bluuebunny/crossref_metadata_2025 huggingface dataset:
Forcing a change: a learn-by-doing workshop on circadian rhythms to understand the complexities of human physiology
Authors: Azpeleta Clara , Santos Pablo , Sobrado Antonio , Lesmes Marta , Gal Beatriz
Published: June 2021

Physiology is an integrative science that requires an understanding of the organism as a whole to acquire a deep comprehension of its functions and avoid misconceptions that may impair further learning. Thus it is necessary to develop resources that promote the integrative vision that Physiology requires. Chronobiology is a challenging discipline and one of the least addressed concepts in Physiology curricula. The activity here presented proposes a workshop with a theoretical-practical perspective in the context of the Neuroscience Conferences held annually at our university. All conference presentations are neuroscience-related topics, in combination with practical activities, some of them analyzing variables of the students themselves. We chose to assess this informal teaching scenario to involve the students with a scientific perspective while learning and hoping to increase their appreciation for different topics related to neuroscience. Specifically for this activity on chronobiology, the evaluation was carried out via a survey study including quantitative and qualitative questions and semistructured personal interviews. In general, the results reveal a very positive opinion from students regarding aspects such as the teaching methodology, the organization before and during the activity or the added value of the experience for their future professional performance. Some of the students stated they were more aware of the importance of their circadian system and even changed some of their personal daily routines after the activity. Such positive feedback encourages us to continue working in this theoretical-practical format in the future, as it contributes to improving students’ perception of their own learning.
An FPGA‐Based Convolutional Neural Network Coprocessor
Authors: Qiu Changpei , Wang Xin’an , Zhao Tianxia , Li Qiuping , Wang Bo , Wang Hu
Published: June 2021

In this paper, an FPGA‐based convolutional neural network coprocessor is proposed. The coprocessor has a 1D convolutional computation unit PE in row stationary (RS) streaming mode and a 3D convolutional computation unit PE chain in pulsating array structure. The coprocessor can flexibly control the number of PE array openings according to the number of output channels of the convolutional layer. In this paper, we design a storage system with multilevel cache, and the global cache uses multiple broadcasts to distribute data to local caches and propose an image segmentation method that is compatible with the hardware architecture. The proposed coprocessor implements the convolutional and pooling layers of the VGG16 neural network model, in which the activation value, weight value, and bias value are quantized using 16‐bit fixed‐point quantization, with a peak computational performance of 316.0 GOP/s and an average computational performance of 62.54 GOP/s at a clock frequency of 200 MHz and a power consumption of about 9.25 W.
A Constitutive Model of Sandy Gravel Soil under Large‐Sized Loading/Unloading Triaxial Tests
Authors: Zhang Pengfei , Liu Han , Feng Zhentu , Jia Chaofeng , Zhou Rui
Published: June 2021

Based on large‐scale triaxial tests of sandy gravel materials, the strength and deformation characteristics under loading/unloading conditions are analyzed. At the same time, the applicability of the hyperbolic constitutive model to sandy gravel is studied using experimental data. The results indicate that sandy gravel under low confining pressures (0.2 and 0.4 MPa) shows a weak softening trend; the higher the confining pressure, the more obvious the hardening tendency (0.6 and 0.8 MPa) and the greater the peak strength. During unloading tests, strain softening occurs, and the peak strength increases with increasing confining pressure. During loading tests, dilatancy appears when the confining pressure is low (0.2 MPa). With increasing confining pressure (0.4, 0.6, and 0.8 MPa), the dilatancy trend gradually weakens, and the cumulative volume tric strain increases, which reflects the relevance of the stress paths. Through research, it is found that the hyperbolic constitutive model has good applicability to sandy gravel soils, and the corresponding model parameters are obtained.
A General Fourier Formulation for In‐Plane and Out‐of‐Plane Vibration Analysis of Curved Beams
Authors: Nie Rui , Li Tianyun , Zhu Xiang , Zhou Huihui
Published: June 2021

Based on the principle of energy variation, an improved Fourier series is introduced as an allowable displacement function. This paper constructs a calculation model that can study the in‐plane and out‐of‐plane free and forced vibrations of curved beam structures under different boundary conditions. Firstly, based on the generalized shell theory, considering the shear and inertial effects of curved beam structures, as well as the coupling effects of displacement components, the kinetic energy and strain potential energy of the curved beam are obtained. Subsequently, an artificial spring system is introduced to satisfy the constraint condition of the displacement at the boundary of the curved beam, obtain its elastic potential energy, and add it to the system energy functional. Any concentrated mass point or concentrated external load can also be added to the energy function of the entire system with a corresponding energy term. In various situations including classical boundary conditions, the accuracy and efficiency of the method in this paper are proved by comparing with the calculation results of FEM. Besides, by accurately calculating the vibration characteristics of common engineering structures like slow curvature (whirl line), the wide application prospects of this method are shown.
Investigation into the Adsorption of Methylene Blue and Methyl Orange by UiO-66-NO2 Nanoparticles
Authors: Dinh Hien Thi , Tran Nam Trung , Trinh Dai Xuan
Published: June 2021

