bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Nitrogen and Phosphorus Nutrients on the Proliferation of Heterosigma Akashiwo under the Background of Mobile Big Data
Authors: Duan Meina , Huang Jiamin , Zheng Erbang , Liu Yaoqian
Published: September 2022

In the era of information explosion, mobile data is developing rapidly, and many fields are facing the challenges of data collection, analysis and operation. Heterosigma akashiwo is a kind of wide temperature and wide salt algae, belonging to the class Echinococcus and the genus heterobenthos. It is widely distributed in the coastal waters of the world. It has formed harmful red tides for many times in many countries, causing a large number of fish deaths, causing great economic losses and serious damage to aquatic resources. If toxic red tides break out frequently, they will pose a great threat to public health. Seawater eutrophication is the main environmental inducement for the formation of red tide by Heterosigma akashiwo. In particular, the content of nutrients in seawater significantly affects the reproduction of Heterosigma akashiwo and the excessive proliferation of plankton such as algae. At the same time, a large number of planktons will devour the dissolved oxygen in the water, thus affecting the photosynthesis of the water body, resulting in the deterioration of the water quality and the damage to the functions of ecology and water resources. As for the effects of nitrogen, phosphorus, iron and different vitamins on the growth of Heterosigma akashiwo, this paper takes Heterosigma akashiwo as the research object, and focuses on the analysis of the effects of ammonium chloride, urea and sodium dihydrogen phosphate on the proliferation of Heterosigma akashiwo. The results showed that the higher or lower the concentration of nitrogen and phosphorus, the slower the proliferation rate of Heterosigma akashiwo; Heterosigma akashiwo had the maximum proliferation rate under the nitrogen concentration of 300–500 μmol/L; At the concentration of 10∼15 μmol/L phosphorus, its growth rate is the fastest and its proliferation level is the highest. The selected nitrogen and phosphorus have a very significant impact on the proliferation of microalgae.
Teaching Practice of College Students’ Marketing Course Based on the Background of the Internet Era
Authors: Chi Zhong , Yang Tianxiao
Published: September 2022

Marketing teaching is still largely based on theoretical teaching. This kind of teaching mode is difficult to greatly improve the marketing practice teaching, students’ practical ability, innovative thinking ability, and so on. At the same time, the teaching arrangement of marketing training is not standardized, which makes it difficult to provide effective guidance for students. This paper attempted to reform the traditional teaching methods of marketing courses in universities, and deeply studied the teaching methods of traditional college students’ marketing courses under the background of the network, as well as conducted marketing practice according to two different Internet algorithm marketing strategy models. The experimental data showed that the average teaching quality score of the traditional marketing course teaching mode was only 6.9, while the teaching quality score of the marketing course teaching mode under the Internet background was 8.15; the market share of water heaters under the neural network-based marketing strategy increased by 8.1% within 4 months, while the market share of water heaters under the data mining-based marketing strategy decreased by 4.8%. Therefore, it can be seen that the marketing course teaching mode under the Internet background can improve the teaching quality, and the marketing effect of the neural network-based marketing strategy is better.
Deep-Learning-Based 3D Reconstruction: A Review and Applications
Authors: Li Yinhai , Wang Fei , Hu Xinhua
Published: September 2022

In recent years, deep learning models have been widely used in 3D reconstruction fields and have made remarkable progress. How to stimulate deep academic interest to effectively manage the explosive augmentation of 3D models has been a research hotspot. This work shows mainstream 3D model retrieval algorithm programs based on deep learning currently developed remotely, and further subdivides their advantages and disadvantages according to the behavior evaluation of the algorithm programs obtained by trial. According to other restoration applications, the main 3D model retrieval algorithms can be divided into two categories: (1) 3D standard restoration methods supported by the model, i.e., both the restored object and the recalled object are 3D models. It can be further divided into voxel-based, point coloring-based, and appearance-based methods, and (2) cross-domain 3D model recovery methods supported by 2D replicas, that is, the retrieval motivation is 2D images, and the recovery appearance is 3D models, including retrieval methods supported by 2D display, 2D depiction-based realistic replication and 3D mold recovery methods. Finally, the work proposed novel 3D fashion retrieval algorithms supported by deep science that are analyzed and ventilated, and the unaccustomed directions of future development are prospected.
Expression of Adenosine Deaminase and NLRP3 Inflammasome in Tuberculous Peritonitis and Their Relationship with Clinical Efficacy
Authors: Su Hongwei , Yan Guorong , Li Zijian , Fu Lin , Li Lingdi
Published: September 2022

Objective. Tuberculous peritonitis (TP) can cause multiple infections of surrounding organs and tissues, leading to organ failure and endangering life safety. In this research, the relationship between adenosine deaminase (ADA), NLRP3 inflammasome, and TP and its clinical significance will be deeply explored, so as to provide new directions and reliable reference opinions for future clinical diagnosis and treatment. Methods. Altogether, 59 TP patients (research group, RG) and 52 non-TP patients (control group, CG) who were admitted to our hospital from May 2014 to June 2018 were regarded as research objects. Ascites samples of RG before treatment (admission) and one month after treatment and CG before treatment were obtained, and the ADA and NLRP3 levels were tested to evaluate the clinical and prognostic significance of the two in TP. Results. Before treatment, ADA and NLRP3 in RG were higher than CG (

