bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Immunophenotyping Clusters of Clear Cell Renal Cell Carcinoma Defined by the Unique Tumor Immune Microenvironment
Authors: Xu Wenhao , Anwaier Aihetaimujiang , Ma Chunguang , Liu Wangrui , Tian Xi , Su Jiaqi , Zhu Wenkai , Shi Guohai , Wei Shiyin , Xu Hong , Qu Yuanyuan , Ye Dingwei , Zhang Hailiang 
Published: December 2021

Background: The tumor microenvironment affects the occurrence and development of cancers, including clear cell renal cell carcinoma (ccRCC). However, how the immune contexture interacts with the cancer phenotype remains unclear.Methods: We identified and evaluated immunophenotyping clusters in ccRCC using machine-learning algorithms. Analyses for functional enrichment, DNA variation, immune cell distribution, association with independent clinicopathological features, and predictive responses for immune checkpoint therapies were performed and validated.Results: Three immunophenotyping clusters with gradual levels of immune infiltration were identified. The intermediate and high immune infiltration clusters (Clusters B and C) were associated with a worse prognosis for ccRCC patients. Tumors in the immune-hot Clusters B and C showed pro-tumorigenic immune infiltration, and these patients showed significantly worse survival compared with patients in the immune-cold Cluster A in the training and testing cohorts (n = 422). In addition to distinct immune cell infiltrations of immunophenotyping, we detected significant differences in DNA variation among clusters, suggesting a high degree of genetic heterogeneity. Furthermore, expressions of multiple immune checkpoint molecules were significantly increased. Clusters B and C predicted favorable outcomes in 64 ccRCC patients receiving immune checkpoint therapies from the FUSCC cohort. In 360 ccRCC patients from the FUSCC validation cohort, Clusters B and C significantly predicted worse prognosis compared with Cluster A. After immunophenotyping of ccRCC was confirmed, significantly increased tertiary lymphatic structures, aggressive phenotype, elevated glycolysis and PD-L1 expression, higher abundance of CD8+ T cells, and TCRn cell infiltration were found in the immune-hot Clusters B and C.Conclusion: This study described immunophenotyping clusters that improved the prognostic accuracy of the immune contexture in the ccRCC microenvironment. Our discovery of the novel independent prognostic indicators in ccRCC highlights the relationship between tumor phenotype and immune microenvironment.
Multi-Omics Analysis of Cancer Cell Lines with High/Low Ferroptosis Scores and Development of a Ferroptosis-Related Model for Multiple Cancer Types
Authors: Shan Guangyao , Zhang Huan , Bi Guoshu , Bian Yunyi , Liang Jiaqi , Valeria Besskaya , Zeng Dejun , Yao Guangyu , Zhan Cheng , Fan Hong 
Published: December 2021

Background: Ferroptosis is a newly identified regulated cell death characterized by iron-dependent lipid peroxidation and subsequent membrane oxidative damage, which has been implicated in multiple types of cancers. The multi-omics differences between cancer cell lines with high/low ferroptosis scores remain to be elucidated.Methods and Materials: We used RNA-seq gene expression, gene mutation, miRNA expression, metabolites, copy number variation, and drug sensitivity data of cancer cell lines from DEPMAP to detect multi-omics differences associated with ferroptosis. Based on the gene expression data of cancer cell lines, we performed LASSO-Logistic regression analysis to build a ferroptosis-related model. Lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), esophageal cancer (ESCA), bladder cancer (BLCA), cervical cancer (CESC), and head and neck cancer (HNSC) patients from the TCGA database were used as validation cohorts to test the efficacy of this model.Results: After stratifying the cancer cell lines into high score (HS) and low score (LS) groups according to the median of ferroptosis scores generated by gene set variation analysis, we found that IC50 of 66 agents such as oxaliplatin (p &lt; 0.001) were significantly different, among which 65 were higher in the HS group. 851 genes such as KEAP1 and NRAS were differentially muted between the two groups. Differentially expressed genes, miRNAs and metabolites were also detected—multiple items such as IL17F (logFC = 6.58, p &lt; 0.001) differed between the two groups. Unlike the TCGA data generated by bulk RNA-seq, the gene expression data in DEPMAP are from pure cancer cells, so it could better reflect the traits of tumors in cancer patients. Thus, we built a 15-signature model (AUC = 0.878) based on the gene expression data of cancer cell lines. The validation cohorts demonstrated a higher mutational rate of NFE2L2 and higher expression levels of 12 ferroptosis-related genes in HS groups.Conclusion: This article systemically analyzed multi-omics differences between cancer cell lines with high/low ferroptosis scores and a ferroptosis-related model was developed for multiple cancer types. Our findings could improve our understanding of the role of ferroptosis in cancer and provide new insight into treatment for malignant tumors.
Investigation of the Effects of Home-Based Exercise and Cognitive Training on Cognitive and Physical Functions in Cardiac Patients: The COVEPICARDIO Study Protocol of a Randomized Clinical Trial
Authors: Besnier Florent , Dupuy Emma Gabrielle , Gagnon Christine , Vincent Thomas , Grégoire Catherine-Alexandra , Blanchette Caroll-Ann , Saillant Kathia , Bouabdallaoui Nadia , Grau Josep Iglésies , Bérubé Béatrice , Olmand Miloudza , Marin Marie-France , Belleville Sylvie , Juneau Martin , Vitali Paolo , Gayda Mathieu , Nigam Anil , Bherer Louis 
Published: December 2021

