bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Serum VEGF-B Level Is Associated With Renal Function Impairment in Patients With Type 2 Diabetes
Authors: Wei Yaping , Han Shiyu , Zhou Ruonan , Xu Pingyuan , Zhou Lingyan , Zhu Ziwei , Kan Yue , Yang Xiaoying , Xiang Yingying , Cao Yue , Jin Yu , Yan Jing , Yu Xizhong , Wang Xin , Shang Wenbin 
Published: March 2022

Aims/IntroductionRenal function impairment related to type 2 diabetes (T2DM) presents serious threat to public health. Previous studies suggest that vascular endothelial growth factor-B (VEGF-B) might contribute to renal injury. Therefore, this study investigated the association of serum VEGF-B level with the risk of renal function impairment in T2DM patients.Materials and MethodsSerum VEGF-B levels were measured in 213 patients with type 2 diabetes and 31 healthy participants. Participants with type 2 diabetes were further divided into a group of 112 participants with eGFR&lt;90 mL/min/1.73m2 and 101 participants with eGFR≥ 90 mL/min/1.73m2. Clinical data were collected, and a binary logistic regression model was employed to test the association between potential predictors and eGFR.ResultsSerum VEGF-B levels evaluated in type 2 diabetes patients compared with healthy controls. In patients with type 2 diabetes, serum VEGF-B level was positively correlated with triglyceride, serum creatinine and cystatin C while negatively correlated with HDL-C and eGFR. Binary logistic regression showed that serum VEGF-B level was an independent risk factor of eGFR&lt;90 mL/min/1.73m2.ConclusionsSerum VEGF-B level is associated with renal function impairment in patients with type 2 diabetes and may be a potential drug target for diabetic kidney disease.
Integrated Analysis of Competitive Endogenous RNA Networks in Acute Ischemic Stroke
Authors: Wu Zongkai , Wei Wanyi , Fan Hongzhen , Gu Yongsheng , Li Litao , Wang Hebo 
Published: March 2022

Background: Acute ischemic stroke (AIS) is a severe neurological disease with complex pathophysiology, resulting in the disability and death. The goal of this study is to explore the underlying molecular mechanisms of AIS and search for new potential biomarkers and therapeutic targets.Methods: Integrative analysis of mRNA and miRNA profiles downloaded from Gene Expression Omnibus (GEO) was performed. We explored differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMirs) after AIS. Target mRNAs of DEMirs and target miRNAs of DEGs were predicted with target prediction tools, and the intersections between DEGs and target genes were determined. Subsequently, Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses, Gene set enrichment analysis (GSEA), Gene set variation analysis (GSVA), competitive endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA) network, protein–protein interaction (PPI) network, and gene transcription factors (TFs) network analyses were performed to identify hub genes and associated pathways. Furthermore, we obtained AIS samples with evaluation of immune cell infiltration and used CIBERSORT to determine the relationship between the expression of hub genes and infiltrating immune cells. Finally, we used the Genomics of Drug Sensitivity in Cancer (GDSC) database to predict the effect of the identified targets on drug sensitivity.Result: We identified 293 DEGs and 26 DEMirs associated with AIS. DEGs were found to be mainly enriched in inflammation and immune-related signaling pathways through enrichment analysis. The ceRNA network included nine lncRNAs, 13 miRNAs, and 21 mRNAs. We used the criterion AUC &gt;0.8, to screen a 3-gene signature (FBL, RPS3, and RPS15) and the aberrantly expressed miRNAs (hsa-miR-125a-5p, hsa-miR-125b-5p, hsa-miR-148b-3p, and hsa-miR-143-3p) in AIS, which were verified by a method of quantitative PCR (qPCR) in HT22 cells. T cells CD8, B cells naïve, and activated NK cells had statistical increased in number compared with the acute cerebral infarction group. By predicting the IC50 of the patient to the drug, AZD0530, Z.LLNle.CHO and NSC-87877 with significant differences between the groups were screened out. AIS demonstrated heterogeneity in immune infiltrates that correlated with the occurrence and development of diseases.Conclusion: These findings may contribute to a better understanding of the molecular mechanisms of AIS and provide the basis for the development of novel treatment targets in AIS.
Comparative Chloroplast Genomics and Phylogenetic Analysis of Thuniopsis and Closely Related Genera within Coelogyninae (Orchidaceae)
Authors: Li Lin , Wu Qiuping , Fang Lin , Wu Kunlin , Li Mingzhi , Zeng Songjun 
Published: March 2022

