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01.
arXiv (CS.AI) 2026-06-11

Are Frontier LLMs Ready for Cybersecurity? Evidence for Vertical Foundation Models from Dual-Mode Vulnerability Benchmarks

arXiv:2605.23243v2 Announce Type: replace-cross Abstract: We evaluate whether frontier LLMs are ready for cybersecurity through a dual-mode benchmark: white-box function-level vulnerability detection (VulnLLM-R, across C/Java/Python) and black-box web application security testing (five production-style applications with 118 ground-truth vulnerabilities across 20+ CWE families, which we will open-source). We test six frontier models (GPT-5.4, Codex~5.3, Claude Opus~4.6, Sonnet~4.6, Gemini~3.1~Pro and Gemini~3~Flash) and two domain-specialized models across four testing paradigms. Our findings are sobering: (1)~every frontier model produces 10-50% false positive rates in white-box detection, systematically over-predicting vulnerabilities; (2)~in black-box testing, frontier models achieve only 4-8% ground-truth coverage, improving to just 10-19% even with external security tools (Playwright MCP, Burp Suite MCP); (3)~structured penetration-testing methodology encoded in domain-specialized agents raises per-family detection above 50%, demonstrating that methodology, not scale, is the primary lever; and (4)~a domain-specialized defense model achieves the highest precision (0.904) and lowest false positive rate (9.7%) among all models, on a single GPU. We identify the absence of structured security testing traces end-to-end request/response sequences, failure-heavy data, and multi-step attack chains as the fundamental training data bottleneck, and propose self-play security testing as a data generation strategy. Our results make the case for vertical foundation models purpose-built for cybersecurity.

02.
arXiv (CS.AI) 2026-06-17

Detecting and Mitigating DDoS Attacks with AI: A Survey

arXiv:2503.17867v3 Announce Type: replace-cross Abstract: Distributed Denial of Service attacks represent an active cybersecurity research problem. Recent research shifted from static rule-based defenses towards AI-based detection and mitigation. This comprehensive survey covers several key topics. Preeminently, state-of-the-art AI detection methods are discussed. An in-depth taxonomy based on manual expert hierarchies and an AI-generated dendrogram are provided, thus settling DDoS categorization ambiguities. An important discussion on available datasets follows, covering data format options and their role in training AI detection methods together with adversarial training and examples augmentation. Beyond detection, AI based mitigation techniques are surveyed as well. Finally, multiple open research directions are proposed.

03.
arXiv (CS.LG) 2026-06-18

P-K-GCN: Physics-augmented Koopman-enhanced Graph Convolutional Network for Deep Spatiotemporal Super-resolution

arXiv:2606.19303v1 Announce Type: new Abstract: High-fidelity simulation of spatiotemporal dynamics is computationally prohibitive, necessitating efficient super-resolution techniques to reconstruct high-resolution data from coarse-grained inputs. Traditional data-driven methods often lack physical constraints, and simple physics-informed learning struggles with irregular spatial geometries and intricately evolving temporal dynamics. To tackle these challenges, we propose a Physics-augmented Koopman-enhanced Graph Convolutional Network (P-K-GCN) for spatiotemporal super-resolution on irregular geometries. Specifically, a continuous spline-based GCN is first designed to extract spatial dependencies directly from coarse graph, and Koopman operator theory is incorporated to project the nonlinear dynamics into a compact latent space where temporal progression is linearized. Second, we augment the optimization objective with a physics-based loss to force the data-driven reconstructions to adhere to physical laws for improving predictive fidelity and robustness. Finally, we provide a rigorous theoretical analysis, establishing that the physics augmentation and Koopman regularization mathematically guarantees a reduction in super-resolution error by diminishing Rademacher complexity and tightening generalization bounds. We evaluate our framework on reconstructing spatially high-resolution cardiac electrodynamics across a 3D heart geometry from sparse low-resolution measurements. Numerical experiments demonstrate that our method achieves superior accuracy compared to baseline models.

04.
arXiv (math.PR) 2026-06-11

Unbiased Derivative Estimation for Stationary Mean of Parameterized Markov chains

arXiv:2606.11487v1 Announce Type: cross Abstract: We propose a new approach to unbiased estimation of the gradients of the stationary means associated with parametrized families of Markov chains. Our estimators are particularly efficient when the Markov chains have slow mixing rate. Our approach does not require a specific parametrization except for an oracle to evaluate the transition density and its gradient at a given data point without any additional knowledge about the density function itself. It makes our estimator suitable for parametrizations associated with neural networks. The estimator can potentially achieve large improvement in terms of efficiency. Numerical experiments confirm the good performance predicted by the theory.

05.
medRxiv (Medicine) 2026-06-17

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

Despite recent advances in next-generation sequencing, genetic diagnostic rates for dilated cardiomyopathy (DCM) remain low. Among paediatric DCM, causes are often heritable, with a greater frequency of de novo, recessive and syndromic causes of disease. Novel diagnostic methods are therefore required to solve monogenic cases. To assess the value of proteomics as a diagnostic tool for paediatric DCM, we obtained left ventricle myocardial samples from paediatric patients undergoing heart transplantation at the Royal Children's Hospital, Melbourne. We performed genome sequencing and proteomics and leveraged this multi-omics dataset to uncover the molecular cause of disease in a gene elusive proband. The proband carried a heterozygous JPH2 frameshift variant identified on clinical exome sequencing. However, proteomic analysis showed a pronounced downregulation of JPH2, suggestive of biallelic loss-of-function. Closer inspection of the genomic data revealed a large inversion (~8.34 Mb) with a breakpoint falling within intron 5 of JPH2 that displaces the 3'UTR from the coding transcript. The two variants were confirmed to be in trans using long read DNA sequencing, consistent with a diagnosis of JPH2 autosomal recessive DCM. Finally, we applied RNA sequencing with total RNA library preparation to show that transcripts containing a 3'UTR were reduced to ~10% relative to controls. As a proof-of-principle, we present the first reported use of proteomics from explanted cardiac tissue to provide a genetic diagnosis. Our methodology has broad relevance to patients with genetically unsolved Mendelian diseases, who might undergo organ transplantation as part of clinical management.

06.
arXiv (quant-ph) 2026-06-15

Inhomogeneous Light-Matter Coupling as a Resource for Noiseless Quantum Memories

arXiv:2605.26783v3 Announce Type: replace Abstract: Inhomogeneous ensembles of two-level systems are central to both fundamental light-matter physics and quantum-network applications. Understanding and optimizing ensemble-based quantum memories and entanglement protocols requires a unified framework that describes how to store quantum states of light as collective matter excitations and retrieve them on demand. Here we develop such a framework, the waveguide model, by mapping the dark collective modes of the ensemble onto an effective waveguide with well-defined input-output relations, valid in both the weak-excitation regime and near population inversion. This model reveals that inhomogeneous coupling – often regarded as a limitation – is instead the physical origin of noisy-echo suppression by adiabatic pulses, a key ingredient for realizing noiseless quantum memories. For entanglement generation, the same mechanism exposes a previously unexplored shortcoming of robust control pulses and leads to a new composite-pulse protocol that overcomes it. These results establish the waveguide model as a practical bridge between fundamental collective physics and quantum-network protocol design, recasting inhomogeneous coupling from an obstacle into a control knob for collective emission.

07.
medRxiv (Medicine) 2026-06-22

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

Authors:

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.

08.
medRxiv (Medicine) 2026-06-22

Mapping abstraction and metacognition onto distinct transdiagnostic symptom profiles

Transdiagnostic psychiatric research on reward-guided learning has largely focused on simple associative processes, leaving it unclear whether or how higher-level processes are disrupted. Here, we studied how abstraction, the ability to extract relevant features from complex information, and metacognition, the ability to monitor and evaluate one's own mental processes, map onto specific transdiagnostic dimensions. Using an online sample (N = 249), we examined associations between these processes and three cross-culturally robust transdiagnostic dimensions derived from a large existing dataset (N = 19,505): Compulsive hypersensitivity, Social withdrawal, and Addictive behaviours. Computational modelling of an abstract representation learning task with confidence judgments revealed that Compulsive hypersensitivity was negatively associated with both abstraction ability (pboot = 0.003) and metacognitive sensitivity (pboot = 0.005), while Social withdrawal was positively associated with metacognitive sensitivity alone (pboot = 0.002). Moreover, transdiagnostic dimensions revealed more coherent associations with higher-order cognition than symptom-level analyses, highlighting the added value of examining psychopathology at the factor rather than the symptom level. These findings portray a hierarchical view of cognitive dysfunctions in psychopathology and point to representational and metacognitive processes as potential targets for transdiagnostic intervention.