Introduction: During the COVID-19 pandemic, confinement measures are likely to produce collateral damage to health (stress, confusion, anxiety), especially in frail individuals and those living with cardiovascular disease (CVD). In cardiac patients in particular, these measures dramatically increase the level of physical inactivity and sedentary lifestyle, which can decrease cardiorespiratory capacity and increase the risk of acute events, rehospitalization, and depressive syndromes. Maintaining a minimum level of physical activity and cognitive stimulation during the COVID-19 crisis is essential for cardiac patients. This study is designed to document the effects of 6 months of home-based physical exercise alone or combined with cognitive training on cognitive and physical functions in patients with CVD over 50 years old.Methods and Analysis: 122 patients (&gt;50 years old) with stable CVD and no contraindication to perform physical exercise training will be recruited and randomly assigned to one of the 2 following arms: (1) Home-based physical exercise alone, (2) Home-based physical exercise combined with cognitive training. The intervention lasts 6 months, with remote assessments performed prior to, mid and post-training. A follow-up 6 months after the end of the intervention (12 month) is also proposed. The primary outcome is cognition, including general functioning (Montreal Cognitive Assessment (MoCA) score), as well as performances on measures of executive functions, processing speed, and episodic memory. The secondary outcome is physical performance, including balance, gait and mobility, leg muscle strength and estimated cardiorespiratory fitness. Tertiary outcomes include mood, anxiety, and health-related quality of life as assessed by self-reported online questionnaires.Discussion: With the COVID-19 crisis, there is a critical need for remote exercise and cognitive training, and to further investigate this topic, in particular for cardiac patients. The present context can be viewed as an opportunity to perform a major shift from center-based programs to home-based physical exercise. This is especially important to reach out to older adults living in remote areas, where access to such interventions is limited.ClinicalTrials.gov: [https://clinicaltrials.gov/ct2/show/NCT04661189], NCT04661189.
Predictive Effect of Renal Function on Clinical Outcomes in Older Adults With Acute Myocardial Infarction: Results From an Observational Cohort Study in China
Authors: Gao Hui , Peng Hui , Shen Aidong , Chen Hui , Li Hongwei 
Published: December 2021

