Multiparametric MRI-based radiomics approach with deep transfer learning for preoperative prediction of Ki-67 status in sinonasal squamous cell carcinoma.

Purpose: Based on comparison of different machine learning (ML) models, we developed the model that integrates traditional hand-crafted (HC) features and ResNet50 network-based deep transfer learning (DTL) features from multiparametric MRI to predict Ki-67 status in sinonasal squamous cell carcinoma (SNSCC). Methods: Two hundred thirty-one SNSCC patients were retrospectively reviewed [training cohort (n = 185), test cohort (n = 46)]. Pathological grade, clinical, and MRI characteristics were analyzed to choose the independent predictor. HC and DTL radiomics features were extracted from fat-saturated T2-weighted imaging, contrast-enhanced T1-weighted imaging, and apparent diffusion coefficient map. Then, HC and DTL features were fused to formulate the deep learning-based radiomics (DLR) features. After feature selection and radiomics signature (RS) building, we compared the predictive ability of RS-HC, RS-DTL, and RS-DLR. Results: No independent predictors were found based on pathological, clinical, and MRI characteristics. After feature selection, 42 HC and 10 DTL radiomics features were retained. The support vector machine (SVM), LightGBM, and ExtraTrees (ET) were the best classifier for RS-HC, RS-DTL, and RS-DLR. In the training cohort, the predictive ability of RS-DLR was significantly better than those of RS-DTL and RS-HC (p< 0.050); in the test set, the area under curve (AUC) of RS-DLR (AUC = 0.817) was also the highest, but there was no significant difference of the performance between DLR-RS and HC-RS. Conclusions: Both the HC and DLR model showed favorable predictive efficacy for Ki-67 expression in patients with SNSCC. Especially, the RS-DLR model represented an opportunity to advance the prediction ability.

Superelastic and superflexible cellulose aerogels for thermal insulation and oil/water separation.

Aerogels with low thermal conductivity and high adsorption capacity present a promising solution to curb water pollution caused by organic reagents as well as mitigate heat loss. Although aerogels exhibiting good adsorption capacity and thermal insulation have been reported, materials with mechanical integrity, high flexibility and shear resistance still pose a formidable task. Here, we produced bacterial cellulose-based ultralight multifunctional hybrid aerogels by using freeze-drying followed by chemical vapor deposition silylation method. The hybrid aerogels displayed a low density of 10-15 mg/cm3, high porosity exceeding 99.1 %, low thermal conductivity (27.3-29.2 mW/m.K) and superior hydrophobicity (water contact angle>120o). They also exhibited excellent mechanical properties including superelasticity, high flexibility and shear resistance. The hybrid aerogels demonstrated high heat shielding efficiency when used as an insulating material. As a selective oil absorbent, the hybrid aerogels exhibit a maximum adsorption capacity of up to approximately 156 times its own weight and excellent recoverability. Especially, the aerogel's highly accessible porous microstructure results in an impressive flux rate of up to 162 L/h.g when used as a filter in a continuous oil-water separator to isolate n-hexane-water mixtures. This work presents a novel endeavor to create high-performance, sustainable, reusable, and adaptable multifunctional aerogels.

A Clinical-Radiomics Nomogram Based on the Apparent Diffusion Coefficient (ADC) for Individualized Prediction of the Risk of Early Relapse in Advanced Sinonasal Squamous Cell Carcinoma: A 2-Year Follow-Up Study.

Purpose: To develop and validate a nomogram model combining radiomic features and clinical characteristics to preoperatively predict the risk of early relapse (ER) in advanced sinonasal squamous cell carcinomas (SNSCCs). Methods: A total of 152 SNSCC patients (clinical stage III-IV) who underwent diffusion-weighted imaging (DWI) were included in this study. The training cohort included 106 patients assessed at the headquarters of our hospital using MR scanner 1. The testing cohort included 46 patients assessed at the branch of our hospital using MR scanner 2. Least absolute shrinkage and selection operator (LASSO) regression was applied for feature selection and radiomic signature (radscore) construction. Multivariable logistic regression analysis was applied to identify independent predictors. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis (DCA). Furthermore, the patients were classified into high- or low-risk ER subgroups according to the optimal cutoff value of the nomogram using X-tile. The recurrence-free survival probability (RFS) of each subgroup was assessed. Results: ER was noted in 69 patients. The radscore included 8 selected radiomic features. The radscore, T stage and surgical margin were independent predictors. The nomogram showed better performance (AUC = 0.92) than either the radscore or the clinical factors in the training cohort (P < 0.050). In the testing cohort, the nomogram showed better performance (AUC = 0.92) than the clinical factors (P = 0.016) and tended to show better performance than the radscore (P = 0.177). The nomogram demonstrated good calibration and clinical utility. Kaplan-Meier analysis showed that the 2-year RFS rate for low-risk patients was significantly greater than that for high-risk patients in both the training and testing cohorts (P < 0.001). Conclusions: The ADC-based radiomic nomogram model is potentially useful in predicting the risk of ER in advanced SNSCCs.

