bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimal Critical Sequences in Model-based Safety and Security Analyses: Commonalities and Differences
Authors: Serru Théo , Nguyen Nga , Batteux Michel , Rauzy Antoine
Published: May 2023

Discrete event systems are increasingly used as a modeling tool to assess safety and cybersecurity of complex systems. In both cases, the analysis relies on the extraction of critical sequences. This approach proves to be very powerful. It suffers, however, from the combinatorial explosion of the number of sequences to look at. To push the limits of what is feasible with reasonable computational resources, extraction algorithms use cutoffs and minimality criteria.

In this article, we review the principles of extraction algorithms, and we show that there are important differences between critical sequences extracted in the context of safety analyses and those extracted in the context of cybersecurity analyses. Based on this thorough comparison, we introduce a new cutoff criterion, so-called footprint, that aims at capturing the willfulness of an intruder performing a cyberattack. We illustrate our presentation by means of three case studies, one focused on the analysis of failures and two focused on the analysis of cyberattacks and their effects on safety. We show experimentally the interest of the footprint criterion.
A Comparative Study of Plastic and Glass Optical Fibers for Reliable Home Networking
Authors: Manea Hussein K. , Molood Yousif N. , Al-Jubouri Qussay , Taha Bakr Ahmed , Chaudhary Vishal , Rustagi Sarvesh , Arsad Norhana
Published: May 2023

Home networking using fiber optics is essential for uninterrupted data transmission in modern communication networks. In this study, we evaluated and compared the reliability of plastic optical fibers (POFs) and glass optical fibers (GOFs) for home networking applications. Furthermore, assess the advantages and disadvantages of POF and GOF over short distances and find that POF is more suitable for home network applications due to its higher reliability. In addition, it has the advantage of being cost-effective and flexible for short-distance applications. The results show that POF indicates higher reliability and better performance at 8.25517 × 101of the Q factors, 2.21355 × 10−3 of the eye height, and 2.8307 × 10−3 of the threshold values at 30 meters, while GOF shows 6.30 × 101 of the Q factor, 3.78087 × 10−3 of the eye heights and 4.34736 × 10−3 of the threshold values. Moreover, this research highlights the importance of reliability in designing and applying optical fiber networks and can help network designers and engineers make informed decisions when selecting the appropriate type of optical fiber for specific applications.
Diversity Analysis of Defect Distribution and Carriers Quantization in Cu
2
ZnSnS
4/Cu2ZnSn(S,Se)
4 Kesterite Quantum Well Solar Cell
Authors: Palanisamy Chandrasekar , Routray Soumyaranjan , Palaniswamy S. K.
Published: May 2023

Kesterite materials, with a major advantage of direct bandgap and earth abundant material,are popular for low cost and thin film solar cell applications. Despite the popularity, the material fails to achieve significant efficiency due to the emergence of defect states during the growth process. In this paper multiple approaches have been investigated focusing on implementation of Quantum Wells(QW) to enhance the performance of solar cell. QW structure are created using CZTS

x

Se
1−x
and Cu
2
ZnSnS
4 as QW and barrier material layers respectively. The performance evaluation of the QW solar cell is also carried out with the presence of most popular donor-like defect states in a gaussian and tail distribution way. The behavior of the device is investigated in presence of broad range of QWs from 2 to 100QWs to ensure the effect of defects on rise in QWs. The worst case performance of the solar cell is obtained to be efficiency of 9.6% under a high level of defect states. A remarkable observation on the effect of increase in number of QWs and defect states on solar cell parameters solar cell are concluded.
Advanced TPU/ZnS:Al Flexible Film with Thermo-Force-Optical Response for Smart Clothing
Authors: Yan Bingyu , Gao Yuan , Sun Tiancai , Sun Dejun , Hui Chao , Li Xiaonan , Zhang Jun , Long Yun-Ze
Published: May 2023

With the continuous development of science and technology, smart sensing wearables have gradually entered people’s lives. However, the prepared wearable material has poor air permeability, poor fit, and does not have multiple modal excitations. In addition, it is not waterproof or even wearable at low temperatures. In this work, a thermoplastic polyurethane (TPU) and ZnS:Al composite film with excellent air permeability has been developed. The TPU/ZnS:Al flexible film can be prepared on a large scale by solution blow spinning (SBS). This fiber membrane can realize the dual response of temperature and stress, and cooperate with the light sensor to realize the transmission of intelligent information. This nanofiber membrane doped with ZnS:Al exhibits a uniform distribution, maintains excellent tensile properties and flexibility, and can adapt to any perfect shape of the fitting surface. Even the average air permeability can be as high as 300 mm s−1, which is 600 times that of conventional spraying methods. The Al introduced in ZnS:Al can stimulate the composite film to emit light, and the luminescence effect can be maintained for about 1 min. These results provide new ideas for the large-scale fabrication of integrated stimulus-responsive photosensitive intelligent wearable devices for various applications.
MicroRNA dysregulation and therapeutic opportunities in esophageal diseases
Authors: Markey Gary E. , Donohoe Claire L. , McNamee Eóin N. , Masterson Joanne C.
Published: May 2023