In this work, the adsorptive removal of methylene blue and methyl orange by UiO-66-NO2 nanoparticles was studied. The influence of pH on the adsorption capacity was assessed. The kinetics of the adsorption process were investigated and compared with pseudo-first-order, pseudo-second-order, Elovich, and intraparticle models. The kinetics of the adsorption fits moderately with the pseudo-first-order, but perfectly fits with pseudo-second-order models, and has a very good fit with the Elovich and intraparticle models. The adsorption isotherms were measured and compared with the Langmuir and Freundlich models. The adsorption capacity of methyl orange (MO) on UiO-66-NO2 nanoparticles (142.9 mg/g) was over three times higher than that of methylene blue (MB) on the nanoparticles (41.7 mg/g). The discrepancy between these capacities was attributed to the presence of the -NO2 functional group, which caused a strong negative mesomeric effect in the metal-organic framework structure.
High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS
Authors: Qin Nankun , Jiang Yue , Shi Wenjun , Wang Liting , Kong Lingbo , Wang Chengxiang , Guo Yuying , Zhang Jiayu , Ma Qun
Published: June 2021

Hyperuricemia (HUA) as a metabolic disease is closely associated with metabolic disorders. The etiology and pathogenesis of HUA are not fully understood, so there is no radical cure so far. Metabolomics, a specialized study of endogenous small molecule substances, has become a powerful tool for metabolic pathway analysis of selected differential metabolites, which is helpful for initially revealing possible development mechanisms of various human diseases. Twenty HUA patients and 20 healthy individuals participated in the experiment, and ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was employed to investigate serum samples to find differential metabolites. The statistical techniques used were principal component analysis and orthogonal partial least-squares discriminant analysis. The differences in metabolomics results of samples after pretreatment with different solvents were compared, 38, 20, 26, 28, 33, 50, and 40 potential differential metabolites were found, respectively, in HUA patient samples, and each group involved different metabolic pathways. Repetitive metabolites were removed, 138 differential metabolites in HUA serum were integrated for analysis, and the human body was affected by 7 metabolic pathways of glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and α-linolenic acid metabolism. In this work, the metabolomics approach based on UPLC-Q-TOF/MS was employed to investigate serum metabolic changes in HUA patients, 138 potential differential metabolites related to HUA were identified, which provided associations of lipids, amino acids, fatty acids, organic acids, and nucleosides profiles of HUA individuals. Metabolic pathways involved in glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and a-linolenic acid metabolism shed light on the understanding of the etiology and pathogenesis process of HUA.
FCNN: An Efficient Intrusion Detection Method Based on Raw Network Traffic
Authors: Wang Yue , Jiang Yiming , Lan Julong
Published: June 2021

When traditional machine learning methods are applied to network intrusion detection, they need to rely on expert knowledge to extract feature vectors in advance, which incurs lack of flexibility and versatility. Recently, deep learning methods have shown superior performance compared with traditional machine learning methods. Deep learning methods can learn the raw data directly, but they are faced with expensive computing cost. To solve this problem, a preprocessing method based on multipacket input unit and compression is proposed, which takes m data packets as the input unit to maximize the retention of information and greatly compresses the raw traffic to shorten the data learning and training time. In our proposed method, the CNN network structure is optimized and the weights of some convolution layers are assigned directly by using the Gabor filter. Experimental results on the benchmark data set show that compared with the existing models, the proposed method improves the detection accuracy by 2.49% and reduces the training time by 62.1%. In addition, the experiments show that the proposed compression method has obvious advantages in detection accuracy and computational efficiency compared with the existing compression methods.
Energy Action Mechanism of Coal and Gas Outburst Induced by Rockburst
Authors: Zhang Wenqing , Mu Chaomin , Xu Dengke , Li Zhongqing
Published: June 2021

The essence of both rockburst and coal and gas outburst lies in fast energy release. In order to explore the energy action mechanism of coal and gas outburst induced by rockburst in rockburst and coal and gas outburst combined mines, the split Hopkinson pressure bar (SHPB) experimental device was firstly used to conduct uniaxial impact failure test of coal specimens prone to outburst under different strain rates, and their energy dissipation laws under impact loading were obtained. Next, under the engineering background of coal and gas dynamic phenomena induced by rockburst with different intensities in Xinyi Coal Mine and Pingdingshan Coal Group No. 12 Colliery in Henan Province and Dingji Coal Mine of Huainan Mining Group in Anhui Province, experimental study results were combined with numerical simulation analysis to discuss the energy mechanism of coal and gas outburst induced by rockburst. The study results show that the outburst can be divided into two different processes—critical outburst and outburst—according to the evolution law of outburst energy, and the critical energy conditions for coal and gas outburst are proposed. The minimum destructive energy range for the critical outburst of coal mass is obtained as (5–10) × 104 J/m3. Under some low gas, high stress, or strong disturbance conditions, applied loads can become the main energy sources causing critical failure and even crushing and throwing of coal mass. The coal mass will present an interval splitting structure under dynamic loading, which is obviously different from the failure mode of coal mass under static actions.
The Impact of Icing on the Airfoil on the Lift-Drag Characteristics and Maneuverability Characteristics
Authors: Wang Kang , Xue Yuan , Tian Hongfeng , Wang Miaosen , Wang Xiaolong
Published: June 2021

