bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of GNPNAT1 Predicts Poor Prognosis and Correlates With Immune Infiltration in Lung Adenocarcinoma
Authors: Liu Wenting , Jiang Kaiting , Wang Jingya , Mei Ting , Zhao Min , Huang Dingzhi 
Published: March 2021

BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a key enzyme in the hexosamine biosynthetic pathway (HBP), which functions as promoting proliferation in some tumors, yet its potential biological function and mechanism in lung adenocarcinoma (LUAD) have not been explored.MethodsThe mRNA differential expression of GNPNAT1 in LUAD and normal tissues was analyzed using the Cancer Genome Atlas (TCGA) database and validated by real-time PCR. The clinical value of GNPNAT1 in LUAD was investigated based on the data from the TCGA database. Then, immunohistochemistry (IHC) of GNPNAT1 was applied to verify the expression and clinical significance in LUAD from the protein level. The relationship between GNPNAT1 and epigenetics was explored using the cBioPortal database, and the miRNAs regulating GNPNAT1 were found using the miRNA database. The association between GNPNAT1 expression and tumor-infiltrating immune cells in LUAD was observed through the Tumor IMmune Estimation Resource (TIMER). Finally, Gene set enrichment analysis (GSEA) was used to explore the biological signaling pathways involved in GNPNAT1 in LUAD.ResultsGNPNAT1 was upregulated in LUAD compared with normal tissues, which was verified through qRT-PCR in different cell lines (P &lt; 0.05), and associated with patients’ clinical stage, tumor size, and lymphatic metastasis status (all P &lt; 0.01). Kaplan–Meier (KM) analysis suggested that patients with upregulated GNPNAT1 had a relatively poor prognosis (P &lt; 0.0001). Furthermore, multivariate Cox regression analysis indicated that GNPNAT1 was an independent prognostic factor for LUAD (OS, TCGA dataset: HR = 1.028, 95% CI: 1.013–1.044, P &lt; 0.001; OS, validation set: HR = 1.313, 95% CI: 1.130–1.526, P &lt; 0.001). GNPNAT1 overexpression was correlated with DNA copy amplification (P &lt; 0.0001), low DNA methylation (R = −0.52, P &lt; 0.0001), and downregulation of hsa-miR-30d-3p (R = −0.17, P &lt; 0.001). GNPNAT1 expression was linked to B cells (R = −0.304, P &lt; 0.0001), CD4+T cells (R = −0.218, P &lt; 0.0001), and dendritic cells (R = −0.137, P = 0.002). Eventually, GSEA showed that the signaling pathways of the cell cycle, ubiquitin-mediated proteolysis, mismatch repair and p53 were enriched in the GNPNAT1 overexpression group.ConclusionGNPNAT1 may be a potential prognostic biomarker and novel target for intervention in LUAD.
Development of a Novel Prognostic Model for Predicting Lymph Node Metastasis in Early Colorectal Cancer: Analysis Based on the Surveillance, Epidemiology, and End Results Database
Authors: Ahn Ji Hyun , Kwak Min Seob , Lee Hun Hee , Cha Jae Myung , Shin Hyun Phil , Jeon Jung Won , Yoon Jin Young 
Published: March 2021

BackgroundIdentification of a simplified prediction model for lymph node metastasis (LNM) for patients with early colorectal cancer (CRC) is urgently needed to determine treatment and follow-up strategies. Therefore, in this study, we aimed to develop an accurate predictive model for LNM in early CRC.MethodsWe analyzed data from the 2004-2016 Surveillance Epidemiology and End Results database to develop and validate prediction models for LNM. Seven models, namely, logistic regression, XGBoost, k-nearest neighbors, classification and regression trees model, support vector machines, neural network, and random forest (RF) models, were used.ResultsA total of 26,733 patients with a diagnosis of early CRC (T1) were analyzed. The models included 8 independent prognostic variables; age at diagnosis, sex, race, primary site, histologic type, tumor grade, and, tumor size. LNM was significantly more frequent in patients with larger tumors, women, younger patients, and patients with more poorly differentiated tumor. The RF model showed the best predictive performance in comparison to the other method, achieving an accuracy of 96.0%, a sensitivity of 99.7%, a specificity of 92.9%, and an area under the curve of 0.991. Tumor size is the most important features in predicting LNM in early CRC.ConclusionWe established a simplified reproducible predictive model for LNM in early CRC that could be used to guide treatment decisions. These findings warrant further confirmation in large prospective clinical trials.
RETRACTED: LncRNA SNHG19 Promotes the Development of Non-Small Cell Lung Cancer via Mediating miR-137/E2F7 Axis
Authors: Zhao Guang-Yin , Ning Zhao-Feng , Wang Rui 
Published: March 2021

