bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of a Six Immune-Related lncRNAs Signature to Predict Outcome, Immune Cell Infiltration and Immunotherapy Response in Patients with Hepatocellular Carcinoma
Authors: Zhou Pengcheng , Wei Jiang , Yuhua Lu , Lei Wang , Yewei Zhang 
Published: September 2020

Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide with poor prognosis. Growing evidence has demonstrated that immune-related long non-coding RNAs (lncRNAs) are relevant to tumor microenvironment (TME) and can help to assess the effects of immunotherapy and evaluate prognosis. This study aimed to identify an immune-related lncRNA signature for the prospective assessment of immunotherapy and prognosis in HCC. Methods: HCC RNA-seq data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) project database. Firstly, we used ESTIMATE to evaluate the tumor microenvironment (TME). Then, cox regression analysis was used to construct a prognostic signature and the risk score. Univariate Cox regression, multivariate Cox regression, principal components analysis (PCA), the receiver operating characteristic (ROC) curve and stratification analyses were applied to conﬁrm. Gene set enrichment analysis (GSEA) analysis was employed to explore the biological processes and pathways. Besides, CIBERSORT was used to estimate the abundance of tumor-inﬁltrating immune cells (TIICs). Furthermore, the relationship between the immune-related lncRNA signature and immune checkpoint genes was investigated. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) assays were used to demonstrated the expression of the six lncRNAs. Results:.We identified a six immune-related lncRNAs (MSC-AS1, AC145207.5, SNHG3, AL365203.2, AL031985.3, NRAV) with the ability to stratify patients into high-risk and low-risk groups with significantly different survival. Univariate Cox regression, multivariate Cox regression, ROC and stratification analyses conﬁrmed that the six immune-related lncRNA signature was a novel independent prognostic factor in HCC patients. The high-risk group and low-risk group illustrated different distributions in PCA. GSEA suggested that the six immune-related lncRNA signature is involved in the immune-related biological processes and pathways. Besides, the six immune-related lncRNA signature was associated with the infiltration of immune cells. Furthermore, the six immune-related lncRNA signature was associated with the expression of critical immune genes and could predict the clinical response of immunotherapy. Finally, qRT-PCR demonstrated that the six lncRNAs were signiﬁcantly differentially expressed in HCC cell lines and normal hepatic cell line. Conclusions: In summary, we identified a six immune-related lncRNA signature with the ability to predict outcome, immune cell infiltration and immunotherapy response in patients with hepatocellular carcinoma.
Combining Renal Cell Arrest and Damage Biomarkers to Predict Progressive AKI in Patient with Sepsis
Authors: Tao Xiaolei , Chen Chunbo , Luo Weihong , Zhou Jing , Tian Jianwei , yang xiaobing , Hou Fan Fan 
Published: September 2020

Abstract
Background: Sepsis is the most common trigger for AKI and up to 40% of mild or moderate septic AKI would progress to more severe AKI, which is associated with significantly increased risk for death and later CKD/ESRD. Early identifying high risk patients for AKI progression is a major challenge in patients with septic AKI. This study aims to evaluated the utility of combining renal cell arrest and damage biomarkers for predicting the progression of AKI in patient with sepsis. Methods: This is a prospective, multicenter cohort study which enrolled adult patients with sepsis and initially developed stage 1 or 2 AKI from January 2014 to March 2018. AKI was diagnosed and staged according to 2012 KDIGO-AKI guidelines. Renal cell arrest biomarkers (urinary TIMP2*IGFBP7, u[TIMP-2]*[IGFBP7]) and renal damage biomarkers (urinary KIM-1[uKIM-1] and urinary IL-18 [uIL-18]) were measured at time of AKI clinical diagnosis, and the utility of biomarkers for predicting septic AKI progression alone or in combination were evaluated. The primary outcome was AKI progression defined as worsening of AKI stage. The second outcome was AKI progression with subsequent death during hospitalization. Results: Among 433 screened patients, 149 patients with sepsis and stage 1 or 2 AKI were included, in which 63 patients developed progressive AKI and 49 patients subsequently died during hospitalization. u[TIMP-2]*[IGFBP7], uKIM-1 and uIL-18 independently predicted the progression of septic AKI in which u[TIMP-2]*[IGFBP7] showed the greatest AUC (0.745; 95%CI, 0.667-0.823) as compared to uKIM-1 (AUC 0.719; 95%CI 0.638-0.800) and uIL-18 (AUC 0.619; 95%CI 0.525-0.731). Combination of u[TIMP-2]*[IGFBP7] with uKIM-1 improved the performance of predicting septic AKI progression with AUC of 0.752. u[TIMP-2]*[IGFBP7], alone or combined with uKIM-1/uIL-18, improved the risk reclassification over the clinical risk factor model alone both for the primary and secondary outcomes, as evidenced by significant category-free net reclassification index. Conclusion: Combination of renal cell arrest and damage biomarkers enhanced the prediction of AKI progression in patients with sepsis and improved risk reclassification over the clinical risk factors.
Association Between Body Mass Index and Severe Infection in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Cohort in Japan
Authors: Sugiyama Hirokazu , Yamaguchi Makoto , Katsuno Takayuki , Nobata Hironobu , Iwagaitsu Shiho , Kinashi Hiroshi , Banno Shogo , Ishimoto Takuji , Ito Yasuhiko 
Published: September 2020

