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BACKGROUND: Data on long-term cancer survivors treated with apatinib are lacking. This study aimed to describe the characteristics of long-term cancer survivors after apatinib-based therapy, and to know about their satisfaction degree with apatinib and severity of depression and insomnia. METHODS: Patients with solid tumors who had received apatinib-based therapy for at least 5 years were invited to complete an online questionnaire. Characteristics of patients and treatment, knowledge of apatinib, satisfaction degree, and severity of depression and insomnia assessed by Patient Health Questionnaire-9 and Insomnia Severity Index were collected. RESULTS: Between December 8, 2023 and March 1, 2024, a total of 436 patients completed the online questionnaire. Most patients were satisfied with the efficacy (96.6%) and safety (93.1%) of apatinib, were willing to continue apatinib treatment (99.5%), and would recommend apatinib to other patients (93.3%). Continuous apatinib treatment resulted in significant negative impact on daily life, work, or study in only two (0.5%) patients. Almost all patients currently had no or mild depression (97.0%) and insomnia (97.9%) problems. The most common patient-reported adverse events were hand-foot syndrome (21.3%) and hypertension (18.3%). CONCLUSIONS: Our survey showed a high satisfaction degree with apatinib in long-term cancer survivors. Long-term apatinib treatment resulted in almost no negative impact on patient's quality of life.

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Laser cladding provides advanced surface treatment capabilities for enhancing the properties of components. However, its effectiveness is often challenged by the formation of hot cracks during the cladding process. This study focuses on the formation mechanism and inhibition of hot cracks in a novel cobalt-based alloy (K688) coating applied to 304LN stainless steel via laser cladding. The results indicate that hot crack formation is influenced by liquid film stability, the stress concentration, and precipitation phases. Most hot cracks were found at 25°-45° high-angle grain boundaries (HAGBs) due to the high energy of these grain boundaries, which stabilize the liquid film. A flat-top beam, compared to a Gaussian beam, creates a melt pool with a lower temperature gradient and more mitigatory fluid flow, reducing thermal stresses within the coating and the fraction of crack-sensitive, high-angle grain boundaries (S-HAGBs). Finally, crack formation was significantly inhibited by utilizing a flat-top laser beam to optimize the process parameters. These findings provide a technical foundation for achieving high-quality laser cladding of dissimilar materials, offering insights into optimizing process parameters to prevent hot crack formation.

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BACKGROUND: Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. METHODS: A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, ß stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson's correlation, multiple linear regression, and analyses of covariance. RESULTS: All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The ß stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 µm/year in women and 5.8 µm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. CONCLUSIONS: The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

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Biomass-based alternatives for the manufacturing of bioplastic materials are important aspects of a more sustainable future; their physicochemical properties need to be able to compete with the existing market to establish them as a viable alternative [...].

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BACKGROUND AND AIMS: The recurrence of papillary thyroid carcinoma (PTC) is not unusual and associated with risk of death. This study is aimed to construct a nomogram that combines clinicopathological characteristics and ultrasound radiomics signatures to predict the recurrence in PTC. METHODS: A total of 554 patients with PTC who underwent ultrasound imaging before total thyroidectomy were included. Among them, 79 experienced at least one recurrence. Then 388 were divided into the training cohort and 166 into the validation cohort. The radiomics features were extracted from the region of interest (ROI) we manually drew on the tumor image. The feature selection was conducted using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. And multivariate Cox regression analysis was used to build the combined nomogram using radiomics signatures and significant clinicopathological characteristics. The efficiency of the nomogram was evaluated by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Kaplan-Meier analysis was used to analyze the recurrence-free survival (RFS) in different radiomics scores (Rad-scores) and risk scores. RESULTS: The combined nomogram demonstrated the best performance and achieved an area under the curve (AUC) of 0.851 (95% CI: 0.788 to 0.913) in comparison to that of the radiomics signature and the clinical model in the training cohort at 3 years. In the validation cohort, the combined nomogram (AUC = 0.885, 95% CI: 0.805 to 0.930) also performed better. The calibration curves and DCA verified the clinical usefulness of combined nomogram. And the Kaplan-Meier analysis showed that in the training cohort, the cumulative RFS in patients with higher Rad-score was significantly lower than that in patients with lower Rad-score (92.0% vs. 71.9%, log rank P < 0.001), and the cumulative RFS in patients with higher risk score was significantly lower than that in patients with lower risk score (97.5% vs. 73.5%, log rank P < 0.001). In the validation cohort, patients with a higher Rad-score and a higher risk score also had a significantly lower RFS. CONCLUSION: We proposed a nomogram combining clinicopathological variables and ultrasound radiomics signatures with excellent performance for recurrence prediction in PTC patients.