P
<
0.05

), and the sensitivity and specificity of combined detection of the two in predicting TP occurrence were 89.83% and 73.08% (

P
<
0.05

). In addition, ADA and NLRP3 in RG patients were positively correlated with the disappearance time of abdominal pain and ascites (

P
<
0.05

) and had excellent predictive effect on the adverse reactions during treatment (

P
<
0.05

). After treatment, both in RG patients decreased, which was inversely proportional to the clinical efficacy (

P
<
0.05

). Prognostic follow-up manifested that ADA and NLRP3 in relapse patients were higher than those without recurrence after treatment (

P
<
0.05

). Conclusion. The increase of ADA and NLRP3 in TP is relevant to the adverse reactions during treatment, clinical efficacy, and prognosis recurrence after treatment. It can be used as a disease marker to confirm, intervene, and evaluate TP progression promptly.
[Retracted] Development Strategy of College Sports Information Management System Using Data Mining in Mobile Internet Environment
Authors: Zhang Yi
Published: September 2022

A strong basis has been set for the digitization of school management by the growth of big data and the Internet. However, there is not specialised software that can be used in schools to handle teaching materials and carry out teaching activities, particularly in school physical education. Most teachers struggle with significant information management issues in the conventional college sports management information system. Along with people’s interest in physical education in colleges and universities, the study of the college sports management information system’s development plan has emerged as the primary research area in the present day. The use of data mining in the development strategy of the sports management information system was therefore considered in conjunction with the actual situation of school sports information management. The experiment also introduced and provided a detailed explanation of the algorithm used in data mining. To fully explore the system strategy’s development impact was the specific goal. In order to realise the management function of the sports management information system, serve the information management of each school, increase information management efficiency by 6.58%, and improve user satisfaction; data mining was introduced into the development strategy of management information system through the discovery of experimental data.
Monitoring and Analysis Solid Formulation Dissolution Phenomenon with Image Recognition Technologies
Authors: Wang Haoyu , Kwong Chiew Foong , Liu Qianyu , Liu Junyao , Liu Zhixin , Lee Boon Giin , Huang Liang
Published: September 2022

The dissolution test has become the most important quality index in the research and development of solid formulation, especially the evaluation of drug bioequivalence. However, it had low operability, was tedious, and was always overlooked. The previously related studies required a fixed tablet and analysed the recorded video by disso GUARO PRO and Microsoft Paint™. Therefore, we have developed a novel image recognition system to automatically track the moving tablet and analyse the volume change at the same time. Image recognition technology is often used to monitor the dissolution process. The camera system with visible light and infrared camera functions was placed on the dissolution tester. The system collects the plate image for binary processing and then records and calculates its pixel area, which can automatically record the volume change of the tablet in the dissolution test, no matter disintegration or corrosion.
Meta-Analysis of the Prognostic and Predictive Role of the CpG Island Methylator Phenotype in Colorectal Cancer
Authors: Wang Jing , Deng Zhujun , Lang Xiaoqiang , Jiang Juan , Xie Kang , Lu Sifen , Hu Qiongxia , Huo Yuwei , Xiong Xinru , Zhu Niu , Zhang Wengeng
Published: September 2022

Background. Various studies have produced contradictory results on the prognostic role of the CpG island methylator phenotype (CIMP) among colorectal cancer (CRC) patients. Although a meta-analysis published in 2014 reported a worse prognosis of CIMP among CIMP-high (CIMP-H) CRC patients, the sample sizes of the major included studies were small. In this study, we included the most recent studies with large sample sizes and performed an updated meta-analysis on the relationship between CIMP and CRC prognosis. Methods. A search of MEDLINE, Web of Science, and Cochrane for studies related to CIMP and CRC published until July 2021 was conducted based on the PICO (participant, intervention, control, outcome) framework. Data extraction and literature analyses were performed according to PRISMA standards. Results. In the present update, 36 eligible studies (20 recently published) reported survival data in 15315 CRC patients, 18.3% of whom were characterized as CIMP-H. Pooled analysis suggested that CIMP-H was associated with poorer overall survival (OS) (

hazard
 
ratio
 

HR

=
1.37

, 95% CI: 1.26–1.48) and disease-free survival/progression-free survival/recurrence-free survival (DFS/PFS/RFS) (

HR
=
1.51

, 95% CI: 1.19–1.91) among CRC patients. Subgroup analysis based on tumor stage and DNA mismatch repair (MMR) status showed that only patients with stages III-IV and proficient MMR (pMMR) tumors showed a significant association between CIMP-H and shorter OS, with HRs of 1.52 and 1.37, respectively. Three studies were pooled to explore the predictive value of CIMP on CRC patient DFS after receiving postoperative chemotherapy, and no significant correlation was found. Conclusion. CIMP-H is associated with a significantly poor prognosis in CRC patients, especially those with stage III-IV and pMMR tumors. However, the predictive value of CIMP needs to be confirmed by more prospective randomized studies.
Green Synthesis of Trimetallic Nanocomposite (Ru/Ag/Pd)-Np and Its In Vitro Antimicrobial and Anticancer Activities
Authors: Hussein Shaimaa , Mahmoud Ayman M. , Elgebaly Hassan A. , Hendawy Omnia Magdy , Hassanein Emad H. M. , Moustafa Shaima M. N. , Alotaibi Nasser F. , Nassar Amr M.
Published: September 2022

