bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Key Network of mRNAs and miRNAs Regulated by HIF1A in Hypoxic Hepatocellular Carcinoma Cells
Authors: Liu Tong , Tang Jing , Li Xiaoyu , Lin Yuan , Yang Yuma , Ma Kai , Hui Zhaoyuan , Ma Hong , Qin Yanyan , Lei Hetian , Yang Yanhui 
Published: June 2022

Purpose: Hypoxia plays an essential role in the progression of hepatocellular carcinoma (HCC), whereas hypoxia inducible factor-1 (HIF-1) is the key transcription factor allowing HCC to survive hypoxia. The aim of this study was to define the essential mRNAs and miRNAs regulated by HIF1A and dissect their functions, interactions, and tumor-infiltrating immune cells in HCC.Methods: A human HCC cell line HepG2 was used as a cell model of HCC. The CRISPR/Cas9 system was used to knock out HIF1A in HepG2 cells, and RNA sequencing was utilized to characterize differentially expressed mRNAs and miRNAs in the HIF1A-knockout HepG2 cells; the identified candidates were then analyzed by GO annotation and KEGG pathway enrichment to study their function and establish a PPI network. Quantitative (q) PCR was used to verify if there were significant differences in the expression of mRNAs, and the association of the selected mRNAs expression with immune cell infiltration levels was further analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data.Results: Using RNA-sequencing, we discovered that there were 1535 mRNAs differentially expressed (adjusted p &lt; 0.05, |fold change|&gt;1.5) in the HIF1A-knockout HepG2 cells, among which there were 644 mRNAs upregulated and 891 mRNAs downregulated. GO annotation and KEGG pathway enrichment showed that these mRNAs were involved in glycolysis/gluconeogenesis, PI3K-Akt signaling pathways, and HIF-1 signaling pathways. In addition, we found that there were 309 miRNAs differentially expressed (adjusted p &lt; 0.05, |fold change|&gt;1.5) in the HIF1A-knockout HepG2 cells, of which there were 213 miRNAs upregulated and 96 miRNAs downregulated. Our further analyses uncovered that these miRNA putative targets were involved in the hippo signaling pathway, axon guidance, and tight junction. Moreover, the construction and analysis of the PPI network showed that OASL, IL6, and TAF1 were recognized as hub genes with the highest connectivity degrees. Importantly, in the HIF1A-knockout HepG2 cells, our qRT-PCR data confirmed the selected mRNA changes revealed by RNA-sequencing, and with TCGA pan-cancer data, we revealed that the expressional levels of these three genes, LUM, SCOC, and CCL2, were associated with immune cell infiltration levels.Conclusion: The identified potential key network of mRNAs and miRNAs regulated by HIF1A in the HCC cells suggests a key role of HIF1A in the tumorigenesis of HCC.
Transcriptome Profiling and Identification of the Candidate Genes Involved in Early Ripening in Ziziphus Jujuba
Authors: Li Baiyun , Li Hui , Xu Zehua , Guo Xinnian , Zhou Tao , Shi Jiangli 
Published: June 2022

The early ripening jujube is an immensely popular fresh fruit due to its high commercial value as well as rich nutrition. However, little is known about the mechanism of jujube fruit’s ripening. In this study, the transcriptome profiles were comprehensively analyzed between the ‘Lingwu Changzao’ jujube and its early-ripening mutant during the fruit development and maturity. A total of 5,376 and 762 differentially expressed genes (DEGs) were presented at 80 and 90 days after the flowering of the jujube fruit, respectively. Furthermore, 521 common DEGs were identified as candidate genes that might be associated with the fruit’s early ripening. Our findings demonstrated that in a non-climacteric jujube fruit, abscisic acid (ABA) was more greatly involved in fruit ripening than ethylene. Meanwhile, the fruit ripening of the early-ripening mutant was regulated by eight promotors of DEGs related to glucose and fructose, seven repressors of DEGs related to brassinosteroid signal transduction, and a series of transcription factor genes (MYB, Bhlh, and ERF). Additionally, the expression of 20 candidate DEGs was further validated by real-time PCR during the late fruit maturation stage. Collectively, the present study sheds light on the metabolic mechanism of the fruit’s early ripening and provides valuable candidate genes for the early-ripening mutant’s breeding.
Transcriptome Analysis Reveals that Exogenous Melatonin Confers Lilium Disease Resistance to Botrytis elliptica
Authors: Xie Xuehua , Han Yu , Yuan Xi , Zhang Man , Li Ping , Ding Aiqin , Wang Jia , Cheng Tangren , Zhang Qixiang 
Published: June 2022

