bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis of N6-Methyladenosine Regulators in the Subcluster Classification and Drug Candidates Prediction of Severe Obstructive Sleep Apnea
Authors: Li Niannian , Gao Zhenfei , Shen Jinhong , Liu Yuenan , Wu Kejia , Yang Jundong , Wang Shengming , Zhang Xiaoman , Zhu Yaxin , Zhu Jingyu , Guan Jian , Liu Feng , Yin Shankai 
Published: April 2022

Background: Obstructive sleep apnea (OSA) is the most common type of sleep apnea that impacts the development or progression of many other disorders. Abnormal expression of N6-methyladenosine (m6A) RNA modification regulators have been found relating to a variety of human diseases. However, it is not yet known if m6A regulators are involved in the occurrence and development of OSA. Herein, we aim to explore the impact of m6A modification in severe OSA.Methods: We detected the differentially expressed m6A regulators in severe OSA microarray dataset GSE135917. The least absolute shrinkage and selection operator (LASSO) and support vector machines (SVM) were used to identify the severe OSA-related m6A regulators. Receiver operating characteristic (ROC) curves were performed to screen and verify the diagnostic markers. Consensus clustering algorithm was used to identify m6A patterns. And then, we explored the character of immune microenvironment, molecular functionals, protein-protein interaction networks and miRNA-TF coregulatory networks for each subcluster. Finally, the Connectivity Map (CMap) tools were used to tailor customized treatment strategies for different severe OSA subclusters. An independent dataset GSE38792 was used for validation.Results: We found that HNRNPA2B1, KIAA1429, ALKBH5, YTHDF2, FMR1, IGF2BP1 and IGF2BP3 were dysregulated in severe OSA patients. Among them, IGF2BP3 has a high diagnostic value in both independent datasets. Furthermore, severe OSA patients can be accurately classified into three m6A patterns (subcluster1, subcluster2, subcluster3). The immune response in subcluster3 was more active because it has high M0 Macrophages and M2 Macrophages infiltration and up-regulated human leukocyte antigens (HLAs) expression. Functional analysis showed that representative genes for each subcluster in severe OSA were assigned to histone methyltransferase, ATP synthesis coupled electron transport, virus replication, RNA catabolic, multiple neurodegeneration diseases pathway, et al. Moreover, our finding demonstrated cyclooxygenase inhibitors, several of adrenergic receptor antagonists and histamine receptor antagonists might have a therapeutic effect on severe OSA.Conclusion: Our study presents an overview of the expression pattern and crucial role of m6A regulators in severe OSA, which may provide critical insights for future research and help guide appropriate prevention and treatment options.
Development and Validation of a Novel Gene Signature for Predicting the Prognosis of Idiopathic Pulmonary Fibrosis Based on Three Epithelial-Mesenchymal Transition and Immune-Related Genes
Authors: Zheng Jiafeng , Dong Hanquan , Zhang Tongqiang , Ning Jing , Xu Yongsheng , Cai Chunquan 
Published: April 2022

Background:Increasing evidence has revealed that epithelial–mesenchymal transition (EMT) and immunity play key roles in idiopathic pulmonary fibrosis (IPF). However, correlation between EMT and immune response and the prognostic significance of EMT in IPF remains unclear.Methods:Two microarray expression profiling datasets (GSE70866 and GSE28221) were downloaded from the Gene Expression Omnibus (GEO) database. EMT- and immune-related genes were identified by gene set variation analysis (GSVA) and the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the functions of these EMT- and immune-related genes. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen prognostic genes and establish a gene signature. Gene Set Enrichment Analysis (GSEA) and Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) were used to investigate the function of the EMT- and immune-related signatures and correlation between the EMT- and immune-related signatures and immune cell infiltration. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to investigate the mRNA expression of genes in the EMT- and immune-related signatures.Results:Functional enrichment analysis suggested that these genes were mainly involved in immune response. Moreover, the EMT- and immune-related signatures were constructed based on three EMT- and immune-related genes (IL1R2, S100A12, and CCL8), and the K–M and ROC curves presented that the signature could affect the prognosis of IPF patients and could predict the 1-, 2-, and 3-year survival well. Furthermore, a nomogram was developed based on the expression of IL1R2, S100A12, and CCL8, and the calibration curve showed that the nomogram could visually and accurately predict the 1-, 2-, 3-year survival of IPF patients. Finally, we further found that immune-related pathways were activated in the high-risk group of patients, and the EMT- and immune-related signatures were associated with NK cells activated, macrophages M0, dendritic cells resting, mast cells resting, and mast cells activated. qRT-PCR suggested that the mRNA expression of IL1R2, S100A12, and CCL8 was upregulated in whole blood of IPF patients compared with normal samples.Conclusion:IL1R2, S100A12, and CCL8 might play key roles in IPF by regulating immune response and could be used as prognostic biomarkers of IPF.
Roles of the m6A Modification of RNA in the Glioblastoma Microenvironment as Revealed by Single-Cell Analyses
Authors: Yuan Feng , Cai Xiangming , Cong Zixiang , Wang Yingshuai , Geng Yuanming , Aili Yiliyaer , Du Chaonan , Zhu Junhao , Yang Jin , Tang Chao , Zhang Aifeng , Zhao Sheng , Ma Chiyuan 
Published: April 2022