MicroRNAs (miRNAs) are a class of small endogenous RNA molecules between 18 and 25 nucleotides long. The primary function of miRNAs is in the posttranscriptional regulation of mRNA targets through RNA interference culminating in mRNA degradation or translational repression. MiRNAs are fundamental in physiological and pathological processes such as cell proliferation, differentiation, apoptosis, and inflammation. Among this includes the uncovered potential of miRNAs in overall esophageal disease with a focus on the clinicopathologic allergic disease eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), and the tumorigenic continuum from Barrett’s esophagus (BE) toward esophageal adenocarcinoma (EAC). Although these pathologies are distinct from one another, they share pathophysiological elements such as an intense inflammatory milieu, esophageal dysfunction, and as presented in this review, an overlap in miRNA expression which contributes to overall esophageal disease. The overlap in the dysregulated miRNA transcriptome of these pathologies highlights the key role miRNAs play in contributing to esophageal disease progression. Owing to this notable dysregulation, there is an attractive utility for miRNAs as diagnostic and prognostic biomarkers in esophageal diseases that already require invasive endoscopies and biopsy retrieval. In this review miRNAs within EoE, GERD, BE, EAC, and esophageal achalasia are discussed, as well as reviewing a core set of miRNAs shared in the disease progression among some of these pathologies, along with the potential utility of targeting miRNAs as therapeutic options in overall esophageal disease.
Effect of CO2 Huff and Puff Rounds on Crude Oil Properties
Authors: Shi Qionglin , Gong Sha , Qin Xiaoping
Published: May 2023

In view of the deterioration of oil well liquid supply capacity and oil increase effect after multiple rounds of carbon dioxide (CO2) huff and puff, according to the actual conditions of the Ng12 reservoir in the XA oilfield, an indoor physical simulation experimental model was established. The experimental parameters were determined, five rounds of CO2 huff and puff experiments were carried out, and the crude oil produced in the water flooding stage and different rounds of CO2 huff and puff were collected. The effects of CO2 huff and puff rounds on crude oil viscosity, density, composition, paraffin content, and gum asphaltene content were studied. The results show that with the increase in CO2 huff and puff rounds, the viscosity and density of produced crude oil decrease. The content of light component (C2∼C6) and intermediate component (C7∼C10) increased, while the content of heavy component (C11+) decreased. CO2 has the strongest extraction effect on light components and the weakest extraction effect on heavy components. At the same time, the content of paraffin and gum asphaltene in the produced crude oil is reduced. For oil wells with multiple rounds of CO2 huff and puff, colloidal asphaltene precipitation inhibitor and scavenger should be considered to reduce the impact of colloidal asphaltene on formation permeability and liquid supply capacity.
A New Version of the Generalized F-Expansion Method for the Fractional Biswas-Arshed Equation and Boussinesq Equation with the Beta-Derivative
Authors: Pandir Yusuf , Gurefe Yusuf
Published: May 2023

In this article, a new version of the generalized F-expansion method is proposed enabling to obtain the exact solutions of the Biswas-Arshed equation and Boussinesq equation defined by Atangana’s beta-derivative. First, the new version generalized F-expansion method is introduced, and then, the exact solutions of the nonlinear fractional differential equations expressed with Atangana’s beta-derivative are given. When the results are examined, it is seen that single, combined, and mixed Jacobi elliptic function solutions are obtained. From the point of view, it is understood that the new version generalized F-expansion method can give significant results in finding the exact solutions of equations containing beta-derivatives.
Development of Self-Swelling Tablets as a Substitute for Soundless Cracking Demolition Agents
Authors: Xu Shuai , Li Runran , Li Zhangchao , Ji Xubo , Suorineni Fidelis T.
Published: May 2023

The low viscosity of soundless cracking demolition agent (SCDA) slurries makes them difficult to use on rock and concrete breakage in horizontal and up holes, or wet holes. In this paper, self-swelling tablet cartridges are developed by use of additives including adhesive, wetting agent, water absorbent, and activator to SCDA powder through newly developed production technologies. The dosages of adhesive and wetting agent were optimized in the process of powder granulation. Their optimal addition amounts are 3.17% and 11.81%. The self-swelling tablet (SST) experiments and optimization tests show the hardness of SST improved with an increase in pressure and mold filling height. Subsequently, laboratory tests were conducted to determine the influence of the contents of water absorbent and activator on the SST water absorption, reaction temperature, and expansion pressure. The water absorption of SST was found to improve with an increase in water absorbent amount and particle size of the granules. The optimum dosage of the water absorbent is 10%. Based on the laboratory experiments, the optimum amount of additives in the SST is 5% for its best performance. The production of SST cartridges is in a safer and healthier environment compared to SCDA powder cartridges, and its production can be automated to reduce labour cost. Finally, the introduction of SST cartridges expands the scope of application of the SCDA to up holes, horizonal holes, and wet holes.
Explore Gap between 3D DNN and Human Vision Utilizing Fooling Point Cloud Generated by MEHHO
Authors: Fan Linkun , He Fazhi , Li Bing , Gao Xiaoxin , Luo Jinkun
Published: May 2023

Deep neural network (DNN) has replaced humans to make decisions in many security-critical senses such as face recognition and automatic drive. Essentially, researchers try to teach DNN to simulate human behavior. However, many evidences show that there is a huge gap between humans and DNN, which has raised lots of security concern. Adversarial sample is a common way to show the gap between DNN and humans in recognizing objects with similar appearance. However, we argue that the difference is not limited to adversarial samples. Hence, this paper explores such differences in a new way by generating fooling samples in 3D point cloud domain. Specifically, the fooling point cloud is hardly recognized by human vision but is classified to the target class by the victim 3D point cloud DNN (3D DNN) with more than

