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01.
medRxiv (Medicine) 2026-06-17

Investigating shared genetic overlap of immune-mediated inflammatory diseases and cardiometabolic diseases

Abstract Background: Immune-mediated inflammatory diseases (IMIDs) are associated with increased risk of cardiometabolic diseases. Investigating genetic overlap among these conditions can provide insights into their clinical management. Methods: Genetic correlation was assessed using linkage disequilibrium score regression (LDSC). Then, a meta-analysis was conducted using Association Analysis Based on SubSETs (ASSET) to pinpoint independent single nucleotide polymorphisms (SNPs) shared across the diseases. Each independent SNP was then used to define a genomic window (+/-500KB) for colocalisation analysis and Local Analysis of [co]Variant Association (LAVA) to offer multiple layers of regional pleiotropic evidence. Over-representation analysis was then run to identify enriched biological pathways, which then were used for drug target analysis. Results: The LDSC analysis showed a significant global genetic correlation for rheumatoid arthritis (RA) and cardiometabolic diseases including hypertension, coronary artery disease (CAD), heart failure (HF), stroke, atrial fibrillation (AF), and type two diabetes mellitus (T2DM) ranging from rg = 0.09 to 0.24. ASSET meta-analysis identified 164 independent SNPs shared across RA and the cardiometabolic diseases with P < 5 x 10- in the overall one-sided meta-analysis P-value, FDR < 0.05 in both individual GWASs, and TRUE phenotype matrix. Colocalisation analysis revealed multiple loci with strong evidence (Posterior probabilities [&ge;] 80) of single causal SNPs between the trait pairs. LAVA analysis was then used as an additional layer of confirmation for the findings generated by ASSET and colocalisation and thus several loci were highlighted. Over-representation analysis showed significant enriched immune-related pathways across RA-hypertension, RA-CAD, RA-AF, and RA-T2DM trait pairs. Drug target analysis highlighted several drugs which could be further tested for their effectiveness in RA and its common comorbidities. Conclusion: The findings revealed a shared genetic architecture and key immune-related biological pathways underlying RA and its associated cardiometabolic comorbidities. The identified genes and drugs provide opportunities for further therapeutic assessment which could improve clinical management strategies.

02.
arXiv (CS.LG) 2026-06-19

Weibull Weight-Scale Parameter Evolution under AdamW Training Dynamics

作者:

arXiv:2606.19367v1 Announce Type: new Abstract: Building on a two-parameter Weibull framework for diagnosing transformer weight distributions, we study why the Weibull weight-scale parameter $\lambda$ grows, overshoots, and then relaxes during AdamW training. We derive a leading-order three-force decomposition of the squared weight norm from the AdamW update: an alignment force measuring the correlation between weights and the adaptive update direction, an injection force from adaptive step magnitude, and a decay force from decoupled weight decay. On self-trained Pythia-70M models with ground-truth optimizer moments, alignment dominates the rise phase, contributing 88-94% of the absolute force budget across four random seeds and remaining robust to super-weight removal. Near saturation, alignment and decay approach balance, explaining the transition from weight-scale growth to relaxation. These force dynamics directly govern the squared-norm component underlying $\lambda(t)$; the remaining RMS-to-Weibull reconstruction offset is measurable and decomposes into bridge and integration components, totaling approximately 5-6% in densely sampled regions. To extend the analysis to real models where optimizer moments are unavailable, we introduce a spline displacement method that recovers the alignment force from sparse checkpoints with approximately 92-94% accuracy, about twice the naive two-point baseline. We further observe that the peak value of $\lambda(t)$ varies with training-data coherence in our experiments, suggesting a data-dependent component of weight-scale growth that we leave to a controlled follow-up study. Code and data are available at https://github.com/tiexinding/NPM-Weibull-public.

