bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Pharmacological Study on the Mechanism of Cynanchum paniculatum (Xuchangqing) in the Treatment of Bungarus multicinctus Bites
Authors: Zeng Linsheng , Hou Jingjing , Ge Cuihong , Li Yanjun , Gao Jianhua , Zhang Congcong , Li Chengbin , Liu Yuxiang , Zeng Zhongyi
Published: July 2022

Background. Bungarus multicinctus is one of the top ten venomous snakes in China. Its venom is mainly neurotoxin‐based. Novel antivenom drugs need to be further researched and developed. Objective. This study aimed to explore the molecular mechanism of Cynanchum paniculatum in treating Bungarus multicinctus bites based on network pharmacology. Material and methods. The potential active ingredients of Cynanchum paniculatum were screened and their SDF structures were obtained using the PubChem database and imported into the SwissTargetPrediction database, and targets were obtained for the antitoxin effects of Cynanchum paniculatum in the treatment of Bungarus multicinctus bites. The Cynanchum paniculatum‐active compound‐potential target network and protein‐protein interaction network were constructed by using Cytoscape software, and then biological function analysis and KEGG pathway enrichment analysis were performed using the DAVID. Results. Seven potential active components (cynapanoside C, cynatratoside B, tomentolide A, sitosterol, sarcostin, tomentogenin, and paeonol) and 286 drug targets were obtained, including 30 key targets for the treatment of bungarotoxin toxicity. The active components mainly acted on PIK3CA, MAPK1, MAP2K1, JAK2, FYN, ACHE, CHRNA7, CHRNA4, and CHRNB2, and they antagonized the inhibitory effect of bungarotoxin on the nervous system through cholinergic synapses and the neurotrophin signaling pathway. Conclusions. Cynanchum paniculatum exerts a therapeutic effect on Bungarus multicinctus bites through multiple active components, multiple targets, and multiple pathways. The findings provide a theoretical basis for the extraction of active components of Cynanchum paniculatum and for related antivenom experiments.
Bioinformatics Analysis of Prognostic Significance and Immune Characteristics of CXC Chemokine Family in Patients with Lung Adenocarcinoma
Authors: Bian Dachen , Chen Yanhua
Published: July 2022

Objective. To screen CXC chemokines related to the risk of lung adenocarcinoma (LUAD) using bioinformatics and construct a CXC-based prognostic risk model to improve the diagnosis and treatment of LUAD patients. Methods. The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were searched to obtain mRNA expression data and clinicopathological information of LUAD patients. CXC genes differentially expressed in LUAD were screened using the R packages. Further, risk factors significantly associated with the survival of LUAD patients were obtained by the univariate Cox proportional hazard regression, LASSO regression, and multivariate Cox proportional hazard regression analysis, following which a risk prediction model was constructed. The performance of the CXCL13-based model in predicting the prognosis of low-risk and high-risk effect LUAD patients was verified, and the association between the model and the degree of tumor immune cell infiltration was investigated. Results. CXCL13 was significantly highly expressed in the cancer tissues of LUAD patients. The risk of death in patients with highly expressed CXCL13 was about 1.5 times higher than in those with lowly expressed CXCL13 (

HR
=
1.5153357

). CXCL13-based risk scoring showed that the high-risk score of LUAD patients was significantly correlated with poor prognosis, but no relation between the two was found in the GEO validation sets, suggesting that this risk model may not be accurate enough. In addition, activated B cells, CD4+ T cells, CD8+ T cells, and dendritic cells were significantly positively correlated with the high risk of LUAD. Conclusions. Although we found that a high expression of CXCL13 was associated with a high risk of death and immune cell infiltration and activation in LUAD patients, the CXCL13-based risk model was not accurate enough for predicting the prognosis of LUAD patients.
Vitamin B2 Prevents Glucocorticoid‐Caused Damage of Blood Vessels in Osteonecrosis of the Femoral Head
Authors: Guo MinKang , Zhang Jian
Published: July 2022

Osteonecrosis of the femoral head (ONFH) is a disorder that can cause collapse of the femoral head. The damage and dysfunction of femoral head microvascular endothelial cells are related to the pathogenesis of glucocorticoid‐induced ONFH. Reports suggest that vitamin B2 can promote osteoblast differentiation and prevent low bone mineral density and prevent reperfusion oxidative injury. To explore the effect and possible molecular mechanism of vitamin B2 on the ONFH and Human Umbilical Vein Endothelial Cells (HUVECs), we performed a rat model of ONFH by dexamethasone. The rats were randomly divided into four groups: control group, vitamin B2 group, dexamethasone group, and dexamethasone combined with vitamin B2 treatment group. HUVECs were used to further prove the role and mechanism of vitamin B2 in vitro. In patients, according to immunohistochemical and qRT‐PCR of the femoral head, the angiogenic capacity of the ONFH femoral head is compromised. In vivo, it showed that vitamin B2 could inhibit glucocorticoid‐induced ONFH‐like changes in rats by suppressing cell apoptosis, promoting the regeneration of blood vessels, and increasing bone mass. According to in vitro results, vitamin B2 could induce the migration of HUVECs, enhance the expression of angiogenesis‐related factors, and inhibit glucocorticoid‐induced apoptosis. The underlying mechanism may be that vitamin B2 activates the PI3K signaling pathway. Vitamin B2 alleviated dexamethasone‐induced ONFH, and vitamin B2 could promote the proliferation and migration of HUVECs and inhibit their apoptosis by activating the PI3K/Akt signaling pathway. Vitamin B2 may be a potentially effective treatment for ONFH.
Perilipin 2 Protects against Lipotoxicity‐Induced Islet Fibrosis by Inducing Islet Stellate Cell Activation Phenotype Changes
Authors: Zhou Yunting , Wang Yuming , Ni Chengming , Wang Huiying , Zhou Junming , Wan Bingying , Li Huiqin , Li Fengfei , Huang Rong , Xu Wei , Shan Ting , Cai Tingting , Kong Xiaoceng , Liu Bingli , Liu Xiaomei , Sun Zilin , Ma Jianhua
Published: July 2022

