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Deep neural networks are widely adopted powerful tools for perceptual tasks. However, recent research indicated that they are easily fooled by adversarial examples, which are produced by adding imperceptible adversarial perturbations to clean examples. In this paper, we utilize the steganalysis rich model (SRM) to generate noise feature maps, and combine them with RGB images to discover the difference between adversarial examples and clean examples. In particular, we propose a two-stream pseudo-siamese network and train it end-to-end to detect adversarial examples. Our approach fuses the subtle difference in RGB images with the noise inconsistency in noise features. The proposed method has strong detection capability and transferability, and can be combined with any classifier without modifying its architecture or training procedure. Our extensive empirical experiments show that, compared with the state-of-the-art detection methods, the proposed method achieves excellent performance in distinguishing adversarial samples generated by popular attack methods on different real datasets. Moreover, our method has good generalization, it trained by a specific adversary can generalize to other adversaries.

The scarcity of two-dimensional (2D) magnetic nanostructures has hindered their applications in spintronics, which is attributed to that most magnetic materials exhibit non-van der Waals (nvdWs) structure and it is hard to reduce their thickness to 2D nanostructures. Thus it is eager to develop a promising strategy for free-standing 2D magnetic nvdWs nanostructures. We have achieved free-standing 2D nvdWs hexagonal FeSe with a thickness of 2.9 nm by the reaction between oleylamine-Se complex and Fe2+ with the assistance of Cl-, where the synergetic effects of Cl- and -NH2 lead to the anisotropic growth. Inspiringly, the 2D hexagonal FeSe exhibits intrinsic antiferromagnetic order rooted in Fe2+ and semiconductor nature. In addition, the temperature variation would result in the chemical environment changes of Fe2+, responsible for the temperature-dependent magnetic transitions. This work promotes the potential applications of 2D hexagonal FeSe and the preparation of other 2D nvdWs materials.

Aim: We investigated the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKIs) for advanced hepatocellular carcinoma (HCC). Method: This retrospective study included HCC patients treated with HAIC, TKIs and anti-PD-1 antibodies between May 2019 and November 2020 in our hospital. Primary end points were progression-free survival and safety. Results: Twenty-seven advanced HCC patients were analyzed. The median follow-up was 12.9 months (range: 4.0–24.0 months) and the median progression-free survival was 10.6 months. The objective response rate and disease control rate were 63.0 and 92.6%, respectively. No treatment-related deaths occurred. Conclusion: In patients with advanced HCC, treatment with HAIC, anti-PD-1 antibodies and oral TKIs was effective and safe.

Background Extrapancreatic perineural invasion (EPNI) is a risk factor for the prognosis of patients with pancreatic cancer. Few reliable clinical indicators can be used to evaluate EPNI. Methods We reviewed clinicopathological information of pancreatic cancer patients received radical surgery in our center from 2014 to 2019. The minimum distance between the tumor boundary and celiac artery (CA), superior mesenteric arteria (SMA) was respectively measured on enhanced-contrast CT images. Receiver Operating Characteristic (ROC) analysis was used to evaluate the diagnostic efficacy, and the optimal cut-off value was determined by Youden index. The latter was used as a diagnostic indicator for imaging perineural invasion (iPNI). K-M method and Cox risk regression model were applied to analyze the prognostic value of iPNI. Results A total of 384 patients were enrolled in this study. ROC analysis showed the minimum distance is an efficient indicator, and the best cut-off value 6.5 mm provided 71.63% sensitivity and specificity 84.31%. Cox regression model showed that iPNI was an independent risk factor for disease-free survival (DFS) and overall survival (OS). Subgroup analysis indicated that patients with larger tumor size and iPNI positive suggested a worse prognosis. Conclusions The minimum distance between tumor boundary and arteries is an efficient imaging indicator for diagnosing EPNI. iPNI is an independent risk factor for DFS and OS. The novel typing method based on plexus pancreaticus capitalis (PLX) potentially invaded may have guiding significance for extent of dissection.

In order to improve the humanization and convenience of online art design, this paper applies digital simulation technology to the art online design system and establishes a set of sequential multi-free-form surface design methods. Based on the obtained front free-form surfaces, this paper establishes the relationship between the discrete points on the subsequent free-form surfaces and their spatial solid angles and, through extremely complex theoretical deduction, finally obtains the subsequent free-form surfaces. In addition, by combining the two free-form surfaces to enter the 3D modeling software, we can obtain an optical lens with multiple free-form surfaces to improve the digital simulation effect. Finally, this paper uses the intelligent system constructed in this paper to conduct multiple sets of simulation experiments to evaluate the digital effect and artistic design effect of the system constructed in this paper. From the experimental research, it can be known that the art online design system based on digital simulation technology constructed in this paper basically meets the expected goals of the system constructed in this paper.

Emission control of volatile organic compounds (VOCs) from industrial sources is a frontline defense against air pollution in China. Owing to the complexity of chemical processing technologies and reaction mechanisms of VOCs, it is extremely difficult to pinpoint specific emission sources in a large-scale industrial region due to the synergy of various chemical processes. In this research, a comprehensive on-site emission profile of a representative petrochemical industrial park in East China is set up with measurements conducted using photochemical assessment monitoring stations (PAMSs) and the TO-15 method as per the United States Environmental Protection Agency. This is followed by a quantitative ozone formation potential (OFP) analysis, toxification analysis, and an on-site health risk assessment, covering each of 18 major facilities’ three sections: the refinery, chemical manufacturing zone, and wastewater treatment zone. The number of facilities and detected species studied in this research exceeds that of a former similar study. This study shows that the majority of VOC emissions from those enterprises possessing the largest impact on the environment are hydrocarbons: alkanes, olefin (alkenes, alkynes), and aromatics (91% in total). Aromatics and olefins show the maximum contribution to OFP, which is consistent with the results of similar studies. VOCs, such as 1,3-butadiene, from refineries are key factors leading to long-term health impacts, with aromatics being a leading carcinogenic and noncarcinogenic factor.

Summary Background A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND). Methods This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0–2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov , NCT02357992 . Findings Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9–5·8). Overall survival was 91% (95% CI 85–98) at 3 years and 87% (79–95) at 5 years. SABR was tolerated well, with no grade 4–5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85–98) at 3 years and 84% (76–93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 [95% CI 0·45–1·65], p=0·65) from a multivariable analysis. Interpretation Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. Funding Varian Medical Systems and US National Cancer Institute (National Institutes of Health).

