bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Pharmacology-Based Prediction of Catalpol and Mechanisms against Stroke
Authors: Wang Jinghui , Zhang Meifeng , Sun Si , Wan Guoran , Wan Dong , Feng Shan , Zhu Huifeng
Published: January 2021

Aim. To apply the network pharmacology method to screen the target of catalpol prevention and treatment of stroke, and explore the pharmacological mechanism of Catalpol prevention and treatment of stroke. Methods. PharmMapper, GeneCards, DAVID, and other databases were used to find key targets. We selected hub protein and catalpol which were screened for molecular docking verification. Based on the results of molecular docking, the ITC was used to determine the binding coefficient between the highest scoring protein and catalpol. The GEO database and ROC curve were used to evaluate the correlation between key targets. Results. 27 key targets were obtained by mapping the predicted catalpol-related targets to the disease. Hub genes (ALB, CASP3, MAPK1 (14), MMP9, ACE, KDR, etc.) were obtained in the key target PPI network. The results of KEGG enrichment analysis showed that its signal pathway was involved in angiogenic remodeling such as VEGF, neurotrophic factors, and inflammation. The results of molecular docking showed that ACE had the highest docking score. Therefore, the ITC was used for the titration of ACE and catalpol. The results showed that catalpol had a strong binding force with ACE. Conclusion. Network pharmacology combined with molecular docking predicts key genes, proteins, and signaling pathways for catalpol in treating stroke. The strong binding force between catalpol and ACE was obtained by using ITC, and the results of molecular docking were verified to lay the foundation for further research on the effect of catalpol on ACE. ROC results showed that the AUC values of the key targets are all >0.5. This article uses network pharmacology to provide a reference for a more in-depth study of catalpol’s mechanism and experimental design.
Analysis and Simulation of Intervention Strategies against Bus Bunching by means of an Empirical Agent‐Based Model
Authors: Quek Wei Liang , Chung Ning Ning , Saw Vee-Liem , Chew Lock Yue
Published: January 2021

In this paper, we propose an empirically based Monte Carlo bus‐network (EMB) model as a test bed to simulate intervention strategies to overcome the inefficiencies of bus bunching. The EMB model is an agent‐based model which utilizes the positional and temporal data of the buses obtained from the Global Positioning System (GPS) to constitute (1) a set of empirical velocity distributions of the buses and (2) a set of exponential distributions of interarrival time of passengers at the bus stops. Monte Carlo sampling is then performed on these two derived probability distributions to yield the stochastic dynamics of both the buses’ motion and passengers’ arrival. Our EMB model is generic and can be applied to any real‐world bus network system. In particular, we have validated the model against the Nanyang Technological University’s Shuttle Bus System by demonstrating its accuracy in capturing the bunching dynamics of the shuttle buses. Furthermore, we have analyzed the efficacy of three intervention strategies: holding, no‐boarding, and centralized‐pulsing, against bus bunching by incorporating the rule set of these strategies into the model. Under the scenario where the buses have the same velocity, we found that all three strategies improve both the waiting and travelling times of the commuters. However, when the buses have different velocities, only the centralized‐pulsing scheme consistently outperforms the control scenario where the buses periodically bunch together.
Hospital Preparedness Assessment against COVID-19 Pandemic: A Case Study in Turkish Tertiary Healthcare Services
Authors: Gul Muhammet , Yucesan Melih
Published: January 2021

Hospitals play a critical role in providing essential health services to people in the healthcare system. Healthcare systems around the world have faced some issues in responding to patients with various disease severity levels. Nowadays, the world as a whole is combating a pandemic called COVID-19. This pandemic causes an increase in the disease spread with fluctuated patient demand that may affect the hospitals’ capacity and overall functioning and risks rising based on hospital site, medical staff, patient, and healthcare process. To deal with the challenges of the COVID-19 pandemic, hospitals must have completed their preparations before these events occur. Therefore, this study proposes an integrated approach based on the decision-making concept with interval-valued spherical fuzzy sets (IVSFSs) to the hospital preparedness assessment problem. A technique for order preference by similarity to ideal solution (TOPSIS) extended with IVSFSs is used to rank hospitals from Turkish tertiary healthcare services. A checklist reported by the World Health Organization (WHO) is adapted to conform to Turkey’s COVID-19 pandemic management. Ninety-nine subcomponents of the adapted checklist under ten components are weighted by interval-valued spherical weighted arithmetic mean (IVSWAM) operator. The hospitals in the problem are then ranked concerning these weighted subcomponents. With the proposed approach, a COVID-19 pandemic preparedness index is determined for the observed hospitals. In addition, a separate index based on each main component (component-based ranking) is determined. These indexes are vital indicators in determining in which aspects hospitals are ready and in what aspects hospitals are not prepared for pandemics. The proposed approach can be adaptable and applied by national policymakers in assessing all hospitals of the country against the COVID-19 pandemic.
The Antioxidant and Anti-Inflammatory Effects of Quercus brantii Extract on TNBS-Induced Ulcerative Colitis in Rats
Authors: Alizade Naini Mahvash , Mehrvarzi Shayan , Zargari-Samadnejadi Asal , Tanideh Nader , Ghorbani Mohammad , Dehghanian Amirreza , Hasanzarrini Maryam , Banaee Farnaz , Koohi-Hosseinabadi Omid , Irajie Cambyz , Iraji Aida
Published: January 2021

