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Improving Retrieval Augmented Generation for Health Care by Fine-Tuning Clinical Embedding Models: Development and Evaluation Study

Background: Embedding models are critical components of Retrieval Augmented Generation (RAG) systems for retrieving and searching unstructured medical data. However, existing models are predominantly trained on publicly available English datasets, limiting their effectiveness in non-English health care settings. More importantly, these models lack training on real-world clinical documents, leading to inaccurate context retrieval when integrated into RAG systems for health care applications. This gap is particularly pronounced in specialized medical documentation containing domain-specific terminology, abbreviations, and nuanced clinical language. Objective: This retrospective study aimed to develop and validate embedding models specifically trained on real-world clinical documents from multiple medical specialties to improve medical information retrieval (IR) and RAG system performance in both German and English language contexts. Methods: We fine-tuned embedding models, so-called sentence transformers, using the multilingual-e5-large architecture as a foundation. Training data consisted of approximately 11 million question-answer pairs synthetically generated from 400,000 diverse clinical documents from a large German tertiary hospital, spanning 163,840 patients and 282,728 clinical cases between 2018 and 2023. The large language model generated medically relevant questions and corresponding answers for each document. The dataset was additionally pseudonymized and translated into English to aim for broader applicability. Models were evaluated in 2 distinct scenarios: IR using questions with multiple relevant passages, and RAG system performance in both cross-patient and patient-centered contexts. Results: In the IR evaluation, the fine-tuned miracle model achieved a mAP@100 of 0.27, outperforming the multilingual-e5-large baseline (0.14) and state-of-the-art models such as bge-m3 (0.11). In the RAG evaluation, the model demonstrated robust performance comparable with the baseline in the constrained patient-centered scenario (BERTScore F1 0.781 vs 0.778) and showed moderate improvements in the unconstrained cross-patient setting (BLEURT 0.56 vs 0.53). Notably, the model trained on pseudonymized data achieved comparable retrieval performance (mAP@100 0.25) and the highest scores for patient-centered contextual precision (0.93). Performance gains were robust in the German dataset, while the translated English model demonstrated promising results as a proof of concept for cross-lingual transfer. Conclusions: By leveraging a comprehensive real-world dataset spanning multiple medical specialties and using large language models for synthetic question generation, we successfully created and validated domain-specific embedding models. These models can improve medical IR in large-scale search spaces and perform competitively in constrained RAG applications. By publishing the models trained on pseudonymized data, other health care institutions can integrate or adapt these embedding models to their needs. This work establishes a reproducible framework for developing domain-specific clinical embedding models, with the potential to improve data retrieval in medical settings.

A fast starburst wind consumes most of the energy from supernovae

Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10231-1

Starburst galaxies are seen to host galaxy-scale winds, which are super-fast and could be powered entirely by the thermal pressure of gas heated by supernovae.

Androgen activity in the male embryonic hindbrain drives lethal PFA ependymoma

Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10264-6

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

Pembrolizumab and olaparib in homologous-recombination-deficient metastatic pancreatic cancer: the phase 2 POLAR trial

Nature Medicine, Published online: 25 March 2026; doi:10.1038/s41591-026-04299-5

Results of the phase 2 POLAR trial show that biomarker-guided treatment in patients with metastatic pancreatic cancer based on homologous repair deficiency leads to encouraging clinical response rates in immune cell-infiltrated tumors.

Parasites trigger epithelial cell crosstalk to drive gut–brain signalling

Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10281-5

Paracrine signalling between tuft cells and enterochromaffin cells is a key mode of immune–sensory and gut–brain communication, and accounts for the pattern of gastrointestinal symptoms that occurs during parasite infections.

Disequilibrium response to tapping crustal magma reveals storage conditions

Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10317-w

Magma drilling data from Krafla volcano, Iceland, are used to reconstruct in situ lithostatic magmatic conditions using disequilibrium simulations that provide a method for improving the understanding of magma storage conditions and evolution.

