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GlobalDentBench: A Multinational Benchmark for Evaluating LLM Clinical Reasoning in Dentistry with Expert Calibration

arXiv:2605.24636v2 Announce Type: new Abstract: While large language models (LLMs) hold transformative potential for medicine, their reasoning robustness and safety in real-world clinical scenarios remain critically underexplored, particularly in dentistry. Here we introduce GlobalDentBench, the first multinational dental benchmark, featuring a taxonomy that encompasses 14 dental specialties across 88 countries and regions spanning six continents. The benchmark comprises 8,978 expert-validated questions across three formats (multiple-choice, short-answer, and case-based questions) and assesses three progressive reasoning levels: knowledge recall (L1), routine reasoning (L2), and individualized reasoning (L3). To ensure data quality, the automated construction framework was calibrated by six senior dentists, achieving expert agreement rates of 99.98% for multiple-choice and short-answer questions and 96.78% for the more complex case-based questions. Evaluation of 12 frontier LLMs on GlobalDentBench revealed a sharp, stepwise performance degradation with increasing reasoning complexity. Specifically, accuracy plummeted from 81.34% on multiple-choice to 64.53% on short-answer and 22.34% on case-based questions, while declining markedly from 74.01% at L1 to 55.64% at L2 and 35.71% at L3. More critically, risk analysis of real-world dental cases demonstrated an alarming overall unsafe rate of 31.01% in LLM-generated clinical recommendations, with 4.51% posing risks of irreversible patient harm and risks particularly pronounced in specialties such as orthodontics. These findings expose fundamental limitations in the medical reasoning and safety of current LLMs. Consequently, GlobalDentBench provides a scalable foundation for trustworthy clinical AI evaluation, underscoring the urgent need for rigorous validation before the safe deployment of these models in healthcare.
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Human pancreatic progenitor organoids define genetic and epigenetic barriers to early PDAC transformation

Dev Cell. 2026 May 19:S1534-5807(26)00159-0. doi: 10.1016/j.devcel.2026.04.012. Online ahead of print.

ABSTRACT

The lack of accurate human models that recapitulate pancreatic ductal adenocarcinoma (PDAC) initiation has hindered therapeutic development. Using pluripotent stem cell-derived pancreatic progenitor organoids, we established a human PDAC model that faithfully reproduces the genetic, epigenetic, and transcriptomic trajectories of tumor initiation and progression, validated against clinical datasets and tumor histopathology. We demonstrate that CDKN2A loss, which is nearly universal in patients but dispensable in mouse models, is essential for neoplastic transformation when combined with KRAS and TP53 mutations, whereas SMAD4 loss promotes tumor progression. Multi-omics profiling reveals epigenetic repression of the pancreatic lineage program during PDAC initiation, alongside AP-1-driven chromatin remodeling. We identify TET1 suppression as a mechanistic link between oncogenic ERK signaling and hypermethylation of essential pancreatic transcription factors. This model captures genetic and epigenetic determinants of human PDAC, reveals antagonism between oncogenic and lineage restriction programs, and supports TET-based lineage restoration as a potential early intervention strategy.

PMID:42161274 | PMC:PMC13196429 | DOI:10.1016/j.devcel.2026.04.012

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Evaluating AI in leukocyte classification: performance of the AI system against 15 morphology experts

npj Digital Medicine, Published online: 11 April 2026; doi:10.1038/s41746-026-02601-w

Evaluating AI in leukocyte classification: performance of the AI system against 15 morphology experts
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A Genetically Engineered Human Organoid Model Reveals Distinct Genetic and Epigenetic Barriers of Lineage Plasticity in Early PDAC Transformation

bioRxiv [Preprint]. 2026 Mar 11:2026.03.09.710586. doi: 10.64898/2026.03.09.710586.