BLADE turbo gradient- and spin-echo in the assessment of sinonasal lesions: a comprehensive comparison of image quality in readout-segmented echo-planar imaging.

BACKGROUND: A two-dimensional turbo gradient-echo and spin-echo diffusion-weighted pulse sequence with a non-Cartesian BLADE trajectory (TGSE BLADE) can eliminate image artifacts and distortion with clinically acceptable scan times. This process has the potential to overcome the shortcomings of current diffusion-weighted imaging (DWI) techniques, especially in the sinonasal region. PURPOSE: To investigate the feasibility of TGSE BLADE in the assessment of sinonasal lesions and compare the quality of TGSE BLADE with RESOLVE images both qualitatively and quantitatively. MATERIAL AND METHODS: A total of 36 patients with sinonasal lesions were included in this prospective study. DW images acquired using TGSE BLADE and RESOLVE were performed with the same acquisition time. Two independent observers evaluated the qualitative parameters (overall image quality, lesion visibility, and geometric distortion) and quantitative parameters (geometric distortion ratio [GDR], signal-to-noise ratio [SNR], contrast, contrast-to-noise ratio [CNR], and apparent diffusion coefficient [ADC] value) of the two sequences. RESULTS: Qualitative assessment revealed that TGSE BLADE exhibited higher overall image quality (P < 0.001) and lesion visibility (P < 0.001) and less geometric distortion (P < 0.001) than RESOLVE. Quantitative assessment showed that TGSE BLADE images exhibited higher contrast (P < 0.001) and CNR (P < 0.001) and lower GDR (P < 0.05) and SNR (P < 0.001) than RESOLVE images. The ADC value of TGSE BLADE was significantly lower than that of RESOLVE (P < 0.05). CONCLUSION: TGSE BLADE can reduce susceptibility artifacts and geometric distortion more than RESOLVE and appears to be a promising diffusion imaging sequence for the assessment of sinonasal lesions.

Expression and Characterization of a Novel Cold-Adapted Chitosanase from Marine Renibacterium sp. Suitable for Chitooligosaccharides Preparation.

(1) Background: Chitooligosaccharides (COS) have numerous applications due to their excellent properties. Chitosan hydrolysis using chitosanases has been proposed as an advisable method for COS preparation. Although many chitosanases from various sources have been identified, the cold-adapted ones with high stability are still rather rare but required. (2) Methods: A novel chitosanase named CsnY from marine bacterium Renibacterium sp. Y82 was expressed in Escherichia coli, following sequence analysis. Then, the characterizations of recombinant CsnY purified through Ni-NTA affinity chromatography were conducted, including effects of pH and temperature, effects of metal ions and chemicals, and final product analysis. (3) Results: The GH46 family chitosanase CsnY possessed promising thermostability at broad temperature range (0-50 °C), and with optimal activity at 40 °C and pH 6.0, especially showing relatively high activity (over 80% of its maximum activity) at low temperatures (20-30 °C), which demonstrated the cold-adapted property. Common metal ions or chemicals had no obvious effect on CsnY except Mn2+ and Co2+. Finally, CsnY was determined to be an endo-type chitosanase generating chitodisaccharides and -trisaccharides as main products, whose total concentration reached 56.74 mM within 2 h against 2% (w/v) initial chitosan substrate. (4) Conclusions: The results suggest the cold-adapted CsnY with favorable stability has desirable potential for the industrial production of COS.

MRI-based radiomic signature as predictive marker for patients with head and neck squamous cell carcinoma.