Abstract
Background: Although previous studies have evaluated risk factors for the incidence of severe infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), the relationship between body mass index (BMI) and severe infection in AAV has not been elucidated. We hypothesized that elderly AAV patients with a low BMI would be at a higher risk of infection. To evaluate this hypothesis, we investigated the association between underweight at AAV diagnosis and subsequent severe infection in elderly AAV patients.Methods: This single-center retrospective cohort study included 98 consecutive elderly AAV patients treated at the Aichi Medical University Hospital in Japan between 2004 and 2018. The relationships between BMI at diagnosis and subsequent first severe infection were assessed using multivariate Cox proportional hazards models.Results: During the entire follow-up period (median, 22 months; interquartile range, 7‒52 months), 32 (32.7%) patients developed at least one severe infection. Low BMI (< 18.5 kg/m2 compared with normal BMI [18.5‒23.0 kg/m2], adjusted hazard ratio [HR] = 2.70, 95% confidence interval [CI]: 1.18–6.17; P = 0.018) and use of methylprednisolone pulse therapy (adjusted HR = 3.09, 95% CI: 1.37–6.99; P = 0.007) were the significant predictors of severe infection. Furthermore, an interaction effect between unintentional body weight loss (> 10%) within 6 months before diagnosis and low BMI was observed (P < 0.001).Conclusions: Low BMI was associated with a higher risk of severe infection in elderly AAV patients, suggesting that careful management may be required to prevent the development of infection in patients with a low BMI. Further studies are needed to elucidate the optimal treatment strategy for these patients.
Phase Specific Pain Localization in Cluster Headache Patients.
Authors: Schröder Philipp , Gaul Charly , Drabik Attyla , Molsberger Albrecht 
Published: September 2020

Abstract
Background and Objective:Applying local treatments like neuromodulation or injections for cluster headache, requires exact knowledge of the anatomical structures and pain topography. However studies with emphasis on exact pain localization are rare although local treatments are increasingly used for patients in whom systemic pharmacotherapy is ineffective or contraindicated. Here, survey results with emphasis on exact pain location in cluster headache attacks for onset of pain, peak pain and radiation of pain, are presented. Methods: Data from 631 respondents were collected for 23 months using an online survey composed of 117 questions on pain location, epidemiology, and clinical features. 5260 datapoints on 44 pain locations were analyzed.Results: There is a periorbital concentration of pain during onset and peak phases of attacks. Pain locations outside the periorbital region were reported more frequently during radiation when compared to the onset and peak of attacks. Dorsal (occipital/nuchal) pain is more frequent during onset and radiation compared to peak: onset pain (13%) vs. peak pain (6%), p < 0,001. Pain radiation (22%) vs. peak pain (6%), p < 0,001. There is no significant difference in dorsal pain frequencies for pain radiation (22%) vs. onset (13%), p = 0,552. Furthermore, single pain spots differ significantly in frequency during the three attack phases.Conclusions: Analysis of the pain location data shows phase specific frequencies and distributions of pain location during the three stages of a cluster headache attack. Single pain spots differ significantly in frequency during the three attack phases. Dorsal pain is more frequent during onset and radiation, compared to peak. Extra-orbital pain locations are more frequent during pain radiation. These findings will help to better understand cluster headache and might help to identify further target structures for local treatments.
Mediating Effects of Risk Perception on Association Between Social Support and Coping with COVID-19: An Online Survey
Authors: Li Dian-Jeng , Ko Nai-Ying , Chang Yu-Ping , Yen Cheng-Fang , Chen Yi-Lung 
Published: September 2020

