Dual-energy computed tomography in a multiparametric regression model for diagnosing lymph node metastases in pancreatic ductal adenocarcinoma.

OBJECTIVE: To investigate the diagnostic value of dual-energy computed tomography (DECT) quantitative parameters in the identification of regional lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective diagnostic study assessed 145 patients with pathologically confirmed pancreatic ductal adenocarcinoma from August 2016-October 2020. Quantitative parameters for targeted lymph nodes were measured using DECT, and all parameters were compared between benign and metastatic lymph nodes to determine their diagnostic value. A logistic regression model was constructed; the receiver operator characteristics curve was plotted; the area under the curve (AUC) was calculated to evaluate the diagnostic efficacy of each energy DECT parameter; and the DeLong test was used to compare AUC differences. Model evaluation was used for correlation analysis of each DECT parameter. RESULTS: Statistical differences in benign and metastatic lymph nodes were found for several parameters. Venous phase iodine density had the highest diagnostic efficacy as a single parameter, with AUC 0.949 [95% confidence interval (CI):0.915-0.972, threshold: 3.95], sensitivity 79.80%, specificity 96.00%, and accuracy 87.44%. Regression models with multiple parameters had the highest diagnostic efficacy, with AUC 0.992 (95% CI: 0.967-0.999), sensitivity 95.96%, specificity 96%, and accuracy 94.97%, which was higher than that for a single DECT parameter, and the difference was statistically significant. CONCLUSION: Among all DECT parameters for regional lymph node metastasis in PDAC, venous phase iodine density has the highest diagnostic efficacy as a single parameter, which is convenient for use in clinical settings, whereas a multiparametric regression model has higher diagnostic value compared with the single-parameter model.

Radiomics-based nomogram guides adaptive de-intensification in locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy.

OBJECTIVES: This study aimed to construct a radiomics-based model for prognosis and benefit prediction of concurrent chemoradiotherapy (CCRT) versus intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) following induction chemotherapy (IC). MATERIALS AND METHODS: A cohort of 718 LANPC patients treated with IC + IMRT or IC + CCRT were retrospectively enrolled and assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from pre-IC and post-IC MRI. After feature selection, a delta-radiomics signature was built with LASSO-Cox regression. A nomogram incorporating independent clinical indicators and the delta-radiomics signature was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated with Kaplan-Meier methods. RESULTS: The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. The nomogram, composed of the delta-radiomics signature, age, T category, N category, treatment, and pre-treatment EBV DNA, showed great calibration and discrimination with an area under the receiver operator characteristic curve of 0.80 (95% CI 0.75-0.85) and 0.75 (95% CI 0.64-0.85) in the training and validation sets. Risk stratification by the nomogram, excluding the treatment factor, resulted in two groups with distinct overall survival. Significantly better outcomes were observed in the high-risk patients with IC + CCRT compared to those with IC + IMRT, while comparable outcomes between IC + IMRT and IC + CCRT were shown for low-risk patients. CONCLUSION: The radiomics-based nomogram can predict prognosis and survival benefits from concurrent chemotherapy for LANPC following IC. Low-risk patients determined by the nomogram may be potential candidates for omitting concurrent chemotherapy during IMRT. CLINICAL RELEVANCE STATEMENT: The radiomics-based nomogram was constructed for risk stratification and patient selection. It can help guide clinical decision-making for patients with locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy, and avoid unnecessary toxicity caused by overtreatment. KEY POINTS: • The benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy. • Radiomics-based nomogram achieved prognosis and benefits prediction of concurrent chemotherapy. • Low-risk patients defined by the nomogram were candidates for de-intensification.

Non-canonical isoforms of the mRNA polyadenylation factor WDR33 regulate STING-mediated immune responses.

The human WDR33 gene encodes three major isoforms. The canonical isoform WDR33v1 (V1) is a well-characterized nuclear mRNA polyadenylation factor, while the other two, WDR33v2 (V2) and WDR33v3 (V3), have not been studied. Here, we report that V2 and V3 are generated by alternative polyadenylation, and neither protein contains all seven WD (tryptophan-aspartic acid) repeats that characterize V1. Surprisingly, V2 and V3 are not polyadenylation factors but localize to the endoplasmic reticulum and interact with stimulator of interferon genes (STING), the immune factor that induces the cellular response to cytosolic double-stranded DNA. V2 suppresses interferon-ß induction by preventing STING disulfide oligomerization but promotes autophagy, likely by recruiting WIPI2 isoforms. V3, on the other hand, functions to increase STING protein levels. Our study has not only provided mechanistic insights into STING regulation but also revealed that protein isoforms can be functionally completely unrelated, indicating that alternative mRNA processing is a more powerful mechanism than previously appreciated.

Radiotherapy alone versus concurrent chemoradiotherapy in patients with stage II and T3N0 nasopharyngeal carcinoma with adverse features: A propensity score-matched cohort study.

BACKGROUND AND PURPOSE: Whether concurrent chemoradiotherapy would provide survival benefits in patients with stage II and T3N0 NPC with adverse factors remains unclear in IMRT era. We aimed to assess the value of concurrent chemotherapy compared to IMRT alone in stage II and T3N0 NPC with adverse features. MATERIALS AND METHODS: 287 patients with stage II and T3N0 NPC with adverse factors were retrospectively analyzed, including 98 patients who received IMRT alone (IMRT alone group) and 189 patients who received cisplatin-based concurrent chemotherapy (CCRT group). The possible prognostic factors were balanced using propensity score matching (PSM). Kaplan-Meier analysis was used to evaluate the survival rates, and log-rank tests were employed to compare differences between groups. RESULTS: The median follow-up duration was 90.8 months (interquartile range = 75.6-114.7 months). The IMRT alone and the CCRT group were well matched; however, for all survival-related endpoints, there were no significant differences between them (5-year failure-free survival: 84.3% vs. 82.7%, P value = 0.68; 5-year overall survival: 87.3% vs. 90.6%, P value = 0.11; 5-year distant metastasis-free survival: 92.8% vs. 92.5%, P value = 0.97; 5-year locoregional relapse-free survival: 93.4% vs. 89.9%, P value = 0.30). The incidence of acute toxicities in the IMRT alone group was significantly lower than that in the CCRT group. CONCLUSION: For patients with stage II and T3N0 NPC with adverse features treated using IMRT, no improvement in survival was gained by adding concurrent chemotherapy; however, the occurrence of acute toxicities increased significantly. For those combined with non-single adverse factors, the comprehensive treatment strategy needs further exploration.

Optimal cut-off value for identifying objective response in patients with nasopharyngeal carcinoma after induction chemotherapy.

BACKGROUND: We aimed to establish the most suitable threshold for objective response (OR) in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in patients with nasopharyngeal carcinoma (NPC). METHODS: According to RECIST 1.1, we retrospectively evaluated MR images of NPC lesions in patients before and after induction chemotherapy (IC). Restricted cubic spline and maximally selected rank statistics were used to determine the cut-off value. Survival rates and differences between groups were compared with Kaplan-Meier curves and log-rank tests. RESULTS: Of 1126 patients, 365 cases who received IC treatment were suitable for RECIST 1.1 evaluation. The 20% cut-off value maximized between-group differences according to maximally selected rank statistics. No difference in distant metastasis-free survival between OR and non-response groups was shown using the primary threshold of OR (30%), while it differed when 20% was employed. CONCLUSIONS: With an optimal cut-off value of 20%, RECIST may assist clinicians to accurately evaluate disease response in NPC patients.

TiCNet: Transformer in Convolutional Neural Network for Pulmonary Nodule Detection on CT Images.

