bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Evaluation Model of Agricultural Enterprise Technology Innovation Based on GA-BP Neural Network
Authors: Kang Jian , Zhao Minjuan
Published: June 2022

With the continuous development of my country’s economy and society, how to effectively evaluate the technical innovation performance of agricultural enterprises has become the focus of research. This paper firstly processes and analyzes the technical innovation performance data of agricultural enterprises, and then processes and converts the technical innovation performance data of agricultural enterprises; then, through the analysis of the technical innovation performance data of agricultural enterprises, the key characteristics of the technical innovation performance of agricultural enterprises are excavated. Finally, a performance evaluation model based on agricultural enterprise technology innovation is proposed, and the validity of the model is verified with examples.
Innovative Construction of Reinforcement Learning Model for Information Fusion in Music Education
Authors: Zhang Zehui
Published: June 2022

In order to improve the effect of modern music education, this paper applies the digital information technology of music resources to the construction of the music teaching system and derives two new types of semi-decision-making process reinforcement learning algorithms based on the Bellman optimality equation base on discrete time. Moreover, this paper uses the comparative research methods to obtain the Q-value learning curve of the incremental value iterative reinforcement learning algorithm based on the semi-Markov decision process and the incremental value iterative reinforcement learning algorithm based on the dichotomy to improve the fusion effect of music teaching resources. Finally, this paper combines the actual needs of modern music education to construct an intelligent music teaching model.
Smart Logistic System for Enhancing the Farmer-Customer Corridor in Smart Agriculture Sector Using Artificial Intelligence
Authors: Ramirez-Asis Edwin , Bhanot Astha , Jagota Vishal , Chandra B. , Hossain Md Shamim , Pant Kumud , Almashaqbeh Hashem Ali
Published: June 2022

In an agriculture sector, the quality of several raw crops depends upon the time factor. After harvesting, it is necessary to bring the crops either to cold storage or directly to customer though wholesale dealers. Keeping crops in cold storage decrease the nutrition value and also increase the overall cost of the crop leading to price hike. So, it will be best if the crops are put in the market as soon as possible. This can only be possible if the logistic system is updated and can handle the real-time requirement of agriculture product transport. This study investigates and highlights the possible IoT-based logistic support using artificial intelligence for the farmers such that a fast corridor is created between farmers’ lands to end-user customers. This will benefit the farmers in two-fold; first, it will increase the revenue of farmers by decreasing the time span avoiding cold storage fees, and second, it will maintain the quality of crops.
Development of a Wireless Sensor Network and IoT-based Smart Irrigation System
Authors: Ndunagu Juliana Ngozi , Ukhurebor Kingsley Eghonghon , Akaaza Moses , Onyancha Robert Birundu
Published: June 2022

This study proposes a smart irrigation system (SIS) using the drip method, which was designed and implemented using wireless sensor networks and an open-source Internet of Things (IoT) cloud computing platform (“Thingspeak.com”) for data collection, storing, data analytics, and visualization. The methodology incorporates the integration of hardware and software components to make irrigation decisions based on web resources like the weather forecast from “weather.com” and sensor values from soil samples. The data collected are then analyzed at the edge server and updated every 15 minutes. Based on the threshold value, the system starts pumping water or stops the irrigation process depending on the irrigation schedule. A web application was developed to display the result so that we could monitor and control the system using an android application edge or a web browser. Based on the data recorded and measured, the data are in comma-separated values (CSV) format and contain 143731 entries with 10 columns. The sample size used contains 5722 rows and 6 columns from the result of our machine learning algorithms using Microsoft Excel and Jupyter Notebook to process and evaluate the performance of the drip SIS, considering the soil moisture, soil temperature, sunlight, rain, and pump. The results confirm the threshold metrics classification evaluation, and some of the metrics computed from our confusion matrix are shown in the classification summary results, showing the accuracy to be 89%, the misclassification rate (error rate) is equal to 10%, the sensitivity is equal to 79%, the specificity is equal to 93%, and the precision of the model is 81%. The evaluation, when compared to K-nearest neighbours using K = 6 and K = 1, shows the prediction accuracy to be 97% and 98%. The results indicate the system is highly efficient and reliable in performing irrigation and managing water resources and can be adopted in rural areas to boost agricultural productivity.
The Theoretical Topology and Implementation of Enterprise Social Security in the Digital Age Based on Big Data and Artificial Intelligence
Authors: Wang Dandan , Lin Ting , Xu Hongmei
Published: June 2022

At present, there are some problems in the social security of employees in enterprises, such as incomplete security and low reliability. According to this background, this paper studies a topological method for enterprise social security data analysis based on data adaptive analysis strategy and strong learning data stream coprocessing. According to this background, this paper studies a topology method of enterprise social security data analysis based on data adaptive analysis strategy and strong learning data flow and designed a convolutional neural network method based on mutual interference deepening strategy and advanced learning classification mode convolution neural network based on mutual interference deepening strategy and intensive learning classification pattern. According to the coverage error strategy of different types of data, the high-precision matching analysis of enterprise employee social security data is realized, and the Cartesian formula is used to correct the error and topology analysis of the analysis results. According to the experimental data and results, the topology method of enterprise social security data analysis is based on the experimental data and results. We can know that the topological method of enterprise social security data analysis is based on convolutional neural network. Enterprise social security theory can effectively improve the scope and speed of social security. This theory effectively completes the high-precision matching of different types of data and indirectly improves employees’ cognition of enterprise values.
Metabolomics of Esophageal Squamous Cell Carcinoma Tissues: Potential Biomarkers for Diagnosis and Promising Targets for Therapy
Authors: Xu Jia , Cao Weiping , Shao Aizhong , Yang Ming , Andoh Vivian , Ge Qi , Pan Hui-wen , Chen Ke-ping
Published: June 2022

