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Leukemia/lymphoma-related factor (LRF), a transcriptional repressor, plays key roles in cell fate decision and tumorigenesis. Here, Liu et al. show that LRF loss results in defective classical non-homologous end joining, genomic instability and hypersensitivity to ionizing radiation, revealing a transcription-independent regulation of DNA-PK complex.

Modulating mitochondrial NAD⁺ levels by changing the expression of the mitochondrial NAD⁺ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD⁺ levels are a key determinant of the rate of liver regeneration.

Patients with kidney failure undergoing maintenance hemodialysis have poor long-term survival. Here the authors use affinity-based proteomics to identify circulating risk factors for mortality in patients with kidney failure on hemodialysis.

As part of a randomized controlled trial in Viet Nam, this study finds that pneumococcal-specific memory B cells (B_mem) are higher following a 1 + 1 compared to a 0 + 1 pneumococcal conjugate vaccine (PCV) schedule and higher for PCV13 compared to PCV10. B_mem did not wane as rapidly as IgG by 24 months of age.

In this study, the authors identify a mechanism for the distinct conformational preferences of tyrosine kinases vs serine/threonine kinases and suggest that the evolution of tyrosine kinase function can explain these conformational differences.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

The species threat abatement and restoration (STAR) metric quantifies the contributions that abating threats and restoring habitats offer towards reducing species’ extinction risk in specific places.

Arterial dissections are one of the most common forms of vascular lesion to affect the cervical carotid and vertebral arteries, second only to atherosclerosis. Arterial dissections are often caused by sudden or unusual stretching of arteries in the neck or head, and can occur as a complication of chiropractic and other neck manipulations. In this article, Louis Caplan reviews the underlying causes and clinical features of dissections of brain-supplying arteries and outlines the current recommendations for treatment of these lesions.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

In this Primer, Ashina et al. discuss the epidemiology, pathophysiology, diagnosis, management and quality of life of patients with trigeminal neuralgia, a chronic neuropathic facial pain disorder involving one or more branches of the trigeminal nerve that causes intense paroxysms of electric shock-like pain.

Investigators found that denileukin diftitox, which targets the interleukin-2 receptor, achieves objective response rates in 44% of patients with cutaneous T-cell lymphoma, with a median duration of response of 7.8 months and 2% incidence of severe vascular leak syndrome. The inclusion of a placebo arm in the study revealed several additional interesting observations.

Immunotherapy is associated with durable clinical benefit in patients with melanoma, and this consensus statement outlines recommendations for its use. The panel has based their guidance on the available evidence and outlines a treatment paradigm using drugs that are FDA approved.

People infected with West Nile virus often experience cognitive side effects including memory loss through unknown mechanisms; mice and humans infected with the virus experience a loss in hippocampal presynaptic terminals, which can be reversed by disrupting complement or microglia in mice.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Direct evidence for the role of BRCA1 in controlling homologous recombination at stalled replication forks has been obtained in mammalian cells using the bacterial Tus/Ter system.

An ancestry-specific and trans-ethnic meta-analysis of Genome-wide Association Study of blood NfL levels identified multiple loci related to neurodegeneration and potential causal association between reduced kidney function and higher blood NfL levels.

A focus group of expert urologists has reviewed the clinical evidence relating to blue-light cystoscopy with hexaminolevulinate photosensitizer, and here sets out consensus statements for the use of this technique in the diagnosis of non-muscle-invasive bladder cancer.

Proteomics can help to define and identify patients that will most benefit from the increasing number of molecular-targeted agents. In particular, reverse phase protein microarray provides detailed information about the state of the cellular 'circuitry' from small samples such as patient biopsy specimens. This review discusses the clinical applications of this emerging technology and how it could be used to help guide individualized treatment approaches.