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01.
arXiv (CS.AI) 2026-06-17

Position: Modular Memory is the Key to Continual Learning Agents

arXiv:2603.01761v2 Announce Type: replace-cross Abstract: Foundation models have transformed machine learning through large-scale pretraining and increased test-time compute. Despite surpassing human performance in several domains, these models remain fundamentally limited in continuous operation, experience accumulation, and personalization, capabilities that are central to adaptive intelligence. While continual learning research has long targeted these goals, its historical focus on in-weight learning (IWL), i.e., updating a single model's parameters to absorb new knowledge, has rendered catastrophic forgetting a persistent challenge. Our position is that combining the strengths of In-Weight Learning (IWL) and the newly emerged capabilities of In-Context Learning (ICL) through the design of modular memory is the missing piece for continual adaptation at scale. We outline a conceptual framework for modular memory-centric architectures that leverage ICL for rapid adaptation and knowledge accumulation, and IWL for stable updates to model capabilities, charting a practical roadmap toward continually learning agents.

02.
bioRxiv (Bioinfo) 2026-06-11

HalluDesign-NA: Extending HalluDesign for De Novo Nucleic Acid Design

AlphaFold3 has revolutionized the prediction of biomolecular structures and interactions, including atomic-level modeling of nucleic acids. However, the de novo design of structured and functional nucleic acids remains a significant challenge. Here, we extend our HalluDesign framework to nucleic acid design by integrating NA-MPNN for nucleic acid sequence optimization and design. This new framework, HalluDesign-NA, enables iterative sequence-structure co-optimization, facilitating the de novo design of nucleic acids. Computational benchmarking across ssDNA, ssRNA, and aptamer design tasks demonstrates consistent improvements in confidence scores (pLDDT, ipTM), supporting the feasibility of de novo nucleic acid design under various constraints, such as sequence length, symmetry, and protein structure context. We anticipate that HalluDesign-NA will accelerate the de novo design of functional nucleic acids for applications in biotechnology and medicine. The source code for HalluDesign-NA is available at https://github.com/MinchaoFang/HalluDesign_NA.

03.
arXiv (CS.AI) 2026-06-17

Quantifying Consistency in LLM Logical Reasoning via Structural Uncertainty

arXiv:2606.17312v1 Announce Type: new Abstract: Large language models can arrive at the same answer through reasoning paths that are unstable, contradictory, or difficult to rank consistently – a failure mode especially prevalent in multi-step deductive reasoning. Existing methods assess reliability primarily through output dispersion – measuring how much sampled answers differ – but this discards a complementary signal: whether the model can consistently rank competing reasoning candidates. We propose structural uncertainty, a consistency-aware framework derived from the stability of self-preference-induced rankings over sampled reasoning solutions. Given a query, we generate multiple candidate solutions and ask the model to judge pairwise preferences among its own outputs. We aggregate self-preferences into ranking distributions via Bradley-Terry modeling with PageRank, and decompose the signal into two entropy-based components: across-trial ranking instability and within-trial candidate ambiguity. Across five LLMs and eight benchmarks, structural signals provide information complementary to answer dispersion: on logical and mathematical reasoning tasks, the combination improves identification of unreliable instances, while on factual retrieval the structural signal collapses toward uniformity, diagnosing a regime boundary where reasoning-level consistency evaluation is uninformative. The two components relate differently to accuracy: within-trial ambiguity correlates positively with correctness – consistent with settings where multiple plausible solution paths remain competitive – while across-trial instability correlates negatively, signaling unreliable reasoning. Structural uncertainty is best understood not as a universal confidence estimator, but as a regime-sensitive evaluator of logical reasoning consistency.

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

Like a Hammer, It Can Build, It Can Break: Large Language Model Uses, Perceptions, and Adoption in Cybersecurity Operations on Reddit