PURPOSE: To develop magnetic resonance imaging (MRI)-based radiomic signature and nomogram for preoperatively predicting prognosis in head and neck squamous cell carcinoma (HNSCC) patients. METHOD: This retrospective study consisted of a training cohort (n = 85) and a validation cohort (n = 85) of patients with HNSCC. LASSO Cox regression model was used to select the most useful prognostic features with their coefficients, upon which a radiomic signature was generated. The receiver operator characteristics (ROC) analysis and association of the radiomic signature with overall survival (OS) of patients was assessed in both cohorts. A nomogram incorporating the radiomic signature and independent clinical predictors was then constructed. The incremental prognostic value of the radiomic signature was evaluated. RESULTS: The radiomic signature, consisted of 7 selected features from MR images, was significantly associated with OS of patients with HNSCC (P < 0.0001 for training cohort, P = 0.0013 for validation cohort). The radiomic signature and TNM stage were proved to be independently associated with OS of HNSCC patients, which therefore were incorporated to generate the radiomic nomogram. In the training cohort, the nomogram showed a better prognostic capability than TNM stage only (P =  0.005), which was confirmed in the validation cohort (P =  0.01). Furthermore, the calibration curves of the nomogram demonstrated good agreement with actual observation. CONCLUSIONS: MRI-based radiomic signature is an independent prognostic factor for HNSCC patients. Nomogram based on radiomic signature and TNM stage shows promising in non-invasively and preoperatively predicting prognosis of HNSCC patient in clinical practice.

ADAMTS13 maintains cerebrovascular integrity to ameliorate Alzheimer-like pathology.

Blood-brain barrier (BBB) defects and cerebrovascular dysfunction contribute to amyloid-ß (Aß) brain accumulation and drive Alzheimer disease (AD) pathology. By regulating vascular functions and inflammation in the microvasculature, a disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) plays a significant protective effect in atherosclerosis and stroke. However, whether ADAMTS13 influences AD pathogenesis remains unclear. Using in vivo multiphoton microscopy, histological, behavioral, and biological methods, we determined BBB integrity, cerebrovascular dysfunction, amyloid accumulation, and cognitive impairment in APPPS1 mice lacking ADAMTS13. We also tested the impact of viral-mediated expression of ADAMTS13 on cerebrovascular function and AD-like pathology in APPPS1 mice. We show that ADAMTS13 deficiency led to an early and progressive BBB breakdown as well as reductions in vessel density, capillary perfusion, and cerebral blood flow in APPPS1 mice. We found that deficiency of ADAMTS13 increased brain plaque load and Aß levels and accelerated cerebral amyloid angiopathy (CAA) by impeding BBB-mediated clearance of brain Aß, resulting in worse cognitive decline in APPPS1 mice. Virus-mediated expression of ADAMTS13 attenuated BBB disruption and increased microvessels, capillary perfusion, and cerebral blood flow in APPPS1 mice already showing BBB damage and plaque deposition. These beneficial vascular effects were reflected by increase in clearance of cerebral Aß, reductions in Aß brain accumulation, and improvements in cognitive performance. Our results show that ADAMTS13 deficiency contributes to AD cerebrovascular dysfunction and the resulting pathogenesis and cognitive deficits and suggest that ADAMTS13 may offer novel therapeutic opportunities for AD.

Memantine selectively prevented the induction of dynamic allodynia by blocking Kir2.1 channel and inhibiting the activation of microglia in spinal dorsal horn of mice in spared nerve injury model.

BACKGROUND: Memantine is one of the important clinical medications in treating moderate to severe Alzheimer disease. The effect of memantine on preventing or treating punctate allodynia has been thoroughly studied but not on the induction of dynamic allodynia. The aim of this study is to investigate whether memantine could prevent the induction of dynamic allodynia and its underlying spinal mechanisms. RESULTS: (1) In in vivo spared nerve injury pain model, pretreatment with memantine at a lower dose (10 nmol, intrathecal; memantine-10) selectively prevented the induction of dynamic allodynia but not the punctate allodynia. (2) Pretreatment with either MK801-10 (MK801-10 nmol, intrathecal) or higher dose of memantine (30 nmol, intrathecal; memantine-30) prevented the induction of both dynamic and punctate allodynia. (3) Memantine-10 showed significant effect on the inhibition of the spared nerve injury-induced overactivation of microglia in spinal dorsal horn. (4) In contrast, in complete freund's adjuvant (CFA) model, memantine-10 neither affected the CFA injection-induced activation of microglia in spinal dorsal horn nor the induction of dynamic allodynia. (5) Immunohistological studies showed Kir2.1 channel distributed widely and co-localized with microglia in the spinal dorsal horn of mice. (6) Pretreatment with either minocycline, a microglia inhibitor, or ML133, a Kir2.1 inhibitor, both selectively prevented the overactivation of microglia in spinal dorsal horn and the induction of dynamic allodynia following spared nerve injury. CONCLUSION: The selective inhibitory effect on the induction of dynamic allodynia in spared nerve injury model by low dose of the memantine (memantine-10) was tightly correlated with the blockade of microglia Kir2.1 channel to suppress the microglia activation.

