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The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

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.

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.

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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.

An alternative mating system, termed parasex, produces progeny with high levels of genotypic diversity and is able to fulfil the roles of meiosis when it is absent in the fungal pathobiont Candida albicans.

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.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

The neural circuits that transmit cool signals remain not fully understood. Here, authors identify a spinal circuit in mice that transmits cool sensations from the skin to the brain, revealing a dedicated neural pathway for detecting innocuous cool temperatures.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Here authors show loss of AKAP11, a strong genetic risk factor for bipolar disorder and schizophrenia, disrupts PKA proteostasis and signaling, leading to widespread transcriptomic alterations across the brain, particularly in striatal neurons, as well as altered behavior.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Van der Waals materials of the MB₂T₄ family (M = transition metal or rare-earth metal, B = Bi or Sb, T = Te, Se, or S) have attracted interest for their magnetic and topological properties, but their direct synthesis into 2D form remains challenging. Here the authors report a flux-assisted, phase-controlled growth strategy to directly grow six magnetic 2D MB₂T₄ crystals.

Sex differences are well established in the prevalence and symptoms of depression. Here, the authors identify a novel X chromosome variant, greater genetic risk, and stronger links to metabolic traits in females, highlighting the importance of sex-aware approaches.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

Animal models of drug use require specialized technical expertise and often differ from how humans consume drugs. Here, the authors establish a robust method which allows mice to self-administer intranasal cocaine, greatly improving face validity and ease of use.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

The ATLAS experiment at the Large Hadron Collider reports a search for charged-lepton-flavour violation in decays of Z bosons into a τ lepton and an electron or muon of opposite charge.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Adjuvants are an important component of modern vaccines. Here, the authors employ a phenotypic screen of ~200k compounds and identify PVP-057, a TLR3 agonist with a simple scalable 3-step synthesis, as an adjuvant that induces durable humoral and cellular immunity to varicella-zoster virus (VZV) gE in mice.

Using voltage imaging, the authors show that interneurons in the hippocampus sharpen memory-encoding-activity by increasing the signal-to-noise ratio of pyramidal neuron sensory representations during working memory in mice.

Turley and colleagues find that Gremlin1-expressing lymph node fibroblastic reticular cells support dendritic cell homeostasis via provision of FLT3L.

A transverse Peierls transition can occur when transverse acoustic phonons couple with conducting p-orbital electrons. Here, the authors observe an incommensurate transverse Peierls transition and signatures of a chiral charge density wave in EuAl₄.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

X-ray study of compressed water shows that superionic ice adopts mixed close-packed structures rather than a single phase - a far more complex behaviour than expected, mirroring solid ice’s rich phases and informing planetary interior models.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Finite momentum superconducting pairing refers to a class of unconventional superconducting states where Cooper pairs acquire a non-zero momentum. Here the authors report a new superconducting state in bulk 4Hb-TaS₂, where magnetic fields induce finite momentum pairing via magnetoelectric coupling.

Mapping of spatial metabolic gradients in the mouse liver and intestine identifies fructose-induced focal derangements in liver metabolism.

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.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

A strongly lensed galaxy at redshift z ≈ 6 is resolved into at least 15 star-forming clumps embedded in a rotating disk. Clump formation in this system, which is not predicted by cosmological zoom-in simulations, may be driven by disk instabilities with weak feedback, rather than past mergers.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Squeezed light field microscopy (SLIM) combines ideas from tomography and compressed sensing with light field microscopy to enable volumetric imaging at kilohertz rates, as demonstrated in blood flow imaging in zebrafish and voltage imaging in leeches and mice.