Lung cancer is the leading cause of cancer death. Since lung cancer appears as nodules in the early stage, detecting the pulmonary nodules in an early phase could enhance the treatment efficiency and improve the survival rate of patients. The development of computer-aided analysis technology has made it possible to automatically detect lung nodules in Computed Tomography (CT) screening. In this paper, we propose a novel detection network, TiCNet. It is attempted to embed a transformer module in the 3D Convolutional Neural Network (CNN) for pulmonary nodule detection on CT images. First, we integrate the transformer and CNN in an end-to-end structure to capture both the short- and long-range dependency to provide rich information on the characteristics of nodules. Second, we design the attention block and multi-scale skip pathways for improving the detection of small nodules. Last, we develop a two-head detector to guarantee high sensitivity and specificity. Experimental results on the LUNA16 dataset and PN9 dataset showed that our proposed TiCNet achieved superior performance compared with existing lung nodule detection methods. Moreover, the effectiveness of each module has been proven. The proposed TiCNet model is an effective tool for pulmonary nodule detection. Validation revealed that this model exhibited excellent performance, suggesting its potential usefulness to support lung cancer screening.

TdDS-UNet: top-down deeply supervised U-Net for the delineation of 3D colorectal cancer.

Automatically delineating colorectal cancers with fuzzy boundaries from 3D images is a challenging task, but the problem of fuzzy boundary delineation in existing deep learning-based methods have not been investigated in depth. Here, an encoder-decoder-based U-shaped network (U-Net) based on top-down deep supervision (TdDS) was designed to accurately and automatically delineate the fuzzy boundaries of colorectal cancer. TdDS refines the semantic targets of the upper and lower stages by mapping ground truths that are more consistent with the stage properties than upsampling deep supervision. This stage-specific approach can guide the model to learn a coarse-to-fine delineation process and improve the delineation accuracy of fuzzy boundaries by gradually shrinking the boundaries. Experimental results showed that TdDS is more customizable and plays a role similar to the attentional mechanism, and it can further improve the capability of the model to delineate colorectal cancer contours. A total of 103, 12, and 29 3D pelvic magnetic resonance imaging volumes were used for training, validation, and testing, respectively. The comparative results indicate that the proposed method exhibits the best comprehensive performance, with a dice similarity coefficient (DSC) of 0.805 ± 0.053 and a hausdorff distance (HD) of 9.28 ± 5.14 voxels. In the delineation performance analysis section also showed that 44.49% of the delineation results are satisfactory and do not require revisions. This study can provide new technical support for the delineation of 3D colorectal cancer. Our method is open source, and the code is available athttps://github.com/odindis/TdDS/tree/main.

LD-UNet: A long-distance perceptual model for segmentation of blurred boundaries in medical images.

The blurriness of boundaries in medical image target regions hinders further improvement in automatic segmentation accuracy and is a challenging problem. To address this issue, we propose a model called long-distance perceptual UNet (LD-UNet), which has a powerful long-|distance perception ability and can effectively perceive the semantic context of an entire image. Specifically, LD-UNet utilizes global and local long-distance induction modules, which endow the model with contextual semantic induction capabilities for long-distance feature dependencies. The modules perform long-distance semantic perception at the high and low stages of LD-UNet, respectively, effectively improving the accuracy of local blurred information assessment. We also propose a top-down deep supervision method to enhance the ability of the model to fit data. Then, extensive experiments on four types of tumor data with blurred boundaries are conducted. The dataset includes nasopharyngeal carcinoma, esophageal carcinoma, pancreatic carcinoma, and colorectal carcinoma. The dice similarity coefficient scores obtained by LD-UNet on the four datasets are 73.35%, 85.93%, 70.04%, and 82.71%. Experimental results demonstrate that LD-UNet is more effective in improving the segmentation accuracy of blurred boundary regions than other methods with long-distance perception, such as transformers. Among all models, LD-UNet achieves the best performance. By visualizing the feature dependency field of the models, we further explore the advantages of LD-UNet in segmenting blurred boundaries.

In Situ Study and Improvement of the Temperature Increase and Isothermal Retention Stages in the Polyacrylonitrile (PAN) Fiber Pre-Oxidation Process.