ObjectiveNon-small cell lung cancer (NSCLC) is a common malignant tumor, which has high incidence and low the 5-year survival rate. Long non-coding RNAs (lncRNAs) play critical roles in carcinoma occurrence and metastasis. Herein, our aim was to investigate the effects of lncRNA SNHG19 in NSCLC progression.Materials and MethodsLong non-coding RNA Small Nucleolar RNA Host Gene 19 (lncRNA SNHG19) expression level was measured by bioinformatics and qRT-PCR. Edu, Transwell, and scratch assays were performed to explore the role of si-SNHG19 or SNHG19 on NSCLC progression. Luciferase assay was used to verify the relationship between SNHG19/E2F7 and miR-137. The experiment of Xenograft was used for exploring the function of SNHG19 in vivo.ResultsSNHG19 was upregulated in cancer tissues, patients plasma and cell lines of NSCLC. Knockdown of SNHG19 inhibited cell proliferation, migration, and invasion. Luciferase assay confirmed that SNHG19 regulated E2F7 expression via interacting with miR-137. Overexpression of SNHG19 accelerated NSCLC tumor progression via miR-137/E2F7 axis both in vitro and in vivo.ConclusionsOur results clarified the SNHG19 function for the first time, and SNHG19 promoted the progression of NSCLC, which was mediated by the miR-137/E2F7 axis. This study might provide new understanding and targets for NSCLC diagnosis and treatment.
Predicting Masaoka-Koga Clinical Stage of Thymic Epithelial Tumors Using Preoperative Spectral Computed Tomography Imaging
Authors: Zhou Qing , Ke Xiaoai , Man Jiangwei , Zhang Bin , Wang Furong , Zhou Junlin 
Published: March 2021

ObjectivesTo investigate the utility of spectral computed tomography (CT) parameters for the prediction of the preoperative Masaoka-Koga stage of thymic epithelial tumors (TETs).Materials and MethodsFifty-four patients with TETs, aged from 37 to 73 years old, an average age of 55.56 ± 9.79 years, were included in the study.According to the Masaoka-Koga staging method, there were 19 cases of stage I, 15 cases of stage II, 8 cases of stage III, and 12 cases of stage IV disease. All patients underwent dual-phase enhanced energy spectral CT scans. Regions of interest (ROIs) were defined in sections of the lesion with homogeneous density, the thoracic aorta at the same level as the lesion, the outer fat layer of the lesion, and the anterior chest wall fat layer. The single-energy CT value at 40-140 keV, iodine concentration, and energy spectrum curve of all lesion and thoracic aorta were obtained. The energy spectrum CT parameters of the lesions, extracapsular fat of the lesions, and anterior chest wall fat in stage I and stage II were obtained. The energy spectrum CT parameters of the lesions, enlarged lymph nodes and intravascular emboli in the 3 groups were obtained. The slope of the energy spectrum curve and the normalized iodine concentration were calculated.ResultsIn stage I lesions, there was a statistically significant difference between the slope of the energy spectrum curve for the lesion and those of the fat outside the lesion and the anterior chest wall in the arteriovenous phase (P&lt;0.001, P&lt;0.001). The energy spectrum curve of the tumor parenchyma was the opposite of that of the extracapsular fat. In stage II lesions, there was a statistically significant difference between the slope of the energy spectrum curve for the anterior chest wall and those of the lesion and the fat outside the lesion in the arteriovenous phase(P&lt;0.001, P&lt;0.001). The energy spectrum curve of the tumor parenchyma was consistent with that of the extracapsular fat. Distinction between stage I and II tumors be evaluated by comparing the energy spectrum curves of the mass and the extracapsular fat of the mass. The accuracy rate of is 79.4%. For stages III and IV, there was no significant difference in the slope of the energy spectrum curve of the tumor parenchyma, metastatic lymph node, and intravascular embolism (P&gt;0.05). The energy spectrum curve of the tumor parenchyma was consistent with that of the enlarged lymph nodes and intravascular emboli. The two radiologists have strong consistency in evaluating TETs Masaoka-Koga staging, The Kappa coefficient is 0.873,(95%CI:0.768-0.978).ConclusionSpectral CT parameters, especially the energy spectrum curve and slope, are valuable for preoperative TET and can be used in preoperative staging prediction.
Preoperative Nomogram for Differentiation of Histological Subtypes in Ovarian Cancer Based on Computer Tomography Radiomics
Authors: Zhu Haiyan , Ai Yao , Zhang Jindi , Zhang Ji , Jin Juebin , Xie Congying , Su Huafang , Jin Xiance 
Published: March 2021

