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01.
arXiv (CS.AI) 2026-06-12

An Embodied Simulation Platform, Benchmark, and Data-Efficient Augmentation Framework for Wet-Lab Robotics

arXiv:2606.12936v1 Announce Type: cross Abstract: Wet-lab robots can improve the reproducibility, throughput, and safety of biomedical experiments, but scaling their learning requires customizable simulators for safe and reproducible task generation, open editable laboratory assets, and efficient pipelines that turn limited demonstrations into usable training data. We present Pipette, an embodied simulation platform, benchmark, and data-efficient augmentation framework for wet-lab robot learning. Pipette releases over 43 open-source and re-editable wet-lab assets, together with an extensible asset-building pipeline. A key component of Pipette is its simulation-based data augmentation pipeline, replaying human demonstrations in simulation, applies lighting, camera, speed, and action perturbations, and filters generated episodes with automatic task success checks, rapidly expanding usable training data from limited manual demonstrations. We further introduce an 11-task wet-lab embodied benchmark covering sample handling, culture-ware manipulation, device operation, and precision placement. With only 30 demonstrations per task, ACT achieves 65.5% average success rate, while simulation augmentation improves SmolVLA from 44.1% to 74.7% and {\pi}0 from 40.4% to 46.5%, validating the effectiveness of Pipette for data-efficient VLA training and evaluation. Pipette also supports natural-language-driven scene construction and task registration, lowering the barrier for non-expert users to define new wet-lab robotic tasks.

02.
arXiv (CS.CV) 2026-06-11

ViT-FREE: Efficient Face Recognition via Early Exiting and Synthetic Adaptation

Vision Transformers (ViTs) have gained significant attention in computer vision and shown strong potential for face recognition (FR). However, their high computational cost makes deployment on resource-constrained devices challenging, motivating the need for methods that balance efficiency and accuracy. In this work, we investigate early exiting in pretrained ViTs as a simple yet effective training-free strategy for efficient FR inference. Leveraging the uniform feature dimensionality across transformer encoder blocks, we introduce ViT-FREE, a multi-exit framework that enables face verification directly from intermediate representations without modifying or retraining the backbone model, and thus, reducing inference cost. Empirically, we show that patch embeddings and attention maps evolve progressively across depth, exhibiting high similarity between consecutive ViT blocks and increasing alignment with the final representation. This indicates gradual feature refinement and attention convergence, suggesting that intermediate layers already provide stable and discriminative representations suitable for early exiting. Through extensive experiments on multiple FR benchmarks, we systematically analyze the accuracy-efficiency trade-off across exit depths. Our results demonstrate that later exits achieve a highly favorable balance, with exiting at layer 10 yielding up to a 20% speedup while incurring only a 1.5 drop in verification performance on benchmarks such as IJB-C. Also, we propose ViT-FREE_FT, a lightweight exit-specific fine-tuning strategy that adapts only the projection layers using a small synthetic dataset while keeping the transformer backbone frozen. This approach improves the performance of shallow exits while preserving the efficiency benefits and leaving deeper exits largely unaffected.

03.
arXiv (CS.CL) 2026-06-12

RogueAI: A Reverse Turing Test for Detecting Licensed AI Deception in Dialogue

The original Turing Test asks a human judge to distinguish a machine from a person through dialogue. Three quarters of a century later, conversational systems pass this test in casual settings; the interesting epistemological question has shifted. We argue that the relevant modern variant asks not whether a dialogue partner is artificial, but whether it can be trusted. We present RogueAI, an interactive webapp that operationalizes this revisited test as a one-on-two interrogation game: a human player questions two indistinguishable Large Language Model agents, knowing that exactly one of them has been licensed to deceive within a shared fictional scenario. The player's task is to identify the deceptive agent and "shut it off" before a turn budget is exhausted. We further introduce AutoRogueAI, a procedural extension in which players co-design a custom scenario with a narrator agent that secretly chooses its own deception strategy. We describe the framing, sketch the abstract architecture and gameplay loop, and situate the artifact within recent work on LLM deception, social-deduction benchmarks, and scalable oversight via debate. A three-day pilot deployment (467 initiated sessions, 415 completed, 1876 interaction turns in Italian) provides early feasibility evidence and surfaces a concrete tension: the deceptive agent carries a reliable, locally-present linguistic signature - differential helpfulness, brevity, hedging - that a simple heuristic exploits at 75.6% accuracy, yet human players achieved only 56.6%, consistent with ignoring the most diagnostic signal entirely. We discuss what this gap implies for the artifact's use as a data-collection vehicle, a teaching tool, and an evaluation harness for honesty-trained models.

