bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies
Authors: Yu Rongguo , Zhang Jiayu , Zhuo Youguang , Hong Xu , Ye Jie , Tang Susu , Zhang Yiyuan 
Published: October 2021

BackgroundRheumatoid arthritis (RA) refers to an autoimmune rheumatic disease that imposes a huge burden on patients and society. Early RA diagnosis is critical to preventing disease progression and selecting optimal therapeutic strategies more effectively. In the present study, the aim was at examining RA’s diagnostic signatures and the effect of immune cell infiltration in this pathology.MethodsGene Expression Omnibus (GEO) database provided three datasets of gene expressions. Firstly, this study adopted R software for identifying differentially expressed genes (DEGs) and conducting functional correlation analyses. Subsequently, we integrated bioinformatic analysis and machine-learning strategies for screening and determining RA’s diagnostic signatures and further verify by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. Moreover, this study employed cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) website for assessing the inflammatory state of RA, and an investigation was conducted on the relationship of diagnostic signatures and infiltrating immune cells.ResultsOn the whole, 54 robust DEGs received the recognition. Lymphocyte-specific protein 1 (LSP1), Granulysin (GNLY), and Mesenchymal homobox 2 (MEOX2) (AUC = 0.955) were regarded as RA’s diagnostic markers and showed their statistically significant difference by qRT-PCR. As indicated from the immune cell infiltration analysis, resting NK cells, neutrophils, activated NK cells, T cells CD8, memory B cells, and M0 macrophages may be involved in the development of RA. Additionally, all diagnostic signatures might be different degrees of correlation with immune cells.ConclusionsIn conclusion, LSP1, GNLY, and MEOX2 are likely to be available in terms of diagnosing and treating RA, and the infiltration of immune cells mentioned above may critically impact RA development and occurrence.
Low GNG12 Expression Predicts Adverse Outcomes: A Potential Therapeutic Target for Osteosarcoma
Authors: Yuan Jinghong , Yuan Zhao , Ye Aifang , Wu Tianlong , Jia Jingyu , Guo Jia , Zhang Jian , Li Tao , Cheng Xigao 
Published: October 2021

BackgroundG protein subunit gamma 12 (GNG12) is observed in some types of cancer, but its role in osteosarcoma is unknown. This study hypothesized that GNG12 may be a potential biomarker and therapeutic target. We aimed to identify an association between GNG12 and osteosarcoma based on the Gene Expression Omnibus and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) databases.MethodsOsteosarcoma samples in GSE42352 and TARGET database were selected as the test cohorts. As the external validation cohort, 78 osteosarcoma specimens from The Second Affiliated Hospital of Nanchang University were collected. Patients with osteosarcoma were divided into high and low GNG12 mRNA-expression groups; differentially expressed genes were identified as GNG12-related genes. The biological function of GNG12 was annotated using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and immune infiltration analysis. Gene expression correlation analysis and competing endogenous RNA regulatory network construction were used to determine potential biological regulatory relationships of GNG12. Overall survival, Kaplan–Meier analysis, and log-rank tests were calculated to determine GNG12 reliability in predicting survival prognosis.ResultsGNG12 expression decreased in osteosarcoma samples. GNG12 was a highly effective biomarker for osteosarcoma [area under the receiver operating characteristic (ROC) curve (AUC) = 0.920], and the results of our Kaplan–Meier analysis indicated that overall survival and progression-free survival differed significantly between low and high GNG-expression group (p &lt; 0.05). Functional analyses indicated that GNG12 may promote osteosarcoma through regulating the endoplasmic reticulum. Expression correlation analysis and competing endogenous RNA network construction showed that HOTTIP/miR-27a-3p may regulate GNG12 expression. Furthermore, the subunit suppresses adaptive immunity via inhibiting M1 and M2 macrophage infiltration. GNG12 was inhibited in metastatic osteosarcoma compared with non-metastatic osteosarcoma, and its expression predicted survival of patients (1, 3, and 5-year AUCs were 0.961, 0.826, and 0.808, respectively).ConclusionThis study identified GNG12 as a potential biomarker for osteosarcoma prognosis, highlighting its potential as an immunotherapy target.
Potential Value of TNF-α (–376 G/A) Polymorphism and Cystatin C (CysC) in the Diagnosis of Sepsis Associated Acute Kidney Injury (S-AK I) and Prediction of Mortality in Critically Ill patients
Authors: Al-Amodi Hiba S , Abdelsattar Shimaa , Kasemy Zeinab A. , Bedair Hanan M. , Elbarbary Hany S. , Kamel Hala F. M. 
Published: October 2021