The pre-oxidation process of Polyacrylonitrile (PAN) fibers is a complex procedure involving multiple stages of temperature increase and isothermal temperature retention. However, the impact of the temperature increase stage on PAN fiber has often been overlooked. To address this, samples were collected before and after the temperature increase and isothermal retention stages, treating them as separate influencing factors. Therefore, the pre-oxidation process can be divided into four distinct stages: (1) A temperature increase stage before the cyclization reactions: the PAN fiber's small-size crystals melt, and the crystal orientation changes under fixed tension, leading to shrinkage and increased orientation of the micropore. (2) An isothermal retention stage before the cyclization reactions: The crystal structure maintains well, resulting in minimal micropore evolution. The PAN fiber's crystal orientation and micropore orientation increased under fixed tension. (3) A temperature increase stage after the cyclization reactions: The PAN fiber's crystal melts again, reducing the average chord length and relative volume of the micropore. However, the PAN fiber can recrystallize under fixed tension. (4) An isothermal retention stage after the cyclization reactions: Significant crystal melting of the PAN fiber occurs, but the highly oriented crystals are maintained well. The average chord length and relative volume of the micropore increase. Recommendations for improving the pre-oxidation process are made according to these stages.

Feasible CT features to distinguish incidental rib enhancement from sclerotic metastasis in patients with malignancies.

OBJECTIVE: To investigate the CT features of incidental rib enhancement (RE) and to summarize the CT characteristics for distinguishing the RE from sclerotic metastasis (SM) in patients with malignancies. MATERIAL AND METHODS: This retrospective observational study enrolled 79 patients with RE (involved 133 ribs) during October 2014 and December 2021. Another 53 patients with SM (160 SM) in the same period were selected randomly for comparison. The location, enhancement patterns of RE were reviewed. The CT values of RE regions and SM were measured and statistically analyzed. RESULTS: Most REs (70 patients, 88.6%) were in the 1st to 6th ribs. 50 patients had solitary RE and 29 with multiple REs in a regional distribution. All the REs were closely connected to the intercostal venous plexus (ICVP) ipsilateral to the injection site. No visible abnormalities on unenhanced scans were detected in all REs. One hundred and twenty REs (90.2%) had nodular/patchy enhancement. The CT value of RE regions in the venous phase was lower than that in the arterial phase (589.8 ± 344.2 HU versus 1188.5 ± 325.3 HU, p < 0.001). During the venous phase, most REs (125, 94.0%) shrank or disappeared. SM appeared similar on both contrast-enhanced and unenhanced scans in terms of shape and CT values. CONCLUSION: The RE demonstrated characteristic CT features. The manifestations of nodular/patchy enhancement in the arterial phase, decreased density and shrinkage or disappearance during the venous phase, and no abnormality on unenhanced scans, as well as a close connection with the ICVP, may help differentiate RE from SM.

Value of radiological depth of invasion in non-pT4 Oral tongue squamous cell carcinoma: implication for preoperative MR T-staging.

OBJECTIVE: The prognostic stratification for oral tongue squamous cell carcinoma (OTSCC) is heavily based on postoperative pathological depth of invasion (pDOI). This study aims to propose a preoperative MR T-staging system based on tumor size for non-pT4 OTSCC. METHODS: Retrospectively, 280 patients with biopsy-confirmed, non-metastatic, pT1-3 OTSCC, treated between January 2010 and December 2017, were evaluated. Multiple MR sequences, including axial T2-weighted imaging (WI), unenhanced T1WI, and axial, fat-suppressed coronal, and sagittal contrast-enhanced (CE) T1WI, were utilized to measure radiological depth of invasion (rDOI), tumor thickness, and largest diameter. Intra-class correlation (ICC) and univariate and multivariate analyses were used to evaluate measurement reproducibility, and factors' significance, respectively. Cutoff values were established using an exhaustive method. RESULTS: Intra-observer (ICC = 0.81-0.94) and inter-observer (ICC = 0.79-0.90) reliability were excellent for rDOI measurements, and all measurements were significantly associated with overall survival (OS) (all p < .001). Measuring the rDOI on axial CE-T1WI with cutoffs of 8 mm and 12 mm yielded an optimal MR T-staging system for rT1-3 disease (5-year OS of rT1 vs rT2 vs rT3: 94.0% vs 72.8% vs 57.5%). Using multivariate analyses, the proposed T-staging exhibited increasingly worse OS (hazard ratio of rT2 and rT3 versus rT1, 3.56 [1.35-9.6], p = .011; 4.33 [1.59-11.74], p = .004; respectively), which outperformed pathological T-staging based on nonoverlapping Kaplan-Meier curves and improved C-index (0.682 vs. 0.639, p < .001). CONCLUSIONS: rDOI is a critical predictor of OTSCC mortality and facilitates preoperative prognostic stratification, which should be considered in future oral subsite MR T-staging. CLINICAL RELEVANCE STATEMENT: Utilizing axial CE-T1WI, an MR T-staging system for non-pT4 OTSCC was developed by employing rDOI measurement with optimal thresholds of 8 mm and 12 mm, which is comparable with pathological staging and merits consideration in future preoperative oral subsite planning. KEY POINTS: • Tumor morphology, measuring sequences, and observers could impact MR-derived measurements and compromise the consistency with histology. • MR-derived measurements, including radiological depth of invasion (rDOI), tumor thickness, and largest diameter, have a prognostic impact on OS (all p < .001). • rDOI with cutoffs of 8 mm and 12 mm on axial CE-T1WI is an optimal predictor of OS and could facilitate risk stratification in non-pT4 OTSCC disease.

Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma.

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.

Optimal Size Threshold for MRI-Detected Retropharyngeal Lymph Nodes to Predict Outcomes in Nasopharyngeal Carcinoma: A Two-Center Study.

BACKGROUND. Retropharyngeal lymph node (RLN) metastases have profound prognostic implications in patients with nasopharyngeal carcinoma (NPC). However, the AJCC staging system does not specify a size threshold for determining RLN involvement, resulting in inconsistent thresholds in practice. OBJECTIVE. The purpose of this article was to determine the optimal size threshold for determining the presence of metastatic RLNs on MRI in patients with NPC, in terms of outcome predictions. METHODS. This retrospective study included 1752 patients (median age, 46 years; 1297 men, 455 women) with NPC treated by intensity-modulated radiotherapy (RT) from January 2010 to March 2014 from two hospitals; 438 patients underwent MRI 3-4 months after treatment. Two radiologists measured the minimal axial diameter (MAD) of the largest RLN for each patient using a consensus process. A third radiologist measured MAD in 260 randomly selected patients to assess interobserver agreement. Initial ROC and restricted cubic spline (RCS) analyses were used to derive an optimal MAD threshold for predicting progression-free survival (PFS). The threshold's predictive utility was assessed in multivariable Cox regression analyses, controlling for standard clinical predictors. The threshold's utility for predicting PFS and overall survival (OS) was compared with a 5-mm threshold using Kaplan-Meier curves and log-rank tests. RESULTS. The intraclass correlation coefficient for MAD was 0.943. ROC and RCS analyses yielded an optimal threshold of 6 mm. In multivariable analyses, MAD of 6 mm and greater independently predicted PFS in all patients (HR = 1.35, p = .02), patients with N0 or N1 disease (HR = 1.80, p = .008), and patients who underwent posttreatment MRI (HR = 1.68, p = .04). In patients with N1 disease without cervical lymph node involvement, 5-year PFS was worse for MAD greater than or equal to 6 mm than for MAD that was greater than or equal to 5 mm but less than 6 mm (77.2% vs 89.7%, p = .03). OS was significantly different in patients with stage I and stage II disease defined using a 6-mm threshold (p = .04), but not using a 5-mm threshold (p = .09). The 5-year PFS rate was associated with a post-RT MAD of 6 mm and greater (HR = 1.68, p = .04) but not a post-RT MAD greater than or equal to 5 mm (HR = 1.09, p = .71). CONCLUSION. The findings support a threshold MAD of 6 mm for determining RLN involvement in patients with NPC. CLINICAL IMPACT. Future AJCC staging updates should consider incorporation of the 6-mm threshold for N-category and tumor-stage determinations.

Semi-automatic fine delineation scheme for pancreatic cancer.