Challenges of Standard Pediatric Epilepsy Monitoring and the Potential Benefits of Contactless Sensor Technologies: Exploratory Qualitative Study

Background: Epilepsy is a common neurological condition in children, and accurate detection of seizures and their frequency is essential for diagnosis and treatment. Standard monitoring using electroencephalography alongside clinical observation is often burdensome in pediatric settings, as electrodes can cause discomfort and restrict mobility. Contactless sensor technologies may offer a promising supplement by enabling monitoring without physical contact. Objective: This study aims to explore challenges in standard pediatric epilepsy monitoring from the perspective of health care professionals and examines the potential benefits and requirements of supplementary contactless sensor technologies in this setting. Methods: Participant observation of routine processes in standard pediatric epilepsy monitoring was conducted at a German university hospital. Field notes from 40 observed procedures were analyzed using structuring content analysis. Building on these findings, a focus group with pediatric neurologists, nurses, and medical technical assistants (n=6) explored the potential benefits and implementation requirements of contactless sensor technologies. Focus group data were analyzed using focus group illustration maps. Results: A reference workflow of standard pediatric epilepsy monitoring was derived, revealing psychosocial, medical, and organizational challenges faced by health care professionals. Electroencephalography recordings and clinical observation required considerable reassurance of patients and parents or carers, were vulnerable to movement artifacts and incomplete seizure documentation, and were labor- and resource-intensive. Focus group participants viewed contactless sensor technologies as a potentially valuable supplement by enabling continuous long-term monitoring with minimal additional burden. Conclusions: By identifying challenges associated with standard pediatric epilepsy monitoring, this study provides a foundation for the needs-based development and implementation of supplementary contactless sensor technologies. Such technologies should be tailored to the clinical setting and designed to address existing burdens, with the potential to complement standard monitoring. Trial Registration: Deutsches Register Klinischer Studien (DRKS) DRKS00027017; https://drks.de/search/de/trial/DRKS00027017

<i>LRRK2</i>-targeting antisense oligonucleotide in Parkinson’s disease: a phase 1 randomized controlled trial

Nature Medicine, Published online: 24 March 2026; doi:10.1038/s41591-026-04262-4

The first-in-human clinical trial of the LRRK2-targeting antisense oligonucleotide BIIB094 in Parkinson’s disease demonstrates that the treatment is well tolerated and produces dose-dependent reductions in cerebrospinal fluid levels of LRRK2 and phosphorylated Rab10, indicating successful target engagement.

Generalist biological artificial intelligence in modeling the language of life

Nature Biotechnology, Published online: 20 March 2026; doi:10.1038/s41587-026-03064-w

This Review discusses the promises and pitfalls of biological AI algorithms and presents a vision for generalist biological artificial intelligence, in which models can perform diverse tasks across biological domains.

Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy

Leigh syndrome is a severe and untreatable mitochondrial disease. Using patient-derived models in 2D and 3D, Zink and colleagues identify the PDE5 inhibitor sildenafil as a repurposable drug candidate, leading to lifespan extension in mammalian models and clinical improvement in six individuals with Leigh syndrome.

Light-directed evolution of dynamic, multi-state, and computational protein functionalities

Optovolution leverages optogenetics and the yeast cell cycle to impose rapid, tunable selection, enabling the continuous evolution of light-responsive regulators, logic gates, and other complex protein behaviors that were previously difficult to evolve.

Molecular architecture of human dermal sleeping nociceptors

Integration of electrophysiology with single-cell transcriptomics defines the molecular signature of human dermal sleeping nociceptors and reveals oncostatin M as a selective modulator of these neurons in humans, providing a therapeutic entry point for neuropathic pain.

First-line zolbetuximab plus mFOLFOX6 and nivolumab in unresectable CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial

Nature Medicine, Published online: 16 March 2026; doi:10.1038/s41591-026-04306-9

In cohort 4 of the ILUSTRO trial, combination of anti-CLDN18.2 zolbetuximab plus mFOLFOX6 and nivolumab in patients with CLDN18.2-positive, HER2-negative metastatic gastric or gastroesophageal junction adenocarcinoma led to encouraging clinical efficacy, supporting the testing of this combination in a phase 3 trial.
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