Abstract
Backgrounds:This study aimed to develop a model for estimating the mediating effects of risk perception and confidence on the association between perceived social support and active coping with the coronavirus disease 2019 (COVID-19) pandemic among people in Taiwan. Methods:The data of 1,970 participants recruited from a Facebook advertisement was analyzed. Perceived social support, active coping with COVID-19, risk perception and confidence were evaluated using self-administered questionnaires.Results:The structural equation modeling was applied to verify the direct and indirect effects between variables. The mediation model demonstrated that lower perceived social support was significantly associated with a higher level of active coping with COVID-19, and this was mediated by a higher level of risk perception. Conclusions:The present study identified the importance of risk perception on the public’s coping strategies during the COVID-19 pandemic.
Microbial Diversity of Co-occurring Heterotrophs in Cultures of Marine Picocyanobacteria
Authors: Kearney Sean Michael , Thomas Elaina , Coe Allison , Chisholm Sallie W. 
Published: September 2020

Abstract
BackgroundProchlorococcus and Synechococcus are responsible for around 10% of global net primary productivity, serving as part of the foundation of marine food webs. Heterotrophic bacteria are often co-isolated with these picocyanobacteria in seawater enrichment cultures that contain no added organic carbon; heterotrophs grow on organic carbon supplied by the photolithoautotrophs. We have maintained these cultures of Prochlorococcus and Synechococcus for 100s to 1000s of generations; they represent ideal microcosms for examining the selective pressures shaping autotroph/heterotroph interactions. ResultsWe examine the diversity of heterotrophs in 74 enrichment cultures of these picocyanobacteria obtained from diverse areas of the global oceans. Heterotroph community composition differed between clades and ecotypes of the autotrophic ‘hosts’ but there was significant overlap in heterotroph community composition. Differences were associated with timing, location, depth, and methods of isolation, suggesting the particular conditions surrounding isolation have a persistent effect on long-term culture composition. The majority of heterotrophs in the cultures are rare in the global ocean; enrichment conditions favor the opportunistic outgrowth of these rare bacteria. We did find a few examples, such as heterotrophs in the family Rhodobacteraceae, that are ubiquitous and abundant in cultures and in the global oceans; their abundance in the wild is also positively correlated with that of picocyanobacteria. ConclusionsCollectively, the cultures converged on similar compositions, likely from bottlenecking and selection that happens during the early stages of enrichment for the picocyanobacteria. We highlight the potential for examining ecologically relevant relationships by identifying patterns of distribution of culture-enriched organisms in the global oceans.
LINC00958 Promotes the Proliferation of TSCC Via miR-211-5p/CENPK Axis and Activating the JAK/STAT3 Signaling Pathway&nbsp;&nbsp;
Authors: JIA BO , DAO JUNFENG , HAN JIUSONG , HUANG ZHIJIE , SUN XIANG , ZHENG XIANGHUAI , XIANG SHIJIAN , ZHOU HUIXI , Liu Shuguan 
Published: September 2020

Abstract
Background：Tongue squamous cell carcinoma (TSCC) is one of the most common oral tumors. Recently, long intergenic noncoding RNA 00958 (LINC00958) has been identified as an oncogenic gene in human cancers. Nevertheless, the role of LINC00958 and its downstream mechanisms in TSCC is still unknown. The expression levels of LINC00958 in human TSCC tissues and adjacent normal tissues were determined. Methods：The effect of LINC00958 on TSCC cells proliferation and growth were assessed by CCK-8, colony formation, 5-Ethynyl-2’-deoxyuridline (EdU) assay, and flow cytometry assays in vitro and tumor xenograft model in vivo. Bioinformatics analysis was used to predict the target of LINC00958 in TSCC, which was verified by RNA immunoprecipitation and luciferase reporter assays. Results：LINC00958 was increased in TSCC tissues, and patients with high LINC00958 expression had a shorter overall survival. LINC00958 knockdown significantly decreased the growth rate of TSCC cells both in vitro and in vivo. In mechanism, LINC00958 acted as a ceRNA by competitively sponging miR-211-5p. In addition, we identified CENPK as a direct target gene of miR-211-5p, which was higher in TSCC tissues than that in adjacent normal tissues. Up-regulated miR-211-5p or down-regulated CENPK could abolish LINC00958-induced proliferation promotion in TSCC cells. Furthermore, The overexpression of CENPK promoted the expression of oncogenic cell cycle regulators and activated the JAK/STAT3 signaling. Conclusions：Our findings suggest that LINC00958 is a potential prognostic biomarker in TSCC.
Construction of a competitive endogenous RNA network and analysis of potential regulatory axis targets in glioblastoma
Authors: Yu Kai , Yang Huan , Lv Qiao-li , Wang Li-chong , Tan Zi-long , Zhang Zhe , Ji Yu-long , Lin Qian-xia , Chen Jun-jun , He Wei , Chen Zhen , Shen Xiao-li 
Published: September 2020

