bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677C>T) gene polymorphism with ischemic stroke risk in different populations: An updated meta-analysis
Authors: Zhao Lili , Li Tao , Dang Meijuan , Li Ye , Fan Hong , Hao Qian , Song Dingli , Lu Jialiang , Lu Ziwei , Jian Yating , Wang Heying , Wang Xiaoya , Wu Yulun , Zhang Guilian 
Published: January 2023

Background: Recently, increasing evidence has implicated methylenetetrahydrofolate reductase (MTHFR) gene mutation as a risk factor for ischemic stroke (IS) in the general population. However, studies have been inconclusive and lack evidence on specific populations. We aim to determine whether the rs1801133 (NC_000001.11 (MTHFR):g. 677C&gt;T (p.Ala222Val) variant, we termed as MTHFR rs1801133 (677 C&gt;T), is linked to an increased risk of IS in different age groups and ancestry groups.Methods: The literature relevant to our study was found by searching the PubMed, Cochrane Library, Web of Science, EMBASE, and CNKI databases. A random effect model analysis was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate any possible association. We conducted a subgroup analysis based on the age and ancestry groups of the included populations.Results: As of March 2022, 1,925 citations had been identified in electronic databases, of which 96 studies involving 34,814 subjects met our eligibility criteria. A strong link was found between IS and the MTHFR gene rs1801133 (677C&gt;T) polymorphism in all genetic models [dominant genetic model (OR = 1.47; 95%CI = 1.33–1.61; p &lt; 0.001), recessive genetic model (OR = 1.52; 95%CI = 1.36–1.71; p &lt; 0.001), heterozygous model (OR = 1.36; 95%CI = 1.24–1.48; p &lt; 0.001), homozygous model (OR = 1.82; 95%CI = 1.58–2.11; p &lt; 0.001), and T allelic genetic model (OR = 1.37; 95%CI = 1.27–1.48; p &lt; 0.001)]. Further subgroup analyses indicated that the MTHFR rs1801133 (677C&gt;T) variant may increase the risk of IS in Asian, Hispanic, or Latin population, middle-aged, and elderly populations (p &lt; 0.001).Conclusion: Our results implied that mutation of the T allele of MTHFR rs1801133 (677C&gt;T) could be a risk factor for IS. A significant association was found among Asian, Hispanic, or Latin population, middle-aged, and elderly people.
Growth performance, survivability and profitability of improved smallholder chicken genetics in Nigeria: A COVID-19 intervention study
Authors: Bamidele Oladeji , Akinsola Oludayo Micheal , Yakubu Abdulmojeed , Hassan Waheed Akinola , Ogundu Uduak Emmanuel , Amole Tunde Adegoke 
Published: January 2023

The impact of COVID-19 pandemic on smallholder farming households (SFH) includes increased poverty, and loss of livelihoods. Provision of livestock to SFH is a helpful intervention to mitigate this impact. This study provided a total of 150 smallholder poultry farmers, randomly selected from three states (Kebbi, Nasarawa, and Imo) in Nigeria, with ten 5-week-old chickens (mixed sexes) each, of either FUNAAB Alpha or Noiler chicken genetics. The improved, dual-purpose chickens were evaluated for growth performance (GP), survivability and profitability. The birds were managed under semi-scavenging production system. Body weight, mortality, and cost of production (COP) were recorded every 4 weeks until 21 weeks of age. Profitability was a function of the COP, and the selling price for live-birds (cocks). Body weight of Noiler (1,927 g) birds was not significantly (p &gt; .05) higher than FUNAAB Alpha (1,792 g) at 21 weeks. Agroecology and genetics had significant (p &lt; .05) effects on GP and survivability. Survivability of FUNAAB Alpha was higher (p &lt; .05) than Noiler, with Nasarawa (81%–96%), having the highest (p &lt; .0001) survival rate compared to Imo (62%–81%), and Kebbi (58%–75%). At 21 weeks, the number of cocks and hens differed significantly (p &lt; .05) within the states (Imo: 2.4 ± .2 and 5.4 ± .3; Kebbi: 2.6 ± .2 and 5.5 ± .3; and Nasarawa: 2.9 ± .2 and 5.8 ± .3). Nasarawa (NGN 7,808; USD 19) ranked best for profitability, followed by Kebbi (NGN 6,545; USD 16) and Imo (NGN 5,875; USD 14). Overall, this study demonstrates that provision of improved chickens to vulnerable SFH in Nigeria holds great potential for economic growth, and resilience during emergencies, such as the COVID-19 pandemic.
Experimental verification and comprehensive analysis of m7G methylation regulators in the subcluster classification of ischemic stroke
Authors: Tian Yunze , Yu Beibei , Lv Boqiang , Zhang Yongfeng , Fu Longhui , Yang Shijie , Li Jianzhong , Gong Shouping 
Published: January 2023