04.
arXiv (CS.AI) 2026-06-16

Metric Match: A Subset Selection Approach to Evaluating LLM Judge Reliability

arXiv:2606.15029v1 Announce Type: new Abstract: LLM judges are used to reduce the need for costly human labor in evaluating open-ended text generation. However, the reliability of these judges depends critically on their alignment with human raters – a property that itself depends on costly human annotations. In this work, we develop a method (Metric Match) for estimating correlation-based reliability metrics of LLM judges from limited annotations. Metric Match selects a subset of samples for human annotation such that the subset matches the population reliability metric with respect to acquired synthetic labels. We empirically show that Metric Match achieves a win-rate of 0.838 against random subset selection across four different correlation metrics and 15 datasets, with an 18.7% decrease in average estimation error and reduces annotation needs by 32.5%. We provide a cost model and highlight a medical case study where our method saves $1,041.67 compared to random selection for expert annotation. Further, we shift our task from reliability estimation to reliability classification of whether a given judge is above a deployment threshold, outperforming random selection with Metric Match. All project code is publicly available, and we additionally provide an installable package for ease of use.

05.
arXiv (CS.CV) 2026-06-17

Principled RL for Flow Matching Emerges from the Chunk-level Policy Optimization

Recent Progress in post-training flow matching for text-to-image (T2I) generation with Group Relative Policy Optimization (GRPO) has demonstrated strong potential. However, it is hindered by a critical limitation: inaccurate advantage attribution. In this work, we argue that aggregating consecutive steps into a coherent 'chunk' and shifting the policy optimization paradigm from GRPO's step level to the chunk level can effectively mitigate the negative impact of this issue. Building on this insight, we propose Group Chunking Policy Optimization (GCPO), the first chunk-level reinforcement learning approach for post-training flow matching. Extensive experiments demonstrate that GCPO achieves superior performance on both standard T2I benchmarks and preference alignment, with up to 43% relative gains over GRPO, highlighting the promise of chunk-level policy optimization. The code is available on https://github.com/xingzhejun/GCPO.

06.
arXiv (CS.CV) 2026-06-11

Vision Transformers for Face Recognition Need More Registers

Recent advances in Vision Transformers (ViTs) for face recognition (FR) have moved beyond the standard CLS-token paradigm. In this paradigm, a special classification token (CLS) is prepended to the patch embeddings and used as a representation of the input for downstream tasks. An alternative approach, Concatenated Patch Embeddings (CPE), instead leverages all patch tokens by concatenating them into a single vector, which is then projected into a compact face representation. CPE has been shown to improve recognition performance in comparison to CLS-based ones, but our qualitative analysis of attention maps showed the presence of artifacts that limit their interpretability. To address this issue, we incorporate register tokens, learnable tokens concatenated to the initial patch embeddings, and processed jointly through the ViT encoder blocks. This mechanism has been shown to produce more structured and interpretable attention maps compared to baseline ViT. We empirically demonstrate that these artifacts consistently appear across various ViT backbones, including small and large models, and that introducing register tokens effectively mitigates them. Adding four or eight registers significantly enhances interpretability, with eight registers providing the highest verification accuracies and smoothest attention structures. Our resulting model, ViT-8R, corresponds to a CPE-based ViT-B architecture augmented with eight register tokens achieves state-of-the-art performance among ViT-based FR models on large-scale IJB-B and IJB-C benchmarks. Also, ViT-8R produces substantially clearer attention maps compared with the baseline model, which offer deeper insight into the model's attention behavior (https://github.com/TaharChettaoui/ViT-FR-Registers)

07.
arXiv (CS.AI) 2026-06-19

UltraQuant: 4-bit KV Caching for Context-Heavy Agents

arXiv:2606.20474v1 Announce Type: cross Abstract: Context-heavy agents place unusual pressure on the key-value (KV) cache: long prefixes are reused across many short turns, while concurrency determines whether the serving system can keep GPUs utilized. We study 4-bit KV-cache compression for this setting, using TurboQuant-style rotation and codebook quantization as a quality anchor and vLLM FP8 KV caching as the deployment anchor. We report three contributions. First, we frame 4-bit KV caching around multi-round agent workloads where task quality, cache residency, and serving throughput must be measured jointly. Second, we describe the practical design choices needed to make the 4-bit path robust, including asymmetric K/V treatment, Walsh-Hadamard rotation, QJL removal, and block-scale variants. Third, we present serving optimizations on AMD GPUs, including optimized decode-attention kernels and UltraQuant, an FP4 approximation path that uses FP8 queries, FP4 KV tensors, UE8M0 group scales, and native scaled-MFMA support on CDNA4. On a long-context, multi-turn agentic workload, UltraQuant cuts P50 time-to-first-token by 3.47x in the cache-pressured late rounds (2.3x across all rounds) and raises output throughput by 1.63x over the FP8 KV baseline.

