Differences in the microbial profiles of early stage endometrial cancers between Black and White women

Objective: Black women suffer a higher mortality from endometrial cancer (EC) than White women. Potential biological causes for this disparity include a higher prevalence of obesity and more lethal histologic/molecular subtypes. We hypothesize that another biological factor driving this racial disparity could be the EC microbiome. Methods: Banked tumor specimens of postmenopausal, Black and White women undergoing hysterectomy for early stage endometrioid EC were identified. The microbiota of the tumors were characterized by bacterial 16S rRNA sequencing. The microbial component of endometrioid ECs in The Cancer Genome Atlas (TCGA) database were assessed for comparison. Results: 95 early stage ECs were evaluated: 23 Black (24%) and 72 White (76%). Microbial diversity was increased (p < 0.001), and Firmicutes, Cyanobacteria and OD1 phyla abundance was higher in tumors from Black versus White women (p < 0.001). Genus level abundance of Dietzia and Geobacillus were found to be lower in tumors of obese Black versus obese White women (p < 0.001). Analysis of early stage ECs in TCGA found that microbial diversity was higher in ECs from Black versus White women (p < 0.05). When comparing ECs from obese Black versus obese White women, 5 bacteria distributions were distinct, with higher abundance of Lactobacillus acidophilus in ECs from Black women being the most striking difference. Similarly in TCGA, Dietzia and Geobacillus were more common in ECs from White women compared to Black. Conclusion: Increased microbial diversity and the distinct microbial profiles between ECs of obese Black versus obese White women suggests that intra-tumoral bacteria may contribute to EC disparities and pathogenesis

Inductively coupled microfluidic pressure meter forin vivomonitoring of cerebrospinal fluid shunt function

A microfluidic pressure sensor with inductively coupled, wireless readout capability has been developed for integration into cerebrospinal fluid shunt valve implants. The sensor consists of a deformable PDMS film that is bonded over a microfluidic reservoir, forming a fluidic capacitor. Deflection of the capacitor membrane is detected remotely through a shift in the resonance frequency of a micro-fabricated LC circuit. Sensors were fabricated by a combination of conventional MEMS technologies and rapid soft lithography. A direct pattern transfer technique was used to pattern the deformable PDMS film with a metal coating for the capacitive readout. The mechanical response of the fluidic capacitor was characterized by measuring the deflection of the PDMS film using an extrinsic Fabry-Perot interferometer (EFPI), and wireless sensing was demonstrated by the shift in resonance frequency of the sensor via an inductively coupled antenna. The sensor transduces pressure into a change in resonant frequency with sensitivity &gt;?3.4?ppm Pa?1 and responsivity 4.6?kHz Pa?1, over a dynamic range of 0 ~ 3 kPa.Keywords CSF shunt, Microfluidic pressure meter, Inductively coupled antenna, Fluidic capacitor, Implantable flowmeter<br/

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes