An integrated tumor, immune and microbiome atlas of colon cancer.

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

Vaginal microbiome: considerations for reproductive health.

The microbial communities are an indispensable part of the human defense system and coexist with humans as symbionts, contributing to the metabolic functions and immune defense against pathogens. An ecologically stable vaginal microbiota is dominated by Lactobacillus species, which plays an important role in the prevention of genital infections by controlling the vaginal pH, reducing glycogen to lactic acid, and stimulating bacteriocins and hydrogen peroxide. In contrast, an abnormal vaginal microbial composition is associated with an increased risk of bacterial vaginosis, trichomoniasis, sexually transmitted diseases, preterm labor and other birth defects. This microbial diversity is affected by race, ethnicity, pregnancy, hormonal changes, sexual activities, hygiene practices and other conditions. In the present review, we discuss the changes in the microbial community of the vaginal region at different stages of a female's life cycle and its influence on her reproductive health and pathological conditions.

Corneal confocal microscopy identifies a reduction in corneal keratocyte density and sub-basal nerves in children with type 1 diabetes mellitus.

PURPOSE: To assess whether alterations in stromal keratocyte density are related to loss of corneal nerve fibres in children with type 1 diabetes mellitus (T1DM). METHODS: Twenty participants with T1DM and 20 age-matched healthy controls underwent corneal confocal microscopy. Corneal sub-basal nerve morphology and corneal keratocyte density (KD) were quantified. RESULTS: Corneal nerve fibre density (CNFD) (p<0.001), corneal nerve branch density (p<0.001), corneal nerve fibre length (CNFL) (p<0.001) and inferior whorl length (IWL) (p<0.001) were lower in children with T1DM compared with healthy controls. Anterior (p<0.03) and mid (p=0.03) stromal KDs were lower with no difference in posterior KD (PKD) in children with T1DM compared with controls. Age, duration of diabetes, height, weight and body mass index did not correlate with anterior (AKD), mid (MKD) or PKD. Inverse correlations were found between glycated haemoglobin and PKD (r=-0.539, p=0.026), bilirubin with MKD (r=-0.540, p=0.025) and PKD (r=-0.531, p=0.028) and 25-hydroxycholecalciferol with MKD (r=-0.583, p=0.018). CNFD, CNFL and IWL did not correlate with AKD, MKD or PKD. CONCLUSION: This study demonstrates a reduction in corneal nerves and anterior and mid stromal KD in children with T1DM, but no correlation between corneal nerve and keratocyte cell loss.

DS86760016, a Leucyl-tRNA Synthetase Inhibitor with Activity against Pseudomonas aeruginosa.

DS86760016 is a new leucyl-tRNA-synthetase inhibitor at the preclinical development stage. DS86760016 showed potent activity against extended-spectrum multidrug-resistant Pseudomonas aeruginosa isolated from clinical samples and in vitro biofilms. In a murine catheter-associated urinary tract infection model, DS86760016 treatment resulted in significant eradication of P. aeruginosa from the kidney, bladder, and catheter without developing drug resistance. Our data suggest that DS86760016 has the potential to act as a new drug for the treatment of Pseudomonas infections.