Leaf blight, caused by Botrytis elliptica (Berk.) Cooke, is a devastating disease that limits the production of Lilium in China and in other countries worldwide. Numerous studies have indicated that plants have evolved sophisticated and effective signal transduction and defense-related pathways in response to pathogen invasion. Recently, particular attention has been given to the action(s) of melatonin in plants in response to biotic stress, and the role of melatonin in plant–pathogen interactions has also been discussed. In this study, RNA-seq was applied to analyze the transcriptomic changes in Lilium leaves that were pre-treated and post-treated with melatonin after B. elliptica infection for 0, 12, 24, 36, and 72 h and then compare those changes with those of the control. Treatment with exogenous melatonin and infection with B. elliptica caused differential expression of a large number of genes in Lilium leaves. KEGG pathway analysis showed that, after melatonin treatment, the defense-related DEGs were mainly enriched in plant–pathogen interactions, plant hormone signal transduction, MAPK signaling pathways, phenylpropanoid biosynthesis, and phenylalanine metabolism. RT–qPCR was used to verify the expression changes of 12 DEGs, the results of which were consistent with the RNA-seq analysis results. The expression of DEGs related to the MAPK pathway were significantly different between the MB group and the HB group, suggesting that, via the MAPK signaling cascade, melatonin may play a role in the disease resistance of Lilium to B. elliptica. This study provides a new perspective and information for molecular-based breeding of Lilium disease resistance.
Identification of Immune-Related Hub Genes in Thymoma: Defects in CD247 and Characteristics of Paraneoplastic Syndrome
Authors: Deng Lin-Fang 
Published: June 2022

Background: Thymomas (Ts) and thymic carcinomas (TCs) are rare primary tumors of the mediastinum. Paraneoplastic syndrome (PNS) is an important feature of thymoma, which presents great challenges to clinicians.Methods: The present study uses the weighted gene co-expression network analysis (WGCNA) to identify possible immunologic mechanisms of thymoma. RNA sequencing data from thymoma samples were downloaded from the TCGA. Core genes were taken from the module that is closely related to the WHO’s stage of classification. Enhanced analysis using the online database “Metascape” and an overall survival (OS) analysis were carried out via the Kaplan–Meier method. The hub genes were obtained from the protein–protein interaction (PPI) network. In addition, we jointly analyzed multiple sets of PNS data related to thymomas from other sources to verify the correlation between thymomas and PNS. The impact of hub genes on the prognosis of PNS was evaluated via the ROC curve, with simultaneous analysis of immune infiltration by CIBERSORT.Findings: The 14 immune hub genes closely related to thymomas were found to be jointly involved in the T-cell receptor signaling pathway. Compared to the normal thymus and type B1/B2 thymoma, there is a lower number of T-cells in type A/B3 thymoma and thymic carcinoma. The expression of genes related to the T-cell receptor signaling pathway appeared defective. The low expression of CD247 and the decrease in the number of mature T-cells are common features among thymomas, specific pulmonary fibrosis, rheumatoid arthritis, and systemic lupus erythematosus.
Development and Validation of a Novel Ferroptosis-Related LncRNA Signature for Predicting Prognosis and the Immune Landscape Features in Uveal Melanoma
Authors: Ma Xiaochen , Yu Sejie , Zhao Bin , Bai Wei , Cui Yubo , Ni Jinglan , Lyu Qinghua , Zhao Jun 
Published: June 2022

