bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Investigation of Immune-Related lncRNA Landscape Reveals a Potential Long Non-Coding RNA Signature for Predicting Prognosis in Renal Cell Carcinoma
Authors: Liu Kepu , Li Zhibin , Ruan Dongli , Wang Huilong , Wang Wei , Zhang Geng 
Published: July 2022

Background: Renal cell carcinoma (RCC) is the predominant type of malignant tumor in kidney cancer. Finding effective biomarkers, particularly those based on the tumor immune microenvironments (TIME), is critical for the prognosis and diagnosis of RCC. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) play a crucial role in cancer immunity. However, the comprehensive landscape of immune infiltration-associated lncRNAs and their potential roles in the prognosis and diagnosis of RCC remain largely unexplored.Methods: Based on transcriptomic data of 261 RCC samples, novel lncRNAs were identified using a custom pipeline. RCC patients were classified into different immune groups using unsupervised clustering algorithms. Immune-related lncRNAs were obtained according to the immune status of RCC. Competing endogenous RNAs (ceRNA) regulation network was constructed to reveal their functions. Expression patterns and several tools such as miRanda, RNAhybrid, miRWalk were used to define lncRNAs-miRNAs-mRNAs interactions. Univariate Cox, LASSO, and multivariate Cox regression analyses were performed on the training set to construct a tumorigenesis-immune-infiltration-related (TIR)-lncRNA signature for predicting the prognosis of RCC. Independent datasets involving 531 RCC samples were used to validate the TIR-lncRNA signature.Results: Tens of thousands of novel lncRNAs were identified in RCC samples. Comparing tumors with controls, 1,400 tumorigenesis-related (TR)-lncRNAs, 1269 TR-mRNAs, and 192 TR-miRNAs were obtained. Based on the infiltration of immune cells, RCC patients were classified into three immune clusters. By comparing immune-high with immune-low groups, 241 TIR-lncRNAs were identified, many of which were detected in urinary samples. Based on lncRNA-miRNA-mRNA interactions, we constructed a ceRNA network, which included 25 TR-miRNAs, 28 TIR-lncRNAs, and 66 TIR-mRNAs. Three TIR lncRNAs were identified as a prognostic signature for RCC. RCC patients in the high-risk group exhibited worse OS than those in the low-risk group in the training and testing sets (p &lt; 0.01). The AUC was 0.9 in the training set. Univariate and multivariate Cox analyses confirmed that the TIR-lncRNA signature was an independent prognostic factor in the training and testing sets.Conclusion: Based on the constructed immune-related lncRNA landscape, 241 TIR-lncRNAs were functionally characterized, three of which were identified as a novel TIR-lncRNA signature for predicting the prognosis of RCC.
Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury
Authors: Zhang Yang , Cai Jieru , Lu Wei , Xu Sujuan , Qu Mengdi , Zhao Shuan , Ding Xiaoqiang 
Published: July 2022

Background: Acute kidney injury (AKI) is a common clinical syndrome with limited methods of treatment and diagnosis. Although several molecules associated with AKI have been discovered, molecular mechanisms underlying AKI still remain unclear. Weighted gene co-expression network analysis (WGCNA) is a novel method to uncover the relationship between co-expression genes and clinical traits at the system level.Methods: First, by employing WGCNA in transcriptional data on 30 patients with well/poor functioning kidney graft, we identified two co-expression modules that were significantly related to serum creatinine (SCr). Second, based on the modules, potential small molecular compound candidates for developing targeted therapeutics were obtained by connectivity map analysis. Furthermore, multiple validations of expression in space/time were carried out with two classical AKI models in vivo and other five databases of over 152 samples.Results: Two of the 14 modules were found to be closely correlated with SCr. Function enrichment analysis illustrated that one module was enriched in the immune system, while the other was in the metabolic process. Six key renal function-related genes (RFRGs) were finally obtained. Such genes performed well in cisplatin-induced or cecal ligation and puncture-induced AKI mouse models.Conclusion: The analysis suggests that WGCNA is a proper method to connect clinical traits with genome data to find novel targets in AKI. The kidney tissue with worse renal function tended to develop a “high immune but low metabolic activity” expression pattern. Also, ACSM2A, GLYAT, CORO1A, DPEP1, ALDH7A1, and EPHX2 are potential targets of molecular diagnosis and treatment in AKI.
Trained Immunity in Primary Sjögren’s Syndrome: Linking Type I Interferons to a Pro-Atherogenic Phenotype
Authors: Huijser Erika , van Helden-Meeuwsen Cornelia G. , Grashof Dwin G. B. , Tarn Jessica R. , Brkic Zana , Huisman Josje M. A. , Wahadat M. Javad , van de Werken Harmen J. G. , Lopes Ana P. , van Roon Joel A. G. , van Daele Paul L. A. , Kamphuis Sylvia , Ng Wan-Fai , Bekkering Siroon , Joosten Leo A. B. , Dik Willem A. , Versnel Marjan A. 
Published: July 2022

BackgroundTrained immunity – or innate immune memory – can be described as the long-term reprogramming of innate immune cells towards a hyperresponsive state which involves intracellular metabolic changes. Trained immunity has been linked to atherosclerosis. A subgroup of patients with primary Sjögren’s syndrome (pSS) exhibits systemic type I interferon (IFN) pathway activation, indicating innate immune hyperactivation. Here, we studied the link between type I IFNs and trained immunity in an in vitro monocytic cell model and peripheral blood mononuclear cells (PBMCs) from pSS patients.MethodsThe training stimuli heat killed Candida albicans, muramyl dipeptide, IFNβ, and patient serum were added to THP-1 cells for 24 hours, after which the cells were washed, rested for 48 hours and subsequently re-stimulated with LPS, Pam3Cys, poly I:C, IFNβ or oxLDL for 4-24 hours. PBMCs from pSS patients and healthy controls were stimulated with LPS, Pam3Cys, poly I:C or IFNβ for 0.5-24 hours.ResultsTraining with IFNβ induced elevated production of pro-atherogenic cytokines IL-6, TNFα and CCL2, differential cholesterol- and glycolysis-related gene expression, and increased glucose consumption and oxLDL uptake upon re-stimulation. Type I IFN production was increased in Candida albicans- and IFNβ-trained cells after LPS re-stimulation, but was reduced after poly I:C re-stimulation. Training with muramyl dipeptide and IFNβ, but not Candida albicans, affected the IFN-stimulated gene expression response to IFNβ re-stimulation. PBMCs from pSS patients consumed more glucose compared with healthy control PBMCs and tended to produce more TNFα and type I IFNs upon LPS stimulation, but less type I IFNs upon poly I:C stimulation.ConclusionsType I IFN is a trainer inducing a trained immunity phenotype with pro-atherogenic properties in monocytes. Conversely, trained immunity also affects the production of type I IFNs and transcriptional response to type I IFN receptor re-stimulation. The phenotype of pSS PBMCs is consistent with trained immunity. This connection between type I IFN, trained immunity and cholesterol metabolism may have important implications for pSS and the pathogenesis of (subclinical) atherosclerosis in these patients.
Bifidobacterium infantis Promotes Foxp3 Expression in Colon Cells via PD-L1-Mediated Inhibition of the PI3K-Akt-mTOR Signaling Pathway
Authors: Zhou Linyan , Xie Ying , Li Yan 
Published: July 2022

AimOur objective was to investigate whether Bifidobacterium infantis inhibits PI3K-Akt-mTOR signaling and upregulates Foxp3 expression through PD-L1 and to explore the possible mechanism of action of B. infantis in cellular immunosuppression. MethodThe effects of B. infantis supernatant on PD-L1, PD-1, Foxp3, and the PI3K-Akt-mTOR signaling pathway were observed by culturing HCT-116 cells. Simultaneously, the effects of blocking PD-L1 on PD-1, on Foxp3 protein and mRNA, and on the PI3K-Akt-mTOR signaling pathway protein were observed.ResultsB. infantis supernatant was able to upregulate the protein and mRNA expression of PD-L1 and Foxp3 and downregulate the phosphorylated protein expression of PI3K, Akt, and mTOR (P &lt; 0.05); however, for PI3K, Akt, and mTOR, there was no change in the total protein expression. After the blocking of PD-L1, the stimulatory effect of B. infantis supernatant on Foxp3 and the inhibitory effect on the phosphorylated protein expression of PI3K, Akt, and mTOR were weakened.ConclusionB. infantis may inhibit the PI3K-Akt-mTOR signaling pathway and promote the expression of Foxp3 through PD-L1, which may be a target via which B. infantis exerts its immunosuppressive effect.
Colchicine Impacts Leukocyte Trafficking in Atherosclerosis and Reduces Vascular Inflammation
Authors: Meyer-Lindemann Ulrike , Mauersberger Carina , Schmidt Anna-Christina , Moggio Aldo , Hinterdobler Julia , Li Xinghai , Khangholi David , Hettwer Jan , Gräßer Christian , Dutsch Alexander , Schunkert Heribert , Kessler Thorsten , Sager Hendrik B. 
Published: July 2022

