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01.
arXiv (CS.CL) 2026-06-24

PORTER: Language-Grounded Event Representations for Portable Structured EHR Foundation Models

Most electronic health record (EHR) foundation models encode clinical events as discrete event tokens from a fixed vocabulary and therefore cannot directly represent events containing unseen concepts or new combinations of concepts and attributes such as numeric values. This limits transfer across institutions and even across deployment pipelines within the same institution. We introduce PORTER, a language-grounded structured EHR foundation model that decouples event representation from this fixed vocabulary. PORTER represents events through their descriptions using a frozen text encoder, integrates numeric values through a dedicated pathway, and learns clinical dynamics over patient timelines with an autoregressively pretrained temporal backbone. Across 74 clinical prediction tasks at a pediatric hospital, PORTER matched the mean AUROC of a fixed-vocabulary model with the same temporal backbone and pretraining objective. When the same patient timelines were rendered using event descriptions not seen during pretraining, PORTER transferred without retraining or vocabulary mapping, recovering 97.1% of the mean AUROC of a model trained directly on the target vocabulary. When transferred to MIMIC, PORTER outperformed the fixed-vocabulary model, which dropped 69% of events because their tokens were unseen. Mechanistic analyses showed cross-vocabulary transfer tracked preservation of patient-level representation geometry rather than the scale of the text encoder, and the numeric pathway improved sensitivity to magnitude without disrupting clinical concept identity. PORTER also achieved higher AUROC than a task-specific text serialization comparator, at 329-fold lower amortized compute. PORTER is a step toward vocabulary-independent EHR foundation models that reduce the need for vocabulary harmonization while preserving in-domain performance and enabling efficient cross-task reuse.

02.
medRxiv (Medicine) 2026-06-22

AI-Assisted Longitudinal Analyses of Environmental and Psychosocial Determinants of Subjective Cognitive Difficulties

作者:

Short-term environmental exposures have been linked to cognitive and behavioral outcomes, although many reported associations may reflect broader geographic and contextual differences. Using longitudinal data from the All of Us Research Program (2018–2024), we linked daily weather and air-pollution exposures to repeated attention-related and subjective cognitive outcomes. Associations were evaluated using pooled, fixed-effects, lagged, and event-study analyses. Additional machine-learning analyses were conducted to explore potential heterogeneity and latent psychosocial structure. Replication analyses were performed using the 2024 Behavioral Risk Factor Surveillance System (BRFSS). Several environmental exposure measures showed small associations with cognitive outcomes in pooled analyses, but most attenuated substantially after accounting for within-location temporal variation. Mediation, sensitivity, and machine-learning analyses yielded similar conclusions. In contrast, mental-health burden, loneliness, and social functioning were consistently associated with subjective cognitive difficulty and exhibited substantially larger effect sizes than environmental exposures. Similar patterns were observed in BRFSS. Exploratory AI-assisted analyses yielded findings broadly consistent with the primary longitudinal analyses. These findings suggest that short-term environmental perturbations may have limited associations with cognitive outcomes after accounting for within-location variation, whereas psychosocial factors appear to be more consistently associated with subjective cognitive burden.

03.
arXiv (CS.AI) 2026-06-15

Causal Object-Centric Models for Planning with Monte Carlo Tree Search

arXiv:2606.14418v1 Announce Type: new Abstract: We introduce COMET (Causal Object-centric Model for Efficient Tree search), a model-based reinforcement learning algorithm that performs Monte Carlo Tree Search in a slot-structured latent space. COMET pairs a frozen unsupervised object-centric encoder with a transformer-based world model, in which actions are bound to objects through a novel action-slot fusion mechanism that is used in slot transition prediction. Policy and value heads use object-causal attention, modulating token interactions by learned per-slot relevance scores so that decision-making concentrates on task-relevant entities. COMET adds an explicit object-level inductive bias to MuZero-style latent planning. Across eight visually and dynamically diverse tasks from the Object-Centric Visual RL benchmark, ManiSkill, Robosuite, and VizDoom, COMET achieves a higher mean normalized score during the early stages of training compared to object-centric and monolithic baselines.