Icing has now become an important factor endangering flight safety. This paper takes the icing data of the NACA 23012 airfoil as an example, establishes an icing influence model for real-time simulation based on icing time and aircraft angle of attack, and analyzes the influence of different icing geometry on aircraft characteristics. The two-dimensional interpolation method is used to improve the model of the aircraft’s stall area, which is mainly divided into the correction of the lift-drag coefficient linear area and the stall area and the correction of the aircraft stability derivative and the control derivative. The aerodynamic equation of the airplane after icing is established, and the modal analysis of the airplane under different icing conditions is completed through the linearization of the flight equation. The closed-loop simulation system of the altitude holding mode and roll attitude holding mode is used to calculate and analyze the flight quality changes of the aircraft after the wing surface is frozen. The analysis results show that, under icing conditions, in the range of small angles of attack, icing has no obvious influence on the aircraft mode. As the degree of icing increases, the throttle skewness and the negative deflection angle of the airplane’s level flight requirements continue to increase. The case of icing flight in altitude hold and roll hold modes shows that flying in the autopilot mode under severe icing conditions is very dangerous and is prone to cause the aircraft to stall.
Skin Diseases in a Pediatric Hospital of Nepal
Authors: Jahan Roushan , Khanal Shreedhar , Shrestha Shraddha , Parajuli Niraj
Published: June 2021

The skin diseases of pediatric population are varied which change according to age and season. There is a rarity of studies on pediatric skin conditions from Nepal. This observational study from the only tertiary care referral pediatric center of the country highlighted the burden of pediatric skin diseases in Nepalese population. All new cases of pediatric patients less than 14 years of age consulting the pediatric dermatological OPD of Kanti Children’s Hospital from January 2017 to December 2017 were included in this study. Demographic details of all the patients such as age and sex were recorded. The diagnosis was made clinically in most instances and appropriate laboratory and histopathological examination were performed wherever necessary. A total of 7683 pediatric patients were included in the study. Among these, there were 4574 (59.53%) males and 3109 (40.47%) females. The most common skin condition was infections among 2463 (32.12%) followed by eczematous conditions in 1711(22.27%) and hypersensitivity reactions in 1510 (19.65%). Infections were more common during the summer months. Overall, both infectious and noninfectious skin diseases were significantly more common during the warmer (summer and spring) months as compared to colder (autumn and winter) months (

p
<
0.001

). This study shows that the pediatric dermatoses are common in Nepalese population.
A Countable System of Fractional Inclusions with Periodic, Almost, and Antiperiodic Boundary Conditions
Authors: Salem Ahmed , Al-Dosari Aeshah
Published: June 2021

This article is dedicated to the existence results of solutions for boundary value problems of inclusion type. We suggest the infinite countable system to fractional differential inclusions written by . The mappings are proposed to be Lipschitz multivalued mappings. The results are explored according to boundary condition σνi(0) = γνi(ρ),   σ, γ ∈ ℝ. This type of condition is the generalization of periodic, almost, and antiperiodic types.
The Method for Determining Optimal Analysis Length of Vibration Data Based on Improved Multiscale Permutation Entropy
Authors: Zhang Jianwei , Li Ziyu , Yan Peng , Li Yang , Huang Jinlin
Published: June 2021

Research on damage diagnosis or safety monitoring based on structural vibration response is one of the hot issues in the engineering field. The characteristic information of the structure is obtained by analyzing the structure response data. In the process of data analysis, the choice of data length is very important, which is related to the validity of the structure monitoring results. At present, the selection of data length is usually subjective, which reduces the rigor of the structure monitoring process. Therefore, a method based on improved multiscale permutation entropy (IMPE) is proposed to determine the optimal data analytical length (ODAL) of vibration data. This method creatively applies multiscale permutation entropy (MPE) to the field of data length analysis when processing nonlinear and nonstationary signals and optimizes MPE with the help of the improved coarse‐grained method to obtain IMPE. IMPE is sensitive to different data lengths, and the entropy changes with the increase of the data length and tends to be stable. Here, the stable value is defined as a standard entropy. The entropy satisfying 97% of the standard entropy is used as the effective entropy, and the corresponding data length value of the effective entropy is selected as the ODAL of the vibration data. This method is suitable for many fields, provides a reliable data analytical length for data analysis, and has good engineering practicability.
Regulation of Dendrobium Polysaccharides on Proliferation and Oxidative Stress of Human Umbilical Vein Endothelial Cells in the High Glucose Environment
Authors: Li Yajia , Cao Ziqin , Jia Limin , Huang Yanfei , Shi Meilan , Li Qiangxiang
Published: June 2021

