bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINC01614 Promotes Osteosarcoma Progression as ceRNA to Target SNX3 by Sponging hsa-miR-520a-3p
Authors: Cai Qixuan , Zhao Xin , Wang Yanbing , Li Shuai , Wang Jincheng , Li Fan 
Published: December 2020

Abstract
Long noncoding RNAs (lncRNAs) have been reported as significant biomarkers for diagnosis and prognosis in osteosarcoma (OS), the most malignant bone tumor usually observed in children and adolescents. In the present study, we detected differentially expressed lncRNAs in three OS and paired adjacent tissues through RNA-seq technology. By comprehensively analyzing the expression profile and bioinformatics, we determined the relationship between noncoding RNA and OS-related functions, signal pathway, regulatory network, patient survival information and selected LINC01614 as the study object. Through related in vitro experiments, we confirmed that LINC01614 knockdown could inhibit the proliferation, invasion, and metastasis of OS cells. Furthermore, we used the luciferase reporter assay and qRT-PCR to confirm the regulatory relationship between LINC01614/hsa-miR-520a-3p/SNX3. We performed relevant in vitro experiments to prove that LINC01614 promotes the proliferation, invasion, and metastasis of OS cells through the LINC01614/hsa-miR-520a-3p/SNX3 axis. In conclusion, we identified that lncRNAs participate in various malignant behaviors in OS. We also proved that LINC01614 could function as competing endogenous RNAs and promote the proliferation, invasion, and metastasis of OS cells, and thus acts as a novel prognostic marker for OS in clinic.
Mining TCGA Data for Key Biomarkers Related to Immune Microenvironment in Endometrial Carcinoma by Immune Score and Weighted Correlation Network Analysis
Authors: Guo Chengbin , Tang Yuqin , Zhang Yongqiang , Li Gen 
Published: December 2020

Abstract
Background: Endometrial cancer (EC) is one of the most lethal gynecological cancer in women. It is imperative to identify the potential immune microenvironment-related biomarkers associated with the prognosis for EC. Methods: RNA-seq data and related clinical information of EC patients were derived from The Cancer Genome Atlas (TCGA). The immune score of each EC sample was obtained by ESTIMATE algorithm. Weighted gene co-expression network analysis (WCGNA) was used to identify the interesting module and potential key genes concerning the immune score. Further, the expression patterns of the key genes were verified via the GEPIA database. Last, CIBERSORT was used to evaluate the relative abundances of 22 immune cell types in EC. Results: Immune scores were significantly associated with tumor grade and histology of EC, and high immune scores may exert a protective influence on the survival outcome for EC. WCGNA indicated that the black module was significantly correlated with the immune score in EC. Function analysis revealed it mainly involved in those terms related to immune regulation and inflammatory response. Moreover, 11 key genes were identified from the black module, validated by the GEPIA database, and revealed strong correlations with infiltration levels of multiple immune cell types, as was the prognosis of EC. Conclusion: In our study, 11 key genes showed abnormal expressions and strong correlations with immune cell infiltration in EC, most of which were significantly associated with the prognosis of EC. These findings made them promising therapeutic targets for the treatment of EC.
Systemic Immune-Inflammation Index Predicts Prognosis of Patients With Esophageal Squamous Cell Carcinoma Undergoing Radical Radiotherapy: A Propensity Score-Matched Analysis
Authors: Zhao Yan , Shen Wen-Bin , Song Chun-Yang , Xu Jin-Rui , Li Shu-Guang , Deng Wen-Zhao , Li Juan , Zhu Shu-Chai 
Published: December 2020

