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Stage pIIIA/N2 non‐small cell lung cancer (NSCLC) is primarily treated by complete surgical resection combined with neoadjuvant/adjuvant therapies. However, up to 40% of patients experience tumor recurrence. Here, we studied 119 stage pIIIA/N2 NSCLC patients who received complete surgery plus adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). The paired tumor and resection margin samples were analyzed using next‐generation sequencing (NGS). Although all patients were classified as negative resection margins by histologic methods, NGS revealed that 47.1% of them had molecularly positive surgical margins. Patients who tested positive for NGS‐detected residual tumors had significantly shorter disease‐free survival (DFS) (P = 0.002). Additionally, metastatic lymph node ratio, erb‐b2 receptor tyrosine kinase 2 (ERBB2) mutations, and SWI/SNF‐related, matrix‐associated, actin‐dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) mutations were also independently associated with DFS. We used these four features to construct a COX model that could effectively estimate recurrence risk and prognosis. Notably, mutational profiling through broad‐panel NGS could more sensitively detect residual tumors than the conventional histologic methods. Adjuvant CT and adjuvant CRT exhibited no significant difference in eliminating locoregional recurrence risk for stage pIIIA/N2 NSCLC patients with molecularly positive surgical margins.

Abstract Background Chemoradiotherapy is a critical treatment for patients with locally advanced and unresectable non-small cell lung cancer (NSCLC), and it is essential to identify high-risk patients as early as possible owing to the high incidence of radiation pneumonitis (RP). Increasing attention is being paid to the effects of endogenous factors for RP. This study aimed to investigate the value of computed tomography (CT)-based radiomics combined with genomics in analyzing the risk of grade ≥ 2 RP in unresectable stage III NSCLC. Methods In this retrospective multi-center observational study, 100 patients with unresectable stage III NSCLC who were treated with chemoradiotherapy were analyzed. Radiomics features of the entire lung were extracted from pre-radiotherapy CT images. The least absolute shrinkage and selection operator algorithm was used for optimal feature selection to calculate the Rad-score for predicting grade ≥ 2 RP. Genomic DNA was extracted from formalin-fixed paraffin-embedded pretreatment biopsy tissues. Univariate and multivariate logistic regression analyses were performed to identify predictors of RP for model development. The area under the receiver operating characteristic curve was used to evaluate the predictive capacity of the model. Statistical comparisons of the area under the curve values between different models were performed using the DeLong test. Calibration and decision curves were used to demonstrate discriminatory and clinical benefit ratios, respectively. Results The Rad-score was constructed from nine radiomic features to predict grade ≥ 2 RP. Multivariate analysis demonstrated that histology, Rad-score, and XRCC1 (rs25487) allele mutation were independent high-risk factors correlated with RP. The area under the curve of the integrated model combining clinical factors, radiomics, and genomics was significantly higher than that of any single model (0.827 versus 0.594, 0.738, or 0.641). Calibration and decision curve analyses confirmed the satisfactory clinical feasibility and utility of the nomogram. Conclusion Histology, Rad-score, and XRCC1 (rs25487) allele mutation could predict grade ≥ 2 RP in patients with locally advanced unresectable NSCLC after chemoradiotherapy, and the integrated model combining clinical factors, radiomics, and genomics demonstrated the best predictive efficacy.

Based on investigation of studies of reclamation survey by remote sensing both at home and abroad and demand analysis of process normalization for reclamation survey by remote sensing of North China Sea, the process of reclamation survey by remote sensing was standardized. The main content of specification for reclamation survey by remote sensing was presented and the future of its application and development was forecasted.

Leptomeningeal metastasis (LM) occurs in 3~5% of non-small cell lung cancer (NSCLC) patients. Diagnosis of patients with LM and disease monitoring remains challenging due to the low sensitivity and specificity of the commonly used approaches, such as cerebrospinal fluid (CSF) cytology and magnetic resonance imaging (MRI). Therefore, new approaches are necessary to improve the detection of LM. Recent studies have shown that circulating tumor DNA (ctDNA) in CSF can be used to detect and monitor LM, but whether it can serve as an early diagnostic biomarker prior to cytological and radiographic evidence of LM involvement requires further evaluation. Here we report a lung adenocarcinoma patient who had detectable oncogenic mutations in the CSF ctDNA prior to confirmation of LM by CSF cytology and MRI, highlighting the potential application of CSF ctDNA in early detection of LM.