Backgrounds. Polysaccharides of Dendrobium candidum (PDC) showed a strong antioxidant effect on islet cells while the effects of PDC on human umbilical vein endothelial cells (HUVECs) under the high glucose condition remain unclear. Material and Method. HUVECs were incubated with high glucose (33.3 mmol/L) for 48 hours to induce injury, and cells were treated with PDC (100, 200, and 400 μg/mL) for 48 hours. The tetrazolium blue colorimetric (MTT) assay was used to detect cell proliferation, superoxide dismutase (SOD), and nitric oxide (NO) content in cell supernatants. Flow cytometry was used to detect reactive oxygen species (ROS) and calcium levels. Results. (1) Compared with the control group, the proliferation of HUVECs cells in the high glucose (33.3 mmol/L) group decreased (

P
<
0.05

). The intracellular calcium ion concentration and the intracellular ROS level increased (

P
<
0.01

and

P
<
0.05

). SOD activity and the level of NO in the culture medium were reduced (P <0.05). (2) Compared with the control group, PDC (50, 100, 200, 400, and 800 μg/mL) did not significantly affect the cell proliferation of HUVECs (

P
>
0.05

). (3) Compared with the high glucose group, the HUVEC cell viability of the high glucose + PDC (100, 200, and 400 μg/mL) group increased while the intracellular calcium ion concentration decreased in a concentration-dependent manner (

P
<
0.05

). Intracellular ROS levels were reduced, while SOD activity and the level of NO in culture fluids increased (

P
<
0.05

). Conclusion. PDC can promote the proliferation of HUVECs in the high glucose environment by reducing oxidative stress injury of HUVECs induced by high glucose.
Prediction of Train Arrival Delay Using Hybrid ELM-PSO Approach
Authors: Bao Xu , Li Yanqiu , Li Jianmin , Shi Rui , Ding Xin
Published: June 2021

In this study, a hybrid method combining extreme learning machine (ELM) and particle swarm optimization (PSO) is proposed to forecast train arrival delays that can be used for later delay management and timetable optimization. First, nine characteristics (e.g., buffer time, the train number, and station code) associated with train arrival delays are chosen and analyzed using extra trees classifier. Next, an ELM with one hidden layer is developed to predict train arrival delays by considering these characteristics mentioned before as input features. Furthermore, the PSO algorithm is chosen to optimize the hyperparameter of the ELM compared to Bayesian optimization and genetic algorithm solving the arduousness problem of manual regulating. Finally, a case is studied to confirm the advantage of the proposed model. Contrasted to four baseline models (k-nearest neighbor, categorical boosting, Lasso, and gradient boosting decision tree) across different metrics, the proposed model is demonstrated to be proficient and achieve the highest prediction accuracy. In addition, through a detailed analysis of the prediction error, it is found that our model possesses good robustness and correctness.
The Prevalence of Dental Anxiety Associated with Pain among Chinese Adult Patients in Guangzhou
Authors: Yu Jiali , Jiang Rui , Nie Er-Min , Zhang Chun-Yuan , Li Xiang
Published: June 2021

Background. Anxious people appear to exaggerate the severity of aversive experiences such as anxiety and pain. Anxiety towards dental procedures is a common difficulty that may be experienced by dental patients all over the world. The goal of the study is to find out the prevalence of dental anxiety and its associated factors in Chinese adult patients. Methods. A cross-sectional study was conducted on 183 dental adult patients whose age ranged from 18 to 70 years. Demographic details, first and most recent dental visits with experience, the MDAS, and the Visual Analogue Scale for Anxiety (VAS-A) were obtained. Data were analyzed by frequency analysis, chi-square test, and Spearman correlation test. Results. Most of the respondents were female (68.9%) and 30–45 years age group. The mean total score for dental anxiety on the MDAS was 13.63 (3.1). 80.3% of participants suffered from moderate or high dental anxiety. Age must show a strong association with dental anxiety among the participants (

p
=
0.011

). The first dental visit experience, the frequency of the dental visit, most recent dental experience, length of time since the most recent dental visit, and postponement of the dental visit are strongly associated with the MDAS score (

p
=
0.001

). Conclusions. The MDAS score exhibits that Chinese adult patients have significant dental anxiety and phobia. Identifying patients with dental anxiety as soon as possible is essential to providing better dental care.
An Efficient Finite Element Method and Error Analysis for Schrödinger Equation with Inverse Square Singular Potential
Authors: Zhang Hui , Lin Fubiao , Cao Junying
Published: June 2021

We provide in this study an effective finite element method of the Schrödinger equation with inverse square singular potential on circular domain. By introducing proper polar condition and weighted Sobolev space, we overcome the difficulty of singularity caused by polar coordinates’ transformation and singular potential, and the weak form and the corresponding discrete scheme based on the dimension reduction scheme are established. Then, using the approximation properties of the interpolation operator, we prove the error estimates of approximation solutions. Finally, we give a large number of numerical examples, and the numerical results show the effectiveness of the algorithm and the correctness of the theoretical results.
Three‐Dimensional Finite Difference Analysis on the Ground‐Sequential Tunneling‐Superstructure Interaction
Authors: Lakirouhani Ali , Jafari Reyhaneh , Hasanzadehshooiili Hadi
Published: June 2021

