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Gamboa et al. develop a chimeric antigen receptor (CAR) T cell therapeutic strategy based on synthetic antigens that are delivered to the tumor by lipid nanoparticles and demonstrate the therapeutic efficacy of their approach using CAR T cells directed against the synthetic antigen.

Here, using multi-omics, the authors reconstruct metabolic models and uncover how disrupted metabolic interactions between gut microbes and the host contribute to IBD, together suggesting that dietary modulation of the microbiome may help restore metabolic balance.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

Easing restrictions amid rising infections raises the risk of new variants emerging and risks the health of those who are not vaccinated, say researchers around the world.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

The authors perform meta-analysis of GWAS studies for asthma from multiancestral cohorts. They identify five new loci and find that the asthma-associated loci are enriched near enhancer marks in immune cells.

Clazosentan—a drug previously demonstrated to reduce angiographic vasospasm in patients with aneurysmal subarachnoid hemorrhage—had no significant effect on vasospasm-related morbidity and mortality in the CONSCIOUS-2 trial. A multifactorial cause for delayed ischemic neurological deficits might partly account for these negative findings.

Properties of relaxor ferroelectrics are governed by polar nanodomains. Polarization rotation facilitated by these domains investigated by means of epitaxial strain reveals a competition between chemistry-driven disorder and strain-driven order.

Spin-charge interactions are at the core of electronic correlation phenomena in Mott insulators. Here, the authors observe a positive anomalous magnetoresistance in a SrIrO₃/SrTiO₃ superlattice, indicative of strong spin-charge fluctuations in this pseudospin-half square-lattice Mott insulator.

In a zebrafish model of human cutaneous and acral melanomas, CRKL amplification causes tumours to favour a fin location, indicating that tumour location is determined by both the driver oncogenes and the pre-existing positional identity gene program.

The relative merits of clipping and endovascular coiling to treat ruptured intracranial aneurysms are the subject of an ongoing debate. The latest results from the International Subarachnoid Aneurysm Trial offer reassurance regarding the long-term outcomes of coiling and provide support for an individualized approach.

A large, retrospective study indicates that in patients with acute ischemic stroke, endovascular interventions performed under conscious sedation carry a lower risk of poor neurological outcome and mortality than those performed under general anesthetic. Owing to a number of potential confounding factors, however, the results must be interpreted with caution.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

Alteration of the epigenetic landscape has been implicated in several disease processes, where targeting histone modifiers may have therapeutic applications. Here the authors report a bifunctional small molecule inhibitor that simultaneously targets the deacetylase (HDAC1) and demethylase (LSD1) activities of the CoREST complex.

A genome-wide association study including 22,389 cases of multiple sclerosis finds an association with disease progression at the DYSF–ZNF638 and DNM3–PIGC loci and identifies a potential of higher educational attainment in slowing disease progression.

Global sampling of microbial communities associated with wastewater treatment plants and application of ecological theory revealed a small, core bacterial community associated with performance and provides insights into the community dynamics in this environment.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

Genome-wide association analyses identify new risk loci for allergic rhinitis and for sensitization to inhalant allergens. The associated regions implicate immune-related pathways, including innate and adaptive IgE-related mechanisms.

A superlattice consisting of SrIrO₃ and SrTiO₃ is shown to display a giant response to sub-tesla external magnetic fields—a direct consequence of its antiferromagnetic nature.

The nuclear factor TOX is highly expressed in antigen-specific dysfunctional T cells in tumours and exhausted T cells during chronic viral infection and is a crucial regulator of the differentiation of tumour-specific T cells.

In this Evidence-Based Guideline article, an international, multidisciplinary group of experts presents evidence-based consensus recommendations on screening for cancer in patients with adult-onset idiopathic inflammatory myopathy, addressing cancer risk stratification, screening modalities and screening frequency.

Amyloid-related imaging abnormalities are the most impactful adverse effect of anti-amyloid-β immunotherapies. Here, the authors review the detection, underlying mechanisms and clinical implications of amyloid-related imaging abnormalities and highlight the need for further research to predict, prevent and treat the condition.

Multiregion spatial histology, exome and transcriptome data from patients with non-small cell lung cancer suggest that cancer subclones from immune cold regions diversify later than subclones from immune hot regions

In this Roadmap, Marrie and colleagues set out the steps needed to improve our understanding of the multiple sclerosis (MS) prodrome and develop standardized criteria for identifying individuals with prodromal MS, thereby facilitating trials of interventions that could slow progression to classical MS.

Lavinia Paternoster and colleagues report the results of a large, multi-ancestry genome-wide association study of atopic dermatitis. They identify ten new susceptibility loci harboring candidate genes involved in innate host defense and T cell function.