ObjectivesNon-invasive method to predict the histological subtypes preoperatively is essential for the overall management of ovarian cancer (OC). The feasibility of radiomics in the differentiating of epithelial ovarian cancer (EOC) and non-epithelial ovarian cancer (NEOC) based on computed tomography (CT) images was investigated.MethodsRadiomics features were extracted from preoperative CT for 101 patients with pathologically proven OC. Radiomics signature was built using the least absolute shrinkage and selection operator (LASSO) logistic regression. A nomogram was developed with the combination of radiomics features and clinical factors to differentiate EOC and NEOC.ResultsEight radiomics features were selected to build a radiomics signature with an area under curve (AUC) of 0.781 (95% confidence interval (CI), 0.666 -0.897) in the discrimination between EOC and NEOC. The AUC of the combined model integrating clinical factors and radiomics features was 0.869 (95% CI, 0.783 -0.955). The nomogram demonstrated that the combined model provides a better net benefit to predict histological subtypes compared with radiomics signature and clinical factors alone when the threshold probability is within a range from 0.43 to 0.97.ConclusionsNomogram developed with CT radiomics signature and clinical factors is feasible to predict the histological subtypes preoperative for patients with OC.
Comprehensive Pan-Cancer Analysis Confirmed That ATG5 Promoted the Maintenance of Tumor Metabolism and the Occurrence of Tumor Immune Escape
Authors: Xu Chunxiao , Zang Yusheng , Zhao Yuxiang , Cui Weiqiang , Zhang Hong , Zhu Yingcui , Xu Man 
Published: March 2021

BackgroundAutophagy related protein 5 (ATG5) is an important autophagosome formation related protein, and its involvement in the biological process of autophagy has been shown to correlate with tumor metabolic patterns and the formation of tumor heterogeneity. However, the role of ATG5 in tumor metabolism and tumor immunity remains unclear.MethodIn order to explore this problem, this study was designed to reveal the role of ATG5 in tumor metabolism and tumor immunity through pan-cancer analysis of multi-database. GTEx database, CCLE database, and TCGA database were used to describe the expression, prognosis, immune microenvironment, immune new antigen, immune checkpoint, TMB, and microsatellite instability of ATG5 in 33 types of tumors. A series of bioinformatics tools and methods were used for quantitative analysis and panoramic description, such as to Estimate, Scanneo and GSEA.ResultThe differential analysis results of multiple databases showed that ATG5 was ubiquitously highly expressed in pan-cancer, especially in solid tumors. Survival analysis revealed that ATG5 was universally associated with the prognosis of pan-cancer, and high ATG5 expression was significantly associated with poor patient prognosis in most cases. Further, the expression level of ATG5 was confirmed to be associated with tumor immune infiltration and tumor microenvironment, especially in BRCA, KIRC, and LIHC. In addition to this, ATG5 expression was confirmed to correlate with these clinically significant phenotypes, in conjunction with immune neoantigens and immune checkpoint gene expression profiles in pan-cancer. In addition to TMB and microsatellite instability in pan-cancer, we confirmed that ATG5 expression affects the expression of DNA repair genes and methyltransferases in pan-cancer, and found through gene set enrichment analysis that ATG5 is involved in the regulation of numerous signaling pathways involved in cancer metabolism and cancer immunity.ConclusionsATG5 participated in the formation of autophagosomal membrane important molecule LC3-II outside, and played an important role in tumor metabolism and tumor immunity. The comprehensive pan-cancer analysis not only revealed the potential of ATG5 in tumor-targeted therapy but also suggested ATG5 as a promising tumor predictive biomarker in most solid tumors.
Antiretroviral Long-Term Efficacy and Resistance of Lopinavir/Ritonavir Plus Lamivudine in HIV-1-Infected Treatment-Naïve Patients (ALTERLL): 144-Week Results of a Randomized, Open-Label, Non-Inferiority Study From Guangdong, China
Authors: Guo Peng-Le , He Hao-Lan , Chen Xie-Jie , Chen Jin-Feng , Chen Xiao-Ting , Lan Yun , Wang Jian , Du Pei-Shan , Zhong Huo-Lin , Li Hong , Liu Cong , Li Li-Ya , Hu Feng-Yu , Tang Xiao-Ping , Cai Wei-Ping , Li Ling-Hua 
Published: March 2021