Background. The incidence of esophageal squamous cell carcinoma in China ranks first in the world. The early diagnosis technology is underdeveloped, and the prognosis is poor, which seriously threatens the quality of life of the Chinese people. Epidemiological findings are related to factors such as diet, living habits, and age. The specific mechanism is not clear yet. Metabolomics is a kind of omics that simultaneously and quantitatively analyzes the comprehensive profile of metabolites in living systems. It has unique advantages in the study of the diagnosis and pathogenesis of tumor‐related diseases, especially in the search for biomarkers. Therefore, it is desirable to perform metabolic profiling analysis of cancer tissues through metabolomics to find potential biomarkers for the diagnosis and treatment of esophageal squamous cell carcinoma. Methods. HPLC‐TOF‐MS/MS technology and Illumina Hiseq Xten Sequencing was used for the analysis of 210 pairs of matched esophageal squamous cell carcinoma tissues and normal tissues in Zhenjiang City, Jiangsu Province, a high‐incidence area of esophageal cancer in China. Bioinformatics analysis was also performed. Results. Through metabolomic and transcriptomic analysis, this study found that a total of 269 differential metabolites were obtained in esophageal squamous cell carcinoma and normal tissues, and 48 differential metabolic pathways were obtained through KEGG enrichment analysis. After further screening and identification, 12 metabolites with potential biomarkers to differentiate esophageal squamous cell carcinoma from normal tissues were obtained. Conclusions. From the metabolomic data, 4 unknown compounds were found to be abnormally expressed in esophageal squamous cell carcinoma for the first time, such as 9,10‐epoxy‐12,15‐octadecadienoate; 3 metabolites were found in multiple abnormal expression in another tumor, but upregulation or downregulation was found for the first time in esophageal cancer, such as oleoyl glycine; at the same time, it was further confirmed that five metabolites were abnormally expressed in esophageal squamous cell carcinoma, which was similar to the results of other studies, such as PE.
Data Verification of Logical Pk-Anonymization with Big Data Application and Key Generation in Cloud Computing
Authors: Kumar Sindhe Phani , Anandan R.
Published: June 2022

Background. As more data becomes available about how frequently the cloud can be updated, a more comprehensive picture of its safety is emerging. The suggested artworks use a cloud-based gradual clustering device to cluster and refresh a large number of informational indexes in a useful manner. Purpose. Anonymization of data is done at the point of collection in order to safeguard the data. More secure than K-Anonymization, Pk-Anonymization is the area’s first randomization method. A cloud service provider (CSP) is an independent company that provides a cloud-based network and computing resources. Customers’ security and connection protection must be verified by an authority before facts may be transferred to cloud servers for storing information. Method. Logical Pk-Anonymization and key era techniques are proposed in this proposed artwork in order to verify the cloud records, as well as to store sensitive information in the cloud. Cloud-based informational indexes are used in the proposed framework, which is effective at handling large amounts of data through MapReduce; a parallel data preparation form is obtained; to get all information as new facts that joins after a while, information anonymization techniques to carry out each protection and immoderate information utilization while updating take place; information loss and clean time is reduced for substantial amounts of data. As a result, the safety and records software might be in sync.
Human Placental Mesenchymal Stem Cells for the Treatment of ARDS in Rat
Authors: Kakabadze Zurab , Kipshidze Nicholas , Paresishvili Teona , Kipshidze Nodar , Vadachkoria Zurab , Chakhunashvili David
Published: June 2022

The acute respiratory distress syndrome (ARDS) is one of the main causes of high mortality in patients with coronavirus (COVID-19). In recent years, due to the coronavirus pandemic, the number of patients with ARDS has increased significantly. Unfortunately, until now, there are no effective treatments for ARDS caused by COVID-19. Many drugs are either ineffective or have a low effect. Currently, there have been reports of efficient use of mesenchymal stem cells (MSCs) for the treatment of ARDS caused by COVID-19. We investigated the influence of freeze-dried human placenta-derived mesenchymal stem cells (HPMSCs) in ARDS rat model. All animals have received intratracheal injection of 6 mg/kg of lipopolysaccharide (LPS). The rats were randomly divided into five groups: I: LPS, II: LPS+dexamethasone, III: LPS+HPMSCs, IV: HPMSC, and V: saline. ARDS observation time was short-term and amounted to 168 hours. The study has shown that HPMSCs are able to migrate and attach to damaged lung tissue, contributing to the resolution of pathology, restoration of function, and tissue repair in the alveolar space. Studies have also shown that the administration of HPMSCs in animals with ARDS model significantly reduced the levels of key cytokines such as IL-1β, IL-6, and TNF-α. Freeze-dried placental stem cell is a very promising biomaterial for the treatment of ARDS. The human placenta can be easily obtained because it is considered as a medical waste. At the same time, a huge number of MSCs can be obtained from the placental tissue, and there is no ethical controversy around their use. The freeze-dried MSCs from human placental tissue can be stored sterile at room temperature for a long time before use.
A Threshold Segmentation Algorithm for Sculpture Images Based on Sparse Decomposition
Authors: Yang Zhao , Wan Jixin
Published: June 2022

