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When John Maddox took over the reins of Nature's editorship in 1966, the journal was in urgent need of reform. Walter Gratzer reflects on how Maddox and his successor (and predecessor) David Davies steered the magazine into its modern format.

A pragmatic, cluster randomized trial in rural Guangdong, China, showed that 12-month implementation of a comprehensive antibiotic stewardship program involving physician training, point-of-care prompts, monthly peer review feedback and smartphone-based patient education substantially reduced antibiotic prescriptions for acute respiratory infections compared to control consultations.

Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

Neuromorphic photonic systems can incur significant energy for moving and converting data between digital and analog domains. This work shows that integrating analog memory into these processors can save 26 × power over conventional digital-to-analog architectures while keeping  > 90% inference accuracy.

The Lancet Diabetes & Endocrinology Commission on Clinical Obesity proposed new diagnostic criteria distinguishing preclinical and clinical obesity. Here the authors report that according to these criteria 80% of individuals with BMI-defined obesity are classified with clinical obesity and have increased risk for cardiovascular diseases and type 2 diabetes. A lifestyle intervention can lower the prevalence of clinical obesity.

Negative data composition critically shapes machine learning robustness in sequence-based biological tasks. Training data composition and its implications are investigated on biological rule discoveries.

Compiling data on floral introductions and European colonial history of regions worldwide, the authors find that compositional similarity of floras is higher than expected among regions once occupied by the same empire and similarity increases with the length of time the region was occupied by that empire.

This research identifies two neural factors linked to externalizing and internalizing symptoms through a longitudinal imaging-genetic cohort. Distinct neural configurations and cognitive-behavioral relevance highlight the need for tailored therapeutic strategies addressing psychiatric comorbidity across developmental stages.

Microscopic imaging and biochemical studies show that sinuses in mouse and human form a highly dynamic surface that regulates fluid movement and immune cell surveillance via RAMP1-dependent regulation of smooth muscle contraction and RAMP2-dependent regulation of the sinus endothelial barrier.

This study presents a clinical-grade autonomous pipeline combining high-resolution whole-slide tomography, edge computing and artificial intelligence, achieving high accuracy in cervical cytology and enabling scalable and objective diagnostics.

Stable fullerenes often follow the isolated pentagon rule, but there are increasing examples of compounds that do not. Now, a maximum pentagon separation rule is proposed, which predicts that the most stable cages are those with pentagons having the largest separation.

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.

Sequencing of marine sediments finds 136 newly identified Heimdallarchaeia and several novel lineages, and indicates that Heimdallarchaeia evolved distinct metabolic capabilities from other Asgardarchaeota, in conditions that may have given rise to early eukaryotes.

A skeletal editing strategy for the direct conversion of oxazoles and isoxazoles into thiazoles and isothiazoles is described. These one-step transformations may be beneficial for drug development programmes by enabling rapid diversification of bioactive compounds and advancing structure–activity relationship studies.

Fang et al. reveal how a bacterial circadian clock turns genes on and off at the right times of day and use the purified proteins to drive circadian gene transcription in a test tube for days.

At single-cell resolution, Tarkhov et al. delineate stochastic and co-regulated components of epigenetic aging, revealing a simultaneous loss of regulation at the epigenetic and transcriptional levels in aging.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

Natural products populate areas of chemical space not occupied by average synthetic molecules. Here, an analysis of more than 180,000 natural product structures results in a library of 2,000 natural-product-derived fragments, which resemble the properties of the natural products themselves and give access to novel inhibitor chemotypes.

Discovery proteomics offers deep insights but is currently not applied clinically in diagnostics. Here, the authors present ADAPT-MS, a flexible machine learning framework that enables fast, personalized diagnostic and prognostic decisions directly from proteome-wide data.

Analysis of the local branching geometries of several physical networks shows violations of predictions of length and volume minimization, leading to the hypothesis that estimating the material cost requires accounting for the full three-dimensional geometry.

Tests of the predictions of the renormalization group in biological experiments have not yet been decisive. Now, a study on the collective dynamics of insect swarms provides a long-sought match between experiment and theory.

Langstein-Skora, Schmid, Huth et al. propose that intrinsically disordered region functionality can be driven by the interplay between linear binding motifs and contextual chemical characteristics such as charge and hydrophobicity.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

How do humans learn complex rules from small available data? Rule et al introduce metaprogram learning as a model that fits human behaviour in complex learning situations. Unlike previous approaches, this model is based on programs revising programs, making it more efficient.

Protein-activity-based identification of hypermorphic, hypomorphic, neomorphic effectors and therapeutically relevant mutations uses transcriptomic data to categorize variants of unknown significance into hypermorphic, hypomorphic and neomorphic mutations based on their effects on transcription factor activity and subsequent gene expression.

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

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

The MICrONS mouse visual cortex dataset shows that neurons with similar response properties preferentially connect, a pattern that emerges within and across brain areas and layers, and independently emerges in artificial neural networks where these ‘like-to-like’ connections prove important for task performance.

Electronic health records are a rich source of clinical data but identifying associations with outcomes is complex. Here, the authors propose a modelling framework ‘InfEHR’ that identifies patient trajectories in electronic health records and generates a likelihood for clinical phenotypes.

Electron transfer in molecular wires is typically dominated by tunnelling at short lengths. Now it is shown that conjugated molecular wires anchored to indium tin oxide electrodes exhibit a hopping mechanism even at 1-nm lengths, enabling charge extraction in tin perovskite solar cells and improved device performance.

People constantly decide whether to stop what they are doing to do something else. Here, the authors show that the quality of available options has a greater influence on people’s decisions to help others than to help themselves.

Mouse models demonstrate that vagal sensory neurons transmit signals from lung adenocarcinoma to the brain, increasing sympathetic efferent activity in the tumour microenvironment and thereby creating a immunologically permissive environment for tumour growth.

A comparative analysis of trait data combined with a mathematical model suggests that dietary specialization drives selection towards the smallest and largest body sizes in terrestrial mammals, as generalists outcompete specialists at intermediate sizes.

Pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, but host factors may better predict benefits for severe outcomes. In this work, authors utilise a machine learning-based approach to evaluate personalized rules for the decision to treat watery diarrhea with azithromycin.

Conventional methods for human motion analysis using sensors tightly attached to the body are often uncomfortable. Here, the authors demonstrate motion recognition and prediction using sensors embedded in garments. The results provide guidance for the development of wearable technology integrated into everyday clothing.

This Perspective synthesizes insights from the past use of nature markets to identify design factors that are necessary if such markets are to achieve their environmental aims—although qualitative scoring of existing markets against these rules identifies pervasive gaps.

Sabatino and colleagues examine expanded CD8⁺ T cell clonotypes from a small cohort of multiple sclerosis patients. They identified several cognate peptide epitopes that derive from Epstein–Barr virus, suggesting EBV reactivation may drive pathogenesis in these patients.

Despite high morbidity and mortality, there are currently no approved vaccines for protection against Middle East respiratory syndrome (MERS) coronavirus. Here the authors develop a ferritin nanoparticle-based MERS-CoV vaccine that elicits high levels of neutralizing antibodies in mice, non-human primates, and alpacas and prevents infection in an alpaca challenge model.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.