Project description:Simple Markov model for a disease model.
The model uses two disease states: Alive and Dead, where the Dead state terminates simulation.
The yearly probability of transition between states Alive and Dead is: 0.05
Initial conditions: 100 people start in Alive and none in Dead.
Output: Number of people in each state for years 1-10.
Project description:Microarray was performed on PBMC with an inflammatory dedicated slide of 340 genes, and target samples labelled with Cy3 for day 0 (reference) and with Cy5 for the other days. Changes in expression levels were evaluated by the ratio Dx/D0. According to outcome and time evolution, a two-dimensional clustering was performed. Keywords: dead vs alive septic shock patients at D1 post-inclusion
Project description:Purpose The role of intestinal flora in carcinogenesis and chemotherapy efficacy has been increasingly studied; however, comparisons between oral and intestinal flora remain limited. This study aimed to identify the microbial changes in urothelial carcinoma (UC) by analyzing oral saliva and stool samples from healthy individuals and patients. We also examined the association between microbial composition and immune checkpoint inhibitor (ICI) response. Methods A total of 20 healthy individuals and 38 patients with UC were analyzed. Among them, 27 patients with UC underwent ICI treatment. Oral saliva and stool samples were analyzed for 16S rRNA sequences to assess bacterial composition. Operational taxonomic units were generated, and phylogenetic analysis was performed using the 16S Metagenomics app whithin the Illumina BaseSpace Sequence Hub. Results Patients with UC showed higher Veillonellaceae and Prevotellaceae levels in saliva and stool, with lower levels of these bacteria associated with more prolonged overall survival and progression-free survival, particularly Veillonellaceae in stool. A higher neutrophil-to-lymphocyte ratio correlated with increased levels of these bacteria. Conclusion Veillonellaceae and Prevotellaceae are potential microbial biomarkers of survival outcomes and ICI efficacy in patients with UC. Non-invasive oral microbial sampling may facilitate personalized cancer treatment strategies.
Project description:Human death marks the end of organismal life under conditions such that the components of the human body continue to be alive. Such postmortem cellular survival depends on the nature (Hardy scale) of human death. Slow and expected death typically result from terminal illnesses and includes a prolonged terminal phase of life. As such organismal death process unfolds, do cells of the human body adapt for postmortem cellular survival? Organs with low energy cost-of-living, such as the skin, are better suited for postmortem cellular survival. In this work, the effect of different durations of terminal phase of human life on postmortem changes in cellular gene expression was investigated using RNA sequencing data of 701 human skin samples from the Genotype-Tissue Expression database. Longer terminal phase (slow-death) was associated with a more robust induction of survival pathways (PI3K-Akt signaling) in postmortem skin. Such cellular survival response was associated with the upregulation of embryonic developmental transcription factors such as FOXO1, FOXO3, ATF4 and CEBPD. Upregulation of PI3K-Akt signaling was independent of sex or duration of death-related tissue ischemia. Analysis of single nucleus RNA-seq of post-mortem skin tissue specifically identified the dermal fibroblast compartment to be most resilient as marked by adaptive induction of PI3K-Akt signaling. Prospective studies depicted hypomethylation of PI3K-Akt signaling genes in slow compared to fast human death. Compared to fast death, slow death also induced angiogenic pathways in the dermal endothelial cell compartment of postmortem human skin. In contrast, specific pathways supporting functional properties of the skin as an organ were downregulated following slow death. Such pathways included melanogenesis and those representing the skin extracellular matrix. Efforts to understand the significance of death as a biological variable in influencing the transcriptomic composition of surviving component tissues has far-reaching implications including rigorous interpretation of experimental data collected from the dead and mechanisms involved in transplant-tissue obtained from dead donors.
Project description:In the present study we evaluated the miRNA expression profile of 31 high risk, stage 4 neuroblastoma patients. We compared miRNA expression profiles of 14 long-survivors (alive with an overall survival time > 36 months) and 17 short-survivors (dead of disease within 36 months from diagnosis. Deaths due to toxicity were censored).
