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Objectives: The first treatment strategy for brain metastases (BM) plays a pivotal role in the prognosis of patients. Among all strategies, stereotactic radiosurgery (SRS) is considered a promising therapy method. Therefore, we developed and validated a radiomics-based prediction pipeline to prospectively identify BM patients who are insensitive to SRS therapy, especially those who are at potential risk of progressive disease. Methods: A total of 337 BM patients (277, 30, and 30 in the training set, internal validation set, and external validation set, respectively) were enrolled in the study. 19,377 radiomics features (3 masks × 3 MRI sequences × 2153 features) extracted from 9 ROIs were filtered through LASSO and Max-Relevance and Min-Redundancy (mRMR) algorithms. The selected radiomics features were combined with 4 clinical features to construct a two-stage cascaded model for the prediction of BM patients' response to SRS therapy using SVM and an ensemble learning classifier. The performance of the model was evaluated by its accuracy, specificity, sensitivity, and AUC curve. Results: Radiomics features were integrated with the clinical features of patients in our optimal model, which showed excellent discriminative performance in the training set (AUC: 0.95, 95% CI: 0.88–0.98). The model was also verified in the internal validation set and external validation set (AUC 0.93, 95% CI: 0.76–0.95 and AUC 0.90, 95% CI: 0.73–0.93, respectively). Conclusions: The proposed prediction pipeline could non-invasively predict the response to SRS therapy in patients with brain metastases thus assisting doctors to precisely designate individualized first treatment decisions. Clinical relevance statement: The proposed prediction pipeline combines the radiomics features of multi-modal MRI with clinical features to construct machine learning models that noninvasively predict the response of patients with brain metastases to stereotactic radiosurgery therapy, assisting neuro-oncologists to develop personalized first treatment plans. Key Points: • The proposed prediction pipeline can non-invasively predict the response to SRS therapy. • The combination of multi-modality and multi-mask contributes significantly to the prediction. • The edema index also shows a certain predictive value. [ABSTRACT FROM AUTHOR]

Three porous nanosphere-structured manganese oxide (MnOx) catalysts were prepared and used for the low-temperature catalytic oxidation of methanol using different organic reagents as structure-directing agents to modulate the surface morphology of the catalysts. The structure-effect relationship between MnOx catalysts with different microsphere structures and the catalytic oxidation activity of methanol were analyzed using various characterization techniques. The MnOx–J catalyst had significantly higher catalytic oxidation activity for methanol (T90 = 130 °C) than the other MnOx catalysts. The characterization results indicate that the regulation of 2-methylimidazole promotes the formation of structural defects, surface-adsorbed oxygen, and Mn3+ on the surface of the manganese-based catalysts and enhances the low-temperature reduction capacity of the catalysts—the primary reason for the high reactivity of the MnOx–J samples. Three MnOx catalysts with porous nanosphere structures were synthesized using different organic reagents as structure-directing agents. Among them, the 2-methylimidazole organo-reagent promoted the formation of structural defects, surface adsorbed oxygen and Mn3+ on the surface of the manganese-based catalysts, thus enhancing the catalytic oxidation activity of the catalysts in low-temperature methanol-catalyzed reactions. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to investigate the clinical prognostic significance of radiomics signature (R-signature) in patients with gastric cancer who had undergone radical resection.Methods: A total of 181 patients with gastric cancer who had undergone radical resection were enrolled in this retrospective study. The association between the R-signature and overall survival (OS) was assessed in the primary cohort and verified in the validation cohort. Furthermore, the performance of a radiomics nomogram integrating the R-signature and significant clinicopathological risk factors was evaluated.Results: The R-signature, which consisted of six imaging features, stratified patients with gastric cancer who had undergone radical resection