Aims. We explored whether and how perilipin 2 (Plin2) protected islets against lipotoxicity‐induced islet dysfunction by regulating islet stellate cells (ISCs) activation. Methods. Six‐week‐old male rats were given a high‐fat diet or a control diet for 28 weeks. Glucose metabolic phenotypes were assessed using glucose/insulin tolerance tests, masson, and immunohistochemical staining. ISCs activation levels were assessed from rats and palmitic acid‐ (PA‐) treated cultured ISCs by immunofluorescence, Oil red O staining, electron microscopy, quantitative PCR, and western blotting. Changes in ISCs phenotype of activation degree and its underlying mechanisms were assessed by target gene lentiviral infection, high‐performance liquid chromatography (HPLC), and western blotting. Results. Obese rats showed glucose intolerance, decreased endocrine hormone profiles, and elevated expression of α‐smooth muscle actin (α‐SMA), a polygonal appearance without cytoplasmic lipid droplets of ISCs in rats and isolated islets. PA‐treated cultured ISCs exhibited faster proliferation and migration abilities with the induction of mRNA levels of lipid metabolism proteins, especially Plin2. The overexpression of Plin2 resulted in ISCs “re‐quiescent” phenotypes associated with inhibition of the Smad3‐TGF‐β signaling pathways. Conclusions. Our observations suggest a protective role of Plin2 in weakening ISCs activation. It may serve as a novel therapeutic target for preventing islet fibrosis for T2DM.
A Multicenter Cohort Study on Children Suffering from Acute Lymphoblastic Leukemia: Effects of Obesity on Mortality
Authors: Wang Xiangwen , Mu Dan , Geng Anyang , Zhao Anqi , Song Yiyuan
Published: July 2022

Background. Overweight and obesity have been reported in specific patients and disease survivors compared to other types of childhood cancer. This study is aimed at determining the effect of children’s obesity on the mortality of acute lymphoblastic leukemia. Method. Children admitted to Inner Mongolia International Mongolian Hospital from 1 January 2017 to 31 December 2020 participated in this study. 1070 children were analyzed. A multi-middle-class poll was conducted. All children under the age of 15 were followed up within 24 months of diagnosis. Overweight and obesity are identified according to the World Health Organization and the Centers for Disease Control and Prevention. Premature death and reoccurrence of emergencies are the main consequences. Results. The initial ethical rate for the first 24 months of testing was 19.9% (NS 213). The lowest cancer survival rate (DFS) was childhood obesity (73%) (24 months), compared with average weight (81%). Diagnosis of overweight/obesity is a predictor of early death (WHO:

HR
=
1.4

, 95% CI: 1.0-2.0; CDC:

HR
=
1.6

, 95% CI: 1.1-2.3). However, there was no association between overweight and obesity (WHO:

HR
=
1.5

, 95% effective interval: 0.9-2.5; CDC:

human
 
resources
=
1.0

, 95% effective interval: 0.6-1.6) and obesity (WHO:

HR
=
1.5

, 95% effective interval: 0.7-3.2; CDC:

HR
=
1.4

, 95% effective interval: 0.9-2.3). Early recurrence was observed. Conclusion. Overweight and obese people belong to the subclass with a high risk of death in the treatment of leukemia.
Gene Mutation and Its Association with Clinicopathological Features in Young Patients with Non-Small-Cell Lung Cancer
Authors: Kong Wencui , Yu Zongyang , Wang Wenwu , Yang Jingrong , Wang Jingfang , Zhao Zhongquan
Published: July 2022

Background. We investigated the correlation between genetic mutations and clinical-pathological features in young patients with NSCLC. Methods. Clinicopathologic information of 102 young NSCLC patients was collected. Direct ctDNA sequencing of a portion of these patients was performed. The correlation between EGFR mutation and ALK fusions with clinicopathologic parameters was analyzed. Results. In young NSCLC patients, adenocarcinoma is the major histology (86.9%), and the misdiagnosis rate was as high as 45.7%. EGFR gene mutation was found in 13 patients (31.7%) and common mutations were with EGFR19del mutation (7 cases, 17.1%) and EGFR21L858R mutation (4 patients, 9.7%). EGFR mutation was constantly found in adenocarcinoma and male gender, and ever smokers (100%,

P
<
0.05

). Furthermore, ALK fusions were found in 7 patients (31.8%), which include EML-4-ALK fusions; there was a trend that ALK fusions were associated with adenocarcinoma and female gender. However, there was no significant difference in overall survival between patients with or without gene mutations. Conclusions. EGFR mutation and ALK fusions are related to histology, gender, and smoke exposure in young NSCLC patients, and may be effective predictive factors.
Research on Named Entity Recognition Method of Metro On-Board Equipment Based on Multiheaded Self-Attention Mechanism and CNN-BiLSTM-CRF
Authors: Lin Junting , Liu Endong
Published: July 2022

