bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Abnormal Behavior Recognition of Buses Based on Improved Support Vector Machine
Authors: Pan Yong , Zhao Xiangmo , Xu Zhigang , Li Junwei , Li Yifei , Liu Li
Published: July 2021

The abnormal driving behavior of buses brings about greater security threat. How to effectively identify the abnormal driving behavior of buses has become one of the problems of cracking public transportation safety. This paper constructs an abnormal behavior recognition model of buses based on improved support vector machine. Through the verification, the model has a high recognition rate, which provides an important means for further improving the safety of public transportation operations.
Existence of Limit Cycles for a Class of Quartic Polynomial Differential System Depending on Parameters
Authors: Abdullah Qadha Sarah , Qadha Muneera Abdullah , Chen Haibo
Published: July 2021

We studied the existence of limit cycles for the quartic polynomial differential systems depending on parameters. To prove that, first, we used the formal series method based on Poincare’ ideas to determine the center-focus. Then, by the Hopf bifurcation theory, we obtained the sufficient condition for the existence of the limit cycles. Finally, we provided some numerical examples for illustration.
Surgical Drill Guide for Insertion of an Infra‐Acetabular Screw Based on an Anatomically Precontoured Plate System: A Cadaveric Study
Authors: Freigang Viola , Gottsauner Maximilian , Rupp Markus , Pfeifer Christian , Grechenig Stephan , Kerner Alexander , Alt Volker , Baumann Florian
Published: July 2021

Purpose. Due to the anatomic structure of the pelvis, free‐hand placement of screws in the acetabular fracture management can be difficult. Infra‐acetabular screw fixation increases acetabular stability by distal fixation of the cup. Aim of this cadaveric study is to investigate if a plate‐referenced drill guide can provide save placement of an infra‐acetabular screw over a precontoured suprapectineal quadrilateral buttress plate (SQBP). Methods. We constructed a drill guide for an infra‐acetabular screw based on the surface of an anatomically precontoured SQBP. A total of 12 adult cadaveric acetabular specimens were used for drill guide‐assisted placement of the infra‐acetabular screw. The drill guide contains a radiopaque spiral to allow longitudinal fine adjustment of the SQBP along the pelvic brim to assure correct position of the plate‐drill‐guide construct in relation to the Koehler’s teardrop. After screw placement, we conducted a computed tomography (CT) scan of all specimens to assess the actual position of the screw in relation of the infra‐acetabular corridor and the acetabular joint surface. Results. The position of the screw was within the infra‐acetabular corridor in all cases. We did not see any intra‐articular or intrapelvic screw penetration. The mean distance of the centerline of the screw to the medial border of the infra‐acetabular corridor was 3.35 mm. The secure distance to the virtual surface of the femoral head to was 7.3 mm. Conclusions. A plate‐referenced drill guide can provide safe placement of an infra‐acetabular screw for treatment of acetabular fractures. Radiographic fine adjustment is necessary to access the optimal entry point.
Automated Amharic News Categorization Using Deep Learning Models
Authors: Endalie Demeke , Haile Getamesay
Published: July 2021

For decades, machine learning techniques have been used to process Amharic texts. The potential application of deep learning on Amharic document classification has not been exploited due to a lack of language resources. In this paper, we present a deep learning model for Amharic news document classification. The proposed model uses fastText to generate text vectors to represent semantic meaning of texts and solve the problem of traditional methods. The text vectors matrix is then fed into the embedding layer of a convolutional neural network (CNN), which automatically extracts features. We conduct experiments on a data set with six news categories, and our approach produced a classification accuracy of 93.79%. We compared our method to well‐known machine learning algorithms such as support vector machine (SVM), multilayer perceptron (MLP), decision tree (DT), XGBoost (XGB), and random forest (RF) and achieved good results.
Industrial Agglomeration Analysis Based on Spatial Durbin Model: Evidence from Beijing‐Tianjin‐Hebei Economic Circle in China
Authors: Gao Lu-Hui , Wang Guo-Qing , Zhang Jing
Published: July 2021

Based on the data of Beijing‐Tianjin‐Hebei Economic Circle from 2010 to 2019, this paper uses the spatial Durbin model to empirically analyze the impact of financial development and technological innovation on industrial agglomeration. The following are the conclusions of this study: (1) financial development has a positive effect on industrial agglomeration; however, a significant difference exists in the weight effect of the geographic distance matrix compared to the weight of the economic distance matrix; (2) in the spatial Durbin model with two matrix weights, technological innovation has a significant positive effect on industrial agglomeration; and (3) in the spatial Durbin model with two matrix weights, the interaction has a significant negative effect on industrial agglomeration. Therefore, the government should further implement the coordinated development strategy, promoting regional technological innovation for a long time to realize its integration with financial development.
Semi‐Supervised Multi‐View Clustering with Weighted Anchor Graph Embedding
Authors: Wang Senhong , Cao Jiangzhong , Lei Fangyuan , Dai Qingyun , Liang Shangsong , Wing-Kuen Ling Bingo
Published: July 2021