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The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd.

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BACKGROUND: The relationships among left heart remodeling, cardiac function, and cardiovascular events (CEs) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) undergoing maintenance hemodialysis (MHD) remain unclear. We evaluated the echocardiographic characteristics and clinical outcomes of such patients with diverse left ventricular geometric (LVG) configurations. METHODS: Overall, 210 patients with HFpEF undergoing MHD (cases) and 60 healthy controls were enrolled. Cases were divided into four subgroups based on LVG and were followed up for three years. The primary outcomes were the first CEs and all-cause mortality. RESULTS: Left ventricular ejection fraction (LVEF) and right ventricular systolic function did significantly differ between cases and controls, whereas echocardiographic parameters of cardiac structure, diastolic function, and left ventricular global longitudinal strain (LVGLS) differed significantly. The proportion of cases with left ventricular hypertrophy (LVH) was 67.1%. In addition, 2.38%, 21.90%, 12.86%, and 62.86% of cases presented with normal geometry (NG), concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH), respectively. The left atrial diameter (LAD) was the largest and cardiac output index was the lowest in the EH subgroup. The score of Acute Dialysis Quality Initiative Workgroup (ADQI) HF class was worse in the EH subgroup than in other subgroups at baseline. The proportions of cases free of adverse CEs in the EH subgroup at 12, 24, and 36 months were 40.2%, 14.8%, and 0%, respectively, and the survival rates were 85.2%, 29.6%, 3.7%, respectively, which were significantly lower than those in other subgroups. Multivariate Cox regression revealed that age, TNI (Troponin I), EH, left ventricular mass index (LVMI), age and EH configuration were independent risk factors for adverse CEs and all-cause mortality in the cases. CONCLUSION: Most patients with HFpEF receiving MHD have LVH and diastolic dysfunction. Among the four LVGs, patients with HFpEF undergoing MHD who exhibited EH had the highest risk of adverse CEs and all-cause mortality.

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This study provides a comprehensive analysis of the vacuum drying process for sludge drying, with a focus on optimizing energy efficiency and emission control. The study used both lab-scale static and pilot-scale vacuum drying systems to test various parameters like vacuum levels, heat source temperatures, and sludge thicknesses. The results indicated that optimal drying conditions were achieved at a vacuum level of -0.06 MPa, a heat temperature of 140 °C, and a sludge thickness of 3.4 mm, where the drying rate reaches 0.13278 g·g-1·min-1. The study underscores the significant influence of vacuum level, temperature, and sludge thickness on drying rates. The Page model was used to analyze drying kinetics, elucidating how changes in these parameters affect drying characteristics. Furthermore, the study also examined the pollutant emissions and energy efficiency at the pilot scale. It found that high vacuum environments could efficiently dry sludge using low-temperature heat source, leading to average energy consumption per unit evaporation of 3020.29 kJ/kg, which is lower compared to traditional methods. By harnessing low-grade industrial waste heat, this can be further reduced to 875.76 kJ/kg. This study offers valuable insights for sustainable sludge management systems, highlighting the environmental and economic benefits of vacuum drying technology. The detailed experimental approach and thorough analysis make a significant contribution to the field of the sludge drying.