04.
arXiv (CS.CL) 2026-06-17

ProvenanceGuard: Source-Aware Factuality Verification for MCP-Based LLM Agents

Tool-using LLM agents increasingly use the Model Context Protocol (MCP) to answer from heterogeneous evidence sources, including search, APIs, databases, clinical records, and formulary tools. Standard factuality metrics usually test whether an answer is supported by pooled evidence, missing a provenance-sensitive failure mode: a claim may be supported somewhere while being attributed to the wrong source. We call this cross-source conflation. We introduce ProvenanceGuard, a source-aware verifier for MCP-grounded answers. It consumes captured MCP traces with stable tool IDs, source IDs, and raw outputs; decomposes answers into atomic claims; routes claims to source-specific evidence; checks support with NLI and a token-alignment proxy; compares stated attribution with the routed source; and returns per-claim verdicts plus an answer-level allow/block decision. Blocked answers can be repaired with retrieval-augmented answer revision and re-verified. We evaluate on 281 medical-domain MCP-agent traces. A 266-trace adjudicated subset yields 2,325 LLM-assisted claim labels split by trace; 361 held-out labels are human-verified. On the 40-trace held-out split, ProvenanceGuard achieves block F1 0.802 and source accuracy 0.858 over 260 source-eligible claims, outperforming source-blind baselines that do not emit claim-to-source IDs. On a harder multi-source benchmark it reaches block F1 0.846, while source-plus-relation accuracy drops to 0.229, showing that exact source ownership remains difficult with semantically close sources. Repair-and-reverify resolves all blocked answers in the full trace set, often via conservative fallback. In 50 controlled clinical conflation probes, ProvenanceGuard detects all injected attribution swaps with no retained wrong attribution. These results show that source attribution is an independent axis for factuality verification in MCP-based agents.

05.
arXiv (CS.CV) 2026-06-24

3D Masked Autoencoders are Robust Learners of Volumetric and Multimodal Cellular Representations for Microscopy

Self-supervised learning in fluorescence microscopy often relies on 2D projections, despite the inherently three-dimensional nature of cells. We present a systematic comparison of 2D and 3D masked autoencoders (MAE-2D vs. MAE-3D) on volumetric microscopy data. Under matched architectures and training protocols, MAE-3D consistently outperforms 2D max-projection and slice-based variants on downstream single-cell tasks. We further align visual representations with a pretrained protein language model (ESM2) and show that cross-modal supervision yields larger gains for volumetric models. Channel cross-attention and frequency-domain regularization are critical for leveraging 3D spatial context. On a protein–protein interaction task, MAE-3D achieves a ROC–AUC of 0.865, outperforming prior methods by up to +0.025. For protein localization, our best 3D model attains state-of-the-art AUC$_{micro}$ (0.952) and F1$_{micro}$ (0.742), improving over previous approaches by +0.003 and +0.010 absolute, respectively. Overall, these results demonstrate the advantages of native 3D modeling and multimodal alignment for representation learning in single-cell microscopy.

06.
arXiv (CS.CV) 2026-06-17

Phenotyping TPF via Self-Supervised Learning: A Label-Agnostic Framework with Expert Validation

The full potential of artificial intelligence in tibial plateau fracture characterisation remains unrealised, constrained by a fundamental dependency on labelled datasets whose consistency cannot be guaranteed: conventional classification schemes such as Schatzker and AO/OTA suffer from inter-observer variability, causing supervised models to learn human disagreement rather than stable fracture morphology. We design, implement, and validate a label-agnostic framework that eliminates this constraint by learning fracture representations directly from imaging data without observer-assigned labels. A RadImageNet-pretrained ResNet-50 encoder is fine-tuned on 154 cleaned knee radiographs using the SimCLR contrastive objective, preceded by a data cleaning protocol and followed by UMAP dimensionality reduction and k-means clustering to discover four imaging-derived phenotypes. Phenotype validity is assessed through a blinded expert review protocol administered to two independent clinicians. The four phenotypes demonstrate robust stability (bootstrap ARI = 0.319 +/- 0.041), strong internal cohesion (silhouette = 0.511), and coherence ratings of 3-5/5 from both reviewers under blinded conditions; one phenotype was unanimously identified as exhibiting comminution – a high-complexity feature isolated without any supervisory signal. Inter-partition comparison against Schatzker labels yields ARI = 0.013, confirming orthogonality to conventional classification boundaries. Notably, expert reviewers anchored to established classification vocabularies perceived imaging-derived groups as heterogeneous precisely where Schatzker alignment was lowest, suggesting that Schatzker-trained perception and label-agnostic embedding geometry measure orthogonal dimensions. These findings establish label-agnostic SSL phenotyping as a reproducible and clinically interpretable complement to conventional classification.