This prospective non-randomized, multicenter clinical trial was performed to investigate efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 months in the TACE+131I-metuximab group (n = 160) and 3 months in the TACE group (n = 160) (hazard ratio, 0.55; 95% confidence interval, 0.43 to 0.70; P < 0.001). The median overall survival was 28 months in the TACE+131I-metuximab group and 19 months in the TACE group (hazard ratio, 0.62; 95% confidence interval, 0.47 to 0.82; P = 0.001). Conclusion: TACE+131I-metuximab showed a greater anti-recurrence benefit, significantly improved the 5-year survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

The problem of springback is one of the most significant factors affecting the forming accuracy for aluminum 3D stretch-bending parts. In order to achieve high-efficiency and high-quality forming of such kind of structural components, the springback behaviors of the AA6082 aluminum profiles are investigated based on the flexible multi-points 3D stretch-bending process (3D FSB). Firstly, a finite element simulation model for the 3D FSB process was developed to analyze the forming procedure and the springback procedure. The forming experiments were carried out for the rectangle-section profile to verify the effectiveness of the simulation model. Secondly, the influence of tension on springback was studied, which include the pre-stretching and the post-stretching. Furthermore, the influences of the bending radius and bending sequence are revealed. The results show that: (1) The numerical model can be used to evaluate the effects of bending radius and process parameters on springback in the 3D FSB process effectively. (2) The pre-stretching has little effect on the horizontal springback reduction, but it plays a prominent role in reducing the springback in the vertical direction. (3) The increase of bending deformation in any direction will lead to an increase of springback in its direction and reduce the springback in the other direction. Besides, it reduces the relative error in both directions simultaneously. This research established a foundation to achieve the precise forming of the 3D stretch-bending parts with closed symmetrical cross-section.

The hydrogenation and co-hydrogenation behaviors of Hami coal and Tahe residue were investigated in an autoclave, and the feasible technical route for co-hydrogenation was explored. The experimental results showed that Hami coal had good hydroliquefaction performance and the suitable reaction temperature was 445°C. At 445°C and 9 MPa, the coal conversion rate reached 98.74%, and the oil yield reached 68.54%. The hydrogenation tests of Tahe residue showed obvious coking tendency at the lower temperature, and it was difficult to achieve lightening. At 430°C, the conversion rate of Tahe residue was only 66.38%, the light oil yield was only 50.01%, and its coking rate was as high as 9.45%. The coking rate increased with the reaction temperature. When the mixtures of Hami coal and Tahe residue were co-hydrogenated directly, the conversion rate of the raw materials was lower, and the coke phenomenon was obvious. At the coal/oil ratio was 40/60, the conversion rate was 97.79%, and oil yield was 73.36%. Adding hydrogen solvents into the co-hydrogenation system could effectively inhibit coke formation, increase the conversion rate, and lighten co-hydrogenation products. When the amount of coal was 45% and Tahe residue was 20%, the conversion rate of raw materials was 98.38% and the oil yield was 74.82%.

Gonococcal meningitis is an exceedingly rare infectious disease, and if not diagnosed and treated in time, it can be severe. We present a case of gonococcal meningitis occurring in a 31-year old healthy woman. She was admitted with fever and persistent headache without urogenital symptoms. Blood cultures were positive and identified as N.gonorrhoeae, but CSF and cervical secretions cultures were both negative. Further testing confirmed the presence of N.gonorrhoeae by 16S ribosomal gene amplification and sequencing in all samples. These results suggest that the case may be a disseminated infection caused by untreated gonorrhea. Our case also shows that nucleic acid detection plays an important role in the rapid and precise diagnosis of gonococcal meningitis and in finding the origin of the pathogen.

The objective of this study was to predict hematoma expansion (HE) by radiomic models based on different machine learning methods and determine the best radiomic model through the comparison. A total of 108 patients with intracerebral hemorrhage were retrospectively evaluated. Images of baseline non-contrast computed tomography (NCCT) and follow-up NCCT scan within 24 h were retrospectively reviewed. An HE was defined as a volume increase of more than 33% or an increase greater than 12.5 mL from the volume of the baseline NCCT. Texture parameters of the baseline NCCT images were selected by the least absolute shrinkage and selection operator (LASSO) regression. We used support vector machine (SVM), decision tree (DT), conditional inference trees (CIT), random forest (RF), k‑nearest neighbors (KNN), back-propagation neural network (BPNet) and Bayes to build models. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) was performed and compared among models. Every model had a relatively high AUC (all > 0.75), SVM and KNN had the highest AUC of 0.91. There were significant differences between SVM and CIT (Z > 2.266, p = 0.02345), KNN and CIT (Z = 2.4834, p = 0.01301), RF and CIT (Z = 2.6956, p = 0.007027), KNN and BPNet (Z = 2.0122, p = 0.0442), RF and BPNet (Z = 1.9793, p = 0.04778). There was no significant difference among SVM, DT, RF, KNN and Bayes (p > 0.05). The SVM obtained the largest net benefit when the threshold probability was less than 0.33, while KNN obtained the largest net benefit when the threshold probability was greater than 0.33. Combined with ROC and DCA, SVM and KNN performed better in all the models for predicting HE. Radiomic models based on different machine learning methods can be used to predict HE and the models generated by SVM and KNN performed best.

Deep learning (DL) is a hot topic in the machine vision. A large number of data sets are necessary for efficient image recognition. Otherwise the overfitting will easily occur. However, most actual samples are limited and unbalanced. To diminish the negative impact of small unbalanced samples on image recognition, the Deep Convolutional Generative Adversarial Network (DC-GAN) was improved to simulate data distribution, and relied on the improved network to generate a highly diverse dataset of balanced fire images in the work. Then, the number of output layer nodes was finetuned for the training of the target dataset by the layer freezing method. The training of small unbalanced samples was realized, using exponentially decaying learning rate, L2 regularization method, and Adam optimization algorithm. Simulation results showed that the proposed algorithm converged faster by fixing the convolutional layer parameters of the pre-trained model and finetuning the fully connected layer through transfer learning. Besides, 99% of fire images were correctly recognized, without inducing the problem of small sample overfitting. The proposed algorithm provides a desirable tool for outdoor fire recognition.

Background FOLFIRINOX and gemcitabine plus albumin-bound paclitaxel (AG) regimens are recommended as first-line therapy for both locally advanced and metastatic pancreatic cancer. However, there were no specific markers to conduct personalized regimen choice. The research is to assess delta Housfield unit (delta HU), which is the difference in CT attenuation value (in HU) between enhanced and nonenhanced phase of region of interest, as a marker for predicting chemotherapy response of unresectable pancreatic cancer. Methods A total of 179 unresectable pancreatic cancer patients were enrolled in the study. Kaplan-Meier analysis and COX regression analysis were performed for progression-free survival (PFS) and overall survival. The differences of clinical characteristics were analyzed by χ 2test. Microvessel density (MVD) was calculated by immunochemistry staining of CD34. Results Delta HU was an independent risk factor for unresectable pancreatic cancer (P = 0.017, HR 0.672, 95%CI 0.485–0.930). Patients with higher delta HU were associated with better PFS (P = 0.004). For modified FOLFIRINOX (mFOLFIRINOX) group, delta HU was an independent risk factor (P = 0.045, HR 0.571), but not for AG group (P = 0.473, HR 0.855). Delta HU was correlated with stroma MVD (P = 0.000, R = 0.483), not with parenchyma MVD (P = 0.074, R = 0.199). Conclusions Delta HU was a marker predicting chemotherapy response for unresectable pancreatic cancer. Higher delta HU was associated with better survival for patients receiving mFOLFIRINOX rather than AG. The delta HU was positively correlated with stroma MVD, explaining the relationship between delta HU and prognosis.