Abstract
Background

Glioblastoma is the most common primary malignant brain tumor. Due to the limited understanding of its pathogenesis, the prognosis of glioblastoma is poor. The purpose of this study is to explore potential ceRNA network chains and biomarkers in glioblastoma through integrated bioinformatics analysis.

Methods

Transcriptome expression data from The Cancer Genome Atlas database and Gene Expression Omnibus were analyzed to identify differentially expressed genes between glioblastoma tissue and normal tissue. The potential biological pathways associated with the differentially expressed genes were explored using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and a protein-protein interaction network was established using the STRING database and Cytoscape. Survival analysis using Gene Expression Profiling Interactive Analysis was based on the Kaplan-Meier curve method. The ceRNA network chain was established using the intersection method to align data from four databases (miRTarBase, miRcode, TargetScan, and lncBace2.0), and expression differences and correlations were verified by using quantitative reverse-transcription polymerase chain reaction analysis and determining the Pearson correlation coefficient.

Results

A total of 2842 DEmRNAs, 2577 DElncRNAs, and 309 DEmiRNAs were dysregulated in glioblastoma. The final ceRNA network consisted of six specific lncRNAs, four miRNAs, and four mRNAs. Among them, four DEmRNAs and one DElncRNA were correlated with overall survival (p < 0.05). We found that C1S was significantly correlated with overall survival (p = 0.015) and could therefore be used as a biomarker for glioblastoma.

Conclusions

Four ceRNA networks were established that may influence the occurrence and development of glioblastoma. Among them, the MIR155HG/has-miR-129-5p/C1S axis may be a potential marker and therapeutic target. In particular, C1S has not yet been reported in glioblastoma studies. These findings clarify the role of the ceRNA regulatory network in glioblastoma and lay a foundation for further research.
Modulation of the Permeability-Inducing Factor Angiopoietin-2 Through Bifonazole in Systemic Inflammation
Authors: Pape Thorben , Idowu Temitayo Opemipo , Etzrodt Valerie Maritta , Stahl Klaus , Haller Hermann , David Sascha 
Published: September 2020

Abstract
BackgroundSepsis is a life-threatening organ dysfunction due to a pathological host response to an infection. Vascular barrier breakdown represents a key component of the maladaptive host response and the release of pre-stored endothelial Angiopoietin-2 (Angpt-2) is a direct driver of endothelial hyperpermeability. Although it has been demonstrated that Angpt-2 is associated with morbidity and mortality, a therapeutic approach targeting this injurious endothelial protein is not available. We screened for FDA approved drugs that might have off-target effects decreasing circulating Angpt-2 levels and therefore, ameliorating capillary leakage.MethodsEndothelial cells were isolated from human umbilical veins (HUVECs) and used for in vitro studies at baseline and after stimulation (FDA-library screening, RT-PCR, ELISA, immunocytochemistry). On the functional level, we assessed real-time transendothelial electrical resistance (TER) using the ECIS (electric cell-substrate impedance sensing) device.ResultsWe identified Bifonazole (BIFO) in an unbiased library screen and found that it is able to reduce spontaneous Angpt-2 release in HUVECs in a time- and dose-dependent manner after 8, 12 and 24 h (24 h: veh: 15.6 ± 0.7 vs. BIFO: 8.6 ± 0.8 ng/mL, p < 0.0001). BIFO reduced not only Angpt-2 release but also its intra-cellular content by 33 % (p < 0.001). Stimulation of HUVECs with a sepsis mediator, i.e. tumor necrosis factor α (TNFα) (10 ng/ml) induced a rapid release of Angpt-2 that could analogously be blocked by additional treatment with BIFO (veh: 1.58 ± 0.2 vs. BIFO: 1.02 ± 0.1, p < 0.0001). On the functional level, the quantification of endothelial permeability by TER revealed that BIFO was sufficient to reduce an acute barrier breakdown induced by Thrombin (veh: 0.82 ± 0.1 vs. BIFO: 1.01 ± 0.02, p < 0.05).ConclusionThe antifungal BIFO can reduce both release and biosynthesis of the endothelial-destabilizing factor Angpt-2 in vitro. Henceforth, our results suggest that BIFO might counterpart the pathophysiology of endothelial permeability in systemic inflammation. Additional studies are needed to further investigate the underlying mechanism and to translate these findings to in vivo models.
Magnetostratigraphic Evidence for Post-Depositional Distortion of Osmium Isotopic Records in Pelagic Clay and Its Implications for Mineral Flux Estimates
Authors: Usui Yoichi , Yamazaki Toshitsugu 
Published: September 2020

