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A post hoc analysis of a multicentre, randomised trial showed that prediabetes remission is possible without total weight loss—providing weight is distributed to subcutaneous deposits as opposed to visceral ones.

Here authors used patient-derived forebrain organoids to reveal how LIS1 mutations cause varying severity in a neurodevelopmental disorder, uncovering links between cytoskeletal defects, protein stress, and potential therapeutic strategies.

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.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Natural product–inspired compounds are primed to interact with and manipulate biological processes, but obtaining these complex molecules poses synthetic challenges. The development of a 12-step, 1-pot cascade reaction leads to the 'centrocountins', tetrahydroindoloquinolizines that modulate mitosis by targeting the centrosome-associated proteins nucleophosmin and Crm1.

A large brain imaging study of over 2000 people worldwide shows that fear conditioning engages brain regions linked to emotion and attention, with differences in individuals with anxiety or depression and strong influences from task design.

A model developed with data from 19,403 patients with colorectal cancer for prediction of 1-year mortality is used as a decision support tool in a prospective cohort, showing promising results in reducing postoperative complications.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

In a phase 1/2a umbrella trial in patients with glioblastoma matching targeted therapies according to tumor molecular profiling, temsirolimus plus radiotherapy improved PFS compared to standard of care in patients with phospho-mTOR activation.

The authors report a meta-analysis of methylome-wide association studies, identifying 15 significant CpG sites linked to major depression, revealing associations with inflammatory markers and suggesting potential causal relationships through Mendelian randomization analysis.

Meteorite impacts can create long-lived hydrothermal systems that may spark onset of microbial life. At Finland’s Lappajärvi crater, minerals in fractures contain biosignatures of microbial life related to the hydrothermal circulation, offering clues to deep microbial colonization of Earth and beyond.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Surprisingly consistent replication failure of gray matter correlates of childhood maltreatment raises questions about publication bias in prior literature and about prevailing models linking maltreatment to brain structure in adult populations.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Analysis of samples from the asteroid Ryugu provide evidence of late fluid flow in a carbonaceous asteroid, indicating that such bodies may have retained two to three times more water than previously thought.

GABA_B receptors are the G-protein-coupled receptors for γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. Here, functional proteomics is used to show that GABA_B receptors in the brain are complexes of GABA_B1, GABA_B2 and members of a subfamily of KCTD proteins. The KCTD proteins increase the potency of agonists and markedly alter the G-protein signalling of the receptors, suggesting that they determine the pharmacology and kinetics of the receptor response.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

At equilibrium, the ferroelectric polarization is proportional to the strain. At ultrafast timescales, an above-bandgap laser excitation decouples strain and polarization, which, out of equilibrium, is mainly determined by the photoexcited electrons.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

An expert recommendation is presented for the design and evaluation of research studies using transcranial electrical stimulation, resulting in the selection of a 66-point checklist aimed at improving the quality of transcranial electrical stimulation studies.

Blood phosphorylated (p)-tau 181 and p-tau 217 have been proposed as accurate biomarkers of Alzheimer’s disease pathology. Here, the authors find p-tau 181 and 217 are elevated in serum and muscle of patients with amyotrophic lateral sclerosis.

Amide synthases catalyse the formation of macrolactam rings from aniline-containing polyketide-derived seco-acids. In this study, the authors solved the crystal structure of the geldanamycin amide synthase GdmF and demonstrated that it catalyses amide formation using synthetically derived substrates.

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.

Here, the authors present a method that enables time-resolved serial protein crystallography over a wide temperature range (10–70 °C). This 5D crystallography approach can be implemented to illuminate protein function at physiologically relevant conditions.

Cancer is subject to immune surveillance, and HIV infection dampens immune capacity, but HIV-induced immune alterations in patients with breast cancer is still unclear. Here the authors profile women living with HIV to find increased CD8 T cell tumor infiltration, enhanced checkpoint molecular expression, and reduced overall survival when compared with controls.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Here the authors report single-cell and spatial transcriptomics of young and aged male fibrotic mouse lungs. Age-related alterations in capillary sub-populations are associated with a proangiogenic phenotype linked to regeneration of the alveolar niche.

Application of a nanopore sequencing workflow for real-time analysis of brain tumors results in molecular classification within a 30-minute intraoperative window, followed by comprehensive profiling within 24 hours.

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

A survey across 90 societies reveals that variation and change in everyday norms are explained by a single value dimension: the priority societies place on individualizing versus binding moral concerns.

HistoPlexer, a deep learning model, generates multiplexed protein expression maps from H&E images, capturing tumour–immune cell interactions. It outperforms baselines, enhances immune subtyping and survival prediction and offers a cost-effective tool for precision oncology.

Interact-omics, a high-throughput cytometry-based framework, resolves the cellular interaction landscape.

A review of observation-based evidence suggests that four interconnected Earth system tipping elements have moved towards their critical thresholds, highlighting the need for better monitoring and increased mitigation efforts.

Sarcomas are morphologically heterogeneous tumours rendering their classification challenging. Here the authors developed a classifier using DNA methylation data from several soft tissue and bone sarcoma subtypes, which has the potential to improve classification for research and clinical purposes.

Fusion-based quantum computing relies on small entangled resource states that are then fused together probabilistically via linear optical circuits. Here, the authors demonstrate temporal fusion—where resource states generated at different times by the same quantum emitter are fused together—using a spin-photon interface in a quantum dot embedded in a photonic crystal waveguide.

The mechanisms underlying T-ALL treatment resistance and relapse remain to be explored. Here, the authors perform single cell RNA sequencing of PDX-derived samples from pediatric T-ALL patients at diagnosis and relapse and without relapse and identify treatment-resistant stem-like cells.

Stojanov et al. updated and internally validated a prediction model for the occurrence of post-operative shoulder stiffness following primary arthroscopic rotator cuff repair in Switzerland. Their findings support the development of further prediction models for an evidence-based and individualized decision-making in orthopedics.

This Perspective article discusses the stratification of patients with knee osteoarthritis (OA) in the context of current guidelines, biomarkers and emerging and future developments of targeted treatment. The authors aim to highlight how these novel developments can enhance the stratification of patients with knee OA to improve patient outcomes.

The relationship between single-neuron activity and theta oscillations in the human brain remains unclear. Here, the authors demonstrate that human theta-phase locking is influenced by various properties of the local field potential and characterize its dynamics during spatial memory encoding and retrieval.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

Here the authors combine a deep generative model with structure-based drug design and prospectively validate functionally active, nanomolar, A_2A adenosine receptor ligands and solve their crystal structures to close the Artificial Intelligence Structure-Based Drug Design loop.

Trumpp and colleagues develop a method to obtain long-term circulating tumor cell-derived organoids from individuals with metastatic breast cancer and identify the neuregulin 1–HER3 axis as important for organoid growth and a promising therapeutic target.

A study describes the assembly and analysis of a haplotype-resolved pangenome of bulbous barley with the potential to improve domesticated barley and illustrates its use in evolutionary research and trait mapping.

In a post-approval study including more than 17,000 patients on the safety of pulsed field ablation, a new method for treatment of atrial fibrillation, the procedure was found to have a low rate of adverse events but was associated with some unexpected rare complications that will need further study.