Objectives. Ulcerative colitis is a common subtype of persistent inflammatory bowel disease with high morbidity consequences. Despite unknown definite pathogenesis, multiple anti-inflammatory medications are used for its treatment. Traditionally, Quercus brantii (QB), mostly available in the Middle East, has been used for gastrointestinal disorders. Other beneficial effects associated with QB include reduction of oxidative stress, inflammations, homeostatic instability, and improvement in clinical conditions. Materials and Methods. This experimental study was designed to assess the possible therapeutic effects of QB on UC and compare its effects with those of sulfasalazine. Of the 70 Wistar rats clustered in seven groups, ten received only alcohols and sixty were confirmed to be suffering from trinitrobenzene sulfonic acid- (TNBS-) induced colitis. Four groups received different dosages of QB extract via oral and rectal routes, one received sulfasalazine, and the other remaining two groups received nothing. The effects of QB were evaluated by assessing macroscopic and histologic scoring, measuring inflammatory mediators, and determining oxidative stress markers. Results. Comparing to the untreated TNBS-induced control groups, QB-treated groups showed a dose- and route-dependent improvement comparable with sulfasalazine. Treating rats with QB reduced the microscopic and macroscopic damage, decreased TNF-α, IL-6, NO, MPO activity, and MDA content, increased superoxide dismutase (SOD) activity, and reduced body weight loss. Conclusions. Our data recommended the anti-inflammatory and antioxidant effects of QB extract in a dose-dependent manner.
Study on the Applicability of an Improved Pile‐Beam‐Arch Method of Metro Station Construction in the Upper‐Soft and Lower‐Hard Stratum
Authors: Guo Xinping , Jiang Annan , Wang Shanyong
Published: January 2021

The main challenge for metro station construction is to ensure the construction schedule while minimizing the impact on the surrounding environment. Based on the characteristics of the upper‐soft and lower‐hard stratum in the Dalian city of China, a special structure with six pilot tunnels and three spans of the pile‐beam‐arch (PBA) method is proposed and applied to the construction of the Labor Park metro station. In this study, laboratory experiments, numerical simulation analysis, and field monitoring data are used to investigate the applicability of six pilot tunnels and three spans of the PBA method in the process of construction. In the process of numerical simulation, the ground surface settlement, arch vertical displacement, the horizontal displacement of rock mass on both sides of the station, and vertical stress of support structure are analyzed. The numerical simulation results are found to be in good agreement with field measurement. Furthermore, the results indicate that, in the construction of six pilot tunnels and three spans of the PBA method, pilot tunnel construction and arch construction have a great influence on the surface settlement. The part of the initial vertical support of the pilot tunnels is removed, which caused the change of the position of maximum vertical stress and the redistribution of vertical stress. Because of reinforcement by side piles on both sides of the station, the horizontal displacement of the rock mass was reduced by 44.76% compared with that without reinforcement. The six pilot tunnels and three spans of the PBA method can effectively control the surface settlement, arch vertical displacement, and horizontal displacement of the rock mass.
Design and Application of a Digital System for Information Management and Synchronous Analysis in a Foundation Pit Group
Authors: Xu Zheng-Liang , Wang Xiong , Li Ming-Guang , Zhang Zhong-Jie , Zeng Fan-Yun , Chen Jin-Jian
Published: January 2021

When several adjacent foundation pits are excavated simultaneously and alternately, the foundation pit group has the interactions which will aggravate the excavation‐induced adverse impact on surrounding environment. However, due to the massive construction information and monitoring data during excavation, the effect of interactions on performance of the foundation pits is hardly examined. In this study, a digital system is developed to manage the construction information and monitoring data of the foundation pit group. On the one hand, a visualization management system based on Autodesk Revit is developed to record information such as geometry information, excavation stages, and instrument layout. The complex construction information can be inquired dynamically. On the other hand, a dynamic and synchronous analysis system is developed based on SQL Server external database, Visio, and Excel software. The SQL Server software is capable to facilitate data classification and standardization management. The excavation process and monitoring data are fused through the secondary development of Visio and Excel software to help visualize, respectively. The developed system is applied to the foundation pit group of Shanghai World Expo Project. The lateral deflection of diaphragm walls is investigated and the rebound phenomenon of diaphragm wall is interpreted. It confirms that the developed system can improve the information management so that the deformation behavior of the foundation pit group can be analyzed efficiently.
Revisiting the Factorization of

x

n

+
1
over Finite Fields with Applications
Authors: Boripan Arunwan , Jitman Somphong
Published: January 2021

The polynomial

x

n

+
1

over finite fields has been of interest due to its applications in the study of negacyclic codes over finite fields. In this paper, a rigorous treatment of the factorization of

x

n

+
1

over finite fields is given as well as its applications. Explicit and recursive methods for factorizing

x

n

+
1

over finite fields are provided together with the enumeration formula. As applications, some families of negacyclic codes are revisited with more clear and simpler forms.
Seismic Damage Prediction Method for Lining Structures Based on the SEDR Principle
Authors: Zheng Q. , Xin C. L. , Shen Y. S. , Huang Z. M. , Gao B.
Published: January 2021