07.
medRxiv (Medicine) 2026-06-12

Room-Specialized Mixture-of-Experts for In-Home ADL Recognition with Ambient Sensors

Monitoring activities of daily living (ADLs) in the home is a promising approach for tracking dementia progression in older adults. While ambient sensor-based ADL systems are well-studied, most existing ADL recognition systems rely on globally trained models that ignore the spatial organization of in-home activities. In real deployments, where training data are sparse and highly home-specific, global transformer models may fail to capture room-dependent behavioral structure. We propose a deterministic Mixture of Experts (MoE) architecture for in-home ADL recognition, in which each expert is a compact transformer specialized to one room of the home (bedroom, kitchen, bathroom, living area). Input segments are routed using a deterministic gating strategy based on room-level motion activity and time-of-day priors for sleep-related behaviors. Unlike learned routing networks, the proposed gate encodes domain knowledge about where ADLs are likely to occur, reducing model complexity under limited per-home training data. By decomposing ADL recognition into room-specific activity spaces, the proposed architecture reduces competition between dominant and low-frequency activities under highly imbalanced residential data. We evaluated the system on data collected via low-cost ambient sensors (motion, light, temperature, humidity) and Raspberry Pi edge devices across five homes, with ground-truth ADL labels provided by participants and caregivers. Across the five homes, the proposed MoE consistently outperformed global transformer, 1D CNN, and Random Forest baselines, achieving macro-F1 scores ranging from 0.60 to 0.88, highlighting the importance of home-specific modeling in real-world deployments. These findings suggest that room-aware expert specialization may provide a practical and interpretable strategy for low-data ADL recognition in real-world residential environments.

08.
arXiv (quant-ph) 2026-06-11

Machine-learned, finite temperature Fermi-operator expansions suitable for GPUs and AI-hardware

arXiv:2605.08523v2 Announce Type: replace Abstract: We present several finite-temperature recursive Fermi-operator expansion schemes based on the second-order spectral projection (SP2) method. Our approach builds on a previous observation that the electronic structure problem, as formulated through a recursive SP2 expansion, can be mapped onto the architecture of a deep neural network. Using this perspective, we generalize SP2 to finite electronic temperatures by constructing machine learning models that determine optimized recursive expansion coefficients. The same approach is also applied to the prediction of the electronic entropy for fractional occupation numbers. The coefficients are trained for a specified chemical potential and electronic temperature and are not available in closed analytical form. However, by employing an appropriate affine rescaling strategy to the Hamiltonian matrix, we eliminate the need to retrain the model for different temperatures and chemical potentials. Our approach avoids explicit diagonalization and relies solely on highly optimized matrix-matrix multiplication kernels. Compared to state-of-the-art diagonalization, we achieve an order-of-magnitude speedup in the single-particle finite-temperature density matrix calculation for small and moderately sized matrices on modern GPUs and dense matrix multiply units.

