Genomic and transcriptomic profiling of localized sarcomatoid carcinoma of the lung to reveal association between immune activation and a lower risk of recurrence.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20058-e20058
Author(s):  
Sahil Seth ◽  
Won-Chul Lee ◽  
Jianhua Zhang ◽  
Junya Fujimoto ◽  
Carmen Behrens ◽  
...  
Keyword(s):  
Immune Activation ◽  
Lower Risk ◽  
Sarcomatoid Carcinoma ◽  
Normal Lung ◽  
P Value ◽  
Cancer Gene ◽  
Rna Seq ◽  
Synonymous Mutations ◽  
Genomic Landscape ◽  
Cluster 2

e20058 Background: The sarcomatoid carcinoma of the lung (SCL) is a rare subtype of non-small cell lung cancers (NSCLC). The prognosis of SCL is poor with 5-year survival of ~20%. There have been only a few studies on genomic landscape of SCL. Comprehensive genomic and transcriptomic profiles of SCL have not been systematically studied. Methods: In this study, we performed whole-exome sequencing and ultra-deep targeted sequencing of 400 cancer genes on 21 resected localized SCLs and matched normal lung tissues. RNA sequencing (RNA-seq) was also performed to 17 SCLs and matched normal lung tissues for those with materials available. Results: On average, 688 mutations including 503 non-synonymous mutations were identified per tumor. Canonical cancer gene analysis demonstrated that the most frequently mutated gene in this cohort was TP53 (detected in 11 out of the 21 tumors) followed by KRAS (detected in 6 out of the 21 patients). The recently discovered potentially targetable MET exon 14-skipping mutation was also detected in 3 patients in our cohort. For the 17 tumors, for, whom RNA-seq was conducted, unsupervised clustering analysis using non-negative matrix factorization (NMF) led to two stable clusters of patients in our cohort. Of particular interest, all patients (7/7) in Cluster 1 have relapsed, while only 3 of 10 patients in Cluster 2 relapsed (p-value < 0.01). Further pathway analyses demonstrated that immune activation pathways are significantly up regulated in tumors from Cluster 2 compared to Cluster 1. Conclusions: SCLs seem to have similar genomic landscape and canonical cancer gene mutations compared to other types of NSCLCs such as squamous cell carcinoma and adenocarcinomas. Immune pathway activation may be associated with lower risk of postsurgical recurrence in patients with localized SCL.

scholarly journals Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation

Immuno ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 499-517
Author(s):  
Bruce R. Southey ◽  
Marissa R. Keever-Keigher ◽  
Haley E. Rymut ◽  
Laurie A. Rund ◽  
Rodney W. Johnson ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Immune Activation ◽  
Fatty Liver Disease ◽  
P Value ◽  
Rna Seq ◽  
Alcoholic Fatty Liver ◽  
Maternal Immune Activation ◽  
Precise Understanding ◽  
Splicing Patterns ◽  
Alcoholic Fatty Liver Disease

The inflammatory response of gestating females to infection or stress can disrupt gene expression in the offspring’s amygdala, resulting in lasting neurodevelopmental, physiological, and behavioral disorders. The effects of maternal immune activation (MIA) can be impacted by the offspring’s sex and exposure to additional stressors later in life. The objectives of this study were to investigate the disruption of alternative splicing patterns associated with MIA in the offspring’s amygdala and characterize this disruption in the context of the second stress of weaning and sex. Differential alternative splicing was tested on the RNA-seq profiles of a pig model of viral-induced MIA. Compared to controls, MIA was associated with the differential alternative splicing (FDR-adjusted p-value < 0.1) of 292 and 240 genes in weaned females and males, respectively, whereas 132 and 176 genes were differentially spliced in control nursed female and male, respectively. The majority of the differentially spliced (FDR-adjusted p-value < 0.001) genes (e.g., SHANK1, ZNF672, KCNA6) and many associated enriched pathways (e.g., Fc gamma R-mediated phagocytosis, non-alcoholic fatty liver disease, and cGMP-PKG signaling) have been reported in MIA-related disorders including autism and schizophrenia in humans. Differential alternative splicing associated with MIA was detected in the gene MAG across all sex-stress groups except for unstressed males and SLC2A11 across all groups except unstressed females. Precise understanding of the effect of MIA across second stressors and sexes necessitates the consideration of splicing isoform profiles.