The safety and stability of lining structures are core concerns of tunnel and underground engineering. It is crucial to determine whether a lining structure would crack and which direction the crack would expand with seismic excitation. In previous literature, the principle based on stress and strain has been widely used to predict the seismic damage of lining structures, whereas it cannot specify the cracking modes. Taking account of that deficiency, this paper introduces the strain energy density ratio (SEDR) principle and proposes a seismic damage prediction method for lining structures, which can precisely predict the crack positions and expansion directions. Moreover, numerical simulations of the typical seismic damage sections of two tunnels in the Great Wenchuan Earthquake and a calculating example of the theoretical equations are conducted to verify the proposed method. In summary, the numerical simulation results show that the arch springing cracks first, and the invert cracks next; then the cracks expand to the spandrel, and finally, they form oblique cracks, annular cracks, and longitudinal cracks, whose positions and patterns are in accordance with the field investigation results. In terms of the calculating example results, the obtained two‐fold SEDR and cracking angle θ are 1.87 and −6.28°, respectively, which are consistent with the numerical simulation results. Therefore, one can see that the proposed seismic damage prediction method based on the SEDR principle is quite accurate. This method can be used to predict the seismic damage of lining structures and provide a reference for the research of the damage mechanism of tunnels.
Determining Factors in the Therapeutic Success of Checkpoint Immunotherapies against PD-L1 in Breast Cancer: A Focus on Epithelial-Mesenchymal Transition Activation
Authors: Segovia-Mendoza Mariana , Romero-Garcia Susana , Lemini Cristina , Prado-Garcia Heriberto
Published: January 2021

Breast cancer is the most common neoplasm diagnosed in women around the world. Checkpoint inhibitors, targeting the programmed death receptor-1 or ligand-1 (PD-1/PD-L1) axis, have dramatically changed the outcome of cancer treatment. These therapies have been recently considered as alternatives for treatment of breast cancers, in particular those with the triple-negative phenotype (TNBC). A further understanding of the regulatory mechanisms of PD-L1 expression is required to increase the benefit of PD-L1/PD-1 checkpoint immunotherapy in breast cancer patients. In this review, we will compile the most recent studies evaluating PD-1/PD-L1 checkpoint inhibitors in breast cancer. We review factors that determine the therapeutic success of PD-1/PD-L1 immunotherapies in this pathology. In particular, we focus on pathways that interconnect the epithelial-mesenchymal transition (EMT) with regulation of PD-L1 expression. We also discuss the relationship between cellular metabolic pathways and PD-L1 expression that are involved in the promotion of resistance in TNBC.
Research on English Translation Based on Functional Equivalence Theory and Genetic Algorithm
Authors: Liu Yuan , Dong Liangfeng
Published: January 2021

With the increasing development of our country and the world, the importance of English as an international language is self‐evident. But we have difficulty in English translation, especially the vocabulary and translation of business English letters, not only because we have different living habits but also because we have different ways of speaking. Based on the research of functional equivalence theory and the calculation of a genetic algorithm, the vocabulary and translation of business English letters will be better improved. This can help us communicate better with each other and learn from the advanced Western experience in China. Through the study of the algorithm, the computational advantages of the algorithm are proved. The study of this English translation model will further improve the progress and promotion of existing translation technology.
Xiaoyaosan Exerts Therapeutic Effects on the Colon of Chronic Restraint Stress Model Rats via the Regulation of Immunoinflammatory Activation Induced by the TLR4/NLRP3 Inflammasome Signaling Pathway
Authors: Zhu Hui-Zheng , Liang Yu-Dan , Hao Wen-Zhi , Ma Qing-Yu , Li Xiao-Juan , Li Yu-Ming , Chen Jia-Xu
Published: January 2021

Depression is the neurological manifestation most commonly associated with gastrointestinal diseases. The release of inflammatory cytokines mediated by TLR4/NLRP3 inflammasome signaling-induced immunoinflammatory activation may represent a common pathogenic process underlying the development of gastrointestinal diseases and depression. Clinical studies have indicated that Xiaoyaosan (XYS) can relieve depressive behavior by improving gastrointestinal symptoms. We previously demonstrated that XYS can reduce colonic inflammation in a rat model of chronic unpredictable mild stress; however, the precise anti-inflammatory mechanisms involved remain unclear. Here, we investigated whether XYS can ameliorate depressive behavior through regulating the TLR4/NLRP3 inflammasome signaling pathway, thereby inhibiting immunoinflammatory activation and reducing colonic proinflammatory cytokine levels. Fifty-two healthy male Sprague–Dawley rats were randomly divided into four groups (control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to generate a model of stress-induced depression. XYS and fluoxetine were administered intragastrically. Behavioral changes in the rats were assessed after 21 days. Serum and colon samples were collected, and the relative levels of the inflammation indicators IL-6, IL-1β, and TNF-α were determined by ELISA. Pathological changes in colon tissue were assessed by hematoxylin and eosin staining. The levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, and TRAF6 were detected by immunohistochemistry, while the gene and protein expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The results indicated that XYS could improve the depressive-like behavior and the weight loss of rats with stress-induced depression. Furthermore, depressed rats treated with XYS exhibited decreased expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 in colonic tissue; reduced colon and serum concentrations of the inflammatory factors IL-6, IL-1β, and TNF-α; and lowered levels of colonic inflammation.
A Novel Stacking Heterogeneous Ensemble Model with Hybrid Wrapper‐Based Feature Selection for Reservoir Productivity Predictions
Authors: Zhou Changlin , Zhou Lang , Liu Fei , Chen Weihua , Wang Qian , Liang Keliang , Guo Wenqiu , Zhou Liying
Published: January 2021