09.
medRxiv (Medicine) 2026-06-23

Social networks and their association with quality of life among older adults in rural Burkina Faso

Objective: This study aimed to identify the types of social networks present among older adults in a rural, low-income country setting and describe their association with quality of life (QoL). Methods: A population-representative, cross-sectional survey was conducted in 60 villages around Nouna in Burkina Faso from July to August 2021. Data were collected from resident adults aged 40 years and older. Variables captured were sociodemographic status; social network characteristics (using the Practitioner Assessment of Network Typology (PANT)); quality of life (using the EuroHIS-8 tool); presence of non-communicable diseases, mental health conditions, and disability. Additionally, social networks were broadly categorised as aggregated integrated and aggregated less-integrated groups. Social network types and the groups were described separately, and a multivariable linear regression model was used to understand the association between social network types and QoL, adjusted for sociodemographic and morbidity factors. Results: Among the 2390 respondents, median age was 55 yrs (IQR: 47-64 yrs) and 55.8% were female. Locally Integrated (35.4%) or Family Dependent (30.3%) were the most common PANT social network types, followed by a mixed group (having characteristics of two or more social network types) (30.5%). Private Restricted (2.1%), Locally Self-Contained (1.2%), and Wider Community-Focussed (0.4%) types were uncommon. Adults with aggregated integrated network groups (36.1%) and aggregated less-integrated group (36.0%) were near equal, while others were non-aggregable. Although Wider Community-Focused type showed a significantly better QoL ({beta}= 8.69, 95%CI: 4.10 to 13.27), the association between social networks and QoL were subdued when controlled for morbidity factors, and hence no significant associations were observed between other types or the aggregated groups. Conclusion: Although having integrated social networks lead to a better QoL, morbidity has a greater effect on the QoL among older adults in Nouna and hence, investing more on improving the physical and mental health needs appears more beneficial.

10.
arXiv (CS.AI) 2026-06-11

Noise-Guided Transport for Imitation Learning

arXiv:2509.26294v2 Announce Type: replace-cross Abstract: We consider imitation learning in the low-data regime, where only a limited number of expert demonstrations are available. In this setting, methods that rely on large-scale pretraining or high-capacity architectures can be difficult to apply, and efficiency with respect to demonstration data becomes critical. We introduce Noise-Guided Transport (NGT), a lightweight off-policy method that casts imitation as an optimal transport problem solved via adversarial training. NGT requires no pretraining or specialized architectures, incorporates uncertainty estimation by design, and is easy to implement and tune. Despite its simplicity, NGT achieves strong performance on challenging continuous control tasks, including high-dimensional Humanoid tasks, under ultra-low data regimes with as few as 20 transitions.

11.
arXiv (math.PR) 2026-06-11

Instability of a nonlinear oscillator with small friction and small additive noise

arXiv:2606.11389v1 Announce Type: new Abstract: Let $\lambda = \lambda(\beta,\sigma,a,b)$ denote the top Lyapunov exponent for the linearization along trajectories of the noisy damped non-linear oscillator $\ddot{x}+\beta \dot{x} + ax+bx^3 = \sigma \dot{W}_t$, where $a$, $b$ and $\beta$ are all positive and $\sigma \neq 0$. In 2004 Arnold, Imkeller and Sri Namachchivaya stated without proof that $\lambda(\varepsilon^2 \beta,\varepsilon \sigma,a,b) \sim \overline{\lambda} \varepsilon^{2/3}$ as $\varepsilon \to 0$ with $\overline{\lambda} > 0$. This paper contains a proof of this assertion.