Dual therapy with lopinavir/ritonavir (LPV/r) plus lamivudine (3TC) has been demonstrated to be non-inferior to the triple drug regimen including LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) in 48-week studies. However, little is known about the long-term efficacy and drug resistance of this simplified strategy. A randomized, controlled, open-label, non-inferiority trial (ALTERLL) was conducted to assess the efficacy, drug resistance, and safety of dual therapy with LPV/r plus 3TC (DT group), compared with the first-line triple-therapy regimen containing tenofovir (TDF), 3TC plus efavirenz (EFV) (TT group) in antiretroviral therapy (ART)-naïve HIV-1–infected adults in Guangdong, China. The primary endpoint was the proportion of patients with plasma HIV-1 RNA &lt; 50 copies/ml at week 144. Between March 1 and December 31, 2015, a total of 196 patients (from 274 patients screened) were included and randomly assigned to either the DT group (n = 99) or the TT group (n = 97). In the primary intention-to-treat (ITT) analysis at week 144, 95 patients (96%) in the DT group and 93 patients (95.9%) in the TT group achieved virological inhibition with plasma HIV-1 RNA &lt;50 copies/ml (difference: 0.1%; 95% CI, –4.6–4.7%), meeting the criteria for non-inferiority. The DT group did not show significant differences in the mean increase in CD4+ cell count (247.0 vs. 204.5 cells/mm3; p = 0.074) or the CD4/CD8 ratio (0.47 vs. 0.49; p = 0.947) from baseline, or the inflammatory biomarker levels through week 144 compared with the TT group. For the subgroup analysis, baseline high viremia (HIV-1 RNA &gt; 100,000 copies/ml) and genotype BC did not affect the primary endpoint or the mean increase in CD4+ cell count or CD4/CD8 ratio from baseline at week 144. However, in patients with genotype AE, the DT group showed a higher mean increase in CD4+ cell count from baseline through 144 weeks than the TT group (308.7 vs. 209.4 cells/mm3; p = 0.038). No secondary HIV resistance was observed in either group. Moreover, no severe adverse event (SAE) or death was observed in any group. Nonetheless, more patients in the TT group (6.1%) discontinued the assigned regimen than those in the DT group (1%) due to adverse events. Dual therapy with LPV/r plus 3TC manifests long-term non-inferior therapeutic efficacy, low drug resistance, good safety, and tolerability compared with the first-line triple-therapy regimen in Guangdong, China, indicating dual therapy is a viable alternative in resource-limited areas.Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1900024611].
Ferulic Acid Ameliorates Atherosclerotic Injury by Modulating Gut Microbiota and Lipid Metabolism
Authors: Gu Yuyan , Zhang Yaxin , Li Mei , Huang Zhiyong , Jiang Jing , Chen Yihao , Chen Junqi , Jia Yuhua , Zhang Lihua , Zhou Fenghua 
Published: March 2021

Atherosclerosis is a leading cause of death worldwide. Recent studies have emphasized the significance of gut microbiota and lipid metabolism in the development of atherosclerosis. Herein, the effects and molecular mechanisms involving ferulic acid (FA) was examined in atherosclerosis using the ApoE-knockout (ApoE-∕-, c57BL/6 background) mouse model. Eighteen male ApoE−/− mice were fed a high-fat diet (HFD) for 12 weeks and then randomly divided into three groups: the model group, the FA (40 mg/kg/day) group and simvastatin (5 mg/kg/day) group. As results, FA could significantly alleviate atherosclerosis and regulate lipid levels in mice. Liver injury and hepatocyte steatosis induced by HFD were also mitigated by FA. FA improved lipid metabolism involving up-regulation of AMPKα phosphorylation and down-regulation of SREBP1 and ACC1 expression. Furthermore, FA induced marked structural changes in the gut microbiota and fecal metabolites and specifically reduced the relative abundance of Fimicutes, Erysipelotrichaceae and Ileibacterium, which were positively correlated with serum lipid levels in atherosclerosis mice. In conclusion, we demonstrate that FA could significantly ameliorate atherosclerotic injury, which may be partly by modulating gut microbiota and lipid metabolism via the AMPKα/SREBP1/ACC1 pathway.
Head-to-Head Comparison of Sedation and Somnolence Among 37 Antipsychotics in Schizophrenia, Bipolar Disorder, Major Depression, Autism Spectrum Disorders, Delirium, and Repurposed in COVID-19, Infectious Diseases, and Oncology From the FAERS, 2004–2020
Authors: Eugene Andy R. , Eugene Beata , Masiak Marek , Masiak Jolanta Sylwia 
Published: March 2021