99.99
%

confidence. Furthermore, to search for the optimal fooling point cloud, a new evolutionary algorithm named Multielites Harris Hawk Optimization (MEHHO) with enhanced exploitation ability is designed. On one hand, our experiments demonstrate that: (1) 3D DNN tends to learn high-level features of one object; (2) 3D DNN that makes decisions relying on more points is more robust; and (3) the gap is hardly learned by 3D DNN. On the other hand, the comparison experiments show that the designed MEHHO outperforms the SOTA evolutionary algorithms w.r.t. statistics and convergence results.
Machine Learning‐Based Model to Predict Heart Disease in Early Stage Employing Different Feature Selection Techniques
Authors: Biswas Niloy , Ali Md Mamun , Rahaman Md Abdur , Islam Minhajul , Mia Md. Rajib , Azam Sami , Ahmed Kawsar , Bui Francis M. , Al-Zahrani Fahad Ahmed , Moni Mohammad Ali
Published: May 2023

Almost 17.9 million people are losing their lives due to cardiovascular disease, which is 32% of total death throughout the world. It is a global concern nowadays. However, it is a matter of joy that the mortality rate due to heart disease can be reduced by early treatment, for which early‐stage detection is a crucial issue. This study is aimed at building a potential machine learning model to predict heart disease in early stage employing several feature selection techniques to identify significant features. Three different approaches were applied for feature selection such as chi‐square, ANOVA, and mutual information, and the selected feature subsets were denoted as SF1, SF2, and SF3, respectively. Then, six different machine learning models such as logistic regression (C1), support vector machine (C2), K‐nearest neighbor (C3), random forest (C4), Naive Bayes (C5), and decision tree (C6) were applied to find the most optimistic model along with the best‐fit feature subset. Finally, we found that random forest provided the most optimistic performance for SF3 feature subsets with 94.51% accuracy, 94.87% sensitivity, 94.23% specificity, 94.95 area under ROC curve (AURC), and 0.31 log loss. The performance of the applied model along with selected features indicates that the proposed model is highly potential for clinical use to predict heart disease in the early stages with low cost and less time.
Systematic Characterization of the Chemical Components of Canna edulis Ker-Gawl Based on UHPLC Q-Exactive Orbitrap MS Technology
Authors: Lv Liqiao , Zhang Chi , Wu Jiahui , Zhang Dachuan , Zhao Fangyuan , Aga Lv Bu , Wang Nan , Li Junling , Tang Leimengyuan , Zhao Baosheng , Wang Chunguo , Wang Xueyong
Published: May 2023

Canna edulis Ker-Gawl is a versatile crop that integrates food, energy, and feed in China. The rhizome is a traditional Chinese medicine with a long history. However, there are few studies on chemical components. Crude plant extracts are a complex mixture of several biologically active secondary metabolites. Therefore, rapid and accurate identification and quantification are critical in phytochemical analysis. An efficient approach based on ultrahigh-performance liquid chromatography coupled with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC Q-Exactive Orbitrap MS) was used to analyze the chemical components systematically. We used retention time, accurate molecular weight, parent peaks, fragment peaks, fragmentation characteristics, comparative analysis with the literature, reference standards, and standard databases, including ChemSpider, mzVault, MassBank, and mzCloud. A total of 54 chemical constituents were identified from the methanol extract of the rhizome, including 36 organic acids (with six phenolic acids), three phenols, one sugar (and its derivatives), one coumarin, one triterpenoid, ten N-containing organic compounds (including seven amino acids), and two other compounds. Moreover, three compounds were quantitatively analyzed and a methodological study of the three components was carried out. The established method provided satisfactory precision and accuracy, acceptable recovery, good linearity, and a reasonable detection limit. The UHPLC Q-Exactive Orbitrap MS method was used for the first time to accurately, quickly, and systematically characterize the compounds of the rhizome, revealing the pharmacodynamic substances and providing a theoretical basis for its quality control, in-depth research, and development.
Appling the Roulette Wheel Selection Approach to Address the Issues of Premature Convergence and Stagnation in the Discrete Differential Evolution Algorithm
Authors: Shakir Hameed Asaad , Alrikabi Haiffa Muhsan B. , Abdul–Razaq Abeer A. , Ahmed Zakir Hussain , Nasser Huda Karem , Mutar Modhi Lafta
Published: May 2023

The discrete differential evolution (DDE) algorithm is an evolutionary algorithm (EA) that has effectively solved challenging optimization problems. However, like many other EAs, it still faces problems such as premature convergence and stagnation during the iterative process. To address these concerns in the DDE algorithm, this work aims to achieve the following objectives: (i) investigate the causes of premature convergence and stagnation in the DDE algorithm; (ii) propose techniques to prevent premature convergence and stagnation in DDE, including a quantitative measurement of premature convergence based on the level of mismatching between the population solutions and then divide the population into individual groups based on the level of mismatching between the population solutions and the best solution; and applying the roulette wheel selection (RWS) approach to determine whether a higher degree of nonmatching is more suitable for choosing a population of separate groups to be able to produce a new solution with more options to prevent the occurrence of premature convergence; (iii) evaluate the effectiveness of the proposed techniques through employing the DDE algorithm to solve the quadratic assignment problem (QAP) as a standard to evaluate our results and their effect on avoiding premature convergence and stagnation issues, which led to the enhancement of the algorithm’s accuracy. Our comparative study based on the statistical analysis shows that the DDE algorithm that uses the proposed techniques is more efficient than the traditional DDE algorithm and the state-of-the-art methods.
Supplementary file 4: Full original pictures. from circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma
Authors: Li Xiang , Wang Chenxing , Zhang Hang , Li Yangjie , Hou Deqiang , Liu Dingshan , Xu Rongyao , Cheng Jie , Liu Laikui , Fu Yu , Ye Jinhai , Jiang Hongbing
Published: May 2023