In this study, we used the aqueous extract of garlic tunicate leaf to reduce a mixture of equal amounts of ruthenium chloride, silver nitrate, and palladium acetate for the biosynthesis of ruthenium/silver/palladium trimetallic nanocomposite (Ru/Ag/Pd)-Np. Some physicochemical tools were used for nanocomposite characterization, including Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), UV-Vis spectroscopy (UV-Vis), scanning electron microscope (SEM), and transmittance electron microscope (TEM). XRD revealed that the crystal size of the nanocomposite is 15.67 nm. The TEM images showed that the particle size ranged 50–90 nm. The antimicrobial efficacy of the nanocomposite was examined against Aspergillus flavus, Aspergillus niger, Candida albicans, Candida glabrata, Escherichia coli, and Bacillus cereus. The results showed a potent antimicrobial activity toward all tested microorganisms. (Ru/Ag/Pd)-Np showed antiproliferative activity against Caco-2, HepG2, and K562 cell lines. The antiproliferative potential of (Ru/Ag/Pd)-Np was significantly improved following UV irradiation.
Application and Safety Performance of Nanomaterials in Clothing Design Engineering
Authors: Cao Yanju , Zhang Jingqiong , Wei Sainan
Published: September 2022

With the rapid development of social economy, people’s living environment has undergone tremendous changes. At the same time as social development, it will also be accompanied by many problems, such as environmental degradation, air quality decline, and frequent diseases. Studies have found that due to the destruction of the ozone layer, the ultraviolet rays in the atmosphere cannot be effectively absorbed, which hinders the reduction, and the risk of skin cancer increases year by year. Environmental pollution is becoming more and more serious, bacteria multiply, and textiles are also polluted. Every year, a large number of textiles are discarded due to pollution, so people have new demands on the functionality of textiles. In recent years, with the breakthrough development of nanomaterials research enterprises, nanomaterials are increasingly used in textiles to meet people’s new needs for textiles. Nano-TiO2 has high antiultraviolet performance and self-cleaning performance and also has excellent performance in antibacterial and bacteriostatic issues. Toxicological experiments were carried out on nano-TiO2 materials. The results showed that the cytotoxicity of different cells in different concentrations of nano-TiO2 was very small, the cell viability was not less than 80%, and there was a certain concentration effect.
A Hybrid Model for Commercial Brand Marketing Prediction Based on Multiple Features with Image Processing
Authors: Wang Furong , Zhao Li
Published: September 2022

Recently, deep learning has been employed in automatic feature extraction and has made remarkable achievements in the fields of computer vision, speech recognition, natural language processing, and artificial intelligence. Compared with the traditional shallow model, deep learning can automatically extract more complex features from simple features, which reduces the intervention of artificial feature engineering to a certain extent. With the development of the Internet and e-commerce, picture advertising, as an important form of display advertising, has the characteristics of high visibility, strong readability, and easy-to-obtain user recognition. An increasing number of Internet companies are paying attention to what kind of advertising pictures can attract more clicks. Based on deep learning technology, this paper studies the prediction model of click-through rate (CTR) for advertising and proposes an end-to-end CTR prediction depth model for display advertising, which integrates the feature extraction of display advertising and CTR prediction to directly predict the probability of an advertisement image being clicked by users. This paper studies the deep-seated nonlinear characteristics through the multilayer network structure of the deep network and carries out several groups of experiments on the private display advertising data set of a commercial advertising platform. The results show that the model proposed in this paper can effectively improve the prediction accuracy of CTR compared with other benchmark models and predict whether an advertisement is clicked or not by given advertisement information and user information. By establishing a reasonable advertising click-through rate prediction model, it can help the platform estimate future revenue so as to make cooperative decisions with advertisers. For advertisers, it is necessary to evaluate the price by predicting the click-through rate and estimate the bidding price of their own advertisements.
Application of Genetic Algorithm and U-Net in Brain Tumor Segmentation and Classification: A Deep Learning Approach
Authors: Arif Muhammad , Jims Anupama , F. Ajesh , Geman Oana , Craciun Maria-Daniela , Leuciuc Florin
Published: September 2022