arXiv:2604.09998v2 Announce Type: replace-cross Abstract: Large language models (LLMs) have recently emerged as promising tools for augmenting Security Operations Center (SOC) workflows, with vendors increasingly marketing autonomous AI solutions for SOCs. However, there remains a limited empirical understanding of how such tools are used, perceived, and adopted by real-world security practitioners. To address this gap, we conduct a mixed-methods analysis of discussions in cybersecurity-focused forums to learn how a diverse group of practitioners use and perceive modern LLM tools for security operations. More specifically, we analyzed 892 posts between December 2022 and September 2025 from three cybersecurity-focused forums on Reddit, and, using a combination of qualitative coding and statistical analysis, examined how security practitioners discuss LLM tools across three dimensions: (1) their stated tools and use cases, (2) the perceived pros and cons of each tool across a set of critical factors, and (3) their adoption of such tools and the expected impacts on the cybersecurity industry and individual analysts. Overall, our findings reveal nuanced patterns in LLM tools adoption, highlighting independent use of LLMs for low-risk, productivity-oriented tasks, alongside active interest around enterprise-grade, security-focused LLM platforms. Although practitioners report meaningful gains in efficiency and effectiveness in LLM-assisted workflows, persistent issues with reliability, verification overheads, and security risks sharply constrain the autonomy granted to LLM tools. Based on these results, we also provide recommendations for developing and adopting LLM tools to ensure the security of organizations and the safety of cybersecurity practitioners.

06.
bioRxiv (Bioinfo) 2026-06-14

Structural Analysis of Prostate Cancer N-Glycans Using Graph-Based Structural Metrics

The N-linked glycans are structurally complex carbohydrate modifications that regulate protein folding, immune recognition, and cellular signaling, and their expression is extensively remodeled during cancer progression, making them promising biomarkers. In this study, prostate cancer-associated N-glycans from a range of relevant peer-reviewed studies were curated and digitized to develop a versatile computational framework that quantitatively encodes their spatial complexity across diverse biological systems. We invented two indices – the Distance & Connectivity Index (DCI) and the Position & Composition Index (PCI) – to capture the spatial information in N-glycans as layered architectures, enabling calculation of residue-level path lengths, branching structure, and compositional diversity. DCI summarizes glycan structure as both a scalar and matrix representation, while PCI does the same but also captures monosaccharide diversity, linkage heterogeneity, and cross-layer branching features. These metrics were computed with GlycoAssessor, an open-source platform that extracts information for the DCI and PCI from glycans drawn via Symbol Nomenclature for Glycans (SNFG) notation. Principal Component Analysis (PCA) was applied to evaluate whether glycans from prostate cancer tissues cluster distinctly in a disease-relevant manner. Results show that the spatial information in N-glycans: (1) increased in a multi-dimensional, non-linear manner, (2) objectively segregated structural themes, (3) could function as a potential prostate cancer biomarker that is distinct from mass-to-charge ratio and relative abundance, and (4) could objectively quantify novel subtype classifications of glycans associated with disease states and progression.

07.
arXiv (CS.CL) 2026-06-12

BLUEmed: Retrieval-Augmented Multi-Agent Debate for Clinical Error Detection

Terminology substitution errors in clinical notes, where one medical term is replaced by a linguistically valid but clinically different term, pose a persistent challenge for automated error detection in healthcare. We introduce BLUEmed, a multi-agent debate framework augmented with hybrid Retrieval-Augmented Generation (RAG) that combines evidence-grounded reasoning with multi-perspective verification for clinical error detection. BLUEmed decomposes each clinical note into focused sub-queries, retrieves source-partitioned evidence through dense, sparse, and online retrieval, and assigns two domain expert agents distinct knowledge bases to produce independent analyses; when the experts disagree, a structured counter-argumentation round and cross-source adjudication resolve the conflict, followed by a cascading safety layer that filters common false-positive patterns. We evaluate BLUEmed on a clinical terminology substitution detection benchmark under both zero-shot and few-shot prompting with multiple backbone models spanning proprietary and open-source families. Experimental results show that BLUEmed achieves the best accuracy (69.13%), ROC-AUC (74.45%), and PR-AUC (72.44%) under few-shot prompting, outperforming both single-agent RAG and debate-only baselines. Further analyses across six backbone models and two prompting strategies confirm that retrieval augmentation and structured debate are complementary, and that the framework benefits most from models with sufficient instruction-following and clinical language understanding.

08.
arXiv (CS.CV) 2026-06-17

Beyond MACs: Hardware Efficient Architecture Design for Vision Backbones

Vision backbone networks play a central role in modern computer vision. Enhancing their efficiency directly benefits a wide range of downstream applications. To measure efficiency, many publications rely on MACs (Multiply Accumulate operations) as a predictor of execution time. In this paper, we experimentally demonstrate the shortcomings of such a metric, especially in the context of edge devices. By contrasting the MAC count and execution time of common architectural design elements, we identify key factors for efficient execution and provide insights to optimize backbone design. Based on these insights, we present LowFormer, a novel vision backbone family. LowFormer features a streamlined macro and micro design that includes Lowtention, a lightweight alternative to Multi-Head Self-Attention. Lowtention not only proves more efficient, but also enables superior results on ImageNet. Additionally, we present an edge GPU version of LowFormer, that can further improve upon its baseline's speed on edge GPU and desktop GPU. We demonstrate LowFormer's wide applicability by evaluating it on smaller image classification datasets, as well as adapting it to several downstream tasks, such as object detection, semantic segmentation, image retrieval, and visual object tracking. LowFormer models consistently achieve remarkable speed-ups across various hardware platforms compared to recent state-of-the-art backbones. Code and models are available at https://github.com/altair199797/LowFormer/blob/main/Beyond_MACs.md.

09.
arXiv (CS.LG) 2026-06-16

Acoustic Prompting via Stage-wise Modulation for Few-Shot Learning in Audio Language Models

arXiv:2606.15751v1 Announce Type: cross Abstract: Audio-Language Models (ALMs) have shown remarkable success in zero-shot audio classification by aligning audio waveforms with text. Recent efforts to improve downstream performance focus on learning optimal text prompts. However, previous approaches focus on the text encoder, leaving the potential of learnable prompts within the audio encoder unexplored. In this paper, we propose a novel framework that introduces trainable prompts into the audio encoder to capture task-specific acoustic features. We demonstrate that integrating audio-side prompt learning with existing text-side approaches enhances few-shot adaptation. Through extensive experiments across 11 datasets show that integrating our method as a plug-and-play module alongside existing text prompt tuning generally leads to performance improvements. These findings suggest that explicitly modulating the audio representation space effectively complements text-only prompting approaches. The code is available at https://github.com/hyebin-c/aspl.

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

UtVAA: Ultra-tiny Vision Transformer with Affix Attention for Mobile Image Classification

Vision Transformers (ViTs) have demonstrated strong representation capability in image classification. However, their quadratic self-attention complexity and large parameter counts limit deployment on resource-constrained mobile and edge devices. This paper introduces UtVAA, an ultra-tiny Vision Transformer architecture designed for efficient visual recognition under strict computational budgets. It incorporates a novel Affix Attention block that combines depthwise-pointwise local feature extraction, linear self-attention, coordinate attention for spatial dependency modelling, and a lightweight ternary fusion strategy to integrate local and global representations. In addition, Dilated Bottleneck blocks expand the receptive field using dilated depthwise separable convolutions while maintaining low FLOPs and stable optimisation through residual connections. UtVAA is implemented in scalable Tiny, Medium, and Large variants, with the smallest model containing 204.67K parameters and 53.95M FLOPs. Experimental results on CIFAR-10, CIFAR-100, PlantVillage-Tomato and SLIF-Tomato datasets show that UtVAA achieves competitive accuracy within a sub-million-parameter regime. Overall, the results demonstrate that transformer-based vision models can be redesigned into ultra-tiny architectures without significant loss in discriminative performance, making UtVAA suitable for mobile and edge deployment. Code is available at https://github.com/romiyal/UtVAA

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

MolGraphBench: A Benchmark of GNN Architectures for Molecular Regression Tasks

arXiv:2602.20573v3 Announce Type: replace Abstract: Molecules are often represented as SMILES strings, which can be readily converted to hand-crafted descriptors or fingerprints (FP) for molecular property prediction. Research has demonstrated that SMILES can be converted to molecular graphs $G = (V, E)$, with atoms as nodes $(V)$ and bonds as edges $(E)$. These molecular graphs can subsequently be used to train graph neural networks (GNN) models. Despite the recent surge in application of GNN (existing and novel architectures) for molecular property prediction, a rigorous benchmark is still lacking. We propose MolGraphBench, a comprehensive benchmark of four commonly used GNN models for molecular property prediction. Benchmarking results demonstrate graph convolutional network (GCN) and graph isomorphism networks (GIN) as the optimal GNN architectures for molecular graph regression tasks, based on absolute performance, training efficiency, transfer learning and prediction quality. The study also indicates the non-complementary nature of molecular fingerprints in the fusion (GNN-FP) framework. Furthermore, our GNN models achieved performance superior or comparable performance to current state-of-the-art GNN baselines across three datasets (GCN with RMSE of $0.518$ on B3DB, GIN-FP with RMSE of $1.022$ on FreeSolv and GIN with MAE of $63.783$ on RT datasets). Findings from this study indicate that type of GNN-layer, should be treated as a tunable hyperparameter rather than a fixed design choice to achieve superior performance.