ABSTRACT

The lack of accurate, human-based models recapitulating early-stage pancreatic ductal adenocarcinoma (PDAC) has hindered therapeutic development. Using pluripotent stem cell-derived pancreatic progenitor organoids, we established a human PDAC model that faithfully reproduces the genetic, epigenetic, and transcriptomic trajectory of tumor initiation and progression in vitro , validated against clinical datasets and histopathology. We demonstrate that CDKN2A loss, nearly universal in patients but dispensable in mouse models, is essential for neoplastic transformation when combined with KRAS and TP53 mutations, while SMAD4 loss promotes tumor progression. Multi-omics profiling reveals epigenetic repression of pancreatic lineage program during PDAC initiation, alongside oncogenic AP-1-driven chromatin remodeling. Notably, we identify TET1 suppression as a mechanistic link between oncogenic ERK signaling and the hypermethylation and silencing of essential pancreatic transcription factors. This model captures the genetic and epigenetic determinants of human PDAC, reveals antagonism between oncogenic and lineage restriction programs, and supports TET-based lineage restoration as a promising early intervention strategy for high-risk individuals.

PMID:41959451 | PMC:PMC13060829 | DOI:10.64898/2026.03.09.710586

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Effects of multisensory stimulation based on immersive virtual reality in postoperative neuropsychiatric recovery after gynecological laparoscopy

npj Digital Medicine, Published online: 24 March 2026; doi:10.1038/s41746-026-02515-7

Effects of multisensory stimulation based on immersive virtual reality in postoperative neuropsychiatric recovery after gynecological laparoscopy
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Research on the compatibility mechanism of the Tingli Dazao Xiefei Decoction by multi-organ metabolomics strategy

J Ethnopharmacol. 2026 Mar 21:121548. doi: 10.1016/j.jep.2026.121548. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The Tingli Dazao Xiefei Decoction (TD) is a traditional phlegm-eliminating prescription composed of Descurainia sophia (L.) Webb. ex Prantl (TLZ) and Ziziphus jujuba Mill. (DZ), which can relieve lung, heart and kidney injury in asthma. TLZ acts as the monarch drug in the TD. Based on the research mode of "material basis of traditional Chinese medicinal properties can be divided and combined", we have confirmed that the flavonoid glycosides components /the oligosaccharide components/the fatty oil component (FG/Oli/FO) are effective components of TLZ. However, the compatibility mechanism of the TD, and the contribution of the effective components of TLZ to the efficacy were still unclear.

AIM OF THE STUDY: To clarify the compatibility mechanism of TD, and the contribution of the effective components of TLZ to the efficacy from a comprehensive perspective of lung, heart, and kidney.

METHODS: First, we chose the asthma model corresponding to the efficacy of TD in purging the lungs and relieving asthma, and the rats were divided into the normal (NC) group, model (M) group, dexamethasone (DEX) group, and treatment groups of TD/TLZ/DZ/FO+DZ/Oli+DZ/FG+DZ. Second, metabolomics and network pharmacology were applied to elucidate the comprehensive protective effect of TD/FG+DZ/Oli+DZ/FO+DZ. Third, the multi-omics results were validated using Western blotting, RT-qPCR, flow cytometry, and immunofluorescence.

RESULTS: FO+DZ/Oli+DZ/FG+DZ had different degrees of protective effects against lung/heart/kidney injury in asthma. In metabolomics research, the principal component analysis (PCA) and cluster analysis results showed that the TLZ group was closer to TD group than DZ group, the FO+DZ and Oli+DZ group clustered with TD/NC groups in the lung and kidney, and the FO+DZ and FG+DZ group clustered with TD/NC groups in the heart. Pathway enrichment analysis suggested that the comprehensive protective effect of TLZ and its effective components combined with DZ on lung/heart/kidney may be achieved by regulating the arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and unsaturated fatty acid biosynthesis. Multi-organ metabolomics and network pharmacology revealed consistent biological functions in KEGG pathways. Validation experiment showed that TLZ and its effective components combined with DZ could reverse the abnormal expression of proteins and RNA related to inflammation, airway remodeling, excitotoxicity, and energy-supply, apoptosis at different levels. Furthermore, FO+DZ may reduce asthma damage by inhibiting the FABP4/PPAR-γ/NF-κB signaling pathway.

CONCLUSION: TLZ played the key role in TD, and FO had the best therapeutic effect on each organ; the efficacy of Oli was mainly reflected in reducing lung and kidney damage, and FG was mainly involved in enhancing energy metabolism in the heart. These findings proved that traditional Chinese medicine could exert comprehensive efficacy in a 'multi-components trigger multi-channel' way.