A number of literature reports have shown that multi‐view clustering can acquire a better performance on complete multi‐view data. However, real‐world data usually suffers from missing some samples in each view and has a small number of labeled samples. Additionally, almost all existing multi‐view clustering models do not execute incomplete multi‐view data well and fail to fully utilize the labeled samples to reduce computational complexity, which precludes them from practical application. In view of these problems, this paper proposes a novel framework called Semi‐supervised Multi‐View Clustering with Weighted Anchor Graph Embedding (SMVC_WAGE), which is conceptually simple and efficiently generates high‐quality clustering results in practice. Specifically, we introduce a simple and effective anchor strategy. Based on selected anchor points, we can exploit the intrinsic and extrinsic view information to bridge all samples and capture more reliable nonlinear relations, which greatly enhances efficiency and improves stableness. Meanwhile, we construct the global fused graph compatibly across multiple views via a parameter‐free graph fusion mechanism which directly coalesces the view‐wise graphs. To this end, the proposed method can not only deal with complete multi‐view clustering well but also be easily extended to incomplete multi‐view cases. Experimental results clearly show that our algorithm surpasses some state‐of‐the‐art competitors in clustering ability and time cost.
Simulation Study of Rear-End Crash Evaluation considering Driver Experience Heterogeneity in the Framework of Three-Phase Traffic Theory
Authors: Yang Haifei , Wu Yao , Xiao Huihui , Zhao Yi
Published: July 2021

Driving safety is considered to have a strong relationship with traffic flow characteristics. However, very few studies have addressed the safety impacts in the three-phase traffic theory that has been demonstrated to be an advancement in explaining the empirical features of traffic flow. Another important issue affecting safety is driver experience heterogeneity, especially in developing countries experiencing a dramatic growth in the number of novice drivers. Thus, the primary objective of the current study is to develop a microsimulation environment for evaluating safety performance considering the presence of novice drivers in the framework of three-phase theory. First, a car-following model is developed by incorporating human physiological factors into the classical Intelligent Driver Model (IDM). Moreover, a surrogate safety measure based on the integration concept is modified to evaluate rear-end crashes in terms of probability and severity simultaneously. Based on a vehicle-mounted experiment, the field data of car-following behavior are collected by dividing the subjects into a novice group and an experienced group. These data are used to calibrate the proposed car-following model to explain driver experience heterogeneity. The results indicate that our simulation environment is capable of reproducing the three-phase theory, and the changes in the modified surrogate safety measure are highly correlated with traffic phases. We also discover that the presence of novice drivers leads to different safety performance outcomes across various traffic phases. The effect of driver experience heterogeneity is found to increase the probability of the rear-end crashes as well as the corresponding severity. The results of this study are expected to provide a scientific understanding of the mechanisms of crash occurrences and to provide application suggestions for improving traffic safety performance.
A Constrained Feature Selection Approach Based on Feature Clustering and Hypothesis Margin Maximization
Authors: Hijazi Samah , Truong Hoang Vinh
Published: July 2021

In this paper, we propose a semisupervised feature selection approach that is based on feature clustering and hypothesis margin maximization. The aim is to improve the classification accuracy by choosing the right feature subset and to allow building more interpretable models. Our approach handles the two core aspects of feature selection, i.e., relevance and redundancy, and is divided into three steps. First, the similarity weights between features are represented by a sparse graph where each feature can be reconstructed from the sparse linear combination of the others. Second, features are then hierarchically clustered identifying groups of the most similar ones. Finally, a semisupervised margin‐based objective function is optimized to select the most data discriminative feature from within each cluster, hence maximizing relevance while minimizing redundancy among features. Eventually, we empirically validate our proposed approach on multiple well‐known UCI benchmark datasets in terms of classification accuracy and representation entropy, where it proved to outperform four other semisupervised and unsupervised methods and competed with two widely used supervised ones.
Edge-Preserving Median Filter and Weighted Coding with Sparse Nonlocal Regularization for Low-Dose CT Image Denoising Algorithm
Authors: Yuan Quan , Peng Zhenyun , Chen Zhencheng , Guo Yanke , Yang Bin , Zeng Xiangyan
Published: July 2021

The impulse noise in CT image was removed based on edge-preserving median filter algorithm. The sparse nonlocal regularization algorithm weighted coding was used to remove the impulse noise and Gaussian noise in the mixed noise, and the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) were calculated to evaluate the quality of the denoised CT image. It was found that in nine different proportions of Gaussian noise and salt-and-pepper noise in Shepp-Logan image and CT image processing, the PSNR and SSIM values of the proposed denoising algorithm based on edge-preserving median filter (EP median filter) and weighted encoding with sparse nonlocal regularization (WESNR) were significantly higher than those of using EP median filter and WESNR alone. It was shown that the weighted coding algorithm based on edge-preserving median filtering and sparse nonlocal regularization had potential application value in low-dose CT image denoising.
Study on an Intelligent Prediction Method of Ticket Price in a Subway System with Public‐Private Partnership
Authors: Wang Shengmin , Fang Jun , Liu Lanjun , Wu Han
Published: July 2021