PurposeGlioblastoma multiforme (GBM) is a common and aggressive form of brain tumor. The N6-methyladenosine (m6A) mRNA modification plays multiple roles in many biological processes and disease states. However, the relationship between m6A modifications and the tumor microenvironment in GBM remains unclear, especially at the single-cell level.Experimental DesignSingle-cell and bulk RNA-sequencing data were acquired from the GEO and TCGA databases, respectively. We used bioinformatics and statistical tools to analyze associations between m6A regulators and multiple factors.ResultsHNRNPA2B1 and HNRNPC were extensively expressed in the GBM microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Immune-related BP terms were enriched in modules of m6A-related genes. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, CD45, and HAVCR2) correlated with that of m6A regulators. Validation experiments revealed that MDK in MK signaling network promoted migration and immunosuppressive polarization of macrophage. Expression of m6A regulators correlated with ICPs in GBM cancer cells, M2 macrophages and T/NK cells. Bulk RNA-seq analysis identified two expression patterns (low m6A/high ICP and high m6A/low ICP) with different predicted immune infiltration and responses to ICP inhibitors. A predictive nomogram model to distinguish these 2 clusters was constructed and validated with excellent performance.ConclusionAt the single-cell level, m6A modification facilitates the stemness state in GBM cancer cells and promotes an immunosuppressive microenvironment through ICPs and the GALECTIN signaling pathway network. And we also identified two m6A-ICP expression patterns. These findings could lead to novel treatment strategies for GBM patients.
Epimicrobiome Shifts With Bleaching Disease Progression in the Brown Seaweed Saccharina japonica
Authors: Ling Fan , Egan Suhelen , Zhuang Yingrui , Chang Lirong , Xiao Luyang , Yang Qin , Wang Gaoge 
Published: April 2022

Recent bacterial induced bleaching disease events of the commercially farmed brown seaweed Saccharina japonica has resulted in significant reduction in healthy sporeling supply. However, to date the host associated epimicrobial community shifts with the disease progression have not been characterized. We investigated the dynamic shifts in the composition of the epibacterial communities of S. japonica with disease progression using 16S rRNA gene amplicon sequencing. We found that the alpha diversity was significantly higher in the control group than in the infected group over disease progression (P &lt; 0.01). There was a significant shift in the composition and predicted functions of the epibacterial communities in both control and infected groups. Indicator species, belonging to Stenotrophomonas, Pseudomonas and Sphingomona were significantly higher in the control group than infected group, suggesting that these taxa are associated with healthy S. japonica. In contrast, Vibrio, Pseudoalteromonas and Colwellia were keystone taxa in the infected group at 24 h, and thus maybe considered to be the secondary opportunistic pathogens. Our study describes the changes of epibacterial communities associated with the progression of bleaching disease in S. japonica. This new information not only extends our baseline knowledge of the S. japonica epimicrobiome, but also paves the way for developing measures to mitigate disease outbreaks for the sustainable aquaculture of S. japonica.
Infrared Heating for Rapid and Localized Shape Transformations of Additively Manufactured Polymer Parts
Authors: Oh Seo-Hyeon , Goo Bona , Park Keun 
Published: April 2022