Sepsis Associated Kidney Injury represents a major health concern as it is frequently associated with increased risk of mortality and morbidity. We aimed to evaluate the potential value of TNF-α (−376 G/A) and cystatin C in the diagnosis of S-AKI and prediction of mortality in critically ill patients. This study included 200 critically ill patients and 200 healthy controls. Patients were categorized into 116 with acute septic shock and 84 with sepsis, from which 142 (71%) developed S-AKI. Genotyping of TNF-α (−376 G/A) was performed by RT-PCR and serum CysC was assessed by Enzyme Linked Immunosorbent Assay. Our results showed a highly significant difference in the genotype frequencies of TNF-α (−376 G/A) SNP between S-AKI and non-AKI patients (p&lt; 0.001). Additionally, sCysC levels were significantly higher in the S-AKI group (p= 0.011). The combination of both sCysC and TNF-α (−376 G/A) together had a better diagnostic ability for S-AKI than sCysC alone (AUC = 0.610, 0.838, respectively). Both GA and AA genotypes were independent predictors of S-AKI (p= &lt; 0.001,p= 0.002 respectively). Additionally, sCysC was significantly associated with the risk of S-AKI development (Odds Ratio = 1.111). Both genotypes and sCysC were significant predictors of non-survival (p&lt; 0.001), suggesting their potential role in the diagnosis of S-AKI and prediction of mortality.
Altered Volume and Structural Connectivity of the Hippocampus in Alzheimer’s Disease and Amnestic Mild Cognitive Impairment
Authors: Feng Feng , Huang Weijie , Meng Qingqing , Hao Weijun , Yao Hongxiang , Zhou Bo , Guo Yan’e , Zhao Cui , An Ningyu , Wang Luning , Huang Xusheng , Zhang Xi , Shu Ni 
Published: October 2021

Background: Hippocampal atrophy is a characteristic of Alzheimer’s disease (AD). However, alterations in structural connectivity (number of connecting fibers) between the hippocampus and whole brain regions due to hippocampal atrophy remain largely unknown in AD and its prodromal stage, amnestic mild cognitive impairment (aMCI).Methods: We collected high-resolution structural MRI (sMRI) and diffusion tensor imaging (DTI) data from 36 AD patients, 30 aMCI patients, and 41 normal control (NC) subjects. First, the volume and structural connectivity of the bilateral hippocampi were compared among the three groups. Second, correlations between volume and structural connectivity in the ipsilateral hippocampus were further analyzed. Finally, classification ability by hippocampal volume, its structural connectivity, and their combination were evaluated.Results: Although the volume and structural connectivity of the bilateral hippocampi were decreased in patients with AD and aMCI, only hippocampal volume correlated with neuropsychological test scores. However, positive correlations between hippocampal volume and ipsilateral structural connectivity were displayed in patients with AD and aMCI. Furthermore, classification accuracy (ACC) was higher in AD vs. aMCI and aMCI vs. NC by the combination of hippocampal volume and structural connectivity than by a single parameter. The highest values of the area under the receiver operating characteristic (ROC) curve (AUC) in every two groups were all obtained by combining hippocampal volume and structural connectivity.Conclusions: Our results showed that the combination of hippocampal volume and structural connectivity (number of connecting fibers) is a new perspective for the discrimination of AD and aMCI.
Role of Blood Neurofilaments in the Prognosis of Amyotrophic Lateral Sclerosis: A Meta-Analysis
Authors: Zhou Yan-ni , Chen You-hong , Dong Si-qi , Yang Wen-bo , Qian Ting , Liu Xiao-ni , Cheng Qi , Wang Jiu-cun , Chen Xiang-jun 
Published: October 2021