scholarly journals Regular exercise is associated with a lower risk of developing dementia in patients with a new diagnosis of atrial fibrillation: a nationwide population-based study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.H Lim ◽  
S.R Lee ◽  
E.K Choi ◽  
J.P Yun ◽  
H.J Ahn ◽  
...  
Keyword(s):  
Physical Activity ◽  
Atrial Fibrillation ◽  
Vascular Dementia ◽  
Lower Risk ◽  
Alzheimer’S Dementia ◽  
P Value ◽  
Regular Exercise ◽  
Newly Diagnosed ◽  
Exercise Habit ◽  
New Diagnosis

Abstract Introduction Regular exercise is known to decrease the risk of dementia. There is a paucity of information about the impact of the change of exercise habit on cardiovascular outcomes after a new diagnosis of atrial fibrillation (AF). We aimed to investigate whether regular exercise is associated with the risk of developing dementia in patients with AF. Methods Using the Korean National Health Insurance Service database, we enrolled patients with newly diagnosed AF who had undergone health screening between 2010 and 2016. The study population was divided into four groups based on the consistency of regular exercise before and after AF diagnosis: (1) persistent non-exerciser, (2) exercise starter, (3) exercise quitter, and (4) exercise maintainer. We investigated the association between exercise and the risk of dementia. Results A total of 126,555 patients were included (mean age 62.7 years, male 62.0%, and mean CHA2DS2-VASc Score 2.7). During a median follow-up duration of 3.0 years, 5,943 patients were newly diagnosed as dementia (1.57 per 100 person-years). Among patients with incident dementia, 4,410 patients had Alzheimer's dementia and 951 patients had vascular dementia (1.16 and 0.25 per 100 person-years, respectively). Persistent non-exerciser, exercise starter, quitter, and maintainer groups were 65.1%, 12.8%, 12.7%, and 9.4%, respectively. After multivariable adjustment, we found that exercise was associated with a lower risk of developing overall dementia. When compared to persistent non-exerciser, exercise starter and maintainer showed reduced risk of developing dementia (hazard ratio [HR] 0.80, 95% confidence interval [95% CI] 0.73–0.88 and HR 0.63, 95% CI 0.54–0.73, respectively, all p-value &lt;0.0001), but exercise quitter showed no significant risk reduction (HR 0.95, 95% CI 0.88–1.03, Figure). Alzheimer's dementia showed consistent results: a 20% lower risk with exercise starter, and a 37% lower risk with exercise maintainer. Change of exercise habit, however, did not affect the risk of vascular dementia (all, p-value &gt;0.05, Figure). Conclusions Regular exercise showed a lower risk of dementia in patients with new-onset AF. Starting exercise even after the diagnosis of AF was beneficial to patients who had little physical activity previously. These findings may support physicians to recommend that AF patients should start exercise or keep their physical activity to reduce the risk of dementia. Funding Acknowledgement Type of funding source: None

scholarly journals Association between End-Stage Renal Disease and Incident Diabetes Mellitus—A Nationwide Population-Based Cohort Study