Massive and complex unstructured fault text data will be generated during the operation of subway trains. A named entity recognition model of subway on-board equipment based on Multiheaded Self-attention mechanism and CNN-BiLSTM-CRF is proposed to address the issue of low recognition accuracy and incomplete recognition features of unstructured fault data named entity recognition task of subway on-board equipment: BiLSTM-CNN parallel network extracts context feature information and local attention information, respectively; In the MHA layer, the features learned from different dimensions are fused through the Multiheaded Self-attention mechanism, and the dependencies of various ranges in the sequence are captured to yield the internal structure information of the features. The conditional random field CRF is used to learn the internal relationship between tags to ensure their sequence. This model is tested with other named entity recognition models on the marked subway on-board fault data. The experimental results demonstrate that this model is able to recognize 10 kinds of labels in the dataset. Moreover, the recognition effect of each label has a good performance in the three evaluation indexes of P, R, and F1 score. Moreover, the weighted average evaluation indexes

Avg
−
P

,

Avg
−
R

, and

Avg
−

F

1

of 10 labels in this model reach the highest 95.39%, 95.48%, and 95.37%, which has high evaluation indexes and can be applied to the named entity recognition of Metro on-board equipment.
Impact of Different Drying Methods on the Acerola-Ceriguela Mixed Pulp: Physicochemical Characteristics, Bioactive Compounds, and Sensory Attributes
Authors: Silva Júnior Marcony , Silva Nathalia , Ribeiro Christine , Veríssimo Caio , Rocha Ana Paula , Grosso Carlos , Maciel Maria Inês
Published: July 2022

Fruit mixed pulp has the objective of improving the nutritional and sensorial characteristics, as well as the development of new flavours and aromas. Different methods of drying (e.g., spray-drying, spouted bed drying, and freeze-drying) can influence the quality of the final product. The objective of this study was to select the drying method that enables the production of acerola-ceriguela mixed pulp (ACMP) with higher quality. For this selection, the powder pulps were evaluated for their physicochemical characteristics (water activity, moisture, soluble solids (SS), titratable acidity (TA), SS/TA, and instrumental colour), retention of the bioactive compounds (ascorbic acid, total carotenoids, and phenolic compounds), and sensory evaluation (acceptance, check-all-that-apply (CATA), and intent to purchase). The physicochemical characteristics of the freeze-dried and spray-dried ACMP were nonsignificant

p
>
0.05

but differed significantly

p
>
0.05

from spouted bed powder. ACMP freeze-drying powder resulted in higher retention of ascorbic acid, total carotenoids, and phenolic compounds. The powder obtained by spray-drying showed higher retention of bioactive compounds compared to the spouted bed drying. Therefore, this study suggests that powder obtained by freeze-drying resulted in greater sensorial acceptance.
Strength Distribution and Damage Constitutive Model of Frozen Sand under Rate-Dependent Evolution
Authors: Song Fangnian , Yang Weihao , Yang Zhijiang , Huang Xin , Wang Baosheng
Published: July 2022

Study of the compressive strength and damage constitutive model of frozen sand has an important significance for construction design and prevention-control of soil destabilization damage in frozen soil engineering. In this paper, a new triaxial apparatus was used to carry out a series of triaxial compression tests of frozen sand under different confining pressure and strain rate, based on which a segmental strength criterion is established to describe the damage of microelement strength of frozen sand. Assuming that the microelement strength of frozen sand obeys the Weibull distribution, a statistical damage constitutive model of frozen sand is established by statistics and continuous medium mechanics. Based on the test data, the model parameters were calculated and the relationship between the strength distribution parameters, the strain rate, and the confining pressure was obtained. Finally, the calculated values of the damage constitutive model are compared with the experimental values, and it is found that the model can simulate the stress-strain process curve of frozen sand well and can reflect the transition of the curve from elasto-plasticity to strain-hardening when the strain rate increases from low to high. The results of this study have an important significance in engineering construction of cold regions and artificial ground freezing projects.
Genesis Analysis and Stability Evaluation of Karst Area in the Mudengdong Village Based on the Geological Investigation and Numerical Simulation Methods
Authors: Xu Hanhua , Liu Kuiming , Liu Wenlian , Zhu Chun , Zhu Sitao , Dong Jiaxiang
Published: July 2022

The large-scale mining of underground mineral resources will lead to the formation of mined-out areas, which will lead to a series of geological and environmental problems. By selecting the Mudengdong village as a case study, this paper uses geodetic satellite remote sensing technologies to perform qualitative analyses and summarize the geological engineering conditions of the factory. Afterwards, the predominant factors that affect the stability of foundation are determined based on the geological survey of karst in goaf structures. Finally, the finite element software ANSYS is used to comprehensively study the karst problem. The results indicate that (1) the karst development pattern in the study area is controlled by the Beiyin mountain fault, in which case the karst in the basin, in the foot slope, or in the pass section is more widespread than in the slope section. Moreover, the karst generally has a vertical form and is in the early karst stage of development; (2) surface rainwater infiltration, earthquakes, and load pressure are the three major factors that affect karst collapse in the study area; (3) by simulating the development of karst caves and the bearing capacity of the karst roof in the goaf structure under different conditions, it is recommended that only civil buildings with not more than three floors can be built in the village. Overburdened soil thicknesses between 6 and 10 m and civil buildings with heights less than 6 m are not suitable parameters for construction activities. If there are hidden soil holes under the overburden layer, dynamic consolidation needs to be applied in order to destroy the structure of the soil layer and to ensure the safety of personnel.
Optimisation of a Mouse Model of Cerebral Ischemia-Reperfusion to Address Issues of Survival and Model Reproducibility and Consistency
Authors: Liu Zhenqian , Chen Mo , Duan Xu , Zhai Yujia , Ma Bin , Duan Zuowei , Xu Jiang , Liu Haiyan
Published: July 2022