09.
arXiv (CS.AI) 2026-06-19

QueryGaussian: Scalable and Training-Free Open-Vocabulary 3D Instance Retrieval

arXiv:2606.19733v1 Announce Type: cross Abstract: Efficiently retrieving specific 3D instances from large-scale scenes via natural language prompts remains a formidable challenge in multimedia analysis. Existing approaches predominantly follow a "scene-level embedding" paradigm, which requires distilling high-dimensional semantic features into every 3D primitive. This strategy suffers from a fundamental architectural bottleneck: memory and computational costs scale linearly with scene complexity, inevitably triggering out-of-memory (OOM) failures in city-scale environments. To address this barrier, we propose QueryGaussian, a training-free framework for expeditious and scalable open-vocabulary 3D instance retrieval. Unlike holistic semantic distillation, QueryGaussian employs an instance-level query mechanism that decouples semantic understanding from geometric representation. Specifically, we leverage pre-trained 2D vision models to interpret user prompts and lift segmentation masks into 3D via a concurrent maximum-weight association strategy, ensuring semantic-visual consistency. To mitigate projection ambiguity, we introduce a temporal fusion module with multi-stage adaptive density clustering. Experimental results demonstrate that QueryGaussian not only matches the accuracy of state-of-the-art methods but also delivers a decisive efficiency leap, reducing GPU memory usage by over 70% and accelerating inference by 180x. Crucially, QueryGaussian enables expeditious instance retrieval on city-scale scenes containing tens of millions of Gaussians using consumer-grade hardware.

10.
arXiv (CS.CV) 2026-06-16

Near–Real-Time Conflict-Related Fire Detection in Sudan Using Unsupervised Deep Learning

Ongoing armed conflict in Sudan highlights the need for rapid monitoring of conflict-related fire-affected areas. Recent advances in deep learning and high-frequency satellite imagery enable near–real-time assessment of active fires and burn scars in war zones. This study presents a near–real-time monitoring approach using a lightweight Variational Auto-Encoder (VAE)–based model integrated with 4-band Planet Labs imagery at 3 m spatial resolution. We demonstrate that these impacted regions can be detected within approximately 24 to 30 hours under favorable observational conditions using accessible, commercially available satellite data. To achieve this, we adapt a VAE–based model, originally designed for 10-band imagery, to operate effectively on high-resolution 4-band inputs. The model is trained in an unsupervised manner to learn compact latent representations of nominal land-surface conditions and identify burn signatures by quantifying changes between temporally paired latent embeddings. Performance is evaluated across five case studies in Sudan and compared against cosine distance, CVA, and IR-MAD using precision, recall, F1-score, and the area under the precision-recall curve (AUPRC) computed between temporally paired image tiles. Results show that the proposed approach consistently outperforms the other methods, achieving higher recall and F1-scores while maintaining viable precision in highly imbalanced fire-detection scenarios. Experiments with 8-band imagery and temporal image sequences yield only marginal performance gains over single 4-band inputs, underscoring the effectiveness of the proposed lightweight approach for scalable, near–real-time conflict monitoring.

11.
medRxiv (Medicine) 2026-06-18

Automated Airways Characterization and Assessment of Cystic Fibrosis from CT Imaging

Background Advancements in medical imaging have enabled non-invasive diagnosis and staging of cystic fibrosis (CF) using CT scans, revealing dilated airways, an increased number of visible airways, and airway generation splits in these patients. However, manual characterization of airways remains time-consuming and challenging due to the numerous structural changes, thereby limiting clinical feasibility. This study aims to develop an automated algorithm to characterize airways from segmented lung CT scans and apply this to a retrospective population. This approach reduces the time required to analyze images and obtain disease-staging results. Methods This framework consists of two stages. The first stage extracts and skeletonizes the airway tree from lung CTs, while the second stage measures lung features, including airway volumes, branch counts, generation splits, diameters, and cross-sectional areas. This permits comprehensive characterization for use in clinical assessment. Results The airways analysis was performed on 169 CT volumes ranging in age from 6 to 18 years of age, revealing substantial differences in detected airway branches, generation splits, and normalized airway volume between the control and CF groups. The framework also measures airway diameters and cross-sectional areas, revealing an increase in the number of small airways in cystic fibrosis patients, due to early bronchiectasis. These findings align with previous research and demonstrate the framework's ability to accurately quantify airway changes in patients with CF. Discussion The framework extracts entire airway trees, facilitating measurements of volume, branch count, diameters, and cross-sectional areas, which change with CF severity and/or treatment. However, partial lung atelectasis can limit the accuracy of airway detection in moderate-to-severe cases. Funding NIA U54 AG054345 and NIA R21 AG07857501

12.
arXiv (CS.CV) 2026-06-19

EventVLA: Event-Driven Visual Evidence Memory for Long-Horizon Vision-Language-Action Policies