The development of unusual cells in the cerebrum causes brain cancer. It is classified primarily into two classes: a noncarcinogenic (benign) type of growth and cancerous (malignant) growth. Early detection of this disease is a quintessential task for all medical practice professionals. For traditional approaches of tumor detections, certain limitations exist. They include less effectiveness, inability to detect due to low-quality processing of images, less dataset for training and testing, less predictive nature to models, and skipping of quintessential stages. All these lead to inaccurate results of tumor detections. To overcome this issue, this paper brings an effective deep learning technique for brain tumor detection with the following stages: (a) data collection from REMBRANDT dataset containing multisequence MRI of 130 patients; (b) preprocessing using conversion to greyscale, skull stripping, and histogram equalization; (c) segmentation uses genetic algorithm; (d) feature extraction using discrete wavelet transform (DWT); (e) particle swarm optimization technique for feature selection; (f) classification using U-Net. Experiment evaluation states that the proposed model (GA-UNET) outperforms (accuracy: 0.97, sensitivity: 0.98, specificity: 0.98) compared to other advanced models.
Potential of Azadirachta indica as a Capping Agent for Antiviral Nanoparticles against SARS‐CoV‐2
Authors: Foka Frank Eric Tatsing , Manamela Nanabi , Mufamadi Steven Maluta , Mufhandu Hazel Tumelo
Published: September 2022

A rare type of pneumonia later on referred to as COVID‐19 was reported in China in December 2019. Investigations revealed that this disease is caused by a coronavirus previously identified as SARS‐CoV‐2, and since then, it has become a global pandemic with new strains emerging rapidly as a result of genetic mutations. Various therapeutic options are being explored in order to eradicate this pandemic even though approved vaccine candidates are being currently rolled out globally. Most medicinal plant extracts have astonishing properties, and they can therefore be used in the biosynthesis of effective antiviral nanoparticles. In this systematic review, we aimed to highlight the specific attributes that make Azadirachta indica (neem plant) a suitable candidate for the biosynthesis of anti‐SARS‐CoV‐2 nanoparticles. A systematic investigation was therefore carried out in PubMed, Scopus, Web of Science, and AJOL databases with the keywords “Nanoparticles,” “Biosynthesis,” “Antivirals,” “SARS‐CoV‐2,” and “Azadirachta indica.” 1216 articles were retrieved by the 21st of February 2022, but we screened studies that reported data on biomedical and antimicrobial assessment of Azadirachta indica extracts. We also screened studies that were reporting nanoparticles possessing antiviral properties against SARS‐C0V‐2, narrowing our results to 98 reports. Herein, the SARS‐CoV‐2 viral structure is briefly discussed with nanoparticles of biomedical importance in the design of SARS‐CoV‐2 antivirals. Most importantly, we focused on the biomedical and antiviral properties of Azadirachta indica extracts that could be of importance in the design of potential anti‐SARS‐CoV‐2 nanoformulations.
Traditional Chinese Medicine Regulates Th17/Treg Balance in Treating Inflammatory Bowel Disease
Authors: Xie Fengjiao , Xiong Qin , Li Yilin , Yao Chengjiao , Wu Ruike , Wang Qiuxiang , Luo Lihong , Liu Hongling , Feng Peimin
Published: September 2022

Inflammatory bowel disease (IBD), also known as chronic nonspecific inflammatory disease of the colon and rectum, is primarily characterized by mucopurulent bloody stools, diarrhea, abdominal pain, and tenesmus. Its cause is uncertain. IBD patients frequently experience a high rate of recurrence, a protracted treatment course, and a high risk of carcinogenesis. Additionally, the difficulty of treatment is significantly increased by these illness characteristics. Currently, the normal treatment for this illness can lessen symptoms to some amount and even meet clinical treatment requirements, but due to serious side effects, unfavorable reactions, and high costs, we need to develop better complementary and alternative medicines. A number of studies have found that the imbalance of T helper cell 17 (Th17)/regulatory T cells (Treg) contributes significantly to the occurrence and progression of IBD and that Th17/Treg balance restoration is frequently useful in the management of IBD. As a result, regulating the Th17/Treg balance has also emerged as a novel approach to treating IBD. Traditional Chinese medicine (TCM) has gained popularity in recent years due to its advantages of low side effects, a variety of targets, and multiple regulatory mechanisms. A number of studies have shown that TCM can successfully intervene in the Th17/Treg imbalance and restore it, and research on the prevention and treatment of IBD by TCM by restoring Th17/Treg has also shown promising results. The characteristics of the Th17/Treg balance and its role in the pathogenesis of IBD, as well as the role of TCM in regulating the Th17/Treg imbalance, are analyzed. The research results are expected to provide a theoretical basis for the clinical treatment and pathology mechanism research of IBD.
Open Sharing Management of Artificial Intelligence Laboratory Based on Deep Fusion of Big Data
Authors: Liang Caizhi
Published: September 2022

In order to improve the efficiency of information management of open laboratories in colleges and universities and reduce the cost of information management of open laboratories in colleges and universities, this paper proposes the open sharing management of artificial intelligence laboratories based on the deep integration of big data. The infrastructure layer of the system transmits the information management data of the university open laboratory to the cloud platform layer. The cloud platform layer completes the data management, cloud computing, and access control and transmits the processed data to the application layer. The application layer realizes the information management of the university open laboratory according to the data fed back by the cloud platform layer. Among them, in the process of data transfer in open laboratories of colleges and universities, pyramid technology is used to realize data transfer, and the optimization calculation of particle swarm optimization algorithm is used to complete the transfer of multidimensional and complex data transmission information, so as to improve the efficiency of data transfer. The experimental results show that the system has high accuracy in transferring multidimensional and complex data in university open laboratories, the average resource utilization rate of the system is as high as 92%, the average response of the system is as fast as 8.5 ms, and the management cost is effectively reduced. Conclusion. The system designed in this paper can reduce the information management cost of open laboratories in colleges and universities.
IoT and Machine Learning‐Based Smart Automation System for Industry 4.0 Using Robotics and Sensors
Authors: Sujatha M. , Priya N. , Beno A. , Blesslin Sheeba T. , Manikandan M. , Tresa I. Monica , Jose P. Subha Hency , Peroumal Vijayakumar , Thimothy Sojan Palukaran
Published: September 2022