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BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is overexpressed in various malignancies. Exostosin-1 (EXT-1), a tumor suppressor, is an intermediate for malignant tumors. Understanding the mechanism behind the interaction between AEG-1 and EXT-1 may provide insights into colon cancer metastasis. METHODS: AOM/DSS was used to induce tumor in BALB/c mice. Using an in vivo-jetPEI transfection reagent, transient transfection of AEG-1 and EXT-1 siRNAs were achieved. Histological scoring, immunohistochemical staining, and gene expression studies were performed from excised tissues. Data from the Cancer Genomic Atlas and GEO databases were obtained to identify the expression status of AEG-1 and itsassociation with the survival. RESULTS: In BALB/c mice, the AOM+DSS treated mice developed necrotic, inflammatory and dysplastic changes in the colon with definite clinical symptoms such as loss of goblet cells, colon shortening, and collagen deposition. Administration of AEG-1 siRNA resulted in a substantial decrease in the disease activity index. Mice treated with EXT-1 siRNA showed diffusely reduced goblet cells. In vivo investigations revealed that PTCH-1 activity was influenced by upstream gene AEG-1, which in turn may affect EXT-1 activity. Data from The Cancer Genomic Atlas and GEO databases confirmed the upregulation of AEG-1 and downregulation of EXT-1 in cancer patients. CONCLUSIONS: This study revealed that AEG-1 silencing might alter EXT-1 expression indirectly through PTCH-1, influencing cell-ECM interactions, and decreasing dysplastic changes, proliferation and invasion.

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Food safety issues have received much attention. Biogenic amines are considered important markers of food spoilage. Accurate detection of biogenic amines is important for food quality monitoring. Herein, we developed two coumarin-difluoroboron ß-diketonate hybrid probes, 1 and 2, for detection of amines. Both probes possess large conjugated structures and donor-acceptor-donor configuration, exhibiting solvatochromic effects due to intramolecular charge transfer mechanism. Upon reaction with amines, the boron atom in difluoroboron unit can interact with lone pair electrons of nitrogen atom, thus resulting in significant changes in absorption and fluorescence properties. These probes were successfully utilized to image amine in live cells and liver tissues. Moreover, by photographing probe-loaded food extract supernatant, we establish the relationship between color parameters and food storage time, which can easily indicate food spoilage process. This work and its findings hold promise for providing potential strategies for real-time and convenient detection of food freshness.

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Chronic inflammation promotes the development of pancreatic ductal adenocarcinoma (PDAC) and PDAC-related inflammatory tumor microenvironment facilitates tumor growth and metastasis. Thus, we aimed to study the association between inflammatory response and prognosis in patients with PDAC. We conducted the whole transcriptomic sequencing using tissue samples collected from patients diagnosed with PDAC (n = 106) recruited from Shandong Cancer Hospital. We first constructed a prognostic signature using 15 inflammation-related genes in The Cancer Genome Atlas (TCGA) cohort (n = 177) and further validated it in an independent International Cancer Genome Consortium (ICGC) cohort (n = 90) and our in-house cohort. PDAC patients with a higher risk score had poorer overall survival (OS) (P < 0.001; HR, 3.02; 95% CI, 1.94-4.70). The association between the prognostic signature and OS remained significant in the multivariable Cox regression adjusting for age, sex, alcohol exposure, diabetes, and stage (P < 0.001; HR, 2.91; 95% CI, 1.73-4.89). This gene signature also robustly predicted prognosis in the ICGC cohort (P = 0.01; HR, 1.94; 95% CI, 1.14-3.30) and our cohort (P < 0.001; HR, 2.40; 95% CI, 1.45-3.97). Immune subtype C3 (inflammatory) was enriched and CD8+ T cells were higher in patients with a lower risk score (P < 0.05). Furthermore, PDAC patients with higher risk scores were more sensitive to chemotherapy, immunotherapy, and PARP inhibitors (P < 0.05). In sum, we identified a novel gene signature that was associated with inflammatory response for risk stratification, prognosis prediction, and therapy guidance in PDAC patients. Future studies are warranted to validate the clinical utility of the signature.

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Achieving white-light emission, especially long-lived white circularly polarized luminescence, is challenging. Herein, chiral phosphorescent carbonized polymer dots (CPDs) have been prepared by using chiral polymer sodium alginate and chiral small molecule L-lysine as precursors. Benefiting from the efficient triplet-to-singlet phosphorescence resonance energy transfer (PRET), CPD-based long-lived warm white CPL has been achieved for the first time. This study provides a universal strategy for the convenient and efficient preparation of CPD-based long-lived white CPL materials.