BackgroundInflammation strongly contributes to atherosclerosis initiation and progression. Consequently, recent clinical trials pharmacologically targeted vascular inflammation to decrease the incidence of atherosclerosis-related complications. Colchicine, a microtubule inhibitor with anti-inflammatory properties, reduced cardiovascular events in patients with recent acute coronary syndrome and chronic coronary disease. However, the biological basis of these observations remains elusive. We sought to explore the mechanism by which colchicine beneficially alters the course of atherosclerosis.Methods and ResultsIn mice with early atherosclerosis (Apoe-/- mice on a high cholesterol diet for 8 weeks), we found that colchicine treatment (0.25 mg/kg bodyweight once daily over four weeks) reduced numbers of neutrophils, inflammatory monocytes and macrophages inside atherosclerotic aortas using flow cytometry and immunohistochemistry. Consequently, colchicine treatment resulted in a less inflammatory plaque composition and reduced plaque size. We next investigated how colchicine prevented plaque leukocyte expansion and found that colchicine treatment mitigated recruitment of blood neutrophils and inflammatory monocytes to plaques as revealed by adoptive transfer experiments. Causally, we found that colchicine reduced levels of both leukocyte adhesion molecules and receptors for leukocyte chemoattractants on blood neutrophils and monocytes. Further experiments showed that colchicine treatment reduced vascular inflammation also in post-myocardial infarction accelerated atherosclerosis through similar mechanisms as documented in early atherosclerosis. When we examined whether colchicine also decreased numbers of macrophages inside atherosclerotic plaques by impacting monocyte/macrophage transitioning or in-situ proliferation of macrophages, we report that colchicine treatment did not influence macrophage precursor differentiation or macrophage proliferation using cell culture experiments with bone marrow derived macrophages.ConclusionsOur data reveal that colchicine prevents expansion of plaque inflammatory leukocytes through lowering recruitment of blood myeloid cells to plaques. These data provide novel mechanistic clues on the beneficial effects of colchicine in the treatment of atherosclerosis and may inform future anti-inflammatory interventions in patients at risk.
Characteristics of Fatty Acid Metabolism in Lung Adenocarcinoma to Guide Clinical Treatment
Authors: Huang Dejing , Tang Enyu , Zhang Tianze , Xu Guangquan 
Published: July 2022

BackgroundLung adenocarcinoma (LUAD) has a very high morbidity and mortality rate, and its pathogenesis and treatment are still in the exploratory stage. Fatty acid metabolism plays a significant role in tumorigenesis, progression, and immune regulation. However, the gene expression of fatty acid metabolism in patients with LUAD and its relationship with prognosis remain unclear.MethodsWe collected 309 fatty acid metabolism-related genes, established a LUAD risk model based on The Cancer Genome Atlas (TCGA) using Least Absolute Shrinkage Selection Operator (LASSO) regression analysis, and divided LUAD patients into high-risk and low-risk groups, which were further validated using the Gene Expression Omnibus (GEO) database. The nomogram, principal component analysis (PCA), and receiver operating characteristic (ROC) curves showed that the model had the best predictive performance. The ROC curves and calibration plots confirmed that the nomogram had good predictive power. We further analyzed the differences in clinical characteristics, immune cell infiltration, immune-related functions, chemotherapy drug sensitivity, and immunotherapy efficacy between the high-risk and low-risk groups. We also analyzed the enrichment pathways and protein–protein interaction (PPI) networks of different genes in the high-risk and low-risk groups to screen for target genes and further explored the correlation between target genes and differences in survival prognosis, clinical characteristics, gene mutations, and immune cells.ResultsRisk score and staging are independent prognostic factors for patients with LUAD. The high-risk group had lower immune cell infiltration, was more sensitive to chemotherapeutic agents, and had a poorer survival prognosis. We also obtained three pivotal genes with poor survival prognosis in the high expression group, which were strongly associated with clinical symptoms and immune cells.ConclusionRisk score and staging are independent prognostic factors for patients with LUAD. The high-risk group had lower immune cell infiltration, was more sensitive to chemotherapeutic agents, and had a poorer survival prognosis. We also obtained three survival prognosis-associated target genes that are closely associated with clinical symptoms and immune cells and may be potential targets for immune-targeted therapy in LUAD.
ETV1 Positively Correlated With Immune Infiltration and Poor Clinical Prognosis in Colorectal Cancer
Authors: Shen Xiaonan , Zhou Chunhua , Feng Haoran , Li Jialu , Xia Tianxue , Cheng Xi , Zhao Ren , Zou Duowu 
Published: July 2022