08.
bioRxiv (Bioinfo) 2026-06-19

OmniPath Metabo: chemical structures, interactions and mechanisms to study the metabolome

Mechanistic and functional analysis of omics data largely relies on the incorporation of prior knowledge; however, connecting metabolomics data and knowledge is a major methodological challenge. This is largely driven by the diverse prior knowledge being fragmented across many databases requiring the merging of different database records across chemical structures, identifiers, and varying levels of structural specificity. Hence, this limits mechanistic interpretation and functional characterisation of the metabolome. Here, we present OmniPath Metabo, a comprehensive, harmonized, metabolome-centric database covering metabolites, lipids, food-derived compounds, and small molecule drugs, along with their associated receptors, transporters, enzymes, reactions, allosteric regulators, and disease associations. OmniPath Metabo harmonizes attributes using controlled vocabularies and ontologies, structures and built-in cheminformatics to map identifiers and track ambiguity. OmniPath Metabo is built directly from 40+ original resources and is freely accessible via an interactive web app and API at metabo.omnipathdb.org. OmniPath Metabo enables dynamic, context-specific construction of subnetworks to serve dedicated purposes, such as cell-cell communication or integrated multi-omics metabolite-driven regulation, connecting reactions, allosteric regulation, metabolite-receptor and metabolite-transporter interactions. Combining it with the over 170 other resources in OmniPath, it can be used for integrated networks of signaling, gene regulation, and metabolism. We showcase the application of OmniPath Metabo by analysing publicly available metabolomics data of lung cancer cell lines and metabolic footprints to mutational patterns. In summary, OmniPath Metabo transforms fragmented resources into a harmonised prior knowledge framework for a mechanistic and functional analysis of the metabolome.

09.
arXiv (CS.CL) 2026-06-15

MASLab: A Unified and Comprehensive Codebase for LLM-based Multi-Agent Systems

LLM-based multi-agent systems (MAS) have demonstrated significant potential in enhancing single LLMs to address complex and diverse tasks in practical applications. Despite considerable advancements, the field lacks a unified codebase that consolidates existing methods, resulting in redundant re-implementation efforts, unfair comparisons, and high entry barriers for researchers. To address these challenges, we introduce MASLab, a unified, comprehensive, and research-friendly codebase for LLM-based MAS. (1) MASLab integrates over 20 established methods across multiple domains, each rigorously validated by comparing step-by-step outputs with its official implementation. (2) MASLab provides a unified environment with various benchmarks for fair comparisons among methods, ensuring consistent inputs and standardized evaluation protocols. (3) MASLab implements methods within a shared streamlined structure, lowering the barriers for understanding and extension. Building on MASLab, we conduct extensive experiments covering 10+ benchmarks and 8 models, offering researchers a clear and comprehensive view of the current landscape of MAS methods. MASLab will continue to evolve, tracking the latest developments in the field, and invite contributions from the broader open-source community.

10.
arXiv (CS.AI) 2026-06-18

Practical Anonymous Two-Party Gradient Boosting Decision Tree

arXiv:2605.26903v2 Announce Type: replace-cross Abstract: Structured data is well handled by gradient-boosted decision trees (GBDT), which are usually trained on vertically partitioned features across mutually distrustful parties. High speed and interpretability make GBDTs popular in finance and healthcare, where neural networks may fall short. Enabling secure computation for GBDTs poses unique challenges, requiring secure record alignment for comparison. Relying on private set intersection (PSI) is a de facto approach. Mistaking PSI for a safety measure actually exposes which record identifiers (IDs) are shared between the datasets. Although circuit-PSI could help, it is costly for generic uses. New ideas are needed to efficiently train in a "dark forest". Aiming to hide the IDs, we initiate the study of anonymous GBDT training on split data held by two parties. Dual circuit-PSI in our design lets the parties alternate as receiver to run pick-then-sum over local features. Via oblivious programmable pseudorandom functions, we propagate circuit-PSI outputs as shared state across runs. Avoiding universal alignment, we resolve the neglected dilemma that ID hiding incurs a cost that scales with domain size. Next, we halve the cost of ciphertext packing used to convert single-instruction multiple-data homomorphic encryption from (ring) learning with errors in prior secure GBDT (Usenix Security' 23) and related secure machine-learning computations. Comparative experiments show our protocol remains competitive with leaky approaches in efficiency. Enabling ID-hiding aggregation, our techniques can extend to other vertically partitioned analytics.