Currently, a large number of mature methods are available for gaze estimation. However, most regular gaze estimation approaches require additional hardware or platforms with professional equipment for data collection or computing that typically involve high costs and are relatively tedious. Besides, the implementation is particularly complex. Traditional gaze estimation approaches usually require systematic prior knowledge or expertise for practical operations. Moreover, they are primarily based on the characteristics of pupil and iris, which uses pupil shapes or infrared light and iris glint to estimate gaze, requiring high-quality images shot in special environments and other light source or professional equipment. We herein propose a two-stage gaze estimation method that relies on deep learning methods and logistic regression, which can be applied to various mobile platforms without additional hardware devices or systematic prior knowledge. A set of automatic and fast data collection mechanism is designed for collecting gaze images through a mobile platform camera. Additionally, we propose a new annotation method that improves the prediction accuracy and outperforms the traditional gridding annotation method. Our method achieves good results and can be adapted to different applications.

Mitochondrial dysfunction contributes to the pathogenesis and prognosis of many common disorders, including neurodegeneration, stroke, myocardial infarction, tumor, and metabolic diseases. Ginsenosides, the major bioactive constituents of Panax ginseng (P. ginseng), have been reported to play beneficial roles in the molecular pathophysiology of these diseases by targeting mitochondrial dysfunction. In this review, we first introduce the types of ginsenosides and basic mitochondrial functions. Then, recent findings are summarized on different ginsenosides targeting mitochondria and their key signaling pathways for the treatment of multiple diseases, including neurological disorders, cancer, heart disease, hyperglycemia, and inflammation are summarized. This review may explain the common targets of ginsenosides against multiple diseases and provide new insights into the underlying mechanisms, facilitating research on the clinical application of P. ginseng., Graphical abstract Image 1

Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is a major health problem in Asian-Pacific regions. Antiviral therapy reduces, but does not completely prevent, HCC development. Thus, there is a need for accurate risk prediction to assist prognostication and decisions on the need for antiviral therapy and HCC surveillance. A few risk scores have been developed to predict the occurrence of HCC in CHB patients. Initially, the scores were derived from untreated CHB patients. With the development and extensive clinical application of nucleos(t)ide analog(s) (NA), the number of risk scores based on treated CHB patients has increased gradually. The components included in risk scores may be categorized into host factors and hepatitis B virus factors. Hepatitis activities, hepatitis B virus factors, and even liver fibrosis or cirrhosis are relatively controlled by antiviral therapy. Therefore, variables that are more dynamic during antiviral therapy have since been included in risk scores. However, host factors are more difficult to modify. Most existing scores derived from Asian populations have been confirmed to be accurate in predicting HCC development in CHB patients from Asia, while these scores have not offered excellent predictability in Caucasian patients. These findings support that more relevant variables should be considered to provide individualized predictions that are easily applied to CHB patients of different ethnicities. CHB patients should receive different intensities of HCC surveillance according to their risk category.

Salmonella, being one of the most widespread foodborne pathogens, is a compulsory test item required by national food safety standard of China and many other countries. More sensitive and specific Salmonella detection method is still needed since traditional methods are time consuming and highly dependent on enormous manpower and material resources. In this research, a bacteria detection method based on CRISPR-Cas13a system (where CRISPR is Clustered Regularly Interspaced Short Palindromic Repeats) was proposed. The target DNA was amplified by PCR and transcribed into RNA by T7 transcriptase, which can activate the RNase activity of the Cas13a protein. The self-folding quenched fluorescent probe can be cleaved by the activated Cas13a protein to generate fluorescent signal. We named this method as PCF detection (PCR-CRISPR-Fluorescence based nucleic acid detection). In this study, PCF detection showed excellent sensitivity, which can detect Salmonella genomic DNA with a minimum of 101 aM or 10° CFU/ml Salmonella bacteria in 2 hr. It also showed good specificity with no cross-reaction with other common foodborne bacteria. PRACTICAL APPLICATION: The PCF detection method proposed in this article can detect Salmonella sensitively and specifically, providing a novel strategy for the detection of foodborne pathogens in food and has great application potential in other microbial detection fields.

Background Malnutrition and muscle wasting are common features frequently observed in pancreatic ductal adenocarcinoma (PDAC) patients with cancer cachexia. They are associated with reduced survival and quality of life. Nutrition therapy is an important part of multimodal cancer care in PDAC. However, due to the complexity of nutrition assessment, only 30–60% of patients with nutritional risks receive nutritional treatment at present. It is important to identify biomarkers that may be used to improve management of PDAC‐associated malnutrition. Serum insulin‐like growth factor binding protein 2 (IGFBP2) has emerged as a potential serum biomarker in a variety of tumours. However, its association with malnutrition and muscle wasting in PDAC is unclear. Methods We evaluated the tumour IGFBP2 expression and serum IGFBP2 level in 98 PDAC patients using immunohistochemistry and enzyme‐linked immunosorbent assay and analysed the correlation between them. Furthermore, we explored the relationship between IGFBP2 of both tumour and serum and nutritional status (Patient‐Generated Subjective Global Assessment and skeletal muscle index). Pan02 IGFBP2 stable transfection cell lines, Pan02 PLV‐IGFBP2 cells, and PLKO‐IGFBP2 cells were injected subcutaneously into the flank of C57BL/6 mouse. Serum IGFBP2 levels, food intake, and body weight of these mice were measured. The degree of muscle atrophy is characterized by haematoxylin and eosin, Oil Red O, and Masson's trichrome staining. The mRNA and protein expression of several essential muscle‐related signal proteins such as atrogin‐1 and muscle RING finger 1 was measured. Results Among 98 patients, we found that tumour IGFBP2 expression is related to plasma IGFBP2 levels (r s = 0.562, P

Cochlear implantation (CI) is a safe and beneficial surgery for children with congenital inner ear malformations, with the exception of cochlear nerve aplasia. The combination of microtia with middle and inner ear abnormalities is extremely uncommon and sufficiently severe to make a surgical approach to the cochlea difficult. We report herein the case of a 2-year-old girl who presented with profound bilateral sensorineural hearing loss, congenital aural atresia, microtia, and inner ear malformations. High-resolution computed tomography revealed poor development of the bilateral middle ear spaces, absence of the incus and stapes, aberrant courses of facial nerves, aplastic lateral semicircular canals, and covered round windows. With intraoperative imaging assistance, sequential bilateral CI was performed using a transmastoid approach with no complication. We propose that CI is feasible in patients with severe external and middle ear malformations. However, major malformations increase the risk of complications. As the facial nerve and cochlea are difficult to locate due to the lack of important anatomical landmarks, detailed planning and adequate preparation, including review of the preoperative imaging data, and the use of facial nerve monitoring and intraoperative imaging are very important. In addition, experienced surgeons should perform CI to ensure the success of the operation.