13.
arXiv (CS.CV) 2026-06-18

When Cars Have Stereotypes: Auditing Demographic Bias in Objects from Text-to-Image Models

While prior research on text-to-image generation has predominantly focused on biases in human depictions, demographic bias in generated objects remains relatively underexplored. We introduce SODA (Stereotyped Object Diagnostic Audit), a novel framework for systematically measuring these biases through automated attribute discovery and three standardized metrics: Base vs. Demographic Divergence (BDS), Cross-Demographic Disparity (CDS), and Visual Attribute Concentration (VAC). Applying SODA to 8,000 images across five state-of-the-art models and eight object categories (e.g., cars), we find that "neutral" prompts produce outputs most visually similar to middle-aged and White people, suggesting these groups are implicitly over-represented in model defaults. Furthermore, demographic cues trigger highly skewed stereotypical outputs: 26.6% of object-model-demographic combinations produce results where all 20 generated images share the exact same attribute value (e.g., rose gold laptops for women). Finally, prompt-level debiasing reduces inter-group disparity but paradoxically collapses within-group diversity, replacing one stereotype with another. SODA offers a practical pipeline for making these implicit associations measurable, serving as a step toward more responsible AI development.

14.
arXiv (CS.CV) 2026-06-17

Attention Sinks in Diffusion Transformers: A Causal Analysis

Attention sinks – tokens that receive disproportionate attention mass – are assumed to be functionally important in autoregressive language models, but their role in diffusion transformers remains unclear. We present a causal analysis in text-to-image diffusion, dynamically identifying dominant attention recipients per timestep and suppressing them via paired, training-free interventions on the score and value paths. Across 553 GenEval prompts on Stable Diffusion~3 (with SDXL corroboration), removing these sinks does not degrade text-image alignment (CLIP-T) or preference proxies (ImageReward, HPS-v2) at $k{=}1$; only under stronger interventions ($k\!\geq\!10$) does HPS-v2 exhibit a metric-dependent boundary, while CLIP-T remains robust throughout. The perceptual shifts induced by suppression are nonetheless sink-specific – $\sim\!6\times$ larger than equal-budget random masking – revealing an empirical dissociation between trajectory-level perturbation and semantic alignment in diffusion transformers. \footnote{Code available at https://github.com/wfz666/ICML26-attention-sink.}

15.
arXiv (CS.LG) 2026-06-11

Anatomy of Post-Training: Using Interpretability to Characterize Data and Shape the Learning Signal

arXiv:2606.12360v1 Announce Type: new Abstract: Language-model post-training is the main stage at which model behavior is shaped, yet it still largely involves optimization of scalar rewards that summarize diverse desiderata. This abstraction gives practitioners little visibility into what their data actually teaches models, allowing spurious correlations to be learned by a model and inducing undesirable behaviors such as over-stylization and sycophancy. To address this problem, we ask: can we inspect a preference dataset before optimization and decide, at the level of concepts, which behaviors a model should be allowed to learn? Motivated by this, we introduce a data-centric post-training pipeline that uses interpretability protocols to develop statistical hypotheses for the latent concepts separating preferred from dispreferred generations, making them explicit for fine-grained user feedback. Building on this view, we unify several interpretability-based training protocols as ways of shaping rewards via feature or data interventions. Empirically, we show that our pipeline diagnoses undesirable signals in existing preference data, mitigates off-target learning, and can also help amplify or shape desired properties such as safeguards and model personality. More broadly, our results suggest that interpretability can turn post-training from optimizing opaque proxy rewards into a process of auditing and sculpting the learning signal itself.

