Search

A new meta-analysis, which evaluated individual patient data from randomized trials of aspirin in patients with non-disabling acute brain ischaemia, found this drug to be much more efficacious at reducing early stroke recurrence than was previously estimated.

Genomic and phenomic screens of 827 wheat landraces from the A. E. Watkins collection provide insight into the wheat population genetic background, unlocking many agronomic traits and revealing haplotypes that could potentially be used to improve modern wheat cultivars.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Aberrant synchronous oscillations have been associated with numerous brain disorders, including essential tremor. The authors show that synchronous cerebellar activity can casually affect essential tremor and that its underlying mechanism may be related to the temporal coherence of the tremulous movement.

Highly pathogenic avian influenza is an increasing global concern but its distribution in remote regions is not known. Here, the authors conduct an environmental influenza surveillance study in remote, uninhabited regions of the Global South by sampling fresh bird guano.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The mechanisms underlying the effects of repetitive transcranial magnetic stimulation (rTMS) are unclear. Ridding and Rothwell argue that a better understanding of these mechanisms and the conditions for which rTMS is used will reveal whether rTMS offers true therapeutic potential.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

Tumour-promoting inflammation is an enabling characteristic of many cancers. Conversely, many cancers can cause inflammation. Inflammation in the tumour microenvironment arises from the interplay of many different inflammatory cells and mediators, many of which are potential treatment targets. Herein, the authors review our current knowledge of the interplay between inflammation and tumorigenesis and discuss the potential of treatments that target cancer-related inflammation.

Pulmonary venous tumor cells disseminating before tumor resection are heterogeneous, predict relapse and seed future metastasis of lung cancer

The association between certain mitochondrial DNA variants and increased risk of late-onset diseases in humans could be explained by a direct role of mitochondrial DNA in the regulation of cellular proteostasis.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Manchester institute will focus on commercial applications of atom-thick carbon sheets.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Patients with colorectal cancer with mutated PIK3CA, identified from two large observational cohorts, had increased cancer-specific and overall survival if they used aspirin regularly after diagnosis compared to non-users. No effect of aspirin was seen in patients with wild-type PIK3CA. Mutated PIK3CA might be a useful biomarker to select patients who would benefit from adjuvant aspirin therapy.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

Exploratory ctDNA analyses from the phase 3 INTRIGUE trial indicate that ripretinib may provide benefits in patients with advanced gastrointestinal stromal tumors with KIT exon 11 + 17/18 mutations

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.