In this paper, a three‐dimensional finite difference analysis is presented to investigate the interactive effects of sequential tunneling and the superstructure on the settlement profile of the ground. To simulate the practical sequential tunneling procedure, tunnel excavation is conducted in a step‐by‐step framework; tunnel excavation starts from the beginning of the model and is updated in a continuous manner, and the installation of the tunnel support system is done with a delay step compared to tunnel excavation. The numerical modeling accuracy is validated using the available analytical and numerical solutions for both two‐dimensional and three‐dimensional simplified cases. The well‐validated modeling procedure is adopted to investigate effects of tunnel diameter, depth of tunneling, and number of superstructure stories on the profile of occurring settlements. Two cases of free‐field and three‐dimensional superstructural modeling are compared with regard to the effect of tunneling. In addition, the effect of tunneling advancement on the generation of excess structural forces and moments are studied as another important factor in the soil‐tunneling‐superstructure interaction problem. It is observed that, in the free‐field case, with advancing the tunnel face, the longitudinal settlement profiles approach the steady‐state condition and the maximum ground settlement tends to converge to a specific value, whereas as the tunnel passes under a structure, the settlement increases steadily as the tunnel progresses. There is a direct relationship between the depth and diameter of the tunnel and the settlement. In addition, the effect of the number of superstructure stories on the maximum settlement is more considerable compared to the free‐field condition. According to the results, when the tunnel passes under 8‐story and 12‐story structures, the maximum settlement increases by 40% and 70%, respectively, compared to the free‐field condition. It is also shown that tunneling‐induced settlements result in the regeneration of structural forces.
Applied Research of Knowledge in the Field of Artificial Intelligence in the Intelligent Retrieval of Teaching Resources
Authors: Bai XuJing , Li JiaJun
Published: June 2021

In the development process of education informatization, digital teaching resources continue to grow, and how to manage and organize massive teaching resources has become a key issue for teaching staff. An efficient and accurate search system is an important part of the teaching resource service system. The use of intelligent search engines can search teaching resources comprehensively and efficiently, and the artificial intelligence search engine provides a reliable and convenient solution for the design and development of intelligent search systems. The article analyzes the design principles and technical standards of the intelligent search system, expounds the system’s functional architecture and database design, and introduces the realization process and principles of the search system. By analyzing the characteristics of basic education resources and existing automatic abstracting methods, this paper proposes to integrate the calculated feature word weights in the field of basic education into the algorithm for calculating the weights of abstract sentences and simultaneously examine the sentence position, sentence length, and other texts. There is an automatic summarization algorithm for surface statistics. This article also introduces the search design ideas and implementation steps based on artificial intelligence, makes a scientific evaluation and summary of the actual situation of the automatic abstract system running in the basic education resource search engine, and looks forward to the next improvement work.
BMSC‐Derived Exosomes Ameliorate LPS‐Induced Acute Lung Injury by miR‐384‐5p‐Controlled Alveolar Macrophage Autophagy
Authors: Liu Xuan , Gao Chengjin , Wang Yang , Niu Lei , Jiang Shaowei , Pan Shuming
Published: June 2021

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common critical diseases. Bone marrow mesenchymal stem cell (BMSC) transplantation is previously shown to effectively rescue injured lung tissues. The therapeutic mechanism of BMSC‐derived exosomes is not fully understood. Here, we investigated the BMSC‐derived exosomal microRNAs (miRNAs) on effecting lipopolysaccharide‐ (LPS‐) induced ALI and its mechanism. In vitro, rat alveolar macrophages were treated with or without exosomes in the presence of 10 μg/ml LPS for 24 h. Cell viability was determined with Cell Counting Kit‐8 assay. Apoptotic ratio was determined with TUNEL and Annexin V‐FITC/PI double staining. The levels of miR‐384‐5p and autophagy‐associated genes were measured by RT‐qPCR and western blot. Autophagy was observed by TEM and assessed by means of the mRFP‐GFP‐LC3 adenovirus transfection assay. In vivo, we constructed LPS‐induced ALI rat models. Exosomes were injected into rats via the caudal vein or trachea 4 h later after LPS treatment. The lung histological pathology was determined by H&E staining. Pulmonary vascular permeability was assessed by wet‐to‐dry weight ratio and Evans blue dye leakage assay, and inflammatory cytokines in serum and BALF were measured by ELISA. Furthermore, the therapeutic mechanism involved in miR‐384‐5p and Beclin‐1 was determined. The results showed that BMSC‐derived exosomes were taken up by the alveolar macrophages and attenuated LPS‐induced alveolar macrophage viability loss and apoptosis. Exosomes effectively improved the survival rate of ALI rats within 7 days, which was associated with alleviating lung pathological changes and pulmonary vascular permeability and attenuating inflammatory response. Furthermore, this study for the first time found that miR‐384‐5p was enriched in BMSC‐derived exosomes, and exosomal miR‐384‐5p resulted in relieving LPS‐injured autophagy disorder in alveolar macrophages by targeting Beclin‐1. Therefore, exosomal miR‐384‐5p could be demonstrated as a promising therapeutic strategy for ALI/ARDS.
Learning Behavior Analysis Using Clustering and Evolutionary Error Correcting Output Code Algorithms in Small Private Online Courses
Authors: Xie Shu-tong , Chen Qiong , Liu Kun-hong , Kong Qing-zhao , Cao Xiu-juan
Published: June 2021