12.
arXiv (CS.LG) 2026-06-11

Multi-agent rendezvous in fluid flows via reinforcement learning

arXiv:2606.11274v1 Announce Type: cross Abstract: Rendezvous is a critical task for multi-agent systems, requiring agents to coordinate to meet at an unspecified location. However, achieving this in fluid environments presents a challenge, as it remains unclear how agents can exploit underlying fluid kinematics to facilitate convergence. In this study, we adopt a multi-agent reinforcement learning (MARL) approach to develop physics-informed rendezvous strategies in vortical flows. Compared to a naive strategy, where agents navigate toward their counterparts, MARL strategies significantly improve the rendezvous rate. MARL strategies also show transferability across varying vortex intensities, vortex scales, and swarm sizes. By breaking the symmetry of the state-action map, MARL strategy leverages a non-intuitive mechanism that prevents agents from becoming trapped in separate vortices, thereby enhancing rendezvous success. Additionally, a heuristic strategy is extracted from the learned strategy and also outperforms the naive strategy. Furthermore, a theoretical analysis demonstrates that fluid deformation impedes the rendezvous process. Large finite-time Lyapunov exponents identify where fluid effects separate adjacent agents, suggesting that targets should be planned in weak-deformation regions. Our findings reveal the important role that agent-fluid interactions play in multi-agent tasks and highlight the MARL capability to explore swarm intelligence in complex flow environments.

13.
Nature (Science) 2026-06-17

Cortical development dynamics across autism spectrum disorder mouse models

Despite the functional diversity of over 100 causal genes1–3, phenotypic convergence across models may reveal common neurobiological processes in autism spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse models of ASD using single-nucleus multi-omic sequencing across three developmental stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. These alterations reflect a transient developmental delay rather than lasting lineage misspecification and resolve by postnatal stages. Molecularly, the largest transcriptional differences emerged in neurons at early postnatal stages. These changes included downregulation of synaptic and ion channel-related genes, consistent with homeostatic adaptation or delayed maturation. Network analysis showed molecular convergence across models within each developmental stage, suggesting that diverse mutations linked to ASD impinge on common, stage-specific processes. Convergence becomes less pronounced by postnatal day 14, highlighting the dynamic nature of ASD-associated changes. Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology corroborated this pattern: mutants generally showed altered neuronal excitability and synaptic properties with model-specific nuances. Our study also highlighted sex-specific gene expression alterations, with female mice often displaying larger effect sizes than male mice. Together, our findings provide a comprehensive view of developmental cellular and molecular dynamics across models of ASD. Using single-nucleus multi-omic sequencing, diverse autism spectrum disorder-linked gene mutations converge on transient, stage-specific disruptions in early brain development, and highlight sex-specific gene expression alterations.

14.
arXiv (CS.CV) 2026-06-11

DroneShield-AI: A Multi-Modal Sensor Fusion Framework for Real-Time Autonomous Drone Threat Detection, Behavioral Intent Classification, and Swarm Intelligence in Contested Airspace

Unmanned Aerial Vehicle (UAV) threats have emerged as a defining security challenge of the 21st century. This paper presents DroneShield-AI, a unified open framework integrating six processing layers: RF signal classification, acoustic motor-signature detection, YOLOv8-based visual detection, evidence-weighted sensor fusion, a Behavioral Intent Classification Engine (BICE), and a Graph Neural Network Swarm Intelligence Module (GNN-SIM). BICE introduces the first systematic six-class threat taxonomy for drone flight patterns, enabling predictive operator alerts with a 30-second advance-warning horizon. GNN-SIM is the first open framework for adversarial multi-drone formation analysis using Graph Attention Networks. Evaluated on three publicly available real-world datasets, the fused pipeline achieves 96.1% detection accuracy, 3.2% false alarm rate, AUC-ROC: 0.981, and 142ms end-to-end latency on commodity CPU-class hardware at approximately $500-$780 USD total system cost. All code, model weights, and simulation datasets are publicly released at submission.