Background: Ischemic stroke (IS) is a fatal cerebrovascular disease involving several pathological mechanisms. Modification of 7-methylguanosine (m7G) has multiple regulatory functions. However, the expression pattern and mechanism of m7G in IS remain unknown. Herein, we aimed to explore the effect of m7G modification on IS.Methods: We screened significantly different m7G-regulated genes in Gene Expression Omnibus datasets, GSE58294 and GSE22255. The random forest (RF) algorithm was selected to identify key m7G-regulated genes that were subsequently validated using the middle cerebral artery occlusion (MCAO) model and quantitative polymerase chain reaction (qPCR). A risk model was subsequently generated using key m7G-regulated genes. Then, “ConsensusClusterPlus” package was used to distinguish different m7G clusters of patients with IS. Simultaneously, between two m7G clusters, differentially expressed genes (DEGs) and immune infiltration differences were also explored. Finally, we investigated functional enrichment and the mRNA–miRNA–transcription factor network of DEGs.Results: RF and qPCR confirmed that EIF3D, CYFIP2, NCBP2, DCPS, and NUDT1 were key m7G-related genes in IS that could accurately predict clinical risk (area under the curve = 0.967). NCBP2 was the most significantly associated gene with immune infiltration. Based on the expression profiles of these key m7G-related genes, the IS group could be divided into two clusters. According to the single-sample gene set enrichment analysis algorithm, four types of immune cells (immature dendritic cells, macrophages, natural killer T cells, and TH1 cells) were significantly different in the two m7G clusters. The functional enrichment of 282 DEGs between the two clusters was mainly concentrated in the “regulation of apoptotic signaling pathway,” “cellular response to DNA damage stimulus,” “adaptive immune system,” and “pyroptosis.” The miR-214–LTF–FOXJ1 axis may be a key regulatory pathway for IS.Conclusion: Our findings suggest that EIF3D, CYFIP2, NCBP2, DCPS, and NUDT1 may serve as potential diagnostic biomarkers for IS and that the m7G clusters developed by these genes provide more evidence for the regulation of m7G in IS.
Prognostic prediction of clear cell renal cell carcinoma based on lipid metabolism-related lncRNA risk coefficient model
Authors: Qu GenYi , Liu Lu , Yi Lai , Tang Cheng , Yang Guang , Chen Dan , Xu Yong 
Published: January 2023

Objective: In order to predict the prognosis in patients with clear cell renal cell carcinoma (ccRCC) so as to understand cancer lipid metabolism and sensitivity to immune-targeting drugs, model algorithms were used to establish a risk coefficient model of long non-coding RNAs (lncRNAs) associated with lipid metabolism.Methods: The transcriptome data were retrieved from TCGA, and lncRNAs associated with lipid metabolism were obtained through Pearson correlation and differential expression analyses. Differentially expressed lipid metabolism-related lncRNAs and lipid metabolism-related lncRNA pairs were obtained using the R language software. The minimum absolute shrinkage method and the selector operation regression method were used to construct the model and draw the receiver operator characteristic curve. High-risk patients were differentiated from low-risk patients through the cut-off value, and the correlation analyses of the high-risk subgroup and low-risk subgroup were performed.Results: This research discovered that 25 pairs of lncRNAs were associated with the lipid metabolism of ccRCC, and 12 of these pairs were utilized to build the model. In combination with clinical data, the areas under the 1-, 3- and 5-year survival curves of ccRCC patients were 0.809, 0.764 and 0.792, separately. The cut-off value was used to perform subgroup analysis. The results showed that high-risk patients had poor prognosis. The results of Cox multivariate regressive analyses revealed that age and risk score were independent prediction factors of ccRCC prognosis. In addition, immune cell infiltration, the levels of gene expression at immune checkpoints, and high-risk patients more susceptible to sunitinib-targeted treatment were assessed by the risk model.Conclusion: Our team identified new prognostic markers of ccRCC and established risk models that could assess the prognosis of ccRCC patients and help determine which type of patients were more susceptible to sunitinib. These discoveries are vital for the optimization of risk stratification and personalized management.
Association of environmental exposure to chromium with differential DNA methylation: An epigenome-wide study
Authors: Zhao Meiduo , Wu Jingtao , Xu Jing , Li Ang , Mei Yayuan , Ge Xiaoyu , Yin Guohuan , Liu Xiaolin , Wei Lanping , Xu Qun 
Published: January 2023