The accurate and rapid prediction of ticket prices for a public‐private partnership (PPP) subway system, which is an important research topic in the field of civil engineering management, is of critical importance to ensure its smooth operation. To effectively cope with the effects of multiple influencing factors and strong nonlinearity among them, the mean impact value (MIV) method and the back‐propagation (BP) feed‐forward neural network improved by the sparrow search algorithm (SSA) are used in this study to develop an intelligent prediction model. First, we considered the relationship of the supply and the subway system service, which is a typical quasi‐public product, and analyzed the relevant factors affecting its price adjustment. Then, we developed an intelligent method for the prediction of ticket prices based on the SSA‐BP. This model not only makes full use of the powerful nonlinear modeling ability of the BP algorithm, but also takes advantage of the strong optimization ability and fast convergence speed of the SSA. Finally, this study screened out the key input factors by adopting the MIV method to simplify the structure of the BP algorithm and achieve a high prediction accuracy. In this study, Beijing Subway Line 4, Wuhan Metro Line 2, and Chengdu Metro Line 1 were selected as case study sites. The results showed that the linear correlations between influencing factors and ticket price for the PPP subway system service were weak, which indicated the need for using nonlinear analysis methods such as the BP algorithm. Compared with other prediction methods (the price adjustment method based on PPP contract, the traditional BP algorithm, the BP neural network improved by the genetic algorithm, the BP algorithm improved by the particle swarm optimization, and the support vector machine), the model proposed in this paper showed better prediction accuracy and calculation stability.
Effect of Single-Dose and Short-Term Administration of Si Jun Zi Tang on the Pharmacokinetics of Gefitinib in Rats
Authors: Li Ying , Zhou Xiaowei , Niu Ming , zhang Mingyu , Gu Qiong , Chen Wei , Dong Bin , Zhang Yuanyuan , Li Ruisheng , Li Chunyu , Li Guohui
Published: July 2021

Background. Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula that has been described for approximately one thousand years, is often prescribed for cancer patients as a complementary therapy in China. However, the mechanism by which Si Jun Zi Tang enhances the efficacy of gefitinib is unclear. Methods. We investigated how Si Jun Zi Tang affected the pharmacokinetics of gefitinib in rats. A rapid, specific, and reliable ultra-performance liquid chromatography method with mass spectrometry was established to determine the plasma concentration of gefitinib. Results. The results showed that a single intragastrically administered dose of Si Jun Zi Tang increased the pharmacokinetic parameters of gefitinib (Cmax, 3156.13 μg/L; A UC, 46281.5 μg/L/h) by 3 folds in rats compared with the administration of gefitinib alone (Cmax, 1352.07 μg/L; AUC, 11823.7 μg/L/h). Si Jun Zi Tang could also alter the pharmacokinetics of gefitinib by prolonging the time to reach Cmax. Conclusions. Potential pharmacokinetic interactions between gefitinib and SJZ were evaluated, and SJZ extended Tmax and T1/2 and increased the Cmax and AUC of gefitinib. Long-term administration of gefitinib in combination with Si Jun Zi Tang would improve the efficacy of gefitinib.
Awareness of Breast Cancer Screening among the Medical and General Population of the North Region of Cameroon
Authors: Tagne Simo Richard , Baiguerel Erika Myriam , Nwabo Kamdje Armel Hervé , Seke Etet Paul Faustin , Ahmadou Mohamadou , Nangue Charlette , Telefo Phelix Bruno
Published: July 2021

Breast cancer has become a real public health problem in Cameroon, particularly in rural areas due to late diagnosis, resulting partly from the absence of national screening programs. This work is aimed at assessing breast cancer awareness in the North Region of Cameroon. Participants were selected in six health centers surrounding the rural area of Garoua, North Region, Cameroon, and administered a questionnaire aimed at assessing their awareness about breast cancer risk factors and screening. Out of the 475 women (including 37 medical personnel) interviewed, 45.5% attended at least secondary school; 91.3% were aware of the disease with the main sources of information from those around them (64.8%), media (46.5%), and health professionals in health facilities (42.7%). 23.3% had misconceptions and myth-based ideas on the origin of the disease. Ignorance was the main reason preventing the performance of breast self-examination, and the high cost prevents individuals from going for mammography. The highest awareness rate was observed in employed women with higher level of education. Our study highlights the need to raise awareness among the populations in North Region, Cameroon, about the risk factors and clinical signs of breast cancer and the importance of screening practice for early diagnosis of breast cancer.
Auxiliary Decision Support Model of Sports Training Based on Association Rules
Authors: Zhang Changnian , Li MeiJie , Wang Hui , Wang Ning
Published: July 2021

In sports or fitness training, nonstandard movements will affect the training effect and even lead to sports injuries. However, the standard movements of various sports activities need professional guidance, so it is difficult to find out whether the movements are standard or not. In recent years, body pose estimation has become a hot topic in computer vision research. A deep learning model can effectively identify the human nodes and movement trajectory in pictures or videos and evaluate the movements of the target human body. However, the movement process is generally covered by others or the situation of nearby personnel, which leads to the deviation of the movement recognition of the human body and affects the evaluation of the movement. Thus, it is unable to effectively correct the wrong movement, but will mislead the training personnel. Therefore, this paper proposes a novel decision support model for sports training based on association rules. We use posterior probability settings to reveal the weights of the discriminative ability of attribute items and set the classification performance to reflect the weights of three measures to evaluate credit contribution. Thus, the learning threshold setting reflects the weight of the decision-making ability of sports training. Furthermore, compared with traditional association rules, attribute items, frequent item sets, and classification rules that can improve the decision-making performance of sports training are discovered, which complement the deficiencies of different measures. Finally, using the weighted voting strategy to fuse the decision-making information of the classification rules, we can effectively assist in sports training so that the coach can work out corresponding countermeasures and realize scientific management.
Anomaly Detection in Videos Using Two‐Stream Autoencoder with Post Hoc Interpretability
Authors: Feng Jiangfan , Liang Yukun , Li Lin
Published: July 2021