Acid fracturing is the most important stimulation method in the carbonate reservoir. Due to the high cost and high risk of acid fracturing, it is necessary to predict the reservoir productivity before acid fracturing, which can provide support to optimize the parameters of acid fracturing. However, the productivity of a single well is affected by various construction parameters and geological conditions. Overfitting can occur when performing productivity prediction tasks on the high‐dimension, small‐sized reservoir, and acid fracturing dataset. Therefore, this study developed a stacking heterogeneous ensemble model with a hybrid wrapper‐based feature selection strategy to forecast reservoir productivity, resolve the overfitting problem, and improve productivity prediction. Compared to other baseline models, the proposed model was found to have the best predictive performances on the test set and effectively deal with the overfitting. The results proved that the hybrid wrapper‐based feature selection strategy introduced in this study reduced data acquisition costs and improved model comprehensibility without reducing model performance.
A Review of the Research Progress of Social Network Structure
Authors: Li Ning , Huang Qian , Ge Xiaoyu , He Miao , Cui Shuqin , Huang Penglin , Li Shuairan , Fung Sai-Fu
Published: January 2021

Social network theory is an important paradigm of social structure research, which has been widely used in various fields of research. This paper reviews the development process and the latest progress of social network theory research and analyzes the research application of social network. In order to reveal the deep social structure, this paper analyzes the structure of social networks from three levels: microlevel, mesolevel, and macrolevel and reveals the origin, development, perfection, and latest achievements of complex network models. The regular graph model, P1 model, P2 model, exponential random graph model, small‐world network model, and scale‐free network model are introduced. In the end, the research on the social network structure is reviewed, and social support network and social discussion network are introduced, which are two important contents of social network research. At present, the research on social networks has been widely used in coauthor networks, citation networks, mobile social networks, enterprise knowledge management, and individual happiness, but there are few research studies on multilevel structure, dynamic research, complex network research, whole network research, and discussion network research. This provides space for future research on social networks.
Exploring the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Glycyrrhizic and Glycyrrhetinic Acids
Authors: Richard Seidu A.
Published: January 2021

Licorice extract is a Chinese herbal medication most often used as a demulcent or elixir. The extract usually consists of many components but the key ingredients are glycyrrhizic (GL) and glycyrrhetinic acid (GA). GL and GA function as potent antioxidants, anti-inflammatory, antiviral, antitumor agents, and immuneregulators. GL and GA have potent activities against hepatitis A, B, and C viruses, human immunodeficiency virus type 1, vesicular stomatitis virus, herpes simplex virus, influenza A, severe acute respiratory syndrome-related coronavirus, respiratory syncytial virus, vaccinia virus, and arboviruses. Also, GA was observed to be of therapeutic valve in human enterovirus 71, which was recognized as the utmost regular virus responsible for hand, foot, and mouth disease. The anti-inflammatory mechanism of GL and GA is realized via cytokines like interferon-γ, tumor necrotizing factor-α, interleukin- (IL-) 1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-17. They also modulate anti-inflammatory mechanisms like intercellular cell adhesion molecule 1 and P-selectin, enzymes like inducible nitric oxide synthase (iNOS), and transcription factors such as nuclear factor-kappa B, signal transducer and activator of transcription- (STAT-) 3, and STAT-6. Furthermore, DCs treated with GL were capable of influencing T-cell differentiation toward Th1 subset. Moreover, GA is capable of blocking prostaglandin-E2 synthesis via blockade of cyclooxygenase- (COX-) 2 resulting in concurrent augmentation nitric oxide production through the enhancement of iNOS2 mRNA secretion in Leishmania-infected macrophages. GA is capable of inhibiting toll-like receptors as well as high-mobility group box 1.
Theoretical and Experimental Study on the Transient Time‐Frequency Characteristics of the Bending‐Torsional Coupling Motions of a Rub‐Impact Dual‐Rotor System
Authors: Gao Tian , Cao Shuqian , Zhang Tiancheng
Published: January 2021