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

StereoFactory: A Unified Merging Framework for Robust Stereo Matching

Stereo matching has advanced through foundation models trained on large-scale datasets, yet this paradigm suffers from a scalability bottleneck: incorporating new data requires costly joint retraining. Model merging offers a scalable post-hoc alternative by integrating knowledge from specialized models after source checkpoints are available. However, existing merging methods typically retain all available models or rely on greedy inclusion, which can preserve harmful task-vector interference. We propose StereoFactory, a coarse-to-fine evolutionary framework for adaptive model merging. Stage~1 employs a genetic algorithm to search the combinatorial space of model subsets, determining which models should participate. Stage~2 addresses module-level knowledge specialization (different functional modules exhibit distinct preferences for knowledge sources) through CMA-ES optimization of architecture-adaptive routing over the selected task vectors, with optional module-level scaling. Experiments across two architectures and four benchmarks demonstrate that StereoFactory consistently achieves the best four-benchmark average under the same checkpoint pool, reducing the average error from 3.80 to 3.30 on NMRF and from 2.88 to 2.19 on FoundationStereo relative to the strongest controlled baseline. The post-hoc search requires only 2.7–3.7\% of the corresponding joint-retraining wall-clock time. Analysis reveals that knowledge contributions are inherently module-specific, and selected subsets can transfer across architectures with minimal degradation. Code will be publicly released upon acceptance at: https://github.com/XiandaGuo/StereoFactory.

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

Edit Knowledge, Not Just Facts via Multi-Step Reasoning over Background Stories

arXiv:2602.02028v2 Announce Type: replace Abstract: Enabling artificial intelligence systems, particularly large language models, to update knowledge and flexibly apply it during reasoning remains a central challenge. Existing knowledge editing approaches emphasize atomic facts, improving factual recall but often failing to integrate updated information into a coherent framework usable across contexts. In this work, we argue that knowledge update is fundamentally a reasoning problem rather than a memorization problem. Consequently, a model should be trained in situations where the new information is instrumental to solving a task, combined with pre-existing knowledge, and exercised through multi-step reasoning. Based on this insight, we propose a training strategy based on three principles. First, new knowledge is introduced as a coherent background story that contextualizes novel facts and explains their relation to existing knowledge. Second, models are trained using self-generated multi-hop questions that require multi-step reasoning involving the new information. Third, training is done using knowledge distillation, forcing a student model to internalize the teacher's reasoning behavior without access to the novel information. Experiments show that models trained with this strategy effectively leverage newly acquired knowledge during reasoning and achieve remarkable performance on challenging questions that require combining multiple new facts.

05.
arXiv (CS.LG) 2026-06-15

Learning the Context of Errors: Black-Box Online Adaptation of Time Series Foundation Models

arXiv:2606.14222v1 Announce Type: new Abstract: The rapid evolution of Time Series Foundation Models (TSFMs) has advanced zero-shot forecasting across diverse domains. Inspired by the current form of Large Language Models, future TSFMs may be offered as commercialized, closed-source API services. However, many existing online adaptation methods still rely on white-box access for parameter fine-tuning or gradient backpropagation. This paradigm mismatch raises a question: In black-box online adaptation for TSFMs, what should we learn? We answer this with an insight: the predictive errors of the base model are conditioned on both the input and output of the base model (i.e., the context of errors). To validate this insight, we propose ORCA (Online Residual Contextual Adaptation). We conduct extensive experiments across 5 state-of-the-art TSFMs and 8 datasets to demonstrate the effectiveness of our approach. Furthermore, through ablation studies, we quantitatively analyze the impact of different adapter learning hypotheses on the final adaptation performance in black-box online adaptation. Code available at https://github.com/Fifthky/ORCA.

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

From Mechanistic to Compositional Interpretability

arXiv:2605.08934v2 Announce Type: replace Abstract: Mechanistic interpretability aims to explain neural model behaviour by reverse-engineering learned computational structure into human-understandable components. Without a formal framework, however, mechanistic explanations cannot be objectively verified, compared, or composed. We introduce compositional interpretability, a category-theoretic framework grounded in the principles of compositionality and minimum description length. Compositional interpretations are pairs of syntactic and semantic mappings that must commute to enforce consistency between a model's decomposition and its observed behaviour. We deconstruct explanation quality into measures of faithfulness and complexity to cast interpretability as a constrained optimisation problem, and introduce compressive refinement to systematically restructure models into simpler parts without altering their function. Finally, we derive a parsimony criterion under which syntactic compression theoretically guarantees more concise, human-aligned explanations. Our framework situates prominent mechanistic methods as subclasses of refinement, and clarifies why their compressibility heuristics tend to align with human interpretability. Our work provides a measurable, optimisable blueprint for automating the discovery and evaluation of mechanistic explanations.