The genusThuniopsiswas recently proposed for a rare orchid speciesT. cleistogamaformerly classified in the genusThunia. The relationships betweenThuniopsisand its related genera have not yet been conclusively resolved. Recognition of the genus provides a new perspective to illustrate the morphological diversity and plastome evolution within Coelogyninae. In this study, we sequenced and assembled complete chloroplast (cp) genomes for three accessions ofThuniopsis cleistogamaand two accessions ofThunia alba.A total of 135 genes were annotated for each cp genome, including 89 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The ENC-plot and neutrality plot analyses revealed that natural selection dominated over mutation pressure in their evolutionary process. Specially, we found that selection played a vital role in shaping the codon usage inThunia albacp genome. General characteristics of the cp genomes were further analyzed and compared with those published plastomes of four other related species. Despite the conserved organization and structure, the whole individual cp genome size ranged from 158,394 bp to 159,950 bp. In all the examined plastomes, sequences in the inverted repeat (IR) regions were more conserved than those in the small single copy (SSC) and large single copy (LSC) regions. However, close examination identified contraction and expansion of the IR/SSC boundary regions, which might be the main reason for the cp genome size variation. Our comparative analysis of the cp genomes revealed that single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) provided valuable information for identifying genetic variations within and among genera. Furthermore, sequence variations in the protein-coding regions were more conserved than those in the non-coding regions. We selected eight divergence hotspots with nucleotide sequence diversities (Pivalues) higher than 0.08. Most of these polymorphisms were located in the intergenic regions. Phylogenomic analyses recovered largely congruent relationships among major clades and strongly supported the monophyly ofThuniopsis. The results obtained in this study can improve our understanding of the classification of this enigmatic genus. The chloroplast genomic data presented here provide valuable insights into the phylogeny and evolutionary patterns of the Coelogyninae as well as the orchids as a whole.
Effects of Luteinizing Hormone Releasing Hormone A2 on Gonad Development in Juvenile Amur Sturgeon, Acipenser schrenckii, Revealed by Transcriptome Profiling Analysis
Authors: Lv Weihua , Jin Shubo , Cao Dingchen , Wang Nianmin , Jin Xing , Zhang Ying 
Published: March 2022

Acipenser schrenckii is an economically important aquatic species whose gonads require particularly long times to reach sexual maturity. Luteinizing hormone plays important roles in gonad development, and luteinizing hormone releasing hormone A2 (LH-A2) is used as an oxytocin to promote ovulation in aquaculture of A. schrenckii. In this study, we aimed to determine the effects of LH-A2 on gonad development in juvenile A. schrenckii through transcriptome profiling analysis of the pituitary and gonads after LH-A2 treatment at a dose of 3 μg/kg. The 17β-estradiol (E2) levels gradually increased with LH-A2 treatment time, and significantly differed from those of the control group on days 5 and 7 (p &lt; 0.01). However, the content of testosterone (Testo) gradually decreased with LH-A2 treatment time and showed significant differences on day 3 (p &lt; 0.05), and on days 5 and 7 (p &lt; 0.01), compared to those in the control group. Thus, LH-A2 promotes the secretion of E2 and inhibits the secretion of Testo. Transcriptome profiling analysis revealed a total of 2,883 and 8,476 differentially expressed genes (DEGs) in the pituitary and gonads, respectively, thus indicating that LH-A2 has more regulatory effects on the gonads than the pituitary in A. schrenckii. Signal transduction, global and overview maps, immune system, endocrine system and lipid metabolism were the main enriched metabolic pathways in both the pituitary and gonads. Sixteen important genes were selected from these metabolic pathways. Seven genes were co-DEGs enriched in both signal transduction and endocrine system metabolic pathways. The other co-DEGs were selected from the immune system and lipid metabolism metabolic pathways, and showed mRNA expression changes of &gt;7.0. The expression of five DEGs throughout LH-A2 treatment was verified to show the same patterns of change as those observed with RNA-seq, indicating the accuracy of the RNA-seq in this study. Our findings provide valuable evidence of the regulation of gonad development of juvenile A. schrenckii by LH-A2 and may enable the establishment of artificial techniques to regulate gonad development in this species.
SUMOylation Pattern Predicts Prognosis and Indicates Tumor Microenvironment Infiltration Characterization in Bladder Cancer
Authors: Xia Qi-Dong , Sun Jian-Xuan , Xun Yang , Xiao Jun , Liu Chen-Qian , Xu Jin-Zhou , An Ye , Xu Meng-Yao , Liu Zheng , Wang Shao-Gang , Hu Jia 
Published: March 2022