Aiming at the problem of low efficiency and insufficient accuracy of threshold solution in multithreshold sculpture image segmentation, this paper proposes a threshold segmentation algorithm for sculpture images based on sparse decomposition. In this paper, sparse decomposition is introduced to optimize the model to reduce the impact of local noise on segmentation accuracy, and an energy functional based on pixel coconstraint is built to make up for the defect that pixels cannot retain local details. At the same time, the weighted sum of elite solution sets is used to determine Neighborhood centers increase communication between groups. Experiments show that compared with other algorithms, the above method has significant advantages in convergence efficiency and accuracy.
Preliminary Evaluation of Potential Properties of Three Probiotics and Their Combination with Prebiotics on GLP-1 Secretion and Type 2 Diabetes Alleviation
Authors: Xiao Ran , Wang Ran , Li Shusen , Kang Xiaohong , Ren Yimei , Sun Erna , Wang Chenyuan , He Jingjing , Zhan Jing
Published: June 2022

Type 2 diabetes (T2D) is a disease of global concern characterized by hyperglycemia and insulin resistance. Many studies found that glucagonlike peptide-1 (GLP-1) is an incretin hormone that can alleviate hyperglycemia and T2D. Recently, probiotics and their combination with prebiotics have been found to show great potentials of blood glucose regulation and T2D alleviation. Given the important role of GLP-1 in T2D, screening probiotics with the capacity of promoting GLP-1 secretion is of great help for providing a novel application of T2D treatment. In the current study, we evaluated the effects of three probiotics, namely, Lactobacillus paracasei LC-37 (LC-37), Bifidobacterium animals MN-Gup (MN-Gup), and Bifidobacterium longum BBMN68 (BBMN68), and their combination with prebiotics on promoting GLP-1 secretion using NCI-H716 cells. The results showed that LC-37 and MN-Gup could stimulate more GLP-1 secretion in NCI-H716 cells, but BBMN68 had no significant effect. Further evaluation suggested that the two combinations of LC-37 with isomaltooligosaccharide (IMO) and MN-Gup with galactooligosaccharide (GOS) had the best performance on promoting GLP-1 secretion in vitro. Subsequently, the effects of the two combinations on promoting GLP-1 secretion and alleviating T2D were investigated in vivo using high fat diet (HFD) and streptozotocin (STZ) treated rats. The results showed that the two combinations could significantly reduce fasting blood glucose levels, improve insulin resistance, and modulate serum lipid profiles in HFD/STZ-treated rats. These results will help understand the potential of promoting GLP-1 secretion of LC-37 and MN-Gup and provide theoretical basis for their applications in fermented milk or other foods.
[Retracted] A Study on Nonvisual Effects of Natural Light Environment in a Maternity Ward of a Hospital in Cold Area
Authors: Song Haihong , Jiang Wei , Cui Peng
Published: June 2022

Thanks to the discovery of human eye photoreceptor cells, ipGRC and human nonvisual channels, the nonvisual effects of light have gradually come to our vision and been rationally utilized. Along with this trend, people have expanded their demand for the light environment to both visual and nonvisual needs from only visual needs. With a good natural daylighting, parturients will find their psychological pressure and physiological pain relieved, their rehabilitation rate increased, and they get rehabilitated more quickly. This study was carried out in a representative maternity ward in Harbin based on the latest research results on nonvisual effects at home and abroad. Specifically, the nonvisual effects on the natural light environment in the ward throughout the year were simulated and analyzed from the aspects of equivalent melanopic lux (EML), stimulus frequency (Stim.freq), and circadian effective area (CEA). During the study, natural light in the ward was measured on site, and the evaluation tool and workflow of nonvisual effects were created with the aid of Grasshopper modeling platform, Ladybug+Honeybee, and VB script editor. The results show that the nonvisual effects of natural light on the body of parturients gradually weaken as they further go inside the ward. What is worse, in the most unfavorable all‐overcast condition, daylighting on beds far away from the window does not meet the stimulus of human circadian rhythm from April to August. Therefore, additional light is required. The wards have the best nonvisual natural light environment when they are south facing and have a window to floor ratio of 0.3.
Optimization of Benefit Allocation in Contracted Water-Saving Projects Based on the Shapley Value Method
Authors: Zhu Jiwei , Wang Jiangrui , Zhu Tingting , Zhai Zhao , Zhao Xin
Published: June 2022

Contracted water-saving management (CWSM) has emerged as a powerful model for water-saving actions. In a CWSM project, whether the benefit allocation among the stakeholders is fair and reasonable will affect the enthusiasm of stakeholders for participating in the project, as well as the stability of the project’s operations. This study identifies core stakeholders in CWSM projects of colleges/universities. Then, a preliminary benefit allocation model is constructed through the Shapley value method, risks are identified, and a modified model is developed based on the COWA-gray fixed weight clustering method. Finally, a CWSM project launched by a Chinese university is studied to verify the applicability of the modified model.
Enterprise Management Decision and Financial Management Based on Dynamic Cost Volume Profit Model
Authors: Guo Yanlin
Published: June 2022

