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In a series of clinically relevant tasks in computational pathology, AI-driven models display marked performance disparities across demographic groups, which can only partially be mitigated by self-supervision on large training datasets and existing debiasing techniques.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

Control of CRISPR-Cas9 activity allows for fine-tuning of editing and gene expression. Here the authors use gRNAs modified with RNA aptamers to enable small molecule control in bacterial systems.

Epithelial tissue mononuclear phagocytes (MNP) can transmit HIV to CD4 T cells, but less is known about sub-epithelial cells. Here, the authors describe MNPs in human anogenital and colorectal tissues and find that CD14⁺CD1c⁺ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 preferentially take up and transmit HIV.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology. Here, the authors use a combination of live cell imaging and in vitro single molecule binding measurements to show that tandem calponin homology domains (CH1–CH2) are sensitive to actin filament conformation, biasing their subcellular localization.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Cox and colleagues develop PXS-5505, a first-in-class selective pan-lysyl oxidase inhibitor and show that it reduces chemotherapy-induced desmoplasia and stiffness, thereby improving chemotherapy response and survival in pancreatic cancer models.

A whole-genome sequencing analysis of 100 pancreatic ductal adenocarcinomas has discovered known and newly identified genetic drivers of pancreatic cancer; these genetic alterations can be classified into four subtypes, which raises the possibility of improved targeting of clinical treatments.

Conventional crystallography focuses on structurally-ordered systems, where interesting physics or novel material functions emerge. Here, Overy et al. propose an approach of designing functional materials with strongly correlated disorder, which can couple with phonons to affect lattice dynamics.

Spin defects in hexagonal boron nitride are a promising platform for nanoscale magnetometry, however inhomogeneous noise degrades performance. C.J. Patrickson et al. use continuous dynamical decoupling to mitigate this noise, and to detect phase, amplitude and frequency of MHz - GHz fields.

CS-Rosetta-RNA is a web tool for determining high-resolution structures of noncoding RNA motifs using ¹H NMR chemical shift data coupled with Rosetta-based modeling.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

Single-cell transcriptomic profiling of fetal liver, skin, kidney and yolk sac reveals the differentiation trajectories of human haematopoietic stem cells and multipotent progenitors, which are validated to produce an integrated map of fetal liver haematopoiesis.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

Autocatalysis is a process whereby a product accelerates its own formation. Here, the authors describe a system whereby two simple components combine irreversibly to give a more complex, amphiphilic product, leading to autocatalytically active micelles.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

A COVID-19 test implemented in an automated microfluidic device and leveraging isothermal RNA amplification followed by T7 transcription and Cas13-mediated cleavage of a quenched fluorophore rapidly detects SARS-CoV-2 RNA in saliva samples.

Creating chemical systems that can model living systems is far from easy. However, the evolution of oil droplets in water through the application of artificial selective pressure to produce droplets with dramatically different — yet specific — behaviours, is an encouraging step in this direction.

Defaunation is linked to the decline of tree species that depend on large animals for seed dispersal, but it is unclear if this affects carbon storage. Here the authors show that defaunation effects on carbon storage vary across continents, driven by relationships between seed dispersal strategies and adult tree size.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

MYCN-amplified neuroblastoma remains an aggressive childhood cancer with its core regulatory circuits less understood. Here, the authors identify that the transcriptional corepressor Runx1t1 is indispensable for MYCN-driven neuroblastoma tumorigenesis.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Synthetic cell adhesion molecules yield customized cell–cell interactions with adhesion properties that are similar to native interactions, and offer abilities for cell and tissue engineering and for systematically studying multicellular organization.

Integrating inventory data with machine learning models reveals the global composition of tree types—needle-leaved evergreen individuals dominate, followed by broadleaved evergreen and deciduous trees—and climate change risks.

Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Crop models suggest that early sowing and slower-developing cultivars could maintain Australian wheat yields despite less-favourable climatic conditions. Field trials now confirm the potential of this adaptation for wheat production across Australia.

Did earthquakes trigger the collapse of ancient civilizations?

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Rising CO₂ levels have been thought to potentially increase plant growth due to improved fertilization, but such a general effect is spatially and temporally affected by precipitation. Grassland experiments show constraints and increases in the fertilization effect due to seasonal-based precipitation, inferring that any potential plant growth could be mitigated by natural rainfall changes.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.