Middle cerebral artery occlusion (MCAO) induced brain ischemia-reperfusion model in Mice is essential for understanding the pathology of stroke and investigating potential treatments, in which a variety of methods may be employed to block the middle cerebral artery (MCA), the most common being through the insertion of a monofilament; however, in vivo ischemia-reperfusion models are associated, particularly in mice, with high variability in lesion volume and high mortality. We aimed to optimise a mouse model of cerebral ischemia-reperfusion, addressing issues of mouse survival, model reproducibility, and consistency. The model was optimised in two ways: first, insert the monofilament directly through the internal carotid artery rather than through the external or common carotid artery, and second, by extending the length of the silicone coating on the monofilament, the length of the silicone coating enables embolization of the beginning of the middle cerebral artery, as well as the anterior cerebral artery and part of the posterior communicating artery. Results: We assessed various parameters, including blood flow changes in the middle cerebral artery, stability of the infarct area, correlation between infarct volume percentages and neurological deficit scores, mortality, weight changes, and wellbeing. We found that optimisation of the surgical procedure may improve mouse wellbeing and reduce mortality, through reduced weight loss and decrease the variability. In conclusion, we suggest that the optimisation of the model is superior for the study of both short and long-term outcomes of ischemic stroke. These results have considerable implications on stroke model selection for researchers.
The Effectiveness Evaluation Model of the Conversion of New and Old Kinetic Energy in the Cloud Computing Environment
Authors: Liu Yu , Zhang Zhengchao , Jing Xin , Yang Yawen
Published: July 2022

This study constructs an index system for the conversion of new and old kinetic energy (NOKE) from three dimensions of electricity, economy, and energy efficiency in the cloud computing environment. First, an annual evaluation model is constructed based on the conversion of NOKE. Second, an evaluation model based on decision-making trial and evaluation laboratory (DEMATEL)-analytic network process (ANP) and improved grey relational method is established. Finally, the annual evaluation is carried out through examples. The results show that the conversion effect of NOKE in Liaoning Province is 0.7956 in 2019, 0.803 in 2020, and 0.9448 in 2021. The evaluation value increases year by year, indicating that the conversion effect of NOKE in Liaoning Province is becoming more and more significant. A series of NOKE conversion measures have achieved positive results. This study provides the theoretical basis and practical guidance for China to promote the transformation of NOKE.
Soccer Player Video Target Tracking Based on Deep Learning
Authors: Zheng Bo
Published: July 2022

Soccer player video target tracking is a very challenging task, which has good practical and commercial value. Traditional soccer game target tracking relies on athletes to carry a recording chip to achieve target tracking, but the cost is very high. With the rapid development of photography technology and deep learning technology, athletes’ target tracking is realized through soccer game video. Deep learning technology is applied to computer vision detection and tracking. How to realize soccer players’ video target tracking under deep learning is a challenging lesson. To solve this problem, this paper takes the video target tracking of football players as the research object, collects the game images of the stadium through multiple cameras, realizes the long-term accurate tracking of multiple players, and establishes a multicamera multitarget tracking system. The KCF algorithm and the improved KCF algorithm formed by replacing the hog feature of the KCF algorithm with the depth convolution neural network are used to compare and analyze the impact of different target tracking ranges and target numbers on the target tracking accuracy of the system, so as to accurately obtain the motion trajectory of football players. The results show that the image data of football matches are collected independently by multiple cameras, and the data of multiple cameras are collected to generate each target motion datum. The KCF algorithm of multicamera multitarget tracking has good robustness and real-time for long-term accurate tracking of football players; the KCF algorithm and the improved KCF algorithm have high accuracy in target tracking. With the increase of tracking frame range, the accuracy of target tracking of the two algorithms is improved. At the same time, multitarget tracking helps to improve the antiocclusion ability of the system. The research results have important practical significance and good application prospects for the analysis technology of video content of football matches.
Selection Strategy of Mining Pool under Various Different Payment Mechanisms
Authors: Xing-Hong Tan , Lu-Xia Fu , Zhuang Zhang , Liang Tan
Published: July 2022

Blockchain is becoming increasingly popular and has received extensive attention in various fields. In a proof-of-work-based blockchain, miners usually choose to join a mining pool for mining to gain revenue. Different mining pools may use other payment mechanisms, and each miner can earn different revenues in different pools. There are currently four common payment mechanisms used by mining pools to distribute mining revenue, namely, PPS, PPLNS, PPS+, and FPPS, and there are no relevant research results on the selection strategies of these four payment mechanisms. To this end, this paper models the pool selection problem as a risky decision problem and proposes the selection strategies of these four mining pool payment mechanisms. Firstly, miners’ income under the four payment mechanisms is given; then, a mining pool selection strategy based on the change of computing power is constructed based on the Laplace criterion; finally, the proposed strategy is verified and analyzed by simulation. The experiments show that the proposed mining pool selection strategy is effective. The results of this paper can provide an essential reference for miners when making pool selection decisions.
An Investigation and Analysis of College English Majors’ Autonomous Learning Ability in Ubiquitous Learning Environment
Authors: Chen Tao
Published: July 2022