Under the background of today’s times, the internal and external environment of enterprises is complex and changeable. It is of great significance for the survival and development of enterprises to continuously reduce the business risks and improve the economic benefits of enterprises by adopting scientific decision-making methods. CVP (cost volume profit) analysis is a model established by sorting out variables related to business decisions in enterprise production through mathematical modeling. Based on the interpretation of cost behavior by multiple cost drivers, this paper establishes a dynamic CVP model of traditional CVP analysis, breaks through the limitations of original assumptions, and improves the application value of CVP analysis in practice. The model is applied to the business decision-making and financial management of a case enterprise, and the products with different characteristics of the enterprise are modeled and analyzed, so as to provide targeted improvement suggestions or strategies for the enterprise’s product production decision-making. The research shows that the dynamic CVP model can be used to formulate the financial management strategy to optimize the profits of enterprises, and it can achieve stable profits and development in the market competition.
Characterizing the Antitumor Effect of Coptis chinensis and Mume Fructus against Colorectal Cancer Based on Pharmacological Analysis
Authors: Gao RuiJiao , Lv Ying
Published: June 2022

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide and is a significant cause of cancer-related deaths. Previous studies have observed that Coptis chinensis (CC) and Mume Fructus (MF) are effective against CRC, enteritis, and intestinal dysbiosis, but the chemical and pharmacological mechanisms remain poorly understood. In this study, we employed pharmacological network analysis to reveal mechanisms underlying the therapeutic effect of CC and MF against CRC. All compounds and targeted genes were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Differentially expressed genes (DEGs) were identified based on GSE146587, GSE156720, and GSE184093 datasets. A protein-protein interaction (PPI) network was constructed to identify putative target genes of CC and MF. Ten key targeted genes were identified, including CCND1, ICAM1, IL1B, IL-6, MMP1, MMP3, MMP9, MYC, SERPINE1, and VEGFA. Among these genes, six (ICAM1, IL1B, IL-6, MMP1, MMP3, MMP9, and SERPINE1) were positively correlated with levels of effector memory CD4 T cells and natural killer T cells, and three (CCND1, MYC, and VEGFA) were negatively correlated with type 17 T helper cells and CD56dim natural killer cells. Molecular docking analysis showed that four compounds of CC and MF (kaempferol, oleanolic acid, quercetin, and ursolic acid) could affect CRC by interacting with target genes. Our study proved that pharmacological analysis could reliably assess the mechanism of traditional Chinese medicines for treating cancer.
Analysis of Clinical Manifestations and Imaging of COVID‐19 Patients in Intensive Care
Authors: Li Lihong , Yao Yongwei , Feng Xiaofei , Chen Lingling , Wu Rui , Chang Yuejin , Lou Qiaoqin , Pan Jinbo , Wang Zhangli
Published: June 2022

Objective. The study aims to summarize and analyze the clinical and CT findings of severe COVID‐19 patients. Methods. From February 11 to March 31, 2020, 61 COVID‐19 patients in intensive care in the E1‐3 ward of Tongji Hospital were analyzed retrospectively. Results. The main clinical manifestations were cough, expectoration in 56 cases (91.8%), shortness of breath, chest tightness in 48 cases (78.7%), fever in 61 cases (100%), muscle ache and weakness in 40 cases (65.6%), diarrhea or vomiting in 8 cases (13.1%), and headache in 4 cases (6.6%). After admission, the leukocyte count was normal in 40 cases (57.7%), higher in 9 cases (15.4%), and lower in 12 cases (26.9%). The lymphocyte count decreased in 53 cases (86.9%). CRP was increased in 29 cases (47.5%); PCT was increased in 15 cases (24.6%); ESR was increased in 38 cases (62.3%); D‐dimer increased in 39 cases (63.9%); ALT/AST increased in 40 cases (65.6%); CK/CK‐MB increased in 8 cases (13.1%); troponin I increased in 6 cases (9.8%); NT‐proBNP increased in 35 cases (57.4%); IL‐1 increased in 5 cases (8.2%); IL‐2 receptor increased in 28 cases (45.9%); IL‐6 increased in 23 cases (37.7%); IL‐8 increased in 15 cases (24.6%); IL‐10 increased in 12 cases (19.7%); and NTF increased in 22 cases (36.1%). The chest CT images showed that 38 cases (65.5%) of right lung lesions were more extensive than those of left lung lesions, 20 cases (34.5%) of left lung lesions were more extensive than those of right lung lesions, 42 cases (72.5%) of lower lobe lesions were more extensive than those of upper lobe lesions, 6 cases (10.3%) of upper lobe lesions were more extensive than those of lower lobe lesions, and 10 cases (17.2%) of upper and lower part lesions were roughly the same. Ground‐glass opacity (GGO) was found in 12 cases (20.7%); GGO with focal consolidation in 38 cases (65.5%); small patchy edge fuzzy density increased in 24 cases (41.4%); large consolidation in 20 cases (34.5%); reticular or fibrous cord in 54 cases (93.1%); and air bronchogram in 8 cases (13.8%). Conclusions. COVID‐19 patients in intensive care have no specific clinical manifestation and CT findings. However, analysis and summary of relevant data can help us assess the severity of the disease, decide the timing of treatment, and predict prognosis.
Leveraging Clinical Trial Populations and Data from the Children's Oncology Group for Cancer Survivorship Research
Authors: Chow Eric J. , Winestone Lena E. , Lupo Philip J. , Diller Lisa R. , Henderson Tara O. , Kadan-Lottick Nina S. , Levine Jennifer M. , Ness Kirsten K. , Bhatia Smita , Armenian Saro H.
Published: June 2022