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

Humor Style Drives Laughter, Topic Shapes Acceptability: Evaluating Bilingual Personal and Political Robot-Delivered AI Jokes

arXiv:2606.13256v1 Announce Type: cross Abstract: Humor plays a central role in human social relationships, and recent advances in computational humor create new opportunities for integrating humor into human-robot interaction (HRI). While large language models (LLMs) can generate diverse forms of humor, it remains unclear how humor style, joke content, and language preference shape perceptions of robot-delivered humor in group settings. In this exploratory study, we employed a mixed factorial design in which participants evaluated AI-generated jokes delivered by a robot in a university classroom. We examined the effects of humor type (Affiliative, Self-Enhancing, Aggressive, Self-Defeating) and joke content (person-related vs. political) on perceived funniness and appropriateness, as well as preferred language. Results show that humor type significantly influences funniness, with Aggressive and Affiliative humor rated higher, while joke content primarily affects appropriateness, with person-related jokes preferred over political ones. Language preference was shaped by both joke content and participants' self-reported fluency and humor practices.

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

Adversarial Attacks Leverage Interference Between Features in Superposition

Why do adversarial examples exist, and why do they transfer between models? Existing explanations appeal to high-dimensional geometry, non-robust patterns in the input, and decision boundary structure, but none provides a representation-level mechanism that explains why specific perturbations succeed and why attacks transfer between models. In this paper, we show that adversarial vulnerability can stem from efficient information encoding in neural networks. Specifically, vulnerability can arise from superposition - the phenomenon where networks represent more concepts than they have dimensions, forcing non-orthogonal representation and thus interference. This interference causes perturbations targeting one representation to affect others, creating vulnerabilities determined by interference patterns. In synthetic settings with precisely controlled superposition, we establish that superposition suffices to create adversarial vulnerability. The resulting attacks are predictable: PGD-discovered perturbations align with theoretically optimal perturbations derived from the interference geometry. Models trained on similar data develop similar interference patterns, explaining attack transferability. We then show that successful attacks on image classifiers exhibit the structure predicted by our proposed mechanism. These findings reveal that adversarial vulnerability can be a byproduct of networks' representational compression, complementing existing explanations based on data properties or architectural factors.

18.
Nature (Science) 2026-06-10

Gene ancestries reveal diverse microbial associations during eukaryogenesis

The origin of eukaryotes remains a central enigma in biology1. Continuing debates agree on the pivotal role of a symbiosis between an alphaproteobacterium and an Asgard archaeon2,3. However, the nature, timing and contributions of other potential bacterial partners4–6 and the role of interactions with viruses7–9 remain contentious. To address these questions, we used advanced phylogenomic approaches and comprehensive datasets spanning the known diversity of cellular life and viruses. Our analysis provided a revised reconstruction of the last eukaryotic common ancestor (LECA) proteome, in which we traced the phylogenetic origin of each protein family. We found compelling evidence for multiple waves of horizontal gene transfer from diverse bacterial donors, with some likely to have preceded mitochondrial endosymbiosis. We inferred plausible traits of the major donors and their functional contributions to the LECA. Our findings support a contribution of horizontal gene transfers to shaping the proteomes of pre-LECA ancestors and suggest a facilitating role of Nucleocytoviricota viruses. Taken together, our results suggest that ancient eukaryotes may have originated within complex microbial ecosystems through a succession of diverse associations that left a footprint of horizontally transferred genes. Phylogenomic reconstruction of the proteome of the last eukaryotic common ancestor sheds light on the origin of eukaryotes, indicating an important role of horizontal transfer of genes from diverse bacterial and viral donors.

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

ACCORD: Action-Conditioned Contextual Grounding for Language Agents

User instructions are often underspecified because humans rely on implicit assumptions about the surrounding environment. For large language model (LLM) agents operating in information-rich digital and physical environments, these assumptions cannot be inferred from the instruction alone; they must be recovered from the current state of tools, data, interfaces, and observations. Effective execution therefore requires agents to identify missing context, ground it in observed evidence, and carry it forward into subsequent actions. We show that current agents often fail to do so. They act from assumed rather than observed specifics, overlook information they could have gathered, and fail to incorporate evidence that has already been returned. Building on this insight, we propose ACCORD (Action-Conditioned Contextual Grounding), a simple and effective agent framework for adaptive grounding. Before each action, ACCORD actively probes the environment for missing information and integrates relevant context from the agent's trajectory that would otherwise be overlooked. Requiring no additional training or task-success signals, ACCORD improves task-goal completion on AppWorld by up to +20.6 points with GPT-5-mini, from 42.0% to 62.6%, compared to strong baselines. These gains persist with a substantially stronger base model (+10.8 with Claude-4.5-sonnet), an open-weight model (+10.1 with Qwen3.5-27B-FP8), and on the embodied AlfWorld benchmark (+7.4 success rate with GPT-5-mini).