Abstract
Chemical stratigraphy is useful for dating deep sea sediments which sometimes lack radiometric or biostratigraphic constraints. Oxic pelagic clay contains Fe-Mn oxyhydroxides that can retain seawater 187Os/188Os values, and its age can be estimated by fitting the isotopic ratios to the seawater 187Os/188Os curve. On the other hand, the stability of Fe-Mn oxyhydroxides is sensitive to redox change, and it is not clear whether the original 187Os/188Os values are always preserved in sediments. However, due to the lack of independent age constraints, the reliability of 187Os/188Os ages of pelagic clay have never been tested. Here we report inconsistency between magnetostratigraphic and 187Os/188Os ages in pelagic clay around Minamitorishima Island. In a ~ 5 m thick interval, previous studies correlated 187Os/188Os data to a brief (< 2 million years) isotopic excursion in the late Eocene. Paleomagnetic measurements revealed at least 12 polarity zones in the interval, indicating a > 3.3–7.4 million years duration. Quartz and feldspars content showed that while the paleomagnetic chronology gives reasonable eolian flux estimates, the 187Os/188Os chronology leads unrealistically high values. These results suggest that the low 187Os/188Os signal has diffused from an original thin layer to the current ~ 5 m interval, causing an underestimate of the deposition duration. The preservation of the polarity patterns indicates that a mechanical mixing such as bioturbation cannot be the main process for the diffusion, so diagenetic re-distribution of Fe-Mn oxyhydroxides and associated Os may be responsible. The paleomagnetic chronology presented here also demands reconsiderations of the timing, accumulation rate, and origins of the high content of rare-earth elements and yttrium in pelagic clay around Minamitorishima Island.
Determinants of Early Marriage and Its Affect on Depression: A Population-based Study&nbsp;
Authors: Azizi Hosein , Fakhari Ali , Farahbakhsh Mostafa , Esmaeili Elham Davtalab , Barzgar Habibeh 
Published: September 2020

Abstract
Background: Early Marriage (EM) has defined as a marriage or union between two people when one or both are below 18. EM has serious side effects on psychological well-being and increases the probability of depression risk in the future. In Iran, EM predictors and the risk of depression among married people are poorly understood.Methods: A community-based descriptive-analytic study was conducted among the married general population in Malekan County. Stratified random sampling was performed. The face-to-face interviews and Beck depression inventory scale II were used by trained interviews. Multiple logistic regression was used to calculate adjusted odds ratios with 95% confidence interval the association between EM and predictor factors.Results: A total of 402 married participated in the study. The prevalence rate of EM was found 87 (21.64%). Out of 87 EM people, 80% were female. Almost 60% and 46.4% of EM and non-EM respondents had depressive symptoms, respectively. In the final analysis, EM was increased risk of depression (AOR=1.60; 95% CI: 1.2 – 2.72). Moreover, educational level of parents (AOR=5.53; 95% CI: 2.14 – 17.22), educational level of participants, (AOR=4.27; 95% CI: 1.28 – 14.35), female (AOR=2.43; 95% CI: 1.32 – 4.46), and family income (AOR=2.74; 95% CI: 1.00 – 7.84), were found significant predictors of EM. Conclusion: The educational level of married people and their parents are strong predictors of EM. Furthermore, EM affects depressive symptoms in the future. A general policy with inter-sectoral collaborations and increasing health literacy and effective training programs are imperative to reduce EM rates.