2018 ◽  
Vol 7 (10) ◽  
pp. 343 ◽  
Author(s):  
Pin-Pin Wu ◽  
Chew-Teng Kor ◽  
Ming-Chia Hsieh ◽  
Yao-Peng Hsieh
Keyword(s):  
Diabetes Mellitus ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Lower Risk ◽  
Incident Diabetes ◽  
P Value ◽  
Comparison Cohort ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Background: Glucose is one of the constituents in hemodialysates and peritoneal dialysates. How the dialysis associates with the incident diabetes mellitus (DM) remains to be assessed. Methods: The claim data of end-stage renal disease (ESRD) patients who initiated dialysis from and a cohort of matched non-dialysis individuals from 2000 to 2013 were retrieved from the Taiwan National Health Insurance Research Database to examine the risk of incident DM among patients on hemodialysis (HD) and peritoneal dialysis (PD). Predictors of incident DM were determined for HD and PD patients using Fine and Gray models to treat death as a competing event, respectively. Results: A total of 2228 patients on dialysis (2092 HD and 136 PD) and 8912 non-dialysis individuals were the study population. The PD and HD patients had 12 and 97 new-onset of DM (incidence rates of 15.98 and 8.69 per 1000 patient-years, respectively), while the comparison cohort had 869 DM events with the incidence rate of 15.88 per 1000 patient-years. The multivariable-adjusted Cox models of Fine and Gray method showed that the dialysis cohort was associated with an adjusted hazard ratio (HR) of 0.49 (95% CI 0.39–0.61, p value < 0.0001) for incident DM compared with the comparison cohort. The adjusted HR of incident DM was 0.46 (95% CI 0.37–0.58, p value < 0.0001) for HD and 0.84 (95% CI 0.47–1.51, p value = 0.56) for PD. Conclusions: ESRD patients were associated with a lower risk of incident DM. HD was associated with a lower risk of incident DM, whereas PD was not.

scholarly journals Comparative RNA-Seq Analyses of Solenopsis japonica (Hymenoptera: Formicidae) Reveal Gene in Response to Cold Stress

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1610
Author(s):  
Mohammad Vatanparast ◽  
Youngjin Park
Keyword(s):  
Gene Expression ◽  
Cold Stress ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Predatory Behavior ◽  
P Value ◽  
Molecular Response ◽  
Rna Seq ◽  
Protein Database ◽  
Brood Chamber

Solenopsis japonica, as a fire ant species, shows some predatory behavior towards earthworms and woodlice, and preys on the larvae of other ant species by tunneling into a neighboring colony’s brood chamber. This study focused on the molecular response process and gene expression profiles of S. japonica to low (9 °C)-temperature stress in comparison with normal temperature (25 °C) conditions. A total of 89,657 unigenes (the clustered non-redundant transcripts that are filtered from the longest assembled contigs) were obtained, of which 32,782 were annotated in the NR (nonredundant protein) database with gene ontology (GO) terms, gene descriptions, and metabolic pathways. The results were 81 GO subgroups and 18 EggNOG (evolutionary genealogy of genes: Non-supervised Orthologous Groups) keywords. Differentially expressed genes (DEGs) with log2fold change (FC) > 1 and log2FC < −1 with p-value ≤ 0.05 were screened for cold stress temperature. We found 215 unigenes up-regulated and 115 unigenes down-regulated. Comparing transcriptome profiles for differential gene expression resulted in various DE proteins and genes, including fatty acid synthases and lipid metabolism, which have previously been reported to be involved in cold resistance. We verified the RNA-seq data by qPCR on 20 up- and down-regulated DEGs. These findings facilitate the basis for the future understanding of the adaptation mechanisms of S. japonica and the molecular mechanisms underlying the response to low temperatures.

scholarly journals Single cell analysis reveals the impact of age and maturation stage on the human oocyte transcriptome

2020 ◽  
Author(s):  
Silvia Llonch ◽  
Montserrat Barragán ◽  
Paula Nieto ◽  
Anna Mallol ◽  
Marc Elosua-Bayes ◽  
...  
Keyword(s):  
Single Cell ◽  
Chromosome Segregation ◽  
Maternal Age ◽  
Maturation Stage ◽  
P Value ◽  
Rna Seq ◽  
Transcript Levels ◽  
Human Oocytes ◽  
The Impact