Introduction: Previous studies have reported that chromium (Cr)-induced epigenetic alterations and DNA methylation play a vital role in the pathogenesis of diseases induced by chromium exposure. Epigenomic analyses have been limited and mainly focused on occupational chromium exposure; their findings are not generalizable to populations with environmental Cr exposure.Methods: We identified the differential methylation of genes and regions to elucidate the mechanisms of toxicity related to environmental chromium exposure. DNA methylation was measured in blood samples collected from individuals in Cr-contaminated (n = 10) and unexposed areas (n = 10) by using the Illumina Infinium HumanMethylation850K array. To evaluate the relationship between chromium levels in urine and CpG methylation at 850 thousand sites, we investigated differentially methylated positions (DMPs) and differentially methylated regions (DMRs) by using linear models and DMRcate method, respectively. The model was adjusted for biologically relevant variables and estimated cell-type compositions.Results: At the epigenome-wide level, we identified five CpGs [cg20690919 (pFDR =0.006), cg00704664 (pFDR =0.024), cg10809143 (pFDR =0.043), cg27057652 (pFDR =0.047), cg05390480 (pFDR =0.024)] and one DMR (chr17: 19,648,718-19,648,972), annotated to ALDH3A1 genes (p &lt; 0.05) as being significantly associated with log2 transformed urinary chromium levels.Discussion: Environmental chromium exposure is associated with DNA methylation, and the significant DMPs and DMR being annotated to cause DNA damage and genomic instability were found in this work. Research involving larger samples is required to further explore the epigenetic effect of environmental chromium exposure on health outcomes through DNA methylation.
Construction of HBV gene-related prognostic and diagnostic models for hepatocellular carcinoma
Authors: Ma Keqiang , Wu Hongsheng , Ji Lei 
Published: January 2023

Background: Hepatocellular carcinoma (HCC) is a main cause of malignancy-related death all over the world with a poor prognosis. The current research is focused on developing novel prognostic and diagnostic models of Hepatocellular carcinoma from the perspective of hepatitis B virus (HBV)-related genes, and predicting its prognostic characteristics and potential reliable biomarkers for Hepatocellular carcinoma diagnosis.Methods: As per the information related to Hepatocellular carcinoma expression profile and the clinical data in multiple public databases, we utilized limma for assessing the differentially expressed genes (DEGs) in HBV vs non- hepatitis B virus groups, and the gene set was enriched, analyzed and annotated by WebGestaltR package. Then, STRING was employed to investigate the protein interactions. A risk model for evaluating Hepatocellular carcinoma prognosis was built with Lasso Cox regression analysis. The effect patients receiving immunotherapy was predicted using Tumor Immune Dysfunction and Exclusion (TIDE). Additionally, pRRophetic was used to investigate the drug sensitivity. Lastly, the Support Vector Machine (SVM) approach was utilized for building the diagnostic model.Results: The Hepatocellular Carcinoma Molecular Atlas 18 (HCCDB18) data set was utilized for the identification of 1344 HBV-related differentially expressed genes, mainly associated with cell division activities. Five functional modules were established and then we built a prognostic model in accordance with the protein-protein interaction (PPI) network. Five HBV-related genes affecting prognosis were identified for constructing a prognostic model. Then, the samples were assigned into RS-high and -low groups as per their relevant prognostic risk score (RS). High-risk group showed worse prognosis, higher mutation rate of TP53, lower sensitivity to immunotherapy but higher response to chemotherapeutic drugs than low-risk group. Finally, the hepatitis B virus diagnostic model of Hepatocellular carcinoma was established.Conclusion: In conclusion, the prognostic and diagnostic models of hepatitis B virus gene-related Hepatocellular carcinoma were constructed. ABCB6, IPO7, TIMM9, FZD7, and ACAT1, the five HBV-related genes that affect the prognosis, can work as reliable biomarkers for the diagnosis of Hepatocellular carcinoma, giving a new insight for improving the prognosis, diagnosis, and treatment outcomes of HBV-type Hepatocellular carcinoma.
Whole-genome characterization of large-cell lung carcinoma: A comparative analysis based on the histological classification
Authors: Wu Xiaowei , Yin Jin , Deng Yu , Zu Yukun 
Published: January 2023