Background: Neurofilaments in cerebrospinal fluid (CSF) and in blood are considered promising biomarkers of amyotrophic lateral sclerosis (ALS) because their levels can be significantly increased in patients with ALS. However, the roles of neurofilaments, especially blood neurofilaments, in the prognosis of ALS are inconsistent. We performed a meta-analysis to explore the prognostic roles of blood neurofilaments in ALS patients.Methods: We searched all relevant studies on the relationship between blood neurofilament levels and the prognosis of ALS patients in PubMed, Embase, Scopus, and Web of Science before February 2, 2021. The quality of the included articles was assessed using the Quality in Prognosis Studies (QUIPS) scale, and R (version 4.02) was used for statistical analysis.Results: Fourteen articles were selected, covering 1,619 ALS patients. The results showed that higher blood neurofilament light chain (NfL) levels in ALS patients were associated with a higher risk of death [medium vs. low NfL level: HR = 2.43, 95% CI (1.34–4.39), p &lt; 0.01; high vs. low NfL level: HR = 4.51, 95% CI (2.45–8.32), p &lt; 0.01]. There was a positive correlation between blood phosphorylated neurofilament heavy chain (pNfH) levels and risk of death in ALS patients [HR = 1.87, 95% CI (1.35–2.59), p &lt; 0.01]. The levels of NfL and pNfH in blood positively correlated with disease progression rate (DPR) of ALS patients [NfL: summary r = 0.53, 95% CI (0.45–0.60), p &lt; 0.01; pNfH: summary r = 0.51, 95% CI (0.24–0.71), p &lt; 0.01].Conclusion: The blood neurofilament levels can predict the prognosis of ALS patients; specifically, higher levels of blood neurofilaments are associated with a greater risk of death.
Alterations of Regional Homogeneity in Children With Congenital Sensorineural Hearing Loss: A Resting-State fMRI Study
Authors: Guo Pingping , Lang Siyuan , Jiang Muliang , Wang Yifeng , Zeng Zisan , Wen Zuguang , Liu Yikang , Chen Bihong T. 
Published: October 2021

Background: Brain functional alterations have been observed in children with congenital sensorineural hearing loss (CSNHL). The purpose of this study was to assess the alterations of regional homogeneity in children with CSNHL.Methods: Forty-five children with CSNHL and 20 healthy controls were enrolled into this study. Brain resting-state functional MRI (rs-fMRI) for regional homogeneity including the Kendall coefficient consistency (KCC-ReHo) and the coherence-based parameter (Cohe-ReHo) was analyzed and compared between the two groups, i.e., the CSNHL group and the healthy control group.Results: Compared to the healthy controls, children with CSNHL showed increased Cohe-ReHo values in left calcarine and decreased values in bilateral ventrolateral prefrontal cortex (VLPFC) and right dorsolateral prefrontal cortex (DLPFC). Children with CSNHL also had increased KCC-ReHo values in the left calcarine, cuneus, precentral gyrus, and right superior parietal lobule (SPL) and decreased values in the left VLPFC and right DLPFC. Correlations were detected between the ReHo values and age of the children with CSNHL. There were positive correlations between ReHo values in the pre-cuneus/pre-frontal cortex and age (p &lt; 0.05). There were negative correlations between ReHo values in bilateral temporal lobes, fusiform gyrus, parahippocampal gyrus and precentral gyrus, and age (p &lt; 0.05).Conclusion: Children with CSNHL had RoHo alterations in the auditory, visual, motor, and other related brain cortices as compared to the healthy controls with normal hearing. There were significant correlations between ReHo values and age in brain regions involved in information integration and processing. Our study showed promising data using rs-fMRI ReHo parameters to assess brain functional alterations in children with CSNHL.
RETRACTED: Circular RNA Circ-0002570 Accelerates Cancer Progression by Regulating VCAN via MiR-587 in Gastric Cancer
Authors: Yang Lei , Zhou Yong-ning , Zeng Miao-miao , Zhou Nan , Wang Bin-sheng , Li Bo , Zhu Xiao-liang , Guan Quan-lin , Chai Chen 
Published: October 2021