BACKGROUND: Pancreatic cancer fine delineation in medical images by physicians is a major challenge due to the vast volume of medical images and the variability of patients. PURPOSE: A semi-automatic fine delineation scheme was designed to assist doctors in accurately and quickly delineating the cancer target region to improve the delineation accuracy of pancreatic cancer in computed tomography (CT) images and effectively reduce the workload of doctors. METHODS: A target delineation scheme in image blocks was also designed to provide more information for the deep learning delineation model. The start and end slices of the image block were manually delineated by physicians, and the cancer in the middle slices were accurately segmented using a three-dimensional Res U-Net model. Specifically, the input of the network is the CT image of the image block and the delineation of the cancer in the start and end slices, while the output of the network is the cancer area in the middle slices of the image block. Meanwhile, the model performance of pancreatic cancer delineation and the workload of doctors in different image block sizes were studied. RESULTS: We used 37 3D CT volumes for training, 11 volumes for validating and 11 volumes for testing. The influence of different image block sizes on doctors' workload was compared quantitatively. Experimental results showed that the physician's workload was minimal when the image block size was 5, and all cancer could be accurately delineated. The Dice similarity coefficient was 0.894 ± 0.029, the 95% Hausdorff distance was 3.465 ± 0.710 mm, the normalized surface Dice was 0.969 ± 0.019. By completing the accurate delineation of all the CT images, the speed of the new method is 2.16 times faster than that of manual sketching. CONCLUSION: Our proposed 3D semi-automatic delineative method based on the idea of block prediction could accurately delineate CT images of pancreatic cancer and effectively deal with the challenges of class imbalance, background distractions, and non-rigid geometrical features. This study had a significant advantage in reducing doctors' workload, and was expected to help doctors improve their work efficiency in clinical application.

Regulation of CD47 expression on CD14+ monocytes by interferon-α in PBC patients.

Background: Primary biliary cholangitis (PBC) is a chronic intrahepatic cholestatic autoimmune liver disease characterized by inflammatory injury of small and medium-sized bile ducts in the liver. The pathogenesis of PBC has yet to be entirely understood. CD47/signal-regulatory protein alpha (SIRPα) is closely related to developing autoimmune diseases by promoting inflammatory response. However, the effect of CD47/SIRPα on inflammatory response in PBC patients is still unclear. Objective: We investigated the expression of CD47/SIRPα and the effect of inflammatory cytokines on the CD47 expression, analyzed potential autoantibodies against CD47 and the effect of anti-CD47 antibody on the inflammatory response in PBC, provided laboratory basis for the study of the pathogenesis and targets for non-invasive diagnosis and treatment on PBC. Methods: The expression levels of CD47 and SIRPα on peripheral blood mononuclear cells (PBMC) were measured in 14 patients with PBC (the PBC group) and 13 healthy subjects (the Control group) by flow cytometry (FCM). The PBMC derived from healthy subjects were stimulated with healthy subjects' serum, PBC patients' serum, IFN-α or TNF-α, and the CD47 expression level on CD14+ monocytes was detected by FCM. The level of serum anti-CD47 antibody or IFN-α in PBC patients and healthy subjects was analyzed by ELISA. FCM was used to examine the TNF-α expression level in CD14+ monocytes of healthy subjects stimulated with isotype control antibody, anti-CD47 antibody, LPS or LPS combined with CD47 antibody. Results: The CD47 expression level on the CD14+ monocytes in PBC patients was statistically higher than that in the Control group (P<0.01). Compared with the Control group (PBMC+healthy serum), the CD47 expression on CD14+ monocyte stimulated with the PBC patients' serum (PBMC+PBC patients' serum) was increased (P<0.001); the CD47 expression on CD14+ monocyte stimulated with IFN-α (PBMC + IFN-α) increased gradually with the increased concentration of IFN-α (P<0.05). However, there was no similar trend on CD14+ monocyte stimulated with the TNF-α (PBMC+TNF-α) (P>0.05). The levels of serum anti-CD47 antibody and IFN-α in the PBC patients were higher than those in healthy subjects (P<0.05). The TNF-α expression level in CD14+ monocyte stimulated with the LPS (PBMC+LPS) or anti-CD47 antibody+LPS group (PBMC+LPS+anti-CD47 antibody) was significantly increased than that in the Control group (PBMC+isotype control antibody) (P<0.01 and P<0.001, respectively). The TNF-α expression level in CD14+ monocyte stimulated with the anti-CD47 antibody + LPS was higher than that with the LPS (P< 0.05). Conclusion: The CD47 may be related to the pathogenesis of PBC by inflammatory response. The CD47/SIRPα signal were imbalanced in PBC patients. The presence of serum anti-CD47 antibodies in PBC patients provides a laboratory basis for clinical diagnosis and treatment.