20.
arXiv (CS.AI) 2026-06-15

History of the Muddy Children Puzzle

arXiv:2606.13703v1 Announce Type: new Abstract: The Muddy Children Puzzle is a puzzle about knowledge and ignorance that has been inspiring for the development of epistemic logic. Who came up with it first? This is unclear. We trace the origin of the Muddy Children Puzzle through logical and literary publications over the past two centuries. The puzzle inspired a numerous variations such as involving numbers or coloured hats. We also present a novel hats puzzle involving self-reference.

21.
arXiv (CS.CL) 2026-06-24

Automatic Part-of-Speech Tagging of Arabic-English Dictionary Senses through WordNet

This paper proposed an algorithm for part-of-speech (POS) tagging senses of a bilingual dictionary. The algorithm is applied on the Al-Mawrid Arabic-English dictionary. The tagging task is accomplished by transferring the POS tags of the English translation equivalences (TEs) to the dictionary senses after dis-ambiguities process. The English POS tags of senses are acquired from the Princeton WordNet. POS tagging of bilingual dictionary senses is prerequisite to link a bilingual dictionary to WordNet and/or standardizing that dictionary into WordNet-LMF format where the synset (set of synonyms), not word, is the basic brick. The registered accuracy is high though the cost is little. Building NLP/HLT tools needs linguistic experts, large investments, and long time. For statistical approach, we need large annotated corpora and for rule-based approach, we need large lexicon that contains rich linguistic and world knowledge. That motivates the appearance of what are called resource-light approaches to develop natural language processing (NLP) tools for poor-resource languages.

22.
arXiv (CS.AI) 2026-06-19

TelcoAgent: A Scalable 5G Multi-KPM Forecasting With 3GPP-Grounded Explainability

arXiv:2606.19821v1 Announce Type: new Abstract: Key Performance Measurement (KPM) forecasting is essential for proactive network management of 5G and next-generation telecom networks. However, existing machine learning (ML) approaches face significant limitations in scalability and explainability, restricting their effectiveness in real-world deployments. We propose TelcoAgent, a foundation model-based framework that enables accurate, scalable, and explainable forecasting of multiple KPMs across diverse network cells without the need for site-specific training. Specifically, the framework comprises three key components: (i) an automated three-agent pipeline that constructs a 3rd Generation Partnership Project (3GPP) knowledge graph directly from specification documents, (ii) a scalable, time-series foundation model (TSFM)-based prediction pipeline to deliver accurate, zero-shot forecasting, and finally (iii) a reasoning and explanation pipeline that provides actionable, domain-grounded diagnostics. Evaluated using a 3-month, real-world, city-scale 5G KPM dataset from a U.S.-based network operator, TelcoAgent demonstrates high forecasting accuracy for all 7 considered KPMs per cell across 200 cells, while delivering explainable insights and actionable instructions to address network degradations.

23.
arXiv (CS.CV) 2026-06-17

SegTME-UNI2: A Foundation Model-Based Framework for Generalisable Multiclass Cell Segmentation and LLM-Driven Tumour Microenvironment Characterisation in Histopathology

Characterising the tumour microenvironment (TME) from routine H&E-stained histology images requires simultaneous cell segmentation, feature extraction, and interpretable clinical reporting. We present SEGTME-UNI2, a unified framework addressing these requirements. Its core is UNI2-UPERHOVER, a dual-head segmentation model pairing the UNI2-H pathology foundation model (ViT-Giant, pretrained on >100M tiles from 100K slides) with two parallel UperNet decoders: one for six-class semantic segmentation and one for horizontal-vertical gradient regression enabling watershed-based nuclear instance separation. To address the lack of pixel-level annotations in large real-world repositories, UNI2-UPERHOVER undergoes a three-stage progressive pseudo-label curriculum. Each stage trains a fresh model without weight transfer, driving improvement entirely via increased pseudo-label quality: Stage 1: Uses human-annotated PanNuke (7,901 images, 189,744 nuclei, 0.25 um/pixel). Stage 2: Uses entropy-filtered pseudo-labels from the Stage 1 model on 271,711 TCGA-UT scale-0 patches (0.5 um/pixel). Stage 3: Uses pseudo-labels from the Stage 2 model on all 1,608,060 TCGA-UT patches across six resolution scales (0.5-1.0 um/pixel). Segmentation outputs feed a structured TME feature extraction pipeline computing 20+ per-patch compositional, morphological, spatial entropy, and intercellular distance metrics. These are encoded as JSON and passed to a fine-tuned NVIDIA BioNeMo GPT model to generate clinically interpretable TME narratives. Preliminary validation on held-out PanNuke and TCGA-UT partitions demonstrates framework feasibility and internal consistency. The pseudo-labelled TCGA-UT dataset and UNI2-UPERHOVER checkpoint are publicly released to support large-scale TME profiling and spatial biology research.