Full original pictures.
Supplementary Table 3 from Spatial Transcriptomics Depict Ligand–Receptor Cross-talk Heterogeneity at the Tumor-Stroma Interface in Long-Term Ovarian Cancer Survivors
Authors: Ferri-Borgogno Sammy , Zhu Ying , Sheng Jianting , Burks Jared K. , Gomez Javier A. , Wong Kwong Kwok , Wong Stephen T.C. , Mok Samuel C.
Published: May 2023

scRNAseq differentially expressed genes
Supplementary Table 1 from Spatial Transcriptomics Depict Ligand–Receptor Cross-talk Heterogeneity at the Tumor-Stroma Interface in Long-Term Ovarian Cancer Survivors
Authors: Ferri-Borgogno Sammy , Zhu Ying , Sheng Jianting , Burks Jared K. , Gomez Javier A. , Wong Kwong Kwok , Wong Stephen T.C. , Mok Samuel C.
Published: May 2023

Clinicopathological characteristics of samples used in the study
Supplementary file 1: Supplementary Materials and Methods. from circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma
Authors: Li Xiang , Wang Chenxing , Zhang Hang , Li Yangjie , Hou Deqiang , Liu Dingshan , Xu Rongyao , Cheng Jie , Liu Laikui , Fu Yu , Ye Jinhai , Jiang Hongbing
Published: May 2023

Supplementary Materials and Methods.
Table S2 from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

Lists of TCGA LUSC and LUAD cases in the discovery and validation cohort
Table 1 from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

. Characteristics of the included patients and their association with the Sintra/immune, Sintra/cancer, and Sintra/tissue.
Supplementary Table S3 from Computational and Functional Analyses of HER2 Mutations Reveal Allosteric Activation Mechanisms and Altered Pharmacologic Effects
Authors: Ishiyama Noboru , O'Connor Matthew , Salomatov Andrei , Romashko Darlene , Thakur Shalabh , Mentes Ahmet , Hopkins Julia F. , Frampton Garrett M. , Albacker Lee A. , Kohlmann Anna , Roberts Christopher , Buck Elizabeth
Published: May 2023

Supplementary Data
Figure 5 from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

Diversity of lymphocyte interactions in intratumoral and peritumoral IH without TLS or LAG. A, Examples of lymphocyte interactions in individual peritumoral and intratumoral IH. Lymphocytes identified on the serial IHC slides were connected by the Delaunay triangle graph. Lymphocyte subsets are represented by dots of different colors. Interactions significant in the univariate logistic regression are denoted by red, otherwise blue. B, Shannon diversity of lymphocyte densities and interactions in individual peritumoral (n = 392) and intratumoral IH (n = 262). Statistical significance was evaluated by the Wilcoxon signed-rank test. C, Univariate logistic regression predicting peritumoral and intratumoral IH with individual lymphocyte interactions as variables, n = 654. The coefficients of the significant variables were all negative, suggesting a higher frequency of the interactions in peritumoral IH compared with intratumoral IH. P values were adjusted by the Benjamini–Hochberg method. Regions identified as TLS or LAG were excluded from the above analyses.
Supplementary Table S1 from Ablation of p57+ Quiescent Cancer Stem Cells Suppresses Recurrence after Chemotherapy of Intestinal Tumors
Authors: Oka Takeru , Higa Tsunaki , Sugahara Osamu , Koga Daisuke , Nakayama Shogo , Nakayama Keiichi I.
Published: May 2023

Supplementary Table S1
Figure 2 from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

B-cell dominance of high-Sintra/immune group in LUSC. A, Gene Ontology (GO) biological processes found to be enriched in the DEGs according to patient groups stratified by Sintra/immune. The red line denotes the ratio of the number of DEGs in a pathway to the total number of genes in that pathway. FDR, false discovery rate. B, Volcano plot showing DEGs in the high-Sintra/immune group compared with the low group. Genes with log-fold change (logFC) smaller than 1 were excluded. Genes involved in immune responses are highlighted in yellow. C, Consistently upregulated B-cell signatures in high-Sintra/immune group across seven bioinformatics methods using the TCGA LUSC cohort, n = 459. Statistical significance was evaluated by the Wilcoxon rank sum test and adjusted by the Benjamini–Hochberg method.
Source Data from Ablation of p57+ Quiescent Cancer Stem Cells Suppresses Recurrence after Chemotherapy of Intestinal Tumors
Authors: Oka Takeru , Higa Tsunaki , Sugahara Osamu , Koga Daisuke , Nakayama Shogo , Nakayama Keiichi I.
Published: May 2023

Source Data
Supplementary Table S5 from RBM10 Loss Promotes EGFR-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition
Authors: Bao Yufang , Zhang Sirui , Zhang Xiaoyu , Pan Yunjian , Yan Yueren , Wang Ning , Ren Yunpeng , Zuo Ji , Zong Wei-Xing , Wang Zefeng , Wang Yongbo
Published: May 2023