Four-dimensional (4D) printing is an advanced application of additive manufacturing which enables additional shape transformations over time in response to external stimuli. For appropriate shape transformation, dedicated materials such as shape memory polymers or 3D printers supporting multi-material printing have been used. Recently, a facile 4D printing method was developed which used a fused filament fabrication type 3D printer and a plain thermoplastic filament. This method used the anisotropic thermal deformation of the FFF-printed part to intentionally impose anisotropy by programming orthogonal printing paths, which resulted in thermoresponsive shape transformation upon a thermal stimulation. While the previous studies used convective heating as the thermal stimulus and thus required a long heating time of more than 10 min, this study uses an infrared (IR) heating to enable rapid thermoresponsive shape transformation. An infrared heating system was developed which included an optical focusing unit, a masking unit and a movable heating stage. To investigate the speed of shape transformation, IR heating was performed on a rectangular strip (60 × 6 × 1.6 mm) and the relevant shape transformation time was compared with the previous convective heating result. The shape transformation proceeded rapidly, and after 70 s formed a fully-closed circular shape, corresponding to the 1/10 reduction compared with the convection type heating (more than 13 min). The IR heating was further applied to 2D-to-3D shape transformations of 2D star-shape and flower-shape specimens. For each specimen, a profiled mask was used to selectively irradiate IR on predefined regions and thus to localize the relevant thermoresponsive shape transformation. The global and local IR irradiations were then compared in terms of heating capability and the variability in shape transformations.
Comparative Analysis of Long Non-Coding RNA Expression and Immune Response in Mild and Severe COVID-19
Authors: Zhang Yongting , Shi Fan , Wang Yuchong , Meng Yuting , Zhang Qiong , Wang Kaihang , Zeng Ping , Diao Hongyan 
Published: April 2022

Background: Coronavirus disease 2019 (COVID-19) is a worldwide emergency, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Long non-coding RNAs (lncRNAs) do not encode proteins but could participate in immune response.Methods: In our study, 39 COVID-19 patients were enrolled. The microarray of peripheral blood mononuclear cells from healthy and COVID-19 patients was applied to identify the expression profiles of lncRNAs and mRNAs. Identified differentially expressed (DE) lncRNAs were validated by qRT-PCR. Then, the lncRNA–mRNA network was constructed and visualized using Cytoscape (3.6.1) based on the Pearson correlation coefficient. The enrichment of DE mRNAs was analyzed using Metascape. The difference in frequencies of immune cells and cytokines was detected using CIBERSORT and ImmPort based on DE mRNAs.Results: All patients with COVID-19 displayed lymphopenia, especially in T cells, and hyper-inflammatory responses, including IL-6 and TNF-α. Four immune-related lncRNAs in COVID-19 were found and further validated, including AC136475.9, CATG00000032642.1, G004246, and XLOC_013290. Functional analysis enriched in downregulation of the T-cell receptor and the antigen processing and presentation as well as increased apoptotic proteins, which could lead to T-cell cytopenia. In addition, they participated in monocyte remodeling, which contributed to releasing cytokines and chemokines and then recruiting more monocytes and aggravating the clinical severity of COVID-19 patients.Conclusion: Taken together, four lncRNAs were in part of immune response in COVID-19, which was involved in the T-cell cytopenia by downregulating the antigen processing and presentation, the T-cell receptor, and an increased proportion of monocytes, with a distinct change in cytokines and chemokines.
Caveolin-1 Promoted Collateral Vessel Formation in Patients With Moyamoya Disease
Authors: Zhao Jinbing , Yu Zhiqiang , Zhang Yanping , Qiu Cheng , Zhang Guangxu , Chen Lijiu , He Shengxue , Ma Jun 
Published: April 2022