BackgroundSUMOylation is an important component of post-translational protein modifications (PTMs), and bladder cancer (BCa) is the ninth most common cancer around the world. But the comprehensive role of SUMOylation in shaping tumor microenvironment (TME) and influencing tumor clinicopathological features and also the prognosis of patients remains unclear.MethodsUsing the data downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we comprehensively evaluated the SUMOylation patterns of 570 bladder cancer samples, and systematically correlated these SUMOylation patterns with TME immune cell infiltrating characteristics. The SUMO score was constructed to quantify SUMOylation patterns of individuals using principal component analysis (PCA) algorithms.ResultsTwo distinct SUMOylation patterns and gene clusters were finally determined. Significant differences in the prognosis of patients were found among two different SUMOylation patterns and gene clusters, so were in the mRNA transcriptome and the landscape of TME immune cell infiltration. We also established a set of scoring system named SUMO score to quantify the SUMOylation pattern of individuals with BCa, which was discovered to be tightly connected with tumor clinicopathological characteristics and could predict the prognosis of patients with BCa. Moreover, SUMO score was a considerable predictive indicator for the survival outcome independent of tumor mutation burden (TMB) and low SUMO score was related to better response to immunotherapy using PD-1 blockade. We also found that there existed a significant relationship between sensitivity to commonly used chemotherapy drugs and SUMO score. Finally, a nomograph based on five features, namely, SUMO score, age, gender, T category, and M category was constructed to predict the survival probability of patients with BCa in 1, 3, and 5 years, respectively.ConclusionsOur work demonstrated and overviewed the complicated regulation mechanisms of SUMOylation in bladder cancer, and better understanding and evaluating SUMOylation patterns could be helpful in guiding clinical therapeutic strategy and improving the prognosis of patients with BCa.
Computed Tomography Imaging-Based Radiogenomics Analysis Reveals Hypoxia Patterns and Immunological Characteristics in Ovarian Cancer
Authors: Feng Songwei , Xia Tianyi , Ge Yu , Zhang Ke , Ji Xuan , Luo Shanhui , Shen Yang 
Published: March 2022

PurposeThe hypoxic microenvironment is involved in the tumorigenesis of ovarian cancer (OC). Therefore, we aim to develop a non-invasive radiogenomics approach to identify a hypoxia pattern with potential application in patient prognostication.MethodsSpecific hypoxia-related genes (sHRGs) were identified based on RNA-seq of OC cell lines cultured with different oxygen conditions. Meanwhile, multiple hypoxia-related subtypes were identified by unsupervised consensus analysis and LASSO–Cox regression analysis. Subsequently, diversified bioinformatics algorithms were used to explore the immune microenvironment, prognosis, biological pathway alteration, and drug sensitivity among different subtypes. Finally, optimal radiogenomics biomarkers for predicting the risk status of patients were developed by machine learning algorithms.ResultsOne hundred forty sHRGs and three types of hypoxia-related subtypes were identified. Among them, hypoxia-cluster-B, gene-cluster-B, and high-risk subtypes had poor survival outcomes. The subtypes were closely related to each other, and hypoxia-cluster-B and gene-cluster-B had higher hypoxia risk scores. Notably, the low-risk subtype had an active immune microenvironment and may benefit from immunotherapy. Finally, a four-feature radiogenomics model was constructed to reveal hypoxia risk status, and the model achieved area under the curve (AUC) values of 0.900 and 0.703 for the training and testing cohorts, respectively.ConclusionAs a non-invasive approach, computed tomography-based radiogenomics biomarkers may enable the pretreatment prediction of the hypoxia pattern, prognosis, therapeutic effect, and immune microenvironment in patients with OC.
Correlation Analysis of Plasma Myeloperoxidase Level With Global Registry of Acute Coronary Events Score and Prognosis in Patients With Acute Non-ST-Segment Elevation Myocardial Infarction
Authors: Zhang Nan , Wang Jing-Xian , Wu Xiao-Yuan , Cui Yan , Zou Zhong-He , Liu Yin , Gao Jing 
Published: March 2022