Abstract Aims To perform a dosimetric evaluation of four different simultaneous integrated boost whole brain radiotherapy modalities with hippocampus and inner ear avoidance in the treatment of limited brain metastases. Methods Computed tomography/magnetic resonance imaging data of 10 patients with limited (1–5) brain metastases were used to replan step-and-shoot intensity-modulated radiotherapy (sIMRT), dynamic intensity-modulated radiation therapy (dIMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (Tomo). The prescribed doses of 40–50 Gy in 10 fractions and 30 Gy in 10 fractions were simultaneously delivered to the metastatic lesions and the whole-brain volume, respectively. The hippocampal dose met the RTOG 0933 criteria for hippocampal avoidance (Dmax ≤17 Gy, D100% ≤10 Gy). The inner ear dose was restrained to Dmean ≤15 Gy. Target coverage (TC), homogeneity index (HI), conformity index (CI), maximum dose (Dmax), minimum dose (Dmin) and dose to organs at risk (OARs) were compared. Results All plans met the indicated dose restrictions. The mean percentage of planning target volume of metastases (PTVmets) coverage ranged from 97.1 to 99.4%. For planning target volume of brain (PTVbrain), Tomo provided the lowest average D2% (37.5 ± 2.8 Gy), the highest average D98% (25.2 ± 2.0 Gy), and the best TC (92.6% ± 2.1%) and CI (0.79 ± 0.06). The two fixed gantry IMRT modalities (step and shot, dynamic) provided similar PTVbrain dose homogeneity (both 0.76). Significant differences across the four approaches were observed for the maximum and minimum doses to the hippocampus and the maximum doses to the eyes, lens and optic nerves. Conclusion All four radiotherapy modalities produced acceptable treatment plans with good avoidance of the hippocampus and inner ear. Tomo obtained satisfactory PTVbrain coverage and the best homogeneity index. Trial registration Clinicaltrials.gov, NCT03414944. Registered 29 January 2018

To reduce the high risk of radiation toxicity and enhance the quality of life of patients with non-small cell lung cancer (NSCLC), we quantified the metabolic tumor volumes (MTVs) from baseline to the late-course of radiotherapy (RT) by fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET-CT) and discussed the potential benefit of late-course adaptive plans rather than original plans by dose volume histogram (DVH) comparisons. Seventeen patients with stage II-III NSCLC who were treated with definitive conventionally fractionated RT were eligible for this prospective study. FDG PET-CT scans were acquired within 1 week before RT (pre-RT) and at approximately two-thirds of the total dose during-RT (approximately 40 Gy). MTVs were taken as gross tumor volumes (GTVs) that included the primary tumor and any involved hilar or mediastinal lymph nodes. An original plan based on the baseline MTVs and adaptive plans based on observations during-RT MTVs were generated for each patient. The DVHs for lung, heart, esophagus and spinal cord were compared between the original plans and composite plans at 66 Gy. At the time of approximately 40 Gy during-RT, MTVs were significantly reduced in patients with NSCLC (pre-RT 136.2±82.3 ml vs. during-RT 64.7±68.0 ml, p = 0.001). The composite plan of the original plan at 40 Gy plus the adaptive plan at 26 Gy resulted in better DVHs for all the organs at risk that were evaluated compared to the original plan at 66 Gy (p

This is a clinical study to compare noninvasive hypoxia imaging using 18F-fluoroerythronitroimidazole (18F-FETNIM) and 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) in patients with inoperable stages III-IV lung cancer.A total of forty-two patients with inoperable stages III-IV lung cancer underwent 18F-FETNIM PET/CT (n = 18) and 18F-FMISO PET/CT (n = 24) before chemo/radiation therapy. The standard uptake values (SUVs) of malignant and normal tissues depict 18F-FETNIM PET/CT and 18F-FMISO PET/CT uptake. Tumor-to-blood ratios (T/B) were used to quantify hypoxia.All patients with lung cancer underwent 18F-FETNIM PET/CT and 18F-FMISO PET/CT successfully. Compared to 18F-FMISO, 18F-FETNIM showed similar uptake in muscle, thyroid, spleen, pancreas, heart, lung and different uptake in blood, liver, and kidney. Significantly higher SUV and T/B ratio with 18F-FMISO (2.56±0.77, 1.98±0.54), as compared to 18F-FETNIM (2.12±0.56, 1.42±0.33) were seen in tumor, P = 0.022, 5cm groups in 18F-FMISO PET/CT, P = 0.015 (or P = 0.029), whereas no difference was detected in 18F-FMISO PET/CT, P = 0.446 (or P = 0.707). Both 18F-FETNIM and 18F-FMISO showed significantly higher SUVs (or T/B ratios) in stage IV than stage III, P = 0.021, 0.013 (or P = 0.032, 0.02).18F-FMISO showed significantly higher uptake than 18F-FETNIM in tumor/non-tumor ratio and might be a better hypoxia tracer in lung cancer.