China's rural e-commerce has been developing quickly over the last decade, and it has shown significant spatial aggregation in some areas. This paper examines this development and investigates factors that impact its spatial aggregation. The development of Taobao Villages is a typical example that reflects the fast development and spatial aggregation of rural e-commerce in villages. Thus, all the Taobao Villages that existed in China by 2017 are used as our research sample for the empirical analysis. Considering that village-level data involving long-term and large-scale observations are lacking in China, we innovatively combine report data from Alibaba, spatial data from Geography Information Systems technology, company data from web crawler technology and nighttime light data from remote sensing technology to quantify the factors of interest for each sample village. Ultimately, the consistent results of a random-effects probit model based on data about 2266 villages across six years and a negative binominal model based on cross-section data of 2092 villages demonstrates that the spatial aggregation at village-level with regard to rural e-commerce is significantly driven by the local industrial base and neighborhood effects. Interestingly, the socioeconomic conditions of the surrounding regions that villages locate in impact the spatial aggregation of rural e-commerce significantly and it presents non-linear relationship between them, but the local socioeconomic conditions of villages per se do not present significant impacts on it. This paper concludes with the policy implication for the promotion of spatial aggregation of rural e-commerce.

We report for the first time that transmission of optical light centered at a wavelength of 1549.8 nm through a tapered dual-core As $_{2}$ Se $_{3}$ -PMMA fiber simultaneously inscribes an antisymmetric long-period grating and an antisymmetric apodized fiber Bragg grating. The evolutions of the transmission spectrum, and the back-reflected spectrum of the dual-core fiber are experimentally measured as the accumulated exposure time increases. The bandwidth of the antisymmetric apodized fiber Bragg grating is measured, and a narrow bandwidth of 3.5 GHz (0.028 nm) with $\sim\! \text{100}\%$ reflectivity (∼32 dB contrast) is observed. A theoretical model of an antisymmetric apodized fiber Bragg grating in a dual-core fiber computationally reproduces the experimentally observed evolution of the transmission spectrum and the back-reflected spectrum. Both theory, and experiment reveal for the first time that such structure requires dual phase-matching conditions. It is also the first time that one single reflection peak of a fiber Bragg grating is observed on a dual-core multimode fiber that supports two modes due to the satisfying of dual-phase matching conditions. The performance of this device as an optical filter is investigated. The antisymmetric apodized structure provides a novel method for achieving apodized fiber Bragg gratings with narrow bandwidth, high reflectivity, and suppression of side-lobes. The simultaneously inscribed antisymmetric long-period grating and antisymmetric apodized fiber Bragg grating in the dual-core As $_{2}$ Se $_{3}$ -PMMA taper opens the path towards the realization of novel sensors and devices.

Resistive random access memories (RRAMs) have attracted tremendous attention due to their miniaturized size, low power consumption, high response speed, and simple fabrication requirements, which are regarded as a promising candidate for future nonvolatile memories. However, the traditional binary storage RRAMs fail to meet the high-density requirement in the area of big data. One of the ways to overcome this obstacle is to realize multilevel state transitions in a unit RRAM. Herein, we propose a facile spin-coating method to develop a multilevel RRAM based on Al/poly(methyl methacrylate) (PMMA)/ZnO quantum dots (QDs)/PMMA/ZnO QDs/PMMA/fluorine-doped tin oxide (FTO) structure, with the significant merits of typical forming-free bipolar resistive switching behavior, low-power operating voltage, stable endurance, and excellent retention. In specific, the ON/OFF ratio of the proposed ZnO QDs-based device can be adjusted by tuning the concentration of the ZnO QDs. Moreover, a multilevel RRAM performance with distinct four-level resistance states is obtained by varying the compliance current, which demonstrates that the proposed device has a specific application in multilevel data storage. The conductive filament model, combining the enhanced internal field and robust formation of the conductive filament, is introduced to explain the mechanism of the resistive switching behavior and multilevel performance. This work paves a new way for its prospect in constructing high-density data storage RRAMs.

Purpose To (i) describe the characteristics of physical fitness and cardiometabolic risk in Chinese university students with normal-weight obesity (NWO); (ii) assess the association between NWO with physical fitness and cardiometabolic risk. Methods A total of 249 participants from the 2018 Shanghai University of Sport Alumni Health Cohort Study in China formed the study cohort. NWO was defined as normal body mass index (17.9-23.9 kg/m2 for males; 17.2-23.9 kg/m2 for females) but with excess body-fat percentage (≥20% for males; ≥30% for females). Body composition was assessed by dual-energy X-ray absorptiometry. Physical-fitness scores were calculated from a battery of sex-specific tests. Cardiometabolic risk was calculated using a continuous clustered risk (MetS) score. Results We found that 16.7% of male and 45.3% of female university students were classified as having NWO. Participants with NWO showed worse cardiorespiratory fitness than those with normal weight (NW) (male NWO (37±8) vs male NW (41±6) mL/kg/min, p

The availability and use of geographic information technologies and data for describing the patterns and processes operating on or near the Earth’s surface have grown substantially during the past ...

Introduction Toxicity of chemotherapy drugs is the leading cause of poor therapeutic outcome in many cancer patients. Gastrointestinal (GI) toxicity and hepatotoxicity are among the most common side effects of current chemotherapies. Emerging studies indicate that many chemotherapy-induced toxicities are driven by drug metabolism, but very few reviews summarize the role of drug metabolism in chemotherapy-induced GI toxicity and hepatotoxicity. In this review, we highlighted the importance of drug metabolizing enzymes (DMEs) in chemotherapy toxicity. Areas covered Our review demonstrated that altered activity of DMEs play important role in chemotherapy-induced GI toxicity and hepatotoxicity. Besides direct changes in catalytic activities, the transcription of DMEs is also affected by inflammation, cell-signaling pathways, and/or by drugs in cancer patients due to the disease etiology. Expert opinion More studies should focus on how DMEs are altered during chemotherapy treatment, and how such changes affect the metabolism of chemotherapy drug itself. This mutual interaction between chemotherapies and DMEs can lead to excessive exposure of parent drug or toxic metabolites which ultimately cause GI adverse effect.