The growing interest in deep learning approaches to video surveillance raises concerns about the accuracy and efficiency of neural networks. However, fast and reliable detection of abnormal events is still a challenging work. Here, we introduce a two‐stream approach that offers an autoencoder‐based structure for fast and efficient detection to facilitate anomaly detection from surveillance video without labeled abnormal events. Furthermore, we present post hoc interpretability of feature map visualization to show the process of feature learning, revealing uncertain and ambiguous decision boundaries in the video sequence. Experimental results on Avenue, UCSD Ped2, and Subway datasets show that our method can detect abnormal events well and explain the internal logic of the model at the object level.
Presentation of a Segmentation Method for a Diabetic Retinopathy Patient’s Fundus Region Detection Using a Convolutional Neural Network
Authors: Valizadeh Amin , Jafarzadeh Ghoushchi Saeid , Ranjbarzadeh Ramin , Pourasad Yaghoub
Published: July 2021

Diabetic retinopathy is characteristic of a local distribution that involves early‐stage risk factors and can forecast the evolution of the illness or morphological lesions related to the abnormality of retinal blood flows. Regional variations in retinal blood flow and modulation of retinal capillary width in the macular area and the retinal environment are also linked to the course of diabetic retinopathy. Despite the fact that diabetic retinopathy is frequent nowadays, it is hard to avoid. An ophthalmologist generally determines the seriousness of the retinopathy of the eye by directly examining color photos and evaluating them by visually inspecting the fundus. It is an expensive process because of the vast number of diabetic patients around the globe. We used the IDRiD data set that contains both typical diabetic retinopathic lesions and normal retinal structures. We provided a CNN architecture for the detection of the target region of 80 patients’ fundus imagery. Results demonstrate that the approach described here can nearly detect 83.84% of target locations. This result can potentially be utilized to monitor and regulate patients.
Complete Denture Fabrication Using Digitally Fabricated Copy Dentures for a Patient with Moderate Dementia
Authors: Arai Korehide , Tanaka Yuto , Matsuda Shinsuke , Okamura Tomohiko , Iwayama Kazufumi , Ono Yoshiaki
Published: July 2021

A 91-year-old woman was referred to our hospital with a chief complaint of unsatisfactory fit and pain associated with her complete dentures. She had moderate dementia with difficulty in communication (Mini-Mental State Examination, 16; Barthel Index, 15). The closed impressions and jaw record were taken with the digitally fabricated copy dentures as follows. First, the tissue conditioner was used to correct the poor fit of the old dentures, following which minor occlusal alterations were made. Second, the copy dentures that copied the morphology of the corrected old dentures using three-dimensional (3D) scanner were fabricated with a 3D printer. The new dentures were then fabricated using conventional methods as follows. The impressions were cast and articulated, and the dentures were subsequently processed. This case report documented the following results. First, the acceptance of new dentures appeared to be easier since the new dentures copied the morphology of the familiar dentures digitally. Moreover, the 3D data of the dentures could be used for immediate denture fabrication in case of fracture or loss of the dentures. Second, only two visits were required for taking an impression and delivering the complete dentures. In addition, her old dentures were brought to our dental office by the patient’s family after the patient’s dinner; immediately after copying the dentures’ morphology, the dentures were returned to the patient’s family, thus avoiding any disturbance to the patient’s eating routine. These reduced the burden on the patient and her family.
Silencing IL12p35 Promotes Angiotensin II-Mediated Abdominal Aortic Aneurysm through Activating the STAT4 Pathway
Authors: Wang Lanlan , Hu Chengyun , Dong Yongfei , Dai Feibiao , Xu Yongxia , Dai Yumeng , Shao Lijie , Zhu Defa
Published: July 2021

Background and Purpose. Abdominal aortic aneurysm (AAA) is a chronic inflammatory disorder and the important causes of death among men over the age of 65 years. Interleukin-12p35 (IL12p35) is an inflammatory cytokine that participates in a variety of inflammatory diseases. However, the role of IL12p35 in the formation and development of AAA is still unknown. Experimental Approach. Male apolipoprotein E-deficient (Apoe-/-) mice were generated and infused with 1.44 mg/kg angiotensin II (Ang II) per day. We found that IL12p35 expression was noticeably increased in the murine AAA aorta and isolated aortic smooth muscle cells (SMCs) after Ang II stimulation. IL12p35 silencing promoted Ang II-induced AAA formation and rupture in Apoe-/- mice. IL12p35 silencing markedly increased the expression of inflammatory cytokines, including IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), in both the serum and AAA aorta. Additionally, IL12p35 silencing exacerbated SMC apoptosis in Apoe-/- mice after Ang II infusion. IL12p35 silencing significantly increased signal transducer and activator of transcription (STAT) 4 phosphorylation levels in AAA mice, and STAT4 knockdown abolished the IL12p35-mediated proinflammatory response and SMC apoptosis. Interpretation. Silencing IL12p35 promotes AAA formation by activating the STAT4 pathway, and IL12p35 may serve as a novel and promising therapeutic target for AAA treatment.
Image Denoising Using Nonlocal Means with Shape‐Adaptive Patches and New Weights
Authors: Zuo Chenglin , Ma Jun , Xiong Hao , Ran Lin
Published: July 2021

Digital images captured from CMOS/CCD image sensors are prone to noise due to inherent electronic fluctuations and low photon count. To efficiently reduce the noise in the image, a novel image denoising strategy is proposed, which exploits both nonlocal self‐similarity and local shape adaptation. With wavelet thresholding, the residual image in method noise, derived from the initial estimate using nonlocal means (NLM), is exploited further. By incorporating the role of both the initial estimate and the residual image, spatially adaptive patch shapes are defined, and new weights are calculated, which thus results in better denoising performance for NLM. Experimental results demonstrate that our proposed method significantly outperforms original NLM and achieves competitive denoising performance compared with state‐of‐the‐art denoising methods.
An Intracranial Extradural Dermoid Cyst Presenting with Two Dermal Sinuses and an Abscess in a Child
Authors: Albastaki Aysha , AlThawadi Reem , Alajaimi Janan , Ali Khawla F. , Almayman Talal
Published: July 2021