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This study aimed to optimize bowel preparation efficacy for colonoscopy in elderly constipation patients. A 71-year-old patient with chronic constipation and a history of poor bowel preparation. To address these challenges, we implemented a personalized strategy combining of PEG administration and walking exercise. The PEG was administered according to a protocol, with intermittent exercise breaks of 10 minute. Bowel cleanliness was assessed using the Boston Bowel Preparation Scale (BBPS). Adverse reactions and tolerance were closely monitored throughout the intervention. The patient's BBPS score improved from 3 to 8 post-intervention. The exercise intervention was well-tolerated (rating I), and mild nausea was observed only after the first PEG dose. No severe adverse reactions occurred. Subsequent Follow-up revealed symptom relief. The personalized approach combining (PEG and exercise intervention) successfully improved bowel preparation quality in the elderly constipation patient undergoing colonoscopy. This approach considers age-related changes in gastrointestinal function and activity level, offering an effective strategy to improve patient tolerance and reduce adverse reactions during bowel preparation. The findings underscore the importance of tailoring interventions for elderly constipation patients to optimize the colonoscopy experience.

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BACKGROUND: While previous studies have indicated variability in distant metastatic potential among different mismatch repair (MMR) states in colorectal cancer (CRC), their findings remain inconclusive, especially considering potential differences across various ethnic backgrounds. Furthermore, the gene regulatory networks and the underlying mechanisms responsible for these variances in metastatic potential across MMR states have yet to be elucidated. METHODS: We collected 2058 consecutive primary CRC samples from the South West of China and assessed the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) using immunohistochemistry. To explore the inconsistencies between different MMR statuses and recurrence, we performed a meta-analysis. To delve deeper, we employed Weighted Gene Co-expression Network Analysis (WGCNA), ClueGo, and iRegulon, pinpointing gene expression networks and key regulatory molecules linked to metastasis and recurrence in CRC. Lastly, both univariate and multivariate Cox regression analyses were applied to determine the impact of core regulatory molecules on metastasis. RESULTS: Of the samples, 8.2% displayed deficient MMR (dMMR), with losses of MLH1 and PSM2 observed in 40.8% and 63.9%, respectively. A unique 24.3% isolated loss of PMS2 without concurrent metastasis was identified, a result that diverges from established literature. Additionally, our meta-analysis further solidifies the reduced recurrence likelihood in dMMR CRC samples compared to proficient MMR (pMMR). Two gene expression networks tied to distant metastasis and recurrence were identified, with a majority of metastasis-related genes located on chromosomes 8 and 18. An IRF1 positive feedback loop was discerned in the metastasis-related network, and IRF1 was identified as a predictive marker for both recurrence-free and distant metastasis-free survival across multiple datasets. CONCLUSION: Geographical and ethnic factors might influence peculiarities in MMR protein loss. Our findings also highlight new gene expression networks and crucial regulatory molecules in CRC metastasis, enhancing our comprehension of the mechanisms driving distant metastasis.

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In eukaryotic organisms, the most common internal modification of messenger RNA (mRNA) is N6-methyladenosine (m6A). This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers. The fat-mass and obesity-associated protein (FTO) catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes. Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles, with an inverse relationship observed for m6A levels and nuclear-localized FTO expression. Application of Fto small interfering RNA (siRNA) altered the expression of genes related to cell proliferation, hormone regulation, and cell chemotaxis, and affected RNA alternative splicing. Overexpression of the full-length Fto gene led to changes in m6A levels, alternative splicing of Cdk5, cell proliferation, cell cycle progression, and proportion of primordial follicles. Conversely, overexpression of Fto lacking a nuclear localization signal (NLS) did not significantly alter m6A levels or primordial follicle assembly. These findings suggest that FTO, localized in the nucleus but not in the cytoplasm, regulates RNA m6A demethylation and plays a role in cell proliferation, cell cycle progression, and primordial follicle assembly. These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.