BACKGROUND Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have shown promising local benefits for advanced hepatocellular carcinoma (HCC). S-1, a composite preparation of a 5-fluorouracil prodrug, has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC. AIM To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC. METHODS In this single-center, open-label, prospective, randomized controlled trial, 117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with (TACE/HAIC + S-1, n = 56) or without (TACE/HAIC, n = 61) oral S-1 between December 2013 and September 2017. Two participants were excluded from final analysis for withdrawing consent. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), objective response rate, disease control rate and safety. RESULTS In total, 115 participants (100 males and 15 females; mean age, 57.7 years ± 11.9) were analyzed. The median PFS and OS were 5.0 mo (0.4–58.6 mo) (95% confidence interval (CI): 3.82 to 6.18) vs 4.4 mo (1.1–54.4 mo) (95%CI: 2.54 to 6.26; P = 0.585) and 8.4 mo (0.4–58.6 mo) (95%CI: 6.88 to 9.92) vs 8.3 mo (1.4–54.4 m) (95%CI: 5.71 to 10.96; P = 0.985) in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. The objective response rate and disease control rate were 30.9% vs 18.4% and 72.7% vs 56.7% in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. Grade 3/4 adverse events had a similar frequency in both treatment groups. CONCLUSION No improvements in tumor response rates, PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC. Both treatment regimens had a similar safety profile.

Multiple superimposed fiber Bragg gratings (FBGs) are fabricated based on a non-uniform single-core As2Se3-Poly methyl methacrylate (PMMA) tapered fiber, by which superimposition of up to nine chirped FBGs is achieved. Multiple superimposed uniform FBGs are first inscribed on the nonuniform waveguide and multiple superimposed chirped FBGs are obtained by stretching the non-uniform waveguide. Simultaneous measurement of temperature and strain is realized based on two superimposed chirped FBGs at wavelengths of 1540 nm (FBG1) and 1550 nm (FBG2), respectively. The central wavelength shifts and bandwidth changes of the two superimposed chirped FBGs, when temperature and strain change, are measured, respectively. Four matrices are defined to predict the temperature and strain change, and the one defined by measuring the bandwidth change of FBG1 and the central wavelength shift of FBG2 gives the most accurate measurement with the sensitivities of 29.1 pm/°C for temperature measurement and 0.373 pm/μe for strain measurement by measuring the bandwidth change of FBG1, and 75.1pm/°C for temperature measurement and 0.245 pm/μe for strain measurement by measuring the central wavelength shift of FBG2, respectively. The resolutions for temperature and strain measurement are enhanced by more than a factor of 10, respectively, compared with those using the matrix defined by measuring the wavelength shifts of FBG1 and FBG2. A large strain change from 0 to 22000 μe is achieved due to the low stiffness of As2Se3-PMMA taper, which is far beyond the operating range of silica materials.

There has not been a time in the history of GIScience when movement analytics and mobility insights have played such an important role in policymaking as in today’s global responses to the COVID-19...

BACKGROUND There is little evidence of combining sorafenib with hepatic arterial infusion chemotherapy (HAIC) after transarterial chemoembolization (TACE) for intermediate and advanced hepatocellular carcinoma (HCC). It is important to identify that patients with intermediate and advanced HCC are most likely to benefit from this combination therapy. AIM To investigate the safety and clinical outcomes of sorafenib combined with HAIC with folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) after TACE for intermediate and advanced HCC. METHODS This prospective phase II study enrolled patients with intermediate and advanced HCC who underwent treatment with sorafenib combined with TACE-HAIC. All patients initially received the standard 400 mg dose of sorafenib twice daily before TACE-HAIC. Participants at our institute with intermediate and advanced HCC underwent routine TACE. Then, the catheter used for embolization was kept in place in the hepatic artery, and oxaliplatin was intra-arterially administered for 6 h, followed by 5-FU for 18 h, and folinic acid was intravenously administered for 2 h. The primary endpoints were safety, as evaluated by the Common Terminology and Criteria for Adverse Events version 4.0, and 12-mo progression-free survival (PFS), as analyzed by the Kaplan-Meier method. As secondary endpoints, the objective response rate (ORR) was evaluated by the modified Response Evaluation Criteria for Solid Tumors, and survival time [overall survival (OS)] was analyzed by the Kaplan-Meier method. RESULTS Sixty-six participants at our institute with intermediate and advanced HCC were enrolled in this prospective study (mean age, 53.3 ± 11.7 years). Approximately 56.1% of participants had Barcelona Clinic Liver Cancer (BCLC) stage C disease, and 43.9% had BCLC stage B disease. The ORR was 42.4%. The disease control rate was 87.9%. The grade 3-4 toxicities consisted of thrombocytopenia (4.5%), neutropenia (3.0%), and elevated aspartate aminotransferase (12.2%). Hand-foot skin reaction was also observed (40.9%). The median PFS was 13.1 mo (13.5 mo in the BCLC stage B participants and 9.4 mo in the BCLC stage C participants). The 6-mo, 12-mo, and 24-mo PFS rates were 75.0%, 54.7%, and 30.0%, respectively. The median OS was 21.8 mo. CONCLUSION Sorafenib combined with HAIC (FOLFOX) after TACE may be a feasible treatment choice for intermediate and advanced HCC because this treatment met the prespecified endpoint of a 6-mo PFS rate exceeding 50% and had good patient tolerance. Prospective randomized controlled trials are needed to confirm the effect of this combination therapy.

Existing evidence has revealed inconsistent results on the association between metabolic syndrome (MetS) and endometrial cancer (EC) risk. Herein, we aim to better understand this association. Systematic searches of PubMed, EMBASE, and Web of Science through 12 December 2019 were conducted. Observational studies that provided risk estimates of MetS and EC risk were eligible. The quality of the included studies was judged based on the Newcastle-Ottawa scale. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Six studies, comprising 17,772 EC cases and 150,371 participants were included. MetS, diagnosed according to the criteria of the National Cholesterol Education Program-Third Adult Treatment Panel, was associated with an increased risk of EC (OR: 1.62; 95% CI = 1.26-2.07) with substantial heterogeneity (I2 = 78.3%). Furthermore, we found that women with MetS, diagnosed according to the criteria of the International Diabetes Federation, had a significantly higher risk of EC compared to healthy controls (OR: 1.45; 95% CI = 1.16-1.81; I2 = 64.6%). Our findings were generally consistent with the main results in the majority of prespecified subgroups, as well as in sensitivity analyses. In conclusion, MetS is associated with EC risk.