To explore the value of a new simple lyophilized kit for labeling PRGD2 peptide (18F-ALF-NOTA-PRGD2, denoted as 18F-alfatide) in the determination of metabolic tumor volume (MTV) with micro-PET in lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice verified by pathologic examination and compared with those using 18F-fluorodeoxyglucose (FDG) PET.All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers 18F-alfatide and 18F-FDG within two days. 18F-alfatide metabolic tumor volume (VRGD) and 18F-FDG metabolic tumor volume (VFDG) were manually delineated slice by slice on PET images. Pathologic tumor volume (VPath) was measured in vitro after the xenografts were removed.A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent 18F-alfatide PET, and 35 of them underwent 18F-FDG PET and all underwent pathological examination. The mean ± standard deviation of VPath, VRGD, and VFDG were 0.59±0.32 cm3 (range,0.13~1.64 cm3), 0.61±0.37 cm3 (range,0.15~1.86 cm3), and 1.24±0.53 cm3 (range,0.17~2.20 cm3), respectively. VPath vs. VRGD, VPath vs. VFDG, and VRGD vs. VFDG comparisons were t = -0.145, P = 0.885, t = -6.239, P

X-ray tomography has been widely used in various research fields thanks to its capability of observing 3D structures with high resolution non-destructively. However, due to the nonlinearity and inconsistency of detector pixels, ring artifacts usually appear in tomographic reconstruction, which may compromise image quality and cause nonuniform bias. This study proposes a new ring artifact correction method based on the residual neural network (ResNet) for X-ray tomography. The artifact correction network uses complementary information of each wavelet coefficient and a residual mechanism of the residual block to obtain high-precision artifacts through low operation costs. In addition, a regularization term is used to accurately extract stripe artifacts in sinograms, so that the network can better preserve image details while accurately separating artifacts. When applied to simulation and experimental data, the proposed method shows a good suppression of ring artifacts. To solve the problem of insufficient training data, ResNet is trained through the transfer learning strategy, which brings advantages of robustness, versatility and low computing cost.

Crystal monochromators are indispensable optical components for the majority of beamlines at synchrotron radiation facilities. Channel-cut monochromators are sometimes chosen to filter monochromatic X-ray beams by virtue of their ultrahigh angular stability. Nevertheless, high-accuracy polishing on the inner diffracting surfaces remains challenging, thus hampering their performance in preserving the coherence or wavefront of the photon beam. Herein, a magnetically controlled chemical–mechanical polishing (MC-CMP) approach has been successfully developed for fine polishing of the inner surfaces of channel-cut crystals. This MC-CMP process relieves the constraints of narrow working space dictated by small offset requirements and achieves near-perfect polishing on the surface of the crystals. Using this method, a high-quality surface with roughness of 0.614 nm (root mean square, r.m.s.) is obtained in a channel-cut crystal with 7 mm gap designed for beamlines at the High Energy Photon Source, a fourth-generation synchrotron radiation source under construction. On-line X-ray topography and rocking-curve measurements indicate that the stress residual layer on the crystal surface was removed. Firstly, the measured rocking-curve width is in good agreement with the theoretical value. Secondly, the peak reflectivity is very close to theoretical values. Thirdly, topographic images of the optics after polishing were uniform without any speckle or scratches. Only a nearly 2.5 nm-thick SiO2 layer was observed on the perfect crystalline matrix from high-resolution transmission electron microscopy photographs, indicating that the structure of the bulk material is defect- and dislocation-free. Future development of MC-CMP is promising for fabricating wavefront-preserving and ultra-stable channel-cut monochromators, which are crucial to exploit the merits of fourth-generation synchrotron radiation sources or hard X-ray free-electron lasers.