AbstractStudy questionTo which degree does maternal age affect the transcriptome of human oocytes at the germinal vesicle (GV) stage or at metaphase II after maturation in vitro (IVM-MII)?Summary answerWhile the oocytes’ transcriptome is predominantly determined by maturation stage, transcript levels of genes related to chromosome segregation, mitochondria and RNA processing are affected by age after in vitro maturation of denuded oocytes.What is known alreadyFemale fertility is inversely correlated with maternal age due to both a depletion of the oocyte pool and a reduction in oocyte developmental competence. Few studies have addressed the effect of maternal age on the human mature oocyte (MII) transcriptome, which is established during oocyte growth and maturation, and the pathways involved remain unclear. Here, we characterize and compare the transcriptomes of a large cohort of fully grown GV and IVM-MII oocytes from women of varying reproductive age.Study design, size, durationIn this prospective molecular study, 37 women were recruited from May 2018 to June 2019. The mean age was 28.8 years (SD=7.7, range 18-43). A total of 72 oocytes were included in the study at GV stage after ovarian stimulation, and analyzed as GV (n=40) and in vitro matured oocytes (IVM-MII; n=32).Participants/materials, setting, methodsDenuded oocytes were included either as GV at the time of ovum pick-up or as IVM-MII after in vitro maturation for 30 hours in G2™ medium, and processed for transcriptomic analysis by single-cell RNA-seq using the Smart-seq2 technology. Cluster and maturation stage marker analysis were performed using the Seurat R package. Genes with an average fold change greater than 2 and a p-value < 0.01 were considered maturation stage markers. A Pearson correlation test was used to identify genes whose expression levels changed progressively with age. Those genes presenting a correlation value (R) >= |0.3| and a p-value < 0.05 were considered significant.Main results and the role of chanceFirst, by exploration of the RNA-seq data using tSNE dimensionality reduction, we identified two clusters of cells reflecting the oocyte maturation stage (GV and IVM-MII) with 4,445 and 324 putative marker genes, respectively. Next we identified genes, for which RNA levels either progressively increased or decreased with age. This analysis was performed independently for GV and IVM-MII oocytes. Our results indicate that the transcriptome is more affected by age in IVM-MII oocytes (1,219 genes) than in GV oocytes (596 genes). In particular, we found that genes involved in chromosome segregation and RNA splicing significantly increase in transcript levels with age, while genes related to mitochondrial activity present lower transcript levels with age. Gene regulatory network analysis revealed potential upstream master regulator functions for genes whose transcript levels present positive (GPBP1, RLF, SON, TTF1) or negative (BNC1, THRB) correlation with age.Limitations, reasons for cautionIVM-MII oocytes used in this study were obtained after in vitro maturation of denuded GV oocytes, therefore, their transcriptome might not be fully representative of in vivo matured MII oocytes.The Smart-seq2 methodology used in this study detects polyadenylated transcripts only and we could therefore not assess non-polyadenylated transcripts.Wider implications of the findingsOur analysis suggests that advanced maternal age does not globally affect the oocyte transcriptome at GV or IVM-MII stages. Nonetheless, hundreds of genes displayed altered transcript levels with age, particularly in IVM-MII oocytes. Especially affected by age were genes related to chromosome segregation and mitochondrial function, pathways known to be involved in oocyte ageing. Our study thereby suggests that misregulation of chromosome segregation and mitochondrial pathways also at the RNA-level might contribute to the age-related quality decline in human oocytes.Study funding/competing interest(s)This study was funded by the AXA research fund, the European commission, intramural funding of Clinica EUGIN, the Spanish Ministry of Science, Innovation and Universities, the Catalan Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) and by contributions of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership and to the “Centro de Excelencia Severo Ochoa”.The authors have no conflict of interest to declare.

scholarly journals Exploration of Alternative Splicing (AS) Events in MDV-Infected Chicken Spleens

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1857
Author(s):  
Lulu Wang ◽  
Gang Zheng ◽  
Yiming Yuan ◽  
Ziyi Wang ◽  
Changjun Liu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Infection Process ◽  
Marek's Disease ◽  
Individual Development ◽  
Control Group ◽  
P Value ◽  
Marek’S Disease ◽  
Rna Seq ◽  
Infected Chicken ◽  
Structural Variations