Background: The impact of estimated glomerular filtration rate (eGFR) on the risk of death and cardiovascular events in individuals with acute myocardial infarction (AMI) is less well established, particularly in the old Chinese population. The aim of this study was to investigate the association of eGFR with clinical outcomes among older subjects with AMI. We further developed a nomogram for the prediction of 1- and 3-year survival in this population.Methods: A cohort of 2,366 AMI subjects aged over 60 years in 2013–2020 were enrolled in the Cardiovascular Center of Beijing Friendship Hospital Database (CBD) Bank. Outcomes including cardiovascular (CV) death, all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke, revascularization, and cardiac rehospitalization were collected overall and by eGFR category at baseline. eGFR was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Subjects were categorized into four groups according to quartiles of eGFR: ≤ 63.02, 63.03–78.45, 78.46–91.50, &gt;91.51 ml/min/1.73 m2. Hazard ratios (HRs), corresponding 95% confidence intervals (CIs) as well as the nomogram were assessed using Cox regression models. Validation of the nomogram was estimated by discrimination and calibration.Results: Incidence rates and multivariable-adjusted hazard ratios of CV and all-cause death decreased significantly across quartiles of eGFR over a median follow-up time of 36.7 months. In adjusted analysis, compared with eGFR ≤ 63.02 ml/min/1.73 m2, patients with eGFR of 63.03–78.45, 78.46–91.50, &gt;91.51 ml/min/1.73 m2 experienced decreased risks of CV death [respective HRs of 0.58 (95% CI, 0.38–0.90), 0.61 (95% CI, 0.38–0.99), and 0.48 (95% CI, 0.25–0.90); all p &lt; 0.05] and all-cause death [respective HRs of 0.64 (95% CI, 0.47–0.88), 0.61 (95% CI, 0.42–0.88), and 0.54 (95% CI, 0.35–0.84); all p &lt; 0.05]. Age, eGFR quartiles, BMI, glycated hemoglobin, LVEF, LM/multi-vessel disease, angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) prescribed at discharge were associated with all-cause death. The developed model predicted 1- and 3-year probability of survival, which performed well in both discrimination and calibration.Conclusion: In older patients with AMI, early identification of eGFR reduced and cardiovascular risks management may prevent poor clinical outcomes.
Northward Growth of the West Kunlun Mountains: Insight From the Age–Elevation Relationship of New Apatite Fission Track Data
Authors: Liu Dongliang , Li Haibing , Ge Chenglong , Bai Mingkun , Wang Yadong , Pan Jiawei , Zheng Yong , Wang Ping , Liu Fucai , Wang Shiguang 
Published: December 2021

The Cenozoic collision between India and Asia promoted the widespread uplift of the Tibetan Plateau, with significant deformation documented in the Pamir Plateau and West Kunlun Mountains. Low-temperature thermochronology and basin provenance analysis have revealed three episodes of rapid deformation and uplift in the Pamir–West Kunlun Mountains during the Cenozoic. However, there is very little low-temperature thermochronology age–elevation relationship (AER) data on fast exhumation events in this area—especially in the West Kunlun Mountains— leading to uncertainty surrounding how these events propagated within and around the mountain range. In this study, we produced an elevation profile across granite located south of Kudi, Xijiang Province, China, to reveal its exhumation history. Apatite fission track AER data show that a rapid exhumation event occurred at ∼26 Ma in the southern West Kunlun Mountains. When combined with published data, we interpret that the initial uplift events related to the India–Asia collision began in the central Pamir, southern West Kunlun, and northern West Kunlun regions during the Late Eocene, Oligocene, and Middle Miocene periods, respectively. Therefore, the Cenozoic northward growth process occurred from south to north around West Kunlun.
Study of Ground Movement in a Mining Area with Geological Faults Using FDM Analysis and a Stacking InSAR Method
Authors: Qin Zhengyuan , Agarwal Vivek , Gee David , Marsh Stuart , Grebby Stephen , Chen Yong , Meng Ningkang 
Published: December 2021