into two prognostic risk groups in both cohorts. The radiomics nomogram incorporating R-signature and significant clinicopathological risk factors (T stage, N stage, and differentiation) exhibited significant prognostic superiority over clinical nomogram and R-signature alone (Harrell concordance index, 0.82 vs 0.71 and 0.82 vs 0.74, respectively, p < 0.001 in both analyses). All calibration curves showed remarkable consistency between predicted and actual survival, and decision curve analysis verified the usefulness of the radiomics nomogram for clinical practice.Conclusions: The R-signature could be used to stratify patients with gastric cancer following radical resection into high- and low-risk groups. Furthermore, the radiomics nomogram provided better predictive accuracy than other predictive models and might aid clinicians with therapeutic decision-making and patient counseling.Key Points: • Radiomics can stratify the gastric cancer patients following radical resection into high- and low-risk groups. • Radiomics can improve the prognostic value of TNM staging system. • Radiomics may facilitate personalized treatment of gastric cancer patients. [ABSTRACT FROM AUTHOR]

Because norcantharidin (NCTD) is unstable and subject to ring opening and hydrolysis, the diacid metabolite of norcantharidin (DM-NCTD) is the stable form of NCTD found in normal saline solution. Conversion of NCTD to DM-NCTD is almost 100 %, making it possible to determine and investigate the pharmacokinetics of DM-NCTD converted from NCTD. In this paper, a sensitive, simple and selective liquid chromatographic-tandem mass spectrometric method was developed and validated for determination of DM-NCTD in beagle plasma. DM-NCTD was detected in multiple-reaction monitoring (MRM) mode by using the dehydrated ion 169.3 as precursor ion and its product ion 123.1 as the detected ion. Ribavirin was used as internal standard and detected in MRM mode by use of precursor ions, resulting in a product ion transition of m/z 267.1 → 135.1. This method was successfully used for a pharmacokinetic study of DM-NCTD in beagles after intravenous administration of DM-NCTD in normal saline solution at doses of 0.39, 0.78, and 1.6 mg kg. DM-NCTD had dose-dependent kinetics across the dosage range investigated, with enhanced T and AUC and apparently decreasing V and CL with increasing dosage. After single-dose administration, T ranged from 0.20 to 0.55 h, AUC from 1.81 to 43.6 μg mL h, V from 228 to 55.9 mL kg, and CL from 220 to 36.5 mL kg h ( P < 0.01). The results indicated nonlinear pharmacokinetic behavior of DM-NCTD in beagles, suggesting that the risk of DM-NCTD in normal saline solution intoxication may be non-proportionally increased at higher doses.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A novel drug carrier for brain delivery, maleimide–poly(ethyleneglycol)–poly(lactide) (maleimide–PEG–PLA) nanoparticles (NPs) conjugated with mouse–anti-rat monoclonal antibody OX26 (OX26–NPs), was developed and its brain delivery property was evaluated. The diblock copolymers of maleimide–PEG–PLA were synthesized and applied to α-cobrotoxin (αCT)-loaded NPs which were characterized by transmission electron micrograph imaging, Fourier-transform IR, and X-ray diffraction. The NPs encapsulating αCT had a round and vesicle-like shape with a mean diameter around 100 nm, and the OX26 had covalently conjugated to the surface of NPs. MTT studies in brain microvascular endothelial cells (BMEC) revealed a moderate decrease in the cell viability of αCT, when incorporated in OX26–NPs compared to free αCT in solution. A higher affinity of the OX26–αCT–NPs to the BMEC was shown in comparison to αCT–NPs. Then, OX26–αCT–NPs were intranasally (i.n.) administered to rats, and αCT in the periaqueductal gray was monitored for up to 480 min using microdialysis technique in free-moving rats, with i.n. αCT–NPs, i.n. OX26–αCT–NPs, intramuscular injection (i.m.) αCT–NPs, and i.m. OX26–αCT–NPs. The brain transport results showed that the corresponding absolute bioavailability ( Fabs) of i.n. OX26–αCT–NPs were about 125 and 155 % with i.n. αCT–NPs and i.m. OX26–αCT–NPs, respectively, and it was found that both the Cmax and AUC of the four groups were as follows: i.n. OX26–αCT–NPs > i.n. αCT–NPs > i.m. OX26–αCT–NPs > i.m. αCT–NPs, while αCT solution, as control groups, could hardly enter the brain. These results indicated that OX26–NPs are promising carriers for peptide brain delivery. [ABSTRACT FROM AUTHOR]