Supplementary Table S5
Supplementary Table 3 from The Macrophage-Associated LncRNA MALR Facilitates ILF3 Liquid–Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer
Authors: Liu Jia , Liu Ze-Xian , Li Jia-Jun , Zeng Zhao-Lei , Wang Jin-Hong , Luo Xiao-Jing , Wong Chau-Wei , Zheng Jia-Bo , Pu Heng-Ying , Mo Hai-Yu , Sheng Hui , Wu Qi-Nian , Li Hao , Wan Gang , Li Bo , Wang De-shen , Xu Rui-Hua , Ju Huai-Qiang
Published: May 2023

Supplementary Table 3
Supplementary Table 2 from The Macrophage-Associated LncRNA MALR Facilitates ILF3 Liquid–Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer
Authors: Liu Jia , Liu Ze-Xian , Li Jia-Jun , Zeng Zhao-Lei , Wang Jin-Hong , Luo Xiao-Jing , Wong Chau-Wei , Zheng Jia-Bo , Pu Heng-Ying , Mo Hai-Yu , Sheng Hui , Wu Qi-Nian , Li Hao , Wan Gang , Li Bo , Wang De-shen , Xu Rui-Hua , Ju Huai-Qiang
Published: May 2023

Supplementary Table 2
Supplementary Table S3 from RBM10 Loss Promotes EGFR-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition
Authors: Bao Yufang , Zhang Sirui , Zhang Xiaoyu , Pan Yunjian , Yan Yueren , Wang Ning , Ren Yunpeng , Zuo Ji , Zong Wei-Xing , Wang Zefeng , Wang Yongbo
Published: May 2023

Supplementary Table S3
Supplementary Movie 1 from The Macrophage-Associated LncRNA MALR Facilitates ILF3 Liquid–Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer
Authors: Liu Jia , Liu Ze-Xian , Li Jia-Jun , Zeng Zhao-Lei , Wang Jin-Hong , Luo Xiao-Jing , Wong Chau-Wei , Zheng Jia-Bo , Pu Heng-Ying , Mo Hai-Yu , Sheng Hui , Wu Qi-Nian , Li Hao , Wan Gang , Li Bo , Wang De-shen , Xu Rui-Hua , Ju Huai-Qiang
Published: May 2023

Supplementary Movie 1
Supplementary Methods from The Macrophage-Associated LncRNA MALR Facilitates ILF3 Liquid–Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer
Authors: Liu Jia , Liu Ze-Xian , Li Jia-Jun , Zeng Zhao-Lei , Wang Jin-Hong , Luo Xiao-Jing , Wong Chau-Wei , Zheng Jia-Bo , Pu Heng-Ying , Mo Hai-Yu , Sheng Hui , Wu Qi-Nian , Li Hao , Wan Gang , Li Bo , Wang De-shen , Xu Rui-Hua , Ju Huai-Qiang
Published: May 2023

Supplementary Methods
Supplementary Data from RBM10 Loss Promotes EGFR-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition
Authors: Bao Yufang , Zhang Sirui , Zhang Xiaoyu , Pan Yunjian , Yan Yueren , Wang Ning , Ren Yunpeng , Zuo Ji , Zong Wei-Xing , Wang Zefeng , Wang Yongbo
Published: May 2023

Supplementary Figs. S1-S6
TableS5 from Enhancer Coamplification and Hijacking Promote Oncogene Expression in Liposarcoma
Authors: Liu Tingting , Wang Juan , Yang Hongbo , Jin Qiushi , Wang Xiaotao , Fu Yihao , Luan Yu , Wang Qixuan , Youngblood Mark W. , Lu Xinyan , Casadei Lucia , Pollock Raphael , Yue Feng
Published: May 2023

Sequence Data Information in Lipo863B
Figure S6 from Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: May 2023

Figure S6 contains total metabolite levels in lung cancer models related to Figure 5
TableS4 from Enhancer Coamplification and Hijacking Promote Oncogene Expression in Liposarcoma
Authors: Liu Tingting , Wang Juan , Yang Hongbo , Jin Qiushi , Wang Xiaotao , Fu Yihao , Luan Yu , Wang Qixuan , Youngblood Mark W. , Lu Xinyan , Casadei Lucia , Pollock Raphael , Yue Feng
Published: May 2023

Patient Sample WGS data statistics
Figure S5 from Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: May 2023

Figure S5 contains the total metabolite levels in liver and pancreas cancer models related to Figure 4
TableS2 from Enhancer Coamplification and Hijacking Promote Oncogene Expression in Liposarcoma
Authors: Liu Tingting , Wang Juan , Yang Hongbo , Jin Qiushi , Wang Xiaotao , Fu Yihao , Luan Yu , Wang Qixuan , Youngblood Mark W. , Lu Xinyan , Casadei Lucia , Pollock Raphael , Yue Feng
Published: May 2023

H3K27Ac ChIP-seq Patient Sample Statistics
Figure S3 from Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: May 2023

Figure S3 contains the total metabolite levels in healthy mouse tissues related to Figure 2
TableS1 from Enhancer Coamplification and Hijacking Promote Oncogene Expression in Liposarcoma
Authors: Liu Tingting , Wang Juan , Yang Hongbo , Jin Qiushi , Wang Xiaotao , Fu Yihao , Luan Yu , Wang Qixuan , Youngblood Mark W. , Lu Xinyan , Casadei Lucia , Pollock Raphael , Yue Feng
Published: May 2023

Patient Sample Information
Figure S1 from Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: May 2023

Figure S1 reports the status of common mutations in the cell lines used in this study.
Data from circFNDC3B accelerates vasculature formation and metastasis in oral squamous cell carcinoma
Authors: Li Xiang , Wang Chenxing , Zhang Hang , Li Yangjie , Hou Deqiang , Liu Dingshan , Xu Rongyao , Cheng Jie , Liu Lai-Kui , Fu Yu , Ye Jinhai , Jiang Hongbing
Published: May 2023