Underground coal mining activities and ground movement are directly correlated, and coal mining-induced ground movement can cause damage to property and resources, thus its monitoring is essential for the safety and economics of a city. Fangezhuang coal mine is one of the largest coalfields in operation in Tangshan, China. The enormous amount of coal extraction has resulted in significant ground movement over the years. These phenomena have produced severe damages to the local infrastructure. This paper uses the finite difference method (FDM) 3D model and the stacking interferometric synthetic aperture radar (InSAR) method to monitor the ground movement in Fangezhuang coalfield during 2016. The FDM 3D model used calibrated Fangezhuang geological parameters and the satellite InSAR analysis involved the use of ascending C-band Sentinel-1A interferometric wide (IW) data for 2016. The results show that the most prominent subsidence signal occurs in mining panel 2553N and the area between panel 2553N and fault F0 with subsidence up to 57 cm. The subsidence observed for the FDM 3D model and stacking InSAR to monitor land deformation under the influence of fault are in close agreement and were verified using a two-sample t-test. It was observed that the maximum subsidence point shifted towards the fault location from the centre of the mining panel. The tectonic fault F0 was found to be reactivated by the coal mining and controls the spatial extent of the observed ground movement. The impact of dominant geological faults on local subsidence boundaries is investigated in details. It is concluded that ground movement in the study area was mainly induced by mining activities, with its spatial pattern being controlled by geological faults. These results highlight that the two methods are capable of measuring mining induced ground movement in fault dominated areas. The study will improve the understanding of subsidence control, and aid in developing preventive measures in Fangezhuang coalfield with fault reactivation.
Characteristics of Regular Pulse Bursts Generated From Lightning Discharges
Authors: Yanhui Wang , Xiangpeng Fan , Tuo Wang , Yingchang Min , Yali Liu , Guo Zhao 
Published: December 2021

In this work, we studied the waveforms of all lightning discharges from about 15 min. Eighty-three percent of all lightning discharges contain particular waveforms called regular pulse bursts (RPBs), which have regular microsecond-scale electric or magnetic field pulses. Maximum proportion of RPBs occur in middle or rear of lightning discharges. Prior to or after RPBs, there is always a chaotic pulse period. The analysis indicated that RPBs are caused by a secondary discharge in the fractured old breakdown channel, likeness to dart-stepped leader occuring in negative cloud-to-ground discharge (-CG). Four types of RPBs, namely, category of normal RPBs, category of back RPBs, category of symmetric RPBs, and category of reversal RPBs, were sorted in the light of the evolution of the pulse amplitude, interval between neighboring pulses and pulse polarity. In addition, the difference between normal RPBs and back RPBs was considered to be caused by the distance between neighboring charge pockets and the magnitude of the charge in every charge pocket. The symmetric RPBs were considered to be caused by a discharge channel with a large central charge area. Reversal RPBs were considered to be caused by a bending channel or superposition of two or more RPBs. We located some RPBs in a typical intra-cloud flash (IC) in three-dimensional. The analysis showed that the developing velocity of RPBs ranged from approximately 1.2 × 106 m/s to 3.0 × 106 m/s, which slower less than both of the dart leader or dart-stepped leader process from previous studies. And we found it is several meters to dozens of meters that the lengths range of discharge step which between two adjacent pulses.
Construction and Analysis of Immune Infiltration-Related ceRNA Network for Kidney Stones
Authors: Xia Yuqi , Zhou Xiangjun , Ye Zehua , Yu Weimin , Ning Jinzhuo , Ruan Yuan , Yuan Run , Lin Fangyou , Ye Peng , Zheng Di , Rao Ting , Cheng Fan 
Published: December 2021