Abstract
BackgroundThe systemic immune-inflammation index (SII) was recently investigated as a prognostic predictor in several kinds of solid tumors, including esophageal squamous cell carcinoma (ESCC) after esophagectomy. However, just few studies regarding SII in patients with ESCC undergoing radical radiotherapy are available. In addition, there has been hardly any report investigating the change trend of SII during radiotherapy. The aim of this study was to identify the prognostic value of SII in ESCC patients undergoing radical radiotherapy. MethodsWe retrospectively reviewed 303 ESCC patients undergoing radical radiotherapy. The change trend of SII was assessed by the box plot and curve fitting method. The time-dependent receiver operating characteristics was used to determine the optimal cutoff value of the SII. The association between SII and survival was determined by Kaplan-Meier method and Cox regression model. Propensity score matching (PSM) was applied to imbalance the baseline characteristics. ResultsHigh SII was associated with poor overall survival (OS) and progression-free survival (PFS) in patients with ESCC undergoing radical radiotherapy. Multivariate analysis showed that SII was a significant predictor for OS and PFS, whether before or after PSM. In addition, SII displayed an exponential increase trend during radiotherapy. The change of SII was also associated with OS and PFS. Conclusions﻿The SII is a significant and independent predictor for OS and PFS of ESCC patients undergoing radical radiotherapy. Based on simple and inexpensive standard laboratory measurements, SII can be a promising marker for ESCC patients.
Molecular Cytogenetic Characterization and Fusarium Head Blight of Five Wheat Thinopyrum Intermedium Partial Amphiploids
Authors: Wang Hui , Cheng Shuwei , Shi Yue , Zhang Shuxin , Yan Wei , Song Weifu , Yang Xuefeng , Song Qingjie , Jang Bo , Qi Xiaoyue , Li Xinling , Friebe Bernd , Zhang Yanming 
Published: December 2020

Abstract
Background: Partial amphiploids created by crossing octoploid tritelytrigia and Thinopyrum intermedium are important intermediates in wheat breeding because of their resistance to major wheat diseases. We examined the chromosome compositions of five wheat Th. intermedium partial amphiploids using GISH and multicolor FISH. Results: The result revealed that five lines had 10 14 J genome chromosomes from Th. intermedium and 42 common wheat chromosomes, using the J genomic DNA from Th. bessarabicum and the oligo probes pAs1 1 , pAs1 3 , AFA 4 , GAA ) 10, and pSc119.2 1 . Five lines resembled the parent Ganmai 8 but had better protein contents. P rotein contents of t wo lines HS2 2 and HS2 5 were up to more than 20%. Evaluation of Fusarium head blight (FHB) resistance revealed that the percent of symptomatic spikelets (PSS) of these lines were below 30%. Lines HS2 2, HS2 4, HS2 5, and HS2 16 were less than 20%. Line HS2 5 with 14 J genome chromosomes from Th. intermedium showed the best disease resistance, with PSS values of 10.8% and 16.6% in 2016 and 2017, respectively. Conclusions: New wheat Th. intermedium amphiploids with the J genome chromosomes were identified and can be considered as a valuable source of FHB resistance in wheat breeding.
A Placental Trisomy 2 Detected by NIPT Evolved in a Fetal Small Supernumerary Marker Chromosome (sSMC).
Authors: Domaradzka Justyna Anna , Deperas Marta , Obersztyn Ewa , Kucińska-Chahwan Anna , Brison Nathalie , Bogaert Kris Van Den , Roszkowski Tomasz , Kędzior Marta , Bartnik-Głaska Magdalena , Łuszczek Alicja , Jakubów-Durska Krystyna , Vermeesch Joris Robert , Nowakowska Beata Anna 
Published: December 2020

Abstract
Background: Non-invasive prenatal testing (NIPT) is known to be more sensitive and more specific for common aneuploidy as well as sex determination at an early pregnancy compared to traditional biochemical and sonographic screening. However, recently the widespread use of the NIPT caused a neglecting of the limitations of this technology. Case presentation: The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar[21]/46,XX[19]) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC.Conclusion: Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity.
Metabolically Healthy Obese Children and the Role of the Gut Microbiota
Authors: Yuan Xin , Chen Ruimin , McCormick Kenneth L. , Zhang Ying , Lin Xiangquan , Yang Xiaohong 
Published: December 2020

