Advances in single-cell long-read sequencing technologies.

With an increase in accuracy and throughput of long-read sequencing technologies, they are rapidly being assimilated into the single-cell sequencing pipelines. For transcriptome sequencing, these techniques provide RNA isoform-level information in addition to the gene expression profiles. Long-read sequencing technologies not only help in uncovering complex patterns of cell-type specific splicing, but also offer unprecedented insights into the origin of cellular complexity and thus potentially new avenues for drug development.

English translation and cross-cultural validation of the patient-reported outcome measurement-haemorrhoidal impact and satisfaction score (PROM-HISS).

Aim: The aim of this study was to translate the Dutch patient-reported outcome measure-haemorrhoidal impact and satisfaction score (PROM-HISS) to English and perform a cross-cultural validation.

Method: The ISPOR good practice guidelines for the cross-cultural validation of PROMs were followed and included two steps: (1) Two forward and two backward translations. The forward translation concerned the translation from the source language (Dutch) to the target language (English), performed by two independent English speakers, one medical doctor and one nonmedical.

Predicting necrotising soft tissue infections in people who inject drugs: poor performance of the Laboratory Risk Indicator for Necrotising Fasciitis score and development of a novel clinical predictive nomogram in a retrospective cohort with internal validation.

Introduction: Necrotising soft tissue infections (NSTI) can threaten life and limb. Early identification and urgent surgical debridement are key for improved outcomes. NSTI can be insidious.

Single-Cell DNA Methylation Analysis in Cancer.

Morphological, transcriptomic, and genomic defects are well-explored parameters of cancer biology. In more recent years, the impact of epigenetic influences, such as DNA methylation, is becoming more appreciated. Aberrant DNA methylation has been implicated in many types of cancers, influencing cell type, state, transcriptional regulation, and genomic stability to name a few.

Structure of phospholipase Cε reveals an integrated RA1 domain and previously unidentified regulatory elements.

Phospholipase Cε (PLCε) generates lipid-derived second messengers at the plasma and perinuclear membranes in the cardiovascular system. It is activated in response to a wide variety of signals, such as those conveyed by Rap1A and Ras, through a mechanism that involves its C-terminal Ras association (RA) domains (RA1 and RA2). However, the complexity and size of PLCε has hindered its structural and functional analysis.

Efficacy of low-dose and/or adjuvant methadone in palliative medicine.

Objectives: To summarise the current body of published evidence on the use of low-dose and/or adjuvant methadone in the palliative care setting.

Methods: The authors searched multiple databases (PubMED, SCORPUS, EMBASE and the Cochrane library) for relevant articles using the terms 'methadone', 'palliative', 'low dose' and 'adjuvant'. The review was restricted to articles published between 2003 and 2018.

Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?

Background: Cancer is first and foremost a disease of the genome. Specific genetic signatures within a tumour are prognostic of disease outcome, reflect subclonal architecture and intratumour heterogeneity, inform treatment choices and predict the emergence of resistance to targeted therapies. Minimally invasive liquid biopsies can give temporal resolution to a tumour's genetic profile and allow the monitoring of treatment response through levels of circulating tumour DNA (ctDNA).

BMP2/BMPR1A is linked to tumour progression in dedifferentiated liposarcomas.

Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type.

BDNF Val66Met polymorphism and lithium response: a meta-analysis.

Aim: To characterize the impact of the Val66Met polymorphism on lithium response in patients with bipolar disorder.

Methods: A systematic literature search of MEDLINE, Web of Science, PsychINFO and Cochrane CENTRAL was conducted from the earliest possible date through to 1 July 2012. The search was performed using the following medical subject headings: bipolar disorder, lithium, lithium carbonate, pharmacogenomics, pharmacogenetics, polymorphism and brain-derived neurotrophic factor.