❌

Normal view

Levetiracetam therapeutically targets GABAergic synapses in diffuse midline glioma

Nature Medicine, Published online: 17 September 2026; doi:10.1038/s41591-026-04646-6

Results of this study show in experimental models and data from patient cohorts that the antiseizure medication levetiracetam is associated with longer survival and reduced tumor growth in diffuse midline glioma, but not hemispheric high-grade glioma, by selectively dampening GABAergic synaptic signaling, independently of its canonical SV2A-mediated primary antiseizure mechanism.

Broadly neutralizing antibodies in adult males living with HIV undergoing analytical treatment interruption: secondary and exploratory outcomes of the phase II randomized controlled RIO trial

Nature Medicine, Published online: 15 September 2026; doi:10.1038/s41591-026-04644-8

In the phase 2 RIO trial, there was delayed viral rebound and resistance to broadly neutralizing antibodies 3BNC117-LS and 10-1074-LS in adult males living with HIV undergoing analytical treatment interruption, and initial reservoir sensitivity to autologous antibodies was associated with a longer time to rebound.

Predicting cellular responses to perturbation across diverse contexts with State

Modeling perturbation effects across large single-cell populations requires flexibility to capture heterogeneity. By training over sets of cells in a shared embedding space, State outperforms baselines at generalizing effects to new contexts. Cell-Eval, the framework used for this comparison, provides a comprehensive benchmark for future models.

The sex and reproductive plasticity of intestinal muscles instruct gut size

Adult intestinal size plasticity is driven not only by epithelial stem cells but also by remodeling of the surrounding visceral musculature. Sex- and reproduction-dependent muscle remodeling controls gut size and transit, revealing the intestinal muscle as an active regulator of adult organ adaptation.

Anonymization of Portuguese Clinical Notes Using Large Language Models and Quantum-Enhanced Hybrid Architectures: Comparative Evaluation Study

Background: The widespread adoption of electronic health records (EHRs) has generated large-scale repositories of highly sensitive clinical information, emphasizing the need for robust anonymization strategies to enable secondary use for research while safeguarding patient privacy. Conventional rule-based and machine learning approaches for deidentifying medical text face limitations with the linguistic complexity, variability, and context dependence inherent to clinical documentation. Recent advances in large language models (LLMs), combined with emerging quantum computing paradigms, present novel opportunities to enhance the accuracy, scalability, and resilience of health care data anonymization. Objective: This study aims to evaluate the efficacy of LLM-based and quantum-enhanced hybrid architectures for medical text anonymization, assessing the effectiveness and computational efficiency across multiple entity types in Portuguese clinical notes. Methods: We constructed a gold-standard corpus of 1000 Portuguese outpatient clinical notes, manually annotated by 5 trained researchers for 5 protected-entity categories: patient names, dates, identifiers, organizations, and geographic locations. Four anonymization strategies were evaluated: 2 stand-alone LLMs (Llama-3.1-8B-instruct and Llama-3.3-70B-instruct) and 2 quantum-enhanced hybrid models (Dynex-QML with 8B and 70B base models) incorporating quantum optimization via Quadratic Unconstrained Binary Optimization (QUBO) formulations. The quantum-enhanced approach transforms the final attention layer of the LLM into a global constraint satisfaction problem solved via neuromorphic quantum annealing. Model performance was measured on a held-out test set of 500 notes using precision, recall, and -score metrics. Computational efficiency was quantified through end-to-end processing time. Results: The quantum-enhanced Dynex-QML-70B model achieved the highest overall performance with a macro-score of 0.855 (95% CI 0.823‐0.880), outperforming the stand-alone Llama-3.3-70B (0.726, 95% CI 0.704‐0.747), Dynex-QML-8B (0.733, 95% CI 0.709‐0.756), and Llama-3.1-8B (0.602, 95% CI 0.588‐0.615). Compared with Llama 3.3 70B, Dynex-QML (Llama 70B) improved macro-score by 0.128 (95% CI 0.091‐0.163; empirical 2-sided bootstrap

Publisher Correction: A scoping review on the mental health harms of LLM-based chatbots

npj Digital Medicine, Published online: 14 September 2026; doi:10.1038/s41746-026-03240-x

Publisher Correction: A scoping review on the mental health harms of LLM-based chatbots

Rethinking the global health system for a new international order

Nature Medicine, Published online: 14 September 2026; doi:10.1038/s41591-026-04622-0

In this Comment, we argue for a global health system that recognizes and supports countries as the primary agents of action, oriented around global public goods and collective action, and served by a leaner set of global and regional institutions. We present a potential vision for the functions and distribution of labor in the system to inform ongoing reform discussions and draw critique, dissent and amendment.

Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial

Nature Medicine, Published online: 11 September 2026; doi:10.1038/s41591-026-04642-w

In the randomized phase 2 ImmunoPRISM trial, patients with high-risk smoldering multiple myeloma (MM) showed higher rates of complete clinical responses in response to treatment with teclistamab compared with lenalidomide–dexamethasone, although longer follow-up is required to determine durable prevention of progression to MM.

“Small” Large Language Models in the Hospital: Evaluation Study on Real-World Data in a Resource-Constrained Setting

Background: Large language models (LLMs) are increasingly being deployed in health care, but their use and deployment in many real-world hospital environments pose significant challenges and concerns. In particular, state-of-the-art commercial models store or process data externally, which is often in conflict with ensuring patient data protection. At the same time, using LLMs locally is limited by the lack of available computing infrastructure. Small open-source LLMs that do not require substantial computing resources could offer a practical way to resolve these tensions, but their medical utility in real-world local contexts, especially in non-English languages, has not been sufficiently evaluated. Objective: This study aimed to evaluate the feasibility of small, locally deployable open-source LLMs for clinically relevant tasks in a resource-constrained hospital setting and to propose a reproducible framework for institution-specific evaluation before deployment. Methods: We evaluated 6 open-source LLMs ranging from 8B to 24B parameters (from the Mistral, Phi4, Falcon3, Llama3.1, and Meditron3 families) in a zero-shot setting across 7 tasks covering 4 clinical use cases: information extraction, medical text translation, text generation, and clinical decision support. We used deidentified French clinical data from a Swiss tertiary hospital, including discharge letters, clinical notes, and structured electronic health records. Performance was assessed using task-specific metrics, such as precision, recall, F1-score, embedding-based semantic similarity, recall-oriented understudy for gisting evaluation (ROUGE) score, readability indices, and human review by clinicians. Results: Model performance varied substantially between tasks. In the simplest retrieval task (needle-in-the-haystack), several models performed strongly, with Llama3.1 achieving an F1-score of 99.81% and Mistral-small achieving 99.71%. In contrast, performance was poor in more complex tasks. For detecting protected health information, the best-performing LLMs achieved only modest overall macro–F1-scores (0.33-0.34), substantially below a fine-tuned Robustly Optimized BERT Pretraining Approach (RoBERTa) baseline (0.94). In the task of extracting immune-related adverse events from discharge notes, the highest overall macro–F1-score was 0.35 with Phi4. For medical text translation, Phi4 ranked highest in embedding-based evaluation, whereas Meditron3-Phi4 performed the worst, with clinician reviews identifying hallucinations in 55% of its outputs. In the task of summarizing discharge letters, quality was low across all models, with the best penalized ROUGE score reaching only 0.169 with Llama3.1. In the tasks of generating patient-friendly discharge note summaries and clinical decision support, clinician ratings generally ranged from dissatisfied to neutral, and no model achieved consistently satisfactory performance. Conclusions: Small open-source LLMs appear feasible for simple retrieval-oriented tasks in local hospital deployments but are currently inadequate for more complex applications, such as clinical decision support, deidentification, extraction of adverse events, and medical summarization. These findings highlight the importance of locally grounded evaluation tailored to specific use cases and the need for robust institutional evaluation frameworks to ensure safe and reliable deployment. Trial Registration:

Breaking timescales with generative sampling of conformational transitions

Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-11025-1

A generative committor-guided path-sampling framework reconstructs rare biomolecular transition pathways and reveals the underlying thermodynamics and kinetics without using predefined collective variables or brute-force sampling, at an acceptable computational cost.

Neocortical long-range inhibition promotes cortical synchrony and sleep

Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-10876-y

In mice, a sparse population of sleep-active long-range inhibitory neurons in the neocortex promote widespread cortical synchronization and sleep, revealing a cortical mechanism that contributes to the regulation of sleep.

Denisovans from southwestern China and their subsistence strategies

Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-10997-4

Evidence from Bianfu Cave shows specialized hunting, expedient stone-tool production and extensive bone use of Denisovans, providing new insights into their ecology, behaviour and cultural legacy in eastern Asia.

Proximity-guided graph learning reveals tumour-associated proximity antigens

Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-11003-7

A proximity-mapping atlas defines tumour-associated proximity antigens, revealing disease-associated membrane spatial communities, and identifies EGFR–CDCP1 as a co-target pair that enhances tumour killing by multispecific therapeutics.

Myeloperoxidase inhibition with mitiperstat in heart failure with preserved or mildly reduced ejection fraction: a randomized phase 2b trial

Nature Medicine, Published online: 09 September 2026; doi:10.1038/s41591-026-04615-z

In a phase 2 randomized clinical trial, treatment with the myeloperoxidase (MPO) inhibitor mitiperstat, intended to target the neutrophil–MPO inflammatory pathway, did not improve symptoms or exercise function in individuals with heart failure with preserved or mildly reduced ejection fraction.
❌