BackgroundFerroptosis is a newly iron-dependent mode of programmed cell death that is involved in a variety of malignancies. But no research has shown a link between ferroptosis-related long non-coding RNAs (FRLs) and uveal melanoma (UM). We aimed to develop a predictive model for UM and explore its potential function in relation to immune cell infiltration.MethodsIdentification of FRLs was performed using the Cancer Genome Atlas (TCGA) and FerrDb databases. To develop a prognostic FRLs signature, univariate Cox regression and least absolute shrinkage and selection operator (LASSO) were used in training cohort. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve analyses were used to assess the reliability of the risk model. The immunological functions of FRLs signature were determined using gene set enrichment analysis (GSEA). Immunological cell infiltration and immune treatment were studied using the ESTIMATE, CIBERSORT, and ssGSEA algorithms. Finally, in vitro assays were carried out to confirm the biological roles of FRLs with known primer sequences (LINC00963, PPP1R14B.AS1, and ZNF667.AS1).ResultsA five-genes novel FRLs signature was identified. The mean risk score generated by this signature was used to create two risk groups. The high-risk score UM patients had a lower overall survival rate. The area under the curve (AUC) of ROC and K-M analysis further validated the strong prediction capacity of the prognostic signature. Immune cells such as memory CD8 T cells, M1 macrophages, monocytes, and B cells showed a substantial difference between the two groups. GSEA enrichment results showed that the FRLs signature was linked to certain immune pathways. Moreover, UM patients with high-risk scores were highly susceptible to several chemotherapy drugs, such as cisplatin, imatinib, bortezomib, and pazopanib. Finally, the experimental validation confirmed that knockdown of three identified lncRNA (LINC00963, PPP1R14B.AS1, and ZNF667.AS1) suppressed the invasive ability of tumor cells in vitro.ConclusionThe five-FRLs (AC104129.1, AC136475.3, LINC00963, PPP1R14B.AS1, and ZNF667.AS1) signature has effects on clinical survival prediction and selection of immunotherapies for UM patients.
Characterizing Mesoscale Eddies of Eastern Upwelling Origins in the Atlantic Ocean and Their Role in Offshore Transport
Authors: Ioannou Artemis , Speich Sabrina , Laxenaire Remi 
Published: June 2022

Motivated by the recurrent formation of eddies in the eastern upwelling areas, we examine cross-basin connectivity that is promoted by coherent, long-lived and long-propagating mesoscale eddies in the Atlantic Ocean. By applying the TOEddies detection and tracking algorithm to daily satellite observations (AVISO/DUACS) of Absolute Dynamic Topography (ADT), we characterize mesoscale eddy activity and variability in the North and South Atlantic. This method provides a robust eddy-network reconstruction, enabling the tracking of eddies formed in the Atlantic eastern upwelling systems together with any merging and splitting events they undergo during their lifetime as long as they remain detectable in the altimetry field. We show that during the years of observations, mesoscale eddies are long-lived coherent structures that can ensure oceanic connectivity between the eastern and the western boundaries, as a result of complex inter-eddy interactions. Moreover, alignment of South Atlantic eddies of eastern boundary origins with available Argo floats achieves a mean cross-basin connectivity signal from both anticyclonic and cyc5lonic eddies which is particularly evident at depth, along thermocline isopycnal layers of γn = 26 - 27 kg m–3. We explore two individual cyclonic eddy trajectories from in-situ measurements gathered by different Argo profiling floats trapped inside the eddy cores. Our results support the hypothesis that mesoscale eddies sustain and transport water masses while subducting during their westward propagation.
Optimal Frailty Dimensions for Assessing Frailty and Predicting Chemotherapy Adverse Events in Older Taiwanese Cancer Patients
Authors: Ho Ya-Wen , Chen Shih-Ying , Hung Yu-Shin , Lin Shinn-Yn , Chou Wen-Chi 
Published: June 2022

BackgroundThis study aimed to investigate the effects of different frailty dimensions on frailty prevalence in older Taiwanese cancer patients receiving chemotherapy, and to analyze the dimensions that should be included in frailty assessment for effectively predicting serious adverse events, unexpected hospitalizations, and emergency department visits.Materials and MethodsThis study prospectively enrolled 234 cancer patients with solid cancer or lymphoma and aged 65 years or older who later received chemotherapy at a medical center in Taiwan from September 2016 to November 2018. First, all patients were subjected to a frailty assessment on eight frailty dimensions within 1 week before their first chemotherapy treatment. The effects of different dimensions on frailty were analyzed using a Poisson regression model. Second, after sequentially excluding one, two, and three dimensions with the lowest effects, frailty was sequentially assessed in the remaining seven, six, and five dimensions for comparison of chemotherapy-related adverse events.ResultsNutritional status, comorbidity, history of falls, cognitive status, and polypharmacy were the top five important dimensions of frailty in older Taiwanese cancer patients. Regardless of the number (five to eight) of dimensions used for frailty assessment, frail patients had higher rates of serious adverse events, unexpected hospitalizations, and emergency room visits than non-frail patients during chemotherapy.ConclusionsFrailty assessment in older Taiwanese cancer patients should be based on at least five dimensions to accurately identify those at high risk of serious adverse events during chemotherapy. It is expected that the present findings may be used to design a frailty scale for older Taiwanese in the future.
Case Report: Early Recognition, Treatment, and Occupational Safety Protection are Crucial for Methanol Toxicity
Authors: Wu Xiaomei , Gu Meifeng , Wang Wei , Zhang Hainan , Tang Zhenchu 
Published: June 2022