Children and adolescents diagnosed with cancer can now expect an average 85% 5-year overall survival, with significant improvements in longer-term morbidity and mortality reported over the past several decades. However, the long-term impact of therapeutic agents and modalities introduced in recent years remains unclear and will require dedicated follow-up in the years ahead. The Children's Oncology Group (COG), a part of the NCI's National Clinical Trials Network, with over 200 sites across North America and beyond, enrolls more than 10,000 patients onto research protocols annually, inclusive of first-line clinical trials and nontherapeutic studies. COG provides a platform to conduct survivorship research with several unique strengths: (i) a huge catchment to ascertain relatively rare but important adverse events, (ii) study populations that are otherwise too rare to study in smaller consortia, including access to highly diverse patient populations, (iii) long-term follow-up of clinical trial populations linked to the original trial data, and (iv) a natural platform for intervention research. Enhancements in COG infrastructure facilitate survivorship research, including a COG patient registry (Project:EveryChild), availability of a long-term follow-up tracking resource, and successful deployment of various remote-based study procedures to reduce the burden on participants and participating institutions.
Osimertinib plus Selumetinib in EGFR-Mutated Non–Small Cell Lung Cancer After Progression on EGFR-TKIs: A Phase Ib, Open-Label, Multicenter Trial (TATTON Part B)
Authors: Yang James Chih-Hsin , Ohe Yuichiro , Chiu Chao-Hua , Ou Xiaoling , Cantarini Mireille , Jänne Pasi A. , Hartmaier Ryan J. , Ahn Myung Ju
Published: June 2022

Purpose:

MEK/ERK inhibition can overcome acquired resistance to osimertinib in preclinical models. Osimertinib [EGFR–tyrosine kinase inhibitor (TKI)] plus selumetinib (MEK1/2 inhibitor) was assessed in the global TATTON study.

Patients and Methods:

This multicenter, open-label, phase Ib study expansion cohort enrolled patients (aged ≥18 years) with MET-negative, EGFRm advanced NSCLC who had progressed on EGFR-TKIs. Patients were assigned to one of two cohorts by prior first- or second-generation or T790M-directed EGFR-TKI and received osimertinib 80 mg every day and intermittent selumetinib 75 mg twice a day orally. Safety and tolerability (primary objective) and antitumor activity determined by objective response rate (ORR), and progression-free survival (PFS) using RECIST v1.1 were assessed. Data cutoff: March 4, 2020.

Results:

Forty-seven patients received treatment (prior first- or second-generation EGFR-TKI, n = 12; prior T790M-directed EGFR-TKI, n = 35). Forty-four (94%) patients were Asian; 30 (64%) had baseline exon 19 deletion. Most common AEs were diarrhea (89%), decreased appetite (40%), and stomatitis (32%); 11/47 patients (23%) had an AE Grade ≥3 possibly causally selumetinib-related. ORR was 66.7% [95% confidence interval (CI), 34.9–90.1] in the prior first- or second-generation EGFR-TKI group, 22.9% (95% CI, 10.4–40.1) in the prior T790M-directed EGFR-TKI group, and 34.0% (95% CI, 20.9–49.3) overall; median PFS was 15.0 (95% CI, 2.7–33.0), 2.8 (95% CI, 1.6–5.5), and 4.2 months (95% CI, 2.7–7.2), respectively.

Conclusions:

In this small study, AEs and tolerability of osimertinib plus selumetinib were as expected, on the basis of previous studies. The combination demonstrated antitumor activity supportive of further investigation in patients with MET-negative, EGFRm advanced NSCLC who had progressed on a previous EGFR-TKI.
OLIG2 Is a Determinant for the Relapse of MYC-Amplified Medulloblastoma
Authors: Xu Zhenhua , Murad Najiba , Malawsky Daniel , Tao Ran , Rivero-Hinojosa Samuel , Holdhof Dörthe , Schüller Ulrich , Zhang Peng , Lazarski Christopher , Rood Brian R. , Packer Roger , Gershon Timothy , Pei Yanxin
Published: June 2022

Purpose:

Patients with MYC-amplified medulloblastoma (MB) have poor prognosis and frequently develop recurrence, thus new therapeutic approaches to prevent recurrence are needed.

Experimental Design:

We evaluated OLIG2 expression in a panel of mouse Myc-driven MB tumors, patient MB samples, and patient-derived xenograft (PDX) tumors and analyzed radiation sensitivity in OLIG2–high and OLIG2–low tumors in PDX lines. We assessed the effect of inhibition of OLIG2 by OLIG2-CRISPR or the small molecule inhibitor CT-179 combined with radiotherapy on tumor progression in PDX models.

Results:

We found that MYC-associated MB can be stratified into OLIG2–high and OLIG2–low tumors based on OLIG2 protein expression. In MYC-amplified MB PDX models, OLIG2–low tumors were sensitive to radiation and rarely relapsed, whereas OLIG2–high tumors were resistant to radiation and consistently developed recurrence. In OLIG2–high tumors, irradiation eliminated the bulk of tumor cells; however, a small number of tumor cells comprising OLIG2– tumor cells and rare OLIG2+ tumor cells remained in the cerebellar tumor bed when examined immediately post-irradiation. All animals harboring residual-resistant tumor cells developed relapse. The relapsed tumors mirrored the cellular composition of the primary tumors with enriched OLIG2 expression. Further studies demonstrated that OLIG2 was essential for recurrence, as OLIG2 disruption with CRISPR-mediated deletion or with the small molecule inhibitor CT-179 prevented recurrence from the residual radioresistant tumor cells.