The concept of Industry 4.0, the fourth industrial revolution, is not yet widespread, despite the extensive research in this domain. Several aspects of human life will be improved with the implementation of Industry 4.0. Various levels of manufacturing processes, the end‐users, cyberphysical system designers, managers, and all employees in the manufacturing process as well as the supply chains, will be influenced by the changes in manufacturing models and business paradigms caused by the implementation of Industry 4.0. Smart automation is enabled in the manufacturing industry with the evolution of Industry 4.0. Smart decision‐making, knowledge, problem‐solving, self‐diagnosis, self‐configuration, and self‐automation are enabled in industries with this technology. In this work, the decision tree algorithm is used for monitoring energy consumption in machines and appliances, predicting future behaviour, and detecting anomalous behaviour. The efficiency of the proposed system is evaluated, and compared with existing methodologies, it offers an efficiency of 78%. Several standardization issues, security issues, resource planning challenges, legal issues, and issues due to changing business paradigms are faced with the implementation of this technology. The implementation of Industry 4.0 and its success or failure is completely dependent on the entire production chain and all the participants, from manufacturers to end‐users.
Research on Mechanical Characteristics of Asphalt Graded Gravel Layer with Ballast Bed under Train Load
Authors: Sun Shu
Published: September 2022

This article carries out laboratory tests, driving tests, and discrete element method simulations to study the mechanical properties of ballasted tracks including asphalt graded gravel and the influence of factors such as the thickness of asphalt graded gravel layer and train speed on the dynamic characteristics of the closed structure of asphalt graded gravel. It was discovered that the asphalt graded gravel can improve the bearing capacity of the ballasted track subgrade structure and improve the stability of the ballast bed. Comparative analysis shows that as the depth of the ballast bed increases, the amplitude and frequency of the velocity fitting function of each layer gradually decrease. Appropriately increasing the depth is beneficial to the stability of the ballast bed; the vertical dynamic deformation and dynamic stress decrease with the increase of the thickness of asphalt graded gravel layer; with the increase of train speed, the peak frequency of the corresponding spectrum of asphalt graded gravel layer acceleration increases. There are currently few research studies on the asphalt graded crushed stone structure laid in the ballast bed, especially the mechanical properties of the asphalt graded crushed stone structure laid by the discrete element simulation are still blank. The acceleration of the asphalt graded gravel layer increases corresponding to the peak frequency of the spectrum. The peak frequency of the acceleration response of the asphalt graded gravel layer increases. The research rules can provide a reference for the research and development of shock absorption equipment. The research results of this article can provide technical support for the application of asphalt graded gravel in railway engineering.
Research on the Evolutionary Game Model and Stable Strategy of Urban Management Law Enforcement
Authors: Xin Fangkun , Wang Zijing
Published: September 2022

As a form of the informal economy, countries around the world have different policies towards street vendors. This paper constructs a law enforcement game model composed of the Chengguan, street vendors, and urban residents in China. Based on the evolutionary game theory, we achieved the evolutionary stable equilibrium points under complying with different constraint conditions by solving the replicator dynamic equations of parties in the dynamic system. Through the gradual stability analysis of the equilibrium point, the stable strategy of the evolutionary game can be calculated. It is found that the flexible law enforcement behavior of urban management departments plays an important leading role in urban street governance. Flexible law enforcement not only requires macro policy arrangements but also tests the executive wisdom of street bureaucrats.
Sample Density Clustering Method Considering Unbalanced Data Distribution
Authors: Wang Changhui
Published: September 2022

The data distribution of the multidimensional array sensor is unbalanced in data sample collection. To improve the clustering ability of data samples, a data density clustering method of sparse scattered points and multisensor array sensor samples based on the analysis of unbalanced data distribution characteristics is proposed. The sparse scattered multisensor array network’s sample data collection structure is created using the Voronoi polygon topology. By analyzing the unbalanced parameters between data classes and reconstructing the characteristic space of data sample sequence, the time series of sample data collected by sparse scattered multisensor array is reorganized, and the statistical characteristic quantity and high-order cumulant of sample data collected by sparsely scattered multisensor array are extracted. Combined with the learning algorithm of unbalanced data distribution sample feature fusion, the fuzzy clustering of sample data information flow collected by sparse scattered multisensor array elements is realized. According to the feature clustering and convergence analysis, the sparse scattered feature detection method is adopted to realize the data density clustering and data structure optimization configuration of sparse scattered multisensor array elements. The test results show that the method in this paper has good convergence, strong spectrum expansion ability, and low error rate of data clustering when collecting samples with sparse scattered points and multisensor arrays.
[Retracted] Cell‐in‐Cell: From Cell Biology to Translational Medicine
Authors: Chen Qiao , Wang Xiaoning , He Meifang
Published: September 2022