In order to solve the problem that there are many places with poor learning ability of college English majors, this study conducts research, evaluation, and research on many places with poor learning ability. The independent learning ability of college students in different majors is obviously different, and majors affect the independent learning ability by 24.2%. Developing students’ ability to succeed is a hot topic in teaching and learning. This study examines the self‐learning ability of English majors in multiple subject areas by means of questionnaires and interviews. The study found that most UK adults had good self‐control, but they showed improvements in self‐planning, literacy and communication skills, and collaboration skills. The overall self‐control ability is at a medium level and needs to be improved. At the same time, it discusses the necessity of improving learning ability and self‐discipline in different learning environments, as well as strategies for improving academic ability, providing important guidance for supporting the academic development of the college new student. Compared with elementary and high school, the breadth and depth of knowledge acquired in school have expanded beyond textbooks. Classroom sound is fast and informative, requiring students to spend a lot of time after class to digest and understand. If students do not perform well in college, the process of assimilation and acquisition can be disrupted. In the case of data being cracked, it is difficult to meet the needs of work due to insufficient learning ability or even to meet the needs, which is based on improving the relationship. For example, it is critical to develop and enhance the ability of college students to succeed in a variety of settings.
A Fast CS-Based Reconstruction Model with Total Variation Constraint for MRI Enhancement in K-Space Domain
Authors: Duan Hongxuan , Lv Xiaochang
Published: July 2022

Due to the fact that Magnetic Resonance Imaging (MRI) is still a relatively slow imaging modality, its application for dynamic imaging is restricted. The total variation is introduced into the CS-based MRI reconstruction model, and three regularization conditions are adopted to ensure that a high-quality reconstructed image is produced. In this paper, a simple yet fast CS-based optimization model for noisy MRI Enhancement is proposed. The alternative direction multiplier method is chosen to optimize the model, and the k-terms power series is applied in order to derive the LogDet function into the augmented Lagrange form. Following this, an approximation of the feature vector is achieved through the iterative process. The quality of the reconstructed image was much better than that of the CS-based MRI image reconstruction algorithm, as shown by experimental results under different noise conditions. The peak signal-to-noise ratio of the reconstructed image was able to be improved anywhere from 5 to 20 percent.
Role and Mechanism of Epithelial-Mesenchymal Transition Mediated by Inflammatory Stress-Induced TGF-β1 in Promoting Arteriovenous Fistula Stenosis
Authors: Duan Qingqing , Shen Xiaogang , He Dongyuan , Xu Yuankai , Zheng Zhigui , Zheng Zhibo , Jiang Xinxin , Ren Min , Chen Lili , Zhang Ting , Lu Yunan , Ye Luxi , Xie Xiaohui
Published: July 2022

Objective. To explore the role and mechanism of epithelial-mesenchymal transition (EMT) mediated by inflammatory stress-induced TGF-β1 in promoting arteriovenous fistula stenosis. Methods. The inflammatory cells HK-2 were cultured by adding TGF-β1. The optimal stimulation time was determined after TGF-β1 was added. HK-2 cells were divided into two groups, DMEM/F12 medium was added to one group (the control group), and the other group was treated with TGF-β1 (10 ng/ml) in serum-free DMEM/F12 medium to stimulate cell differentiation to mesenchymal. Results. TGF-β1 was stably expressed after being transfected into EMT. The expression of TGF-β1 in the experimental group was higher than that in the control group (

P
<
0.05

) 7 days after transfection. Western blot showed that TGF-β1 protein expression was higher in the experimental group 7 days after transfection, and no TGF-β1 protein expression was detected in the control group. The smooth muscle cells showed α-SMA expression in the control group, but no cells with expression of SMA and CD31/vWF were found at the same time; α-SMA expression was shown in smooth muscle cells and proliferative myofibroblasts, but no cells with expressions of SMA and CD31/vWF were found at the same time. The observation group showed that the expression of α-SMA was detected in smooth muscle cells and proliferative myofibroblasts, CD31/vWF was also expressed in endothelial cells, and α-SMA and vWF were also observed in endothelial cells, but no CD31 expression was found. Conclusion. The inflammatory stress-induced TGF-β1 could act on epithelial-mesenchymal transition and promote the degree of arteriovenous fistula stenosis
[Retracted] Antigallbladder Carcinoma Activity Analysis of a New Nanometer Drug Delivery System Based on Data Acquisition
Authors: Li Weidong , Liu Zhiye , Liu Yuanyuan , Qian Lei , Zhang Zhiyong , Nie Lei , Qu Xiusheng
Published: July 2022

In order to solve the problem of the application of data acquisition in the new nanometer drug delivery system of microscope, a research of antigallbladder carcinoma activity analysis was proposed. Gallbladder carcinoma (GBC) is a common malignant tumor in biliary tract diseases. Due to the lack of specific clinical manifestations in the early stage, GBC has the shortcomings of the hidden onset, the difficult diagnosis, and the high misdiagnosis rate. GBC ranks in the top position among the most common tumors of the digestive system worldwide. The preoperative diagnosis rate is low, and the incidence of accidental gallbladder carcinoma is gradually increasing. Domestic gallbladder carcinoma related to cholecystectomy is not sensitive to radiotherapy and chemotherapy. Surgical resection is still the only effective method for the treatment of accidental gallbladder carcinoma.
Analysis of English Translation Model Based on Artificial Intelligence Attention Mechanism
Authors: Lihua Zhao
Published: July 2022