BackgroundCircular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression.MethodsCircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells via qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored in vitro and in vivo. Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments.ResultsCirc-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth in vivo. Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression.ConclusionThe circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC.
Identification of a Nuclear Mitochondrial-Related Multi-Genes Signature to Predict the Prognosis of Bladder Cancer
Authors: Jiang Xuewen , Xia Yangyang , Meng Hui , Liu Yaxiao , Cui Jianfeng , Huang Huangwei , Yin Gang , Shi Benkang 
Published: October 2021

IntroductionBladder cancer (BC) is one of the most prevalent urinary cancers, and its management is still a problem causing recurrence and progression, elevating mortality.Materials and MethodsWe aimed at the nuclear mitochondria-related genes (MTRGs), collected from the MITOMAP: A Human Mitochondrial Genome Database. Meanwhile, the expression profiles and clinical information of BC were downloaded from the Cancer Genome Atlas (TCGA) as a training group. The univariate, multivariate, and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a nuclear mitochondrial-related multi-genes signature and the prognostic nomogram.ResultsA total of 17 nuclear MTRGs were identified to be correlated with the overall survival (OS) of BC patients, and a nuclear MTRGs signature based on 16 genes expression was further determined by the LASSO Cox regression analysis. Based on a nuclear MTRGs scoring system, BC patients from the TCGA cohort were divided into high- and low- nuclear MTRGs score groups. Patients with a high nuclear MTRGs score exhibited a significantly poorer outcome (median OS: 92.90 vs 20.20 months, p&lt;0.0001). The nuclear MTRGs signature was further verified in three independent datasets, namely, GSE13507, GSE31684, and GSE32548, from the Gene Expression Omnibus (GEO). The BC patients with a high nuclear MTRGs score had significantly worse survival (median OS in GSE13507: 31.52 vs 98.00 months, p&lt;0.05; GSE31684: 32.85 months vs unreached, p&lt;0.05; GSE32548: unreached vs unreached, p&lt;0.05). Furthermore, muscle-invasive bladder cancer (MIBC) patients had a significantly higher nuclear MTRGs score (p&lt;0.05) than non-muscle-invasive bladder cancer (NMIBC) patients. The integrated signature outperformed each involved MTRG. In addition, a nuclear MTRGs-based nomogram was constructed as a novel prediction prognosis model, whose AUC values for OS at 1, 3, 5 years were 0.76, 0.75, and 0.75, respectively, showing the prognostic nomogram had good and stable predicting ability. Enrichment analyses of the hallmark gene set and KEGG pathway revealed that the E2F targets, G2M checkpoint pathways, and cell cycle had influences on the survival of BC patients. Furthermore, the analysis of tumor microenvironment indicated more CD8+ T cells and higher immune score in patients with high nuclear MTRGs score, which might confer sensitivity to immune checkpoint inhibitors.ConclusionsNot only could the signature and prognostic nomogram predict the prognosis of BC, but it also had potential therapeutic guidance.
Can the Childhood Physical Activity Questionnaire Be Used to Identify Physical Activity Levels in Children With Asthma?
Authors: van der Kamp Mattienne R. , Nieuwdorp Bram W. , Thio Boony J. , Tabak Monique , Kamps Arvid W. A. , Hermens Hermie J. , Driessen Jean M. M. 
Published: October 2021