PMID:41871629 | DOI:10.1016/j.jep.2026.121548

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Research on the compatibility mechanism of the Tingli Dazao Xiefei Decoction by multi-organ metabolomics strategy

J Ethnopharmacol. 2026 Mar 21:121548. doi: 10.1016/j.jep.2026.121548. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The Tingli Dazao Xiefei Decoction (TD) is a traditional phlegm-eliminating prescription composed of Descurainia sophia (L.) Webb. ex Prantl (TLZ) and Ziziphus jujuba Mill. (DZ), which can relieve lung, heart and kidney injury in asthma. TLZ acts as the monarch drug in the TD. Based on the research mode of "material basis of traditional Chinese medicinal properties can be divided and combined", we have confirmed that the flavonoid glycosides components /the oligosaccharide components/the fatty oil component (FG/Oli/FO) are effective components of TLZ. However, the compatibility mechanism of the TD, and the contribution of the effective components of TLZ to the efficacy were still unclear.

AIM OF THE STUDY: To clarify the compatibility mechanism of TD, and the contribution of the effective components of TLZ to the efficacy from a comprehensive perspective of lung, heart, and kidney.

METHODS: First, we chose the asthma model corresponding to the efficacy of TD in purging the lungs and relieving asthma, and the rats were divided into the normal (NC) group, model (M) group, dexamethasone (DEX) group, and treatment groups of TD/TLZ/DZ/FO+DZ/Oli+DZ/FG+DZ. Second, metabolomics and network pharmacology were applied to elucidate the comprehensive protective effect of TD/FG+DZ/Oli+DZ/FO+DZ. Third, the multi-omics results were validated using Western blotting, RT-qPCR, flow cytometry, and immunofluorescence.

RESULTS: FO+DZ/Oli+DZ/FG+DZ had different degrees of protective effects against lung/heart/kidney injury in asthma. In metabolomics research, the principal component analysis (PCA) and cluster analysis results showed that the TLZ group was closer to TD group than DZ group, the FO+DZ and Oli+DZ group clustered with TD/NC groups in the lung and kidney, and the FO+DZ and FG+DZ group clustered with TD/NC groups in the heart. Pathway enrichment analysis suggested that the comprehensive protective effect of TLZ and its effective components combined with DZ on lung/heart/kidney may be achieved by regulating the arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and unsaturated fatty acid biosynthesis. Multi-organ metabolomics and network pharmacology revealed consistent biological functions in KEGG pathways. Validation experiment showed that TLZ and its effective components combined with DZ could reverse the abnormal expression of proteins and RNA related to inflammation, airway remodeling, excitotoxicity, and energy-supply, apoptosis at different levels. Furthermore, FO+DZ may reduce asthma damage by inhibiting the FABP4/PPAR-γ/NF-κB signaling pathway.

CONCLUSION: TLZ played the key role in TD, and FO had the best therapeutic effect on each organ; the efficacy of Oli was mainly reflected in reducing lung and kidney damage, and FG was mainly involved in enhancing energy metabolism in the heart. These findings proved that traditional Chinese medicine could exert comprehensive efficacy in a 'multi-components trigger multi-channel' way.

PMID:41871629 | DOI:10.1016/j.jep.2026.121548

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PRAM-R: A Perception-Reasoning-Action-Memory Framework with LLM-Guided Modality Routing for Adaptive Autonomous Driving

arXiv:2603.04222v1 Announce Type: cross Abstract: Multimodal perception enables robust autonomous driving but incurs unnecessary computational cost when all sensors remain active. This paper presents PRAM-R, a unified Perception-Reasoning-Action-Memory framework with LLM-Guided Modality Routing for adaptive autonomous driving. PRAM-R adopts an asynchronous dual-loop design: a fast reactive loop for perception and control, and a slow deliberative loop for reasoning-driven modality selection and memory updates. An LLM router selects and weights modalities using environmental context and sensor diagnostics, while a hierarchical memory module preserves temporal consistency and supports long-term adaptation. We conduct a two-stage evaluation: (1) synthetic stress tests for stability analysis and (2) real-world validation on the nuScenes dataset. Synthetic stress tests confirm 87.2% reduction in routing oscillations via hysteresis-based stabilization. Real-world validation on nuScenes shows 6.22% modality reduction with 20% memory recall while maintaining comparable trajectory accuracy to full-modality baselines in complex urban scenarios. Our work demonstrates that LLM-augmented architectures with hierarchical memory achieve efficient, adaptive multimodal perception in autonomous driving.
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