This paper focuses on the fault characteristics of the bending and torsional motions of a rub‐impact dual‐rotor system caused by aircraft flight maneuvers. The equations of the bending‐torsional coupling motion of a dual‐rotor system are established considering a low‐pressure rotor rub‐impact fault and the transient barrel roll flight of an aircraft. The 4th Runge‐Kutta method with varied steps is used to obtain the bending and torsional responses. Then, the influences of the system parameters, including the rub‐impact stiffness, friction coefficient, and rotating speed, on the bending and torsional motions of the dual‐rotor system are investigated in detail. At last, a rotor rubbing experiment is carried out, verifying the validity of the simulation results. The results show that the rub‐impact stiffness affects bending vibration significantly and the torsional motion is sensitive to the friction coefficient. Correspondingly, the torsional responses show apparent fractional fault frequencies and rotating fault frequencies within the whole region of the rub‐impact stiffness. The bending responses can only display fault frequencies at certain rub‐impact stiffness. As for the rotating speed, the torsional responses are also more effective than the bending responses for the rub‐impact fault detection at the low‐ and high‐speed regions. The results will contribute to a comprehensive basis for the rub‐impact fault detection.
Cardiotoxicity: A Major Setback in Childhood Leukemia Treatment
Authors: Lazăr Diana R. , Farcaş Anca D. , Blag Cristina , Neaga Alexandra , Zdrenghea Mihnea T. , Căinap Călin , Lazăr Florin L. , Stef Adrian , Căinap Simona S.
Published: January 2021

Ongoing research in the field of pediatric oncology has led to an increased number of childhood cancer survivors reaching adulthood. Therefore, ensuring a good quality of life for these patients has become a rising priority. Considering this, the following review focuses on summarizing the most recent research in anthracycline-induced cardiac toxicity in children treated for leukemia. For pediatric cancers, anthracyclines are one of the most used anticancer drugs, with over half of the childhood cancer survivors believed to have been exposed to them. Anthracyclines cause irreversible cardiomyocyte loss, leading to chronic, progressive heart failure. The risk of developing cardiotoxicity has been known to increase with the treatment-free interval and total cumulative dose. However, because of individual variations in anthracycline metabolism, it has recently been shown that there is no risk-free dose. Moreover, studies have shown that diagnosing anthracycline-induced cardiomyopathy in the symptomatic phase is associated with poor treatment response and prognosis. Thus, early and systematic evaluation of these patients is crucial to allow optimal therapeutic intervention. Although currently echocardiographic assessment of left ventricle ejection fraction and cardiac biomarker evaluation are being used for cardiac function monitoring in oncologic patients, there is no established follow-up and treatment protocol for these patients, and these methods are neither specific nor sensitive for identifying early cardiac dysfunction. All things considered, the need for ongoing research in the field of pediatric cardiooncology is crucial to offer these patients a chance at a good quality of life as adults.
Trajectory Tracking Control for Uncertain Robot Manipulators with Repetitive Motions in Task Space
Authors: Liu Jiutai , Dong Xiucheng , Yang Yong , Chen Hongyu
Published: January 2021

This paper aims at the trajectory tracking problem of robot manipulators performing repetitive tasks in task space. Two control schemes are presented to conduct trajectory tracking tasks under uncertain conditions including unmodeled dynamics of robot and additional disturbances. The first controller, pure adaptive iterative learning control (AILC), is based upon the use of a proportional-derivative-like (PD-like) feedback structure, and its design seems very simple in the sense that the only requirement on the learning gain and control parameters is the positive definiteness condition. The second controller is designed with a combination of AILC and neural networks (NNs) where the AILC is adopted to learn the periodic uncertainties that attribute to the repetitive motion of robot manipulators while the add-on NNs are used to approximate and compensate all nonperiodic ones. Moreover, a combined error factor (CEF), which is composed of the weighted sum of tracking error and its derivative, is designed for network updating law to improve the learning speed as well as tracking accuracy of the system. Stabilities of the controllers and convergence are proved rigorously by a Lyapunov-like composite energy function. The simulations performed on two-link manipulator are provided to verify the effectiveness of the proposed controllers. The results of compared simulations illustrate that our proposed control schemes can significantly conduct trajectory tracking tasks.
The Risk Assessment of Debris Flow Hazards in Banshanmen Gully Based on the Entropy Weight‐Normal Cloud Method
Authors: Gu X. B. , Wu S. T. , Ji X. J. , Zhu Y. H.
Published: January 2021

The debris flow is one of the geological hazards; its occurrence is complex, fuzzy, and random. And it is affected by many indices; a new multi‐index assessment method is proposed to analyze the risk level of debris flow based on the entropy weight‐normal cloud model in Banshanmen gully. The index weight is calculated by using the entropy weight method. Then, the certainty degree of each index belonging to the corresponding cloud is obtained by using the cloud model. The final risk level of debris flow is determined according to the synthetic certainty degree. The conclusions are drawn that the method is feasible and accurate rate of risk estimation for debris flow is very high, so a new method and thoughts for the risk assessment of debris flow can be provided in the future.
Case Report on Anastomosing Haemangioma: An Unusual Vascular Tumor in Kidney
Authors: Lo Chun-hai , Cheng Shui-ying
Published: January 2021