ObjectiveNumerous studies recently suggested that the immune microenvironment could influence the development of colorectal cancer (CRC). These findings implied that the infiltration of immune cells could be a promising prognostic biomarker for CRC.MethodsFurthermore, the Oncomine database and R2 platform analysis were applied in our research to validate CRC clinical prognosis via expression levels of polyoma enhancer activator 3 (PEA3) members. We explored the correlation of ETV1, ETV4, and ETV5 with tumor-infiltrating immune cells (TIICs) in CRC tumor microenvironments via the Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). Immunohistochemistry (IHC) was used to validate our CRC clinical data.ResultsOur findings indicated that the upregulation of PEA3 members including ETV1 and ETV5 was positively associated with poor prognosis in CRC patients. Meanwhile, ETV1 and ETV5 may play significant roles in the development progress of CRC. Furthermore, ETV1 tends to be associated with immune infiltration of CRC, especially with cancer-associated fibroblasts and M2 macrophages.ConclusionThese findings revealed that ETV1 and ETV5 played significant roles in the development of CRC. Moreover, ETV1 was significantly associated with the infiltration of cancer-associated fibroblasts and M2 macrophages in CRC. Targeting ETV1 can be a potential auspicious approach for CRC treatment.
Improving Extreme Anchor Tension Prediction of a 10-MW Floating Semi-Submersible Type Wind Turbine, Using Highly Correlated Surge Motion Record
Authors: Gaidai Oleg , Xing Yihan , Wang Fang , Wang Shuaishuai , Yan Ping , Naess Arvid 
Published: July 2022

Extreme value prediction of the load-effect responses of complex offshore structures such as the floating wind turbine (FWT) is crucial in ultimate limit state (ULS) design. This paper considers two cases to understand the feasibility of the bivariate correction on the extreme load and motion responses of a 10-MW semi-submersible type FWT. The empirical anchor tension force and surge motion used in this study are obtained from the FAST simulation tool (developed by the National Renewable Energy Laboratory) with the load cases stimulated at under-rated, rated and above rated speeds. Then, the bivariate correction method is applied to model FWT extreme response for a 5-years return period prediction with a 95% confidence interval (CI), based on just 2 min short response record. The proposed methodology permits accurate correction of the bivariate extreme value in case of, for example, corrupted measurement sensor data. Based on the proposed novel method’s performance, it is concluded that the bivariate correction method can offer better robust and precise bivariate predictions of coupled surge motion and anchor tension of the FWT.
Subfoveal Choroidal Thickness After Femtosecond Laser-Assisted Cataract Surgery for Age-Related Cataracts
Authors: Chen Wan , Chen Hui , Mi Lan , Li Jing , Lin Haotian , Chen Weirong 
Published: July 2022

PurposeTo compare the effects of femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification surgery (CPS) on subfoveal choroidal thickness (SFCT) in patients with age-related cataracts.MethodsIn this prospective consecutive study, 26 patients (26 eyes) with age-related cataracts without previous ocular surgery or other ocular diseases who had FLACS were included as the study group. Twenty-six age-matched patients (26 eyes) who underwent CPS in the same period were also included as the control group. The SFCT and the foveal retinal thickness (FRT) were measured at baseline and at 1 day (D1), 7 days (D7), 1 month (M1), and 3 months (M3) postoperatively by spectral-domain optical coherence tomography. Aqueous flare was also measured with a laser flare meter.ResultsThe mean SFCTs of the FLACS group at baseline and at D1, D7, M1, and M3 were 185.2, 174.3, 184.2, 180.8, and 184.1 μm, respectively. A Bonferroni posttest showed that the choroid became thinner on postoperative D1 (P = 0.006). The measurements at 1 week, 1 month, and 3 months postoperatively showed no significant differences in the SFCTs compared with that at baseline (P = 0.66, P = 0.22, and P = 0.53, respectively). A different trend was observed in the CPS group. The choroid became thicker by the 3-month postoperative measurement, as follows: 1 day (P = 0.28), 1 week (P = 0.016), 1 month (P = 0.020), and 3 months (P &lt; 0.001).ConclusionThe mean SFCT significantly and temporarily decreased following FLACS. In contrast, an increased SFCT was observed following CPS.
The Impact of Low-Level Viraemia on Virological Failure—Results From a Multicenter HIV Antiretroviral Therapy Cohort Study in Yunnan, China
Authors: An Jing , Lao Yunfei , Tang Songyuan , Lou Jincheng , Li Tianshu , Dong Xingqi 
Published: July 2022