In recent years, online and offline teaching activities have been combined by the Small Private Online Course (SPOC) teaching activities, which can achieve a better teaching result. Therefore, colleges around the world have widely carried out SPOC-based blending teaching. Particularly in this year’s epidemic, the online education platform has accumulated lots of education data. In this paper, we collected the student behavior log data during the blending teaching process of the “College Information Technology Fundamentals” course of three colleges to conduct student learning behavior analysis and learning outcome prediction. Firstly, data collection and preprocessing are carried out; cluster analysis is performed by using k-means algorithms. Four typical learning behavior patterns have been obtained from previous research, and these patterns were analyzed in terms of teaching videos, quizzes, and platform visits. Secondly, a multiclass classification framework, which combines a feature selection method based on genetic algorithm (GA) with the error correcting output code (ECOC) method, is designed for training the classification model to achieve the prediction of grade levels of students. The experimental results show that the multiclass classification method proposed in this paper can effectively predict the grade of performance, with an average accuracy rate of over 75%. The research results help to implement personalized teaching for students with different grades and learning patterns.
CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?
Authors: Miggelbrink Alexandra M. , Jackson Joshua D. , Lorrey Selena J. , Srinivasan Ethan S. , Waibl-Polania Jessica , Wilkinson Daniel S. , Fecci Peter E.
Published: June 2021

In chronic infections and in cancer, persistent antigen stimulation under suboptimal conditions can lead to the induction of T-cell exhaustion. Exhausted T cells are characterized by an increased expression of inhibitory markers and a progressive and hierarchical loss of function. Although cancer-induced exhaustion in CD8 T cells has been well-characterized and identified as a therapeutic target (i.e., via checkpoint inhibition), in-depth analyses of exhaustion in other immune cell types, including CD4 T cells, is wanting. While perhaps attributable to the contextual discovery of exhaustion amidst chronic viral infection, the lack of thorough inquiry into CD4 T-cell exhaustion is particularly surprising given their important role in orchestrating immune responses through T-helper and direct cytotoxic functions. Current work suggests that CD4 T-cell exhaustion may indeed be prevalent, and as CD4 T cells have been implicated in various disease pathologies, such exhaustion is likely to be clinically relevant. Defining phenotypic exhaustion in the various CD4 T-cell subsets and how it influences immune responses and disease severity will be crucial to understanding collective immune dysfunction in a variety of pathologies. In this review, we will discuss mechanistic and clinical evidence for CD4 T-cell exhaustion in cancer. Further insight into the derivation and manifestation of exhaustive processes in CD4 T cells could reveal novel therapeutic targets to abrogate CD4 T-cell exhaustion in cancer and induce a robust antitumor immune response.
Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening
Authors: Lalazar Gadi , Requena David , Ramos-Espiritu Lavoisier , Ng Denise , Bhola Patrick D. , de Jong Ype P. , Wang Ruisi , Narayan Nicole J.C. , Shebl Bassem , Levin Solomon , Michailidis Eleftherios , Kabbani Mohammad , Vercauteren Koen O.A. , Hurley Arlene M. , Farber Benjamin A. , Hammond William J. , Saltsman James A. , Weinberg Ethan M. , Glickman J. Fraser , Lyons Barbara A. , Ellison Jessica , Schadde Erik , Hertl Martin , Leiting Jennifer L. , Truty Mark J. , Smoot Rory L. , Tierney Faith , Kato Tomoaki , Wendel Hans-Guido , LaQuaglia Michael P. , Rice Charles M. , Letai Anthony , Coffino Philip , Torbenson Michael S. , Ortiz Michael V. , Simon Sanford M.
Published: June 2021

To repurpose therapeutics for fibrolamellar carcinoma (FLC), we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the antiapoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable.

Significance:

Therapeutics informed by genomics have not yielded effective therapies for FLC. A functional screen identified TOPO1, HDAC inhibitors, and napabucasin as efficacious and synergistic with inhibition of Bcl-xL. Validation on cells dissociated directly from patient tumors demonstrates the ability for functional precision medicine in a solid tumor.

This article is highlighted in the In This Issue feature, p. 2355
Characterizing the Complexities of Neutrophils with Suppressive Properties
Authors: Cassatella Marco Antonio
Published: June 2021

Several not-yet fully described neutrophil populations exerting either antitumor or suppressive/protumor functions may appear in the circulation of patients with cancer and/or infiltrate tumor tissues. In this issue, Emmons and colleagues provide new information on how complement-dependent “activation” of normal mature neutrophils renders the cells able to inhibit T-cell responsiveness in vitro. The data highlight the complexities of understanding the biology of neutrophil-mediated T-cell suppression.

