bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Tumor Red Blood Cell Immunity and Tumor Cell Cycle in Mice Bearing Solid Liver Cancer with Intelligent Cancer Zhongning Therapeutic Apparatus
Authors: Ge Yakun , Zhang Zhehan
Published: June 2021

People’s unhealthy lifestyles, especially the number of smoking and passive smoking populations, are increasing year by year and the population is aging. With the development and progress of lung cancer cell and molecular biology, the incidence rate and mortality rate of lung cancer are increasing year by year. The existing tumor biochemotherapy has rapidly developed from preliminary research and animal research to clinical research. The smart cancer Zhongning therapeutic device can induce necrosis and apoptosis of tumor cells. The effect of treating tumors is getting more and more attention. Therefore, this article focuses on the effect of the smart cancer Zhongning therapeutic device on the tumor red blood cells and tumor cell cycle of mice with solid liver cancer. The immunological effects of the drug were discussed. Forty mice were randomly divided into high-dose group, low-dose group, 5-FU group, and model group. The effects of different treatment stages on tumor red blood cell immune function and cell cycle were recorded and evaluated, and the survival rate by multiplying the positive limit method was calculated. The model group is controlled by the exact probability method, and the Pss18.0 system is used to test the hypothesis of survival rate comparison. The experimental results showed that the tumor inhibition rate in this group was 65.8%. Compared with the 5-FU group and model group, the dose group has shown an antitumor effect and had significantly improved the tumor-bearing body’s antitumor red blood cell immune function and tumor cell cycle.
Construction of WeChat Mobile Teaching Platform in the Reform of Physical Education Teaching Strategy Based on Deep Neural Network
Authors: Ba Yufeng , Qi Lin
Published: June 2021

Physical education is an important part of school education. Doing a good job of physical education can not only increase students’ interest in sports but also improve their physical fitness. However, traditional physical education methods lack new ideas and fail to reach the goals of physical education. Therefore, it is extremely urgent to conduct physical education teaching strategies. Based on this, this paper proposes the construction of WeChat mobile teaching platform in the reform of physical education teaching strategy based on deep neural network. This paper adopts literature method and experimental analysis method to conduct in-depth research on the application of deep neural network in physical education and its characteristics, shortcomings, and improvements and build a WeChat mobile based on deep neural network in physical education strategy reform teaching platform. The comparison between the control group and the experimental group is used to compare multiple physical test indicators before and after the test to reflect the teaching effectiveness after the change in the physical education strategy of this paper. This paper mainly analyzes the results of the physical education teaching scale and the results of the students’ physical fitness test, including the students’ learning motivation, learning attitude, and learning process in the physical education process, as well as the male and female students’ results of the experimental group and the control group before and after the test compared. The

P

values of the boys in the experimental class and the control class are all greater than 0.05, which is limited to the relatively short time of the experiment. The data of the boys in the two classes on these three items show no significant difference. The t-test was performed on the posttest results of the three items of the girls, the

P

values were all less than 0.05, and there were significant differences, especially in the comparison of the results of the postthrowing solid ball and the corner running. The

P

values of the two test items were all less than 0.01; there is a very significant difference.
The Electrophysiology of Atrial Fibrillation: From Basic Mechanisms to Catheter Ablation
Authors: Ioannidis Panagiotis , Zografos Theodoros , Christoforatou Evangelia , Kouvelas Konstantinos , Tsoumeleas Andreas , Vassilopoulos Charalambos
Published: June 2021

The electrophysiology of atrial fibrillation (AF) has always been a deep mystery in understanding this complex arrhythmia. The pathophysiological mechanisms of AF are complex and often remain unclear despite extensive research. Therefore, the implementation of basic science knowledge to clinical practice is challenging. After more than 20 years, pulmonary vein isolation (PVI) remains the cornerstone ablation strategy for maintaining the sinus rhythm (SR). However, there is no doubt that, in many cases, especially in persistent and long-standing persistent AF, PVI is not enough, and eventually, the restoration of SR occurs after additional intervention in the rest of the atrial myocardium. Substrate mapping is a modern challenge as it can reveal focal sources or rotational activities that may be responsible for maintaining AF. Whether these areas are actually the cause of the AF maintenance is unknown. If this really happens, then the targeted ablation may be the solution; otherwise, more rough techniques such as atrial compartmentalization may prove to be more effective. In this article, we attempt a broad review of the known pathophysiological mechanisms of AF, and we present the recent efforts of advanced technology initially to reveal the electrical impulse during AF and then to intervene effectively with ablation.
A Novel Ruthenium‐Fluvastatin Complex Downregulates SNCG Expression to Modulate Breast Carcinoma Cell Proliferation and Apoptosis via Activating the PI3K/Akt/mTOR/VEGF/MMP9 Pathway
Authors: Liang Wei , Shi Junfeng , Xia Haiyan , Wei Xiaowei
Published: June 2021