Dermoid cysts account for only a small fraction of intracranial masses, with extradural dermoid cysts being considered a much rarer entity than those located intradurally. Intracranial dermoid cysts vary in clinical presentations: some maybe asymptomatic whilst others harbor features of raised intracranial pressure, neurological deficits, or even aseptic meningitis. Dermoid cysts may also present with cutaneous lesions. Herein, we report a rare case of a 1-year-old female presenting with a midline, scalp abscess. Brain MRI revealed an intracranial, extradural tumor, with features suggestive of a dermoid cyst, unusually located in the crista galli, and complicated by the formation of two cutaneous sinus tracts. After identification and characterization by MRI, bitemporal craniotomy was performed with complete excision of the mass and sinus tracts. Histological analysis confirmed dermoid cyst as the final diagnosis. Postoperatively, the patient recovered fully and had no evidence of recurrence in subsequent visits. The case mentioned above highlights the rarity of such a presentation for an intracranial extradural dermoid cyst and the vitality of early imaging for midline cutaneous lesions for identification of intracranial extensions and avoidance of detrimental consequences.
Association of Low High‐Density Lipoprotein Cholesterol Levels with Poor Outcomes in Hepatitis B‐Associated Decompensated Cirrhosis Patients
Authors: He Xia , Liu XiaoYun , Peng SongQing , Han Zhong , Shen Jianjiang , Cai Ming
Published: July 2021

Background. Lipid levels become decreased in cirrhotic patients and are correlated with disease severity. In the present study, we investigated the impact of serum high‐density lipoprotein cholesterol (HDL‐C) on prognosis in patients with HBV‐associated decompensated cirrhosis (HBV‐DeCi). Methods. The medical records of 153 HBV‐DeCi patients were analyzed. Patients were separated into survivors and nonsurvivors according to their 30‐day survival. Univariate and multivariate analyses were performed to identify predictors of poor outcomes, and the performance of these predictors was evaluated by receiver operating characteristic (ROC) curve analysis. Results. The 30‐day mortality in the cohort was 18.9%. HDL‐C levels differed markedly between survivors and nonsurvivors. On multivariate analysis, Model for End‐stage Liver Disease (MELD) score and HDL‐C level were identified as independent risk factors for mortality in HBV‐DeCi patients. In the ROC analyses, the prognostic accuracy for mortality was similar between HDL‐C (area under ROC curve: 0.785) and MELD score (area under ROC curve: 0.853). Conclusions. Low HDL‐C level had a significant correlation with mortality in HBV‐DeCi patients and can be used as a simple marker for risk assessment and selection of therapeutic options.
Ferritinophagy‐Mediated Ferroptosis Involved in Paraquat‐Induced Neurotoxicity of Dopaminergic Neurons: Implication for Neurotoxicity in PD
Authors: Zuo Yong , Xie Jinhong , Li Xincheng , Li Yan , Thirupathi Anand , Zhang Jianhua , Yu Peng , Gao Guofen , Chang Yanzhong , Shi Zhenhua
Published: July 2021

Parkinson’s disease (PD) is a progressive nervous system disorder. Until now, the molecular mechanism of its occurrence is not fully understood. Paraquat (PQ) was identified as a neurotoxicant and is linked to increased PD risk and PD‐like neuropathology. Ferroptosis is recognized as a new form of regulated cell death. Here, we revealed a new underlying mechanism by which ferritinophagy‐mediated ferroptosis is involved in PD induced by PQ. The effect of PQ on movement injury in mice was investigated by the bar fatigue and pole‐climbing test. SH‐SY5Y human neuroblastoma cells were used to evaluate the mechanism of ferroptosis. Our results showed that PQ induced movement injury by causing the decrease in tyrosine hydroxylase in mice. In vitro, PQ significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression significantly, which were important markers in ferroptosis. Fer‐1, an inhibitor of ferroptosis, could significantly ameliorate the ferroptosis induced by PQ. Meanwhile, Bcl2, Bax, and p‐38 were involved in apoptosis induced by PQ. In conclusion, ferritinophagy‐mediated ferroptosis pathway played an important role in PD occurrence. Bcl2/Bax and P‐p38/p38 pathways mediated the cross‐talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of PD occurrence. The inhibition of the ferroptosis and apoptosis together may be a new strategy for the prevention of neurotoxicity or PD in the future.
Heat Transfer Analysis for Viscous Fluid Flow with the Newtonian Heating and Effect of Magnetic Force in a Rotating Regime
Authors: Ayub Rashid , Ahmad Shahzad , Asjad Muhammad Imran , Ahmad Mushtaq
Published: July 2021