BackgroundHIV viral load (VL) is an important indicator to monitor treatment response in antiretroviral therapy (ART). Patients on ART may experience viral blips, with low-level elevations of VL between 50 and 999 copies/mL known as low-level viraemia (LLV), but not reaching the threshold for virological failure (≥1,000 copies/mL) defined by WHO guidelines. The objective was to investigate the long-term impact of LLV on virological failure.MethodsWe analyzed adults who were ART naïve at baseline. LLV was defined as having an VL of 51–999 copies/mL at least once. The subjects with LLV were grouped into three categories: 51–199, 200–399, and 400–999 copies/mL. Patients with multiple episodes of LLV were classified based on the highest VL result. The subjects with LLV were also grouped by the frequency of LLV, i.e., a single episode, two consecutive episodes, two intermittent episodes, more than two consecutive episodes, and more than two intermittent episodes. Multivariable Cox models were used to predict the association of LLV with virological failure.ResultsA total of 93,944 subjects were included. The median number of VL tests performed was 3. There were 21,203 LLV cases, with an overall incidence of 22.6%. Most of the LLV cases were found in subjects with LVs of 50–199 copies/mL, followed by 400–999 and 200–399 copies/mL. Most of the LLV cases experienced single episodes, and the numbers of LLV with two consecutive episodes, two intermittent episodes, more than two consecutive episodes and more than two intermittent episodes were decreased successively. The risk factors associated with virological failure include: intermediate-level (200–399 copies/mL) and high-level (400–999 copies/mL) LLV, single episodes of LLV and two or more than two consecutive episodes of LLV, which may put the subjects at a 1.28–2.26-fold higher risk for virological failure.ConclusionStrengthened immediate medical attention should be placed on patients with VL of 200–999 copies/mL. The patients having experienced LLV once should be targeted for case management and repeat VL testing within 24 weeks to determine persistent LLV and monitor virological failure.
Retinal Neurovascular Changes in Patients With Ischemic Stroke Investigated by Optical Coherence Tomography Angiography
Authors: Liang Yingying , Liu Baoyi , Xiao Yu , Zeng Xiaomin , Wu Guanrong , Du Zijing , Fang Ying , Hu Yijun , Yang Xiaohong , Yu Honghua 
Published: July 2022

BackgroundTo investigate retinal neurovascular structural changes in patients with ischemic stroke (IS) using optical coherence tomography angiography (OCTA).Materials and MethodsThe cross-sectional study was conducted in Guangdong Provincial People’s Hospital, China, consisting of 159 eyes from IS patients and 109 eyes from age-matched control subjects. Retinal microvascular parameters including the vessel density (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC), and neural parameters such as ganglion cell complex thickness (GCCt) and retinal nerve fibre layer thickness (RNFLt) were measured by OCTA.ResultsThe VD of SCP and DCP in the macular area were significantly reduced in IS patients compared to the control group (all p &lt; 0.001). The VD of RPC at the optic disc was also significantly reduced in IS patients (all p &lt; 0.05). IS patients showed reduced GCCt and RNFLt and increased GCC focal loss volume and global loss volume compared with the controls (all p &lt; 0.05). Among patients with IS, the parafovea SCP VD was positively correlated with GCCt (r = 0.346–0.408, all p &lt; 0.001) but not with DCP VD (all p &gt; 0.1). In the optic disc region, the whole image RPC VD was positively correlated with mean RNFLt (r = 0.467–0.548, all p &lt; 0.001).ConclusionReduction of retinal VD, GCCt and RNFLt was observed in patients with IS. The parafovea SCP VD and RPC VD were positively correlated with GCCt and RNFLt, respectively.