Conclusions:

Our studies reveal that OLIG2 is a biomarker and an effective therapeutic target in a high-risk subset of MYC-amplified MB, and OLIG2 inhibitor combined with radiotherapy represents a novel effective approach for treating this devastating disease.
FDA Approval Summary: Cabozantinib for Differentiated Thyroid Cancer
Authors: Duke Elizabeth S. , Barone Amy K. , Chatterjee Somak , Mishra-Kalyani Pallavi S. , Shen Yuan-Li , Isikwei Emasenyie , Zhao Hong , Bi Youwei , Liu Jiang , Rahman Nam Atiqur , Wearne Emily , Leighton John K. , Stephenson Maritsa , Ojofeitimi Idara , Scepura Barbara , Nair Abhilasha , Pazdur Richard , Beaver Julia A. , Singh Harpreet
Published: June 2022

On September 17, 2021, the FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine (RAI)-refractory or ineligible. This is the first approval for patients with RAI-refractory locally advanced or metastatic DTC who have progressed following prior therapy and the first approval in pediatric patients with DTC. The approval was based on data from COSMIC-311 (Study XL184-311, NCT03690388), an international, randomized, double-blind trial in which patients with locally advanced or metastatic RAI-refractory DTC that progressed during or following treatment with at least one VEGFR-targeting tyrosine kinase inhibitor were treated with either cabozantinib 60 mg orally once daily (N = 170) or placebo with best supportive care (N = 88). The primary efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) by blinded independent central review per RECIST 1.1. The median PFS was 11.0 months [95% confidence interval (CI), 7.4–13.8] in the cabozantinib arm compared with 1.9 months (95% CI, 1.9–3.7) in the control arm, with an HR of 0.22 (95% CI, 0.15–0.31). The endpoint of ORR was not met. No new safety signals were identified with the exception of hypocalcemia, which was added as a warning in the product labeling.
Phenotype, Function, and Clinical Significance of CD26+ and CD161+Tregs in Splenic Marginal Zone Lymphoma
Authors: Tang Xinyi , Yang Zhi-Zhang , Kim Hyo Jin , Anagnostou Theodora , Yu Yue , Wu Xiaosheng , Chen Jun , Krull Jordan E. , Wenzl Kerstin , Mondello Patrizia , Bhardwaj Vaishali , Wang Junwen , Novak Anne J. , Ansell Stephen M.
Published: June 2022

Purpose:

Regulatory T-cells (Treg) are essential to Tregs homeostasis and modulate the antitumor immune response in patients with lymphoma. However, the biology and prognostic impact of Tregs in splenic marginal zone lymphoma (SMZL) have not been studied.

Experimental Design:

Biopsy specimens from 24 patients with SMZL and 12 reactive spleens (rSP) from individuals without lymphoma were analyzed by using CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), CyTOF (mass cytometry) analysis, and flow cytometry to explore the phenotype, transcriptomic profile, and clinical significance of intratumoral Tregs and their subsets. The biological characteristics and cell signaling pathways of intratumoral Treg subsets were confirmed by in vitro functional assays.

Results:

We found that Tregs are more abundant in SMZL patients' spleens than rSP, and Tregs from patients with SMZL and rSP can be separated into CD161+Treg and CD26+Treg subsets. CD161+Tregs are increased in SMZL but have dysregulated immune function. We found that CD161+Treg and CD26+Tregs have unique gene expression and phenotypic profiles and are differentially correlated with patient outcomes. Specifically, increased CD161+Tregs are significantly associated with a favorable prognosis in patients with SMZL, whereas CD26+Tregs are associated with a poor prognosis. Furthermore, activation of the IL2/STAT5 pathway contributes to the induction of CD26+Tregs and can be reversed by STAT5 inhibition.

Conclusions:

IL2/STAT5-mediated expansion of CD26+Tregs contributes to a poor clinical outcome in SMZL and may represent a therapeutic opportunity in this disease.
YES1: A Novel Therapeutic Target and Biomarker in Cancer
Authors: Garmendia Irati , Redin Esther , Montuenga Luis M. , Calvo Alfonso
Published: June 2022

YES1 is a nonreceptor tyrosine kinase that belongs to the SRC family of kinases (SFK) and controls multiple cancer signaling pathways. YES1 is amplified and overexpressed in many tumor types, where it promotes cell proliferation, survival, and invasiveness. Therefore, YES1 has been proposed as an emerging target in solid tumors. In addition, studies have shown that YES1 is a prognostic biomarker and a predictor of dasatinib activity. Several SFKs-targeting drugs have been developed, and some of them have reached clinical trials. However, these drugs have encountered challenges to their utilization in the clinical practice in unselected patients due to toxicity and lack of efficacy. In the case of YES1, novel specific inhibitors have been developed and tested in preclinical models, with impressive antitumor effects. In this review, we summarize the structure and activation of YES1 and describe its role in cancer as a target and prognostic and companion biomarker. We also address the efficacy of SFKs inhibitors that are currently in clinical trials, highlighting the main hindrances for their clinical use. Current available information strongly suggests that inhibiting YES1 in tumors with high expression of this protein is a promising strategy against cancer.
Inhibition of the Translation Initiation Factor eIF4A Enhances Tumor Cell Radiosensitivity
Authors: Lehman Stacey L. , Wechsler Theresa , Schwartz Kayla , Brown Lauren E. , Porco John A. , Devine William G. , Pelletier Jerry , Shankavaram Uma T. , Camphausen Kevin , Tofilon Philip J.
Published: June 2022