Anastomosing haemangioma is a rare benign vascular neoplasm, which may mimic angiosarcoma histologically. We here present a case of anastomosing haemangioma arising from the kidney. This patient presented with a large kidney mass and adrenal mass. The clinical and radiological findings were suspicious for renal cell carcinoma with metastasis. Radical nephrectomy and adrenalectomy were thus performed. Histopathological examination and immunohistochemical studies concluded a diagnosis of anastomosing haemangioma of the kidney and concurrent adrenal cortical adenoma. It is important to differentiate this tumor from other borderline or malignant vascular neoplasms.
Comparison of Modular Control during Side Cutting before and after Fatigue
Authors: Matsunaga Naoto , Aoki Kenta , Kaneoka Koji
Published: January 2021

The purpose of this study was to clarify the coordination between the trunk and lower limb muscles during sidestep and to compare this coordination before and after fatigue intervention. The intervention was lateral jump until exhaustion. Nonnegative matrix factorization (NMF) was used to extract muscle synergies from electromyography. Subsequently, to compare the muscle synergies, a scalar product that evaluates the coincidence of synergies was calculated. Three muscle synergies were extracted before and after the intervention from the NMF analysis. In accordance with the evaluation of the scalar product, these synergies were the same before and after the intervention. One of these synergies that engaged the internal oblique/transversus abdominis, rectus femoris, and adductor muscle was activated from before landing to midstance during sidestep motion; therefore, this synergy is thought to suppress excessive hip abduction. However, the activation timing of this synergy was delayed after the intervention (P=0.028, effect size: 0.54, Wilcoxon test). This delay is considered to decrease hip stability. Thus, this change may induce a reduction in hip control function.
Study on the Potential Mechanism of Fructus Tribuli in the Treatment of Hypertensive Vascular Remodeling Based on Network Pharmacology and Molecular Docking
Authors: Wang Shuyue , Guo Fei , Sun Xiaochen , Song Xiao , Yuan Yaohui , Zhang Chao , Lin Guitao , Sheng Huagang
Published: January 2021

Background. Hypertensive vascular remodeling (HVR) is the pathophysiological basis of hypertension, which is also an important cause of vascular disease and target organ damage. Treatment with Fructus Tribuli (FT), a traditional Chinese medicine, has a positive effect on HVR. However, the pharmacological mechanisms of FT are still unclear. Therefore, this study aimed to reveal the potential mechanisms involved in the effects of FT on HVR based on network pharmacology and molecular docking. Materials and Methods. We selected the active compounds and targets of FT according to the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Swiss Target Prediction database, and the targets of HVR were collected from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and DrugBank databases. The protein-protein interaction network (PPI) was established using the STRING database. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and network analysis were performed to further explore the potential mechanisms. Finally, molecular docking methods were used to evaluate the affinity between the active compounds and the main target. Results. Seventeen active compounds of FT  and 164 potential targets for the treatment of HVR were identified. Component-target and PPI networks were constructed, and 12 main active components and 33 main targets were identified by analyzing the topological parameters. Additionally, GO analysis indicated that the potential targets were enriched in 483 biological processes, 52 cellular components, and 110 molecular functions. KEGG analysis revealed that the potential targets were correlated with 122 pathways, such as the HIF-1 signaling pathway, ErbB signaling pathway, and VEGF signaling pathway. Finally, molecular docking showed that the 12 main active components had a good affinity for the top five main targets. Conclusion. This study demonstrated the multiple compounds, targets, and pathway characteristics of FT in the treatment of HVR. The network pharmacology method provided a novel research approach to analyze potential mechanisms.
Some Results on Iterative Proximal Convergence and Chebyshev Center
Authors: Shanjit Laishram , Rohen Yumnam , Chandok Sumit , Devi M. Bina
Published: January 2021

In this paper, we prove a sufficient condition that every nonempty closed convex bounded pair

M
,
N

in a reflexive Banach space

B

satisfying Opial’s condition has proximal normal structure. We analyze the relatively nonexpansive self-mapping

T

on

M
∪
N

satisfying

T

M

⊆
M

and

T

N

⊆
N

, to show that Ishikawa’s and Halpern’s iteration converges to the best proximity point. Also, we prove that under relatively isometry self-mapping

T

on

M
∪
N

satisfying

T

N

⊆
N

and

T

M

⊆
M

, Ishikawa’s iteration converges to the best proximity point in the collection of all Chebyshev centers of

N

relative to

M

. Some illustrative examples are provided to support our results.
Tumor Mutational Burden Is Polygenic and Genetically Associated with Complex Traits and Diseases
Authors: Sun Xiwei , Xue Angli , Qi Ting , Chen Dan , Shi Dandan , Wu Yang , Zheng Zhili , Zeng Jian , Yang Jian
Published: January 2021

Tumor mutational burden (TMB) is an emerging biomarker of response to immunotherapy in solid tumors. However, the extent to which variation in TMB between patients is attributable to germline genetic variation remains elusive. Here, using 7,004 unrelated patients of European descent across 33 cancer types from The Cancer Genome Atlas, we show that pan-cancer TMB is polygenic with approximately 13% of its variation explained by approximately 1.1 million common variants altogether. We identify germline variants that affect TMB in stomach adenocarcinoma through altering the expression levels of BAG5 and KLC1. Further analyses provide evidence that TMB is genetically associated with complex traits and diseases, such as smoking, rheumatoid arthritis, height, and cancers, and some of the associations are likely causal. Overall, these results provide new insights into the genetic basis of somatic mutations in tumors and may inform future efforts to use genetic variants to stratify patients for immunotherapy.

