Interpretable machine learning based on CT-derived extracellular volume fraction to predict pathological grading of hepatocellular carcinoma.

PURPOSE: To develop a non-invasive auxiliary assessment method based on CT-derived extracellular volume (ECV) to predict the pathological grading (PG) of hepatocellular carcinoma (HCC). METHODS: The study retrospectively analyzed 238 patients who underwent HCC resection surgery between January 2013 and April 2023. Six machine learning algorithms were employed to construct predictive models for HCC PG: logistic regression, extreme gradient boosting, Light Gradient Boosting Machine (LightGBM), random forest, adaptive boosting, and Gaussian naive Bayes. Model performance was evaluated using receiver operating characteristic curve analysis, including area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and F1 score. Calibration plots were used for visual evaluation of model calibration. Clinical decision curve analysis was performed to assess potential clinical utility by calculating net benefit. RESULTS: 166 patients from Hospital A were allocated to the training set, while 72 patients from Hospital B (constituting 30.25% of the total sample) were assigned to the test set. The model achieved an AUC of 1.000 (95%CI: 1.000-1.000) in the training set and 0.927 (95%CI: 0.837-0.999) in the validation set, respectively. Ultimately, the model achieved an AUC of 0.909 (95%CI: 0.837-0.980) in the test set, with an accuracy of 0.778, sensitivity of 0.906, specificity of 0.789, negative predictive value of 0.556, and F1 score of 0.908. CONCLUSION: This study successfully developed and validated a non-invasive auxiliary assessment method based on CT-derived ECV to predict the HCC PG, providing important supplementary information for clinical decision-making.

[Zero profile anchored spacer(ROI-C) for the treatment of cervical spondylosis with osteoporosis].

OBJECTIVE: To investigate the clinical efficacy of zero-profile anchored spacer (ROI-C) in treating cervical spondylosis with osteoporosis. METHODS: From May 2013 to May 2018, a total of 145 patients with cervical spondylosis were treated by ROI-C through anterior cervical spine approach. Among them, 31 patients were aged ≥60 years and had osteoporosis by bone density measurement, and they were retrospectively analyzed. Including 9 males and 22 females, aged 60-84 years old with an average of (69.12±7.65) years. There were 23 cases of single-segment fusion, 6 cases of two-stage fusion, and 2 cases of three-stage fusion;and 41 devices of ROI-C fusion was placed in the patients. Operation time and intraoperative blood loss were recorded;Japanese Orthopaedic Association (JOA) scores and visual analogue scale(VAS) were respectively used to evaluate the neurological function and neck pain before and after operation. The cervical curvature (expressed as Cobb angle), the height of the intervertebral space at the surgical segment, and the intervertebral fusion were observed at postoperative and follow-up periods were observed by image data. RESULTS: All patients were followed up for 12-24(15.6±4.4) months after operation. The operation time were from 75 to 113 (101.33±10.25) min and intraoperative blood loss were from 14 to 51 (33.18 ± 16.56) ml. Among these 23 patients with fusion of single segment, the operation time were 75 to 98 (85.47±8.70) min and intraoperative blood loss were 14 to 30(21.18±6.56) ml. JOA scores of all included patients were increased from 9.66±2.12 preoperatively to 14.36±1.24 at the final follow-up (P<0.05);VAS scores were decreased form 4.21±0.83 preoperatively to 1.12± 0.57 at the final follow-up (P<0.05);Cobb angles of the cervical spine were improved from (13.14±4.54)° preoperatively to (22.31±5.42)° at the final follow-up(P<0.05);the heights of the intervertebral space were changed from (3.28±0.73) mm preoperatively to (4.87±0.45) mm at the final follow-up(P<0.05). All the fusions of the surgical segments were satisfactory at the final follow-up and no failure of the fusion device was found. At the final follow-up, no complications such as difficulty swallowing and hoarseness, etc. were reported. CONCLUSION: Anterior cervical approach with ROI-C for the treatment of elderly patients with cervical spondylosis and osteoporosis had reliable clinical effect, short operation time, less intraoperative blood loss, and can effectively restore cervical curvature and intervertebral space height, and has advantages of fewer complications and higher successful rate of fusion.

Identifying anomalous nuclear radioactive sources using Poisson kriging and mobile sensor networks.