Abstract
Background The term “metabolically healthy obese (MHO)” denotes a hale and salutary status, yet this connotation has not been validated in children, and may, in fact, be a misnomer. As pertains to obesity, the gut microbiota has garnered attention as conceivably a nosogenic or, on the other hand, protective participator.Objective This study explored the characteristics of the fecal microbiota of obese Chinese children and adolescents of disparate metabolic status, and the associations between their gut microbiota and circulating proinflammatory factors, such as IL-6 and TNF-α, and a cytokine up-regulator and mediator, leptin. Results Based on weight and metabolic status, the 86 Chinese children (ages 5-15 years) were divided into three groups: metabolically healthy obese (MHO, n=42), metabolic unhealthy obesity (MUO, n=23), and healthy normal weight controls (Con, n=21). In the MUO subjects, the phylum Tenericutes, as well as the alpha and beta diversity, were significantly reduced compared with the controls. Furthermore, Phylum Synergistetes and genus Bacteroides were more prevalent in the MHO population compared with controls. For the MHO subgroup, Spearman’s correlation analysis revealed that serum IL-6 positively correlated with genus Paraprevotella, and leptin correlated positively with genus Phascolarctobacterium and negatively with genus Dialister (all p<0.05).Conclusion Dysbiosis of gut microsystem prevails in the MHO cohort, and the abundance of some metabolism-related bacteria associates with the degree of circulating inflammatory compounds. As for a role in the etiology or facilitation of obesity- or perhaps vice versa- this childhood microbial imbalance awaits long-term, longitudinal investigation.
Single-cell Transcriptomic Analysis of Eutopic Endometrium and Ectopic Lesions of Adenomyosis
Authors: Liu Zhiyong , Sun Zhonghua , Liu Hongyun , Niu Weipin , Wang Xin , Liang Na , Wang Xin , Wang Yanfei , Shi Yaxin , Xu Li , Shi Wei 
Published: December 2020

Abstract
Background: Adenomyosis (AM) is a common benign chronic gynaecological disorder; however, the precise pathogenesis of adenomyosis is still poorly understood. Single-cell RNA sequencing (scRNA-seq) can uncover rare subpopulations, explore genetic and functional heterogeneity, and reveal the uniqueness of each cell. It provides us a new approach to reveal biological issues from a more detailed and microscopic perspective. Here, we utilize this revolutionary technology to identify the changes of gene expression patterns between ectopic lesions and the eutopic endometrium at the single-cell level and explore a potential novel pathogenesis of AM.Methods: A control endometrium (sample with leiomyoma excluding endometrial disorders, n=1), eutopic endometrium and ectopic lesion (from a patient with adenomyosis, n=1) samples were analysed by scRNA-seq, and additional leiomyoma (n=3) and adenomyosis (n=3) samples were used to confirm colocalization and vasculogenic mimicry (VM) formation. Protein colocalization was visualized by immunofluorescence, and CD34-periodic acid-Schiff (PAS) double staining was used to assess the formation of VM.Results: The scRNA-seq results suggest that cancer-, cell motility- and inflammation- (CMI) associated terms, cell proliferation and angiogenesis play important roles in the progression of AM. Moreover, the colocalization of EPCAM and PECAM1 increased significantly in the ectopic endometrium group (P < 0.05), cell subpopulation with high copy number variation (CNV) levels possessing tumour-like features existed in the ectopic lesion sample, and VNN1- and EPCAM-positive cell subcluster displayed active cell motility in endometrial epithelial cells. Furthermore, the epithelial cells transformed to endothelial cells with the obvious accumulation of vasculogenic mimicry formations (positively stained with PAS but not CD34, P < 0.05) in ectopic lesions.Conclusions: In the present study, our results support the theory of adenomyosis derived from the invasion and migration of the endometrium. Moreover, cell subcluster with high CNV level and tumour-associated characteristics is identified. Furthermore, epithelial-endothelial transition (EET) and the formation of VM in tumours, the latter of which facilitates the blood supply and plays an important role in maintaining cell growth, were also confirmed to occur in AM. These results indicated that the inhibition of EET and VM formation may be a potential strategy for AM management.
Identification of a Potent Antagonist of Smoothened in Hedgehog Signaling
Authors: Fan Junwan , Li Haowen , Zhao Zichen , Kuang Lun , He Wenyan , Wang Yongjun , Cheng Steven Y. , Chen Wei 
Published: December 2020