Significance:

This study provides evidence for a polygenic architecture of tumor mutational burden and opens an avenue for the use of whole-genome germline genetic variations to stratify patients with cancer for immunotherapy.
Interventional Radiology for Local Immunotherapy in Oncology
Authors: Tselikas Lambros , Champiat Stephane , Sheth Rahul A. , Yevich Steve , Ammari Samy , Deschamps Frederic , Farhane Siham , Roux Charles , Susini Sandrine , Mouraud Severine , Delpla Alexandre , Raoult Thibault , Robert Caroline , Massard Christophe , Barlesi Fabrice , Soria Jean-Charles , Marabelle Aurélien , de Baere Thierry
Published: January 2021

Human intratumoral immunotherapy (HIT-IT) is under rapid development, with promising preliminary results and high expectations for current phase III trials. While outcomes remain paramount for patients and the referring oncologists, the technical aspects of drug injection are critical to the interventional radiologist to ensure optimal and reproducible outcomes. The technical considerations for HIT-IT affect the safety, efficacy, and further development of this treatment option. Image-guided access to the tumor allows the therapeutic index of a treatment to be enhanced by increasing the intratumoral drug concentration while minimizing its systemic exposure and associated on-target off-tumor adverse events. Direct access to the tumor also enables the acquisition of cancer tissue for sequential sampling to better understand the pharmacodynamics of the injected immunotherapy and its efficacy through correlation of immune responses, pathologic responses, and imaging tumor response. The aim of this article is to share the technical insights of HIT-IT, with particular consideration for patient selection, lesion assessment, image guidance, and technical injection options. In addition, the organization of a standard patient workflow is discussed, so as to optimize HIT-IT outcome and the patient experience.
Network for Biomarker Immunoprofiling for Cancer Immunotherapy: Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC)
Authors: Chen Helen X. , Song Minkyung , Maecker Holden T. , Gnjatic Sacha , Patton David , Lee J. Jack , Adam Stacey J. , Moravec Radim , Liu Xiaole Shirley , Cerami Ethan , Lindsay James , Tang Ming , Hodi F. Stephen , Wu Catherine J. , Wistuba Ignacio I. , Al-Atrash Gheath , Bernatchez Chantale , Bendall Sean C. , Hewitt Stephen M. , Sharon Elad , Streicher Howard , Enos Rebecca A. , Bowman Melissa D. , Tatard-Leitman Valerie M. , Sanchez-Espiridion Beatriz , Ranasinghe Srinika , Pichavant Mina , Del Valle Diane M. , Yu Joyce , Janssens Sylvie , Peterson-Klaus Jenny , Rowe Cathy , Bongers Gerold , Jenq Robert R. , Chang Chia-Chi , Abrams Jeffrey S. , Mooney Margaret , Doroshow James H. , Harris Lyndsay N. , Thurin Magdalena
Published: January 2021

Purpose:

Immunoprofiling to identify biomarkers and integration with clinical trial outcomes are critical to improving immunotherapy approaches for patients with cancer. However, the translational potential of individual studies is often limited by small sample size of trials and the complexity of immuno-oncology biomarkers. Variability in assay performance further limits comparison and interpretation of data across studies and laboratories.

Experimental Design:

To enable a systematic approach to biomarker identification and correlation with clinical outcome across trials, the Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC) Network was established through support of the Cancer MoonshotSM Initiative of the National Cancer Institute (NCI) and the Partnership for Accelerating Cancer Therapies (PACT) with industry partners via the Foundation for the NIH.

Results:

The CIMAC-CIDC Network is composed of four academic centers with multidisciplinary expertise in cancer immunotherapy that perform validated and harmonized assays for immunoprofiling and conduct correlative analyses. A data coordinating center (CIDC) provides the computational expertise and informatics platforms for the storage, integration, and analysis of biomarker and clinical data.

Conclusions:

This overview highlights strategies for assay harmonization to enable cross-trial and cross-site data analysis and describes key elements for establishing a network to enhance immuno-oncology biomarker development. These include an operational infrastructure, validation and harmonization of core immunoprofiling assays, platforms for data ingestion and integration, and access to specimens from clinical trials. Published in the same volume are reports of harmonization for core analyses: whole-exome sequencing, RNA sequencing, cytometry by time of flight, and IHC/immunofluorescence.
The Tumor Microenvironment Impairs Th1 IFNγ Secretion through Alternative Splicing Modifications of Irf1 Pre-mRNA
Authors: Bernard Antoine , Hibos Christophe , Richard Corentin , Viltard Etienne , Chevrier Sandy , Lemoine Sophie , Melin Joséphine , Humblin Etienne , Mary Romain , Accogli Théo , Chalmin Fanny , Bruchard Mélanie , Peixoto Paul , Hervouet Eric , Apetoh Lionel , Ghiringhelli François , Végran Frédérique , Boidot Romain
Published: January 2021

