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An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

The diversity of ponerine ants varies widely across the globe. This study finds that the origin and early colonization in Gondwana’s tropical regions mainly shaped this distribution, while differences in diversification and dispersal have balanced regional diversity over time.

PDGrapher uses large datasets of genetic and chemical interventions to find genetic targets that shift a gene expression phenotype from a diseased to a normal state.

Nature Biotechnology’s annual survey highlights university startups that are, among other things, rethinking how to deliver gene-editing therapy and tackling various metabolic conditions, immune disorders and cancer with microbiome treatments or immunotherapy. Michael Eisenstein, Ken Garber, Esther Landhuis, Caroline Seydel and Laura DeFrancesco report.

A horizon scan of international respondents identifies and discusses ten developing challenges in Antarctic conservation, revealing an increased emphasis on challenges related to governance, geopolitics and economics compared to a similar scan from 2012.

Determining how replication forks move across the human genome is critical for the effective use of agents that target replication stress. Here, the authors present DNAscent, an AI supported assay for DNA replication stress in human cells using Nanopore sequencing data.

Nature Biotechnology’s annual survey highlights academic start ups that are, among other things, correcting misfolded or disordered proteins, creating second-generation GPCR agonists, building a new gene delivery platform and mining cancer genomes for novel targets.

A theoretical foundation for entrapment methods is presented, along with a method that enables more accurate evaluation of false discovery rate (FDR) control in proteomics mass spectrometry analysis pipelines. Evaluation of popular data-dependent acquisition tools indicates that these generally seem to control the FDR, but data-independent acquisition tools exhibit inconsistent control of the FDR at both the peptide and protein levels.

Decisions are typically associated with a sense of confidence and can be followed by an impulse to change our minds. Here, the authors use intracranial recordings in humans to show that confidence and changes of mind derive from a cortical process called evidence accumulation.

This systematic review and meta-analysis of 53 randomized controlled trials finds that educational interventions can help students reduce cognitive biases, with a small but statistically significant overall effect.

Our annual survey highlights startups tackling intractable viruses with new vaccine design, engineering a reliable source of platelets, universalizing cell therapies, improving cancer screening, developing RNA-editing platforms and targeting protein–RNA interactions. Michael Eisenstein, Ken Garber, Caroline Seydel and Laura DeFrancesco report.

The combinatorial synthesis of ionizable lipids allows for the identification of an antioxidant lipid exhibiting low immunogenicity for lipid nanoparticle-mediated mRNA delivery in vivo.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Inflammatory monocytes in the brain meninges promote stress-induced fear behaviour, and the pathways involved can be modulated using psychedelic compounds.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

Bond et al. show that inducible PolG mutation in muscle causes mtDNA damage and muscle wasting. This is driven by the integrated stress response (ISR) and reduction in folate intermediates, linking impaired folate metabolism with ISR/disease induction.

This study identifies long-lived closed and pre-open states of GORK K+ channel through structural and functional analysis, suggesting semi-independent conformational transitions underlying channel activity and promising sites for stomata engineering.

An analysis of the localization and intensity of intracortical microstimulation in three participants with cervical spinal cord injury shows that overlapping projected fields from multiple electrodes produce sensations that are more easily localizable.

Association analyses that capture rare and noncoding variants in whole genome sequencing data are limited by factors like statistical power. Here, the authors present KnockoffScreen, a statistical method using the knockoff framework to detect, localise and prioritise rare and common risk variants at genome-wide scale.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

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).

Inorganic–organic hybrid dye-sensitized solar cells featuring a perovskite compound as a light harvester and a polymer as a hole transporter provide an open-circuit voltage of almost 1 V and a power conversion efficiency of 12% under standard illumination conditions.

Despite high levels of trade, the basic characteristics of the aquatic food trade are largely unknown. Here, the authors present a global seafood trade database showing the increasing globalization of farmed and wild aquatic foods.

Decreased brain coenzyme Q₁₀ levels cause encephalopathy and are associated with neurodegeneration; supplementation with 4-HMA or 4-HB restores coenzyme Q₁₀ synthesis in mice and humans with HPDL variants, improving survival and neurological symptoms in HPDL-driven mitochondrial encephalopathy.

The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

In vivo chimeric antigen receptor (CAR)-T cell engineering uses targeted delivery systems to generate CAR-T cells directly in patients, bypassing ex vivo manufacturing. This Review examines emerging viral and lipid nanoparticle platforms, early clinical proof of concept and potential applications beyond cancer.

Generative models for chemical structures are often trained to create output in the common SMILES notation. Michael Skinnider shows that training models with the goal of avoiding the generation of incorrect SMILES strings is detrimental to learning other chemical properties and that allowing models to generate incorrect molecules, which can be easily removed post hoc, leads to better performing models.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Many perturbations affect only a subset of cells, while the rest remain largely unaffected. Existing single-cell analysis methods may fail to isolate the affected cells and their markers. Here, authors introduce HiDDEN, a machine learning method that reveals the perturbation status of individual cells.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

The pseudopterosins are a family of natural products whose interesting anti-inflammatory and pain-relieving properties have inspired many synthetic approaches. Now, an unusual approach that starts with an axially chiral hydrocarbon that engages in a triple Diels–Alder sequence has been shown to result in the shortest total synthesis of a pseudopterosin so far.

A class of cationic—amidine-based degradable—lipids can now be readily synthesized through a tandem multi-component amine–thiol–acrylate conjugation reaction. Mechanistic studies provided key insights, from which the observed lead lipid enabled mRNA delivery to multiple organs, highlighting the potential for developing mRNA vaccines and therapeutics to treat various 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.

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.

Monitoring samples from hospital patients, wastewater, or air travel may enable early detection of pathogens. Here, the authors assess how these surveillance systems could have impacted detection of COVID-19 and their potential benefits for detection of other emerging pathogens.

Brissenden et al. demonstrate that spatial cognition adaptively shifts to counteract errors in the allocation of visual attention, indicating error-driven learning mechanisms previously ascribed solely to motor control contribute to visual cognition.

Ryan et al. report a highly conserved mechanism by which arginine induces changes in hypervirulent Klebsiella pneumoniae bacterial cell surface capsule. K. pneumoniae arginine sensing is critical for full virulence potential.

Here the authors identify age-associated changes in the epithelial cell compartment of the thymus that form high-density nonproductive microenvironmental niches that contribute toward thymic involution and inhibit its repair following injury.

Using modelling and experimental data, the authors provide evidence that risk aversion may arise from relative underestimation of larger monetary payoffs, a perceptual bias rooted in the noisy logarithmic coding of numerical magnitudes.

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.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.