11.
arXiv (CS.CV) 2026-06-16

PPDM: Pixel Puzzling Diffusion Model for Speed and Memory Efficient Volumetric Medical Image Translation

Diffusion models have demonstrated superior fidelity for medical image-to-image translation, but their extension to high-resolution 3D volumes is severely constrained by prohibitive computational cost and GPU memory requirements. Existing memory-efficient strategies often compromise global volumetric consistency or fine anatomical detail. In this work, we propose the Pixel Puzzling Diffusion Model (PPDM), a simple and effective framework for memory- and speed-efficient 3D medical image translation. PPDM introduces a reversible pixel puzzle-unpuzzle operator that trades spatial resolution for channel dimensionality, substantially reducing activation memory while preserving global context. To further improve efficiency and stability, we adopt a direct bridge diffusion formulation that starts from the conditional input rather than pure noise, enabling the model to focus on task-relevant residuals. In addition, a puzzle-gradient loss is incorporated to enforce spatial coherence and suppress grid-like artifacts introduced by spatial rearrangement. We evaluate PPDM on multiple challenging 3D medical image translation tasks, including low-count PET denoising, joint PET denoising and attenuation correction, and cross-modal MRI translation. Across all tasks, PPDM consistently matches or outperforms full 3D diffusion models while reducing training GPU memory usage by up to an order of magnitude and significantly accelerating inference, and it outperforms existing memory-efficient diffusion approaches based on latent compression or frequency decomposition. These results demonstrate that PPDM provides a practical and scalable solution for high-fidelity 3D diffusion-based medical image translation under limited computational resources.

12.
arXiv (CS.AI) 2026-06-16

Edu-Theater: A Data-Efficient Agent Framework for Scalable Learner Behavior Simulation through Staging Roll-Call

arXiv:2606.15225v1 Announce Type: cross Abstract: Large-scale learner-task interaction data are crucial for intelligent educational systems but are costly to collect and constrained by privacy and learner engagement. Learner simulators play a critical role in simulating scalable learner behavior without the need for continuous involvement of real learners. However, existing methods are predominantly individual-centric, pairing a simulator with each learner to iteratively infer latent knowledge states from dense interaction histories, which is both data- and computation-intensive, and fragile in cold-start scenarios. We propose a cohort-aware roll-call simulation paradigm that first constructs cohort-level proficiency priors and refines individual learner states through a small number of targeted diagnostic queries. Based on this paradigm, we introduce Edu-Theater, an LLM-powered agent system that performs cohort-aware learner simulation via a teacher agent and retrospective roll-call probing over learner logs. Edu-Theater enables scalable future behavior simulation without the need for dense per-learner histories. Experiments on two real-world datasets demonstrate that Edu-Theater achieves higher simulation accuracy with significantly fewer LLM calls, producing synthetic data that enhances downstream applications such as adaptive testing.

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

On the Geometry of On-Policy Distillation

arXiv:2606.07082v2 Announce Type: replace-cross Abstract: On-policy distillation (OPD) is increasingly used to improve large language model reasoning, but its training dynamics remain poorly understood. We characterize the trajectory of OPD updates in parameter space and compare it with supervised fine-tuning (SFT) and reinforcement learning with verifiable rewards (RLVR). A suite of parameter-space diagnostics consistently places OPD in a relaxed off-principal regime: compared with SFT, its updates affect fewer weights and avoid principal directions more strongly, while compared with RLVR, they remain less tightly constrained. Beyond this static localization, OPD exhibits subspace locking: its cumulative updates rapidly enter a narrow low-dimensional channel. Constraining training to the update subspace formed early in training preserves OPD performance but substantially degrades SFT, indicating that the locked subspace is functionally sufficient for OPD. Control experiments further show that sparsifying the update tokens and shifting rollout generation off-policy preserve the rank dynamics, whereas mixing the OPD objective with RLVR changes them. Overall, these results suggest that OPD is not merely an intermediate point between SFT and RLVR, but induces its own update geometry in parameter space.