BackgroundDespite significant progress in treating methanol poisoning, the lack of training, hazard communication, and occupational safety protection education contributes to the risk of occupational exposure and methanol toxicity. In addition, early diagnosis and timely medical care are essential to reduce the risk of morbidity and mortality, yet it remains a challenging procedure.Case ReportA 35-year-old man working in a fireworks factory came to our emergency department with acute mental change and progressive disturbance of consciousness. The patient's vital signs were stable, and he presented with enlargement of both pupils with a weak reaction to light. Head computed tomography showed low signal intensities in the bilateral basal ganglia. He was admitted to the neurologic intensive care unit, where additional laboratory workup showed high anion-gap metabolic acidosis. Methanol poisoning was thus considered. Before being treated with sodium bicarbonate infusion, hemodialysis, folate, and high-dose vitamin B, the blood and urine samples were collected for toxicity tests, which turned out to be methanol poisoning. After 8 hours of hemodialysis, the patient's consciousness recovered, but he complained of a complete loss of vision in both eyes. Brain and optic nerve magnetic resonance images showed bilateral symmetric putamen lesions and optic neuropathy. Ophthalmic tests indicated visual pathway impairment and optic disc swelling but no fluorescein leakage. The right eye's vision was partially restored on the third day, but he could only count fingers at 20 cm. Unfortunately, his eyesight ceased to improve during the 6 months of follow-up.ConclusionsEarly diagnosis and prompt treatment will improve the prognosis of methanol poisoning in terms of vision and patient survival. Awareness and supervision of commercial alcohol use are indispensable for similar industrial processes.
Automated Classification of Mild Cognitive Impairment by Machine Learning With Hippocampus-Related White Matter Network
Authors: Zhou Yu , Si Xiaopeng , Chao Yi-Ping , Chen Yuanyuan , Lin Ching-Po , Li Sicheng , Zhang Xingjian , Sun Yulin , Ming Dong , Li Qiang 
Published: June 2022

BackgroundDetection of mild cognitive impairment (MCI) is essential to screen high risk of Alzheimer’s disease (AD). However, subtle changes during MCI make it challenging to classify in machine learning. The previous pathological analysis pointed out that the hippocampus is the critical hub for the white matter (WM) network of MCI. Damage to the white matter pathways around the hippocampus is the main cause of memory decline in MCI. Therefore, it is vital to biologically extract features from the WM network driven by hippocampus-related regions to improve classification performance.MethodsOur study proposes a method for feature extraction of the whole-brain WM network. First, 42 MCI and 54 normal control (NC) subjects were recruited using diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI), and T1-weighted (T1w) imaging. Second, mean diffusivity (MD) and fractional anisotropy (FA) were calculated from DTI, and the whole-brain WM networks were obtained. Third, regions of interest (ROIs) with significant functional connectivity to the hippocampus were selected for feature extraction, and the hippocampus (HIP)-related WM networks were obtained. Furthermore, the rank sum test with Bonferroni correction was used to retain significantly different connectivity between MCI and NC, and significant HIP-related WM networks were obtained. Finally, the classification performances of these three WM networks were compared to select the optimal feature and classifier.Results(1) For the features, the whole-brain WM network, HIP-related WM network, and significant HIP-related WM network are significantly improved in turn. Also, the accuracy of MD networks as features is better than FA. (2) For the classification algorithm, the support vector machine (SVM) classifier with radial basis function, taking the significant HIP-related WM network in MD as a feature, has the optimal classification performance (accuracy = 89.4%, AUC = 0.954). (3) For the pathologic mechanism, the hippocampus and thalamus are crucial hubs of the WM network for MCI.ConclusionFeature extraction from the WM network driven by hippocampus-related regions provides an effective method for the early diagnosis of AD.
Association of Visual, Hearing, and Dual Sensory Impairment With Incident Dementia
Authors: Hu Wenyi , Wang Yueye , Wang Wei , Zhang Xinyu , Shang Xianwen , Liao Huan , Chen Yifan , Huang Yu , Zhang Xueli , Tang Shulin , Yu Honghua , Yang Xiaohong , He Mingguang , Zhu Zhuoting 
Published: June 2022