Objective: Antipsychotic compounds are known to induce sedation somnolence and have expanded clinical indications beyond schizophrenia to regulatory approval in bipolar disorder, treatment-resistant depression, and is being repurposed in infectious diseases and oncology. However, the medical sciences literature lacks a comprehensive association between sedation and somnolence among a wide-range of antipsychotic compounds. The objective of this study is to assess the disproportionality of sedation and somnolence among thirty-seven typical and atypical antipsychotics.Materials and Methods: Patient adverse drug reactions (ADR) cases were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS) between January 01, 2004 and September 30, 2020 for a wide-array of clinical indications and off-label use of antipsychotics. An assessment of disproportionality were based on cases of sedation and somnolence and calculated using the case/non-case methodology. Statistical analysis resulting in the reporting odds-ratio (ROR) with corresponding 95% confidence intervals (95% CI) were conducted using the R statistical programming language.Results: Throughout the reporting period, there were a total of 9,373,236 cases with 99,251 specific ADRs reporting sedation and somnolence. Zuclopenthixol (n = 224) ROR = 13.3 (95% CI, 11.6–15.3) was most strongly associated of sedation and somnolence and haloperidol decanoate long-acting injection (LAI) was not statistically associated sedation and somnolence. Further, among atypical antipsychotic compounds, tiapride and asenapine were the top two compounds most strongly associated with sedation and somnolence. Comprehensively, the typical antipsychotics ROR = 5.05 (95%CI, 4.97–5.12) had a stronger association with sedation and somnolence when compared to atypical antipsychotics ROR = 4.65 (95%CI, 4.47–4.84).Conclusion: We conducted a head-to-head comparison of thirty-seven antipsychotics and ranked the compounds based on the association of sedation and somnolence from ADR data collected throughout 16 years from the FAERS. The results are informative and with recent interests in repurposing phenothiazine antipsychotics in infectious disease and oncology provides an informative assessment of the compounds during repurposing and in psychopharmacology.
Nicotinamide Mononucleotide Combined With Lactobacillus fermentum TKSN041 Reduces the Photoaging Damage in Murine Skin by Activating AMPK Signaling Pathway
Authors: Zhou Xianrong , Du Hang-Hang , Ni Luyao , Ran Jie , Hu Jian , Yu Jianjun , Zhao Xin 
Published: March 2021

Long-term exposure to UVB (280–320 nm) can cause oxidative skin damage, inflammatory injury, and skin cancer. Research on nicotinamide mononucleotide (NMN) and lactic acid bacteria (LAB) with regard to antioxidation, anti-inflammation, and prevention of other age-related diseases has received increasing attention. In the present study, the in vitro antioxidant analysis showed that NMN combined with Lactobacillus fermentum TKSN041 (L. fermentum TKSN041) has a high scavenging ability on hydroxyl (OH), 2, 2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH), and it also possess a good total antioxidant capacity. The animal experimental results show that NMN combined with LAB maintained normal liver morphology of mice and reduced pathological damage to murine skin. NMN combined with LAB significantly increased the serum levels of total superoxide dismutase (T-SOD), catalase (CAT), and interleukin (IL)-10, but reduced the levels of malondialdehyde, advanced glycation end products, tumor necrosis factor (TNF)-α, and IL-6. NMN combined with LAB increased T-SOD, CAT, IL-10, Na+-K+-ATPase, and NAD+ levels in the skin, but reduced TNF-α level in the skin. NMN combined with LAB increased the mRNA expression levels of SOD1, CAT, glutathione (GSH), inhibitor of NF-κB (IκB-α), IL-10, AMP-activated protein kinase (AMPK), adaptor protein, phosphotyros ineinteraction, PH domain and leucine zipper containing 1 (APPL1), peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α), and forkhead transcription factor O (FOXO) in the skin and liver, but decreased the mRNA expression levels of nuclear factor (NF)-κBp65, TNF-α, IL-6, and rapamycin target protein (mTOR). NMN combined with LAB increased the protein expression levels of AMPK, IκB-α, SOD1, and CAT in the skin tissues and reduced protein expression of NF-κBp65. NMN combined with L. fermentum TKSN041 improved murine skin damage caused by UVB irradiation, and the protective mechanism may be related to activation of the AMPK signaling pathway. The results of this study are expected to provide a reference for preventing and the treating skin photoaging.