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

OGPO: Sample Efficient Full-Finetuning of Generative Control Policies

arXiv:2605.03065v2 Announce Type: replace Abstract: Generative control policies (GCPs), such as diffusion- and flow-based control policies, have emerged as effective parameterizations for robot learning. This work introduces Off-policy Generative Policy Optimization (OGPO), a sample-efficient algorithm for finetuning GCPs that maintains off-policy critic networks to maximize data reuse and propagate policy gradients through the full generative process of the policy via a modified PPO objective, using critics as the terminal reward. OGPO achieves state-of-the-art performance on manipulation tasks spanning multi-task settings, high-precision insertion, and dexterous control. To our knowledge, it is also the only method that can fine-tune poorly-initialized behavior cloning policies to near full task-success with no expert data in the online replay buffer, and does so with few task-specific hyperparameter tuning. Through extensive empirical investigations, we demonstrate that OGPO drastically outperforms methods alternatives on policy steering and learning residual corrections, and identify the key mechanisms behind its performance. We further introduce practical stabilization tricks, including success-buffer regularization, two-sided conservative advantages, and Q-variance reduction, to mitigate critic over-exploitation across state- and pixel-based settings. Beyond proposing OGPO, we conduct a systematic empirical study of GCP finetuning, identifying the stabilizing mechanisms and failure modes that govern successful off-policy full-policy improvement.

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

Seeing Roads Through Words: A Language-Guided Framework for RGB-T Driving Scene Segmentation

Robust semantic segmentation of road scenes under adverse illumination, lighting, and shadow conditions remain a core challenge for autonomous driving applications. RGB-Thermal fusion is a standard approach, yet existing methods apply static fusion strategies uniformly across all conditions, allowing modality-specific noise to propagate throughout the network. Hence, we propose CLARITY that dynamically adapts its fusion strategy to the detected scene condition. Guided by vision-language model (VLM) priors, the network learns to modulate each modality's contribution based on the illumination state while leveraging object embeddings for segmentation, rather than applying a fixed fusion policy. We further introduce two mechanisms - one which preserves valid dark-object semantics that prior noise-suppression methods incorrectly discard, and a hierarchical decoder that enforces structural consistency across scales to sharpen boundaries on thin objects. Experiments on the MFNet dataset demonstrate that CLARITY establishes a new state-of-the-art (SOTA), achieving 62.3% mIoU and 77.5% mAcc.

17.
arXiv (CS.LG) 2026-06-15

Curvature-Informed Potential Energy Surface for Protein-Ligand Binding Affinity Prediction

arXiv:2606.14217v1 Announce Type: new Abstract: Accurate prediction of protein-ligand binding affinity is essential for structure-based drug discovery. Recent geometric deep learning methods have achieved promising performance by representing protein-ligand complexes as three-dimensional graphs. However, most existing approaches mainly rely on static interaction geometry from a single bound conformation, while neglecting molecular flexibility and binding-induced conformational changes. To address this limitation, we propose a curvature-informed potential energy surface (CPES) graph neural network for protein-ligand binding affinity prediction, which incorporates physics-informed curvature representations to model conformational flexibility. CPES first derives curvature spectral descriptors from the Hessian of the potential energy surface evaluated at equilibrium configurations, whose eigenvalues define the local principal curvatures of the potential energy surface. It then uses spectral cross-attention to compare the unbound ligand and protein with the bound complex, thereby capturing binding-induced changes in conformational dynamics. In parallel, hierarchical protein-ligand interaction representations are learned from static structural features through geometry-aware message passing, soft clustering, and bidirectional cross-attention. Finally, CPES fuses the curvature-informed dynamic representations with static interaction representations for affinity regression. Extensive evaluations on multiple benchmark datasets demonstrate that CPES achieves improved predictive performance and offers physical interpretability.

18.
arXiv (math.PR) 2026-06-16

Sharp freezing time estimates for the subcritical Facilitated Exclusion Process

arXiv:2606.15233v1 Announce Type: new Abstract: We investigate the exact transience time of the Facilitated Exclusion Process (FEP) on the one-dimensional torus with $N$ sites. The FEP exhibits an active/inactive phase transition at critical density $1/2$, such that in the subcritical density regime $(0,1/2)$, it becomes frozen after a finite time period – the transience time or freezing time. We first show that for the FEP starting from a Bernoulli product measure of marginal density $\rho \in (0,1/2)$, the transience time has exactly the scale of $\Theta(\log^3 N)$. Secondly, we prove that in the near-critical case $\rho \simeq 1/2 - N^{-\alpha}$ for $\alpha \in (0,1)$, the transience time is polynomial and has a scale of $N^{1 \wedge (2\alpha)}$. The key idea is to estimate the typical size of locally supercritical intervals of the initial distribution, which has order $\log N$ in the subcritical case and $N^{1 \wedge (2\alpha)}$ in the near-critical case. In the subcritical case this is enough, whereas in the near-critical case we need additional dynamical decorrelation inequalities to apply this static result to estimate the freezing time.

