bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Economic Impact of ‘ROS1-Testing’ Strategy Compared to a ‘No- ROS1-Testing’ Strategy in Advanced NSCLC in Spain
Authors: Rojo Federico , Conde Esther , Torres Héctor , Cabezón-Gutiérrez Luis , Bautista Dolores , Ramos Inmaculada , Carcedo David , Arrabal Natalia , García J. Francisco , Galán Raquel , Nadal Ernest 
Published: December 2021

Abstract
Background: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain.Methods: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty.Results: A target population of 8,755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis.Conclusions: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.
Soil Microbial Community Composition and Diversity Remained Unchanged in a Semiarid Grassland in Northwestern China After 7 Years of Nitrogen Addition
Authors: Guo Qian , Wen Zhongming , Ghanizadeh Hossein , Zheng Cheng , Fan Yongming , Lu Jinxin , Yang Xue , Yan Xinhui , Chen Sihui , Li Wei 
Published: December 2021

Abstract
Aims

Nitrogen (N) deposition is a global environmental problem that can alter community compositions and functions, and consequently, the ecosystem services. In this study, we assessed the responses of aboveground vegetation, surface soil properties and microbial communities to N addition, and explored the drivers of microbial community in a semiarid steppe ecosystem in northwest of China.
Methods

Thirty-six 6×10-m2 plots composed of six N addition levels and six replicates were distributed in six columns and six rows. Nine vegetation characteristics and seven soil properties were measured and calculated. Soil microbial characteristics were analyzed by 16S rRNA high-throughput sequencing.
Results

N addition positively affected aboveground vegetation traits such as the community weighted-mean of leaf nitrogen content (LNCWM). High N inputs significantly altered the microbial community assembly process from random to deterministic. The microbial community diversity and composition, however, were not sensitive to N addition. A piecewise structural equation model (SEM) further showed that the microbial community composition was affected by both aboveground vegetation and soil properties. The composition of bacterial communities was mainly regulated by the composition of plant communities and soil total N. In contrast, the composition of fungal communities was driven by soil pH and the community weighted-mean of specific leaf area (SLACWM). Microbial diversity and composition remained unchanged because their drivers were not affected by N addition. The results of this research improved our understanding of the response of grassland ecosystems to N deposition, and provided a theoretical basis for grassland utilization and management under N deposition.
Regression-Based Beam Training for UAV mmWave Communications
Authors: Zhang Junjie , Zhong Weizhi , Gu Yong , Zhu Qiuming , Zhang Lulu 
Published: December 2021

Abstract
For the unmanned aerial vehicle (UAV) Millimeter-Wave (mmWave) communication systems, an efficient and accurate beam training method is urgently required to overcome the severe path loss. By taking into account the mmWave propagation environment,a three-dimensional (3D) intelligent beam training strategy by leveraging the polynomial regression model and optimized beam patterns is proposed in this paper. We treat the mmWave beam selection as a polynomial regression problem. The regression function is obtained by a machine learning (ML) method based on the dataset and a special beam pattern is achieved to obtain the dataset consisting of measured powers and estimated angles. Furthermore, a noise suppression method involving the use of denoising autoencoder (DAE) is developed to improve the robustness of the proposed regression model.Numerical simulation results demonstrate that our proposed beam training strategy is capable of getting the same precision as the exhaustive search methods with a shorter time.
Efficacy of First-Third generation EGFR inhibitor combined with chemotherapy as first-line treatment for advanced lung adenocarcinoma in a real-world setting
Authors: Chen Ming-Wei Chen Ming-Wei , . An-Tai He , . Yi Pei 
Published: December 2021