Objective: Children with asthma who are physically active have a better quality of life, emphasizing the importance of activity monitoring and promotion in daily life. The validity of self-reported activity measurements has been questioned in pediatric populations. In this study, we aim to compare the Physical Activity Questionnaire for Children (PAQ-C) with objectively measured PA using accelerometry.Design: In this comparison study, the pooled dataset of two cross-sectional studies was used, which prospectively home-monitored PA using the alternative self-report PAQ-C questionnaire as well as with the criterion standard accelerometry (Actigraph wGT3X-BT and GT1M).Participants:Ninety children with pediatrician-diagnosed asthma participated in the study.Main Outcome Measures:Correlation coefficients were calculated to determine the relation between the PAQ-C and accelerometer data. The predictive value of the PAQ-C in differentiating between achieving and failing the recommended daily level of moderate-to-vigorous activity (MVPA) was evaluated with receiver operator characteristic (ROC) analysis.Results: The results showed weak to moderate correlations of the PAQ-C with the accelerometer data (r = 0.29–0.47). A PAQ-C cutoff of 3.09 showed the best performance on predicting whether the recommended level of MVPA was achieved. With this cutoff, 21 of the 39 children that did achieve their daily MVPA level (53.8% sensitivity) and 33 of the 46 children that did fail their daily MVPA level (71.7% specificity) were correctly classified. A PAQ-C score of 3.5 revealed a negative predictive value of 100% for assessing physical inactivity.Conclusion: This study revealed a weak relation between the PAQ-C and PA assessed with accelerometry. However, a PAQ-C score of 3.5 or higher might be used as a low-cost and easy-to-use PA screening tool for ruling out physical inactivity in a portion of the pediatric asthma population.Clinical Trial Registration: Netherlands Trial Register: Trial NL6087.
Case Report: Subtherapeutic Vancomycin and Meropenem Concentrations due to Augmented Renal Clearance in a Patient With Intracranial Infection Caused by Streptococcus intermedius
Authors: Fransson Marcus , Helldén Anders , Östholm Balkhed Åse , Nezirević Dernroth Dženeta , Ha Maria , Haglund Mats , Milos Peter , Hanberger Håkan , Kågedal Bertil 
Published: October 2021

Streptococcus intermedius occasionally causes brain abscesses that can be life-threatening, requiring prompt antibiotic and neurosurgical treatment. The source is often dental, and it may spread to the eye or the brain parenchyma. We report the case of a 34-year-old man with signs of apical periodontitis, endophthalmitis, and multiple brain abscesses caused by Streptococcus intermedius. Initial treatment with meropenem and vancomycin was unsuccessful due to subtherapeutic concentrations, despite recommended dosages. Adequate concentrations could be reached only after increasing the dose of meropenem to 16 g/day and vancomycin to 1.5 g × 4. The patient exhibited high creatinine clearance consistent with augmented renal clearance, although iohexol and cystatin C clearances were normal. Plasma free vancomycin clearance followed that of creatinine. A one-day dose of trimethoprim–sulfamethoxazole led to an increase in serum creatinine and a decrease in both creatinine and urea clearances. These results indicate that increased tubular secretion of the drugs was the cause of suboptimal antibiotic treatment. The patient eventually recovered, but his left eye needed enucleation. Our case illustrates that augmented renal clearance can jeopardize the treatment of serious bacterial infections and that high doses of antibiotics are needed to achieve therapeutic concentrations in such cases. The mechanisms for regulation of kidney tubular transporters of creatinine, urea, vancomycin, and meropenem in critically ill patients are discussed.
TeleParallax: Low-Motion-Blur Stereoscopic System With Correct Interpupillary Distance for 3D Head Rotations
Authors: Amemiya Tomohiro , Aoyama Kazuma , Hirose Michitaka 
Published: October 2021

Binocular parallax provides cues for depth information when a scene is viewed with both eyes. In visual telepresence systems, stereo cameras are commonly used to simulate human eyes. However, motion blur occurs when these cameras are rotated quickly. The use of omnidirectional cameras can reduce the motion blur, but does not provide the correct interpupillary distance (IPD) when viewers tilt or turn their heads sideways. We propose a method called TeleParallax, in which two omnidirectional cameras are separated by the IPD and the direction of the lenses are kept constant in world coordinates by robotic arms during three-dimensional head rotations. TeleParallax can suppress the increase in image buffering during head rotations because each camera can capture an omnidirectional image with the lens direction fixed. We conducted three user studies to evaluate the perceptual effect of head tilt, eye asynchrony, and delays in IPD correction for a particular rotation. The results indicate that TeleParallax can provide depth perception that is independent of the head movement with less visual discomfort. Although the results show that the users were sensitive to the asynchrony between their eyes and to camera motion during IPDs, they retained the feeling of depth perception within interocular delays of 70 ms and motion velocity of 75°/s. These results imply that TeleParallax has remarkable potential for visual telepresence systems.