Abstract
Emerging evidence has demonstrated that circular RNAs (circRNAs) are involved in cancer metastasis. Further elucidation of the role of circRNAs in oral squamous cell carcinoma (OSCC) could provide insights into mechanisms driving metastasis and potential therapeutic targets. Here, we identify a circRNA, circFNDC3B, that is significantly upregulated in OSCC and is positively associated with lymph node (LN) metastasis. In vitro and in vivo functional assays showed that circFNDC3B accelerated the migration and invasion of OSCC cells and the tube-forming capacity of human umbilical vein endothelial cells (HUVEC) and human lymphatic endothelial cells (HLEC). Mechanistically, circFNDC3B regulated ubiquitylation of the RNA-binding protein FUS and the deubiquitylation of HIF1A through the E3 ligase MDM2 to promote VEGFA transcription, thereby enhancing angiogenesis. Meanwhile, circFNDC3B sequestered miR-181c-5p to upregulate SERPINE1 and PROX1, which drove epithelial-mesenchymal transition (EMT) or partial-EMT (p-EMT) in OSCC cells and promoted lymphangiogenesis to accelerate lymph node metastasis. Overall, these findings uncovered the mechanistic role of circFNDC3B in orchestrating cancer cell metastatic properties and vasculature formation, suggesting circFNDC3B could be a potential target to reduce OSCC metastasis.
Data from circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma
Authors: Li Xiang , Wang Chenxing , Zhang Hang , Li Yangjie , Hou Deqiang , Liu Dingshan , Xu Rongyao , Cheng Jie , Liu Laikui , Fu Yu , Ye Jinhai , Jiang Hongbing
Published: May 2023

Abstract
Emerging evidence has demonstrated that circular RNAs (circRNA) are involved in cancer metastasis. Further elucidation of the role of circRNAs in oral squamous cell carcinoma (OSCC) could provide insights into mechanisms driving metastasis and potential therapeutic targets. Here, we identify a circRNA, circFNDC3B, that is significantly upregulated in OSCC and is positively associated with lymph node (LN) metastasis. In vitro and in vivo functional assays showed that circFNDC3B accelerated the migration and invasion of OSCC cells and the tube-forming capacity of human umbilical vein endothelial cells and human lymphatic endothelial cells. Mechanistically, circFNDC3B regulated ubiquitylation of the RNA-binding protein FUS and the deubiquitylation of HIF1A through the E3 ligase MDM2 to promote VEGFA transcription, thereby enhancing angiogenesis. Meanwhile, circFNDC3B sequestered miR-181c-5p to upregulate SERPINE1 and PROX1, which drove epithelial–mesenchymal transition (EMT) or partial-EMT (p-EMT) in OSCC cells and promoted lymphangiogenesis to accelerate LN metastasis. Overall, these findings uncovered the mechanistic role of circFNDC3B in orchestrating cancer cell metastatic properties and vasculature formation, suggesting circFNDC3B could be a potential target to reduce OSCC metastasis.
Significance:
Dual functions of circFNDC3B in enhancing the metastatic ability of cancer cells and promoting vasculature formation through regulation of multiple pro-oncogenic signaling pathways drive lymph node metastasis of OSCC.
Data from Spatial positioning of immune hotspots reflects the interplay between B and T cells in lung squamous cell carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey , Jamal-Hanjani Mariam , Raza Shan E Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

Abstract
Beyond tertiary lymphoid structures, a significant number of immune rich areas without germinal center-like structures are observed in non-small cell lung cancer. Here, we integrated transcriptomic data and digital pathology images to study the prognostic implications, spatial locations, and constitution of immune rich areas (immune hotspots) in a cohort of 935 lung cancer patients from the TCGA. A high intratumoral immune hotspot score, which measures the proportion of immune hotspots interfacing with tumor islands, was correlated with poor overall survival in lung squamous cell carcinoma but not in lung adenocarcinoma. Lung squamous cell carcinomas with high intratumoral immune hotspot scores were characterized by consistent upregulation of B cell signatures. Spatial statistical analyses conducted on serial multiplex immunohistochemistry slides further revealed that only 4.87% of peritumoral immune hotspots and 0.26% of intratumoral immune hotspots were tertiary lymphoid structures. Significantly lower densities of CD20+CXCR5+ and CD79b+ B cells and less diverse immune cell interactions were found in intratumoral immune hotspots compared to peritumoral immune hotspots. Furthermore, there was a negative correlation between the percentages of CD8+ T cells and T regulatory cells in intratumoral but not in peritumoral immune hotspots, with tertiary lymphoid structures excluded. These findings suggest that the intratumoral immune hotspots reflect an immunosuppressive niche compared to peritumoral immune hotspots, independent of the distribution of tertiary lymphoid structures. A balance towards increased intratumoral immune hotspots is indicative of a compromised anti-tumor immune response and poor outcome in lung squamous cell carcinoma.
Data from Computational and Functional Analyses of HER2 Mutations Reveal Allosteric Activation Mechanisms and Altered Pharmacologic Effects
Authors: Ishiyama Noboru , O'Connor Matthew , Salomatov Andrei , Romashko Darlene , Thakur Shalabh , Mentes Ahmet , Hopkins Julia F. , Frampton Garrett M. , Albacker Lee A. , Kohlmann Anna , Roberts Christopher , Buck Elizabeth
Published: May 2023