Breast cancer is the most common cause of malignancy and cancer‐related morbidity and death worldwide that requests effective and safe chemotherapy. Evaluation of metallodrug‐based anticancer agents and statins as chemotherapeutics with fewer side effects is a largely unexplored research field. Synthesis and characterization of the ruthenium‐fluvastatin complex were achieved using multiple spectroscopic techniques and thus further examined to evaluate its chemotherapeutic prospects in both MDA‐MB‐231 and MCF‐7 cancer lines and eventually in vivo models of DMBA‐induced mammary carcinogenesis in rodents. Our studies indicate that the metal and ligand chelation was materialized by the ligand’s functional groups of carbonyl (=O) oxygen and hydroxyl (‐OH), and the complex has been observed to be crystalline and able to chelate with CT‐DNA. The complex was able to reduce cell proliferation and activate apoptotic events in breast carcinoma cell lines MCF‐7 and MDA‐MB‐231. In addition, the complex was able to modify p53 expressions to interfere with apoptosis in the carcinoma of the breast, stimulated by the intrinsic apoptotic path assisted by Bcl2 and Bax in vivo, yet at the same point, controlling the PI3K/Akt/mTOR/VEGF pathway, as obtained from western blotting, correlates with the MMP9‐regulated tumor mechanisms. Our research reveals that ruthenium‐fluvastatin chemotherapy may disrupt, rescind, or interrupt breast carcinoma progression by modifying intrinsic apoptosis as well as the antiangiogenic cascade, thereby taking the role of a potential candidate in cancer therapy for the immediate future.
Research for Expression and Prognostic Value of GABRD in Colon Cancer and Coexpressed Gene Network Construction Based on Data Mining
Authors: Liu Tao , Fang Yuejun
Published: June 2021

Colon cancer is one of the top five cancers with the highest incidence rate in the world. In order to better understand the pathogenesis and progression of colon cancer, it is still necessary to investigate the abnormally expressed genes in cancer tissue. In this study, the Oncomine database was used for expression analysis, and it was found that the expression level of gamma-aminobutyric acid type A receptor subunit delta (GABRD) gene was upregulated in colon cancer tissue compared with that in normal tissue. UALCAN was used to analyze the expression of GABRD in different groups of age, gender, cancer stage, N stage, and histological subtype. Then, it was also found that the expression of GABRD in each subgroup of colon cancer tissue was all high compared with that in normal tissue. LinkedOmics was used to screen out the differentially expressed genes related to GABRD expression in colon cancer. GO annotation and KEGG pathway enrichment analyses found that the correlated genes may be related to breast cancer, human papillomavirus infection, Notch signaling pathway, and other pathways. Thereafter, GSEA was performed to obtain GABRD-related kinases, miRNAs, and transcription factors, and gene interaction networks were constructed. It was found that GABRD may be involved in cell cycle regulation. Finally, websites like GEPIA were used to detect the predictive ability of GABRD on the prognosis of patients with colon cancer. Kaplan-Meier analysis suggested that the upregulation of GABRD expression was related to the poor prognosis of patients with colon cancer. Overall, in this study, the potential role and prognostic ability of GABRD in colon cancer were explored through data mining, which can be a clue for further research on GABRD.
Lack of Catch-Up Growth with Growth Hormone Treatment in a Child Born Small for Gestational Age Leading to a Diagnosis of Noonan Syndrome with a Pathogenic PTPN11 Variant
Authors: Olivieri Daniel J. , Massingham Lauren J. , Schwab Jennifer L. , Quintos Jose Bernardo
Published: June 2021

Background. Growth hormone (GH) treatment increases the adult height of short children born small for gestational age (SGA). Catch-up growth is associated with a younger age, shorter height, and prepubertal status at the onset of GH treatment. We report a 12 11/12-year-old girl born SGA who received GH for 5 years without catch-up growth and was diagnosed with Noonan Syndrome (NS). Results. A 5-year-and-9-month-old 46, XX girl born SGA was started on GH treatment at a dose of 0.32 mg/kg/week. Her midparental target height is 158.6 cm. Endocrine work up showed an IGF-1 level 69 ng/ml (Normal (N): 55–238 ng/ml), IGFBP3 2.6 mg/L (N: 1.9–5.2 mg/L), TSH 3.2 mIU/L (N: 0.35–5.5 mIU/L), and a normal skeletal survey. Height was 96 cm (0.1%; Ht SDS −2.9), weight 14 kgs (1%; Wt SDS −2.3), and Tanner 1 breast and pubic hair were observed. Due to the poor catch-up growth on GH treatment, she was referred to Genetics to elucidate genetic or syndromic causes of short stature. She was noted to have posteriorly rotated ears and slight down slanting of the palpebral fissures. Genetic findings showed a heterozygous pathogenic variant in PTPN11 (c.922A > G (p.Asn308Asp)) diagnostic for NS. This finding is de novo given negative parental testing. She was noted to have a heterozygous missense variant of unknown significance (VUS) in FGFR3: c.746C > A (p.Ser249Tyr). FGFR3 is associated with multiple skeletal dysplasias including thanatophoric dysplasia, achondroplasia, and Crouzon syndrome and hypochondroplasia. Clinical correlation is poor for these syndromes. Conclusion. Diminished catch-up growth and response to GH treatment in a child born SGA led to the diagnosis of NS. The concomitant diagnosis of SGA and NS may have affected the responsiveness of this child to the growth promoting effect of GH treatment.
Developing a Robust Model Based on the Gaussian Process Regression Approach to Predict Biodiesel Properties
Authors: Pustokhina Inna , Seraj Amir , Hafsan Hafsan , Mostafavi Seyed Mojtaba , Alizadeh S. M.
Published: June 2021

Biodiesel is assumed a renewable and environmentally friendly fuel that possesses the potential to substitute petroleum diesel. The basic purpose of the present study is to design a precise algorithm based on Gaussian Process Regression (GPR) model with several kernel functions, i.e., Rational Quadratic, Squared Exponential, Matern, and Exponential, to estimate biodiesel properties. These properties include kinematic viscosity (KV), pour point (PP), iodine value (IV), and cloud point (CP) as a function of fatty acid composition. In order to develop this model, some variables are assumed, such as molecular weight, carbon number, double bond numbers, monounsaturated fatty acids, polyunsaturated fatty acid, weight percent of saturated acid, and temperature. The performance and efficiency of the GPR model are measured through several statistical criteria and the results are summarized in root mean square error (RMSE) and coefficients of determination (

R

2

).

