameters were recorded. The patients were assigned to a training cohort (n = 280) and a validation cohort (n = 120) in a 7:3 ratio using a stratified random splitting method. The area under the receiver operating characteristics curve (AUC) was used to evaluate the predictive abilities of conventional parameters (model 1), radiomics features (model 2), and their combination (model 3). RESULTS: FAI and NCPB were identified as independent risk factors for coronary plaque progression in the training cohort. Both model 2 (training cohort AUC: 0.814, p < 0.001; validation cohort AUC: 0.729, p = 0.288) and model 3 (training cohort AUC: 0.824, p < 0.001; validation cohort AUC: 0.758, p = 0.042) had better diagnostic performances in predicting plaque progression than model 1 (training cohort AUC: 0.646; validation cohort AUC: 0.654). Moreover, model 3 was slightly higher than model 2, although not statistically significant. CONCLUSIONS: The combination of conventional coronary plaque parameters and CCTA-derived radiomics features had a better ability to predict plaque progression than conventional parameters alone. CLINICAL RELEVANCE STATEMENT: The conventional coronary plaque characteristics such as noncalcified plaque burden, pericoronary fat attenuation index, and radiomics features derived from CCTA can identify plaques prone to progression, which is helpful for further clinical decision-making of coronary artery disease. KEY POINTS: • FAI and NCPB were identified as independent risk factors for predicting plaque progression. • Coronary plaque radiomics features were more advantageous than conventional parameters in predicting plaque progression. • The combination of conventional coronary plaque parameters and radiomics features could significantly improve the predictive ability of plaque progression over conventional parameters alone.