24.
bioRxiv (Bioinfo) 2026-06-23

VCBench: A Multi-Dimensional Benchmark for Single-Cell Foundation Models

Single-cell foundation models are increasingly positioned as virtual cells, yet their capabilities are assessed by fragmented, largely single-task benchmarks that obscure where these models improve on simple baselines. VCBench addresses this by synthesizing four independent virtual-cell frameworks into seven capability dimensions: perturbation response prediction, cross-species universality, gene regulatory network (GRN) inference, modality integration, temporal dynamics, multi-scale integration, and in silico experimentation. Each dimension is assessed for operational testability under current architectures and datasets: five admit direct or proxy evaluation, while multi-scale integration and in silico experimentation are structurally untestable as end-to-end tasks. We evaluate five foundation models (Geneformer, scGPT, UCE, TranscriptFormer, Arc State) against pre-registered linear and nearest-neighbor baselines across the five testable dimensions, and report three findings. First, the baselines match or exceed every foundation model on four of the five scored dimensions, replicating the reported competitiveness of linear baselines on perturbation prediction and extending it to cross-species transfer, GRN inference, and temporal ordering. Second, TranscriptFormer alone exceeds the strongest baseline on cross-modal RNA-to-protein prediction (53% Pearson improvement, with a documented contamination caveat) and is the only model to reach Level 2 in the pre-registered Virtual Cell (VC) Level rubric; the architectural choice behind this advantage simultaneously causes a spectral collapse that destroys its temporal-ordering performance, a tradeoff invisible to single-task benchmarks. Third, no foundation model publishes a complete cell-level training manifest, leaving data contamination undetectable to users. Alongside the benchmark, VCBench releases a Contamination Reporting Schema and contributes two further methodological tools: a common-label-set protocol that controls for class-count confounds in cross-species transfer, and a spread-error correlation probe for epistemic calibration.

25.
medRxiv (Medicine) 2026-06-10

Assessment of the accuracy of lung lesions diagnosis in adolescents with osteosarcoma using artificial intelligence

Background. Lung metastases in osteosarcoma (OS) are the main cause of the death. The accuracy of the diagnosis of nodules by computed tomography (CT) of the lungs is critically important for determining the disseminated stage of the disease and planning surgical treatment. The use of artificial intelligence (AI) in the search for lung nodules increases the accuracy of diagnosis and reduces the chance of missing metastases. Objective: to evaluate the accuracy of lung nodules diagnosis in adolescents with OS using AI. Methods. A retrospective assessment of CT scans of adolescents with OS was performed. A pathological nodule with an average size of [≥]4 mm was considered a target finding. The diagnostic accuracy of an AI algorithm previously trained on an adult dataset was evaluated, and the number of false positives (FP) and false negatives (FN) was determined. Sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value, negative predictive value, and F1-measure were calculated. Based on the obtained results, the effectiveness of the algorithm was assessed. Results. 248 CT scans of adolescents with OS were evaluated. The following results were obtained: in 5 cases, the AI algorithm showed a FP result (2.02%), in 34 cases, it showed a FN result (13.71%), and in 209 cases, a correct result (both true positive and true negative) (84.27%). The diagnostic accuracy of the algorithm was 0.843 (95% CI 0.794-0.887). The application of the AI algorithm in the practice of an X-ray doctor in a specific clinical task would allow to increase the sensitivity from 0.805 to 0.891, while ensuring an absolute decrease in the number of FN results by 8.59% and a relative decrease by 44%. Conclusion. The obtained results confirm the practical value of the application of the AI algorithm and justify the implementation of AI-assisted systems in the diagnostic protocols for lung metastases in adolescents with OS.