The longitudinal associations between handgrip strength (HGS) and depressive symptoms remain unclear, especially in developing countries. The aim of this cohort study was to explore the associations between HGS and the incidence of depressive symptoms in China.This prospective cohort study enrolled 8470 participants living in 450 urban communities and rural villages within 28 provinces of China. Depressive symptoms were assessed using the 10-item Center for Epidemiological Studies Depression Scale. Cox proportional hazards regression models were used to examine the associations between baseline HGS and the incidence of depressive symptoms.During the following period (mean follow-up, 3.75 years; 95% confidence interval [CI], 3.73-3.76 years), 2,027 (23.93%) out of 8470 participants developed depressive symptoms. The risk of depressive symptoms decreased progressively with both increasing weighted HGS (P for trend = 0.04) and absolute HGS (P for trend 0.001) after multivariate-adjustments. Compared with participants in the lowest quartiles of weighted and absolute HGS, the multivariate-adjusted hazard ratios (HRs) (95% CIs) of depressive symptoms for participants in the highest quartiles were 0.83 (0.71, 0.98) and 0.74 (0.62, 0.89), respectively. The interaction terms of weighted HGS-place of residence (P for interaction 0.001) and absolute HGS-place of residence (P for interaction = 0.03) were both significant. Higher weighted and absolute HGS were associated with a lower incidence of depressive symptoms for participants living in rural villages but not urban communities.The results suggest that HGS predicts a lower risk of depressive symptoms in Chinese rural populations.

Xin Tian, Ying Xuan, Rong Wu, Song Gao Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of ChinaCorrespondence: Song GaoDepartment of Clinical Oncology, Shengjing Hospital of China Medical University, 36 San Hao Street, Shenyang 110004, People’s Republic of ChinaEmail gaogao0229@hotmail.comObjective: To investigate the curative and adverse effects (AEs) of additional use of nimotuzumab combined with induction chemotherapy and concurrent chemoradiotherapy in unresectable locoregionally advanced hypopharyngeal carcinoma.Patients and Methods: We retrospectively evaluated 36 patients with stage III or IVA hypopharyngeal carcinoma who received induction chemotherapy followed by concurrent chemoradiotherapy with or without nimotuzumab. The induction chemotherapy included two or three cycles of TPF regimen. The intensity-modulated radiation therapy (IMRT) dose was 70 Gy to the planning target volume. Concurrent with radiotherapy, patients received chemotherapy consisting of cisplatin q3w. Adjuvant chemotherapy consisting of TPF regimen was administered 1 month later after concurrent chemoradiotherapy. Nimotuzumab (200 mg day 1, q3w) was given to patients concurrently with induction chemotherapy and was administered concurrently with IMRT at a weekly dose of 200 mg.Results: After induction chemotherapy, the objective response rate in patients treated with nimotuzumab (group A) versus those treated without nimotuzumab (group B) was 91.7% versus 58.3% (p=0.029). After concurrent chemoradiotherapy, the objective response rate was 95.8% in group A versus 83.3% in group B (p=0.253). The median follow-up was 22.6 months (range 8.9– 39.5 months). The 2-year OS rate in group A and group B were 62.5% (95% CI 55– 70%) and 51.8% (95% CI 45– 59%), respectively, the 2-year OS rate in group A was better than group B, P< 0.05. PFS was 23 months (95% CI 19– 27) in group A versus 18 months (95% CI 12– 22) in group B, PFS was longer in group A than group B, P< 0.05. There was no significant difference in AEs between the two groups.Conclusion: Additional use of nimotuzumab combined with induction chemotherapy and concurrent chemoradiotherapy in unresectable locoregionally advanced hypopharyngeal carcinoma yielded better short-term efficacy, also may improve overall survival and progression-free survival than patients without using nimotuzumab. The toxicity was tolerable.Keywords: nimotuzumab, induction chemotherapy, chemoradiotherapy, unresectable, locoregionally advanced, hypopharyngeal carcinoma

Epidemiological studies have investigated the relationship between infertility and the risk of ovarian cancer (OC); however, the results have been inconsistent. We therefore conducted the first meta-analysis to update and quantify the aforementioned association based on prospective cohort studies. Studies were identified by searching PubMed, EMBASE and Web of Science databases up to January 8, 2020. We extracted data from the studies and performed quality assessments. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Publication bias, and subgroup, meta-regression and sensitivity analyses were also conducted. Nine prospective cohort studies with a total of 10 383 OC cases and 6 278 830 participants were included in the present study. The summary RR of the association between infertility and the risk of OC was 1.51 (95% CI: 1.35-1.69), with low heterogeneity. Positive associations were observed in most subgroup analyses stratified by predefined factors, including region, duration of follow-up, study quality, causes of infertility, invasiveness of OC, infertility treatment status and adjustment of potential confounding parameters. No significant publication bias was detected. Our findings suggest that infertility in women were associated with an increased risk of OC.

The paper presents a model set adaptive filtering algorithm based on variational Bayesian approximation (MSA-VB) for the target tracking system with the model and noise uncertainties. The Rényi information divergence, as a criterion, is to choose the best match model that has the minimum divergence between candidate models and true mode. Subsequently, the model-conditioned estimation based on variational Bayesian approximation is proposed to estimate system state and measurement noise variances. To deal with the coupled noise intractability, the moments matching technique is used to obtain the mixed statistics of measurement noise at the fusion stage. The proposed algorithm is compared with the interacting multiple models (IMM) algorithm and the variational Bayesian-interacting multiple models (IMM-VB) algorithm via two scenarios for maneuvering target tracking, and simulation results show that the MSA-VB has improved estimation and tracking performance.

Purpose To investigate the relationship between hypoxia-inducible factor 1-alpha (HIF-1α), Twist family BHLH transcription factor 1 (TWIST-1), and β1 integrin (ITGB-1) expression and tumor stiffness, and evaluate performance of HIF-1α, TWIST-1, and ITGB-1 alone and in combination with Ki-67 for predicting pathological responses to neoadjuvant chemotherapy (NACT) in breast cancer (BC). Patients and methods This was a prospective cohort study of 104 BC patients receiving NACT. Tumor stiffness and oxygen score (OS) were evaluated before NACT by shear-wave elastography and optical imaging; HIF-1α, TWIST-1, ITGB-1, and Ki-67 expression were quantitatively assessed by immunohistochemistry of paraffin-embedded tumor samples obtained by core needle biopsy. Indexes were compared among different residual cancer burden (RCB) groups, and associations of HIF-1α, TWIST-1, ITGB-1, and Ki-67 with tumor stiffness and OS were examined. The value of HIF-1α, TWIST-1, ITGB-1, and Ki-67, and a possible new combined index (predRCB) for predicting NACT responses was assessed by receiver operating characteristic (ROC) curves. Results HIF-1α, TWIST-1, and ITGB-1 expression were positively correlated with tumor stiffness and negatively with OS. Area under the ROC curves (AUCs) measuring the performance of HIF-1α, TWIST-1, ITGB-1, and Ki-67 for predicting responses to NACT were 0.81, 0.85, 0.79, and 0.80 for favorable responses, and 0.83, 0.86, 0.84, and 0.85 for resistant responses, respectively. PredRCB showed better prediction than the other individual indexes for favorable responses (AUC = 0.88) and resistant responses (AUC = 0.92). Conclusion HIF-1α, TWIST-1, ITGB-1, and Ki-67 performed well in predicting favorable responses and resistance to NACT, and predRCB improved the predictive power of the individual indexes. These results support individualized treatment of BC patients receiving NACT.