07.
medRxiv (Medicine) 2026-06-17

Accounting for Human Movement to Improve Exposure-Health Models

Background. Current exposure-health models rely on averaged, residential-based environmental exposures, failing to account for human movement. This aggregation can lead to exposure misclassification and biased exposure-response estimates, potentially distorting our understanding of the true health effects of environmental conditions. We developed exposure disaggregation regression models that explicitly account for human movement when linking environmental exposures to health outcomes. Methods. By weighting pixel-level exposures according to distance from home as a simple proxy for human movement, our model linked disaggregated environmental exposures to individual-level health outcomes. Weights were either fixed a priori or derived from a latent distance-decay power parameter learned from the data. We additionally evaluated model performance under a nonlinear exposure-response relationship. Model performance was assessed across multiple sample sizes (N = 1,114; 50,000; and 100,000). A simulation study examined parameter recovery using bias, empirical standard error (EmpSE), and credible interval coverage. As a case study, Demographic and Health Surveys (DHS) data from Albania were used to link acute respiratory infection (ARI) outcomes among children under five to pixel-level NDVI within a 3 km buffer around DHS cluster centroids, and the proposed models were applied to these data. Results. Across all models (fixed-weight, learned-weight, and restricted cubic spline models), parameter recovery improved with increasing sample size. At N = 1,114, estimates were biased and imprecise, with incorrect effect direction for exposure-response parameters (e.g., learned-weight {beta}1 bias = - 0.79; EmpSE = 2.61; coverage = 0.88). In contrast, the models accurately recovered parameters at larger sample sizes, including the latent distance-decay parameter (bias = - 0.02; EmpSE = 0.15; coverage = 0.95 at N = 100,000), demonstrating their ability to reliably learn movement-based exposure weights when sufficient data were available. Conclusion. Instead of relying on arbitrarily-sized buffers, this statistical framework provides a novel method for studying environmental exposure-health relationships whilst accounting for human movement. With sufficiently large sample sizes, it can accurately estimate the influence of disaggregated environmental exposures on individual-level health and help address exposure misclassification arising from residential-only metrics. This methodological framework remains scalable, interpretable, and adaptable to other exposures and outcomes, offering a foundation for future work that integrates richer mobility-informed exposure-health research.

08.
arXiv (CS.CV) 2026-06-15

Gefen: Optimized Stochastic Optimizer

AdamW is a default optimizer for modern deep learning, but its first and second moment states add roughly two parameter-sized buffers to training memory. We propose Gefen, a memory-efficient optimizer that automatically shares second-moment estimates across parameter blocks and quantizes the first moment using a learned codebook, thereby reducing AdamW's memory footprint by ~8x while maintaining the same performance, corresponding to a reduction of 6.5 GiB per billion parameters. The method is motivated by a theoretical result showing that large mixed Hessian entries constrain the ratio of squared gradients toward one, suggesting that Hessian-aligned parameters are natural candidates for sharing second-moment statistics. Since computing Hessians is impractical at scale, Gefen infers block structure from the initial squared gradients, requiring no architecture-specific metadata or hyperparameters beyond AdamW defaults. Gefen learns an exact histogram-based dynamic-programming quantization codebook and reuses the same blocks for first-moment scaling. Across diverse experiments, Gefen achieves the lowest peak optimizer memory among the compared AdamW-like methods while maintaining AdamW-level performance. In FSDP and DDP training, the reduced memory footprint enables larger microbatches and improves throughput significantly over AdamW, providing a practical drop-in replacement with lower memory usage that can increase throughput and enable training larger models or using larger batch sizes. We provide the complete Python implementation, including fused CUDA kernels at https://github.com/ndvbd/Gefen

09.
arXiv (math.PR) 2026-06-12

Mixing times of one-sided $k$-transposition shuffles

arXiv:2112.05085v2 Announce Type: replace Abstract: We study mixing times of the one-sided $k$-transposition shuffle. We prove that this shuffle mixes relatively slowly, even for $k$ big. Using the recent ``lifting eigenvectors'' technique of Dieker and Saliola and applying the $\ell^2$ bound, we prove different mixing behaviors and explore the occurrence of cutoff depending on $k$.