Cell‐in‐cell structures (CICs) refer to cytoplasmic internalization of a cell by another cell, which are found throughout various biological systems and have been a part of scientific dogma for a long time. However, neither the mechanisms underlying this phenomenon nor their possible roles in disease development have resulted in major breakthroughs until recent years. In view of the ubiquity of CICs in inflammatory tissue and tumors, it is tempting to think that these specific structures could be associated with clinical diagnosis and treatment and thus would become a new hotspot for translational medicine. Translational medicine is a new concept in the field of international biomedical research that appeared in the last 20 years, which transforms basic research into clinical application. With the growing interest in this field, this review addresses recent research on CICs and their potential clinical implications in cytomorphological diagnosis and the pathology of human diseases, while discussing as yet unanswered questions. We also put forward future directions to reduce the gap in our knowledge caused by our currently limited understanding of CICs.
Proteochemometric Method for pIC50 Prediction of Flaviviridae
Authors: Singh Divye , Mahadik Avani , Surana Shraddha , Arora Pooja
Published: September 2022

Viruses remain an area of concern despite constant development of antiviral drugs and therapies. One of the contributors is the Flaviviridae family of viruses causing diseases that need attention. Among other anitviral methods, antiviral peptides are being studied as viable candidates. Although antiviral peptides (AVPs) are emerging as potential therapeutics, it is important to assess the efficacy of a given peptide in terms of its bioactivity. Experimental identification of the bioactivity of each potential peptide is an expensive and time consuming task. Computational methods like proteochemometric modeling (PCM) is a promising method for prediction of bioactivity (pIC50) based on peptide and target sequence pair. In this study, we propose a prediction of pIC50 of AVP against the Flaviviridae family that may help make the decision to choose a peptide with desired efficacy. The peptides data was collected from a public database and target sequences were manually curated from literature. Features are calculated using peptide and target sequence PCM descriptors which consist of individual and cross‐term features of peptide and respective target. The resultant R2 and MAPE values are 0.85 and 8.44%, respectively, for prediction of pIC50 value of AVPs.
Abstract A017: Multiple intratumoral sources of kit ligand promote oncogenic kit signaling in gastrointestinal stomal tumor
Authors: Tieniber Andrew D. , Rossi Ferdinando , Hanna Andrew , Liu Mengyuan , Etherington Mark , Do Kevin , Wang Laura , DeMatteo Ronald P.
Published: September 2022

Introduction: Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and is typically driven by a single mutation in the Kit receptor. While highly effective, tyrosine kinase inhibitors like imatinib are not curative. The natural ligand for the Kit receptor is Kit Ligand (KitL), which exists in both soluble and membrane-bound forms. We sought to determine the role of KitL in the oncogenic Kit signaling of GIST. Methods: KitV558Δ/+ mice, which spontaneously develop an intestinal GIST, were treated with imatinib or vehicle for 1 week, and sorted non-immune (CD45-) cells from tumors were submitted for single-cell RNA sequencing (n=3/group). GIST T1 cells were treated with KitL with or without imatinib and oncogenic Kit signaling was evaluated. KitV558Δ/+ mice were crossed with various KitL mutant and inducible models and tumor weights were measured (n=3-4/group). Human GISTs were stained for KitL expression by IHC, and an existing bulk RNA sequencing human GIST dataset with matched human serum was analyzed. Results: Unsupervised clustering revealed endothelial, smooth muscle, and tumor cells had high expression of KitL RNA in untreated tumors from KitV558Δ/+ mice. Imatinib therapy increased KitL RNA in all 3 cell types, suggesting that extra-tumoral KitL expression is dependent on oncogenic signaling (p<0.05). In GIST T1 cells, exogenous KitL increased Kit activation and reduced imatinib’s efficacy. Tumors from mice with homozygous KitL deletion (KitV558Δ/+;Etv1Cre-ERT2/+;KitLflox/flox) were smaller than tumors from littermates with heterozygous KitL deletion (KitV558Δ /+;Etv1Cre-ERT2/+;KitLflox/+), providing evidence that KitL contributes to GIST development in vivo despite the presence of mutated Kit (p<0.05). Furthermore, tumors from KitV558Δ/+;KitLKitL1Δ/KitL1Δ mice, which lack the proteolytic cleavage site for soluble KitL, were smaller than matched KitV558Δ/+ mice, indicating that soluble KitL is important for maximal tumor growth in vivo (p<0.05). Heterogeneous KitL expression was confirmed in human GISTs by IHC. Human serum contained more KitL in patients with tumors resistant to imatinib and in those with tumors expressing more KitL RNA(p<0.05). Conclusions: KitL is produced by multiple cell types within GIST and contributes to oncogenesis. Targeting KitL may be important for optimal tumor therapy.