It is clearly established that the immune system can affect cancer response to therapy. However, the influence of the tumor microenvironment (TME) on immune cells is not completely understood. In this respect, alternative splicing is increasingly described to affect the immune system. Here, we showed that the TME, via a TGFβ-dependent mechanism, increased alternative splicing events and induced the expression of an alternative isoform of the IRF1 transcription factor (IRF1Δ7) in Th1 cells. We found that the SFPQ splicing factor (splicing factor, proline- and glutamine-rich) was responsible for the IRF1Δ7 production. We also showed, in both mice and humans, that the IRF1 alternative isoform altered the full-length IRF1 transcriptional activity on the Il12rb1 promoter, resulting in decreased IFNγ secretion in Th1 cells. Thus, the IRF1Δ7 isoform was increased in the TME, and inhibiting IRF1Δ7 expression could potentiate Th1 antitumor responses.
Chicken Second Branchial Arch Progenitor Cells Contribute to Heart Musculature in vitro and in vivo
Authors: Yahya Imadeldin , Al Haj Abdulatif , Brand-Saberi Beate , Morosan-Puopolo Gabriela
Published: January 2021

In the past, the heart muscle was thought to originate from a single source of myocardial progenitor cells. More recently, however, an additional source of myocardial progenitors has been revealed to be the second heart field, and chicken embryos were important for establishing this concept. However, there have been few studies in chicken on how this field contributes to heart muscles in vitro. We have developed an ex vivo experimental system from chicken embryos between stages HH17–20 to investigate how mesodermal progenitors in the second branchial arch (BA2) differentiate into cardiac muscles. Using this method, we presented evidence that the progenitor cells within the BA2 arch differentiated into beating cardiomyocytes in vitro. The beating explant cells were positive for cardiac actin, Nkx2.5, and ventricular myosin heavy chain. In addition, we performed a time course for the expression of second heart field markers (Isl1 and Nkx2.5) in the BA2 from stage HH16 to stage HH21 using in situ hybridization. Accordingly, using EGFP-based cell labeling techniques and quail-chicken cell injection, we demonstrated that mesodermal cells from the BA2 contributed to the outflow tract and ventricular myocardium in vivo. Thus, our findings highlight the cardiogenic potential of chicken BA2 mesodermal cells in vitro and in vivo.
Acute Renal Failure Secondary to an Unusual Familial Metabolic Myopathy
Authors: Arana Carolt , Del Carpio Jacqueline , Fayos Leonor , Ars Elisabet , Ayasreh Nadia , Guirado Lluís , Bover Jordi
Published: January 2021

Rhabdomyolysis is a major cause of acute kidney failure. The etiology is diverse, from full-blown crush syndrome to less frequent causes, such as metabolic myopathy. We describe the case of a 35-year-old male with a history of intermittent myalgias who was admitted to hospital with acute renal failure secondary to rhabdomyolysis. Moderate to intense diffuse uptake of technetium-99m was seen in soft tissues at scintigraphy. The diagnosis of metabolic myopathy was confirmed after careful workup and genetic testing.
COVID-19: Risiko für Patienten mit chronisch entzündlichen Erkrankungen?
Authors: Makrantonaki Evgenia
Published: January 2021

COVID-19, caused by the SARS-CoV-2 virus, has become pandemic. With sharply rising infection rates, patient groups characterized by an enhanced infection risk will be challenged by the virus. In this context, patients with chronic immune-mediated inflammatory diseases are of particular interest, as these diseases are characterized by an intrinsic immune dysfunction leading to inflammation that may enhance risk for severe infection.
Aktinische Keratose: Drei therapeutische Verfahren im direkten Vergleich
Authors: Lehmann Percy
Published: January 2021

Background: The efficacy for actinic keratosis (AK) clearance of field-directed treatments has been investigated in randomized studies against placebo, but the comparison of results is difficult for several methodological reasons. Objectives: The present study aims to compare efficacy of MAL-photodynamic therapy (MAL-PDT), ingenol mebutate gel (IMB) and diclofenac plus hyaluronate gel (DHA) on multiple AKs assessing a new performance index of efficacy, the cumulative AK area and evaluating dermoscopical and high-frequency ultrasound (HFUS) changes. Methods: Patients with ≥5 Olsen II AKs in a 25 cm2 area of the scalp and face were enrolled and randomized to one of the treatment choices. Number of AKs and cumulative area were assessed before and after treatment. Dermoscopy and HFUS were performed on a single AK and surrounding photo-damaged skin in the treatment area. Results: Cumulative AKs area reduced significantly more with PDT compared to other treatment options and with IMB in comparison to DHA. PDT was also the only treatment option that increased at a significant level the dermal density in both target AK and the surrounding skin and decreased significantly the SLEB thickness in the perilesional skin at HFUS. Conclusions: MAL-PDT is more effective than IMB and DHA for reducing the cumulative AK area which is calculated digitally from 3D pictures and should be the preferred performance index for the evaluation of the efficacy of treatments for AKs, rolling out clinical and dermoscopy evaluation. MAL-PDT improves all HFUS features of chronic photodamages of the dermis of the skin underlying and surrounding the AK spots.