In this article, an unsteady free convection flow of MHD viscous fluid over a vertical rotating plate with Newtonian heating and heat generation is analyzed. The dimensionless governing equations for temperature and velocity fields are solved using the Laplace transform technique. Analytical solutions are obtained for the temperature and components of velocity fields. The obtained solutions satisfy the initial and boundary conditions. Some physical aspects of flow parameters on the fluid motion are presented graphically.
Tumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti–PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast Cancer
Authors: Gonzalez-Ericsson Paula I. , Wulfkhule Julia D. , Gallagher Rosa I. , Sun Xiaopeng , Axelrod Margaret L. , Sheng Quanhu , Luo Na , Gomez Henry , Sanchez Violeta , Sanders Melinda , Pusztai Lajos , Petricoin Emanuel , Blenman Kim R.M. , Balko Justin M. ,   I-SPY2 Trial Team
Published: July 2021

Purpose:

Immunotherapies targeting PD-1/L1 enhance pathologic complete response (pCR) rates when added to standard neoadjuvant chemotherapy (NAC) regimens in early-stage triple-negative, and possibly high-risk estrogen receptor–positive breast cancer. However, immunotherapy has been associated with significant toxicity, and most patients treated with NAC do not require immunotherapy to achieve pCR. Biomarkers discerning patients benefitting from the addition of immunotherapy from those who would achieve pCR to NAC alone are clearly needed. In this study, we tested the ability of MHC-II expression on tumor cells, to predict immunotherapy-specific benefit in the neoadjuvant breast cancer setting.

Patients and Methods:

This was a retrospective tissue-based analysis of 3 cohorts of patients with breast cancer: (i) primary nonimmunotherapy-treated breast cancers (n = 381), (ii) triple-negative breast cancers (TNBC) treated with durvalumab and standard NAC (n = 48), and (iii) HER2-negative patients treated with standard NAC (n = 87) or NAC and pembrolizumab (n = 66).

Results:

HLA-DR positivity on ≥5% of tumor cells, defined a priori, was observed in 10% and 15% of primary non-immunotherapy–treated hormone receptor–positive and triple-negative breast cancers, respectively. Quantitative assessment of MHC-II on tumor cells was predictive of durvalumab + NAC and pembrolizumab + NAC (ROC AUC, 0.71; P = 0.01 and AUC, 0.73; P = 0.001, respectively), but not NAC alone (AUC, 0.5; P = 0.99).

Conclusions:

Tumor-specific MHC-II has a strong candidacy as a specific biomarker of anti–PD-1/L1 immunotherapy benefit when added to standard NAC in HER2-negative breast cancer. Combined with previous studies in melanoma, MHC-II has the potential to be a pan-cancer biomarker. Validation is warranted in existing and future phase II/III clinical trials in this setting.
Pharmaceutical Interference of the EWS-FLI1–driven Transcriptome By Cotargeting H3K27ac and RNA Polymerase Activity in Ewing Sarcoma
Authors: Heisey Daniel A.R. , Jacob Sheeba , Lochmann Timothy L. , Kurupi Richard , Ghotra Maninderjit S. , Calbert Marissa L. , Shende Mayuri , Maves Yuki Kato , Koblinski Jennifer E. , Dozmorov Mikhail G. , Boikos Sosipatros A. , Benes Cyril H. , Faber Anthony C.
Published: July 2021

The EWSR1-FLI1 t(11;22)(q24;q12) translocation is the hallmark genomic alteration of Ewing sarcoma, a malignancy of the bone and surrounding tissue, predominantly affecting children and adolescents. Although significant progress has been made for the treatment of localized disease, patients with metastasis or who relapse after chemotherapy have less than a 30% five-year survival rate. EWS-FLI1 is currently not clinically druggable, driving the need for more effective targeted therapies. Treatment with the H3K27 demethylase inhibitor, GSK-J4, leads to an increase in H3K27me and a decrease in H3K27ac, a significant event in Ewing sarcoma because H3K27ac associates strongly with EWS-FLI1 binding at enhancers and promoters and subsequent activity of EWS-FLI1 target genes. We were able to identify targets of EWS-FLI1 tumorigenesis directly inhibited by GSK-J4. GSK-J4 disruption of EWS-FLI1-driven transcription was toxic to Ewing sarcoma cells and slowed tumor growth in patient-derived xenografts (PDX) of Ewing sarcoma. Responses were markedly exacerbated by cotreatment with a disruptor of RNA polymerase II activity, the CDK7 inhibitor THZ1. This combination together suppressed EWS-FLI1 target genes and viability of ex vivo PDX Ewing sarcoma cells in a synergistic manner. In PDX models of Ewing Sarcoma, the combination shrank tumors. We present a new therapeutic strategy to treat Ewing sarcoma by decreasing H3K27ac at EWS-FLI1–driven transcripts, exacerbated by blocking phosphorylation of the C-terminal domain of RNA polymerase II to further hinder the EWS-FLI1–driven transcriptome.
Phase I Open-Label Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Dilpacimab in Patients with Advanced Solid Tumors
Authors: Gordon Michael S. , Nemunaitis John , Barve Minal , Wainberg Zev A. , Hamilton Erika P. , Ramanathan Ramesh K. , Sledge George W. , Yue Huibin , Morgan-Lappe Susan E. , Blaney Martha , Kasichayanula Sreeneeranj , Motwani Monica , Wang Lan , Naumovski Louie , Strickler John H.
Published: July 2021

