Aneuploidy and complex genomic rearrangements in cancer evolution.

Mutational processes that alter large genomic regions occur frequently in developing tumors. They range from simple copy number gains and losses to the shattering and reassembly of entire chromosomes. These catastrophic events, such as chromothripsis, chromoplexy and the formation of extrachromosomal DNA, affect the expression of many genes and therefore have a substantial effect on the fitness of the cells in which they arise.

Single-cell analysis reveals prognostic fibroblast subpopulations linked to molecular and immunological subtypes of lung cancer.

Fibroblasts are poorly characterised cells that variably impact tumour progression. Here, we use single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry (CIBERSORTx) to identify and characterise three major fibroblast subpopulations in human non-small cell lung cancer: adventitial, alveolar and myofibroblasts. Alveolar and adventitial fibroblasts (enriched in control tissue samples) localise to discrete spatial niches in histologically normal lung tissue and indicate improved overall survival rates when present in lung adenocarcinomas (LUAD).

A genetic model for central chondrosarcoma evolution correlates with patient outcome.

Background: Central conventional chondrosarcoma (CS) is the most common subtype of primary malignant bone tumour in adults. Treatment options are usually limited to surgery, and prognosis is challenging. These tumours are characterised by the presence and absence of IDH1 and IDH2 mutations, and recently, TERT promoter alterations have been reported in around 20% of cases.

Characterising cancer-associated fibroblast heterogeneity in non-small cell lung cancer: a systematic review and meta-analysis.

Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with evidence suggesting they represent a heterogeneous population. This study summarises the prognostic role of all proteins characterised in CAFs with immunohistochemistry in non-small cell lung cancer thus far. The functions of these proteins in cellular processes crucial to CAFs are also analysed.

A non-linear optimisation method to extract summary statistics from Kaplan-Meier survival plots using the published P value.

Background: Meta-analyses of studies evaluating survival (time-to-event) outcomes are a powerful technique to assess the strength of evidence for a given disease or treatment. However, these studies rely on the adequate reporting of summary statistics in the source articles to facilitate further analysis. Unfortunately, many studies, especially within the field of prognostic research do not report such statistics, making secondary analyses challenging.

An Optimized Method to Isolate Human Fibroblasts from Tissue for Analysis.

Despite their involvement in many physiological and pathological processes, fibroblasts remain a poorly-characterized cell type. Analysis of primary fibroblasts while maintaining their phenotype is challenging: standard methods for fibroblast isolation require cell culture , which is known to alter phenotypes. Previously-described protocols for the dissociation of primary tissues fail to extract sufficient numbers of fibroblasts, instead largely yielding immune cells.

An optimised tissue disaggregation and data processing pipeline for characterising fibroblast phenotypes using single-cell RNA sequencing.

Single-cell RNA sequencing (scRNA-Seq) provides a valuable platform for characterising multicellular ecosystems. Fibroblasts are a heterogeneous cell type involved in many physiological and pathological processes, but remain poorly-characterised. Analysis of fibroblasts is challenging: these cells are difficult to isolate from tissues, and are therefore commonly under-represented in scRNA-seq datasets.

Reducing the incidence of post-dural puncture headache.

First reported in 1898, post-dural puncture headache (PDPH) remains a significant clinical issue. Here, we present a brief case history and a summary of the current evidence for methods to reduce PDPH rates, along with the experience in our department of implementing these methods in clinical practice. The key points to note are that needle design, gauge and orientation, as well as stylet reinsertion, are factors known to affect the incidence of PDPH, and that there is no evidence to support the use of hydration and bed rest to reduce headache following dural puncture.