Nuclear security is a critical concept for public health, counter-terrorism efforts, and national security. Nuclear radioactive materials should be monitored and secured in near real-time to reduce potential danger of malicious usage. However, several challenges have arose to detect the anomalous radioactive source in a large geographical area. Radiation naturally occurs in the environment. Therefore, a non-zero level of radiation will always exist with or without an anomalous radioactive source present. Additionally, radiation data contain high levels of uncertainty, meaning that the measured radiation value is significantly affected by the velocity of the detector and background noise. In this article, we propose an innovative approach to detect anomalous radiation source using mobile sensor networks combined with a Poisson kriging technique. We validate our results using several experiments with simulated radioactive sources. As results, the accuracy of the model is extremely high when the source intensity is high or the anomalous source is close enough to the detector.

Blood glucose lowering activity of aloe based composition, UP780, in alloxan induced insulin dependent mouse diabetes model.

BACKGROUND: There are a few nutritional approaches to address the increased needs of managing diabetic conditions. Previously it has been reported that UP780, a standardized composition of aloe chromone formulated with an aloe polysaccharide, has a significant impact in reducing HbA1C, fasting blood glucose, fructosamine and plasma insulin level in humans and improved impaired glucose and insulin resistance in high-fat diet-induced and db/db non-insulin dependent diabetic mouse models. Here we describe activity of UP780 and its constituents to improve insulin sensitivity in alloxan induced insulin dependent diabetic mouse model. MATERIALS AND METHOD: Insulin dependent diabetes was induced by administering a single intraperitoneal injection of alloxan monohydrate at a dose of 150 mg/kg to CD-1 mice. Aloesin (UP394) was formulated with an Aloe vera inner leaf gel powder polysaccharide (Qmatrix) to yield a composition designated UP780. Efficacy of oral administration of UP780 at 2000 mg/kg and its constituents (aloesin at 80 mg/kg and Qmatrix at 1920 mg/kg) were evaluated in this model. Glyburide, a sulfonylurea drug used in the treatment of type 2 diabetes, was used at 5 mg/kg as a positive control. Effect of UP780 on non-diabetic normal mice was also addressed. RESULTS: Mice administered intraperitoneal alloxan monohydrate developed progressive type-1 diabetes like symptom. After 4 weeks of daily oral administration, reductions of 35.9%, 17.2% and 11.6% in fasting blood glucose levels were observed for UP780, the UP780 Aloe vera inner leaf gel polysaccharide preparation without chromone (Qmatrix), and Aloesin (UP394), treated animals respectively, compared to vehicle treated animals. UP780 has no impact on blood glucose level of non-diabetic healthy mice. UP780 showed statistically significant improvement for blood glucose clearance in oral glucose tolerance tests. Similarly, enhanced improvement in plasma insulin level and statistically significant reduction in triglyceride level was also observed for animals treated with the composition. CONCLUSION: These findings suggest that UP780, a chromone standardized Aloe based composition, could possibly be used as a natural supplement alternative to facilitate maintenance of healthy blood glucose levels.

UP780, a chromone-enriched aloe composition improves insulin sensitivity.

BACKGROUND: Diabetic individuals experience elevated fasting glucose, glycosylated hemoglobin (HbA1c), and plasma insulin and impaired glucose tolerance. Adiponectin is a hormone inversely correlated with insulin resistance. Here we describe the activity of aloesin, an aloe chromone that increases adiponectin production and, when formulated with an aloe polysaccharide composition, improves the insulin sensitivity in db/db and diet-induced obese-diabetic mice. METHODS: Two aloe chromones, aloesin and aloesinol, were tested in vitro for adiponectin production. Following confirmation of glucose-lowering activity in a high-fat diet (HFD)-induced mouse model, aloesin was formulated with an Aloe vera inner leaf gel powder polysaccharide preparation to yield a composition designated UP780. Efficacy of UP780 was evaluated in HDF-induced and db/db mouse models. GW1929, a synthetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist, was used as a positive control. RESULTS: After 3 weeks of treatment of HDF-induced mice, plasma insulin levels were decreased 37.9% and 46.7% by aloesin and aloesinol, respectively. In db/db mice, the chromone- (2% chromone:98% aloe polysaccharide) enriched UP780 aloe composition showed a 33.7% and 46.0% decrease in fasting triglyceride and plasma glucose levels after 10 weeks of oral treatment, respectively. Diabetic mice gavaged with 200 mg/kg of UP780 for 10 weeks showed a 30.3% decrease in fasting blood glucose levels and a 32.2% reduction in plasma insulin. In both animal models, UP780 showed a statistically significant improvement in blood glucose clearance. CONCLUSION: These findings indicate that UP780, a chromone-standardized, aloe-based composition, could potentially be used as a natural product option to facilitate the maintenance of healthy blood glucose levels.