Dilpacimab (formerly ABT-165), a novel dual-variable domain immunoglobulin, targets both delta-like ligand 4 (DLL4) and VEGF pathways. Here, we present safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy data from a phase I study (trial registration ID: NCT01946074) of dilpacimab in patients with advanced solid tumors. Eligible patients (≥18 years) received dilpacimab intravenously on days 1 and 15 in 28-day cycles at escalating dose levels (range, 1.25–7.5 mg/kg) until progressive disease or unacceptable toxicity. As of August 2018, 55 patients with solid tumors were enrolled in the dilpacimab monotherapy dose-escalation and dose-expansion cohorts. The most common treatment-related adverse events (TRAE) included hypertension (60.0%), headache (30.9%), and fatigue (21.8%). A TRAE of special interest was gastrointestinal perforation, occurring in 2 patients (3.6%; 1 with ovarian and 1 with prostate cancer) and resulting in 1 death. The PK of dilpacimab showed a half-life ranging from 4.9 to 9.5 days, and biomarker analysis demonstrated that the drug bound to both VEGF and DLL4 targets. The recommended phase II dose for dilpacimab monotherapy was established as 3.75 mg/kg, primarily on the basis of tolerability through multiple cycles. A partial response was achieved in 10.9% of patients (including 4 of 16 patients with ovarian cancer). The remaining patients had either stable disease (52.7%), progressive disease (23.6%), or were deemed unevaluable (12.7%). These results demonstrate that dilpacimab monotherapy has an acceptable safety profile, with clinical activity observed in patients with advanced solid tumors.
Imaging Reveals Importance of Shape and Flexibility for Glomerular Filtration of Biologics
Authors: Rafidi Hanine , Estevez Alberto , Ferl Gregory Z. , Mandikian Danielle , Stainton Shannon , Sermeño Lauren , Williams Simon P. , Kamath Amrita V. , Koerber James T. , Boswell C. Andrew
Published: July 2021

Advances in antibody engineering have enabled the construction of novel molecular formats in diverse shapes and sizes, providing new opportunities for cancer immunotherapeutic drug discovery while also revealing limitations in knowledge of structure–activity relationships. The current understanding of renal filtration originates largely from data reported for dextrans, IgG, albumin, and selected globular proteins. For a one-armed IgG-based T-cell imaging agent, we observed higher renal signal than typically observed for bivalent IgGs, prompting us to explore the factors governing renal filtration of biologics. We constructed a small representative library of IgG-like formats with varied shapes and hinge flexibilities falling broadly into two categories: branched molecules including bivalent IgG and (scFv)2Fc, and nonbranched molecules including one-armed IgG, one-armed IgG with stacked Fab, and one-armed IgG with a rigid IgA2 hinge. Transmission electron microscopy revealed Y-shaped structures for the branched molecules and pseudo-linear structures for the nonbranched molecules. Single-photon emission CT imaging, autoradiography, and tissue harvest studies demonstrated higher renal uptake and catabolism for nonbranched molecules relative to branched molecules. Among the nonbranched molecules, the one-armed IgG with rigid IgA2 hinge molecule demonstrated higher kidney uptake and decreased systemic exposure relative to molecules with a more flexible hinge. Our results show that differences in shape and hinge flexibility drive the increased glomerular filtration of one-armed relative to bivalent antibodies and highlight the practical advantages of using imaging to assess renal filtration properties. These findings are particularly relevant for T-cell–dependent bispecific molecules, many of which have nonstandard antibody structures.
Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Analysis of Microvascular Permeability in Peritumor Brain Edema of Fibrous Meningiomas
Authors: Xiang Li , Sun Li-Hua , Liu Bin , Wang Long-Sheng , Gong Xi-Jun , Qiu Ju , Ge Ya-Qiong , Yao Wen-Jun , Gu Kang-Chen
Published: July 2021

Introduction: This study aims to analyze the permeability of intra- and peri-meningiomas regions and compare the microvascular permeability between peritumoral brain edema (PTBE) and non-PTBE using DCE-MRI. Methods: This was a retrospective of patients with meningioma who underwent surgery. The patients were grouped as PTBE and non-PTBE. The DCE-MRI quantitative parameters, including volume transfer constant (Ktrans), rate constant (Kep), extracellular volume (Ve), and mean plasma volume (Vp), obtained using the extended Tofts-Kety 2-compartment model. Logistic regression analysis was conducted to explore the risk factor of PTBE. Results: Sixty-three patients, diagnosed as fibrous meningioma, were included in this study. They were 17 males and 46 females, aged from 32 to 88 years old. Kep and Vp were significantly lower in patients with PTBE compared with those without (Kep: 0.1852 ± 0.0369 vs. 0.5087 ± 0.1590, p = 0.010; Vp: 0.0090 ± 0.0020 vs. 0.0521 ± 0.0262, p = 0.007), while there were no differences regarding Ktrans and Ve (both p > 0.05). The multivariable analysis showed that tumor size ≥10 cm3 (OR = 4.457, 95% CI: 1.322–15.031, p = 0.016) and Vp (OR = 0.572, 95%CI: 0.333–0.981, p = 0.044) were independently associated with PTBE in patients with meningiomas. Conclusion: DCE-magnetic resonance imaging·Meningioma·Blood vessel MRI can be used to quantify the microvascular permeability of PTBE in patients with meningioma.
Develop a Clinical Prediction Model for Postoperative Cognitive Dysfunction after Major Noncardiac Surgery in Elderly Patients: A Protocol for a Prospective Observational Study
Authors: Shen Yang , Li Xianchen , Yao Junyan
Published: July 2021