Citation Format: Andrew D. Tieniber, Ferdinando Rossi, Andrew Hanna, Mengyuan Liu, Mark Etherington, Kevin Do, Laura Wang, Ronald P. DeMatteo. Multiple intratumoral sources of kit ligand promote oncogenic kit signaling in gastrointestinal stomal tumor [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr A017.
Abstract B020: Multimodal single-cell analyses reveal identification of unique transcriptional subgroups in ewing sarcoma
Authors: Apfelbaum April A. , Waltner Olivia , Bhise Shruti S. , Kanaan Sami , Sarthy Jay F. , Furlan Scott N. , Lawlor Elizabeth R.
Published: September 2022

Ewing sarcoma (EwS) tumors are driven by pathognomonic fusions between FET proteins and ETS family transcription factors (most frequently EWS::FLI1). EWS::FLI1 drives tumorigenesis through massive transcriptomic and epigenomic rewiring. Despite mutational homogeneity, EwS are highly transcriptionally heterogeneous suggesting that cell context is a key determinant of EWS::FLI1-driven gene signatures. Fusion protein activity has been revealed as a core source of EwS heterogeneity. However, deep investigation into the transcriptomic and epigenomic heterogeneity of EwS cells has yet to be described. Molecular subtyping of EwS has thus far proven to be difficult to achieve with bulk RNA-sequencing approaches. We hypothesized that single-cell characterization of EwS cells would provide the necessary resolution to allow identification and characterization of transcriptionally distinct tumor subgroups. We subjected eight established EwS cell lines, one PDX-derived EwS line, and five non-EwS cell lines to single-cell multiomic (ATAC + RNA) sequencing. A range of 1300-3800 live cells were captured per sample, with an average of 25,000 transcript and accessible reads per cell. Initial analysis of transcriptomes confirmed the EwS-specific, EWS::FLI1-dependent signature gene sets in EwS samples. Integrated analysis of the multiome data from the 9 EwS samples identified inter-tumor heterogeneity and unsupervised k-means clustering revealed three molecular subgroups that were not evident from expression data alone. Subgroup 1 comprised only the A673 cell line, while the remaining 8 EwS samples were split between subgroups 2 and 3. Gene ontology analysis defined enrichment of distinct gene sets across the 3 subgroups. Interestingly, expression of subgroup 2-defining genes was reduced following knockdown of EWSR1::FLI1, while expression of subgroup 3-defining genes increased. Thus, these data show that transcriptionally distinct subgroups of EwS exist and these are defined, in part, by whether EWS::FLI1-dependent gene activation or gene repression dominates transcriptional rewiring. Our ongoing studies suggest that these molecular subgroups are defined by cooperation between the fusion and cell context-dependent transcription factors. Future analyses will determine if these distinct multiomic programs exist in primary patients tumors and test the pathobiologic and clinical significance of these novel molecular subgroups.

Citation Format: April A. Apfelbaum, Olivia Waltner, Shruti S. Bhise, Sami Kanaan, Jay F. Sarthy, Scott N. Furlan, Elizabeth R. Lawlor. Multimodal single-cell analyses reveal identification of unique transcriptional subgroups in ewing sarcoma [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr B020.
Abstract IA017: Impact of oxygen and nutrient availability on sarcoma tumor neighborhood
Authors: Simon M. Celeste
Published: September 2022

Molecular oxygen (O2) sustains intracellular bioenergetics and is consumed by numerous biochemical reactions, making it essential for most species on Earth. Accordingly, decreased oxygen concentration (hypoxia) is a major stressor that generally subverts life of aerobic species and is a prominent feature of pathological states encountered in bacterial infection, inflammation, wounds, cardiovascular defects and cancer. Therefore, key adaptive mechanisms to cope with hypoxia have evolved in mammals. Systemically, these adaptations include increased ventilation, cardiac output, blood vessel growth and circulating red blood cell numbers. On a cellular level, ATP- consuming reactions are suppressed, and metabolism is altered until oxygen homeostasis is restored. A critical question is how mammalian cells sense oxygen levels to coordinate diverse biological outputs during hypoxia. The best- studied mechanism of response to hypoxia involves hypoxia inducible factors (HIFs), which are stabilized by low oxygen availability and control the expression of a multitude of genes, including those involved in cell survival, angiogenesis, glycolysis and invasion/metastasis. Importantly, changes in oxygen can also be sensed via other stress pathways as well as changes in metabolite levels and the generation of reactive oxygen species by mitochondria. Collectively, this leads to cellular adaptations of protein synthesis, energy metabolism, mitochondrial respiration, lipid and carbon metabolism as well as nutrient acquisition. These mechanisms are integral inputs into fine- tuning the responses to hypoxic stress.

Citation Format: M. Celeste Simon. Impact of oxygen and nutrient availability on sarcoma tumor neighborhood [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA017.
Abstract IA030: A population-based, whole genome sequencing approach to mapping the genetic basis of mesenchymal malignancies
Authors: Thomas David M.
Published: September 2022

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify novel pathways specific to mesenchymal cancers, whole genome germline sequencing was performed on 1,644 sporadic cases, and 3,205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare variant burden and ontologic analysis identified two new sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, while heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas.

