Defining the role of the gut microbiome in colorectal cancer: an analysis of molecular mechanisms

Colorectal cancer (CRC) has the 3rd highest incidence and 2nd highest mortality of all cancers in the United States. These numbers have improved with proper screening and the development of new therapies, but CRC continues to evade detection and resist therapy in late stages. The gut microbiome has emerged as a possible explanation for heterogeneity in this disease. In order to help develop screening techniques and accurate, targeted therapies, this review covers the molecular mechanisms by which the microbiome induces CRC. An analysis of current research has confirmed its physiological roles of maintaining intestinal immune homeostasis and metabolizing products produced by the host. When these functions are impaired, CRC can develop. This may occur through damage to the intestinal barrier, inflammation, and production of genotoxins and other metabolites with carcinogenic potential

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Fibrosarcomas of the Paranasal Sinuses: A Systematic Review

Fibrosarcomas are rare, malignant neoplasms of mesenchymal origin. Fibrosarcomas appear to be sporadic, but cases of fibrosarcomas secondary to radiation of nasopharyngeal carcinomas have been reported. Paranasal sinus fibrosarcomas (PNFS) are even rarer with few cases being reported since the 1950s. There have been several retrospective cohort studies examining PNFS; however, to our knowledge, no comprehensive review exists. This review aims to summarize the findings of all published cases of PNFS from the 1950s to the 2020s. We hope that a comprehensive review will assist in accurate and early diagnoses of PNFS, and help guide treatment as early treatment is associated with a favorable prognosis.This systematic review reports results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search was conducted on PubMed, Embase, and Cochrane Library. Studies were screened using established inclusion/exclusion criteria. A total of 26 studies were included for data extraction, and relevant data were collected and analyzed.In our study, the most common study type was case reports (n = 19). The most common presentation for PNFS included male gender (n = 17) with maxillary sinus (n = 57) involvement. Patients commonly presented with complaints of nasal obstruction (n = 15), epistaxis (n = 11), and facial fullness/pain (n = 9). Surgical resection was the mainstay treatment, with the use of chemotherapy or radiation depending on surgical margins and resectability. The diagnosis was commonly made with histological analysis. This review of the literature provides a summary and reference of important presenting factors, elements of diagnosis, and treatment options regarding PNFS to help bring awareness and guide the treatment of such a rare disease. Moving forward, there is a greater need for larger standardized studies that can further complement our findings, as well as more consistent reporting of cases

Formalin fixation increases deamination mutation signature but should not lead to false positive mutations in clinical practice.

Genomic analysis of cancer tissues is an essential aspect of personalized oncology treatment. Though it has been suggested that formalin fixation of patient tissues may be suboptimal for molecular studies, this tissue processing approach remains the industry standard. Therefore clinical molecular laboratories must be able to work with formalin fixed, paraffin embedded (FFPE) material. This study examines the effects of pre-analytic variables introduced by routine pathology processing on specimens used for clinical reports produced by next-generation sequencing technology. Tissue resected from three colorectal cancer patients was subjected to 2, 15, 24, and 48 hour fixation times in neutral buffered formalin. DNA was extracted from all tissues twice, once with uracil-N-glycosylase (UNG) treatment to counter deamination effects, and once without. Of note, deamination events at methylated cytosine, as found at CpG sites, remains unaffected by UNG. After extraction a two-step PCR targeted sequencing method was performed using the Illumina MiSeq and the data was analyzed via a custom-built bioinformatics pipeline, including filtration of reads with mapping quality T/A mutations that is not represented in DNA treated with UNG. This suggests these errors may be due to deamination events triggered by a longer fixation time. However the allelic frequency of these events remained below the limit of detection for reportable mutations in this assay (<2%). We do however recommend that suspected intratumoral heterogeneity events be verified by re-sequencing the same FFPE block

Social constructionism and medical sociology: a reply to M. R. Bury

M. R. Bury has recently published a wide‐ranging criticism of social constructionism as it has been applied to the sociology of medicine. Bury's major misgivings are identified and replied to. It is argued that the constructionist sociology of medical knowledge is not in fact inherently weakened by incoherence or by a failure to recognise the difficulties which surround the questions of realism, reflexivity, or relativism. Nor does social constructionism necessarily cast doubt upon the sincerity of medical practitioners or the possibility of medical progress

Total reads mapped in the baseline group does not change by DNA extraction type.

<p>GR UNG = GeneRead uracil-N-glycosylase, QA = QiaAmp FFPE kit.</p

Experimental workflow.

<p>DNA extracted from three patient groups was sequenced after treatment with and without UNG. The fixation group consisted of three patients from 2015 where paired tissue samples were snap frozen or put into formalin for a determined length of times. A baseline group consisting of 20 patients all from 2015/16 were fixed in formalin for an unknown amount of time. The block age group consisted of three patients from 1994, three from 2004 and three from 2014; all samples had an unknown fixation time. DNA was extracted from normal (N) and tumor (T) tissue when available.</p