R

2

and RMSE are sorted as 0.992 & 0.15697, 0.998 & 0.96580, 0.966 & 1.38659, and 0.968 & 1.56068 for four properties such as KV, IV, CP, and PP, respectively. It is worth to mention this point that the kernel function Squared Exponential shows a great performance for IV and PP and kernel functions Exponential and Matern indicate appropriate efficiency for CP and KV properties, respectively. On the other hand, the results of the offered GPR models are compared with those of the previous models, LSSVM-PSO and ANFIS. The outcomes proved the superiority of this model over two former models in point of estimating the biodiesel properties.
Effect of Intravenous Lidocaine on Inflammatory and Apoptotic Response of Ischemia‐Reperfusion Injury in Pigs Undergoing Lung Resection Surgery
Authors: Romera Andrea , Cebollero María , Romero-Gómez Bárbara , Carricondo Francisco , Zapatero Sara , García-Aldao Uxío , Martín-Albo Lorena , Ortega Javier , Vara Elena , Garutti Ignacio , Simón Carlos
Published: June 2021

Background. Ischemia‐reperfusion injury is one of the most critical phenomena in lung transplantation and causes primary graft failure. Its pathophysiology remains incompletely understood, although the inflammatory response and apoptosis play key roles. Lidocaine has anti‐inflammatory properties. The aim of this research is to evaluate the effect of intravenous lidocaine on the inflammatory and apoptotic responses in lung ischemia‐reperfusion injury. Methods. We studied the histological and immunohistochemical changes in an experimental model of lung transplantation in pigs. Twelve pigs underwent left pneumonectomy, cranial lobectomy, caudal lobe reimplantation, and 60 minutes of graft reperfusion. Six of the pigs made up the control group, while six other pigs received 1.5 mg/kg of intravenous lidocaine after induction and a 1.5 mg/kg/h intravenous lidocaine infusion during surgery. In addition, six more pigs underwent simulated surgery. Lung biopsies were collected from the left caudal lobe 60 minutes after reperfusion. We conducted a double study on these biopsies and assessed the degree of inflammation, predominant cell type (monocyte‐macrophage, lymphocytes, or polymorphous), the degree of congestion, and tissue edema by hematoxylin and eosin stain. We also conducted an immunohistochemical analysis with antibodies against CD68 antigens, monocyte chemoattractant protein‐1 (MCP‐1), Bcl‐2, and caspase‐9. Results. The lungs subjected to ischemia‐reperfusion injury exhibited a higher degree of inflammatory infiltration. The predominant cell type was monocyte‐macrophage cells. Both findings were mitigated by intravenous lidocaine administration. Immunohistochemical detection of anti‐CD68 and anti‐MCP‐1 showed higher infiltration in the lungs subjected to ischemia‐reperfusion injury, while intravenous lidocaine decreased the expression. Ischemia‐reperfusion induced apoptotic changes and decreased Bcl‐2 expression. The group treated with lidocaine showed an increased number of Bcl‐2‐positive cells. No differences were observed in caspase‐9 expression. Conclusions. In our animal model, intravenous lidocaine was associated with an attenuation of the histological markers of lung damage in the early stages of reperfusion.
An Audit of CT Chest Reports and Their Potential Impact on the Workup of Patients with Suspected Lung Cancer
Authors: Weinstock Andrew , Jeagal Luke , Savard Chantal , Taylor Jana , Gonzalez Anne V.
Published: June 2021

Background. Quality gaps exist in the diagnostic evaluation of lung cancer patients. The initial CT chest guides the workup of patients with suspected lung cancer. We sought to determine how frequently CT reports provided guideline-concordant recommendations with regard to additional imaging studies and/or invasive diagnostic procedures. Methods. This was a retrospective study. The records of patients referred for investigation of suspected lung cancer between January 1, 2015, and June 30, 2016, were reviewed. Patients with confirmed lung cancer, for whom CT scan images and reports were available, are included. CT reports were reviewed, with attention to additional imaging studies and/or invasive diagnostic procedures suggested. These recommendations were examined against current guidelines for lung cancer diagnosis and staging, based on suspected disease stage. Results. One hundred forty-six patients are included in the analysis. Most patients were diagnosed with non-small-cell lung cancer (NSCLC), and 63% had advanced disease (stages III and IV). Only 12% of CT reports contained guideline-concordant recommendations for additional imaging studies, with PET scan suggested in only 6% of reports. Potential invasive diagnostic procedures were suggested in one fifth of CT reports, and only 58% of these recommendations were in keeping with current guidelines. In particular, transthoracic needle aspiration (TTNA) was suggested in 26% of patients despite advanced stage disease. Conclusion. Guideline-concordant recommendations for investigation of suspected lung cancer are rarely available on CT reports. This is true with respect to both imaging studies and invasive diagnostic procedures. Incorporation of more evidence-based suggestions may reduce quality gaps in lung cancer diagnosis and staging.
Experimental Study on Consolidation Characteristics of Compacted Loess
Authors: Li Jinhua , Zhao Songwei , Wang Xiong , Hao Jiaqi , Zhi Bin , Zhang Hui , Deng Botuan
Published: June 2021