Marek’s disease (MD) was an immunosuppression disease induced by Marek’s disease virus (MDV). MD caused huge economic loss to the global poultry industry, but it also provided an ideal model for studying diseases induced by the oncogenic virus. Alternative splicing (AS) simultaneously produced different isoform transcripts, which are involved in various diseases and individual development. To investigate AS events in MD, RNA-Seq was performed in tumorous spleens (TS), spleens from the survivors (SS) without any lesion after MDV infection, and non-infected chicken spleens (NS). In this study, 32,703 and 25,217 AS events were identified in TS and SS groups with NS group as the control group, and 1198, 1204, and 348 differently expressed (DE) AS events (p-value < 0.05 and FDR < 0.05) were identified in TS vs. NS, TS vs. SS, SS vs. NS, respectively. Additionally, Function enrichment analysis showed that ubiquitin-mediated proteolysis, p53 signaling pathway, and phosphatidylinositol signaling system were significantly enriched (p-value < 0.05). Small structural variations including SNP and indel were analyzed based on RNA-Seq data, and it showed that the TS group possessed more variants on the splice site region than those in SS and NS groups, which might cause more AS events in the TS group. Combined with previous circRNA data, we found that 287 genes could produce both circular and linear RNAs, which suggested these genes were more active in MD lymphoma transformation. This study has expanded the understanding of the MDV infection process and provided new insights for further analysis of resistance/susceptibility mechanisms.

scholarly journals Impact of Labor Induction at 39 Weeks Gestation Compared with Expectant Management on Maternal and Perinatal Morbidity among a Cohort of Low-risk Women

2021 ◽  
Author(s):  
Sabrina C. Burn ◽  
Ruofan Yao ◽  
Maria Diaz ◽  
Jordan Rossi ◽  
Stephen Contag
Keyword(s):  
Cesarean Delivery ◽  
Lower Risk ◽  
Fetal Death ◽  
Expectant Management ◽  
Low Risk ◽  
P Value ◽  
Cesarean Hysterectomy ◽  
Increased Risk ◽  
Nicu Admission ◽  
Low Risk Women

Abstract Objective: To determine rates of maternal and perinatal outcomes after induction of labor (IOL) at 39 weeks compared with expectant management.Methods: Cohort study of low risk women delivered between 39-42 weeks from 2015 to 2018. We excluded births with fetal abnormalities, previous cesarean, multiple pregnancies or those with spontaneous onset of labor (SOL) or indicated delivery at 39 weeks. Data was abstracted from National Center for Health Statistics birth files. Relative risks (aRR) were estimated with multivariable log-binomial regression. Main Outcome Measures: Maternal outcomes: chorioamnionitis (Triple I), blood transfusion, neonatal intensive care unit (NICU) admission, uterine rupture, cesarean delivery and cesarean hysterectomy. Fetal and infant outcomes: fetal death, 5-minute Apgar ≤3, prolonged ventilation, seizures, ICU admission, and death within 28 days. Results: There were 15,900,956 births, with 8,540,063 after exclusions. The IOL group included 1,177,790 births excluding women with diabetes or hypertensive disease. There were 3,835,185 births after 39 weeks excluding women with diabetes or chronic hypertension. With IOL at 39 weeks the risk for blood transfusion (p-value < 0.01; aRR 0.78; 95% CI [0.75-0.82]), Triple I (p-value < 0.01; aRR 0.71; 95% CI [0.70-0.73]) and cesarean delivery (p-value <0.01; aRR 0.87; 95% CI [0.87-0.88]) were lower, albeit increased risk of cesarean hysterectomy (p-value <0.01; aRR 1.23; 95% CI [1.07-1.41]). Neonates had a lower risk for 5-minute Apgar ≤3 (p-value < 0.01; aRR 0.68; 95% CI [0.66-0.71]), prolonged ventilation (p-value < 0.01; aRR 0.84; 95% CI [0.81-0.87]), NICU admission (p-value < 0.01; aRR 0.86; 95% CI [0.85-0.87]), and neonatal seizures (p-value <0.01; aRR 0.85; 95% CI [0.76-0.96]). There was no difference in risk for neonatal death 0.99% (p-value 0.99; aRR 1.00; 95%CI [0.99-1.00]), or fetal death (p-value 0.78; aRR 1.0002; 95%CI [0.99-1.002]. This benefit was greater compared with each subsequent week.Conclusions: Induction of labor at 39 weeks of gestation in a low risk cohort is associated a lower risk of cesarean delivery, transfusions and infection, as well as lower neonatal morbidity, without difference in fetal or neonatal death. This appears to be associated with increased risk for cesarean hysterectomy.