Abstract
BackgroundTo explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head-to-head study was performed to compare chemotherapy and gefitinib-erlotinip, osimertinib treatment in combination or with either agent alone as first-line therapy, in terms of efficacy and safety.MethodsA total of 200 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib-erlotinip combined with pemetrexed and carboplatin group, gefitinib-erlotinip osimertinib combined with pemetrexed and carboplatin group, pemetrexed plus carboplatin alone group, or gefitinib-erlotinip alone group, osimertinib alone group.ResultsThe progression-free survival (PFS) of patients in the gefitinib-erlotinip combination group Mean Survival Time PFS 22.00 month,95%CI[16.29,27.70] and osimertinib gefitinib-erlotinip combination group Mean Survival Time PFS 40.00 month,95%CI[28.12,51.87]was longer than that of patients in the chemotherapy alone group PFS10,81 months, 95% CI,[ 8.99–12.64],gefitinib-erlotinip alone group PFS14.00 month.95%CI[11.98-20.01], osimertinib alone group PFS 26.66 month 95%CI[24.77-29.22].The gefitinib-erlotinip osimertinib combinational resulted in longer overall survival (OS) than chemotherapy alone (HR = 0.46, p = 0.016) or gefitinib-erlotinip alone (HR = 0.36, p = 0.01). osimertinib alone (HR = 0.26, p = 0.01).ConclusionsOur finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib-erlotinip and pemetrexed plus carboplatin combined with gefitinib-erlotinip osimertinib group could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.
Identification of Key Genes Involved in the Pathogenesis of Recurrent Pelvic Organ Prolapse Using Bioinformatics Analysis
Authors: Zhu Ling , Ni Xiaoling , Tang Shanshan , Liu Wenhua 
Published: December 2021

Abstract
Background: The causes of the recurrence of pelvic organ prolapse (POP) are sufficiently understood. However, few studies investigate the key genes of recurrence POP. The present study aimed to screen the hub genes of recurrence POP. Microarray data of 4 recurrent POP and 4 primary POP uterosacral ligaments in the GSE28660 gene expression dataset were used as research objects. we used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset to identify differentially expressed genes (DEGs). Also, functional enrichment and protein-protein interaction (PPI) network analyses were performed, and the key modules were identified. Then, we investigated the differential immune cell infiltration between recurrent POP and primary POP tissues using the CIBERSORT algorithm.Results: In total, 84 upregulated and 32 downregulated genes were identified in the differential expression analysis.Conclusion: This human genome DNA microarrays analysis identified a recurrence POP signature of 116 genes, and 2 hub genes, including cell death-inducing DFFA-like effector (CIDEA) and hemoglobin subunit delta (HBD) may participate in the pathogenesis of recurrence POP, giving them a certain diagnostic and therapeutic value.
Engineered Exosomes for the Targeted Delivery of a Novel Therapeutic Cargo to Enhance Sorafenib-Mediated Ferroptosis in Hepatocellular Carcinoma.
Authors: Li Xiaoju , Yu Qianqian , Guo Xinyan , Liu Chenlin , Zhao Runze , Zhang Kuo , Zhang Wangqian , Liu Jinghan , Sun Guanchao , Wang Shuning , Hao Qiang , Li Weina , Li Meng , Zhang Yingqi , Zhang Cun , Gao Yuan 
Published: December 2021

Abstract
Background

Sorafenib is one of the few effective first-line drugs approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common among individuals with HCC. Thus, there is an urgent need to solve this problem.
Results

Recent evidence indicated that the anticancer activity of sorafenib mainly relies on the induction of ferroptosis. In our study, genes that suppress ferroptosis, especially GPX4 and DHODH, were enriched in sorafenib-resistant cells and primary tissues and were associated with poor prognosis of HCC patients who received sorafenib treatment. Therefore, silencing GPX4 and DHODH might be a novel and effective strategy to overcome sorafenib resistance. Here, a novel ferroptosis inducer comprising a multiplex small interfering RNA (multi-siRNA) capable of simultaneously silencing GPX4 and DHODH was created. Then, exosomes with high multi-siRNA loading and HCC-specific targeting were established by fusing the SP94 peptide and the N-terminal RNA recognition motif (RRM) of U1-A with the exosomal membrane protein Lamp2b. The results from the in vitro and in vivo experiments indicate that this tumor-targeting nanodelivery system (ExoSP94−lamp2b−RRM-multi-siRNA) could enhance sorafenib-induced ferroptosis and overcome sorafenib resistance, which might open a new avenue for clinically overcoming sorafenib resistance.
Conclusions