Abstract
Background Hedgehog signaling is essential to the regulation of embryonic development, tissue homeostasis, and stem cell self-renewal, making it a prime target for developing cancer therapeutics. Given the close link between aberrant Hedgehog signaling and cancers, many small molecular compounds have been developed to inhibit this pathway for treating cancer and several of such compounds have been approved by FDA (GDC-0449 and LDE-225). As we known, acquired drug resistance is the main obstacle of first generation of Smoothened inhibitors. Therefore, new Smoothened inhibitors that could inhibit wild-type and mutant receptors are essential for refractory cancers. ResultsWe established the Smoothened β arrestin 2 GFP high throughput screening platform based on the mechanistic discovery of Hedgehog signaling pathway, and discovered several active small molecules targeting Smoothened including 0025A 0025A. Here we show that 0025A can block the translocation of β arrestin 2 GFP to Smoothened , displace Bodipycyclopamine binding to wild type Smoothened or mutant Smoothened D473H and reduce the expression of Gli upon Hedgehog stimulation. In addition, we reveal that 0025A can effectively suppress hair follicle morphogenesis and hair growth in mice. Conclusions Thus, our results demonstrate that 0025A is a potent antagonist targeting Smoothened wild-type and mutant type and mutant receptors in the Hreceptors signaling pathway and may provide a new new therapy for refractory cancers.
K-Seq, An Affordable, Reliable, and Open Klenow NGS-Based Genotyping Technology
Authors: Ziarsolo Peio , Hasing Tomas , Hilario Rebeca , Garcia-Carpintero Victor , Blanca Jose , Bombarely Aureliano , Canizares Joaquin 
Published: December 2020

Abstract
Background K-seq, a new genotyping methodology based on the amplification of genomic regions using two steps of Klenow amplification with short oligonucleotides, followed by standard PCR and Illumina sequencing, is presented. The protocol was accompanied by software developed to aid with primer set design.Results As the first examples, K-seq in species as diverse as tomato, dog and wheat was developed. K-seq provided genetic distances similar to those based on WGS in dogs. Experiments comparing K-seq and GBS in tomato showed similar genetic results, although K-seq had the advantage of finding more SNPs for the same number of Illumina reads. The technology reproducibility was tested with two independent runs of the tomato samples, and the correlation coefficient of the SNP coverages between samples was 0.8 and the genotype match was above 94%. K-seq also proved to be useful in polyploid species. The wheat samples generated specific markers for all subgenomes, and the SNPs generated from the diploid ancestors were located in the expected subgenome with accuracies greater than 80%.Conclusion K-seq is an open, patent-unencumbered, easy-to-set-up, cost-effective and reliable technology ready to be used by any molecular biology laboratory without special equipment in many genetic studies.
Full-Length Transcriptome Sequences by A Combination of Sequencing Platforms Applied to Isoflavonoid and Triterpenoid Saponin Biosynthesis of Astragalus Mongholicus Bunge
Authors: Yin Minzhen , Chu Shanshan , Shan Tingyu , Zha Liangping , Peng Huasheng 
Published: December 2020

Abstract
Background: Astragalus mongholicus Bunge is an important medicinal plant and has been used in traditional Chinese medicine for a long history, which is rich in isoflavonoids and triterpenoid saponins. Although these active constituents in A. mongholicus have been discovered for a long time, the molecular genetic basis of the isoflavonoid and triterpenoid saponin biosynthesis pathways is virtually unknown due to the lack of a reference genome. The combination of next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing to analyze genes involved in the biosynthetic pathways of secondary metabolites in medicinal plants has been widely recognized.Results: In this study, NGS, SMRT sequencing, and targeted compounds were combined to investigate the association between isoflavonoids and triterpenoid saponins and gene expression in roots, stems and leaves of A. mongholicus. A total of four main isoflavonoids and four astragalosides (belong to triterpenoid saponins) were measured, and 44 differentially expressed genes (DEGs) of nine gene families, 44 DEGs of 16 gene families that encode for enzymes involved in isoflavonoid and triterpenoid saponin biosynthesis were identified, separately. Additionally, transcription factors (TFs) associated with isoflavonoid and triterpenoid saponin biosynthesis were analyzed, including 72 MYBs, 53 bHLHs, 64 AP2-EREBPs and 11 bZIPs. The above transcripts exhibit different expression trends in different organs.Conclusions: Our study provides important genetic information for the essential genes of isoflavonoid and triterpenoid saponin biosynthesis in A. mongholicus, and provides a basis for developing its medicinal value.
No association of serum sTREM2 and MRI-based brain volume in elderly people living in a rural community: a 7-year follow-up study
Authors: Orihashi Ryuzo , Mizoguchi Yoshito , Imamura Yoshiomi , Yamada Shigeto , Monji Akira 
Published: December 2020