See related article by Emmons et al., p. 790.
Heparin for Vertebral Intraluminal Thrombus Causing Retroperitoneal Hemorrhage from Occult Renal Angiomyolipoma
Authors: Hsieh Billie , Tariq Muhammad B. , Ibrahim Lamya , Khanpara Shekhar D. , Kramer Larry A. , Savitz Sean I.
Published: June 2021

Stroke is a common cause of mortality and serious long-term disability worldwide. In the acute setting, current American Heart Association/American Stroke Association guidelines do not recommend routine anticoagulation for the management of acute ischemic strokes. However, short-term use of unfractionated heparin (UFH) in select subpopulations has demonstrated improved outcomes. While tools such as CHADSVASC and HASBLED scores are useful in stratifying risk of long-term anticoagulation in patients with nonvalvular atrial fibrillation and additional risk factors, the carefully selected patient populations for the design of these studies do not account for risk of hemorrhage from other preexisting conditions. Here, we present a patient with a posterior circulation intraluminal thrombus treated with UFH, who manifested with a near-fatal intra-abdominal hemorrhage from a previously undetected renal angiomyolipoma (AML).
Myopia Control with Combination Low-Dose Atropine and Peripheral Defocus Soft Contact Lenses: A Case Series
Authors: Erdinest Nir , London Naomi , Levinger Nadav , Morad Yair
Published: June 2021

The goal of this retrospective case series is to demonstrate the effectivity of combination low-dose atropine therapy with peripheral defocus, double concentric circle design with a center distance soft contact lenses at controlling myopia progression over 1 year of treatment. Included in this series are 3 female children aged 8–10 years with progressing myopia averaging −4.37 ± 0.88 D at the beginning of treatment. Their average annual myopic progression during the 3 years prior to therapy was 1.12 ± 0.75 D. They had not attempted any myopia control treatments prior to this therapy. The children were treated with a combination of 0.01% atropine therapy with spherical peripheral defocus daily replacement soft lenses MiSight® 1 day (Cooper Vision, Phoenix, AZ, USA). They underwent cycloplegic refraction, and a slit-lamp evaluation every 6 months which confirmed no adverse reactions or staining was present. Each of the 3 children exhibited an average of 0.25 ± 0.25 D of myopia progression at the end of 1 year of treatment. To the best of the authors’ knowledge, this is the first published study exhibiting that combining low-dose atropine and peripheral defocus soft contact lenses is effective at controlling children’s moderate to severe myopia progression during 1 year of therapy.
Extracorporeal Blood Purification in Moderate and Severe COVID-19 Patients: A Prospective Cohort Study
Authors: Rosalia Rodney Alexander , Ugurov Petar , Neziri Dashurie , Despotovska Simona , Kostoska Emilija , Veljanovska-Kiridjievska Lidija , Kuzmanov Dimche , Trifunovski Aleksandar , Popevski Dijana , Villa Gianluca , Mitrev Zan
Published: June 2021

Introduction: Coronavirus disease 2019 (COVID-19) is characterized by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and with critical cases progressing to acute respiratory distress syndrome. Control of hyperinflammation has been proposed as a possible therapeutic avenue for COVID-19; extracorporeal blood purification (EBP) modalities offer an attractive mean to ameliorate maladaptive inflammation. With this work, we evaluated the longitudinal changes of systemic inflammatory markers in critically ill COVID-19 patients treated with blood purification using AN69ST (oXiris®) haemofilter. Methods: We performed a time-series analysis of 44 consecutive COVID-19 cases treated with the AN69ST (oXiris®) cytokine adsorbing haemofilter (CAH) according to local practice; we visualize longitudinal results of biochemical, inflammatory, blood gas, and vital sign parameters focussing on systemic levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. Results: All patients were treated with ≥1 cycle extracorporeal continuous venovenous haemofiltration (CVVH) with CAH; of these, 30 severe patients received CVVH-CAH within 4–12 h of admission after recognizing a hyper-inflammatory state. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and were placed on EBP during hospitalization. The treatment was associated with a reduction of ferritin, CRP, fibrinogen, several inflammatory markers, and a resolution of numerous cytopenias. The observed mortality across the cohort was 36.3%. Conclusion: EBP with CAH was associated with a decrease in CRP, and control of IL-6 and procalcitonin.
Rituximab Treatment in a Patient with Kimura Disease and Membranous Nephropathy: Case Report
Authors: Vissing-Uhre Roald , Hansen Alastair , Frevert Susanne , Hansen Ditte
Published: June 2021