We designed HCC-targeted exosomes (ExoSP94−Lamp2b−RRM) that can deliver a novel ferroptosis inducer. Our data show that ExoSP94−lamp2b−RRM-multi-siRNA could enhance sorafenib-induced ferroptosis by silencing GPX4 and DHODH expression and consequently increase HCC sensitivity to sorafenib. This is the first study to describe the use of engineered exosomes to overcome acquired sorafenib resistance with respect to ferroptosis.
Fixed-Time Adaptive Neural Network Tracking Control for Output-Constrained High-Order Systems Using Command Filtered Strategy
Authors: Chen Lian , Wang Qing 
Published: December 2021

Abstract

This paper proposes a fixed time adaptive neural command filtered controller for a category of high-order systems based on adding a power integrator technique. Different from existing research, the presented controller has the following distinguishing advantages: i) fixed-time control framework is extended to the tracking control problem of high-order systems. ii) the error compensation mechanism eliminates filter errors that arise from dynamic controllers. iii) growth assumptions about unknown functions are relaxed with the help of adaptive neural networks. iv) more general systems: the developed controller can apply to high-order systems subject to uncertain dynamics, unknown gain functions and asymmetric constraints. Stability analysis shows that all states are semi-globally bounded, and the convergence rate of tracking error is independent of initial conditions. The main innovation of our work is that the presented controller considers simultaneously filter errors, fixed-time convergence, growth conditions and asymmetric output constraint for the tracking control issue of high-order systems. Finally, the simulation results validate the advantages and efficacy of the developed control scheme.
Nomogram Models Based on Gene Expression in Prediction of Breast Cancer Bone Metastasis
Authors: Fan Teng-di , Bei Di-kai , Li Song-wei 
Published: December 2021

Abstract
Objective: To design a weighted co-expression network and build gene expression signature-based nomogram (GESBN) models for predicting the likelihood of bone metastasis in breast cancer (BC) patients. Methods: Dataset GSE124647 was used as a training set, and GSE14020 was taken as a validation set. In the training cohort, limma package in R was adopted to obtain differentially expressed genes (DEGs) between BC non-bone metastasis and bone metastasis patients, which were used for functional enrichment analysis. After weighted co-expression network analysis (WGCNA), univariate Cox regression and Kaplan-Meier plotter analyses were performed to screen potential prognosis-related genes. Then, GESBN models were constructed and evaluated. Further, the expression levels of genes in the models were explored in the training set, which was validated in GSE14020. Finally, the prognostic value of hub genes in BC was explored. Results: A total of 1858 DEGs were obtained. WGCNA result showed that the blue module was most significantly related to bone metastasis and prognosis. After survival analyses, GAJ1, SLC24A3, ITGBL1, and SLC44A1 were subjected to construct a GESBN model for overall survival. While GJA1, IGFBP6, MDFI, ITGFBI, ANXA2, and SLC24A3 were subjected to build a GESBN model for progression-free survival. Kaplan-Meier plotter and receiver operating characteristic analyses presented the reliable prediction ability of the models. Besides, GJA1, IGFBP6, ITGBL1, SLC44A1, and TGFBI expressions were significantly different between the two groups in GSE124647 and GSE14020. The hub genes had a significant impact on patient prognosis. Conclusion: Both the four-gene signature and six-gene signature could accurately predict patient prognosis, which may provide novel treatment insights for BC bone metastasis.
Enhanced Biosynthesis of D-arabitol by Metschnikowia Reukaufii Through Optimizing Medium Composition and Fermentation Conditions
Authors: Huang Jiaqi , An Yingfeng , Zabed Hossain M. , Ravikumar Yuvaraj , Zhao Mei , Yun Junhua , Zhang Guoyan , Zhang Yufei , Li Xiaolan , Qi Xianghui 
Published: December 2021