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

Distinguishing quantum processes with bounded coherent memory

arXiv:2606.19511v1 Announce Type: new Abstract: Distinguishing multi-time quantum processes is a fundamental task underlying the diagnosis, benchmarking, and learning of temporally correlated quantum dynamics. The standard benchmark for distinguishing two processes is the strategy-norm distance, which optimizes over arbitrary adaptive probing strategies but can require large coherent memory and time-dependent control. We introduce machines for autonomous distinction~($\mathsf{MAD}$s): probing strategies that apply the same quantum instrument at each time step, retain the full classical outcome record, and carry a coherent memory of dimension $d_A$. Optimizing over these strategies defines a memory-parametrized distinguishability measure, $d^{(N)}_{\mathsf{MAD}}(\mathbf{P}^N,\mathbf{Q}^N;d_A)$. We show that the resulting hierarchy is monotone in coherent memory and complete at finite times. Specifically, any admissible $N$-step probing strategy can be compiled into a single $\mathsf{MAD}$ with an internal counter and sufficiently large coherent memory, so the hierarchy saturates the strategy-norm benchmark. For recurrent processes generated by repeated system–environment interactions, we derive a single-step description that separates the generation of new distinguishing information from the propagation and decay of information generated at earlier times. Numerical results in a repeated-interaction model show that increasing coherent memory systematically improves the $\mathsf{MAD}$ success probability and closes the gap to the strategy-norm distance while remaining substantially more tractable to evaluate. $\mathsf{MAD}$ distinguishability therefore provides an operational and scalable framework for quantifying what can be learned about genuinely multi-time quantum processes with bounded coherent memory.

20.
arXiv (CS.CV) 2026-06-17

Enhancing Pathological VLMs with Cross-scale Reasoning

Pathological images are inherently multi-scale, requiring pathologists to integrate evidence from global tissue architecture at low magnification to cellular morphology at higher magnification for accurate diagnosis. While existing pathological datasets for vision-language model (VLM) include various scales, they often lack an explicit cross-scale reasoning objective. This limitation prevents VLMs from capturing essential cross-scale representations and learning evidence-based reasoning. To bridge this gap, we introduce the first cross-scale training and evaluation paradigm that formulates pathology interpretation as multi-magnification reasoning. However, creating such a task reveals a critical challenge: multi-image visual question answering (VQA) is prone to text-only shortcuts, which allow models to guess answers using magnification-dependent artifacts rather than visual evidence. To address this, we propose a leakage-aware curation pipeline that combines adversarial text-only screening with constraint-guided question design. Using this pipeline, we construct Scale-VQA, a high-quality benchmark with 4,685 multiple-choice questions grounded in 2,537 pathology images across multiple magnification levels. Finally, we present ScaleReasoner-R1, a model trained via reinforcement learning to optimize performance on the cross-scale VQA task. ScaleReasoner-R1 achieves state-of-the-art performance on our cross-scale reasoning benchmark and generalizes to SOTA performance on established single-scale benchmarks. Findings suggest that even the limited cross-scale supervision can significantly improve pathological understanding. The code and demos will be open-sourced.

21.
medRxiv (Medicine) 2026-06-15

Multidimensional nutritional assessment in Crohns disease: cross-sectional comparison of active disease and remission

Malnutrition is common in Crohns disease (CD), and its assessment requires multiple tools. Comprehensive evaluation of nutritional status in a population with CD, predominantly characterized by metabolic phenotype, was inadequately reported. This study evaluated the nutritional status of CD patients using anthropometric, clinical, and biochemical measures and compared patients with active disease with those in remission. This cross-sectional study included 127 adults with CD: 63 with active disease and 64 in remission. Disease activity was classified using the Crohns Disease Activity Index, the Simple Endoscopic Score for Crohns Disease, and magnetic resonance enterography. Nutritional assessment included body mass index (BMI), mid-upper arm circumference, calf circumference, triceps skinfold thickness, mid-arm muscle circumference, Mini Nutritional Assessment-Short Form (MNA-SF), and biochemical markers including hemoglobin, serum iron, folate, vitamin B12, albumin, and zinc. Malnutrition was defined using the Global Leadership Initiative on Malnutrition criteria. Overall, 47.2% of participants were malnourished. Malnutrition was significantly more frequent in active disease than in remission (81.0% vs. 14.1%, P

22.
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.