The particularity and quantity of English translation terms have a great impact on the quality and effect of machine translation and can not meet the requirements of English translation of terms. At the same time, technical exchange and communication in different fields need the expression of professional terms. In addition, although the neural machine translation model has good translation performance, it is not ideal for target languages with small translation needs and limited corpus resources. In order to solve the problems existing in the English translation model, this paper constructs the transformer model by replacing the cyclic neural network variables and introducing the attention mechanism. The term information is integrated into two pretraining models to improve the learning ability of model language sentence relationship. Maintain the integrity of terminology information by fully completing the training. The experimental results show that, compared with the other three term translation models, the translation model in this paper has the advantage of term information. At the same time, the deep neural network English term translation model can obtain more fine-grained word relevance. In different corpora, the Bleu score of the model is good, showing obvious translation performance advantages. This study provides a good professional reference value for the translation of English terms.
Shining a FLASHlight on Ultrahigh Dose-Rate Radiation and Possible Late Toxicity
Authors: Maity Amit , Koumenis Constantinos
Published: July 2022

A recent study reported results from a clinical trial in cats and from experiments in mini-pigs in which a single dose of radiotherapy was delivered at ultrahigh dose rates (FLASH). There was acceptable acute toxicity; however, some animals suffered severe late toxicity, raising caution in the design of future trials.

See related article by Rohrer Bley et al., p. 3814
Agonizing over the Stimulatory Immune Checkpoint ICOS
Authors: Lee Jerry C. , Fong Lawrence
Published: July 2022

Vopratelimab, an anti-ICOS (inducible costimulator of T cells) agonist, alone and in combination with nivolumab, possesses limited toxicity and modest clinical activity in a large phase I/II trial. This treatment induced ICOS expression of CD4+ T cells, which may enable biomarkers for patient selection. Nevertheless, T-cell agonists as cancer immunotherapies continue to be challenging.

See related article by Yap et al., p. 3695
Inhibition of Integrin αVβ3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma
Authors: Cayrol Florencia , Revuelta Maria V. , Debernardi Mercedes , Paulazo Alejandra , Phillip Jude M. , Zamponi Nahuel , Sterle Helena , Díaz Flaqué María C. , Magro Cynthia , Marullo Rossella , Mulvey Erin , Ruan Jia , Cremaschi Graciela A. , Cerchietti Leandro
Published: July 2022

Bexarotene is a specific retinoid X receptor agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). Because bexarotene causes hypothyroidism, it requires the administration of levothyroxine. However, levothyroxine, in addition to its ubiquitous nuclear receptors, can activate the αVβ3 integrin that is overexpressed in CTCL, potentially interfering the antineoplastic effect of bexarotene. We thus investigated the biological effect of levothyroxine in relation to bexarotene treatment. Although in isolated CTCL cells levothyroxine decreased, in an αVβ3-dependent manner, the antineoplastic effect of bexarotene, levothyroxine supplementation in preclinical models was necessary to avoid suppression of lymphoma immunity. Accordingly, selective genetic and pharmacologic inhibition of integrin αVβ3 improved the antineoplastic effect of bexarotene plus levothyroxine replacement while maintaining lymphoma immunity. Our results provide a mechanistic rationale for clinical testing of integrin αVβ3 inhibitors as part of CTCL regimens based on bexarotene administration.

Teaser:

Inhibiting αVβ3 integrin improves the antineoplastic effect of bexarotene while maintaining lymphoma immunity.
Efficacy, Tolerability, and Pharmacokinetic Studies of Antibody–Drug Conjugates Containing a Low-Potency Pyrrolobenzodiazepine Dimer
Authors: Gregson Stephen J. , Pugh Kathryn , Patel Neki , Afif-Rider Shameen , Vijayakrishnan Balakumar , Santos Kathleen , Riedl Jitka , Hutchinson Ian , Kang Gyoung-Dong , Chooi K. Phin , Beard Rhiannon , Adams Lauren , Barry Conor S. , Ball Kathryn , Masterson Luke A. , McFarlane Mary , Hartley John A. , Howard Philip W.
Published: July 2022

Antibody–drug conjugate (ADC) research has typically focused on the release of highly potent cytotoxic agents to achieve antitumor efficacy. However, recently approved ADCs trastuzumab deruxtecan and sacituzumab govitecan release lower-potency topoisomerase inhibitors. This has prompted interest in ADCs that release lower-potency cytotoxic drugs to potentially enhance therapeutic index and reduce unwanted toxicity. Pyrrolobenzodiazepine (PBD) dimer ADCs have been widely investigated in human clinical trials, which have focused on high-potency PBDs. In this study, we evaluated five ADCs that release the low-potency PBD dimer SG3650. The relatively low clogD for this agent facilitated higher drug-to-antibody ratio (DAR) conjugation without the need for antibody engineering or functionalization of the drug. The rank order of potency for DAR 2 site-specific ADCs (conjugated at the C239i position) matched the order for the corresponding free drugs in vitro. Despite free drug SG3650 being inactive in vivo, the DAR 2 ADCs derived from the corresponding drug-linker SG3584 showed antitumor efficacy in solid (anti-HER2) and hematologic (anti-CD22) xenograft models. Antitumor activity could be enhanced by conjugating SG3584 to trastuzumab at higher DARs of 4 and 8 and by adjusting dosing and schedule. Higher-DAR conjugates were stable and displayed good rat pharmacokinetic profiles as measured by ELISA and LC/MS-MS. A single intravenous dose of isotype control SG3584 DAR 2 ADC resulted in no mortality in rats or monkeys at doses of up to 25 and 30 mg/kg, respectively. These findings suggest that further investigations of low-potency PBD dimers in ADCs that target hematologic and solid tumors are warranted.
An Enzymatically Cleavable Tripeptide Linker for Maximizing the Therapeutic Index of Antibody–Drug Conjugates
Authors: Ha Summer Y.Y. , Anami Yasuaki , Yamazaki Chisato M. , Xiong Wei , Haase Candice M. , Olson Scott D. , Lee Jangsoon , Ueno Naoto T. , Zhang Ningyan , An Zhiqiang , Tsuchikama Kyoji
Published: July 2022