1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane, a novel tyrosinase inhibitor with strong depigmenting effects.

A series of diarylpropane compounds was isolated by screening a plant extract library for inhibitors of mushroom tyrosinase. The most potent compound, 1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane (UP302: CAS# 869743-37-3), was found in the medicinal plant Dianella ensifolia. Synthetic and plant-derived versions of UP302 inhibited mushroom tyrosinase with similar potencies. UP302 inhibited mushroom tyrosinase with K(i)=0.3 microM, in a competitive and reversible fashion. UP302 was 22 times more potent than Kojic acid in inhibiting murine tyrosinase, with IC(50) values of 12 and 273 microM respectively. Experiments on mouse melanoma cells B16-F1 and on human primary melanocytes demonstrated that UP302 inhibits melanin formation with IC(50) values of 15 and 8 microM respectively. Long-term treatment of cultured melanocytes with up to 62 microM of UP302 revealed no detectable cytotoxicity. In a reconstructed skin model (MelanoDerm) topical application of 0.1% UP302 resulted in significant skin lightening and decrease of melanin production without effects on cell viability, melanocyte morphology or overall tissue histology. In conclusion, UP302 is a novel tyrosinase inhibitor that suppresses melanin production in both cultured melanocytes and reconstructed skin with high potency and without adverse side effects.

Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis.

This study reports in vivo therapeutic efficacy of silymarin against skin tumors with mechanistic rationale. 7,12-Dimethylbenz[a]anthracene-12-O-tetradecanoyl-phorbol-13-acetate (DMBA-TPA)-induced established skin papilloma (tumor)-bearing SENCAR mice were fed with 0.5% silymarin in AIN-93M-purified diet (w/w), and both tumor growth and regression were monitored during 5 weeks of feeding regimen. Silymarin feeding significantly inhibited (74%, P < 0.01) tumor growth and also caused regression (43%, P < 0.01) of established tumors. Proliferating cell nuclear antigen and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling immunohistochemical staining of tumors showed that silymarin decreases proliferation index by 48% (P < 0.001) and increases apoptotic index by 2.5-fold (P < 0.001), respectively. Skin tumor growth inhibition and regression by silymarin were also accompanied by a strong decrease (P < 0.001) in phospho-ERK1/2 levels in tumors from silymarin-fed mice compared with controls. In the studies evaluating bioavailability and physiologically achievable level of silymarin (as silibinin) in plasma, skin tumor, skin, liver, lung, mammary gland and spleen, we found 10, 6.5, 3.1, 13.7, 7.7, 5.9 and 4.4 microg silibinin/ml plasma or per gram tissue, respectively. In an attempt to translate these findings to human skin cancer and to establish biological significance of physiologically achievable level, effect of plasma concentration of silibinin was next examined in human epidermoid carcinoma A431 cells. Silibinin treatment of cells in culture at 12.5, 25 (plasma level) and 50 microM doses resulted in 30-74% (P < 0.01-0.001) growth inhibition and 7-42% death of A431 cells in a dose- and time-dependent manner; apoptosis was identified as a cell death response by silibinin. Similar silibinin treatments also resulted in a significant decrease in phospho-mitogen-activated protein kinase/extracellular signal-regulated protein kinase 1/2 (MAPK/ERK1/2) levels, but an up-regulation of stress-activated protein kinase/jun NH(2)-terminal kinase (SAPK/JNK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) activation in A431 cells. The use of MEK1 inhibitor, PD98059, showed that inhibition of ERK1/2 signaling, in part, contributes to silibinin-caused cell growth inhibition. Together, the data suggest that an inhibition of ERK1/2 activation and an increased activation of JNK1/2 and p38 by silibinin could be possible underlying molecular events involved in inhibition of proliferation and induction of apoptosis in A431 cells. These data suggest that silymarin and/or its major active constituent silibinin could be an effective agent for both prevention and intervention of human skin cancer.