Health outcomes in SARS survivors 18 years after infection: A longitudinal cohort study
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ABSTRACT:
PROVIDER: PRJNA893211 | ENA |
REPOSITORIES: ENA
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Project description:We aimed to characterize the long-term health outcomes of survivors of severe acute respiratory syndrome (SARS) and determine their recovery status and possible immunological basis. Although health outcomes continued to improve, SARS survivors still suffered from physical fatigue, osteoporosis, and necrosis of the femoral head 18 years after discharge, possibly related to plasma metabolic disorders and immunological alterations.
2023-09-06 | GSE216357 | GEO
Project description:Millions of sepsis survivors annually face long-term neuropsychiatric sequelae of their illness. Corticosteroids are frequently administered in sepsis, and their use affects neuropsychiatric outcomes, but the mechanisms are unknown. We used the cecal ligation and puncture method to induce acute infection in mice and test the hypothesis that corticosteroid treatment during illness has long-term effects on hippocampal function. Functional phenotyping and hippocampal RNA-sequencing were performed in the same survivor mice to identify underlying mechanisms of behavioral and neuroendocrine outcomes. Long-term CLP survivors exhibited anxiety-like behavior, increased central hypothalamic-pituitary-adrenal (HPA) axis activity, and persistent systemic and neuro-inflammation. The relationship between gene expression and behavior suggested a protective role for inflammation and oxidative metabolism after CLP. Corticosterone treatment during illness had distinct effects on hippocampal function in survivors, including object memory impairment. The long-term behavioral effects of corticosterone treatment were associated with persistent downregulation of activity-dependent gene expression in the hippocampus. The results suggest that corticosteroid treatment for sepsis influences hippocampal function in survivors via long-lasting changes to basal hippocampal activity. Neural activity, inflammation, and oxidative metabolism should be explored as future treatment targets to modify neuropsychiatric outcomes in sepsis survivors.
2023-07-31 | GSE225868 | GEO
Project description:Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention. Longitudinal study including 15 samples
2016-06-15 | E-GEOD-83334 | biostudies-arrayexpress
Project description:Less than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSC) survive more than five years post-diagnosis but those who have an exceptionally long survival could provide new insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage, HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome, and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair, and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes, and differential immune responses appear to contribute to long-term survival in HGSC.
2022-08-26 | GSE211669 | GEO
Project description:Background: It is well-established that cancer treatment substantially increases risk of long-term adverse health outcomes among childhood cancer survivors. However, there is limited research on the underlying mechanisms. To elucidate the pathophysiology and a possible causal pathway from treatment exposures to cardiometabolic conditions, we conducted epigenome-wide association studies (EWAS) to identify DNA methylation (DNAm) sites associated with cancer treatment exposures and examined whether treatment-associated DNAm sites mediate associations between specific treatments and cardiometabolic conditions. Methods: We included 2,052 survivors (median age 33.7 years) of European ancestry from the St. Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Cumulative doses of chemotherapy and region-specific radiation were abstracted from medical records. Seven cardiometabolic conditions were clinically assessed. DNAm profile was measured using MethylationEPIC BeadChip with blood-derived DNA. Results: By performing multiple treatment-specific EWAS, we identified 935 5’-cytosine-phosphate-guanine-3′ (CpG) sites mapped to 538 genes/regions associated with one or more cancer treatments at epigenome-wide significance level (P<9×10-8). Among the treatment-associated CpGs, 8 were associated with obesity, 63 with hypercholesterolemia, and 17 with hypertriglyceridemia (False-Discovery-Rate-Adjusted P<0.05). We observed substantial mediation by methylation at four independent CpGs (cg06963130, cg21922478, cg22976567, cg07403981) for association between abdominal field radiotherapy (abdominal-RT) and risk of hypercholesterolemia (70.3%) and by methylation at three CpGs (cg19634849, cg13552692, cg09853238) for association between abdominal-RT and hypertriglyceridemia (54.6%). In addition, three CpGs (cg26572901, cg12715065, cg21163477) partially mediated the association between brain-RT and obesity with 32.9% mediation effect and two CpGs mediated the association between corticosteroids and obesity (cg22351187, 14.2%) and between brain-RT and hypertriglyceridemia (cg13360224, 10.5%). Notably, several mediator CpGs reside in the proximity of well-established dyslipidemia genes: cg21922478 (ITGA1) and cg22976567 (LMNA). Conclusions: In childhood cancer survivors, cancer treatment exposures are associated with DNAm patterns present decades following the exposure. Treatment-associated DNAm sites may mediate the causal pathway from specific treatment exposures to certain cardiometabolic conditions, suggesting the utility of DNAm sites as risk predictors and potential mechanistic targets for future intervention studies.
2021-03-19 | GSE169156 | GEO
Project description:The Preterm Infant Microbiome: Biological, Behavioral and Health Outcomes at 2 and 4 Years of Age
| PRJNA449987 | ENA
Project description:The Preterm Infant Microbiome: Biological, Behavioral and Health Outcomes at 2 and 4 Years of Age
| PRJNA449986 | ENA
Project description:Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention.
2016-06-15 | GSE83334 | GEO
Project description:Less than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSC) survive more than five years post-diagnosis but those who have an exceptionally long survival could provide new insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage, HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome, and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair, and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes, and differential immune responses appear to contribute to long-term survival in HGSC. Methylation profiling was done on 58 high grade serous ovarian cancer samples, 53 of which were primary tumors and and 5 were relapse tumors. 73 primary tumors from GSE65820 were also used as part of the cohort.
2022-08-26 | GSE211686 | GEO
Project description:Genome wide DNA methylation profiling of samples from adult survivors of childhood and young adult cancer, using the Illumina Infinium Human MethylationEPIC Beadchip arrays. Samples included 32 samples, all sampled at least 10 years after diagnosis . Specific therapies and duration between sampling and diagnosis varied.
2020-12-31 | GSE162559 | GEO