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Controlled manipulation of particles from very large volumes of fluid at high throughput is critical for many real-world applications. Here, the authors show bioparticle focusing in a microchannel for a previously unattained regime of inertio-elastic flow at Reynolds numbers up to 10,000.

A new study considers how disruption to energy systems is experienced and takes on meaning. On the basis of workshop data, the study finds that public views of heat decarbonization in the United Kingdom are shaped by relationships to family, cultural expectations, housing and financial position.

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes.

In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

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.

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.

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.

Richard Houlston, Gareth Morgan, Kari Hemminki and colleagues report the results of a genome-wide association study of multiple myeloma. They identify two regions influencing susceptibility to this hematological malignancy.

‘Treatment resistance is common in ovarian high grade serous carcinoma, often leading to relapse. Here, the authors leverage shallow whole genome and panel sequencing of 276 patients with available diagnostic and relapse samples and show high concordance of copy number and mutation status.

The impact of the DART spacecraft on the asteroid Dimorphos is reported and reconstructed, demonstrating that kinetic impactor technology is a viable technique to potentially defend Earth from asteroids.

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.

The authors report on a determination of the momentum transferred to an asteroid by kinetic impact, showing that the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

This study uses in situ respirometry assays and transplant experiments with salmonid fish to disentangle the effects of chronic and acute thermal exposure. They show that chronic exposure to warming can attenuate salmonid thermal sensitivity, highlighting the need to incorporate the potential for thermal acclimation or adaptation when forecasting global warming consequences.

IgE antibodies have shown anti-tumor activity, even superior to IgG, in preclinical models. However, all monoclonal antibodies in clinical use for cancer therapy are members of the IgG class. Here the authors report the results of a phase I clinical trial of a chimeric monoclonal IgE antibody, specific for the folate receptor-alpha, in patients with advanced solid cancer.

Evidence for a past large explosive eruption within the Santorini caldera suggests that early stages of silicic caldera cycles can be more hazardous than previously assumed, according to analyses of intra-caldera deposits from the Kameni Volcano.

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.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

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

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.

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.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

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.

Molnupiravir is an antiviral that forces lethal error catastrophe in SARS-CoV-2 RNAs. Here, the authors confirm the mechanism of action of molnupiravir in humans using samples obtained from the UK’s AGILE phase IIa clinical trial investigating the antiviral efficacy of the drug against SARS-CoV-2. No treatment-associated SARS-CoV-2 mutations were identified.

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

Kiourtis et al. show that liver senescence triggers senescence and dysfunction in other organs through TGFβ secretion from the liver.

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.

Plant root activity increased soil carbon loss by 31%, with rhizosphere priming effects persisting longer in permafrost than active layer soils, indicating greater permafrost carbon vulnerability to microbial decomposition.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

A study using a mouse solid tumour model suggests that adjusting the dosing frequency of the PI3Kδ inhibitor AMG319 in the treatment of human cancers could decrease tumour growth with fewer adverse effects.

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

Random mutagenesis can uncover novel genes involved in phenotypic traits. Here the authors perform a large-scale phenotypic screen on over 100 mouse strains generated by ENU mutagenesis to identify mice with age-related diseases, which they attribute to specific mutations revealed by whole-genome sequencing.

Chromosomal instability enables the continuous selection of somatic copy number alterations, which are established as ordered events that often occur in parallel, throughout tumour evolution and metastasis.

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.

By using exome sequencing and extremes of phenotype, McAllister et al. identify rare coding variants with clinical effect in Huntington’s disease. They show that FAN1 nuclease activity slows CAG expansion and is associated with later onset of HD.

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.

The process by which actinic keratosis differentiates to malignant invasive cutaneous squamous cell carcinoma is unclear. Here, the authors use RNA-seq to illustrate a disease continuum between the two states, and use in vivo models to confirm the role of Tgfbr2, Trp53, and Notch1 in this process.

The efficacy of carbapenem antibiotics can be compromised by metallo-β-lactamases, but a high-throughput screen followed by optimization has now enabled the discovery of indole-2-carboxylates (InCs) as potent broad-spectrum metallo-β-lactamase inhibitors. The results highlight the potential of InC–carbapenem combinations for clinical use as well as mechanism-guided approaches to combatting globally disseminated antibiotic resistant mechanisms.

How anti-helminth and allergic immune responses are initiated is poorly understood. Here the authors show that to trigger these responses, dendritic cells specifically require methyl-CpG-binding domain-2, a protein promoting repressed chromatin state.

Transcriptomic signatures of highly connected network hubs in the newborn brain reveal how early gene expression shapes brain network connectivity during prenatal development.

THOC2 is an essential subunit of Transcription mRNA Export complex of eukaryotic cells and its compromise causes adverse (neuro)development. Using mouse model and patient cells the authors unravel molecular pathology of the syndrome, from R-loops dysregulation, to altered transcriptome and DNA damage triggered cell death.

The third trimester of human gestation is characterised by rapid increases in cortical surface area. Here, authors show that increased rates of cortical expansion are associated with differences in the timing of neurogenesis.

The ages and geochemical compositions of inclusions of sublithospheric diamonds indicate additions to the mantle keel of Gondwana by the underplating of buoyant subducted material, originating from 300–700-km depth, which may have contributed to supercontinent stability during long-distance migration.

McHugh et al. identify COPI trafficking as a vulnerability of senescent cells. N-myristoyltransferase inhibitors phenocopy COPI inhibition and are potent senolytics.