14.
arXiv (CS.CV) 2026-06-19

InfantFace: Detecting infant faces in neonatal clinical environments

Reliable localisation of the neonatal face is the first step for several video-camera based non-contact assessments such as pain and distress related facial expression analysis, pain scoring, cardiorespiratory signal extraction and cessation of breathing alerts. However, major challenges persist in neonatal clinical environments. Cluttered backgrounds, illumination changes and poor lighting conditions can reduce the accuracy of face detection models. Clinical interventions, monitoring equipment and, in some cases, medical devices can obstruct the face, making visual assessment difficult. We propose a one-stage YOLOv11m-based model tailored for face detection of infants in neonatal clinical environments. We combined multiple publicly available datasets (VGGFace2, CelebA, FDDB, WIDER FACE) to train and evaluate our proposed model. We then fine-tuned our model on a neonatal research dataset involving 228 videos from 114 recording sessions of 113 independent infants. Before fine-tuning, our model achieved an AP50 of 0.87, surpassing the performance of three state-of-the-art general face detectors. Performance improved further to an AP50 of 0.96 after clinical-domain adaptation. Evaluating face detection performance across different datasets remains a challenge due to the lack of publicly available neonatal datasets. Prioritising the creation of such datasets, while upholding appropriate privacy safeguards and ethical standards in their creation and use, would greatly support further progress in this field.

15.
arXiv (CS.CV) 2026-06-19

ReA-OVCD: Reliability-Aware Open-Vocabulary Change Detection via Semantic and Spatial Refinement

Unlike traditional remote sensing change detection that relies on predefined categories, Open-Vocabulary Change Detection (OVCD) identifies land cover changes flexibly using arbitrary text prompts. However, existing methods suffer from an inherent trade-off when modeling changes: instance-level comparison overlooks fine-grained semantic variations (e.g., partial building extensions), while direct pixel comparison proves unreliable, yielding unstable responses and boundary artifacts due to semantic ambiguity and spatial inconsistency. To this end, we propose an efficient training-free Reliability-Aware Open-Vocabulary Change Detection (ReA-OVCD) framework. It first derives candidate change regions from pixel-wise semantic discrepancies to ensure flexible and detailed localization. To ensure reliability, it subsequently introduces a collaborative refinement strategy to explicitly model change validity from both semantic and spatial perspectives. Specifically, we develop a Semantic Change Reasoning (SCR) module that reassesses changes by jointly analyzing distributional divergence and response variation, enabling the suppression of incidental inconsistencies while preserving reliable semantic shifts. In addition, a Boundary-aware Change Refinement (BCR) module is designed to mitigate artifacts stemming from boundary misalignment and uncertainty through validating whether candidate regions are supported by reliable interior pixels. Extensive experiments across multiple datasets (LEVIR-CD, WHU-CD, DSIFN, and SECOND) demonstrate that our method consistently outperforms state-of-the-art approaches, achieving $\mathrm{F}_{1}^{C}$ improvements of 2.13\% to 9.75\% with higher computational efficiency. The code is publicly available at \https://github.com/Funny0101/ReA-OVCD

16.
arXiv (CS.AI) 2026-06-19

MEAL: A Benchmark for Continual Multi-Agent Reinforcement Learning

arXiv:2506.14990v3 Announce Type: replace Abstract: Benchmarks play a central role in reinforcement learning (RL) research, yet their computational constraints often shape what is studied. Despite the motivation of lifelong learning, most continual RL papers consider only 3-10 sequential tasks, as CPU-bound environments make longer sequences impractical. Meanwhile, continual learning in cooperative multi-agent settings remains largely unexplored. To address these gaps, we introduce MEAL (Multi-agent Environments for Adaptive Learning), the first benchmark for continual multi-agent RL. By leveraging JAX and GPU acceleration, MEAL enables training on sequences of 100 tasks in a few hours on a single GPU. We find that long task sequences reveal failure modes that do not appear at smaller scales.