Abstract
D-arabitol is an important functional sugar alcohol, which can be used in the preparation of foods, chemicals, and medicines. Despite biological production of D-arabitol from low-cost substrates has recently been the focus of research, low yield of this technology has limited its large-scale exploitation. Optimization of this bioprocess could be a promising option to improve the yield of D-arabitol. In this study, one-factor-at-a-time (OFAT) strategy and Box-Behnken design (BBD) were used to increase D-arabitol production by Metschnikowia reukaufii CICC 31858 through optimizing the fermentation conditions and medium composition. The OFAT optimization provided the optimal conditions for temperature, agitation speed, and fermentation time of 30℃, 220 rpm, and 144 h, respectively. Likewise, the optimum concentrations of peptone, ammonium sulfate, KH2PO4, MgSO4·7H2O, and fumaric acid in the fermentation medium were (g/L) 7.5, 1, 2 , 0.5 and 7.5, respectively. Under these optimum conditions, 80.43 g/L of D-arabitol was produced from 200 g/L of glucose, with a productivity of 0.56 g/L/h. The BBD optimization with three important components of fermentation medium (KH2PO4, MgSO4·7H2O and fumaric acid) showed that the predicted titer of D-arabitol varied from 47.21 g/L to 89.27 g/L, and the actual titer of D-arabitol ranged from 47.36 to 89.83 g/L. The optimum concentrations (g/L) of KH2PO4, MgSO4·7H2O, and fumaric acid in the fermentation medium were found to be 1.0, 0.5, and 4.7g/L, respectively. Under the optimum conditions, 92.45 g/L of D-arabitol was finally produced with the yield and productivity of 0.46 g/g and 0.64 g/L/h, respectively.
Targeting CDA-Directed Metabolism With 5-Formyl-2'-Deoxycytidine For ALK Inhibitor–Resistant Lung Cancer Therapy
Authors: Heo Haejeong , Kim Jong-Hwan , Lim Hyun Jung , Kim Jeong-Hwan , Kim Miso , Koh Jaemoon , Im Joo-Young , Kim Bo-Kyung , Won Misun , Park Ji-Hwan , Yun Mi Ran , Cho Byoung Chul , Kim Yong Sung , Kim Seon-Young , Kim Mirang 
Published: December 2021

Abstract
Background: Acquired resistance to inhibitors of anaplastic lymphoma kinase (ALK) is a major clinical challenge for ALK fusion–positive non-small-cell lung cancer (NSCLC). In the absence of secondary ALK mutations, epigenetic reprogramming is one of the main mechanisms of drug resistance as it leads to phenotype switching that occurs during the epithelial-to-mesenchymal transition (EMT). While drug-induced epigenetic reprogramming is believed to alter the sensitivity of cancer cells to anticancer treatments, there is still much to learn about overcoming drug resistance. Methods: We used an in vitro model of ceritinib-resistant NSCLC and employed genome-wide DNA methylation analysis in combination with single-cell (sc) RNA-seq to identify cytidine deaminase (CDA), a pyrimidine salvage pathway enzyme, as a candidate drug target. Molecular biology was used to characterize the role of CDA in drug resistance. Integrated analysis of scRNA-seq and scATAC-seq identified gene regulatory networks in resistant cells. Clinical relevance of CDA was evaluated using TCGA datasets, patient-derived cells, and tumor biopsies. Results: CDA was hypomethylated and upregulated in ceritinib-resistant cells. CDA-overexpressing cells were rarely but definitively detected in the na¨ıve cell population by scRNA-seq, and their abundance increased in the acquired-resistance population. Knockdown of CDA had antiproliferative e↵ects on resistant cells and reversed the EMT phenotype. Treatment with epigenome-related nucleosides such as 5-formyl-2’-deoxycytidine selectively ablated CDA-overexpressing resistant cells via accumulation of DNA damage. Conclusions: Targeting CDA metabolism using epigenome-related nucleosides represents a potential new therapeutic strategy for overcoming ALK-inhibitor resistance in NSCLC.
Complete Genome Sequence of Vallota Mosaic Virus Detected In A Narcissus Bulb Imported From The United States to Japan
Authors: Imamura Yuya , Oishi Moritsugu , Fujiwara Yuji , Yanagisawa Hironobu 
Published: December 2021