Abstract
BackgroundThis study aimed to investigate the association between serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble form of an innate immune receptor expressed on the microglia, and brain volume in elderly people.MethodsThe survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum sTREM2 level measurements, brain MRI, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) were performed at Time 1 (2009–2011). Follow-up brain MRI, MMSE, and CDR were performed at Time 2 (2016–2017). The interval between Time 1 and Time 2 was approximately 7 years. Sixty-nine participants (16 men, mean age 72.69 ± 3.18 years; 53 women, mean age 72.68 ± 4.64 years) completed this study. We analyzed the correlation between serum sTREM2 levels (Time 1) and brain volume (Time 1, Time 2, and Time 1–Time 2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping.ResultsParticipants in this study had lower MMSE and CDR scores 7 years after the baseline evaluation. However, analyses at the cluster level by applying multiple comparison corrections (family wise error; P < 0.05) showed no correlation between serum sTREM2 levels and volume of different brain regions, either cross-sectional or longitudinal. ConclusionsSerum sTREM2 level could not serve as an immune biomarker of aging-related volume changes in brain regions closely related to cognitive function in elderly people aged 65 years and above.
Diagnostic Value of Apparent Diffusion Coefficient Maps for the Differentiation of Brain Metastases from Lung cancer
Authors: Mueller Sebastian Johannes , Khadhraoui Eya , Neef Nicole , Ernst Marielle-Sophie , Riedel Christian Heiner 
Published: December 2020

Abstract
Background: Brain metastases are particularly common in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC showing a more aggressive clinical course and lower chemo- and radio sensitivity compared to SCLC. Early adequate therapy is highly desirable and depends on a reliable classification of tumor type. The apparent diffusion coefficient is a noninvasive neuroimaging marker with the potential to differentiate between major histological subtypes. Here we determine the sensitivity and specificity of the apparent diffusion coefficient to distinguish between NSCLC and SCLC.Methods: We enrolled all NSCLC and SCLC patients diagnosed between 2008 and 2019 at the University Medical Center Göttingen. Cranial MR scans were visually inspected for brain metastases and the ratio of the apparent diffusion coefficient (ADC) was calculated by dividing the ADC measured within the solid part of a metastasis by a reference ADC extracted from an equivalent region in unaffected tissue on the contralateral hemisphere.Results: Out of 411 enrolled patients, we detected 129 patients (83 NSCLC, 46 SCLC) with sufficiently large brain metastases with histologically classified lung cancer and no hemorrhage. We analyzed 185 brain metastases, 84 of SCLC and 101 of NSCLC. SCLC brain metastases showed an ADC ratio of 0.68 ± 0.12 SD, and NSCLC brain metastases showed an ADC ratio of 1.47 ± 0.31 SD. Receiver operating curve statistics differentiated brain metastases of NSCLC from SCLC with an area under the curve of 0.99 and a 95% CI of 0.98 to 1, p < 0.001. Youden's J cut-point is 0.97 at a sensitivity of 0.989 and a specificity of 0.988. Conclusions: In patients with lung cancer and brain metastases with solid tumor parts, ADC ratio enables an ad hoc differentiation of SCLC and NSCLC, easily achieved during routine neuroradiological examination. Non-invasive MR imaging enables an early-individualized management of brain metastases from lung cancer.Trial registration: The study was registered in the German Clinical Trials Register (DRKS00023016).