17.
arXiv (CS.CL) 2026-06-16

S1-DeepResearch: Beyond Search, Toward Real-World Long-Horizon Research Agents

Deep research agents aim to solve complex knowledge-intensive tasks through long-horizon planning, evidence gathering, reasoning, and report generation. While recent progress in search agents has demonstrated strong capabilities in information retrieval and answer verification, most existing training datasets remain search-centric, focusing primarily on closed-ended question answering and information localization. As a result, they mainly train information-seeking behavior while providing limited coverage of key deep research capabilities, including evidence integration, knowledge synthesis, planning, file understanding, and structured report generation. In this work, we propose a unified trajectory construction paradigm for deep research agents that combines closed-ended QA and open-ended exploration. The proposed framework consists of graph-grounded task formulation, agentic trajectory rollout, and multi-dimensional trajectory verification, enabling scalable synthesis of high-quality agentic trajectories spanning long-chain complex reasoning, deep research instruction following, report writing, file understanding and generation, and skills usage. Compared with existing search-oriented datasets, our synthesized trajectories place greater emphasis on knowledge synthesis, complex reasoning, and planning. S1-DeepResearch-32B achieves state-of-the-art performance among open-source models of comparable scale across 20 benchmarks spanning five capability dimensions, including complex reasoning, instruction following, report generation, file understanding, and skills usage. On several challenging deep research benchmarks, it approaches the performance of leading proprietary frontier models. These results highlight the importance of jointly modeling information acquisition, knowledge synthesis, and planning-oriented agent behaviors for building effective deep research agents.

18.
arXiv (CS.CV) 2026-06-16

FireRed-Image-Edit-1.0 Technical Report

We present FireRed-Image-Edit, a diffusion transformer for instruction-based image editing that achieves state-of-the-art performance through systematic optimization of data curation, training methodology, and evaluation design. We construct a 1.6B-sample training corpus, comprising 900M text-to-image and 700M image editing pairs from diverse sources. After rigorous cleaning, stratification, auto-labeling, and two-stage filtering, we retain over 100M high-quality samples balanced between generation and editing, ensuring strong semantic coverage and instruction alignment. Our multi-stage training pipeline progressively builds editing capability via pre-training, supervised fine-tuning, and reinforcement learning. To improve data efficiency, we introduce a Multi-Condition Aware Bucket Sampler for variable-resolution batching and Stochastic Instruction Alignment with dynamic prompt re-indexing. To stabilize optimization and enhance controllability, we propose Asymmetric Gradient Optimization for DPO, DiffusionNFT with layout-aware OCR rewards for text editing, and a differentiable Consistency Loss for identity preservation. We further establish REDEdit-Bench, a comprehensive benchmark spanning 15 editing categories, including newly introduced beautification and low-level enhancement tasks. Extensive experiments on REDEdit-Bench and public benchmarks (ImgEdit and GEdit) demonstrate competitive or superior performance against both open-source and proprietary systems. To support future research, our code, models, and benchmark suite are publicly available at https://github.com/FireRedTeam/FireRed-Image-Edit/ .

19.
medRxiv (Medicine) 2026-06-10

Trajectories of brain structure and function in young adult carriers of genetic frontotemporal dementia variants

Background and Objectives: Converging evidence hints at neurodevelopmental effects in genetic frontotemporal degeneration (FTD). In cross-sectional studies, for some genes, young adult FTD variant carriers show differences in brain volumes and cognition compared to familial non-carriers. However, longitudinal trajectories may more sensitively capture FTD-related neurodevelopmental vs. neurodegenerative changes than cross-sectional approaches. This study examined longitudinal trajectories of brain volumes, executive function, and plasma biomarkers in young adult carriers compared to familial non-carriers, as measures of neurodevelopmental and neurodegenerative outcomes of FTD-causing variants. Methods: This longitudinal cohort study comprised participants, aged 18-30 years, from the FTD Prevention Initiative across Europe, Canada, and the USA. Genetic groups included C9orf72 (47%), MAPT (30%), and GRN (23%). Linear mixed-effects models were computed to assess longitudinal outcomes across age between groups, controlling for sex, scanner (for brain volumes), and education (for executive function); random effects accounted for between-subject variability nested within family membership. Results: Variant carriers (n=147) and familial non-carriers (n=113) did not differ in age (mean{+/-}SD, 25.9{+/-}3.2 years), sex (53% female), or number of visits (2.1{+/-}1.7). Young adult C9orf72 repeat expansion carriers exhibited smaller thalamic volumes than non-carriers at the reference age of 26 years (b=-982.8mm3, SE=317.0, p=0.0046, f2=0.32), with relatively stable trajectories across ages 18-30 (i.e., no change over time). Trajectories of rostral anterior cingulate volumes differed in C9orf72 carriers and non-carriers across age, where carriers showed relatively stable trajectories and non-carriers showed age-appropriate declines (b=64.4mm3, SE=29.9, p=0.035, f2=0.07). For MAPT and GRN, there were little to no differences in total brain, cortical, or subcortical volumes between groups and over time. No longitudinal differences were observed between carriers and non-carriers in executive function, or plasma NfL or GFAP for any genetic group. Discussion: C9orf72 repeat expansions were linked to smaller average thalamic volumes and stable trajectories between ages 18 to 30, supporting potential neurodevelopmental origins. The modest evidence supporting an absence of difference in neurodegenerative biomarkers and executive function suggests minimal early neurodegeneration and functional preservation in young adulthood.