Memory remains a critical bottleneck for long-horizon robotic manipulation, as standard Vision-Language-Action (VLA) policies often fail when task-relevant cues become occluded or unobservable over time. While existing memory-augmented methods utilize historical context, they either suffer from severe information bottlenecks, incur high latency via decoupled dual systems, or rely on unselective buffers that accumulate massive visual redundancies. To address these limitations, we introduce EventVLA, an end-to-end framework founded on the concept of sparse visual evidence memory that comprises two core components: foundational visual anchors to retain initial and short-term contexts, and a dynamic Keyframe Evidence Memory (KEM) module. Specifically, KEM directly predicts future keyframe probabilities from the VLA's latent embeddings to autonomously capture and store sparse, task-critical visual events. This foresight-driven mechanism empowers the policy to dynamically evaluate the future causal utility of current observations, preserving transient visual evidence before it becomes unobservable. Furthermore, we propose RoboTwin-MeM, a diagnostic benchmark specifically designed to evaluate non-Markovian manipulation tasks with interactive visual evidence. Extensive evaluations show that across 17 memory-requiring simulation tasks and 4 real-world bimanual tasks, EventVLA achieves an average success rate improvement of +40% over state-of-the-art memory-augmented VLAs.

13.
arXiv (CS.CL) 2026-06-11

LifeSentence: Language models can encode human life course trajectories from longitudinal panel data

Forecasting human life outcomes is important to gain insights into how individuals attain long and healthy lives. Conventional statistical approaches yield limited accuracy, potentially due to discarding the sequential structure of the life course. Modern methods such as transformer architectures require large scale training data that most longitudinal panel studies lack. Here we introduce LifeSentence, a model for life-course reasoning that bridges large language models with longitudinal panel data. By representing each life event as a structured natural-language record and instruction-tuning a pretrained 24-billion-parameter language model across an 18-task evaluation taxonomy spanning prediction, robustness and reasoning, LifeSentence supplements panel data with distributional knowledge already encoded during pretraining. Trained on approximately 65,000 individuals from the German Socio-Economic Panel - roughly 45 times fewer than prior transformer-based approaches - LifeSentence outperforms classical and deep learning baselines across all task families, achieving a threefold improvement in joint event-and-timing prediction from best baselines and 91.2% Kendall's tau when reconstructing chronological order from timestamp-stripped event sets. Without explicit supervision, the model recovers documented patterns of social stratification, including the education premium, the gender wage gap and the motherhood penalty, from discrete event sequences alone. A natural-language interface further enables qualitatively new research queries, such as connecting an early-life history to a specified late-life endpoint, establishing LifeSentence as both a predictive tool and a probe for counterfactual exploration of human biographies.

14.
arXiv (CS.CV) 2026-06-16

FrameOracle: Learning What to See and How Much to See in Videos

Vision-language models (VLMs) advance video understanding but operate under tight computational budgets, making performance dependent on selecting a small, high-quality subset of frames. Existing frame sampling strategies, such as uniform or fixed-budget selection, fail to adapt to variations in content density or task complexity. To address this, we present FrameOracle, a lightweight, plug-and-play module that predicts both (1) which frames are most relevant to a given query and (2) how many frames are needed. FrameOracle is trained via a curriculum that progresses from weak proxy signals, such as cross-modal similarity, to stronger supervision with FrameOracle-41K, the first large-scale VideoQA dataset with validated keyframe annotations specifying minimal sufficient frames per question. Extensive experiments across five VLMs and six benchmarks show that FrameOracle reduces 16-frame inputs to an average of 10.4 frames without accuracy loss. When starting from 64-frame candidates, it reduces inputs to 13.9 frames on average while improving accuracy by 1.5%, achieving state-of-the-art efficiency-accuracy trade-offs for scalable video understanding.