BackgroundCaveolin-1 (Cav-1) plays pivotal roles in the endothelial function and angiogenesis postischemia. Moyamoya disease (MMD) is characterized by progressive artery stenosis with unknown etiology. We aim to determine whether serum Cav-1 levels of patients with MMD were associated with collateral vessel formation after bypass surgery.MethodsWe studied serum Cav-1 levels of 130 patients with MMD (16 with RNF213 p.R4810K mutation and 114 without RNF213 p.R4810K mutation), 15 patients with acute stroke, and 33 healthy controls. Cerebral perfusion and collateral circulation were evaluated preoperation and at 6 months after operation using pseudocontinuous arterial spin labeling MRI (pCASL-MRI) and digital subtraction angiography (DSA), respectively. Endothelial expression of Cav-1 was verified in the superficial temporal artery (STA) wall of patients with MMD by immunofluorescence double staining. We also investigated whether overexpression of Cav-1 affects cell migration and tube formation using human microvascular endothelial cells (HMECs).ResultsThe serum Cav-1 level of patients with MMD intermediated between the stroke group and healthy controls and it was enhanced after the bypass surgery (681.87 ± 311.63 vs. 832.91 ± 464.41 pg/ml, p = 0.049). By 6 months after bypass surgery, patients with MMD with better collateral compensation manifested higher postoperative/preoperative Cav-1 ratio (rCav-1) than bad compensation patients. Consistently, cerebral blood flow (CBF) determined by pCASL-MRI (nCBFMCA ratio) was positively in line with rCav-1 ratio (r = 0.8615, p &lt; 0.0001). Cav-1 was expressed in the endothelial cells of the STA vessels of patients with MMD. Overexpression of Cav-1 by plasmid transfection in HMECs promoted tube formation and cell migration.ConclusionThis study indicated that Cav-1 may be a potential driver to promote angiogenesis and collateral formation after bypass surgery in patients with MMD, providing a better understanding of MMD pathophysiology and potential non-surgical targets of MMD.
Children With PANS May Manifest POTS
Authors: Chan Avis , Gao Jaynelle , Houston Madison , Willett Theresa , Farhadian Bahare , Silverman Melissa , Tran Paula , Jaradeh Safwan , Thienemann Margo , Frankovich Jennifer 
Published: April 2022

ObjectivesPediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by an abrupt-onset of severe psychiatric symptoms including OCD, anxiety, cognitive difficulties, and sleep issues which is thought to be a post-infection brain inflammatory disorder. We observed postural orthostatic tachycardia syndrome (POTS) which resolved with immunomodulation in a patient with Pediatric acute-onset neuropsychiatric syndrome (PANS). Here, we aim to present a case of POTS and to examine the prevalence of (POTS) in our PANS cohort, and compare the clinical characteristics of patients with and without POTS.Study DesignWe conducted this cohort study of patients meeting PANS criteria who had at least three clinic visits during the study period. We included data from prospectively collected questionnaires and medical record review. We present a case followed by statistical comparisons within our cohort and a Kaplan-Meier analysis to determine the time-dependent risk of a POTS diagnosis.ResultsOur study included 204 patients: mean age of PANS onset was 8.6 years, male sex (60%), non-Hispanic White (78%). Evidence of POTS was observed in 19/204 patients (9%) with 5/19 having persistent POTS defined as persistent abnormal orthostatic vitals, persistent POTS symptoms, and/or continued need for pharmacotherapy for POTS symptoms for at least 6 months). In this PANS cohort, patients with POTS were more likely to have comorbid joint hypermobility (63 vs 37%, p = 0.04), chronic fatigue (42 vs 18%, p = 0.03), and a family history of chronic fatigue, POTS, palpitations and syncope. An unadjusted logistic regression model showed that a PANS flare (abrupt neuropsychiatric deterioration) was significantly associated with an exacerbation of POTS symptoms (OR 3.3, 95% CI 1.4–7.6, p &lt; 0.01).ConclusionsOur study describes a high prevalence of POTS in patients with PANS (compared to the general population) and supports an association between POTS presentation and PANS flare within our cohort.
Diabetes: Chronic Metformin Treatment and Outcome Following Acute Stroke
Authors: Akhtar Naveed , Singh Rajvir , Kamran Saadat , Babu Blessy , Sivasankaran Shobana , Joseph Sujatha , Morgan Deborah , Shuaib Ashfaq 
Published: April 2022

