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Developing chemotherapeutic regimens that can be given at the optimal dose and schedule continues to be one of the greatest challenges in clinical oncology. Simon and Norton discuss how they used guiding principles to derive the Norton–Simon hypothesis, and describe how this has improved clinical trial design and helped to achieve the goal of more effective and less toxic chemotherapeutic regimens.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

Greenwald, Nederlof and colleagues developed a computational pipeline analyzing multiplex imaging data and established spatial patterns within breast cancer microenvironment that are predictive of immune checkpoint blockade response across treatment time course.

In this article, the authors characterise genetic variation in CARTaGENE, a population-based cohort from Quebec, Canada. This genomic resource enables population and disease genetic studies in a founder population and other under-represented groups.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Although noise is typically detrimental to quantum devices, it can serve as a resource for quantum thermal machines. Here, the authors demonstrate a device based on a superconducting quantum circuit that leverages noise to function as either a quantum heat engine or a refrigerator.

Gravitational lens modelling of a million-solar-mass dark object reveals that it cannot be a free-floating black hole or dark-matter halo as predicted by cold dark matter, instead indicating a peculiar and highly concentrated mass distribution.

Using food residues on pottery vessels and dental calculus, and faunal remains, Casanova et al. find evidence that Neolithic communities in Iran were milking goats or sheep as early as the seventh millennium BC.

Approved antibody–drug conjugates (ADCs) remain constrained by a limited repertoire of payloads with restricted modes of action. Here, the authors present phosphoramidate-based self-immolative linker units that facilitate stable attachment in serum and traceless drug release in the target cell from aliphatic and aromatic alcohols with various modes of action.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

High-resolution 3D simulations reveal that rotation dramatically amplifies wave-driven mixing in red giant stars, providing a natural explanation for observed changes in surface chemistry that have long puzzled astronomers.

Clock precision is thought to be fundamentally limited by entropy production in out-of-equilibrium systems. A theoretical work now introduces a quantum clock design where precision grows exponentially with dissipation.

A mode-locked laser is achieved by coupling two ring resonators in a parity–time-symmetric configuration. Stable pulses emerge through a balance of gain in one cavity and loss in the other, combined with symmetry-breaking induced by the Kerr effect.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Although our nearest neighbour, the Andromeda galaxy, is falling towards us, slightly more distant galaxies all move away with the cosmic expansion because they are being pulled by a giant dark matter sheet.

In a case series of eight pediatric patients with systemic lupus erythematosus, dermatomyositis or systemic sclerosis, autologous anti-CD19 CAR T cell therapy was feasible, safe and effective in reducing disease activity.

Based on two waves of data collection from 748 households in Hong Kong, this analysis sheds light on the number of transmission events that occurred before manifestation of symptoms in influenza A and B cases.

HORBEC are protein complexes involved in the regulation of redox balance and energy conservation. The authors develop a bioinformatic tool for HORBEC annotation in bacterial and archaeal genomes and reconstruct the evolutionary history of these fundamental enzymes.

A bookkeeping approach shows that disturbed tropical humid forests experienced net aboveground carbon loss during 1990–2020, primarily driven by small but persistent deforestation clearings owing to persistent land-use conversion without forest regrowth.

Superlubric arrays of double-bilayer graphene enable elastically coupled switching between Bernal and rhombohedral graphene polytypes under shear forces below 1 nN with an estimated energy cost of less than 1 fJ per switching event.

Non-Annex I countries—mostly developing countries under the UN climate framework—excluding China accounted for approximately 61% of hydrofluorocarbon emission growth during 2011–2020, while China’s emissions have been overestimated since 2017, according to atmospheric observational data and inverse modelling.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The emergence of SARS-CoV-2 variants resistant to neutralizing antibodies poses a constant threat. Here, the authors identify a camelid antibody targeting ACE2 which broadly inhibits infection and provides antiviral protective effects in vivo after nasal inoculation.

Respiratory virus genomic surveillance output is unevenly distributed globally. Here, the authors show that addressing this imbalance could substantially reduce the time to first detection of novel (variant) viruses, enhancing surveillance effectiveness and efficiency.

Africa will drive much future urbanization. Using data from 1950–2020 and techniques from urban science, this study finds increasing economies of scale in land use and increasing concentrations of people in larger cities, contributing to broader patterns of urban evolution.

Baked sediment, heat-shattered artefacts and introduced pyrite in a 400,000-year-old Palaeolithic occupation site in Suffolk, UK provide evidence of intentional fire-making, marking a pivotal moment in human development.

Here the authors show that PARP inhibition activates SIRT-1–FOXO1 signaling to drive transcriptional and metabolic reprogramming of CD8⁺ T cells into central memory T cells with superior recall capacity and efficacy in adoptive therapy.

A cavity-array microscope is realized using intra-cavity lenses to create a two-dimensional array of over 40 modes, each coupled to a single atom in free-space.

This study applies a global food and land system modelling framework to quantify the impact of 23 food system measures on 15 outcome indicators related to public health, the environment, social inclusion and the economy—from today until 2050.

Liu and colleagues demonstrate that biomimetic fractal patterns derived from glomerular histology can enhance the maturation of podocytes (highly differentiated glomerular cells) that are grown in culture. This work presents a bioengineered platform for improved cell culture fidelity.

It is shown that clusters of tree canopies within Kalahari landscape in southern Africa lack characteristic size, with the size distributions following power laws. Model results indicate that this apparent self-organized behaviour can be explained by positive feedbacks that operate in this water-limited ecosystem as a result of preferential environments formed within the vicinity of existing trees.

The study presents an updated global inventory of glacial lake outburst floods, revealing a sharp rise in event frequency since the 1980s and a strong delayed link to climate warming, highlighting growing risks to downstream communities.

Carbonate production and accretion is negatively affected by ocean warming and acidification, threatening coral reef persistence. This Review synthesizes understanding of environmental impacts on reefs, highlighting the dominant role of heatwaves in reef decline and the importance of thermal adaption for future reef persistence.

A recent study highlights how data changes not only how we can assess the performance of legal firms in the US, but more broadly how computational science is expanding beyond its traditional scope and into the legal field.

Tumour-reactive CD8⁺ T cells are enriched in functional clusters with tumour cells and/or antigen-presenting cells and can be isolated and expanded from clinical samples.

In a multicenter, randomized trial of patients with atrial fibrillation and a low risk of thromboembolic events, treatment with the anticoagulant rivaroxaban showed no benefit in reducing cognitive decline, stroke or transient ischemic attack when compared to placebo.

Arrays of nanowire loops consisting of two temperature-dependent superconducting switches and a variable kinetic inductor can be used to create a robust and scalable superconducting memory.

The emerging field of imaging-by-sequencing aims to perform spatial biological analyses by molecular interactions. Here, authors used previously undiscovered spatial networks within Slide-tags data to reconstruct cell positions and capture biological information comparable to the original method.

Attosecond control of electrons in nanostructures requires resolving dynamics in the optical near field. Now, an experiment finds low-energy spectral stripes that track subcycle electron emission and allow the isolation of attosecond electron bursts.

The extreme hot and dry conditions of 2023 reduced soil respiration and enhanced net forest carbon sequestration in Canada, offsetting wildfire emissions, according to satellite-based and in situ observations of CO₂ fluxes.

We show that FOXF2 maintains cerebrovascular function through Tie2 signaling, and that pharmacological activation of Tie2 with AKB-9778 rescues deficits in cerebral small vessel disease and stroke.