23.
bioRxiv (Bioinfo) 2026-06-10

SPARQ-MI leverages end-to-end spatial single-cell analysis of the tumor microenvironment

Detailed spatial analysis of the tumor micro-environment (TME) through multiplexed fluorescence imaging requires quantitative image-processing and data-analysis methods. While data-preprocessing down to segmentation of individual cells is captured by available methods, statistical analysis of single-cell features is compromised by the uneven noise distribution especially in complex tissues such as the TME, as well as by labor-intensive manual cell-type annotation and region segmentation. Here, we present SPARQ-MI (Spatial Phenotyping, Architecture Reconstruction and Quantification from Multiplexed Imaging) for streamlined spatial single-cell analysis, along with a tissue microarray PhenoCycler data-set with 37 fluorescent channels from melanoma patients under immunotherapy. We demonstrate that SPARQ-MI enables robust reconstruction of the cellular and spatial composition in this and other tissue types. Our analysis reveals associations of the cell-state and spatial location of CD8 T cells with response to immunotherapy. Overall, SPARQ-MI allows for quantitative analysis of complex fluorescence histology samples under minimal user input, and accounting for spatially uneven coverage of antibody signals, setting the stage for quantitative analysis of clinical samples.

24.
arXiv (CS.LG) 2026-06-16

A Multimodal Approach to Alzheimer's Diagnosis: Geometric Insights from Cube Copying and Cognitive Assessments

arXiv:2512.16184v2 Announce Type: replace Abstract: Early and accessible detection of Alzheimer's disease (AD) remains a critical clinical challenge, and cube-copying tasks offer a simple yet informative assessment of visuospatial function. This work proposes a multimodal framework that converts hand-drawn cube sketches into graph-structured representations capturing geometric and topological properties, and integrates these features with demographic information and neuropsychological test (NPT) scores for AD classification. Cube drawings are modeled as graphs with node features encoding spatial coordinates, local graphlet-based topology, and angular geometry, which are processed using graph neural networks and fused with age, education, and NPT features in a late-fusion model. Experimental results show that graph-based representations provide a strong unimodal baseline and substantially outperform pixel-based convolutional models, while multimodal integration further improves balanced classification performance and discriminative ability. SHAP-based interpretability analysis identifies specific graphlet motifs associated with corner integrity and edge continuity as key predictors, closely aligning with clinical observations of distorted cube drawings in AD. Together, these findings establish graph-based analysis of cube-copying behavior as an interpretable, non-invasive, and scalable framework for Alzheimer's disease screening.

25.
arXiv (CS.LG) 2026-06-18

Do as the Romans Do: Learning Universal Behaviors from Heterogeneous Agents

arXiv:2606.18537v1 Announce Type: new Abstract: Humans often acquire new skills by observing others, since observed behaviors implicitly reveal how to act in an environment. However, observations drawn from a heterogeneous population introduce conflicting behavioral signals, making it difficult to determine which behaviors are worth imitating. We address this challenge with General Reward Inference and Disentanglement (GRID), a social learning method that extracts universally useful behaviors from a heterogeneous population of demonstrators pursuing different goals. GRID decomposes per-agent reward functions into a general reward, capturing behaviors shared across all agents, and specific rewards, capturing individual preferences and objectives. Training exclusively on the general reward provides a new paradigm of generalist pretraining. It yields a generalist agent that internalizes universal environmental competencies, such as safety and basic task proficiency, without the mode-averaging bias that afflicts standard learning from demonstration techniques. This generalist serves as a superior prior for fine-tuning to downstream tasks, including preferences unseen during training. Experiments across a synthetic basis function decomposition, multi-agent Craftax, and a continuous autonomous driving simulator (Highway-Env) confirm that GRID successfully disentangles reward structure in a semantically meaningful way, outperforms standard learning from demonstration baselines, and enables more efficient and stable specialization.