AimTo evaluate if in patients with known diabetes, pretreatment metformin will lead to less severe stroke, better outcome, and lower mortality following acute stroke.MethodsThe Qatar stroke database was interrogated for stroke severity and outcome in patients with ischemic stroke. Outcome was compared in nondiabetic vs. diabetic patients and in diabetic patients on metformin vs. other hypoglycemic agents. The National Institute of Health Stroke Scale was used to measure stroke severity and 90-day modified Rankin scale (mRS) score to determine outcome following acute stroke.ResultsIn total, 4,897 acute stroke patients [nondiabetic: 2,740 (56%) and diabetic: 2,157 (44%)] were evaluated. There were no significant differences in age, risk factors, stroke severity and type, or thrombolysis between the two groups. At 90 days, mRS (shift analysis) showed significantly poor outcome in diabetic patients (p &lt; 0.001) but no differences in mortality. In the diabetic group, 1,132 patients were on metformin and 1,025 on other hypoglycemic agents. mRS shift analysis showed a significantly better outcome in metformin-treated patients (p &lt; 0.001) and lower mortality (8.1 vs. 4.6% p &lt; 0.001). Multivariate negative binomial analyses showed that the presence of diabetes negatively affected the outcome (90-day mRS) by factor 0.17 (incidence risk ratio, IRR, 1.17; CI [1.08–1.26]; p &lt; 0.001) when all independent variables were held constant. In diabetic patients, pre-stroke treatment with metformin improved the outcome (90-day mRS) by factor 0.14 (IRR 0.86 [CI 0.75–0.97] p = 0.006).ConclusionSimilar to previous reports, our study shows that diabetes adversely affects stroke outcome. The use of prior metformin is associated with better outcome in patients with ischemic stroke and results in lower mortality. The positive effects of metformin require further research to better understand its mechanism.
Trapezius Motor Evoked Potentials From Transcranial Electrical Stimulation and Transcranial Magnetic Stimulation: Reference Data, Characteristic Differences and Intradural Motor Velocities in Horses
Authors: Journée Sanne Lotte , Journée Henricus Louis , Berends Hanneke Irene , Reed Steven Michael , Bergmann Wilhelmina , de Bruijn Cornelis Marinus , Delesalle Cathérine John Ghislaine 
Published: April 2022

Reason for Performing StudySo far, only transcranial motor evoked potentials (MEP) of the extensor carpi radialis and tibialis cranialis have been documented for diagnostic evaluation in horses. These allow for differentiating whether lesions are located in either the thoraco-lumbar region or in the cervical myelum and/or brain. Transcranial trapezius MEPs further enable to distinguish between spinal and supraspinal located lesions. No normative data are available. It is unclear whether transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) are interchangeable modalities.ObjectivesTo provide normative data for trapezius MEP parameters in horses for TES and TMS and to discern direct and indirect conduction routes by neurophysiological models that use anatomical geometric characteristics to relate latency times with peripheral (PCV) and central conduction velocities (CCV).MethodsTranscranial electrical stimulation-induced trapezius MEPs were obtained from twelve horses. TES and TMS-MEPs (subgroup 5 horses) were compared intra-individually. Trapezius MEPs were measured bilaterally twice at 5 intensity steps. Motoneurons were localized using nerve conduction models of the cervical and spinal accessory nerves (SAN). Predicted CCVs were verified by multifidus MEP data from two horses referred for neurophysiological assessment.ResultsMean MEP latencies revealed for TES: 13.5 (11.1–16.0)ms and TMS: 19.7 (12–29.5)ms, comprising ∼100% direct routes and for TMS mixed direct/indirect routes of L:23/50; R:14/50. Left/right latency decreases over 10 &gt; 50 V for TES were: –1.4/–1.8 ms and over 10 &gt; 50% for TMS: –1.7/–3.5 ms. Direct route TMS-TES latency differences were 1.88–4.30 ms. 95% MEP amplitudes ranges for TES were: L:0.26–22 mV; R:0.5–15 mV and TMS: L:0.9 – 9.1 mV; R:1.1–7.9 mV.ConclusionThis is the first study to report normative data characterizing TES and TMS induced- trapezius MEPs in horses. The complex trapezius innervation leaves TES as the only reliable stimulation modality. Differences in latency times along the SAN route permit for estimation of the location of active motoneurons, which is of importance for clinical diagnostic purpose. SAN route lengths and latency times are governed by anatomical locations of motoneurons across C2-C5 segments. TES intensity-dependent reductions of trapezius MEP latencies are similar to limb muscles while MEP amplitudes between sides and between TES and TMS are not different. CCVs may reach 180 m/s.