15.
arXiv (math.PR) 2026-06-12

A mathematical study of the excess growth rate

arXiv:2510.25740v2 Announce Type: replace-cross Abstract: The excess growth rate, defined as the gap in Jensen's inequality for the logarithm, is a fundamental functional in portfolio theory. In this paper, we present a mathematical study motivated by information theory. We begin by establishing its properties and showing that it has rich connections with information theoretic concepts such as the Helmholtz free energy, L. Campbell's measure of average code length and large deviations. Our main results consist of three axiomatic characterization theorems of the excess growth rate, in terms of (i) the relative entropy, (ii) the gap in Jensen's inequality, and (iii) the logarithmic divergence that generalizes the Bregman divergence. Furthermore, we study maximization of the excess growth rate and compare it with the growth optimal portfolio. Our results not only provide theoretical justifications of the significance of the excess growth rate, but also establish new connections between information theory and quantitative finance.

16.
medRxiv (Medicine) 2026-06-22

AI-driven Multimodal Representation Learning for Latent Mediation Structure Discovery of Socioeconomic Disadvantage, Psychosocial Factors, and Cardiometabolic Multimorbidity

作者:

Social disadvantage is associated with multimorbidity, but the pathways linking social conditions to disease burden remain poorly understood. We developed an AI-driven multimodal mediation framework that integrates socioeconomic, psychosocial, clinical, laboratory, behavioral, and genomic data from the All of Us Research Program. Modality-specific variational autoencoders were used to derive latent representations of each data domain, and mediation analyses were subsequently performed in latent space to evaluate indirect associations between socioeconomic disadvantage, psychosocial factors, and multimorbidity. The final analytic cohort included 20,804 participants with complete multimodal data. Across 800 exposure–mediator–outcome combinations, mediation signals were concentrated within a small number of latent dimensions. The strongest indirect association linked a socioeconomic disadvantage dimension, a psychosocial vulnerability dimension, and a cardiometabolic multimorbidity dimension (NIE = 0.002517). The psychosocial dimension was characterized by poorer mental health, greater loneliness, lower social well-being, and lower health literacy, whereas the outcome dimension was associated with hypertension, diabetes, hyperlipidemia, obesity, chronic kidney disease, and heart disease. Bootstrap analyses supported the stability of the leading pathway. These findings suggest that psychosocial vulnerability may contribute to the association between socioeconomic disadvantage and cardiometabolic multimorbidity. More broadly, the proposed framework illustrates how AI-based representation learning can be used to investigate complex relationships across high-dimensional multimodal health data.

17.
bioRxiv (Bioinfo) 2026-06-12

Evaluating cell type annotations in single-cell omics in the absence of ground truth

Accurate cell type annotation is essential for single-cell transcriptomics, directly shaping downstream analyses and biological interpretations. Yet, objective evaluation of annotation quality remains a major challenge. Here, we argue that a cell type or cell state label has practical utility only if it captures a molecular pattern that is reproducible across biological replicates. Based on this principle, we introduce inter-sample consistency (ISC), a quantitative framework to assess annotation quality in single-cell RNA-seq datasets. Unlike existing cluster validation approaches, ISC distinguishes annotations that generalize across samples and individuals from those driven by technical or unwanted variation, thereby providing principled criteria for annotation quality and transferability. When applied to published single-cell atlases, ISC reveals widespread reproducibility gaps and provides actionable guidance for repairing inconsistent annotations. Notably, ISC enables benchmarking of automated cell type annotation tools even when ground-truth labels are unavailable, providing interpretable metrics to guide their development and evaluation. Implemented as the scTypeEval Bioconductor package, this framework offers a broadly applicable resource for evaluating and improving cell type annotations in single-cell RNA-seq experiments.

18.
arXiv (CS.AI) 2026-06-12

scLLM-DSC: LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering for Single-Cell RNA Sequencing

arXiv:2606.13007v1 Announce Type: cross Abstract: Clustering is fundamental to scRNA-seq analysis, serving as a cornerstone for identifying cell populations and resolving tissue heterogeneity. However, existing methods focus on mining numerical statistical patterns, suffering from semantic agnosticism by neglecting the intrinsic biological functions encoded by genes. While Large Language Models (LLMs) offer promising semantic capabilities, their direct adaptation to cell clustering is hindered by the structural mismatch between generative pre-training objectives and discriminative downstream tasks. To bridge this gap, we propose scLLM-DSC, a novel LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering framework. Diverging from data-driven paradigms, scLLM-DSC establishes a semantically-grounded representation by synergizing two views: a Knowledge-Driven Semantic View derived from NCBI gene priors and contextualized Cell2Sentence embeddings, and a Structure-Aware Topological View extracted via a graph-guided encoder. Crucially, we introduce a cross-modal contrastive alignment mechanism to enforce consistency between biological semantics and transcriptomic features within a unified latent space. Extensive benchmarks demonstrate that scLLM-DSC significantly outperforms eleven state-of-the-art baselines in clustering accuracy.