Citation Format: David M. Thomas. A population-based, whole genome sequencing approach to mapping the genetic basis of mesenchymal malignancies [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA030.
Loss of Epigenetic Regulation Disrupts Lineage Integrity, Induces Aberrant Alveogenesis, and Promotes Breast Cancer
Authors: Langille Ellen , Al-Zahrani Khalid N. , Ma Zhibo , Liang Minggao , Uuskula-Reimand Liis , Espin Roderic , Teng Katie , Malik Ahmad , Bergholtz Helga , Ghamrasni Samah El , Afiuni-Zadeh Somaieh , Tsai Ricky , Alvi Sana , Elia Andrew , Lü YiQing , Oh Robin H. , Kozma Katelyn J. , Trcka Daniel , Narimatsu Masahiro , Liu Jeff C. , Nguyen Thomas , Barutcu Seda , Loganathan Sampath K. , Bremner Rod , Bader Gary D. , Egan Sean E. , Cescon David W. , Sørlie Therese , Wrana Jeffrey L. , Jackson Hartland W. , Wilson Michael D. , Witkiewicz Agnieszka K. , Knudsen Erik S. , Pujana Miguel Angel , Wahl Geoffrey M. , Schramek Daniel
Published: September 2022

Systematically investigating the scores of genes mutated in cancer and discerning disease drivers from inconsequential bystanders is a prerequisite for precision medicine but remains challenging. Here, we developed a somatic CRISPR/Cas9 mutagenesis screen to study 215 recurrent “long-tail” breast cancer genes, which revealed epigenetic regulation as a major tumor-suppressive mechanism. We report that components of the BAP1 and COMPASS-like complexes, including KMT2C/D, KDM6A, BAP1, and ASXL1/2 (“EpiDrivers”), cooperate with PIK3CAH1047R to transform mouse and human breast epithelial cells. Mechanistically, we find that activation of PIK3CAH1047R and concomitant EpiDriver loss triggered an alveolar-like lineage conversion of basal mammary epithelial cells and accelerated formation of luminal-like tumors, suggesting a basal origin for luminal tumors. EpiDriver mutations are found in ∼39% of human breast cancers, and ∼50% of ductal carcinoma in situ express casein, suggesting that lineage infidelity and alveogenic mimicry may significantly contribute to early steps of breast cancer etiology.

Significance:

Infrequently mutated genes comprise most of the mutational burden in breast tumors but are poorly understood. In vivo CRISPR screening identified functional tumor suppressors that converged on epigenetic regulation. Loss of epigenetic regulators accelerated tumorigenesis and revealed lineage infidelity and aberrant expression of alveogenesis genes as potential early events in tumorigenesis.

This article is highlighted in the In This Issue feature, p. 2711
Serial Profiling of Circulating Tumor DNA Identifies Dynamic Evolution of Clinically Actionable Genomic Alterations in High-Risk Neuroblastoma
Authors: Bosse Kristopher R. , Giudice Anna Maria , Lane Maria V. , McIntyre Brendan , Schürch Patrick M. , Pascual-Pasto Guillem , Buongervino Samantha N. , Suresh Sriyaa , Fitzsimmons Alana , Hyman Adam , Gemino-Borromeo Maria , Saggio Jennifer , Berko Esther R. , Daniels Alexander A. , Stundon Jennifer , Friedrichsen Megan , Liu Xin , Margolis Matthew L. , Li Marilyn M. , Tierno Marni Brisson , Oxnard Geoffrey R. , Maris John M. , Mossé Yael P.
Published: September 2022

Neuroblastoma evolution, heterogeneity, and resistance remain inadequately defined, suggesting a role for circulating tumor DNA (ctDNA) sequencing. To define the utility of ctDNA profiling in neuroblastoma, 167 blood samples from 48 high-risk patients were evaluated for ctDNA using comprehensive genomic profiling. At least one pathogenic genomic alteration was identified in 56% of samples and 73% of evaluable patients, including clinically actionable ALK and RAS–MAPK pathway variants. Fifteen patients received ALK inhibition (ALKi), and ctDNA data revealed dynamic genomic evolution under ALKi therapeutic pressure. Serial ctDNA profiling detected disease evolution in 15 of 16 patients with a recurrently identified variant—in some cases confirming disease progression prior to standard surveillance methods. Finally, ctDNA-defined ERRFI1 loss-of-function variants were validated in neuroblastoma cellular models, with the mutant proteins exhibiting loss of wild-type ERRFI1's tumor-suppressive functions. Taken together, ctDNA is prevalent in children with high-risk neuroblastoma and should be followed throughout neuroblastoma treatment.

Significance:

ctDNA is prevalent in children with neuroblastoma. Serial ctDNA profiling in patients with neuroblastoma improves the detection of potentially clinically actionable and functionally relevant variants in cancer driver genes and delineates dynamic tumor evolution and disease progression beyond that of standard tumor sequencing and clinical surveillance practices.

See related commentary by Deubzer et al., p. 2727.

This article is highlighted in the In This Issue feature, p. 2711