A fundamental component of cellular radioresponse is the translational control of gene expression. Because a critical regulator of translational control is the eukaryotic translation initiation factor 4F (eIF4F) cap binding complex, we investigated whether eIF4A, the RNA helicase component of eIF4F, can serve as a target for radiosensitization. Knockdown of eIF4A using siRNA reduced translational efficiency, as determined from polysome profiles, and enhanced tumor cell radiosensitivity as determined by clonogenic survival. The increased radiosensitivity was accompanied by a delayed dispersion of radiation-induced γH2AX foci, suggestive of an inhibition of DNA double-strand break repair. Studies were then extended to (-)-SDS-1–021, a pharmacologic inhibitor of eIF4A. Treatment of cells with the rocaglate (-)-SDS-1–021 resulted in a decrease in translational efficiency as well as protein synthesis. (-)-SDS-1–021 treatment also enhanced the radiosensitivity of tumor cell lines. This (-)-SDS-1–021-induced radiosensitization was accompanied by a delay in radiation-induced γH2AX foci dispersal, consistent with a causative role for the inhibition of double-strand break repair. In contrast, although (-)-SDS-1–021 inhibited translation and protein synthesis in a normal fibroblast cell line, it had no effect on radiosensitivity of normal cells. Subcutaneous xenografts were then used to evaluate the in vivo response to (-)-SDS-1–021 and radiation. Treatment of mice bearing subcutaneous xenografts with (-)-SDS-1–021 decreased tumor translational efficiency as determined by polysome profiles. Although (-)-SDS-1–021 treatment alone had no effect on tumor growth, it significantly enhanced the radiation-induced growth delay. These results suggest that eIF4A is a tumor-selective target for radiosensitization.
Effects of Dental Factors on Fungal Sinusitis
Authors: Basurrah Mohammed , Kim Do Hyun , Lee Il Hwan , Kim Sung Won , Kim Soo Whan
Published: June 2022

Objectives: This study aimed to investigate the associations between dental treatments and fungal maxillary sinusitis (FMS). Methods: We retrospectively reviewed medical charts between July 2014 and March 2019. In total, 100 cases of FMS were included in this study. We also recruited 200 patients as a control group in the same period. Therefore, each of the FMS, chronic rhinosinusitis (CRS), and normal sinus groups consisted of 100 patients. We recorded all endodontic treatments (EDTs), tooth extractions, dental implantations, and apical lesions (ALs). Results: The FMS group had higher incidences of tooth extraction (49% vs. 11%, respectively) and EDT (29% vs. 16%, respectively) compared to the normal sinus group and fewer ALs compared to the CRS group (6% vs. 24%, respectively). There were significant differences between the CRS and normal sinus groups in the extraction rate (53% vs. 11%, respectively) and frequency of ALs (24% vs. 4%, respectively). The dental implantation prevalence rates were similar across all 3 groups. Conclusion: The rates of tooth extraction were significantly higher in the FMS and CRS groups compared to the normal sinus group. In addition, of the 3 conditions, FMS was related to EDT, and CRS was related to ALs.
Molecular Biologic Milieu in Rhegmatogenous Retinal Detachment and Proliferative Vitreoretinopathy: A Literature Review
Authors: Ananikas Konstantinos , Stavrakas Panagiotis , Kroupis Christos , Christou Evita Evangelia , Brouzas Dimitrios , Petrou Petros , Papakonstantinou Dimitrios
Published: June 2022

Multiple lines of evidence support an immunologic response along with inflammation to be implicated in the pathophysiology of primary rhegmatogenous retinal detachment (RRD) and the development of proliferative vitreoretinopathy (PVR). The purpose of this review is to provide an update on the signaling molecules in the vitreous and subretinal fluid (SRF) involved in these processes. A detailed literature search was performed in PubMed database until November 2021. We identified all papers referring to inflammatory and immunological mediators in the context of primary RRD and in cases complicated by PVR. We analyzed prospective and retrospective cohort studies and reference lists of the retrieved articles. A comprehensive investigation of immunological and inflammatory responses provides significant evidence for the implication of varying signaling molecules in the pathophysiology of RRD and the development of PVR. The reviewed series has revealed that disruption of the normal equilibrium during these processes may be present in the vitreous and SRF of these eyes. The precise role of cytokines, chemokines, and growth factors in the pathophysiology of these disorders remains to be clearly elucidated. Overall, immunological and inflammatory signaling molecules are widely implicated in both primary RRD and PVR. The reviewed literature indicates that precise knowledge concerning the pathological milieu sheds light on the underlying pathophysiology and potential therapeutic targets and highlights unmet needs to be addressed by future research.
Estudos culturais africanos e latino-americanos: perspectivas do sul-global
Authors: Jacks Nilda , Libardi Guilherme , Fuel Isaias
Published: June 2022

Este texto tem como objetivo discutir a chamada internacionalização dos estudos culturais a partir de duas versões: a latino-americana e a africana. A originalidade da contribuição está na apresentação da corrente africana, pouco abordada na literatura brasileira e da América Latina. Descrevemos a conjuntura política em que os estudos culturais latino-americanos e africanos se desenvolvem, o contexto institucional, e apresentamos os principais pontos que caracterizam estas versões. Finalizamos nossas considerações tecendo aproximações entre ambas.
Retrato do espectador interativo como músico
Authors: Jost Francois
Published: June 2022