Abstract
Narcissus (Narcissus albidus) imported from the United States exhibited leaf chlorosis during post-entry quarantine. We employed next-generation sequencing (NGS) on symptomatic leaf samples and detected vallota mosaic virus (ValMV) belonging to the genus Potyvirus, family Potyviridae, as the viral agent. Sanger sequencing of PCR and rapid amplification of cDNA ends based on NGS contigs revealed that ValMV was 9,451 nucleotides (nt) in length, excluding the poly(A) tail. Nucleotide and amino acid (aa) sequences of the coat protein region had over 98% identity to previously reported ValMV isolates. At each of the 10 mature protein regions, however, sequence identity with other potyviruses was 49.5–71.9% nt and 18.3–78.9% aa, values that are below the species demarcation criteria for Potyviridae. Phylogenetic analysis revealed that our ValMV isolate is most closely related to known ValMV and is grouped within other potyviruses. Taken together, our results indicate that the newly isolated ValMV belongs to a distinct species of Potyvirus. This study provides the first report of the complete ValMV genome sequence and the first record of this virus from the narcissus.
Hamming Distance and the onset of quantum criticality
Authors: Yi TianCheng , Scalettar Richard , Mondaini Rubem 
Published: December 2021

Abstract
Simulating models for quantum correlated matter unveils the inherent limitations of deterministic classical computations. In particular, in the case of quantum Monte Carlo methods, this is manifested by the emergence of negative weight configurations in the sampling, that is, the sign problem (SP). There have been several recent calculations which exploit the SP to locate underlying critical behavior. Here, utilizing a metric that quantifies phase-space ergodicity in such sampling, the Hamming distance, we suggest a significant advance on these ideas to extract the location of quantum critical points in various fermionic models, in spite of the presence of a severe SP. Combined with other methods, exact diagonalization in our case, it elucidates both the nature of the different phases as well as their location, as we demonstrate explicitly for the honeycomb and triangular Hubbard models, in both their U(1) and SU(2) forms. Our approach charts a path to circumvent inherent limitations imposed by the SP, allowing the exploration of the phase diagram of a variety of fermionic quantum models hitherto considered to be impractical via quantum Monte Carlo simulations.
A mathematical justification for metronomic chemotherapy in oncology
Authors: Fernández Luis Alberto Fernández , Pola Cecilia , Sáinz-Pardo: Judith 
Published: December 2021

Abstract
We mathematically justify metronomic chemotherapy as the best strategy to apply most cytotoxic drugs in oncology for both curative and palliative approaches, assuming the classical pharmacokinetic model together with the Emax pharmacodynamic and the Norton-Simon hypothesis.From the mathematical point of view, we will consider two mixed-integer nonlinear optimization problems, where the unknowns are the number of the doses and the quantity of each one, adjusting the administration times a posteriori.Mathematics Subject Classification: 93C15, 92C50, 90C30
Multi-Elliptic Rogue Wave Clusters of the Nonlinear Schrodinger Equation on Different Backgrounds
Authors: Nikolic Stanko N , Washahi Sarah Al , Ashour Omar A. , Chin Siu A. , Aleksic Najdan B. , Belic Milivoj R. 
Published: December 2021

Abstract
In this work we analyze the multi-elliptic rogue wave clusters as new solutions of the nonlinear Schr\"odinger equation (NLSE). Such structures are obtained on uniform backgrounds by using the Darboux transformation scheme of order $n$ with the first $m$ evolution shifts that are equal, nonzero, and eigenvalue-dependent, while the imaginary parts of all eigenvalues tend to one. We show that an Akhmediev breather of $n-2m$ order appears at the origin of the $(x,t)$ plane and can be considered as the central rogue wave of the cluster. We show that the high-intensity narrow peak, with characteristic intensity distribution in its vicinity, is enclosed by $m$ ellipses consisting of the first-order Akhmediev breathers. The number of maxima on each ellipse is determined by its index and the solution order. Since rogue waves in nature usually appear on a periodic background, we utilize the modified Darboux transformation scheme to build these solutions on a Jacobi elliptic dnoidal background. We analyze the minor semi-axis of all ellipses in a cluster as a function of an absolute evolution shift. We show that the cluster radial symmetry in the $(x,t)$ plane is violated when the shift values are increased above a threshold. We apply the same analysis on Hirota equation, to examine the influence of a free real parameter and Hirota operator on the cluster appearance. The same analysis can be extended to the infinite hierarchy of extended NLSEs.