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The heterogenous nature of rheumatoid arthritis renders the prediction of responsiveness to biological treatments difficult. Here the authors analyze bulk RNA-seq data from the STRAP trial (n = 208) to build a machine-learning model for predicting responses to etanercept, tocilizumab and rituximab with AUCs around 0.75 to potentially assist in therapy planning.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

It is unknown how cortical stimulation identifies brain regions critical to speech and language when they depend upon broader brain networks. Here the authors show that these critical areas function as connectors between modules in the language network.

Biomarker analysis of the phase 4 R4RA trial identifies pretreatment synovial biopsy features selectively associated with response to rituximab or tocilizumab, and leads to the development of models that might predict treatment benefit in patients with rheumatoid arthritis

This isoform-centric microglia genomic atlas includes 35,879 novel human microglia isoforms identified by long-read RNA sequencing. A multi-ancestry quantitative trait locus meta-analysis of known and novel isoforms in 555 samples from 391 donors finds associations with genetic risk loci in Alzheimer’s and Parkinson’s diseases.

Integrated analysis of microbiome and host cell transcriptional data on clinically annotated cohorts of patients with melanoma who were treated with anti-programmed cell death protein-1, uncovers new associations of streptococcus species with immune-related adverse effects and finds consistent microbiome associations with clinical outcomes.

A key challenge for compact accelerators is boosting an electron beam’s energy without

sacrificing its brightness. Here, the authors demonstrate the concept of a plasma wakefield

‘dual transformer’, which simultaneously increases both beam energy and brightness of an

electron bunch injected from the plasma at SLAC.

Oldupai Gorge, Tanzania is a key site for understanding early human evolution. Here, the authors report a multiproxy dataset from the Western basin of Oldupai Gorge dating to 2 million years ago, enabling the in situ comparison of lithic assemblages, paleoenvironments and hominin behavioral adaptability.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

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.

The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection.

Proteomics is often used to map protein-drug interactions but identifying a drug’s protein targets along with the binding interfaces has not been achieved yet. Here, the authors integrate limited proteolysis and machine learning for the proteome-wide mapping of drug protein targets and binding sites.

Sequencing and deep analysis of mRNA and miRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project reveal widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent, and the analyses point to putative causal variants for dozens of disease-associated loci.

Switching to air-to-air heat pumps in Toulouse cuts energy use and eliminates CO₂ emissions. While efficiency is high, cities transitioning from fossil fuel heating may see increased electricity use, stressing the need for sustainable power sources.

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.

A massive field study whereby many different treatments are tested synchronously in one large sample using a common objectively measured outcome, termed a megastudy, was performed to examine the ability of interventions to increase gym attendance by American adults.

Dysfunction in dorsal striatum, a brain region important for reward and habits, is linked to opioid use disorder (OUD). Here, authors delineate diverse cell populations in human dorsal striatum, revealing altered inflammatory and DNA damage signaling in OUD.

The molecular and cellular causes of glaucoma are not well understood. Here, the authors integrate GWAS with genetic regulation and single cell expression from multiple eye tissues to identify genes and key cell types that affect glaucoma pathogenesis.

Here, the authors study the interplay between the microbiome and faecal and blood metabolome, and how the microbiome interacts in the dialogue between these metabolic compartments, identifying a key role for microbial functions and underscoring their relevance for microbiome therapeutic strategies.

A significant proportion of individuals with inherited neuromuscular disease do not receive a genetic diagnosis. Here, the authors establish CCG expansions in the 5’ untranslated region of ABCD3 as a cause of oculopharyngodistal myopathy (OPDM) in individuals of European ancestry and identify increased expression of expansion-containing ABCD3 transcripts as a possible disease mechanism underlying muscle degeneration.

In patients with chronic coronary syndrome and an indication for oral anticoagulation, whether continuation of antiplatelet therapy in the initial phase after percutaneous coronary intervention is appropriate in Western populations with high atherothrombotic risk was previously unclear. The AQUATIC trial now shows that continuation of antiplatelet therapy increases the risk of both bleeding and ischaemic events in these patients.

Temozolomide therapy seems to lead to mismatch repair deficiency and hypermutation in gliomas, but not to an increase in response to immunotherapy.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Gene expression, alternative splicing and DNA methylation profiles from human kidney samples provide insights into the effects of common variants influencing blood pressure. Mendelian randomization uncovers the effects of blood pressure on renal outcomes.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.