The prediction of foundation settlement is an important topic in loess filling engineering. Based on a filled foundation in Yan’an, China, this study explores the consolidation characteristics of compacted loess with different compaction energy and consolidation pressure through consolidation tests, analyzes the strain‐time curve and refines the curve within 2 h, separates the primary and secondary consolidations, and obtains the critical time point between the primary and secondary consolidations. Deformation rate and cumulative deformation St were introduced to analyze the  − St curve at the secondary consolidation stage; the secondary consolidation coefficient was employed to describe the secondary consolidation characteristics of compacted loess. According to the secondary consolidation characteristics, a prediction model of loess settlement considering different compaction energy and fill thickness was proposed, and the applicability of the model was further analyzed. The model will facilitate in guiding the design and construction of loess filling engineering.
Numerical Simulation of the Nonlinear Flow Properties in Self‐Affine Aperture‐Based Fractures
Authors: Zhou Xin , Sheng Jianlong , Lu Ruili , Ye Zuyang , Luo Wang
Published: June 2021

In order to study the effect of fracture geometry on the nonlinear flow properties in aperture‐based fractures, a fractal model based on the self‐affinity is proposed to characterize the three‐dimensional geometry of rough‐walled fractures. By solving the N–S (Navier–Stokes) equation directly, the relationships between the Forchheimer‐flow characteristics, fractal dimension, and standard deviation of the aperture have been obtained. The Forchheimer equation is validated to describe the nonlinear relationship between flow rate and pressure gradient. For lower flow rate, the influence of the fractal dimension almost can be ignored, but the linear coefficient increases and the hydraulic aperture decreases with increasing standard deviation of the aperture, respectively. For larger flow rate, the nonlinear coefficient increases with the growth of the standard deviation of the aperture and fractal dimension. Thus, an empirical relationship between the nonlinear coefficient, fractal dimension, and standard deviation of aperture is proposed. In addition, the critical Reynolds number decreases with the increase of the standard deviation of the aperture and the fractal dimension, and the numerical results are generally consistent with the experimental data.
Actin-Binding Proteins as Potential Biomarkers for Chronic Inflammation-Induced Cancer Diagnosis and Therapy
Authors: Zhang Yu-Gui , Niu Jiang-Tao , Wu Hong-Wei , Si Xin-Lei , Zhang Shu-Juan , Li Dong-Hui , Bian Tian-Tian , Li Yue-Feng , Yan Xing-Ke
Published: June 2021

Actin-binding proteins (ABPs), by interacting with actin, regulate the polymerization, depolymerization, bundling, and cross-linking of actin filaments, directly or indirectly, thereby mediating the maintenance of cell morphology, cell movement, and many other biological functions. Consequently, these functions of ABPs help regulate cancer cell invasion and metastasis when cancer occurs. In recent years, a variety of ABPs have been found to be abnormally expressed in various cancers, indicating that the detection and interventions of unusual ABP expression to alter this are available for the treatment of cancer. The early stages of most cancer development involve long-term chronic inflammation or repeated stimulation. This is the case for breast cancer, gastric cancer, lung cancer, prostate cancer, liver cancer, esophageal cancer, pancreatic cancer, melanoma, and colorectal cancer. This article discusses the relationship between chronic inflammation and the above-mentioned cancers, emphatically introduces relevant research on the abnormal expression of ABPs in chronic inflammatory diseases, and reviews research on the expression of different ABPs in the above-mentioned cancers. Furthermore, there is a close relationship between ABP-induced inflammation and cancer. In simple terms, abnormal expression of ABPs contributes to the chronic inflammation developing into cancer. Finally, we provide our viewpoint regarding these unusual ABPs serving as potential biomarkers for chronic inflammation-induced cancer diagnosis and therapy, and interventions to reverse the abnormal expression of ABPs represent a potential approach to preventing or treating the corresponding cancers.
Research on IT English Flipped Classroom Teaching Model Based on SPOC
Authors: Liu Lili
Published: June 2021

In order to improve the existing problems in the teaching process of IT English courses and improve the quality of IT English, this paper conducts a research on the flipped classroom teaching mode of IT English based on SPOC. The present situation of IT English teaching is analyzed, and the problems existing in the teaching process are also analyzed. On the basis of the above thought, with the support of SPOC platform build IT turn English classroom teaching mode, namely, by setting the course target, learning for class in advance, choose high-quality class, learning information collection, upload the related resources, and do a good job in teaching design complete teacher preparation, and design the specific teaching unit of teaching process, teaching quality evaluation model was constructed. In this way, the teaching quality evaluation results of IT English flipped classroom are obtained, in order to further improve the teaching quality. The experimental results show that the flipped English teaching mode based on SPOC can effectively improve students’ performance and increase students’ average daily learning time and course satisfaction, and the practical application effect is good.
[Retracted] Target Tracking Algorithm Based on Adaptive Scale Detection Learning
Authors: Yang Dawei
Published: June 2021

