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This study develops and validates a prognostic staging framework for Alzheimer’s disease by integrating cognitive status with blood-based biomarkers, and neuroimaging data, to improve risk stratification across the disease continuum.

The authors show that plasma AT(N) biomarkers can distinguish Alzheimer’s disease and frontotemporal lobar degeneration in diverse Latin American populations. Using machine learning and integrating neuroimaging, significant diagnostic accuracy was achieved, enhancing clinical assessments of these conditions in Latin America.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

Post-acute infection syndromes often have heterogeneous symptoms that are difficult to interpret. Here, the authors develop a latent trajectory analysis framework designed to categorise complex relationships in longitudinal data into distinct disease phenotypes and analyse transitions between them.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

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.

Bright electron bunches power particle physics and photon science. Here, reproducible bunches were generated in a plasma with simultaneous high charge per unit energy and low emittance, advancing a scheme to produce ultra-bright bunches in future.

A spatial and single-cell transcriptomics study across multiple mammalian species identifies epidermal BMP signalling as a functional requirement for rete ridge formation, providing insight into mechanisms underlying hair density loss and wound healing.

Emissions from croplands are an important source of GHG emissions that can be shaped by management. This study presents maps of emissions globally for different crops, showing that drained peatlands, rice paddies and fertilizer were the main drivers, and highlights differences in emission intensity.

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.

By combining satellite observations with ground-based data and expert validation, this analysis demonstrates considerable misestimation of grassland extent and thereby carbon stock estimates in previous global assessments based on remote sensing.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Ribas and colleagues report the results of a phase 2 clinical trial of neoadjuvant PD-1 blockade in patients with surgically resectable desmoplastic melanoma.

The study of the interplay between topological states and correlated states such as charge density waves (CDW) requires a thorough understanding of their electronic structure. In this work, the authors resolve the fully CDW reconstructed electronic structure of TaTe4, a candidate topological material, using a combined theoretical and experimental approach based on magnetotransport measurements, which also reveal the existence of large magnetic breakdown orbits and linear magnetoresistance.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

The authors present the results of a phase I/II clinical trial using autologous CD133+ bone marrow stem cell therapy to restore fertility in patients with Asherman Syndrome. The intervention was safe and showed promising results for the restoration of menstruation and reproductive function.

Organisms vary in their nitrogen and phosphorus content, shaping ecological and evolutionary processes. This study shows that nitrogen deposition is a consistent global factor associated with plant and animal stoichiometry.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Early- and late-onset preeclampsia pose serious maternal-fetal risks, yet non-invasive early prediction remains challenging. Here, the authors show that cfRNA signatures reveal distinct decidual and multiorgan signals, enabling accurate, externally validated prediction of both subtypes.

By performing a CAR-adapted base-editing screen of phosphatidylinositol-3-kinase delta (PI3Kδ, PIK3CD), Bucher et al. identify mutations affecting endogenous PI3K–AKT signaling that enhances CAR T cell antitumor potency.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

The combination of JWST and ALMA data here unravel the history of the gas content of a quiescent galaxy, which became quenched through an act of self-sabotage. Black-hole accretion feedback heated the galaxy’s surrounding material, preventing its accretion.

Early postnatal interneuron-oligodendroglia communication may shape neuronal networks underlying cognition. Here, the authors show that disrupting this signaling in mice impairs interneuron myelination, gamma rhythms, and fear-related learning.

Apollo is a GPU-accelerated simulator of within-host viral evolution, spanning host populations, tissues, and cells. It scales to millions of viral genomes and supports complex demographic and population genetic models.

How landscapes are arranged affects soil pathogenic fungi worldwide. The authors reveal the global pattern and pronounced scale-dependency of landscape complexity and land-cover quantity on soil pathogenic fungal diversity.

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

Dielectric materials are crucial for advancing nanoelectronics, yet their miniaturization poses significant challenges. Here, the authors synthesize atomically thin gallium oxide on graphene, achieving a clean interface and robust electronic properties, paving the way for scalable integration of conducting and insulating components in nanoelectronics and offering a versatile method for oxide synthesis.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

While oral bacteria rarely colonize the healthy gut, they dominate the gut microbiome of patients with chronic liver disease. Here a bacterial gene encoded by microbial translocators is linked to gut barrier disruption and fibrosis.

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.

Low- and middle-income countries face unique challenges when it comes to balancing growing energy needs with broader, long-term development needs. This Perspective argues for innovative, context-specific modelling practices to support these goals.

The intestinal microbiome is shaped by genetics and environment. Here, the authors show in rats that host genetic effects, including indirect social effects, influence microbiome composition, identify replicated loci, and reveal mechanisms contributing to microbiome heritability.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Reliably probing rejuvenation and memory effects in spin glasses by means of simulations is difficult. Now, a state-of-the-art numerical study shows that at least three different length scales play a crucial role in aging dynamics of spin glasses.

The effects of current protected areas on freshwater biodiversity are poorly understood. Here, the authors show that European protected areas have overall limited influence on changes in river biodiversity, underscoring the urgent need for improved effectiveness.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Examining human brain organoids and ex vivo neonatal murine cortical slices demonstrates that structured neuronal sequences emerge independently of sensory input, highlighting the potential of brain organoids as a model for neuronal circuit assembly.

A previously unsampled deep lineage in central Argentina was discovered that had distinctive genetic drift by 8,500 bp and persisted as the main Native American ancestry component in the region up to the present day.