19.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

作者:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

20.
arXiv (CS.LG) 2026-06-11

Bypassing Prompt Guards in Production with Controlled-Release Prompting

arXiv:2510.01529v4 Announce Type: replace Abstract: Ball et al. recently established that prompt filtering for AI alignment faces a fundamental barrier: under standard cryptographic assumptions, no filter running significantly faster than the protected model can universally distinguish adversarial prompts from benign ones. We investigate whether this impossibility result translates to real-world vulnerabilities in deployed large language model (LLM) systems. We answer affirmatively by introducing controlled-release prompting, a practical instantiation of the theoretical framework that exploits the resource asymmetry between lightweight input filters and the main models they protect. Unlike the theoretical construction, our attack does not require model modification: it generates malicious prompts that are indecipherable by any bounded filter yet remain tractable to the target LLM. We find our attack to be successful on four major chat platforms (Google Gemini, DeepSeek Chat, xAI Grok, and Mistral Le Chat) where baseline methods fail. Additionally, we apply our attack to extract copyrighted data from Gemini. Finally, we provide a systematic evaluation of 14 open-weight prompt guard models, revealing that even reasoning-capable filters cannot reliably detect our attack without incurring prohibitive resource overhead.

21.
arXiv (CS.AI) 2026-06-17

Embedded Machine Learning for Microcontroller-Class Edge Devices: Data, Feature, Evaluation, and Deployment Pipelines

arXiv:2606.18122v1 Announce Type: cross Abstract: Embedded machine learning moves inference from cloud services to resource-constrained devices that must acquire data, preprocess signals, run a model, and act within tight limits on memory, energy, and latency. This paper presents a systems-oriented synthesis of an embedded machine-learning workflow for microcontroller-class platforms. The emphasis is placed on engineering decisions that are often hidden in generic machine-learning introductions: sampling and buffering, feature extraction as dimensionality reduction, validation under class imbalance, model/runtime co-design, and streaming deployment. Two representative signal families are used throughout the paper. The first is inertial motion recognition, where a two-second, three-axis accelerometer window is transformed from raw samples into root-mean-square and spectral features before classification. The second is keyword spotting, where audio is sampled, anti-aliased, transformed into mel-frequency cepstral coefficients, and processed by a compact one-dimensional convolutional network. The paper concludes with practical design rules for robust on-device inference, including data curation, quantization, thresholding, scheduling, and field monitoring.

22.
arXiv (CS.CL) 2026-06-17

Atlas: Orchestrating Heterogeneous Models and Tools for Multi-Domain Complex Reasoning

The integration of large language models (LLMs) with external tools has significantly expanded the capabilities of AI agents. However, as the diversity of both LLMs and tools increases, selecting the optimal model-tool combination becomes a high-dimensional optimization challenge. Existing approaches often rely on a single model or fixed tool-calling logic, failing to exploit the performance variations across heterogeneous model-tool pairs. In this paper, we present ATLAS (Adaptive Tool-LLM Alignment and Synergistic Invocation), a dual-path framework for dynamic tool usage in cross-domain complex reasoning. ATLAS operates via a dual-path approach: (1) training-free cluster-based routing that exploits empirical priors for domain-specific alignment, and (2) RL-based multi-step routing that explores autonomous trajectories for out-of-distribution generalization. Extensive experiments across 15 benchmarks demonstrate that our method outperforms closed-source models like GPT-4o, surpassing existing routing methods on both in-distribution (+10.1%) and out-of-distribution (+13.1%) tasks. Furthermore, our framework shows significant gains in visual reasoning by orchestrating specialized multi-modal tools.