Investigation of Crystallization, Morphology, and Mechanical Properties of Polypropylene/Polypropylene-Polyethylene Block Copolymer Blends.

Polyethylene (PE)-based elastomers are the ideal choice for enhancing the compatibility of polypropylene/polyethylene (PP/PE) blends and improving the mechanical properties of PP-based materials. However, the issue of blend systems lies in the interplay between the crystallization processes. Therefore, we investigated the crystallization behavior during the cooling process of a new generation of PP/PE block copolymers (PP-b-PE) and random polypropylene (PPR, a copolymer of propylene and a small amount of ethylene or an alpha-olefin) blends using in-situ X-ray diffraction/scattering and differential scanning calorimetry (DSC) techniques. We also conducted mechanical performance tests on PPR/PP-b-PE blends at room temperature and low temperature (-5 °C). The results indicate that during the cooling process, the PP phase of PP-b-PE will follow the PPR to crystallize in advance and form a eutectic mixture, thereby enhancing the compatibility of PP/PE. Moreover, the PPR/PP-b-PE blend will form stable ß-(300) crystals with excellent mechanical properties. Due to the improved compatibility of PP/PE with PP-b-PE, PE crystals are dispersed within PP crystals, providing bonding that improves the toughness of PPR under the low stiffness failure conditions of PPR/PP-b-PE blends, thereby enhancing their impact performance at low and room temperatures. This research has great significance for both recycling waste plastics and enhancing the low-temperature toughness of PPR.

A novel fusion algorithm for benign-malignant lung nodule classification on CT images.

The accurate recognition of malignant lung nodules on CT images is critical in lung cancer screening, which can offer patients the best chance of cure and significant reductions in mortality from lung cancer. Convolutional Neural Network (CNN) has been proven as a powerful method in medical image analysis. Radiomics which is believed to be of interest based on expert opinion can describe high-throughput extraction from CT images. Graph Convolutional Network explores the global context and makes the inference on both graph node features and relational structures. In this paper, we propose a novel fusion algorithm, RGD, for benign-malignant lung nodule classification by incorporating Radiomics study and Graph learning into the multiple Deep CNNs to form a more complete and distinctive feature representation, and ensemble the predictions for robust decision-making. The proposed method was conducted on the publicly available LIDC-IDRI dataset in a 10-fold cross-validation experiment and it obtained an average accuracy of 93.25%, a sensitivity of 89.22%, a specificity of 95.82%, precision of 92.46%, F1 Score of 0.9114 and AUC of 0.9629. Experimental results illustrate that the RGD model achieves superior performance compared with the state-of-the-art methods. Moreover, the effectiveness of the fusion strategy has been confirmed by extensive ablation studies. In the future, the proposed model which performs well on the pulmonary nodule classification on CT images will be applied to increase confidence in the clinical diagnosis of lung cancer.

Transition Metal High-Entropy Nanozyme: Multi-Site Orbital Coupling Modulated High-Efficiency Peroxidase Mimics.

Strong substrate affinity and high catalytic efficiency are persistently pursued to generate high-performance nanozymes. Herein, with unique surface atomic configurations and distinct d-orbital coupling features of different metal components, a class of highly efficient MnFeCoNiCu transition metal high-entropy nanozymes (HEzymes) is prepared for the first time. Density functional theory calculations demonstrate that improved d-orbital coupling between different metals increases the electron density near the Fermi energy level (EF ) and shifts the position of the overall d-band center with respect to EF , thereby boosting the efficiency of site-to-site electron transfer while also enhancing the adsorption of oxygen intermediates during catalysis. As such, the proposed HEzymes exhibit superior substrate affinities and catalytic efficiencies comparable to that of natural horseradish peroxidase (HRP). Finally, HEzymes with superb peroxidase (POD)-like activity are used in biosensing and antibacterial applications. These results suggest that HEzymes have great potential as new-generation nanozymes.