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Rectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence. However, therapeutic radiation-induced radioresistance to rectal cancer cells and toxicity to normal tissues are major drawbacks. Therefore, understanding the mechanistic basis of developing radioresistance during and after radiation therapy would provide crucial insight to improve clinical outcomes of radiation therapy for rectal cancer patients. Studies by various groups have shown that radiotherapy-mediated changes in the tumor microenvironment play a crucial role in developing radioresistance. Therapeutic radiation-induced hypoxia and functional alterations in the stromal cells, specifically tumor-associated macrophage (TAM) and cancer-associated fibroblasts (CAF), play a crucial role in developing radioresistance. In addition, signaling pathways, such as - the PI3K/AKT pathway, Wnt/ß-catenin signaling, and the hippo pathway, modulate the radiation responsiveness of cancer cells. Different radiosensitizers, such as small molecules, microRNA, nanomaterials, and natural and chemical sensitizers, are being used to increase the effectiveness of radiotherapy. This review highlights the mechanism responsible for developing radioresistance of rectal cancer following radiotherapy and potential strategies to enhance the effectiveness of radiotherapy for better management of rectal cancer.

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Conventional molecularly imprinted polymers (MIPs) perform their functions principally depended on their three dimensional (3D) imprinted cavities (recognition sites) of templates. Here, retaining the function of recognition sites resulted from the imprinting of template molecules, the role of functional monomers is explored and expanded. Briefly, a class of dual-functional renin imprinted poly(methyldopa) (RMIP) is prepared, consisting of a drug-type function monomer (methyldopa, clinical high blood pressure drug) and a corresponding disease biomarker (renin, biomarker for high blood pressure disease). To boost target-to-receptor binding ratio and sensitivity, the microstructure of recognition sites is beforehand calculated and designed by Density Functional Theory calculations, and the whole interfacial structure, property and thickness of RMIP film is regulated by adjusting the polymerization techniques. The dual-functional applications of RMIP for biomarker detection and disease therapy in vivo is explored. Such RMIP-based biosensors achieves highly sensitive biomarker detection, where the LODs reaches down to 1.31 × 10-6 and 1.26 × 10-6 ng mL-1 for electrochemical and chemical polymers, respectively, and the application for disease therapy in vivo has been verified where displays the obviously decreased blood pressure values of mice. No acute and long-term toxicity is found from the pathological slices, declaring the promising clinical application potential of such engineered RMIP nanostructure.

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OBJECTIVES: To evaluate the additional advantages of integrating contrast-enhanced ultrasound (CEUS) into the Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound (US) for the characterization of adnexal lesions with solid components. MATERIALS AND METHODS: This prospective multicenter study recruited women suspected of having adnexal lesions with solid components between September 2021 and December 2022. All patients scheduled for surgery underwent preoperative CEUS and US examinations. The lesions were categorized according to the O-RADS US system, and quantitative CEUS indexes were recorded. Pathological results served as the reference standard. Univariable and multivariable analyses were performed to identify risk factors for malignancy in adnexal lesions with solid components. Receiver operating characteristic (ROC) curve analysis was employed to assess diagnostic performance. RESULTS: A total of 180 lesions in 175 women were included in the study. Among these masses, 80 were malignant and 100 were benign. Multivariable analysis revealed that serum CA-125, the presence of acoustic shadowing, and peak intensity (PI) ratio (PImass/PIuterus) of solid components on CEUS were independently associated with adnexal malignancy. The modified CEUS risk stratification model demonstrated superior diagnostic value in assessing adnexal lesions with solid components compared to O-RADS US (AUC: 0.91 vs 0.78, p < 0.001) and exhibited comparable performance to the Assessment of Different NEoplasias in the adnexa (ADNEX) model (AUC 0.91 vs 0.86, p = 0.07). CONCLUSION: Our findings underscore the potential value of CEUS as an adjunctive tool for enhancing the precision of diagnostic evaluations of O-RADS US. CLINICAL RELEVANCE STATEMENT: The promising performance of the modified CEUS risk stratification model suggests its potential to mitigate unnecessary surgeries in the characterization of adnexal lesions with solid components. KEY POINTS: • The additional value of CEUS to O-RADS US in distinguishing between benign and malignant adnexal lesions with solid components requires further evaluation. • The modified CEUS risk stratification model displayed superior diagnostic value and specificity in characterizing adnexal lesions with solid components when compared to O-RADS US. • The inclusion of CEUS demonstrated potential in reducing the need for unnecessary surgeries in the characterization of adnexal lesions with solid components.

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