IntroductionThe relationship between sensory impairments and the risk of dementia is inconclusive. We aim to investigate the association of visual impairment (VI), hearing impairment (HI), and dual sensory impairment (DSI) with incident dementia.MethodsThe UK Biobank study recruited more than 500,000 participants aged 40–69 years across the United Kingdom. Participants with available visual acuity (VA) measurements and speech-reception-threshold (SRT) information and free of dementia at the baseline assessment were included in the analysis. VI was defined as VA worse than 0.3 LogMAR units and HI were defined as an SRT of −5.5 dB or over. DSI was defined as the presence of both VI and HI. Incident dementia was identified through linked data to primary care or hospital admission records and death registries. Multivariable Cox proportional hazard regression models were used to examine the association of VI, HI, and DSI with incident dementia.ResultsAmong 113,511 participants (mean age: 56.8 ± 8.09 years, female: 54.4%), a total number of 1,135 (1.00%) cases of incident dementia were identified during a median follow up period of 11.1 years [interquartile range (IQR): 10.9–11.4 years]. The incidence of dementia showed significant differences among the non-sensory impairment (NSI) group, VI-only group, HI-only group, and DSI group (p &lt; 0.001). After adjusting for demographic, lifestyle, health, and genetic factors, isolated VI (HR = 1.50, 95% CI: 1.06–2.12, p = 0.023), isolated HI (HR = 1.42, 95% CI:1.20–1.69, p &lt; 0.001), and DSI (HR = 1.82, 95% CI: 1.10–3.00, p = 0.020) were independently associated with higher risks of incident dementia.ConclusionsVisual, hearing, and dual sensory impairments were associated with an increased risk of developing dementia, suggesting that visual and hearing impairments are modifiable risk factors that can be targeted to prevent dementia.
Balloon Angioplasty vs. Stenting for Symptomatic Intracranial Arterial Stenosis
Authors: Sun Yaxuan , Li Xihua , Ding Yongxia , Han Bin , Wang Jing , Meng Kun , Han Yan 
Published: June 2022

AimsWe performed a meta-analysis to indirectly compare the treatment effectiveness of balloon angioplasty and stenting for patients with intracranial arterial stenosis.MethodsLiterature searches were performed in well-known databases to identify eligible studies published before January 04, 2021. The incidence of restenosis, transient ischemic attack (TIA), stroke, death, and dissection after balloon angioplasty or stenting were pooled. An indirect comparison of balloon angioplasty vs. stenting was performed, and the ratios of incidence (RIs) with 95% confidence intervals (CIs) were calculated using the random-effects model.Results120 studies that recruited 10,107 patients with intracranial arterial stenosis were included. The pooled incidence of restenosis after balloon angioplasty and stenting were 13% (95%CI: 8-17%) and 11% (95%CI: 9-13%), respectively, with no significant difference between them (RI: 1.18; 95%CI: 0.78–1.80; P = 0.435). Moreover, the pooled incidence of TIA after balloon angioplasty and stenting was 3% (95%CI: 0–6%) and 4% (95%CI: 3%-5%), and no significant difference was observed (RI: 0.75; 95%CI: 0.01–58.53; P = 0.897). The pooled incidence of stroke after balloon angioplasty and stenting was 7% (95%CI: 5–9%) and 8% (95%CI: 7–9%), respectively, and the difference between groups was found to be statistically insignificant (RI: 0.88; 95%CI: 0.64–1.20; P = 0.413). Additionally, the pooled incidence of death after balloon angioplasty and stenting was 2% (95%CI: 1–4%) and 2% (95%CI: 1–2%), with no significant difference between groups (RI: 1.00; 95%CI: 0.44–2.27; P = 1.000). Finally, the pooled incidence of dissection after balloon angioplasty and stenting was 13% (95%CI: 5–22%) and 3% (95%CI: 2–5%), respectively, and balloon angioplasty was associated with a higher risk of dissection than that with stenting for patients with intracranial arterial stenosis (RI: 4.33; 95%CI: 1.81–10.35; P = 0.001).ConclusionThis study found that the treatment effectiveness of balloon angioplasty and stenting were similar for patients with symptomatic intracranial arterial stenosis.