Kimura disease (KD) is a chronic, inflammatory disorder with slowly developing subcutaneous tumor-like swellings, often occurring in the head and neck region. KD is diagnosed based on histology, elevated levels of immunoglobulin type E, and increased peripheral eosinophil granulocytes. KD may coexist with glomerular renal diseases, and this case report is based on a patient with KD-associated membranous nephropathy. Patients with membranous nephropathy without KD have demonstrated responsiveness to treatment with monoclonal anti-CD20 antibodies. This case report is the first to investigate the effect of rituximab treatment in a patient with KD-associated membranous nephropathy. A 30-year-old Italian man living in Denmark was diagnosed with Kimura’s disease based on subcutaneous nodules with eosinophil angiolymphoid hyperplasia. The patient was admitted to the hospital due to nephrotic syndrome. Serology showed eosinophil granulocytosis and negative PLA2-receptor antibody. Renal biopsy showed membranous nephropathy, and the patient was treated with systemic methylprednisolone followed by cyclosporin and then cyclophosphamide with only partial remission. Ultimately, treatment with intravenous rituximab was initiated, which resulted in overall remission and no nephrotic relapses at 30 months of follow-up. Thus, intravenous rituximab effectively decreased proteinuria and prevented nephrotic relapses in a patient with treatment-refractory membranous nephropathy due to KD.
Lenin’s Stroke
Authors: Nighoghossian Norbert , Cho Tae-Hee , Mechtouff Laura
Published: June 2021

Lenin’s stroke remains a matter of debate. Here, we propose to assess the potential mechanisms. Lenin died on January 21, 1924 at the age of 53 years. Although some doctors suggested that the origin of his health problems was neurosyphilis, the autopsy findings were consistent with a severe atherosclerosis. This process might account for his recurrent ischemic strokes. In view of the family vascular history, an early hereditary atherosclerosis may be proposed.
Successful Early Non-Operative Management of Congenital Knee Dislocation: Demonstration via a Case Report
Authors: Tiwari Punit , Kaur Harmeet , Leonchuk Sergey S.
Published: June 2021

Congenital knee dislocation (CKD) is a deformity in which unnatural hyperextension is possible at the knee much beyond the normal 0° full extension while the flexion is severely restricted. Incidence of this rare congenital malformation is 1/100,000 live births. We present a clinical case of unilateral CKD in a 2-week-old female child and our approach of treatment using serial casting. We have been able to demonstrate that if initiated early, within first few weeks of life, the congenital deformity of knee can be managed conservatively without any surgical intervention even in higher grades.
A Case of Miller-Fisher Syndrome with Syndrome of Inappropriate Secretion of Antidiuretic Hormone
Authors: Fujiwara Shunya , Manabe Yasuhiro , Nakano Yumiko , Omote Yoshio , Narai Hisashi , Abe Koji
Published: June 2021

We report a 72-year-old woman with Miller-Fisher syndrome (MFS) with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). She developed diplopia and unsteady gait a week after an upper respiratory infection. Neurologic examination revealed ophthalmoplegia, ataxia, symmetrical weakness, numbness, and areflexia. She underwent intravenous immunoglobulin therapy. Her serum sodium concentration decreased to 119 mEq/L on day 12. She had low plasma osmolarity (254 mosm/kg), high urine osmolarity (457 mosm/kg), and high urine sodium level (73 mEq/L), while the blood level of antidiuretic hormone was normal. Anti-GD1b immunoglobulin G (IgG), -GQ1b IgG, -GT1a IgG, and -Gal-C IgM antibodies were positive. We diagnosed her with MFS overlapping with SIADH. Four weeks after onset, her symptoms recovered. The elevation of anti-GD1b, -GQ1b, and -GT1a antibodies that recognize disialosyl residue may be pathologically related to SIADH.
Relationship Between the Aldosterone-to-Renin Ratio and Blood Pressure in Young Adults: A Longitudinal Study
Authors: Yang Jun , May Gwini Stella , Beilin Lawrence J. , Schlaich Markus , Stowasser Michael , Young Morag J. , Fuller Peter J. , Mori Trevor A.
Published: June 2021

Hypertension tracks throughout childhood into adulthood. Elevated aldosterone in the setting of low renin predicts incident hypertension in normotensive adults, but the relationship is unclear in adolescents and young adults. To explore this relationship, we analyzed data from the offsprings (Gen2) of women enrolled during pregnancy into the Raine Study (population-based birth cohort), who had blood pressure (BP) measurements and blood samples at age 17 years (N=871) and age 27 years (N=758). At 17 years, females had similar median aldosterone levels (349 versus 346 pmol/L) but significantly lower direct renin concentration (20.6 versus 25.7 mU/L) and thus a higher aldosterone-to-renin ratio (ARR; 18.3 versus 13.5) compared with males. However, females had lower systolic BP (109 versus 118 mm Hg) versus males. A significant association between ARR and systolic BP was detected in 17 years males when adjusted for alcohol consumption, physical activity, and body mass index. This was true whether the ARR was expressed as a continuous variable (β-coefficient 0.1,
P
=0.009) or categorical variable (highest versus lowest quartile, β-coefficient 3.15,
P
=0.003). No such correlation was observed in females at 17 years. However, the ARR at 17 years was significantly associated with both systolic (β-coefficient 0.15,
P
=0.009) and diastolic BP (β-coefficient 0.14,
P
=0.003) at 27 years among females, but not males. The sexually dimorphic relationship between the ARR and BP in 17 and 27 years participants suggests that the ARR, calculated from the plasma aldosterone concentration and direct renin concentration, could be a useful tool for BP prediction and assessment in young people, but require sex-specific interpretation.