Valine–citrulline is a protease-cleavable linker commonly used in many drug delivery systems, including antibody–drug conjugates (ADC) for cancer therapy. However, its suboptimal in vivo stability can cause various adverse effects such as neutropenia and hepatotoxicity, leading to dose delays or treatment discontinuation. Here, we report that glutamic acid–glycine–citrulline (EGCit) linkers have the potential to solve this clinical issue without compromising the ability of traceless drug release and ADC therapeutic efficacy. We demonstrate that our EGCit ADC resists neutrophil protease–mediated degradation and spares differentiating human neutrophils. Notably, our anti-HER2 ADC shows almost no sign of blood and liver toxicity in healthy mice at 80 mg kg−1. In contrast, at the same dose level, the FDA-approved anti-HER2 ADCs Kadcyla and Enhertu show increased levels of serum alanine aminotransferase and aspartate aminotransferase and morphologic changes in liver tissues. Our EGCit conjugates also exert greater antitumor efficacy in multiple xenograft tumor models compared with Kadcyla and Enhertu. This linker technology could substantially broaden the therapeutic windows of ADCs and other drug delivery agents, providing clinical options with improved efficacy and safety.
Walking the Tightrope: Balancing Delicate Inflammation Response to Eradicate Acute Myeloid Leukemia
Authors: Puissant Alexandre , Medyouf Hind
Published: July 2022

Ellegast and colleagues show that monocytic acute myeloid leukemias (AML), enriched in inflammatory and immune gene sets, exploit a transcriptional repressor—namely, IRF2BP2—to mitigate their cell-intrinsic inflammatory output and ensure their maintenance. IRF2BP2 ablation results in heightened inflammatory signals that reach a set point that triggers apoptotic AML cell death in an NF-κB–IL1β–dependent manner. The study identifies IRF2BP2 as a cell-intrinsic vulnerability with potential therapeutic significance in monocytic AML.

See related article by Ellegast et al., p. 1760 (6).
Inducing Hypermutability to Promote Anti–PD-1 Therapy Response
Authors: Willis Jason A. , Overman Michael J.
Published: July 2022

The lack of clinical activity from various immune-checkpoint blockade approaches in mismatch repair– proficient (MMRp) colorectal cancer has demonstrated a critical need for novel approaches. In this issue, Crisafulli and colleagues provide proof of concept for the induction of hypermutability through the use of temozolomide as a potential pathway for enabling a productive anti–PD-1 immune response in MMRp colorectal cancer.

See related article by Crisafulli et al., p. 1656 (1) .
Metabolomics: Die neuen Verlaufsparameter in der Rehabilitation?
Authors: Heeb Patrick , Spielmanns Marc
Published: July 2022

Chronic obstructive pulmonary disease (COPD) is characterized by different phenotypes and clinical presentations. Therefore, a single strategy of pulmonary rehabilitation (PR) does not always yield the expected clinical outcomes as some individuals respond excellently, others discreetly, or do not respond at all. Fifty consecutive COPD patients were enrolled. Of them, 35 starting a 5-week PR program were sampled at admission (T0), after 2 (T2W) and 5 (T5W) weeks, while 15 controls not yet on PR were tested at T0 and T5W. Nuclear magnetic resonance (NMR) profiling of exhaled breath condensate (EBC) and multivariate statistical analysis were applied to investigate the relationship between biomarkers and clinical parameters. The model including the three classes correctly located T2W between T0 and T5W, but 38.71% of samples partially overlapped with T0 and 32.26% with T5W, suggesting that for some patients PR is already beneficial at T2W (32.26% overlapping with T5W), while for others (38.71% overlapping with T0) more time is required. Rehabilitated patients presented several altered biomarkers. In particular, methanol from T0 to T5W decreased in parallel with dyspnea and fatigue, while the walk distance increased. Methanol could be ascribed to lung inflammation. We demonstrated that the metabolic COPD phenotype clearly evolves during PR, with a strict relationship between clinical and molecular parameters. Methanol, correlating with clinical parameters, represents a useful biomarker for monitoring personalized outcomes and establishing more targeted protocols.
Prevalence of Occult Hepatitis B Virus Infection in Blood Donors with Negative ID-NAT in Switzerland
Authors: Zbinden Andrea , Ries Judith , Redli Patrick M. , Shah Cyril , Glauser Andreas , Goslings David , Huzly Daniela , Böni Jürg , Gottschalk Jochen , Frey Beat M.
Published: July 2022