Perioperative neurocognitive disorders (PNDs) refer to cognitive decline identified in the preoperative or postoperative period. It has been reported that the incidence of postoperative neurocognitive impairment after noncardiac surgery in patients older than 65 at 1 week was 25.8∼41.4%, and at 3 months 9.9∼12.7%. PNDs will last months or even develop to permanent dementia, leading to prolonged hospital stays, reduced quality of life, and increased mortality within 1 year. Despite the high incidence and poor prognosis of PNDs in the aged population, no effective clinical prediction model has been established to predict postoperative cognitive decline preoperatively. To develop a clinical prediction model for postoperative neurocognitive dysfunction, a prospective observational study (Clinical trial registration number: ChiCTR2000036304) will be performed in the Shanghai General Hospital during January 2021 to October 2022. A sample size of 675 patients aged >65 years old, male or female, and scheduled for elective major noncardiac surgery will be recruited. A battery of neuropsychological tests will be used to test the cognitive function of patients at 1 week, 1 month, and 3 months postoperatively. We will evaluate the associations of PNDs with a bunch of candidate predictors including general characteristics of patients, blood biomarkers, indices associated with anesthesia and surgery, retinal nerve-fiber layer thickness, and frailty index to develop the clinical prediction model by using multiple logistic regression analysis and least absolute shrinkage and the selection operator (LASSO) method. The k-fold cross-validation method will be utilized to validate the clinical prediction model. In conclusion, this study was aimed to develop a clinical prediction model for postoperative cognitive dysfunction of old patients. It is anticipated that the knowledge gained from this study will facilitate clinical decision-making for anesthetists and surgeons managing the aged patients undergoing noncardiac surgery.
ALT Levels in Treatment-Naive, Chronic Hepatitis B Patients with Concurrent Fatty Liver Disease: A US Nationwide Study
Authors: Chang Christine Y. , Kam Leslie , Dang Nolan , Cheung Ramsey , Nguyen Mindie H.
Published: July 2021

Introduction: Treatment criteria for chronic hepatitis B (CHB) relies on ALT, which can be impacted by concurrent nonalcoholic fatty liver disease (NAFLD), but ALT data on patients with CHB and NAFLD are limited. We aimed to characterize ALT distribution in untreated CHB patients with NAFLD. Methods: We retrospectively analyzed untreated US adults with CHB (533 with NAFLD, 3,172 without NAFLD) using the Clinformatics™ Data Mart Database (2003–2019). The main outcome was ALT elevation (>1× upper limit of normal, 35/25 U/L for men/women, respectively). Secondary outcomes were advanced fibrosis (via FIB-4 index) and factors associated with fibrosis. Results: The majority of patients were Asian (61.0%) and hepatitis B e-antigen (HBeAg)-negative (90.4%). Patients with CHB and NAFLD were older (57.2 vs. 49.5 years, p < 0.001), more likely male (59.3% vs. 46.2%, p < 0.001), with higher percentages of advanced fibrosis (3.6% vs. 2.6%, p < 0.001) than those with CHB alone. CHB-NAFLD patients were more likely to have elevated ALT than those with CHB only, but this difference was only significant among those with low hepatitis B virus (HBV) DNA (38.1% vs. 25.6%, p < 0.001), not those with higher HBV DNA (>2,000 IU/mL). After adjusting for HBeAg, HBV DNA, and diabetes, NAFLD was not independently associated with advanced fibrosis (odds ratio 1.18, 95% confidence interval: 0.30–4.59, p = 0.81). Discussion: CHB-NAFLD patients with HBV DNA below treatment threshold were more likely to have elevated ALT but not those with higher HBV DNA, suggesting that ALT threshold does not need to be raised for antiviral eligibility for CHB with NAFLD.
Secured protection of transmission line by distance relay using data mining approach
Authors: Kiruthika M. , S. Bindu
Published: July 2021

Distance relay is one of the most important protection element of a transmission line used in protection schemes. Relay may malfunction if it is not able to distinguish faults from system stressed conditions. This work mainly focusses on enhancing the performance of the distance relay in a secured manner based on data mining approach which uses two phases of classification. Level 1 classifier identifies the system conditions like normal, fault, and power swing and level 2 classifier gets initiated when there is a power swing and distinguishes between the persistence of power swing condition and a three-phase fault. In both the phases, the protection scheme in the respective zone where the fault occurred gets activated. The proposed methodology is tested for an IEEE 9-bus system wherein the data is collected from phasor measurement units placed in optimal locations. Optimal PMU placement is economical since it overcomes issues like cost, communication infrastructure issues, maintenance and complexity. The results proved that the proposed method is effective with good efficiency and higher accuracy with less number of PMUs.
Work function variations on electrostatic and RF performances of JLSDGM Device
Authors: E. Kaharudin K K. , Salehuddin F. , M. Zain A. S. , Roslan Ameer F. , Ahmad I
Published: July 2021

This paper offers a systematic analysis on the impact of work function (WF) variations on electrostatic and radio frequency (RF) performances of nchannel junctionless strained double gate (DG) (n-JLSDGM) metal oxide semiconductor field effect transistor (MOSFET). The study has been performed under othe constant level of design parameters that operates in saturation as a transconductance amplifier, considering the dependence of electrostatic and RF performance on the variation of WF. Furthermore, this paper aims to provide physical insight into the improved electrostatic and RF performances of the proposed n-JLSDGM device. The device layout and characteristics were designed and extracted respectively via a comprehensive 2-D simulation. Device performances such as on-state current (ION), off-state current (IOFF), on-off current ratio, subthreshold swing (SS), intrinsic capacitances, dynamic power dissipation (Pdyn), cut-off frequency (fT) and maximum oscillation frequency (fmax) are intensively investigated in conjunction with WF variations.