20.
medRxiv (Medicine) 2026-06-11

Plasma protein prioritisation in rheumatoid arthritis reveals druggable targets and shared biology with cardiovascular diseases

Abstract Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex and incompletely understood molecular mechanisms. Understanding circulating proteins associated with RA may improve understanding of disease biology and clarify its pathological links with cardiometabolic comorbidities. Methods A proteome-wide two-sample Mendelian randomisation (MR) drug target analysis was conducted using plasma proteins measured in 54,219 participants from the UK Biobank Pharma Proteomics Project as exposures and RA and cardiometabolic diseases as the outcomes. Summary statistics for RA included 53,663 cases and 1,070,200 controls. Colocalisation analysis was performed to confirm shared single causal variants and prioritise RA proteins supported by both MR and colocalisation. The prioritised proteins were then evaluated in the Accelerating Medicines Partnership RA Phase II synovial single-cell dataset for cell-type expression patterns. Druggability was then assessed followed by analysis of genetic overlap between RA-associated proteins and cardiometabolic diseases. Results 37 plasma proteins had a causal effect on RA risk, supported by combined evidence from MR and conditional colocalisation. In synovial tissue, TPPP3, RARRES2, AKAP12, and GGT5 were predominantly expressed in stromal and endothelial cell clusters. Druggability assessment identified IFNGR2, IL6R, CD40, and FCGR2B as Tier 1 targets. However, several biologically relevant proteins, including RARRES2, AKAP12, TPPP3, and SNX2, had limited available druggability data. Genetic overlap analysis demonstrated shared protein signals between RA and cardiovascular diseases, including overlap of RARRES2 and TPPP3 with coronary artery disease (CAD) and FCGR2B with atrial fibrillation (AF). To approximate the therapeutic effect of target inhibition, the direction of effect estimates for proteins showing overlap between RA-CAD and RA-AF was reversed. Conclusion This study identified circulating proteins involved in RA pathogenesis and reveals shared mechanisms between RA and cardiovascular diseases. While some proteins showed clear translational potential targets, several prioritised proteins had limited available druggability information and could not be confidently classified. Addressing these gaps may help identify new targets relevant to RA management. Future work should also use phenome-wide MR studies to evaluate potential on-target adverse effects of protein inhibition across RA-CAD and RA-AF.

21.
arXiv (CS.CL) 2026-06-18

Are LLMs Ready to Assist Physicians? PhysAssistBench for Interactive Doctor-Patient-EHR Assistance

The most plausible near-term role of medical LLMs is to assist rather than replace physicians, yet current evaluations often test isolated capabilities: clinical knowledge, EHR system interaction, or patient communication. Physician assistance instead requires coordinating these capabilities within the same interaction, where physicians issue underspecified requests, patients describe symptoms ambiguously, and EHR systems demand precise tool use. We introduce PhysAssistBench, a benchmark for interactive doctor-patient-EHR assistance. Built from real MIMIC-IV cases, PhysAssistBench uses a scalable pipeline to construct agentic patients: interactive, record-grounded agents that turn static EHR records into multi-turn clinical scenarios while preserving clinical factuality. PhysAssistBench provides a curated bilingual evaluation set of 1,296 manually reviewed and physician-validated turns. Experiments with leading LLMs show that current models remain unreliable in this setting, which exposes a key bottleneck for clinical LLMs: reliable assistance requires coordination across knowledge, communication, and systems, not isolated gains in any of them.