Introduction: Screening of hepatitis B surface antigen (HBsAg) and individual-donation nucleic acid amplification testing (ID-NAT) of blood donors have become standard to detect hepatitis B virus (HBV) infection. However, there is still a residual risk of HBV transmission by blood components of donors suffering from occult HBV infection (OBI). Therefore, many countries implemented universal testing of anti-HBV core antigen (anti-HBc) antibodies in order to increase blood safety. In Switzerland, anti-HBc testing is not part of the routine blood donor-screening repertoire. Therefore, we sought to assess prevalence of donors with OBI in a Swiss blood donor collective. Methods: Blood donations were prospectively investigated for the presence of anti-HBc antibodies during two time periods (I: all donors, March 2017; II: first-time donors only, April 2017 until February 2018). Anti-HBc-positive findings were confirmed by an anti-HBc neutralization test. Discarded plasma samples of anti-HBc-confirmed positive donors were ultracentrifuged and subsequently retested by regular HBV-ID-NAT to search for traces of HBV. Results: During time period I, 78 (1.6%) individuals out of 4,923 donors were confirmed anti-HBc-positive. Sixty-nine (88%) anti-HBc-positive samples were available and processed by ultracentrifugation followed by repeat HBV-ID-NAT. Four samples (5.8%) were found positive for HBV DNA. Sixty-five (94.2%) samples remained HBV NAT-negative upon ultracentrifugation. During time period II, 56 (0.9%) donor samples out of 6,509 exhibited anti-HBc-confirmed positive. Fifty-five (98%) samples could be reassessed by HBV-ID-NAT upon ultracentrifugation. Three (5.5%) samples contained HBV DNA and 52 (94.5%) samples remained HBV NAT-negative. Conclusion: Overall, we detected 7 viremic OBI carriers among 11,432 blood donors, which tested negative for HBV by standard HBV-ID-NAT and HBsAg screening. In contrast, OBI carriers showed positive anti-HBc findings which could be confirmed in 83.8% of the cases. Thus, OBI might be missed by the current HBV screening process of Swiss blood donors. We suggest to review current HBV screening algorithm. Extended donor screening by anti-HBc testing may unmask OBI carriers and contribute to blood safety for the recipient of blood products.
Os sentidos da ''determinação'' em Espinosa: afirmação, negação e constituição do finito
Authors: Keller Arion
Published: July 2022

Este estudo tem como principal objetivo uma análise do conceito de determinação em Espinosa. Historicamente, o pensamento de Espinosa foi assimilado a uma filosofia acosmista, isto é, uma filosofia que nega a realidade das coisas finitas em um mundo onde apenas Deus ou a substância seria real. Tal interpretação se consolida a partir das considerações hegelianas em suas Lições sobre a História da Filosofia e na Ciência da Lógica, em que Hegel lê todo o sistema de Espinosa a partir do princípio "omnis determinatio est negatio". Nosso estudo se desenvolve então, primeiramente, apresentando as consequências contemporâneas desta leitura hegeliana; em seguida analisamos a interpretação hegeliana e algumas contribuições de Deleuze a respeito do conceito de determinação em Espinosa; e, por fim, analisamos no texto espinosano a função que o conceito de determinação desempenha e como ela se distancia do consagrado marco de leitura hegeliano de que “omnis determinatio est negatio”.
As Regulae de Descartes e o reformismo lógico seiscentista
Authors: Rezende Cristiano Novaes de
Published: July 2022

Seguindo de perto a caracterização que Robert Blanché faz da lógica dos modernos em seu livro História da Lógica de Aristóteles a Bertrand Russell, pretendo mostrar como as Regulae de Descartes instanciam paradigmaticamente algumas das principais características das lógicas reformadas, típicas desse momento histórico. O próprio Blanché oferece vários exemplos do pertencimento de Descartes a esse contexto. De minha parte, pretendo contribuir com a discussão realizando um exame mais detalhado da parte final da Regra X, na qual desponta, já nesta que é uma das primeiras obras de Descartes, certa noção de atividade mental, que está em relação tanto com as críticas cartesianas às matemáticas, no Discurso do Método, quanto com o argumento do cogito, nas Meditações.
Cerebral Dural Arteriovenous Fistulas
Authors: Gross Bradley A.
Published: July 2022

Dural arteriovenous fistulas are contained within the dural leaflets, making them a unique arteriovenous shunt of the central nervous system. Those without cortical venous drainage may be found incidentally or in a workup of pulsatile tinnitus or ocular symptoms. These symptoms may also occur in the setting of cortical venous drainage, but additionally, seizures, neurological deficits, or even frank hemorrhage may occur because of disruption of normal parenchymal venous outflow and resultant venous hypertension. In the setting of debilitating symptomatology or cortical venous drainage, management is most often via endovascular therapy via transarterial or transvenous access to the fistulous site and subsequent obliteration. Surgical disconnection and radiosurgical obliteration are excellent alternative treatment options for appropriately selected lesions as well. In this article, background demographic and natural history data as well as treatment approaches are reviewed.
A new species of Gegeneophis Peters (Amphibia: Gymnophiona: Caeciliidae) from Goa, India
Authors: BHATTA GOPALAKRISHNA , DINESH K. P. , PRASHANTH P. , KULKARNI NIRMAL U.
Published: July 2022

A new species of Indian caecilian, Gegeneophis goaensis (Amphibia: Gymnophiona: Caeciliidae) is described from three specimens collected from the Western Ghats region of Goa. This species is distinguished from all other members of the genus in having more than 120 primary annuli with more than 75 of these having secondary annular grooves.