Abstract
Amplification of HER2 can drive the proliferation of cancer cells, and several inhibitors of HER2 have been successfully developed. Recent advances in next-generation sequencing now reveal that HER2 is subject to mutation, with over 2000 unique variants observed in human cancers. Several examples of oncogenic HER2 mutations have been described, and these primarily occur at allosteric sites outside the ATP-binding site. To identify the full spectrum of oncogenic HER2 driver mutations aside from a few well-studied mutations, we developed mutation-allostery-pharmacology (MAP), an in silico prediction algorithm based on machine learning. By applying this computational approach to 820 single-nucleotide variants, a list of 222 known and potential driver mutations was produced. Of these 222 mutations, 111 were screened by Ba/F3-retrovirus proliferation assays; 37 HER2 mutations were experimentally determined to be driver mutations, comprising 15 previously characterized and 22 newly identified oncogenic mutations. These oncogenic mutations mostly affected allosteric sites in the extracellular domain (ECD), transmembrane domain, and kinase domain of HER2, with only a single mutation in the HER2 orthosteric ATP site. Covalent homodimerization was established as a common mechanism of activation among HER2 ECD allosteric mutations, including the most prevalent HER2 mutation, S310F. Furthermore, HER2 allosteric mutants with enhanced covalent homodimerization were characterized by altered pharmacology that reduces the activity of existing anti-HER2 agents, including the monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib. Overall, the MAP-scoring and functional validation analyses provided new insights into the oncogenic activity and therapeutic targeting of HER2 mutations in cancer.
Data from Ablation of p57+ Quiescent Cancer Stem Cells Suppresses Recurrence after Chemotherapy of Intestinal Tumors
Authors: Oka Takeru , Higa Tsunaki , Sugahara Osamu , Koga Daisuke , Nakayama Shogo , Nakayama Keiichi I.
Published: May 2023

Abstract
Quiescent cancer stem cells (CSC) are resistant to conventional anticancer treatments and have been shown to contribute to disease relapse after therapy in some cancer types. The identification and characterization of quiescent CSCs could facilitate the development of strategies to target this cell population and block recurrence. Here, we established a syngeneic orthotopic transplantation model in mice based on intestinal cancer organoids to profile quiescent CSCs. Single-cell transcriptomic analysis of the primary tumors formed in vivo revealed that conventional Lgr5high intestinal CSCs comprise both actively and slowly cycling subpopulations, the latter of which specifically expresses the cyclin-dependent kinase inhibitor p57. Tumorigenicity assays and lineage tracing experiments showed that the quiescent p57+ CSCs contribute in only a limited manner to steady-state tumor growth but they are chemotherapy resistant and drive posttherapeutic cancer recurrence. Ablation of p57+ CSCs suppressed intestinal tumor regrowth after chemotherapy. Together, these results shed light on the heterogeneity of intestinal CSCs and reveal p57+ CSCs as a promising therapeutic target for malignant intestinal cancer.
Significance:
A quiescent p57+ subpopulation of intestinal CSCs is resistant to chemotherapy and can be targeted to effectively suppress the recurrence of intestinal cancer.
Data from RBM10 loss promotes EGFR-driven lung cancer and confers sensitivity to spliceosome inhibition
Authors: Bao Yufang , Zhang Sirui , Zhang Xiaoyu , Pan Yunjian , Yan Yueren , Wang Ning , Ren Yunpeng , Zuo Ji , Zong Wei-Xing , Wang Zefeng , Wang Yongbo
Published: May 2023

Abstract
In lung adenocarcinoma (LUAD), loss-of-function mutations in the splicing factor RBM10 frequently co-occur with oncogenic EGFR mutations. A detailed understanding of the functional consequences and therapeutic impact of RBM10 loss in EGFR-mutant LUAD could help identify more effective treatment strategies. Here, analysis of LUAD datasets indicated that RBM10 mutations are mutually exclusive with mutations in the tumor suppressor gene TP53. In an EGFR-driven LUAD mouse model, lung-specific ablation of either Rbm10 or Trp53 similarly promoted tumor development, leading to overlapping gene expression changes enriched in cancer-related pathways. RBM10 loss induced key RNA splicing changes concordant in mice and LUAD patients. Importantly, RBM10 deficiency conferred high sensitivity to spliceosome inhibition in EGFR-mutated LUAD cells. Combined treatment with spliceosome inhibitor improved the therapeutic efficacy of EGFR tyrosine kinase inhibitor osimertinib and overcame drug resistance, especially in RBM10-deficient LUAD. Together, this study establishes RBM10 as a tumor suppressor akin to p53 and provides a therapeutic strategy of targeting the splicing machinery in EGFR-driven LUAD.
Data from The Macrophage-Associated LncRNA MALR Facilitates ILF3 Liquid–Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer
Authors: Liu Jia , Liu Ze-Xian , Li Jia-Jun , Zeng Zhao-Lei , Wang Jin-Hong , Luo Xiao-Jing , Wong Chau-Wei , Zheng Jia-Bo , Pu Heng-Ying , Mo Hai-Yu , Sheng Hui , Wu Qi-Nian , Li Hao , Wan Gang , Li Bo , Wang De-shen , Xu Rui-Hua , Ju Huai-Qiang
Published: May 2023