In this paper, to better solve the problem of low tracking accuracy caused by the sudden change of target scale, we design and propose an adaptive scale mutation tracking algorithm using a deep learning network to detect the target first and then track it using the kernel correlation filtering method and verify the effectiveness of the model through experiments. The improvement point of this paper is to change the traditional kernel correlation filtering algorithm to detect and track at the same time and to combine deep learning with traditional kernel correlation filtering tracking to apply in the process of target tracking; the addition of deep learning network not only can learn more accurate feature representation but also can more effectively cope with the low resolution of video sequences, so that the algorithm in the case of scale mutation achieves more accurate target tracking in the case of scale mutation. To verify the effectiveness of this method in the case of scale mutation, four evaluation criteria, namely, average accuracy, cross‐ratio accuracy, temporal robustness, and spatial robustness, are combined to demonstrate the effectiveness of the algorithm in the case of scale mutation. The experimental results verify that the joint detection strategy plays a good role in correcting the tracking drift caused by the subsequent abrupt change of the target scale and the effectiveness of the adaptive template update strategy. By adaptively changing the number of interval frames of neural network redetection to improve the tracking performance, the tracking speed is improved after the fusion of correlation filtering and neural network, and the combination of both is promoted for better application in target tracking tasks.
The Many Faces of Purpura: Vancomycin-Induced Leukocytoclastic Vasculitis
Authors: Zadroga John A. , Mogulla Vanajakshi , Grant Christopher , Jevtic Djordje , Virata Andrew , Dumic Igor
Published: June 2021

Leukocytoclastic vasculitis is a rare form of immune-mediated vasculitis that might be caused by infections or autoimmune diseases or might be precipitated by specific medications. We describe a 65-year-old patient, who was receiving vancomycin for a methicillin-sensitive Staphylococcus aureus permacath infection. Vancomycin was chosen due to medication non-adherence and the patient’s desire to receive antimicrobial therapy in conjunction with his scheduled dialysis sessions. The patient’s medical history was notable for untreated hepatitis C infection and end-stage renal disease, requiring hemodialysis three times a week. Vancomycin was administered during dialysis sessions. After one week of therapy, the patient developed bilateral lower extremity purpura. Skin biopsy was suggestive of leukocytoclastic vasculitis with an absence of intravascular thrombi. Serum cryoglobulins were negative, making cryoglobulinemia due to HCV infection unlikely. Following cessation of vancomycin therapy, the rash gradually disappeared with scarring in the form of post-purpuric hyperpigmentation. Despite its widespread use, vancomycin is a rare cause of leukocytoclastic vasculitis. Clinicians should keep in mind a wide range of differential diagnosis of bilateral lower extremity purpura as treatment differs depending on its underlying etiology.
FLT3 Amplification as Double Minute Chromosomes in a Patient with Chronic Myelomonocytic Leukemia
Authors: Zhang Heyang , Wang Xiaoxue , Li Shibo , Wang Xianfu , Lu Xianglan , Li Ming , Wang Hua , Liu Ying , Pang Hui , Zhang Lijun
Published: June 2021

Double minute chromosomes (dmins) are a form of gene amplification presenting as small spherical paired chromatin bodies. Dmins are rare in hematologic malignancies and are generally associated with a poor prognosis. Some case reports identified MYC or MLL gene amplification performing as dmin in myeloid neoplasms. FLT3 (FMS-related tyrosine kinase 3) acts as an oncogene in myeloid neoplasms which is associated with several signal transduction pathways. Genomic amplification of FLT3 has not been reported in hematological disease. The current study attempts to demonstrate the existence of double minute chromosomes via FLT3 gene amplification in a patient diagnosed with chronic myelomonocytic leukemia (CMML). Routine G-banded karyotype, array-based comparative genomic hybridization, and fluorescence in situ hybridization analyses were used to characterize the cytogenetic abnormality in the patient’s bone marrow. FLT3 amplification as dmins in a patient with CMML was revealed. This case study reports a rare double minute chromosome via FLT3 amplification in CMML by using array-based comparative genomic hybridization and fluorescence in situ hybridization analyses. The study also proposed another possible mechanism of FLT3 genes in leukemogenesis.
Long Noncoding RNA WDFY3-AS2 Represses the Progression of Esophageal Cancer through miR-18a/PTEN Axis
Authors: Kong Qingling , Li Guangcai , Yin Gang , Li Kun , Zhang Dongqing , Xu Weihao
Published: June 2021

Background. Understanding the role of lncRNAs in the development of human malignancies is necessary for the targeted therapy of malignant tumors, including esophageal cancer (EC). Nevertheless, the specific role and regulatory mechanism of lncRNA WDFY3-AS2 in EC are still unclear. Here, we examined the functional role and regulatory mechanism of WDFY3-AS2 in EC. Materials and Methods. RT-qPCR assay was applied to measure the expression of WDFY3-AS2 and miR-18a in EC samples and cells. The luciferase reporter and RIP assays were used to check the relationship between WDFY3-AS2, miR-18a, and PTEN. Counting Clock Kit-8 (CCK-8) assay was carried out to detect cell viability, and transwell assays were used for measuring cell migration and invasion. Results. Underexpression of WDFY3-AS2 was found in EC specimens and cells, which predicted a poor prognosis of EC patients. Reexpression of WDFY3-AS2 repressed the progression of EC via inhibiting cell proliferation, migration, and invasion. Additionally, WDFY3-AS2 was negatively correlated with miR-18a and positively with PTEN. Furthermore, we discovered that the expression of PTEN decreased by miR-18a mimic was rescued by WDFY3-AS2 overexpression. Conclusions. WDFY3-AS2 modulates the expressional level of PTEN as a competitive endogenous RNA via sponging miR-18a in EC, which suggests that the WDFY3-AS2/miR-18a/PTEN pathway might be involved in the progression of EC.
Investigating the Multitarget Pharmacological Mechanism of Ursolic Acid Acting on Colon Cancer: A Network Pharmacology Approach
Authors: Zhao Jun , Leng Ping , Xu Wen , Sun Jia-Lin , Ni Bei-Bei , Liu Guang-Wei
Published: June 2021