Purpose: Kidney stones is a common medical issue that mediates kidney injury and even kidney function loss. However, the exact pathogenesis still remains unclear. This study aimed to explore the potential competing endogenous RNA (ceRNA)-related pathogenesis of kidney stones and identify the corresponding immune infiltration signature.Methods: One mRNA and one long non-coding RNA (lncRNA) microarray dataset was obtained from the GEO database. Subsequently, we compared differentially expressed mRNAs (DE-mRNAs) and lncRNAs between Randall’s plaques in patients with calcium oxalate (CaOx) stones and controls with normal papillary tissues. lncRNA-targeted miRNAs and miRNA–mRNA pairs were predicted using the online databases. lncRNA-related DE-mRNAs were identified using the Venn method, and GO and KEGG enrichment analyses were subsequently performed. The immune-related lncRNA–miRNA–mRNA ceRNA network was developed. The CIBERSORT algorithm was used to estimate the rate of immune cell infiltration in Randall’s plaques. The ceRNA network and immune infiltration were validated in the glyoxylate-induced hyperoxaluric mouse model and oxalate-treated HK-2 cells.Results: We identified 2,340 DE-mRNAs and 929 DE-lncRNAs between Randall’s plaques in patients with CaOx stones and controls with normal papillary tissues. lncRNA-related DE-mRNAs were significantly enriched in extracellular matrix organization and collagen-containing extracellular matrix, which were associated with kidney interstitial fibrosis. The immune-related ceRNA network included 10 lncRNAs, 23 miRNAs, and 20 mRNAs. Moreover, we found that M2 macrophages and resting mast cells were differentially expressed between Randall’s plaques and normal tissues. Throughout kidney stone development, kidney tubular injury, crystal deposition, collagen fiber deposition, TGF-β expression, infiltration of M1 macrophages, and activation of mast cells were more frequent in glyoxylate-induced hyperoxaluric mice compared with control mice. Nevertheless, M2 macrophage infiltration increased in early stages (day 6) and decreased as kidney stones progressed (day 12). Furthermore, treatment with 0.25 and 0.5 mM of oxalate for 48 h significantly upregulated NEAT1, PVT1, CCL7, and ROBO2 expression levels and downregulated hsa-miR-23b-3p, hsa-miR-429, and hsa-miR-139-5p expression levels in the HK-2 cell line in a dose-dependent manner.Conclusion: We found that significant expressions of ceRNAs (NEAT1, PVT1, hsa-miR-23b-3p, hsa-miR-429, hsa-miR-139-5p, CCL7, and ROBO2) and infiltrating immune cells (macrophages and mast cells) may be involved in kidney stone pathogenesis. These findings provide novel potential therapeutic targets for kidney stones.
Transcutaneous Electrical Acupoint Stimulation for the Prevention of Postoperative Cognitive Dysfunction: A Systematic Review and Meta-Analysis
Authors: Zhang Tiantian , Ou Liang , Chen Zehua , Li Jiamin , Shang Yan , Hu Guoheng 
Published: December 2021

Background: No specific treatment is available for postoperative cognitive dysfunction (POCD). Recently, interest in the prevention of POCD during the perioperative period has increased. Although some studies suggest that transcutaneous electrical acupoint stimulation (TEAS) may be beneficial, the relevant evidence remains uncertain.Objective: To evaluate the preventive effects of TEAS on POCD.Methods: Seven databases including PubMed, EMBASE, CENTRAL, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Wanfang Database, and Chinese Biomedical Literature Database (CBM) were electronically searched up to April 2021. Two reviewers independently selected the studies, collected data, and assessed the risks of bias and grading of recommendations, assessment, development, and evaluations certainty of the evidence. A meta-analysis of the incidence of POCD, cognitive function score, pain, adverse reactions, and length of hospital stay after surgery was also performed.Results: Twenty-nine randomized controlled trials with 1,994 participants were included. The results of the meta-analysis showed that the TEAS group has a significantly lower incidence of POCD compared with the control group on postoperative days 1 [OR = 0.33 (95%CI: 0.23, 0.47); p &lt; 0.001, I2 = 0%, moderate certainty], 3 [OR = 0.38 (95%CI: 0.29, 0.50); p &lt; 0.001, I2 = 0%, low certainty], and 7 [OR = 0.51 (95%CI: 0.32, 0.81); p = 0.005, I2 = 0%, low certainty] but not on day 5 (p &gt; 0.05, low certainty). Moreover, TEAS improved the Mini-Mental State Examination scores on postoperative days 1, 3, and 7 [MD = 2.44 (95%CI: 1.61, 3.27); p &lt; 0.001, I2 = 93%, low certainty]; [MD = 2.07 (95%CI: 1.53, 2.62); p &lt; 0.001, I2 = 87%, low certainty]; and [MD = 0.49 (95%CI: 0.18, 0.79); p = 0.002, I2 = 21%, low certainty], respectively, but not on day 5 (p &gt; 0.05, very low certainty). TEAS promoted a postoperative analgesic effect within 24 h after surgery. Furthermore, patients receiving TEAS showed a lower incidence of postoperative nausea and vomiting and a shorter hospital stay.Conclusions: Limited evidence suggests that the application of TEAS in the perioperative period is associated with a reduced POCD rate and a protected early postoperative cognitive function.