A Rulefit-based prognostic analysis using structured MRI report to select potential beneficiaries from induction chemotherapy in advanced nasopharyngeal carcinoma: A dual-centre study.

BACKGROUND AND PURPOSE: Structured MRI report facilitate prognostic prediction for nasopharyngeal carcinoma (NPC). However, the intrinsic association among structured variables is not fully utilised. This study aimed to investigate the performance of a Rulefit-based model in feature integration behind structured MRI report and prognostic prediction in advanced NPC. MATERIALS AND METHODS: We retrospectively enrolled 1207 patients diagnosed with non-metastatic advanced NPC from two centres, and divided into training (N = 544), internal testing (N = 367), and external testing (N = 296) cohorts. Machine learning algorithms including multivariate analysis, deep learning, Lasso, and Rulefit were used to establish corresponding prognostic models. The concordance indices (C- indices) of three clinical and six combined models with different algorithms for overall survival (OS) prediction were compared. Survival benefits of induction chemotherapy (IC) were calculated among risk groups stratified by different models. A website was established for individualised survival visualisation. RESULTS: Incorporating structured variables into Stage model significantly improved the prognostic prediction performance. Six prognostic rules with structured variables were identified by Rulefit. OS prediction of Rules model was comparable to Lasso model in internal testing cohort (C-index: 0.720 vs. 0.713, P = 0.100) and achieved the highest C-index of 0.711 in external testing cohort, indicating better generalisability. The Rules model stratified patients into risk groups with significant 5-year OS differences in each cohort, and revealed significant survival benefits from additional IC in high-risk group. CONCLUSION: The Rulefit-based Rules model, with the revelation of intrinsic associations behind structured variables, is promising in risk stratification and guiding individualised IC treatment for advanced NPC.

Reduced-dose radiotherapy for Epstein-Barr virus DNA selected staged III nasopharyngeal carcinoma: A single-arm, phase 2 trial.

BACKGROUND: Radiotherapy-related toxicities of nasopharyngeal carcinoma (NPC) caused by a standard dose of 70 Gy remain a critical issue. Therefore, we assessed whether a radiotherapy dose of 60 Gy was non-inferior to the standard dose in patients with low-risk stage III NPC with a favourable response to induction chemotherapy (IC). PATIENTS AND METHODS: We did a single-arm, single-centre, phase II clinical trial in China. Patients with low-risk (Epstein-Barr virus [EBV] DNA level <4000 copies/ml) stage III NPC were treated with two cycles IC. Patients with complete/partial response and undetectable EBV DNA level were assigned 60 Gy intensity-modulated radiotherapy concurrently with three cycles of cisplatin. The primary end-point was 2-year progression-free survival (PFS). This trial is registered with ClinicalTrials.gov, number NCT03668730. RESULTS: One patient quit because of withdrawal of informed consent after IC. In total, 215 patients completed two cycles of IC, after which 116 (54.0%) and 99 (46.0%) patients were assigned 60 and 70 Gy radiotherapy, respectively. For 215 patients, the 2-year PFS was 90.7% (95% CI, 86.8%-94.6%) with a median follow-up of 43.9 months (interquartile range [IQR], 39.8-46.2). For patients treated with 60 Gy radiotherapy, the 2-year PFS rate was 94.8% (95%CI 90.7%-98.9%) with a median follow-up of 43.9 months (IQR 40.2-46.2). The most common late toxicity was grade 1-2 dry mouth (incidence rate: 54.3%). No grade 3+ long-term adverse event was observed, and most quality-of-life items, domains, and symptom scores returned to baseline by 6 months. CONCLUSION: Reduced-dose radiation (60 Gy) is associated with favourable survival outcomes and limited treatment-related toxicities in patients with low-risk stage III NPC sensitive to IC.