As a prominent alternative to toxic dyes/pigments, nanostructural color pixels have garnered tremendous attention in applications related to display/imaging devices and color printings. However, current color pixels mostly offer static color responses. In relation to this, dynamic color tuning properties must be investigated in order to expand their functionalities and promote their use in the fields of encryption and anti-counterfeiting. In this study, a simple array of hydrogenated amorphous silicon nanogratings is proposed to realize polarization-encrypted full-color images via the coupling of incident light into different leaky mode resonances within the nanogratings. The proposed pixels can readily switch from vivid full colors to indistinguishable orange color by altering the incident polarization state. Hence, unlike the reported polarization-tuned color generation schemes that merely allow for the color variation of the image or require complicated designs to hide the color information, the proposed approach can encrypt arbitrary full-color images via a simple tuning of the incident polarization state. Owing to the localized leaky mode resonances supported by the nanogratings, the pixel can still implement the polarization-encrypted functionality even when it contains only four gratings, thus enabling a remarkably high resolution. The proposed simple scheme may provide a credible new pathway for accelerating the practical applications of high-resolution encryption and anti-counterfeiting.

Geospatial artificial intelligence (GeoAI) is an interdisciplinary field that has received tremendous attention from both academia and industry in recent years. This article reviews the series of GeoAI workshops held at the Association for Computing Machinery (ACM) International Conference on Advances in Geographic Information Systems (SIGSPATIAL) since 2017. These workshops have provided researchers a forum to present GeoAI advances covering a wide range of topics, such as geospatial image processing, transportation modeling, public health, and digital humanities. We provide a summary of these topics and the research articles presented at the 2017, 2018, and 2019 GeoAI workshops. We conclude with a list of open research directions for this rapidly advancing field.

This study sought to evaluate short-term treatment with COX-2 inhibitors and acute changes in colonic PGE2 levels as predictors of long-term efficacy in a genetic model of colorectal cancer. Celecoxib oral suspension (40 mg/kg BID) was dosed to Apc-mutant Pirc (F344/NTac-Apcam1137) rats for 4 days (short-term group), or the equivalent dose of 1500 ppm celecoxib was administered in the diet for 4 months (long-term group). Percent inhibition of colonic PGE2 was calculated, and the reduction in colonic PGE2 was assessed in relation to suppression of adenomatous colon polyps. Colonic mucosa PGE2 was fourfold higher in Pirc than in F344 wild-type rats (21 vs. 5.6 pg/mg epithelial tissue), due at least in part to higher COX-2 expression, and this was confirmed by elevated PGE2-d11 levels in Pirc colonic S9 incubations. In the 4-day study, dose-dependent reductions in PGE2 were observed in colonic epithelium (-33% (P>0.05) and -57% (P=0.0012)), after low- and high-dose celecoxib treatments of 4 mg/kg and 40 mg/kg (bid), respectively. In the 4-month study, 1500 ppm celecoxib suppressed colonic epithelium PGE2 by 43.5%, and tumor multiplicity by 80% (P

Hidden biases of racial and socioeconomic preferences shape residential neighborhoods throughout the USA. Thereby, these preferences shape neighborhoods composed predominantly of a particular race or income class. However, the assessment of spatial extent and the degree of isolation outside the residential neighborhoods at large scale is challenging, which requires further investigation to understand and identify the magnitude and underlying geospatial processes. With the ubiquitous availability of location-based services, large-scale individual-level location data have been widely collected using numerous mobile phone applications and enable the study of neighborhood isolation at large scale. In this research, we analyze large-scale anonymized smartphone users’ mobility data in Milwaukee, Wisconsin, to understand neighborhood-to-neighborhood spatial interaction patterns of different racial classes. Several isolated neighborhoods are successfully identified through the mobility-based spatial interaction network analysis.

With the ubiquitous use of location-based services, large-scale individual-level location data has been widely collected through location-awareness devices. Geoprivacy concerns arise on the issues of user identity de-anonymization and location exposure. In this work, we investigate the effectiveness of geomasking techniques for protecting the geoprivacy of active Twitter users who frequently share geotagged tweets in their home and work locations. By analyzing over 38,000 geotagged tweets of 93 active Twitter users in three U.S. cities, the two-dimensional Gaussian masking technique with proper standard deviation settings is found to be more effective to protect user's location privacy while sacrificing geospatial analytical resolution than the random perturbation masking method and the aggregation on traffic analysis zones. Furthermore, a three-dimensional theoretical framework considering privacy, analytics, and uncertainty factors simultaneously is proposed to assess geomasking techniques. Our research offers insights into geoprivacy concerns of social media users' georeferenced data sharing for future development of location-based applications and services.