Com apoio em Goodman e Genette, o autor desenvolve dois conceitos centrais previamente cunhados pelo primeiro – autografia e alografia – para ajudar a responder se a oposição entre filme e TV está relacionada com diferenças na qualidade artística, um debate exacerbado pelo ingresso da Netflix em festivais de cinema. Usando também uma comparação com partituras musicais, o artigo indaga se o espectador do trabalho interativo pode ser chamado de operador, executante, ator ou intérprete.
Dichotomous Roles of Smooth Muscle Cell–Derived MCP1 (Monocyte Chemoattractant Protein 1) in Development of Atherosclerosis
Authors: Owsiany Katherine M. , Deaton Rebecca A. , Soohoo Karen G. , Tram Nguyen Anh , Owens Gary K.
Published: June 2022

Background:

Smooth muscle cells (SMCs) in atherosclerotic plaque take on multiple nonclassical phenotypes that may affect plaque stability and, therefore, the likelihood of myocardial infarction or stroke. However, the mechanisms by which these cells affect stability are only beginning to be explored.

Methods:

In this study, we investigated the contribution of inflammatory MCP1 (monocyte chemoattractant protein 1) produced by both classical Myh11 (myosin heavy chain 11)
+
SMCs and SMCs that have transitioned through an Lgals3 (galectin 3)
+
state in atherosclerosis using smooth muscle lineage tracing mice that label all Myh11
+
cells and a dual lineage tracing system that targets Lgals3-transitioned SMC only.

Results:

We show that loss of MCP1 in all Myh11
+
smooth muscle results in a paradoxical increase in plaque size and macrophage content, driven by a baseline systemic monocytosis early in atherosclerosis pathogenesis. In contrast, knockout of MCP1 in Lgals3-transitioned SMCs using a complex dual lineage tracing system resulted in lesions with an increased Acta2 (actin alpha 2, smooth muscle)
+
fibrous cap and decreased investment of Lgals3-transitioned SMCs, consistent with increased plaque stability. Finally, using flow cytometry and single-cell RNA sequencing, we show that MCP1 produced by Lgals3-transitioned SMCs influences multiple populations of inflammatory cells in late-stage plaques.

Conclusions:

MCP1 produced by classical SMCs influences monocyte levels beginning early in disease and was atheroprotective, while MCP1 produced by the Lgals3-transitioned subset of SMCs exacerbated plaque pathogenesis in late-stage disease. Results are the first to determine the function of Lgals3-transitioned inflammatory SMCs in atherosclerosis and highlight the need for caution when considering therapeutic interventions involving MCP1.
Probe Specification and Agreement Variation: Evidence from the Algonquian Inverse
Authors: Oxford Will
Published: June 2022

The distribution of a special agreement pattern known as the “inverse” varies across the Algonquian languages. This article shows that, under an interaction-and-satisfaction model of ϕ-agreement (Deal 2015, 2021), twelve distinct distributions of inverse agreement can be derived simply by varying the interaction and satisfaction conditions of the probe on Infl. This syntax-based approach to agreement variation has strong predictive power: it not only accounts for the twelve attested patterns but also rules out the unattested patterns, a result that a less restrictive postsyntactic approach cannot deliver. The Algonquian data thus provide support for a syntactic model of agreement patterns in general, and for the interaction-and-satisfaction model in particular.
Visibility and Intervention in Allomorphy: Lessons from Modern Greek
Authors: Paparounas Lefteris
Published: June 2022

An often discussed dimension of the locality conditions on allomorphy is visibility: when do the trigger and target of allomorphy “see” each other? An equally important dimension is intervention: when do the trigger and target stop seeing each other? Through the lens of a detailed analysis of Greek verbal morphology, I examine the conditions under which intervention forces the insertion of a default exponent. On the basis of two case studies on affixal allomorphy and one on stem allomorphy, I argue that patterns of intervention are easily accommodated under adjacency-based theories of the locality of allomorphy, and mysterious under less restrictive alternatives.
Forecaster (Mis-)Behavior
Authors: Broer Tobias , Kohlhas Alexandre N.
Published: June 2022

We document two stylized facts in expectational survey data. First, professional forecasters overrevise their macroeconomic expectations. Second, such overrevisions mask evidence of both over- and underreactions to public signals. We show that the first fact is inconsistent with standard models of noisy rational expectations, but consistent with behavioral and strategic models. The second fact, in contrast, presents a puzzle for existing theories. We propose an extension of noisy rational expectations that allows forecasters to be overconfident in their information. We show that this feature when combined with the endogeneity of public signals leads to over- and undereactions consistent with the data.
Higher Education and Local Educational Attainment: Evidence from the Establishment of U.S. Colleges
Authors: Russell Lauren C. , Yu Lei , Andrews Michael J.
Published: June 2022

We investigate how the presence of a college affects local educational attainment. As counterfactuals for current college locations, we use historical “runner-up” locations that were strongly considered to become college sites but were ultimately not chosen. We find that winning counties today have college degree attainment rates 56% higher than runner-up counties and more private-sector employment in human-capital-intensive industries. These effects are not driven primarily by recent in-migration of educated adults, and alternative public investments did not have similar effects on local educational attainment. The results indicate that colleges played an important role in shaping long-run local outcomes.