23.
arXiv (quant-ph) 2026-06-11

A semi-definite programming formulation of the device-dependent guessing probability

arXiv:2606.12079v1 Announce Type: new Abstract: In quantum mechanics, a measurement applied to a state in general produces some amount of intrinsic randomness. This is not only a fundamental feature of the theory, but is also at the basis of any quantum process to generate random numbers. The simplest of such processes consists of a single, fully charaterized, measurement acting on a single, fully characterized, state. Unfortunately, no general method to estimate the intrinsic randomness produced in such setups is known. In this work, we address this issue by presenting a semidefinite programming formulation of the maximum probability with which an adversary, Eve, can guess the outcomes of characterized but untrusted prepare-and-measure setups. We then present several applications of this construction. First, we apply our method to a variety of specific setups, allowing us both to benchmark the approach and, more importantly, to determine the exact amount of certifiable randomness in scenarios where only upper bounds were previously available. Then, we show that the presence of entanglement between the device preparing the state and the measurement strictly increases Eve's predictive power, already in the most elementary setup of a binary measurement acting on a qubit state.

24.
arXiv (CS.CL) 2026-06-15

Did You Forget What I Asked? Prospective Memory Failures in Large Language Models

作者:

Large language models often fail to satisfy formatting instructions when they must simultaneously perform demanding tasks. We study this behaviour through a prospective memory inspired lens from cognitive psychology, using a controlled paradigm that combines verifiable formatting constraints with benchmark tasks of increasing complexity. Across three model families and over 8,000 prompts, compliance drops by 2-21% under concurrent task load. Vulnerability is highly type-dependent: terminal constraints (requiring action at the response boundary) degrade most, with drops up to 50%, while avoidance constraints remain comparatively robust. A salience-enhanced format (explicit instruction framing plus a trailing reminder) recovers much of the lost compliance, restoring performance to 90-100% in many settings. Interference is bidirectional: formatting constraints can also reduce task accuracy, with one model's GSM8K accuracy dropping from 93% to 27%. In additional stacking experiments, joint compliance declines sharply as constraints accumulate. All results use deterministic programmatic checkers without an LLM-as-judge component on publicly available datasets.

25.
medRxiv (Medicine) 2026-06-17

Sao Tome and Principe on the verge of eliminating lymphatic filariasis as a public health problem: evidence from IDA impact assessment surveys

Background Accelerated efforts to eliminate lymphatic filariasis (LF) as a public health problem have been supported by the introduction of the triple-drug regimen of ivermectin, diethylcarbamazine and albendazole (IDA) in endemic settings. In Sao Tome and Principe, nationwide mass drug administration (MDA) with diethylcarbamazine and albendazole was implemented in 2018, followed by IDA in 2019 and 2020. This study assesses progress towards elimination using post-MDA impact assessment surveys conducted after cessation of treatment. Methods Cross-sectional surveys were conducted among adults aged 20 years and older in 2022 and again between December 2024 and January 2025. Circulating filarial antigen (CFA) was detected using the filarial test strip (FTS). Individuals who tested positive were examined for microfilaremia using nocturnal calibrated thick blood smear microscopy. Additionally, programme data on MDA coverage and morbidity were obtained from national surveillance records. Results Three rounds of nationwide MDA achieved high epidemiological coverage (86.4% in 2018, 74.2% in 2019 and 80.0% in 2020). The impact assessment surveys conducted in 2022 evaluated 14 132 adults, with 21 individuals (0.15%) testing positive for CFA, while the follow-up survey conducted between December 2024 and January 2025 assessed 14 653 adults and detected seven positive cases (0.05%). No microfilariae were detected among the 28 antigen-positive individuals examined using nocturnal calibrated thick blood smears. National morbidity records documented 190 cases of lymphoedema and nine cases of hydrocoele. Conclusions Infection indicators remain well below WHO decision thresholds, suggesting that LF transmission is unlikely to be sustained. Sao Tome and Principe appears to be close to eliminating LF as a public health problem. However, strengthening morbidity management services will be essential to support the preparation of the national elimination dossier.