Abstract
Tumor-associated macrophages (TAM) are among the most abundant immune cells in the tumor microenvironment and are important mediators of tumor development and progression. Here, we identified a macrophage-associated long noncoding RNA (lncRNA), MALR, that facilitates progression of esophageal squamous cell carcinoma (ESCC). TAM-mediated secretion of TNFα drove MALR upregulation in ESCC cells. MALR promoted aerobic glycolytic activity and facilitated angiogenesis by activating the HIF1α signaling pathway. Mechanistically, MALR bound the dsRBD1 domain of interleukin enhancer-binding factor 3 (ILF3), promoting ILF3 protein stability and ILF3-mediated liquid–liquid phase separation (LLPS), thereby enhancing HIF1α mRNA stability by preventing PARN-mediated degradation. Loss of MALR suppressed cell line–based and patient-derived xenograft tumor growth. Clinically, high expression of MALR positively correlated with HIF1α target gene expression and indicated poor prognoses for patients with esophageal cancer. Overall, this study uncovers the physiologic roles of MALR/ILF3-mediated LLPS in tumor microenvironment remodeling, highlighting the MALR–ILF3–HIF1α axis as a potential target for cancer therapy.
Significance:
Secretion of TNFα by tumor-associated macrophages stimulates cancer cells to upregulate lncRNA MALR, which induces ILF3 liquid–liquid phase separation and activation of HIF1α signaling to promote cancer progression.
Data from Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: May 2023

Abstract
Cysteine plays critical roles in cellular biosynthesis, enzyme catalysis, and redox metabolism. The intracellular cysteine pool can be sustained by cystine uptake or de novo synthesis from serine and homocysteine. Demand for cysteine is increased during tumorigenesis for generating glutathione to deal with oxidative stress. While cultured cells have been shown to be highly dependent on exogenous cystine for proliferation and survival, how diverse tissues obtain and use cysteine in vivo has not been characterized. We comprehensively interrogated cysteine metabolism in normal murine tissues and cancers that arise from them using stable isotope 13C1-serine and 13C6-cystine tracing. De novo cysteine synthesis was highest in normal liver and pancreas and absent in lung tissue, while cysteine synthesis was either inactive or downregulated during tumorigenesis. In contrast, cystine uptake and metabolism to downstream metabolites was a universal feature of normal tissues and tumors. However, differences in glutathione labeling from cysteine were evident across tumor types. Thus, cystine is a major contributor to the cysteine pool in tumors, and glutathione metabolism is differentially active across tumor types.
Significance:
Stable isotope 13C1-serine and 13C6-cystine tracing characterizes cysteine metabolism in normal murine tissues and its rewiring in tumors using genetically engineered mouse models of liver, pancreas, and lung cancers.
Data from Enhancer co-amplification and hijacking promote oncogene expression in liposarcoma
Authors: Liu Tingting , Wang Juan , Yang Hongbo , Jin Qiushi , Wang Xiaotao , Fu Yihao , Luan Yu , Wang Qixuan , Youngblood Mark W. , Lu Xinyan , Casadei Lucia , Pollock Raphael , Yue Feng
Published: May 2023

Abstract
Liposarcoma (LPS) is the most common soft-tissue sarcoma in adults with two major subtypes, well differentiated and dedifferentiated. Both subtypes are characterized with the pathognomonic giant ring or marker chromosomes that harbor high copy-numbers of known oncogenes. Here, we reported a comprehensive molecular characterization of both tumor and normal tissues from the same LPS patients, including whole genome sequencing (WGS), transcriptome, enhancer landscape, and genome-wide 3D genome structure by Hi-C. Tumor-specific transcripts and regulatory elements were identified, and enhancer co-amplification and hijacking events were discovered as novel mechanisms upregulating oncogenes such as MDM2, CDK4 and HMGA2. Combining Hi-C, optical mapping, nanopore long reads and WGS data partially resolved complex structural variations and reconstructed the local genome and the giant chromosome. Overall, this study provides a comprehensive resource for LPS research and offers insights into how altered enhancers and the 3D genome contribute to gene dysregulation in cancer.
Inhibition of ACAA1 Restrains Proliferation and Potentiates the Response to CDK4/6 Inhibitors in Triple-Negative Breast Cancer
Authors: Peng Wen-Ting , Jin Xi , Xu Xiao-En , Yang Yun-Song , Ma Ding , Shao Zhi-Ming , Jiang Yi-Zhou
Published: May 2023

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with unfavorable outcomes. Developing therapeutic targets for TNBC remains a challenge. Here, we identified that acetyl-CoA acyltransferase 1 (ACAA1) is highly expressed in the luminal androgen receptor (LAR) subtype of TNBC compared with adjacent normal tissues in our TNBC proteomics dataset. Inhibition of ACAA1 restrained TNBC proliferation and potentiated the response to the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor abemaciclib. Mechanistically, ACAA1 interacted with CDK4, and the inhibition of ACAA1 blocked RB transcriptional corepressor 1 (RB1) phosphorylation, resulting in G1–S cell-cycle arrest. Importantly, trimetazidine, a traditional drug for ischemic heart disease, caused a decrease in ACAA1 protein levels and enhanced the efficacy of abemaciclib in preclinical TNBC models. In conclusion, this study identifies that ACAA1 is a therapeutic target in TNBC and suggests the combination of trimetazidine and abemaciclib could be beneficial for ACAA1-high TNBCs.

Significance:

ACAA1 is highly expressed in TNBC, serving as a potential therapeutic target in ACAA1-high tumors and a predictive biomarker of resistance to CDK4/6 inhibitors for RB1-proficient patients.