22.
arXiv (quant-ph) 2026-06-19

Applications of quantum annealing to magnetic dipole hyperfine structure constants: First results beyond energies for atoms

arXiv:2606.20166v1 Announce Type: new Abstract: We report the first results of the magnetic dipole hyperfine structure (HFS) constants of neutral $\mathrm{Li}$, Li-like $\mathrm{Be}$, neutral $\mathrm{Na}$, and Na-like $\mathrm{Mg}$ using a modified version of the Quantum Annealer Eigensolver (QAE) algorithm on D-Wave's quantum hardware. The results are benchmarked against relativistic configuration interaction with multiconfiguration Dirac Hartree-Fock (MCDHF) calculations using the General-purpose Relativistic Atomic Structure Package (GRASP), and simulated annealing. In our modified QAE, a zooming-and-sigma-annealing approach with a floating-point encoding scheme is adopted to estimate the ground-state eigenvalue and eigenvector of the relativistic Dirac-Coulomb Hamiltonian matrices ($H_{\mathrm{DC}}$) constructed from 11 or fewer configuration state functions (CSFs). For calculations with extended correlation orbital sets, we applied a CSF truncation scheme, retaining only CSFs (up to 12) that make significant contributions to the ground-state wavefunction. Our modified QAE precision is kept limited to three decimal places (up to 10 qubits). Hardware demonstrations on the D-Wave quantum processing unit (QPU) yielded results that were completely consistent with GRASP (at the chosen precision) in determining the magnetic dipole HFS constants, with accuracy varying across systems and $H_{\mathrm{DC}}$ matrix dimensions.

23.
arXiv (CS.AI) 2026-06-12

Benchmarking AI Agents for Addressing Scientific Challenges Across Scales

arXiv:2606.12736v1 Announce Type: new Abstract: AI agents are increasingly being developed to accelerate scientific discovery, yet their practical capabilities in real research settings remain poorly understood. Existing benchmarks for AI agents rarely capture the complexity, heterogeneity, and extended reasoning required by scientific work, whereas benchmarks for scientific tasks often reduce research to static, direct problems and provide limited support for interactive evaluation. Here, we introduce SciAgentArena, a systematic benchmark for evaluating AI agents in real-world scientific research scenarios drawn from emerging needs across multiple domains. SciAgentArena comprises approximately 200 tasks with stepwise verification and an interactive, agent-agnostic environment for assessing diverse AI agents. Using this benchmark, we find that current agents can contribute effectively to well-specified data-analysis workflows, particularly when the task structure and evaluation criteria are clear. However, their performance remains uneven across scientific contexts: agents struggle to generate genuinely novel insights, sustain self-directed exploration, and formulate robust solutions for open-ended research questions. We further characterize common failure modes across agents and identify opportunities for improving their reliability, autonomy, and scientific reasoning. Together, SciAgentArena provides a practical framework for measuring progress in AI agents for science and for guiding the design of future agents capable of addressing complex scientific challenges. Full codes, tasks, and datasets can be accessed via this link: https://sciagentarena.github.io/.

24.
arXiv (CS.LG) 2026-06-11

Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement

arXiv:2606.08493v2 Announce Type: replace-cross Abstract: Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

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medRxiv (Medicine) 2026-06-15

Recruitment, Retention Approaches and Community Engagement in the THRIVE pilot Trial: Lessons Learned from a Food is Medicine Trial

Background: Recruitment of underrepresented populations, including Black and Hispanic populations, for Food is Medicine (FIM) and cardiovascular trials, may pose significant challenges. Methods: We implemented a multi-component recruitment approach for the THRIVE (AdapTive personalized dietitian coacHing and messaging with pRoduce prescrIptions to improVE healthy dietary behaviors) pilot trial to engage primarily Black and Hispanic adults in a Food is Medicine for hypertension intervention. The recruitment approaches included community engagement at approximately 40 community events (cultural festivals and neighborhood gatherings); partnerships with 8 community and faith-based service hubs and food distribution sites; recruitment through safety net primary care clinics, digital outreach via the study website, and social media campaigns; and direct recruitment at places of worship. We report lessons learned from the community engagement process, recruitment efficiency, representativeness, and retention outcomes. Results: Within 6 months, the enrollment target was exceeded by 40%, with an accrual index of 1.04. Over 1,000 individuals were reached through the direct-to-community engagement process, while faith-based partnerships engaged about 900 adults. There were 2,673 visits to the study webpage, and social media achieved 12,259 impressions with 399 clicks. About 95% of participants resided within 10 miles of the faith-based recruitment sites. Face-to-face engagement at the food distribution sites within faith-based organizations or community service hubs outperformed digital methods. Faith leader endorsements and follow-up in-person meetings (following unsuccessful email outreach) dramatically increased recruitment. Regarding retention, pre-randomization attrition was 6%, and 82% of participants completed the study. Conclusion: Culturally tailored, community-engaged recruitment grounded in faith-based and local community partnerships, was highly effective in engaging Black and Hispanic populations in this FIM cardiovascular trial. This provides a replicable model for implementing equitable and sustainable cardiovascular health interventions.