Fusion welding of 7000 series aluminum alloy is plagued by cracking from a fine equiaxed zone (FQZ). Here, the authors quantify key softening mechanisms, show the damage accumulation sequence, and propose a hybrid laser/arc welding strategy to mitigate the FQZ and increase weld strength and toughness.

Abstract Rational design of porous conductive hosts with high electrical conductivity, large surface area, and adequate interior space is desirable to suppressing dendritic lithium growth and accommodating large volume change of lithium metal anode during the Li plating/stripping process. However, due to the conductive nature of the conductive hosts, Li is easily deposited directly on the top of the hosts, which hinders it from fully functioning. To circumvent the issue, in this study, we designed a novel porous carbon host with a gradient‐pore‐size structure based on one‐dimensional (1D) carbon with different diameters. With this kind of host, stable cycling with high and stable Coulombic efficiency of ~98% is achieved at 0.5 mA cm−2 with an areal capacity of 1 mAh cm−2 over 320 cycles. In contrast, the normal three‐dimensional (3D) carbon nanotube host presents a moss‐like Li morphology with wildly fluctuating Coulombic efficiency after 100 cycles. The results reveal that the unique gradient‐pore‐size structure of the 3D conductive host greatly improves the performance of lithium metal batteries.

There is no effective treatment for acute lung injury (ALI) at present. Some studies have reported the anti-inflammatory effect of Ejiao, but no study has addressed the underlying action mechanism. In this study, the CCK8 assay displayed Ejiao had a protective effect against LPS-elicited inflammatory lung epithelial Beas 2B cells (LILEB 2B cells). Beas 2B cells treated with LPS and Ejiao were challenged with NFκB inhibitor Bay11–7082 and ROS scavenger N-acetyl cysteine (NAC) alone and in combination. The results of qRT-PCR, Western blotting and fluorescence labeling experiments using Bay11–7082 and NAC demonstrated Ejiao could significantly decrease the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1β related to pyroptosis of LILEB 2B cells. Moreover, Ejiao reduced the production of mitochondrial ROS and reversed the change of mitochondrial membrane potential of LILEB 2B cells. Then, HE staining demonstrated Ejiao had a protective effect against the LPS-elicited ALI mouse model (LAMM). Ejiao also dramatically decreased the cell amount and the overall protein concentration of bronchoalveolar lavage fluid in LAMM. Immunohistochemical staining showed Ejiao remarkably reduced the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1β. The ELISA of IL-1β revealed Ejiao could dose-dependably decrease the concentration of IL-1β in lung tissues, serum and BALF of LAMM. Finally, fluorescence labeling demonstrated Ejiao significantly reduced the mitochondrial ROS generation in the lung tissue of LAMM. This finding may afford a novel strategy for the precaution and therapy of ALI.

A new shear strength determination of reinforced concrete (RC) deep beams was proposed by using a statistical approach. The Bayesian–MCMC (Markov Chain Monte Carlo) method was introduced to establish a new shear prediction model and to improve seven existing deterministic models with a database of 645 experimental data. The bias correction terms of deterministic models were described by key explanatory terms identified by a systematic removal process. Considering multi-parameters, the Gibbs sampling was used to solve the high dimensional integration problem and to determine optimum and reliable model parameters with 50,000 iterations for probabilistic models. The model continuity and uncertainty for key parameters were quantified by the partial factor that was investigated by comparing test and model results. The partial factor for the proposed model was 1.25. The proposed model showed improved accuracy and continuity with the mean and coefficient of variation (CoV) of the experimental-to-predicted results ratio as 1.0357 and 0.2312, respectively.

Lithium-rich layered material deserves in-depth understanding because it has large capacity enabled by both cation and anion activities. Here, authors apply 3D spectro-tomography with nano resolution to reveal the multi-layer morphology and depth-dependent transition metal valence distribution associated with oxygen redox.

Here the authors demonstrate a spectroscopic and imaging approach to study redox solid-state phase transformation in lithium ion cathode materials under thermal abuse conditions. The valence curvature of the propagation front alternates as a result of local chemical and structural heterogeneities.