Flexible pressure sensors have garnered enormous attention in recent years as they hold great promise in wearable electronic devices. However, the realization of a high-performance flexible pressure sensor via a facile and cost-effective approach still remains a challenge. In this work, a capacitive pressure sensor based on a poly(vinylidenefluoride-co-trifluoroethylene) [P(VDF-TrFE)] dielectric film that incorporates nanopillars into both sides is demonstrated. Unlike the previous complicated and expensive methods, large-scale regular and uniform nanopillars are easily and economically achieved by the pattern transfer of anodized aluminum oxide templates. The double-sided nanopillars constituting the P(VDF-TrFE) dielectric layer enable the pressure sensor with high sensitivity (∼0.35 kPa-1), wide working range (4 Pa to 25 kPa), short response time (∼48 ms), and excellent durability. In addition to these salient features, our sensor also exhibits superior performances under bending states, ensuring that it can be used for detecting diverse practical stimuli as experimentally validated by perceiving real-time and in-site human physiological signals and body motions that, respectively, correspond to the low- and high-pressure range. A sensor array is finally constructed and is shown to be capable of perceiving the spatial pressure distribution of either a contact or noncontact object. These demonstrations show a promising future of our sensor in healthcare monitoring, smart robot skin, and human-machine interfaces.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)‐mutant lung cancer remains an orphan of specific targeted therapy. The variable responses to anti‐HER2 therapies in these patients prompt us to examine impact of HER2 variants and co‐mutations on responses to anti‐HER2 treatments in lung cancer. PATIENTS AND METHODS: Patients with stage IV/recurrent HER2‐mutant lung cancers identified through next‐generation sequencings were recruited from seven hospitals. The study comprised a cohort A to establish the patterns of HER2 variants and co‐mutations in lung cancer and a cohort B to assess associations between HER2 variants, co‐mutations, and clinical outcomes. RESULTS: The study included 118 patients (cohort A, n = 86; cohort B, n = 32). Thirty‐one HER2 variants and 35 co‐mutations were detected. Predominant variants were A775_G776insYVMA (49/118, 42%), G778_P780dup (11/118, 9%), and G776delinsVC (9/118, 8%). TP53 was the most common co‐mutation (61/118, 52%). In cohort B, objective response rates with afatinib were 0% (0/14, 95% confidence interval [CI], 0%–26.8%), 40% (4/10, 14.7%–72.6%), and 13% (1/8, 0.7%–53.3%) in group 1 (A775_G776insYVMA, n = 14), group 2 (G778_P780dup, G776delinsVC, n = 10), and group 3 (missense mutation, n = 8), respectively (p = .018). Median progression‐free survival in group 1 (1.2 months; 95% CI, 0–2.4) was shorter than those in group 2 (7.6 months, 4.9–10.4; hazard ratio [HR], 0.009; 95% CI, 0.001–0.079; p < .001) and group 3 (3.6 months, 2.6–4.5; HR, 0.184; 95% CI, 0.062–0.552; p = .003). TP53 co‐mutations (6.317; 95% CI, 2.180–18.302; p = .001) and PI3K/AKT/mTOR pathway activations (19.422; 95% CI, 4.098–92.039; p < .001) conferred additional resistance to afatinib. CONCLUSION: G778_P780dup and G776delinsVC derived the greatest benefits from afatinib among HER2 variants. Co‐mutation patterns were additional response modifiers. Refining patient population based on patterns of HER2 variants and co‐mutations may help improve the efficacy of anti‐HER2 treatment in lung cancer. IMPLICATIONS FOR PRACTICE: Human epidermal growth factor receptor 2 (HER2)‐mutant lung cancers are a group of heterogenous diseases with up to 31 different variants and 35 concomitant genomic aberrations. Different HER2 variants exhibit divergent sensitivities to anti‐HER2 treatments. Certain variants, G778_P780dup and G776delinsVC, derive sustained clinical benefits from afatinib, whereas the predominant variant, A775_G776insYVMA, is resistant to most anti‐HER2 treatments. TP53 is the most common co‐mutation in HER2‐mutant lung cancers. Co‐mutations in TP53 and the PI3K/AKT/mTOR pathway confer additional resistance to anti‐HER2 treatments in lung cancer. The present data suggest that different HER2 mutations in lung cancer, like its sibling epidermal growth factor receptor, should be analyzed independently in future studies.

Based on the notion of “emergence”, Xu et al. (Usenix Security 2012; TDSC 2013) developed the first concrete instantiation of emerging-image moving-object (EIMO) CAPTCHAs using 2D hollow objects (codewords), shown to be usable and believed to be secure. In this paper, we highlight the hidden security weaknesses of such a 2D EIMO CAPTCHA design. A key vulnerability is that the camera projection on 2D objects is constant (unlike 3D objects), making it possible to reconstruct the underlying codewords by superimposing and aggregating the temporally scattered parts of the object extracted from consecutive frames. We design and implement an automated attack framework to defeat this design using image processing techniques, and show that its accuracy in recognizing moving codewords is up to 89.2 percent, under different parameterizations. Our framework can be broadly used to undermine the security of different instances of 2D EIMO CAPTCHAs ( not just the current state-of-the-art by Xu et al. ), given the generalized and robust back-end theories in our attack, namely the methods to locate a codeword, reduce noises and accumulate objects’ contour information from consecutive frames corresponding to multiple time periods. As a countermeasure, we propose a fundamentally different design of EIMO CAPTCHAs based on pseudo 3D objects , and examine its security as well as usability. We argue that this design can resist our attack against 2D EIMO CAPTCHAs, although at the cost of reduced usability compared to the - now insecure - 2D EIMO CAPTCHAs.

Recent progress in Artificial Intelligence (AI) techniques, the large-scale availability of high-quality data, as well as advances in both hardware and software to efficiently process these data, a...

The field of urban analytics and city science has seen significant growth and development in the past 20 years. The rise of data science, both in industry and academia, has put new pressures on urb...

Validate that a two-dimensional (2D) ionization chamber array (ICA) combined with a double-wedge plate (DWP) can track changes in electron beam energy well within 2.0 mms as recommended by TG-142 for monthly quality assurance (QA). Electron beam profiles of 4-22 MeV were measured for a 25 × 25 cm2 cone using an ICA with a DWP placed on top of it along one diagonal axis. The relationship between the full width half maximum (FWHM) field size created by DWP energy degradation across the field and the depth of 50% dose in water (R50 ) is calibrated for a given ICA/DWP combination in beams of know energies (R50 values). Once this relationship is established, the ICA/DWP system will report the R50 FWHM directly. We calibrated the ICA/DWP on a linear accelerator with energies of 6, 9, 12, 16, 20, and 22 MeV. The R50 FWHM values of these beams and eight other beams with different R50 values were measured and compared with the R50 measured in water, that is, R50 Water. Resolving changes of R50 up to 0.2 cm with ICA/DWP was tested by adding solid-water to shift the energy and was verified with R50 Water measurements. To check the long-term reproducibility of ICA/DWP we measured R50 FWHM on a monthly basis for a period of 3 yr. We proposed a universal calibration procedure considering the off-axis corrections and compared calibrations and measurements on three types of linacs (Varian TrueBeam, Varian C-series, and Elekta) with different nominal energies and R50 values. For all 38 beams on same type of linac with R50 values over a range of 2-8.8 cm, the R50 FWHM reported by the ICA/DWP system agreed with that measured in water within 0.01 ± 0.03 cm (mean ± 1σ) and maximum discrepancy of 0.07 cm. Long-term reproducibility results show the ICA/DWP system to be within 0.04 cm of their baseline over 3 yr. With the universal calibration the maximum discrepancy between R50 FWHM and R50 Water for different types of linac reduced from 0.25 to 0.06 cm. Comparison of R50 FWHM values and R50 Water values and long-term reproducibility of R50 FWHM values indicates that the ICA/DWP can be used for monitoring of electron beam energy constancy well within TG-142 recommended tolerance.