Objective. To explore the mechanisms of ursolic acid for treating colon cancer based on network pharmacology. Method. In this study, the potential targets of ursolic acid against colon cancer were predicted and screened through the TCMSP, SYMMAP, Drug Bank, UNI-PROT, and DISGENET databases. The protein interaction (PPI) network was constructed based on the STRING database, and graphs were drawn with the help of Cytoscape software. GO and KEGG enrichment analyses were performed on the targets by using the DAVID database for biological information annotation. Results. Ursolic acid has 113 targets in the treatment of colon cancer. The core targets included interleukin-6 (IL-6), mitogen-activated protein kinase 3 (MAPK3), vascular endothelial growth factor receptor (VEGFA), prostaglandin endoperoxide synthase 2 (PTGS2), caspase-3 (CASP3), mitogen-activated protein kinase 8 (MAPK8), tumor necrosis factor (TNF), cyclin D1 (CCND1), JUN, signal transducer and transcriptional activator 3 (STAT3), and other targets. The first 10 pathways related to colon cancer were screened out. The main signaling pathways included the TNF signaling pathway and the AGE-RAGE signaling pathway in diabetic complications and human colon cancer infections. Conclusion. This study revealed that ursolic acid played a multitarget and multichannel antitumor role by inhibiting the proliferation of tumor cells, inducing apoptosis, and enhancing antiangiogenesis.
A Wnt-Independent LGR4–EGFR Signaling Axis in Cancer Metastasis
Authors: Yue Fei , Jiang Weiyu , Ku Amy T. , Young Adelaide I.J. , Zhang Weijie , Souto Eric P. , Gao Yankun , Yu Zihan , Wang Yi , Creighton Chad J. , Nagi Chandandeep , Wang Tao , Hilsenbeck Susan G. , Feng Xin-Hua , Huang Shixia , Coarfa Cristian , Zhang Xiang H.-F. , Liu Qingyun , Lin Xia , Li Yi
Published: June 2021

Leucine-rich repeat-containing G protein–coupled receptors 4, 5, and 6 (LGR4/5/6) play critical roles in development and cancer. The widely accepted mechanism is that these proteins, together with their R-spondin ligands, stabilize Wnt receptors, thus potentiating Wnt signaling. Here we show that LGR4 enhanced breast cancer cell metastasis even when Wnt signaling was deactivated pharmacologically or genetically. Furthermore, LGR4 mutants that cannot potentiate Wnt signaling nevertheless promoted breast cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Multiomic screening identified EGFR as a crucial mediator of LGR4 activity in cancer progression. Mechanistically, LGR4 interacted with EGFR and blocked EGFR ubiquitination and degradation, resulting in persistent EGFR activation. Together, these data uncover a Wnt-independent LGR4–EGFR signaling axis with broad implications for cancer progression and targeted therapy.

Significance:

This work demonstrates a Wnt-independent mechanism by which LGR4 promotes cancer metastasis.

See related commentary by Stevens and Williams, p. 4397
COVID-19 in CKD Patients: Lessons from 553 CKD Patients with Biopsy-Proven Kidney Disease
Authors: Román Juan León , García-Carro Clara , Agraz Irene , Toapanta Nestor , Vergara Ander , Gabaldón Alejandra , Torres Irina , Bury Roxana , Baldallo Cinthia , Serón Daniel , Soler María José
Published: June 2021

Introduction: Chronic kidney disease (CKD) patients infected with COVID-19 are at risk of serious complications such as hospitalization and death. The prognosis and lethality of COVID-19 infection in patients with established kidney disease has not been widely studied. Methods: Data included patients who underwent kidney biopsy at the Vall d’Hebron Hospital between January 2013 and February 2020 with COVID-19 diagnosis during the period from March 1 to May 15, 2020. Results: Thirty-nine (7%) patients were diagnosed with COVID-19 infection. Mean age was 63 ± 15 years and 48.7% were male. Hypertension was present in 79.5%, CKD without renal replacement therapy in 76.9%, and cardiovascular disease in 64.1%. Nasopharyngeal swab was performed in 26 patients; older (p = 0.01), hypertensive (p = 0.005), and immunosuppressed (p = 0.01) patients, those using RAS-blocking drugs (p = 0.04), and those with gastrointestinal symptoms (p = 0.02) were more likely to be tested for CO­VID-19. Twenty-two patients required hospitalization and 15.4% died. In bivariate analysis, mortality was associated with older age (p = 0.03), cardiovascular disease (p = 0.05), chronic obstructive pulmonary disease (p = 0.05), and low hemoglobin levels (p = 0.006). Adjusted Cox regression showed that low hemoglobin levels at admission had 1.81 greater risk of mortality. Conclusions: Patients with CO­VID-19 infection and kidney disease confirmed by kidney biopsy presented a mortality of 15.4%. Swab test for COVID-19 was more likely to be performed in older, hypertensive, and immunosuppressed patients, those using RAS-blocking drugs, and those with gastrointestinal symptoms. Low hemoglobin is a risk factor for mortality.
Insulin-like Growth Factor 1, but Not Insulin-Like Growth Factor-Binding Protein 3, Predicts Central Precocious Puberty in Girls 6–8 Years Old: A Retrospective Study
Authors: Escagedo Patricia Diaz , Deal Cheri L. , Dwyer Andrew A. , Hauschild Michael
Published: June 2021