scholarly journals Clinical Value of lncRNA LUCAT1 Expression in Liver Cancer and its Potential Pathways

2019 ◽  
Vol 28 (4) ◽  
pp. 439-447 ◽  
Author(s):  
Yan Jiao ◽  
Yanqing Li ◽  
Bai Ji ◽  
Hongqiao Cai ◽  
Yahui Liu
Keyword(s):  
Liver Cancer ◽  
Roc Curve ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Rank Test ◽  
P Value ◽  
Rna Seq ◽  
Cox Regression Analysis

Background and Aims: Emerging studies indicate that long noncoding RNAs (lncRNAs) play a role as prognostic markers in many cancers, including liver cancer. Here, we focused on the lncRNA lung cancer-associated transcript 1 (LUCAT1) for liver cancer prognosis. Methods: RNA-seq and phenotype data were downloaded from the Cancer Genome Atlas (TCGA). Chisquare tests were used to evaluate the correlations between LUCAT1 expression and clinical features. Survival analysis and Cox regression analysis were used to compare different LUCAT1 expression groups (optimal cutoff value determined by ROC). The log-rank test was used to calculate the p-value of the Kaplan-Meier curves. A ROC curve was used to evaluate the diagnostic value. Gene Set Enrichment Analysis (GSEA) was performed, and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanism. Results: Data mining of the TCGA -Liver Hepatocellular Carcinoma (LIHC) RNA-seq data of 371 patients showed the overexpression of LUCAT1 in cancerous tissue. High LUCAT1 expression was associated with age (p=0.007), histologic grade (p=0.009), T classification (p=0.022), and survival status (p=0.002). High LUCAT1 patients had a poorer overall survival and relapse-free survival than low LUCAT1 patients. Multivariate analysis identified LUCAT1 as an independent risk factor for poor survival. The ROC curve indicated modest diagnostic performance. GSEA revealed the related signaling pathways, and the ceRNA network uncovered the underlying mechanism. Conclusion: High LUCAT1 expression is an independent prognostic factor for liver cancer.

scholarly journals Sequence diversity and evolution of an iflavirus family associated with ticks

2020 ◽  
Author(s):  
Romain Daveu ◽  
Caroline Hervet ◽  
Louane Sigrist ◽  
Davide Sassera ◽  
Aaron Jex ◽  
...  
Keyword(s):  
Cell Line ◽  
Complete Genome ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Rna Viruses ◽  
Ixodes Scapularis ◽  
Fine Scale ◽  
Rna Seq ◽  
Strong Positive Selection ◽  
Synonymous Mutations

AbstractWe studied a family of iflaviruses, a group of RNA viruses frequently found in arthropods, focusing on viruses associated with ticks. Our aim was to bring insight on the evolutionary dynamics of this group of viruses, which may interact with the biology of ticks. We explored systematically de novo RNA-Seq assemblies available for species of ticks which allowed to identify nine new genomes of iflaviruses. The phylogeny of virus sequences was not congruent with that of the tick hosts, suggesting recurrent host changes across tick genera along evolution. We identified five different variants with a complete or near-complete genome in Ixodes ricinus. These sequences were closely related, which allowed a fine-scale estimation of patterns of substitutions: we detected a strong excess of synonymous mutations suggesting evolution under strong positive selection. ISIV, a sequence found in the ISE6 cell line of Ixodes scapularis, was unexpectedly nearidentical with I. ricinus variants, suggesting a contamination of this cell line by I. ricinus material. Overall, our work constitutes a step in the understanding of the interactions between this family of viruses and ticks.

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