Background: According to the 2015 World Health Organization classification, large cell neuroendocrine carcinoma (LCNEC) was isolated from Large-cell lung cancer (LCLC) tumors, which constitutes 2%–3% of non-small cell lung cancer (NSCLC). However, LCLC tumors are still fairly vaguely defined at the molecular level compared to other subgroups.Materials and Methods: In this study, whole-genome sequencing (WGS) was performed on 23 LCLC and 15 LCNEC tumor specimens. Meanwhile, data from the TCGA (586 LUADs and 511 LUSCs) and U Cologne (120 SCLCs) were analyzed and compared.Results: The most common driver mutations were found in TP53 (13/23, 57%), FAM135B (8/23, 35%) and FAT3 (7/23, 30%) in LCLC, while their counterparts in LCNEC were TP53 (13/15, 87%), LRP1B (6/15, 40%) and FAT1 (6/15, 40%). Notably, FAM135B mutations only occurred in LCLC (P = 0.013). Cosmic signature analysis revealed widespread defective DNA mismatch repair and tobacco-induced mutations in both LCLC and LCNEC. Additionally, LCNEC had a higher incidence of chromosomal copy number variations (CNVs) and structural variations (SVs) compared with LCLC, although the differences were not statistically significant. Particularly, chromothripsis SVs was significantly associated with CNVs. Furthermore, mutational landscape of different subtypes indicated differences between subtypes, and there seems to be more commonalty between our cohort and SCLC than with other subtypes. SMARCA4 mutations may be specific driver gene alteration in our cohort.Conclusion: Our results support that LCLC and LCNEC tumors follow distinct tumorigenic pathways. To our knowledge, this is the first genome-wide profiling comparison of LCLC and LCNEC.
CRISPR/Cas9-editing of KISS1 to generate pigs with hypogonadotropic hypogonadism as a castration free trait
Authors: Flórez Julio M. , Martins Kyra , Solin Staci , Bostrom Jonathan R. , Rodríguez-Villamil Paula , Ongaratto Felipe , Larson Sabreena A. , Ganbaatar Uyanga , Coutts Alexander W. , Kern Doug , Murphy Thomas W. , Kim Eui-Soo , Carlson Daniel F. , Huisman Abe , Sonstegard Tad S. , Lents Clay A. 
Published: January 2023

Introduction: Most male pigs are surgically castrated to avoid puberty-derived boar taint and aggressiveness. However, this surgical intervention represents a welfare concern in swine production. Disrupting porcine KISS1 is hypothesized to delay or abolish puberty by inducing variable hypogonadotropism and thus preventing the need for castration.Methods: To test this hypothesis, we generated the first KISS1-edited large animal using CRISPR/Cas9-ribonucleoproteins and single-stranded donor oligonucleotides. The targeted region preceded the sequence encoding a conserved core motif of kisspeptin. Genome editors were intracytoplasmically injected into 684 swine zygotes and transferred to 19 hormonally synchronized surrogate sows. In nine litters, 49 American Yorkshire and 20 Duroc liveborn piglets were naturally farrowed.Results: Thirty-five of these pigs bore KISS1-disruptive alleles ranging in frequency from 5% to 97% and did not phenotypically differ from their wild-type counterparts. In contrast, four KISS1-edited pigs (two boars and two gilts) with disruptive allele frequencies of 96% and 100% demonstrated full hypogonadotropism, infantile reproductive tracts, and failed to reach sexual maturity. Change in body weight during development was unaffected by editing KISS1. Founder pigs partially carrying KISS1-disruptive alleles were bred resulting in a total of 53 KISS1+/+, 60 KISS1+/−, and 34 KISS1−/− F1 liveborn piglets, confirming germline transmission.Discussion: Results demonstrate that a high proportion of KISS1 alleles in pigs must be disrupted before variation in gonadotropin secretion is observed, suggesting that even a small amount of kisspeptin ligand is sufficient to confer proper sexual development and puberty in pigs. Follow-on studies will evaluate fertility restoration in KISS1 KO breeding stock to fully realize the potential of KISS1 gene edits to eliminate the need for surgical castration.
Construction of an original anoikis-related prognostic model closely related to immune infiltration in gastric cancer
Authors: Zhao Zhihong , Li Cun , Peng Ye , Liu Rui , Li Qian 
Published: January 2023