Although the possibility of developing cardiac steroids/cardiac glycosides as novel cancer therapeutic agents has been recognized, the mechanism of their anticancer activity is still not clear enough. Toad venom extract containing bufadienolides, which belong to cardiac steroids, has actually long been used as traditional Chinese medicine in clinic for cancer therapy in China. The cytotoxicity of arenobufagin, a bufadienolide isolated from toad venom, on human cervical carcinoma HeLa cells was checked. And, the protein expression profile of control HeLa cells and HeLa cells treated with arenobufagin for 48 h was analyzed using two-dimensional electrophoresis, respectively. Differently expressed proteins in HeLa cells treated with arenobufagin were identified and the pathways related to these proteins were mapped from KEGG database. Computational molecular docking was performed to verify the binding of arenobufagin and Na, K-ATPase. The effects of arenobufagin on Na, K-ATPase activity and proteasome activity of HeLa cells were checked. The protein-protein interaction network between Na, K-ATPase and proteasome was constructed and the expression of possible intermediate proteins ataxin-1 and translationally-controlled tumor protein in HeLa cells treated with arenobufagin was then checked. Arenobufagin induced apoptosis and G2/M cell cycle arrest in HeLa cells. The cytotoxic effect of arenobufagin was associated with 25 differently expressed proteins including proteasome-related proteins, calcium ion binding-related proteins, oxidative stress-related proteins, metabolism-related enzymes and others. The results of computational molecular docking revealed that arenobufagin was bound in the cavity formed by the transmembrane alpha subunits of Na, K-ATPase, which blocked the pathway of extracellular Na+/K+ cation exchange and inhibited the function of ion exchange. Arenobufagin inhibited the activity of Na, K-ATPase and proteasome, decreased the expression of Na, K-ATPase α1 and α3 subunits and increased the expression of WEE1 in HeLa cells. Antibodies against Na, K-ATPase α1 and α3 subunits alone or combinated with arenobufagin also inhibited the activity of proteasome. Furthermore, the expression of the possible intermediate proteins ataxin-1 and translationally-controlled tumor protein was increased in HeLa cells treated with arenobufagin by flow cytometry analysis, respectively. These results indicated that arenobufagin might directly bind with Na, K-ATPase α1 and α3 subunits and the inhibitive effect of arenobufagin on proteasomal activity of HeLa cells might be related to its binding with Na, K-ATPase.

BACKGROUND:Sinus fungus ball, an accumulation of fungal dense concretions, is a common disease in practice, and might cause fatal complications or lead to death once converted into invasive type. Early preoperative diagnosis of this disease can lead to appropriate treatment for patients and prevent multiple surgical procedures. Up to now, the diagnostic criteria of sinus fungus ball have been defined and computed tomography (CT) scan was considered as a valuable preoperative diagnostic tool. However, the sensitivity of clinical CT is only about 62%. Thus, investigating the factors which influence sensitivity is necessary for clinical CT to be a more valuable preoperative diagnosis tool. Furthermore, CT scan usually presents micro-calcifications or spots with metallic density in sinus fungus ball. Previous literatures show that there are some metallic elements such as calcium and zinc in fungus ball, and they concluded that endodontic treatment has a strong correlation with the development of maxillary sinus fungus ball and zinc ion was an exogenous risk factor. But the pathogenesis of sinus fungus ball still remains unclear because fungus ball can also develop in other non-maxillary sinuses or the maxillary sinus without root canal treatment. Is zinc ion the endogenous factor? Study on this point might be also helpful for investigating the pathogenesis of sinus fungus ball. In this paper, we tried to investigate the factors which influence the sensitivity of clinical CT by imaging sinus fungus ball with microCT. The origin of zinc ion was also studied through elements test for different fungal ball samples using x-ray fluorescence technique. METHODS:Specimens including fungal ball material and sinus mucosa from patients confirmed by pathological findings were extracted after surgery. All fungal ball specimens came from sphenoid sinus, ethmoidal sinus and maxillary sinus with or without previous endodontic treatment respectively. All of them were imaged by microCT with spatial resolution up to 5μm to acquire three-dimensional structure, and then the heavy metal elements were detected with x-ray fluorescence spectrometer analysis. RESULT:High concentration of zinc and calcium were detected in all fungal ball specimens compared to sinus mucosa membrane. Particles with different size varied from disperse to density, which have similar shape to the result of clinical CT but with different size, were found in three-dimensional reconstruction results of microCT. CONCLUSIONS:Spatial resolution is an influent factor of clinical CT sensitivity for sinus fungus ball. Improving the resolution of clinical CT will help to improve its sensitivity. Besides iatrogenic endodontic materials, endogenous metal elements of zinc and calcium might associate with the growth of fungal ball and the micro-calcifications or spots with metallic density of CT imaging.