BackgroundMyeloperoxidase (MPO) and global registry of acute coronary events (GRACE) risk scores were independently used to predict adverse outcomes in patients with acute coronary syndrome (ACS). However, the relationship between MPO level and GRACE score, and whether the combination of MPO and GRACE can better predict major adverse cardiovascular events (MACEs) in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI), have not been previously investigated.MethodsA prospective cohort of 271 consecutive patients with NSTEMI were enrolled in this study. Plasma MPO levels were measured by ELISA. Baseline demographic and clinical information was collected, and GRACE scores were calculated at admission. The correlation between MPO and MACEs was evaluated with the GRACE score during a 1-year follow-up.ResultsThe results showed that plasma MPO level was correlated with inflammatory indices (including high-sensitivity C-reactive protein (hs-CRP), leukocyte count, neutrophil count, and fibrinogen), N-terminal pro-B type natriuretic peptide (NT-proBNP), and hypersensitive troponin T (hsTNT) levels (All p-values &lt; 0.05), and there was a statistically significant correlation between plasma MPO level and GRACE score (r = 0.22, p &lt; 0.001). The Kaplan-Meier curves showed that patients with higher MPO levels had lower event-free survival (Log-rank P &lt; 0.001). The multivariate Cox model showed MPO was an independent risk factor for 1-year MACEs in patients with NSTEMI (HR: 3.85, 95% CI: 1.4–10.6, p = 0.009). Subgroup analysis showed that MPO was a strong prognostic biomarker, and its prognostic value was more significant in patients with age &gt;65 years and N-terminal pro-B type natriuretic peptide (NT-proBNP) level &gt;1,000 pg/ml. For high-risk patients with GRACE scores, a higher level of MPO has a higher prognostic value.ConclusionElevated plasma MPO levels are associated with high inflammatory status and GRACE scores in patients with NSTEMI. For high-risk patients with GRACE scores, higher MPO levels were more predictive of future MACEs.
Medication Errors and Type 2 Diabetes Management: A Qualitative Exploration of Physicians' Perceptions, Experiences and Expectations From Quetta City, Pakistan
Authors: Habib Muhammad Kashif , Khan Muhammad Naeem , Sadiq Abdul , Iqbal Qaiser , Raziq Abdul , Ahmad Nafees , Iqbal Zaffar , Haider Sajjad , Anwar Muhammad , Khilji Fazal ur Rehman , Saleem Fahad , Khan Amer Hayat 
Published: March 2022

BackgroundType 2 Diabetes-related medication errors are frequently reported from the hospitals and consequently are of major concern. However, such reports are insufficient when developing healthcare settings are pursued in literature. Keeping this inadequacy in mind, we therefore aimed to explore physicians' perceptions, experiences and expectations of medication errors when managing patients with Type 2 Diabetes Mellitus.MethodsA qualitative design was adopted. By using a semi-structured interview guide through the phenomenology-based approach, in-depth, face-to-face interviews were conducted. Physicians practicing at the medicine ward of Sandeman Provincial Hospital, Quetta, were purposively approached for the study. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework.ResultsAlthough the saturation was reached at the 13th interview, we conducted additional two interviews to ensure the saturation. Fifteen physicians were interviewed, and thematic content analysis revealed six themes and nine subthemes. Mixed conceptualization and characterization of medication errors were identified. Medication errors were encountered by all physicians however poor understanding of the system, deficiency of logistics and materials were rated as barriers in reporting medication errors. Among contributors of medication errors, physicians themselves as well as dispensing and patient-related factors were identified. Physicians suggested targeted training sessions on medication error-related guidelines and reporting system. Parallel, establishment of an independent unit, involving the pharmacists, and strict supervision of paramedics to minimize medication errors was also acknowledged during data analysis.ConclusionWith a longer life expectancy and a trend of growing population, the incidences of medication errors are also expected to increase. Our study highlighted prescribing, dispensing and administration phases as contributing factors of medication errors. Although, physicians had poor understanding of medication errors and reporting system, they believed getting insights on guidelines and reporting system is essential. A review of admission and discharge reconciliation must be prioritized and a culture of teamwork, communication and learning from mistakes is needed.
Contrast Sensitivity Is Associated With Chorioretinal Thickness and Vascular Density of Eyes in Simple Early-Stage High Myopia
Authors: Liu Xinting , Wang Yanli , Ying Xiaoxiao , Zhang Fen , Huang Jing , Yu Hang , Wang Qian , Zheng Miaoran , Hou Fang , Lesmes Luis , Lu Zhong-Lin , Lu Fan , Mao Xinjie 
Published: March 2022

