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DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

Sabatino and colleagues examine expanded CD8⁺ T cell clonotypes from a small cohort of multiple sclerosis patients. They identified several cognate peptide epitopes that derive from Epstein–Barr virus, suggesting EBV reactivation may drive pathogenesis in these patients.

Microglia can alter their properties to adopt a wide spectrum of cellular phenotypes. Here, the authors show that remodeling of microglial mitochondria accompanies microglial responses to challenges and aging, and provide evidence that these organelles play a role in regulating basal microglial morphology, gene expression, and inflammatory profile.

This study shows how escalating floods, droughts, heatwaves, fires, and landslides in the Amazon create unequal risks for Indigenous and traditional communities, urging climate justice in the world’s largest tropical forest.

A well-preserved skeleton of a nearly mature tyrannosaur from the Hell Creek Formation in Montana, USA supports the existence of a second Nanotyrannus species, Nanotyrannus lethaeus sp. nov., and validates the recognition of Nanotyrannus as a genus separate from Tyrannosaurus.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

In this study, the authors report that post-vaccination neutralizing and binding antibody levels in the ENSEMBLE trial associate with Ad26.COV2.S vaccine efficacy (VE) against severe-critical COVID-19, with substantial VE even at unquantifiable neutralizing antibody titer.

International testing that is used to predict the grim future of US science and technology is being vastly misinterpreted, say Hal Salzman and Lindsay Lowell.

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

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.

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.

Unlike Amazonian forests, African forests have maintained their carbon sink until recently but by 2030 the African carbon sink will have shrunk by 14 per cent and the Amazonian sink will reach almost zero.

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.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

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.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

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.

The scavenger receptor Scara1, expressed on microglia and macrophages, binds beta amyloid aggregates. In a mouse model of Alzheimer’s disease, the authors show that Scara1deficiency is associated with reduced clearance and increased deposition of aggregates in the brain, which results in early mortality.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

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.

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.

The ability to genetically modify haematopoietic stem cells would allow the durable treatment of a diverse range of genetic disorders but gene delivery to the bone marrow has not been achieved. Here lipid nanoparticles that target and deliver mRNA to 14 unique cells within the bone marrow are presented.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

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.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

A catalogue of the vascular flora of New Guinea indicates that this island is the most floristically diverse in the world, and that 68% of the species identified are endemic to New Guinea.

Engineered neutralizing antibodies are potential therapeutics for numerous viruses, such as respiratory syncytial virus (RSV). Here, the authors develop an mRNA-based approach to express membrane-anchored neutralizing antibodies in the lung and demonstrate that it inhibits RSV infections in mice.

Tissue-preserving focal therapies that target individual cancer lesions rather than the whole prostate have emerged as potential interventions for localized prostate cancer. In this article, the Prostate Cancer RCT Consensus Group recommends the development of a cohort-embedded randomized controlled trial methodology to evaluate focal therapy use in men with clinically significant localized disease. The importance for a randomized controlled trial design to provide cost-efficient practice-changing data is highlighted.

Analyses of in vivo models, cell lines and patient-derived samples show that apolipoprotein B mRNA-editing catalytic subunit 3B (APOBEC3B) not only restrains lung tumor initiation but also that its upregulation is associated with resistance to targeted therapies. This study highlights the complex and context-dependent role of APOBEC3B in lung cancer.

Effective government partly depends on effective communications to citizens. Over six studies in three different policy contexts, Linos et al. identify a counter-intuitive formality effect: citizens are more likely to respond to formal government communications than informal ones.

The impacts of SARS-CoV-2 infection and COVID-19 vaccination in pregnancy are not fully understood. Here, the authors perform a cohort study using data from Scotland and find that infection was associated with increased risk of preterm birth and some adverse maternal outcomes, but there was no evidence of adverse outcomes associated with vaccination.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Data on the safety of COVD-19 vaccines in early pregnancy are limited. Here, the authors assess the rates of miscarriage and ectopic pregnancy following vaccination using electronic health record data from Scotland, and find no evidence of increased risks.

The risks of major congenital anomalies associated with SARS-CoV-2 vaccination in early pregnancy are not well understood. Here, the authors conduct a population-based cohort study using electronic health records from Scotland and find no evidence of an association, supporting vaccine safety in pregnancy.

Gold-standard evidence for correlates of protection is provided by analysis of a randomized phase 3 trial of Ad26.COV2.S for protection against moderate to severe-critical COVID-19 disease.

Loss of inner ear hair cells leads to permanent hearing loss and balance dysfunction. Whether human utricular cells regenerate is unknown. Here, the authors present a single-cell resource of utricular cells from organ donors and schwannoma patients and describe transcriptional changes during homeostasis and in response to damage.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

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.

Iris Heid, Gonçalo Abecasis, Sudha Iyengar and colleagues report the results of a large genome-wide association meta-analysis of macular degeneration based on over 43,000 subjects. They identify 16 new risk loci, including some very rare coding variants.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

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.