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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.

In this work, an exotic nuclear decay in one dimension is simulated using IonQ trapped-ion quantum computers. The coherent evolution of many decay channels is classically hard and quantum simulation of these processes may impact future searches for new physics.

We examine the historical development and underlying principles of foundation models realized in language and vision, and propose how physics-infused machine learning interaction potentials could dramatically transform at scale to create transformative foundation models for chemistry and materials science.

When doubly-degenerate band crossings known as Kramers nodal lines intersect the Fermi level, they form exotic three-dimensional Fermi surfaces composed of massless Dirac fermions. Here, the authors present evidence that the 3R polytypes of TaS₂ and NbS₂ are Kramers nodal line metals with open octdong and spindle-torus Fermi surfaces, respectively.

Haines et al. developed an MEK–RAF molecular glue called IK-595 that blocks MAPK pathway activation in RAS-mutant and BRAF-mutant cancer cells. IK-595 exhibited high tolerability and strong antitumor effects in preclinical models across cancer types.

This work challenges the view of nucleation governing halide perovskite grain morphology, showing that most additives act post-nucleation by boosting ion mobility across grain boundaries, triggering grain coarsening, similar to post-processing effects.

Stability issues hinder the commercialization of perovskite solar cells. An evaporated, highly oriented wide-bandgap perovskite film is reported, enabled through an intermediate phase evolution, resulting in enhanced stability and efficiency.

Proving sustainable chemical plastic recycling must rely on realistic feedstocks and sustainability-driven catalyst design. Here, the authors report titania-supported Ru–Ni alloy nanoparticles achieving up to 55% liquid (C6 to C45) products for low-carbon and profitable polyethylene hydrogenolysis and determine a metric for sustainable product distributions.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

Garnet-type LLZO electrolytes are considered among the most promising solid-state electrolytes for all-solid-state batteries; however, numerous challenges need to be addressed before they are integrated into a cell. By precipitating amorphous zirconium oxide onto grain boundaries, increased ionic conductivity is observed and dendrite growth is suppressed.

Automated iterative small-molecule synthesis has generally been limited to around one carbon–carbon bond-forming step per day. Now, a next-generation automated synthesizer enables rapid, automated, iterative synthesis of a variety of small molecules. Improvements to chemistry and automation leads to a tenfold decrease in reaction time over previous automated platforms.

The authors demonstrate strain-induced morphotropic phase boundary-like nanodomains in lead-free NaNbO₃ thin films, enabling multi-state switching and large enhancements in dielectric susceptibility and tunability over a broad frequency range.

Glycans are structurally complex biomolecules and very challenging to analyse. Here the authors show atomically resolved imaging of β-cyclodextrins with non-contact atomic force microscopy, revealing the structure of individual glycans with atomic detail.

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.

A recently proposed structure of an N₂-bound Mo-nitrogenase has sparked considerable attention, although the direct evidence for N₂ binding and sulfur mobilization during turnover has remained elusive. Now, additional spectroscopic and kinetic measurements further support this state and provide evidence that belt-sulfur displacement is an essential aspect of the nitrogenase mechanism.

Crystal structures with two sublattice pairs per primitive cell can host so-called dark states which interact minimally with light due to destructive interference. Here, the authors reveal that in the semiconductor (NbSe₄)₃I these states lead to an indirect-gap optical behavior, despite the band structure displaying an almost direct band gap, having significant impact on its optoelectronic properties.

Γ and K valleys in twisted transition metal dichalcogenides have emerged as highly tunable knobs for accessing different correlated electronic states in solid-state devices. Here, the authors tune a Mott-Hubbard state to a charge-transfer insulator state in twisted double-bilayer WSe₂.

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.

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.

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.

The authors reveal an inherent trade-off between logarithmic average phonon frequency and the electron-phonon coupling constant in conventional BCS superconductors. The analysis suggests that achieving room-temperature conventional superconductivity at ambient pressure is extremely unlikely.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

At the hybrid interface between an organic molecular layer and a metallic magnetic surface, spin-filtering effects may be exploited for the generation of spin polarization. Here, the authors demonstrate a dynamic spin-filtering effect across the Co/Alq₃ interface, mediated via a second Alq₃layer.

Green hydrogen production via water electrolysis requires a low-cost solution to provide efficient catalysts. Here, the authors report an industrially scalable method for synthesizing NiFe layered double hydroxide at room temperature and atmospheric pressure, enhancing alkaline electrolysis.

Here, the authors observe that in thin films of antiferroelectric PbZrO₃, substrate clamping enhances the electromechanical response, with expansion purely in the out-of-plane direction, achieving 1.7% strain for 100-nm-thick films.

Phase-change materials are widely used as non-volatile memories, for example in optical data storage, but the search for improved phase-change materials has proved difficult. Based on a fundamental understanding of their bonding characteristics, a systematic prediction of phase-change properties has now become possible.

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

Development of organic electronic materials relies on understanding structure-function relationships in conjugated polymers but the synthetic workload to make large numbers of new compounds presents a practical barrier to properly survey conjugated organic derivatives. Here, the authors use automated synthesis to prepare a library of conjugated oligomers with systematically varied side chain composition followed by single-molecule characterization of charge transport.

The random orientation of spontaneously formed 2D phase atop 3D perovskites limits the performance of solar cells. Here, authors introduce a meta-amidinopyridine ligand with solvent post dripping to generate highly ordered 2D perovskites, achieving maximum efficiency of 26.05% for stable devices.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

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.

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 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.

On-surface synthesis enables highly reactive structures to be produced under vacuum, but they need to be passivated to be incorporated into practical devices. Here, the facile protection of air-sensitive chiral graphene nanoribbons has been shown, by either hydrogenation or synthesis of an oxidized form. The chemically stable forms can subsequently be deprotected.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.