Background: Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum luteinizing hormone (LH) ≥0.3 IU/L or LH-releasing hormone (LHRH)-stimulated LH ≥5 IU/L). Stimulation testing is the diagnostic gold standard but is time-consuming and costly. Serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are increased in girls with CPP. Objective: The aim of the study was to assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6–8 years. Methods: The study was a single-center retrospective study. Girls with confirmed CPP (n = 44) and isolated premature precocious adrenarche/ precocious thelarche (PA/PT, n = 16) had baseline biochemical profiling and LHRH stimulation testing. Serum IGF-1 and IGFBP-3 results were converted to standard deviation scores (SDS). Correlations were calculated and receiver operating characteristic curves were plotted. Results: Girls with CPP had higher basal and peak LH, IGF-1 SDS, and growth velocity (p < 0.05). IGF-1 SDS correlated positively with basal and peak LH (p < 0.05). IGF-1 SDS (1.75–2.15) differentiated CPP and PA/PT with 89% sensitivity and 56% specificity (basal LH) and 94% specificity and 55% sensitivity (peak LH). IGFBP-3 SDS did not differ between groups or by CPP parameters. Conclusions: In clinical practice, IGF-1 SDS may be an additional tool for identifying CPP in girls aged 6 to 8 years when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more time-consuming and costly procedures.
Oncosuppressor-Mutated Cell-Based Diagnostic Platform for Liquid Biopsy Diagnoses Benign Head and Neck Masses and Predicts Malignancy in Thyroid Nodules: Results from a Consecutive Cohort of Patients
Authors: Abdouh Mohamed , Tabah Roger , Arena Vincenzo , Arena Manuel , Gao Zu-hua , Lorico Aurelio , Arena Goffredo Orazio
Published: June 2021

Background: We reported that a novel oncosuppressor-mutated cell (OMC)-based platform has the potential for early cancer detection in healthy individuals and for identification of cancer patients at risk of developing metachronous metastases. Objective: Herein, we sought to determine the diagnostic accuracy of this novel OMC-based platform in a consecutive cohort of patients operated for suspicious head and neck masses. Methods: OMCs (BRCA1-deficient fibroblasts) were exposed to blood serum from patients with head and neck nodules before surgical removal. These cells were analyzed for their proliferation and survival. Treated OMCs were inoculated subcutaneously in NOD/SCID mice, and tumor growth was monitored over time. Results: OMCs exposed to serum from patients with malignant lesions displayed increased proliferation compared to those exposed to serum from patients with benign lesions. Only OMCs exposed to serum from patients diagnosed with malignant thyroid neoplasia generated a cancerous mass. The sensitivity of the test was 92%, with only 1 false negative out of 34 patients. Immunohistochemical staining showed that the cancerous masses were poorly differentiated adenocarcinomas with high proliferative index. Conclusions: These data show that liquid biopsy combined with an OMC-based in vivo platform has the potential to diagnose benign head and neck masses and predict whether a thyroid nodule is malignant. These results strengthen the concept that OMCs can be used to detect circulating malignant factors in cancer patients.
Feasibility and Safety of High-Risk Percutaneous Coronary Intervention Without Mechanical Circulatory Support
Authors: Khalid Nauman , Rogers Toby , Torguson Rebecca , Zhang Cheng , Shea Corey , Shlofmitz Evan , Chen Yuefeng , Musallam Anees , Wermers Jason P. , Case Brian , Hashim Hayder , Ben-Dor Itsik , Bernardo Nelson L. , Satler Lowell , Waksman Ron
Published: June 2021

Background:

Recommendations to broaden the use of mechanical circulatory support (MCS) for high-risk percutaneous coronary intervention (PCI) remain controversial with the absence of robust evidence from randomized clinical trials and the risk of device-related complications. This investigation examined whether performing high-risk PCI without elective MCS is feasible and safe.

Methods:

We performed a single-center, retrospective analysis for patients meeting contemporary high-risk PCI criteria as defined by the Interventional Council of the American College of Cardiology. These criteria include unprotected left main disease, last remaining conduit, left ventricular ejection fraction <35%, three-vessel coronary artery disease, severe aortic stenosis, or severe mitral regurgitation. Clinical, procedural, and major in-hospital and 30-day cardiovascular outcomes were assessed.

Results:

The analysis included a cohort of 1680 patients (2887 lesions) with stable coronary artery disease who met high-risk PCI criteria and were treated from 2003 to 2018. The study population comprised 75% men and 68% whites. Mean age was 69.16±11.19 years. Conventional cardiovascular risk factors among our cohort were as follows: hypertension, 91%; hypercholesterolemia, 91%; diabetes, 44%; and cigarette smoking, 14%. Intravascular ultrasound was performed on 53% of the lesions. Rescue MCS was required in 0.8% of the patients. Procedural success was observed in 98.2% of the patients, while the 30-day mortality rate was 1.6%. The incidence of major complications was as follows: all-cause mortality, 1.6%; cardiac death, 0.8%; acute renal failure, 4.6%; stroke, 0.2%; and major bleeding, 1.1%.