Kir2.1 Channel Regulation of Glycinergic Transmission Selectively Contributes to Dynamic Mechanical Allodynia in a Mouse Model of Spared Nerve Injury.

Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia. It occurs in distinct forms, including brush-evoked dynamic and filament-evoked punctate mechanical allodynia. Potassium channel 2.1 (Kir2.1), which exhibits strong inward rectification, is and regulates the activity of lamina I projection neurons. However, the relationship between Kir2.1 channels and mechanical allodynia is still unclear. In this study, we first found that pretreatment with ML133, a selective Kir2.1 inhibitor, by intrathecal administration, preferentially inhibited dynamic, but not punctate, allodynia in mice with spared nerve injury (SNI). Intrathecal injection of low doses of strychnine, a glycine receptor inhibitor, selectively induced dynamic, but not punctate allodynia, not only in naïve but also in ML133-pretreated mice. In contrast, bicuculline, a GABAA receptor antagonist, induced only punctate, but not dynamic, allodynia. These results indicated the involvement of glycinergic transmission in the development of dynamic allodynia. We further found that SNI significantly suppressed the frequency, but not the amplitude, of the glycinergic spontaneous inhibitory postsynaptic currents (gly-sIPSCs) in neurons on the lamina II-III border of the spinal dorsal horn, and pretreatment with ML133 prevented the SNI-induced gly-sIPSC reduction. Furthermore, 5 days after SNI, ML133, either by intrathecal administration or acute bath perfusion, and strychnine sensitively reversed the SNI-induced dynamic, but not punctate, allodynia and the gly-sIPSC reduction in lamina IIi neurons, respectively. In conclusion, our results suggest that blockade of Kir2.1 channels in the spinal dorsal horn selectively inhibits dynamic, but not punctate, mechanical allodynia by enhancing glycinergic inhibitory transmission.

Magnetic resonance imaging based radiomics signature for the preoperative discrimination of stage I-II and III-IV head and neck squamous cell carcinoma.

PURPOSE: This study aimed to investigate the predictive ability of magnetic resonance imaging (MRI) based radiomics signature for the preoperative staging in HNSCC. METHODS: This study involved127 consecutive patients (training cohort: n = 85; testing cohort, n = 42) with stage I-IV HNSCC. A total of 970 radiomics features were extracted from T2-weighted (T2W) (n = 485) and contrast-enhanced T1-weighted (ceT1W) (n = 485) MRI for each case. Radiomics signatures were constructed with least absolute shrinkage and selection operator (LASSO) logistic regression. Associations between radiomics signatures and HNSCC staging were explored. Areas under the receiver operating characteristic curve (AUC) and classification performance of radiomics signatures were determined and compared with those of the visual assessment. RESULTS: Ten features from T2W images, six from ceT1W images, and six from combined T2W and ceT1W images were selected by LASSO logistic regression. The three radiomics signatures of stage III-IV HNSCC were significantly higher than that for stage I-II in both cohorts (all P < 0.05). The radiomics signatures from ceT1W and combined images performed well in the discrimination of stage I-II and III-IV HNSCC, with AUCs of 0.828 and 0.850 in the training cohort, and AUCs of 0.853 and 0.849 in the testing cohort. Based on the cut-off value of the training cohort, the radiomics signature from combined images achieved best classification performance in both cohorts, with accuracies of 0.788 and 0.857, sensitivities of 0.836 and 0.885, and specificities of 0.700 and 0.813. Significant differences in accuracy and sensitivity were found between the radiomics signature from combined images and the visual assessment of the radiologists in the training cohort. CONCLUSION: Radiomics signature based on MRI could discriminate stage I-II from stage III-IV HNSCC, which may serve as a complementary tool for preoperative staging.

Histogram analysis of apparent diffusion coefficient maps in the prognosis of patients with locally advanced head and neck squamous cell carcinoma: Comparison of different region of interest selection methods.