Project description:Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AMs) in patients with acute respiratory distress syndrome (ARDS) could identify dynamic biologic processes that are associated with clinical outcomes. Objectives: To identify associations between AM transcriptional programs and the composite endpoint of ventilator-free days (VFDs) over the course of ARDS. Methods: We performed unbiased genome-wide transcriptional profiling of AMs purified from bronchoalveolar lavage fluid collected from patients with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset. We assessed pathway enrichment in subjects with VFDs > 0 (VFD-Extubated/Alive) versus VFDs = 0 (VFD-Intubated/Dead) at each time point. Measurements and Main Results: We found highly divergent AM transcriptional patterns at all time points between ARDS patients based on their VFD status (FDR < 0.05). “M1-like” and pro-inflammatory gene sets such as IL-6-JAK-STAT signaling were significantly enriched in AMs isolated on Day 1 in VFD-Extubated/Alive versus VFD-Intubated/Dead subjects. In contrast, many of these same gene sets were associated with the VFD-Intubated/Dead subjects on Day 8. In patients who had samples from each time point, we identified multiple AM gene clusters whose temporal expression patterns were associated with VFD status. The relationship between AM expression profiles and VFDs was distinct in subjects with Direct (pulmonary) versus Indirect (extrapulmonary) ARDS. Conclusion: Clinically meaningful outcomes over the course of ARDS are associated with highly distinct AM transcriptional programs. Our findings suggest that interventions targeting the alveolar immune response should be tested within strictly defined time periods.
2019-03-31 | GSE116560 | GEO
Project description:RNA-seq for macrophages infected by dead or alive bacterial
Project description:A healthy existence relationship between mussels and environment relies on suitable PH, adequate oxygen and suitable temperature. Besides ocean acidification, ocean warming has been shown to cause mussel dead, a phenomenon responsible for extensive mussel dead around the word. How heat stress impacts mussel alive is poorly understood. We founded that. The superoxide dismutase (SOD) activity of two treatment groups were significantly higher than that of control group, and the activity of acid phosphatase (ACP) was significantly higher in two treatment groups than control group. The lactate dehydrogenase (LDH) activity of 26 ℃ treatment group was significantly higher than that of control group, and the LDH activity of 33 ℃ treatment group was significantly lower than that of control group. Cellular content of lysozyme (LZM) was significantly higher in two treatment groups than control group. In this study, we applied TMT quantification to investigate how Mytilus coruscus responds to heat stress (26 ℃, 33 ℃). We identified 1652 to 1878 differentially expressed proteins (DEPs) from these heat conditions, among which 897 were commonly regulated by all the two temperature and were significantly enriched in nutrients digestion and absorption (e. g. fat digestion and absorption). Furthermore, proteins associated with nutrients metabolism, signaling pathways (p53 signaling pathway and MAPK signaling pathway)and energy metabolism (e. g. TCA cycle) were impacted, suggesting that the ability of basic metabolism of Mytilus coruscus may be altered by heat stress.
Project description:Villin-Cre+ Lsd1fl/fl (cKO) mice display an immature intestinal epithelium characterized by an incomplete differentiation of enterocytes and secretory lineages, reduced number of goblet cells and a complete loss of Paneth cells. This experiment aims to elucidate the differences in stool microbial composition derived from WT (Villin-Cre- Lsd1fl/fl) and cKO mice both in adult (2-month-old) and neonatal (14 days postpartum P14) stages. Different timepoints are crucial to understand the role of intestinal maturation in microbiome composition since said maturation is dependent on time-dependent external cues happening at P14-21 (weaning and transition from milk to solid foods).
Project description:Clinical data from IMblaze370: Clinical data include disease, treatment arm, MSI status, KRAS oncogenic mutation status, sex, and overall survival (1=dead, 0=alive)