ObjectiveTo evaluate the contrast sensitivity function (CSF), chorioretinal thickness and vascular density as well as their relationships in subjects with simple early-stage high myopia.MethodsEighty-one young subjects were enrolled in this study. They were categorized into the simple high myopia group (sHM, n = 51) and the low-moderate myopia group (control group, n = 30). Monocular CSF under best correction was measured with the qCSF method. Retinal superficial and deep vascular density, inner and outer retinal thickness and choroidal thickness were measured using optical coherence tomography angiography.ResultsThe area under log CSF (AULCSF) and cutoff spatial frequency (Cutoff SF) of the sHM group were significantly reduced compared to those of the control group (P = 0.003 and P &lt; 0.001, respectively). The parafoveal and perifoveal retinal thickness, deep vascular density and choroidal thickness were also significantly reduced in the sHM group (all P &lt; 0.05). Multiple regression analysis revealed that AULCSF was significantly correlated with retinal deep vascular density, outer retinal thickness in the parafoveal and perifoveal areas (all P &lt; 0.05).ConclusionCompared to low to moderate myopic eyes, patients with simple high myopia have thinner retinal and choroidal thickness, lower retinal vascular density, and reduced contrast sensitivity. Moreover, the CSF was correlated with the measures of chorioretinal structure and vasculature. The results suggest that the CSF is a sensitive functional endpoint in simple early-stage high myopia.
Identification of 27 Novel Variants in Genes COL4A3, COL4A4, and COL4A5 in Lithuanian Families With Alport Syndrome
Authors: Cerkauskaite Agne , Savige Judy , Janonyte Karolina , Jeremiciute Ieva , Miglinas Marius , Kazenaite Edita , Laurinavicius Arvydas , Strupaite-Sileikiene Rasa , Vainutiene Vija , Burnyte Birute , Jankauskiene Augustina , Rolfs Arndt , Bauer Peter , Schröder Sabine , Cerkauskiene Rimante 
Published: March 2022

Introduction:Alport syndrome (AS) is an inherited disorder characterized by hematuria, proteinuria, and kidney function impairment, and frequently associated with extrarenal manifestations. Pathogenic variants in COL4A5 usually cause X-linked Alport syndrome (XLAS), whereas those in the COL4A3 or COL4A4 genes are associated with autosomal dominant (AD) or recessive (AR) inheritance. To date, more than 3000 different disease-causing variants in COL4A5, COL4A3, and COL4A4 have been identified. The aim of this study was to evaluate the clinical and genetic spectrum of individuals with novel, pathogenic or likely pathogenic variants in the COL4A3-A5 genes in a previously unstudied cohort.MethodsIn this study molecular analysis by next generation sequencing (NGS) was performed on individuals from a Lithuanian cohort, with suspected AS. The presence of AS was assessed by reviewing clinical evidence of hematuria, proteinuria, chronic kidney disease (CKD), kidney failure (KF), a family history of AS or persistent hematuria, and specific histological lesions in the kidney biopsy such as thinning or lamellation of the glomerular basement membrane (GBM). Clinical, genetic, laboratory, and pathology data were reviewed. The novelty of the COL4A3-A5 variants was confirmed in the genetic variant databases (Centogene, Franklin, ClinVar, Varsome, InterVar). Only undescribed variants were included in this study.ResultsMolecular testing of 171 suspected individuals led to the detection of 99 individuals with 44 disease causing variants including 27, previously undescribed changes, with the frequency of 9/27 (33,3%) in genes COL4A5, COL4A3 and COL4A4 equally. Three individuals were determined as having digenic AS causing variants: one in COL4A3 and COL4A4, two in COL4A4 and COL4A5. The most prevalent alterations in genes COL4A3-5 were missense variants (n = 19), while splice site, frameshift, unknown variant and stop codon changes were detected more in genes COL4A4 and COL4A5 and accounted for 3, 3, 1 and 1 of all novel variants, respectively.ConclusionGenotype-phenotype correlation analysis suggested that some variants demonstrated intra-familial phenotypic variability. These novel variants represented more than half of all the variants found in a cohort of 171 individuals from 109 unrelated families who underwent testing. Our study expands the knowledge of the genetic and phenotypic spectrum for AS.