OBJECTIVE: To investigate the influence of different region of interest (ROI) selection methods on the histogram analysis of apparent diffusion coefficient (ADC) maps and to compare their performance in predicting overall survival (OS) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 73 patients with locally advanced HNSCC who underwent pretreatment diffusion-weighted magnetic resonance imaging were included. Based on the largest slice ROI (ROILS) and whole tumor ROI (ROIWT), ADC histogram parameters including mean ADC (ADCmean); median ADC (ADCmedian); 10th, 25th, 75th, and 90th percentiles of ADC values (ADC10, ADC25, ADC75, and ADC90); kurtosis; and skewness were obtained. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to evaluate measurement reproducibility. The association of ADC histogram parameters and clinicopathological factors with OS was analyzed using log-rank tests and Cox regression. RESULTS: The measurements of ADC histogram parameters based on ROIWT showed better reproducibility than ROILS (ICCs for ROIWT: 0.772-0.961; ICCs for ROILS: 0.511-0.851). The higher ADC values (ADCmean, ADCmedian, ADC10, and ADC25 based on both ROIs; ADC75 based on ROILS) and lower kurtosis based on ROILS were significantly associated with worse OS of patients with locally advanced HNSCC (all P < 0.05). In the multivariate Cox analysis, ADC10 measured with ROIWT (P = 0.019, hazard ratio = 2.63, 95% confidence interval 1.17-5.90) was an independent prognostic factor after adjusting for clinicopathological factors. CONCLUSIONS: ROI selection methods could influence ADC histogram analysis. ADC10 based on ROIWT had the best independent prognostic value for patients with locally advanced HNSCC.

Incremental Prognostic Value of Apparent Diffusion Coefficient Histogram Analysis in Head and Neck Squamous Cell Carcinoma.

RATIONALE AND OBJECTIVES: We aimed to investigate the incremental prognostic value of apparent diffusion coefficient (ADC) histogram analysis in patients with head and neck squamous cell carcinoma (HNSCC) and integrate it into a multivariate prognostic model. MATERIALS AND METHODS: A retrospective review of magnetic resonance imaging findings was conducted in patients with pathologically confirmed HNSCC between June 2012 and December 2015. For each tumor, six histogram parameters were derived: the 10th, 50th, and 90th percentiles of ADC (ADC10, ADC50, and ADC90); mean ADC values (ADCmean); kurtosis; and skewness. The clinical variables included age, sex, smoking status, tumor volume, and tumor node metastasis stage. The association of these histogram and clinical variables with overall survival (OS) was determined. Further validation of the histogram parameters as independent biomarkers was performed using multivariate Cox proportional hazard models combined with clinical variables, which was compared to the clinical model. Models were assessed with C index and receiver operating characteristic curve analyses for the 12- and 36-month OS. RESULTS: Ninety-six patients were eligible for analysis. Median follow-up was 877 days (range, 54-1516 days). A total of 29 patients died during follow-up (30%). Patients with higher ADC values (ADC10 > 0.958 × 10-3 mm2/s, ADC50 > 1.089 × 10-3 mm2/s, ADC90 > 1.152 × 10-3 mm2/s, ADCmean > 1.047 × 10-3 mm2/s) and lower kurtosis (≤0.967) were significant predictors of poor OS (P < .100 for all). After adjusting for sex and tumor node metastasis stage, the ADC90 and kurtosis are both significant predictors of OS with hazard ratios = 1.00 (95% confidence interval: 1.001-1.004) and 0.58 (95% confidence interval: 0.37-0.90), respectively. By adding the ADC parameters into the clinical model, the C index and diagnostic accuracies for the 12- and 36-month OS showed significant improvement. CONCLUSIONS: ADC histogram analysis has incremental prognostic value in patients with HNSCC and increases the performance of a multivariable prognostic model in addition to clinical variables.

Chemotherapeutic activities of Carthami Flos and its reversal effect on multidrug resistance in cancer cells.

Multidrug-resistance (MDR) represents a major cause of failure in cancer chemotherapy. The need for a reduction in MDR by natural-product-based drugs of low toxicity led to the current investigation of applying medicinal herbs in future cancer adjuvant therapy. Carthami Flos (CF), the dried flower of safflower (Carthamus tinctorius L.), is one of the most popular traditional Chinese medicinal herbs used to alleviate pain, increase circulation, and reduce blood-stasis syndrome. The drug resistance index of the total extract of CF in MDR KB-V1 cells and its synergistic effects with other chemotherapeutic agents were studied. SRB cell viability assays were used to quantify growth inhibition after exposure to single drug and in combinations with other chemotherapeutic agents using the median effect principle. The combination indexes were then calculated according to the classic isobologram equation. The results revealed that CF showed a drug resistance index of 0.096. In combination with other chemotherapeutic agents, it enhanced their chemo-sensitivities by 2.8 to 4.0 folds and gave a general synergism in cytotoxic effect. These results indicate that CF could be a potential alternative adjuvant antitumour herbal medicine representing a promising approach to the treatment of some malignant and MDR cancers in the future.