Background: Anoikis is considered as a particular type of programmed cell death, the weakness or resistance of which contributes greatly to the development and progression of most malignant solid tumors. However, the latent impact of anoikis-related genes (ARGs) on gastric cancer (GC) is still ambiguous. Based on these, this study established an anoikis-related prognostic model of GC to identify the prognosis of patients and provide more effective treatment in clinical practice.Methods: First, we extracted four public datasets containing the gene expression and clinicopathological information of GC, which were worked as the training and validating sets, separately. Then, an anoikis-related survival-predicted model of GC was developed via Lasso and COX regression analyses and verified by using the Kaplan-Meier (KM) curve and receiver operating characteristic (ROC) curve analyses. Next, we assigned GC patients to two groups characterized by the risk score calculated and analyzed somatic mutation, functional pathways, and immune infiltration between the different two groups. Finally, a unique nomogram was offered to clinicians to forecast the personal survival probability of GC patients.Results: Based on seven anoikis-related markers screened and identified, a carcinogenic model of risk score was produced. Patients placed in the high-score group suffered significantly worse overall survival (OS) in four cohorts. Additionally, the model revealed a high sensitivity and specificity to prognosticate the prognoses of GC patients [area under the ROC curve (AUC) at 5-year = 0.713; GSE84437, AUC at 5-year = 0.639; GSE15459, AUC at 5-year = 0.672; GSE62254, AUC at 5-year = 0.616]. Apart from the excellent predictive performance, the model was also identified as an independent prediction factor from other clinicopathological characteristics. Combining anoikis-related prognostic model with GC clinical features, we built a more comprehensive nomogram to foresee the likelihood of survival of GC patients in a given year, showing a well-accurate prediction performance.Conclusion: In summary, this study created a new anoikis-related signature for GC, which has potentially provided new critical insights into survival prediction and individualized therapy development.
Differential methylation of microRNA encoding genes may contribute to high myopia
Authors: Swierkowska Joanna , Vishweswaraiah Sangeetha , Mrugacz Malgorzata , Radhakrishna Uppala , Gajecka Marzena 
Published: January 2023

Introduction: High myopia (HM), an eye disorder with a refractive error ≤−6.0 diopters, has multifactorial etiology with environmental and genetic factors involved. Recent studies confirm the impact of alterations in DNA methylation and microRNAs (miRNAs) on myopia. Here, we studied the combined aspects evaluating to the role of methylation of miRNA encoding genes in HM.Materials and Methods: From the genome-wide DNA methylation data of 18 Polish children with HM and 18 matched controls, we retrieved differentially methylated CG dinucleotides localized in miRNA encoding genes. Putative target genes of the highest-ranked miRNAs were obtained from the miRDB and included in overrepresentation analyses in the ConsensusPathDB. Expression of target genes was assessed using the RNA sequencing data of retinal ARPE-19 cell line.Results: We identified differential methylation of CG dinucleotides in promoter regions of MIR3621, MIR34C, MIR423 (increased methylation level), and MIR1178, MIRLET7A2, MIR885, MIR548I3, MIR6854, MIR675, MIRLET7C, MIR99A (decreased methylation level) genes. Several targets of these miRNAs, e.g. GNAS, TRAM1, CTNNB1, EIF4B, TENM3 and RUNX were previously associated with myopia/HM/refractive error in Europeans in genome-wide association studies. Overrepresentation analyses of miRNAs’ targets revealed enrichment in pathways/processes related to eye structure/function, such as axon guidance, transcription, focal adhesion, and signaling pathways of TGF-β, insulin, MAPK and EGF-EGFR.Conclusion: Differential methylation of indicated miRNA encoding genes might influence their expression and contribute to HM pathogenesis via disrupted regulation of transcription of miRNAs’ target genes. Methylation of genes encoding miRNAs may be a new direction in research on both the mechanisms determining HM and non-invasive indicators in diagnostics.