Conclusions:

High-risk PCI as defined by the professional societies without elective MCS is feasible and safe in the majority of patients, challenging the current recommendations and practice. A randomized trial comparing unprotected versus protected high-risk PCI for these broad recommendations is warranted to best ascertain which patients would benefit from MCS.
HDL in the 21st Century: A Multifunctional Roadmap for Future HDL Research
Authors: Rohatgi Anand , Westerterp Marit , von Eckardstein Arnold , Remaley Alan , Rye Kerry-Anne
Published: June 2021

Low high-density lipoprotein cholesterol (HDL-C) characterizes an atherogenic dyslipidemia that reflects adverse lifestyle choices, impaired metabolism, and increased cardiovascular risk. Low HDL-C is also associated with increased risk of inflammatory disorders, malignancy, diabetes, and other diseases. This epidemiologic evidence has not translated to raising HDL-C as a viable therapeutic target, partly because HDL-C does not reflect high-density lipoprotein (HDL) function. Mendelian randomization analyses that have found no evidence of a causal relationship between HDL-C levels and cardiovascular risk have decreased interest in increasing HDL-C levels as a therapeutic target. HDLs comprise distinct subpopulations of particles of varying size, charge, and composition that have several dynamic and context-dependent functions, especially with respect to acute and chronic inflammatory states. These functions include reverse cholesterol transport, inhibition of inflammation and oxidation, and antidiabetic properties. HDLs can be anti-inflammatory (which may protect against atherosclerosis and diabetes) and proinflammatory (which may help clear pathogens in sepsis). The molecular regulation of HDLs is complex, as evidenced by their association with multiple proteins, as well as bioactive lipids and noncoding RNAs. Clinical investigations of HDL biomarkers (HDL-C, HDL particle number, and apolipoprotein A through I) have revealed nonlinear relationships with cardiovascular outcomes, differential relationships by sex and ethnicity, and differential patterns with coronary versus noncoronary events. Novel HDL markers may also have relevance for heart failure, cancer, and diabetes. HDL function markers (namely, cholesterol efflux capacity) are associated with coronary disease, but they remain research tools. Therapeutics that manipulate aspects of HDL metabolism remain the holy grail. None has proven to be successful, but most have targeted HDL-C, not metrics of HDL function. Future therapeutic strategies should focus on optimizing HDL function in the right patients at the optimal time in their disease course. We provide a framework to help the research and clinical communities, as well as funding agencies and stakeholders, obtain insights into current thinking on these topics, and what we predict will be an exciting future for research and development on HDLs.
The Corporate Dimension of the Cold War in Hungary: ITT and the Vogeler/Sanders Case Reconsidered
Authors: Manchester Margaret Murányi
Published: June 2021

In 1949, two executives at the Hungarian subsidiary of the U.S. conglomerate International Telephone & Telegraph (ITT), Robert Vogeler of the United States and Edgar Sanders of Great Britain, along with five Hungarian nationals, were arrested, tortured, given peremptory trials, and imprisoned for espionage and economic sabotage. This article reexamines the case in light of the diplomatic efforts to secure their release. The case needs to be understood in the context of U.S. intelligence agencies’ policies during the early Cold War. Numerous organizations that were not necessarily well coordinated embarked on intelligence-gathering and a variety of covert operations, some of which were undertaken with the cooperation of multinational corporations such as ITT. Vogeler and Sanders were indeed guilty of many of the charges leveled against them, and their ordeal was significant because it revealed the ineffectiveness of Cold War policies to influence behavior behind the Iron Curtain during the Stalin era.
U.S.-Soviet Handshakes in Space and the Cold War Imaginary
Authors: Jenks Andrew
Published: June 2021

This article examines the Apollo-Soyuz Test Project in 1975 as an instrument of diplomacy and as a catalyst for East-West détente. The topic has received little attention in either the general literature on the Cold War—which has only recently begun to address the political significance of science and technology more generally—or in the literature on space history, which has focused mostly on the earlier race to land on the moon and has devoted little attention to the collaboration in space that has dominated crewed space missions from the 1970s, leading up to the International Space Station. The article connects two previously separate spheres of study—space history and diplomatic history—to shed light on the importance of space exploration in the bigger story of Cold War diplomacy.
Frequency Selectivity of Neural Circuits With Heterogeneous Discrete Transmission Delays
Authors: Houben Akke Mats
Published: June 2021

Neurons are connected to other neurons by axons and dendrites that conduct signals with finite velocities, resulting in delays between the firing of a neuron and the arrival of the resultant impulse at other neurons. Since delays greatly complicate the analytical treatment and interpretation of models, they are usually neglected or taken to be uniform, leading to a lack in the comprehension of the effects of delays in neural systems. This letter shows that heterogeneous transmission delays make small groups of neurons respond selectively to inputs with differing frequency spectra. By studying a single integrate-and-fire neuron receiving correlated time-shifted inputs, it is shown how the frequency response is linked to both the strengths and delay times of the afferent connections. The results show that incorporating delays alters the functioning of neural networks, and changes the effect that neural connections and synaptic strengths have.