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

Budget-Aware Adaptive Adversarial Patches for Black-Box Object Detection

Adversarial patches pose a practical threat to modern object detectors. Prior work shows vulnerability, but three gaps limit actionable insight: (i) few score-based black-box attacks jointly optimize patch location, texture, and size under tight query budgets; (ii) success is rarely tied to the patch's visual footprint; and (iii) evaluations often conflate EOT robustness with plain-view suppression. We present \method{}, a query-efficient, budget-adaptive black-box attack that couples a lightweight Contextual Thompson-Sampling placer with NES-style pixel updates, growing the patch only when progress stalls. Reporting is anchored by a strict plain-image suppression test; EOT is audited but never used as a substitute for success, and optional appearance/printability weights expose strength–visibility trade-offs. Across YOLOv5, Faster R-CNN, and YOLOS, \method{} achieves strong suppression on CNN-based detectors and substantial suppression on the transformer-based detector, using compact patches and exposing clear query–footprint trade-offs relative to fixed-size and heuristic baselines. A print–capture pilot further shows transfer across unseen physical objects and viewpoints.

11.
medRxiv (Medicine) 2026-06-18

A Brain-Aging Transcriptomic Signature Reclassifies WHO Glioma Grade and Predicts Survival Independently of IDH Status: A Multi-Cohort Study

Background Despite WHO grade and IDH status, significant survival differences remain in diffuse gliomas. We hypothesized that a brain-aging transcriptomic signature, reflecting neuroinflammation, myeloid infiltration, and synaptic loss, would independently predict survival and allow for molecular reclassification. Methods A neurodegeneration score was derived via PCA of brain MRI volumes from 1,057 OASIS-3 subjects and projected onto 888 TCGA-LGG/GBM (discovery) and 693 CGGA gliomas (validation). A 14-gene signature of glial/myeloid (GFAP, AQP4, TYROBP, TREM2, C1QA, CD68, ITGAM) and neuronal (SYP, DLG4, GRIN1, GRIA1, SNAP25, SYN1, RBFOX3) genes were computed. Elastic-net Cox regression identified a 3-gene panel (C1QA, CD68, GRIA1). Kaplan-Meier, multivariate Cox, decision curve, and single-cell RNA-seq analyses were performed. Results High brain-aging scores predicted poorer overall survival (p < 0.0001) and remained an independent prognostic factor after adjusting for WHO grade and IDH status (z = 4.72, p < 0.001); chronological age was non-significant (p = 0.231). In IDH-mutant gliomas, significance was confirmed in both cohorts (TCGA p = 0.027; CGGA p < 0.0001). Bidirectional reclassification showed high-risk Grade 2 tumors with Grade 3-like survival (p = 0.00089), and indolent Grade 3 tumors resembling Grade 2 by Ki-67. Single-cell RNA-seq confirmed macrophage localization of signature genes; DCA demonstrated net benefit over grade alone at 5-30% probability thresholds. Conclusions A brain-aging transcriptomic signature independently predicts glioma survival beyond WHO grade and IDH status, validated in an independent Chinese cohort, with clinical utility for identifying high-risk Grade 2 and sparing over-treatment of indolent Grade 3 tumors.

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

Region-Adaptive Sampling for Diffusion Transformers

Diffusion models (DMs) have become the leading choice for generative tasks across diverse domains. However, their reliance on multiple sequential forward passes significantly limits real-time performance. Previous acceleration methods have primarily focused on reducing the number of sampling steps or reusing intermediate results, failing to leverage variations across spatial regions within the image due to the constraints of convolutional U-Net structures. By harnessing the flexibility of Diffusion Transformers (DiTs) in handling variable number of tokens, we introduce RAS, a novel, training-free sampling strategy that dynamically assigns different sampling ratios to regions within an image based on the focus of the DiT model. Our key observation is that during each sampling step, the model concentrates on semantically meaningful regions, and these areas of focus exhibit strong continuity across consecutive steps. Leveraging this insight, RAS updates only the regions currently in focus, while other regions are updated using cached noise from the previous step. The model's focus is determined based on the output from the preceding step, capitalizing on the temporal consistency we observed. We evaluate RAS on Stable Diffusion 3 and Lumina-Next-T2I, achieving speedups up to 2.36x and 2.51x, respectively, with minimal degradation in generation quality. Additionally, a user study reveals that RAS delivers comparable qualities under human evaluation while achieving a 1.6x speedup. Our approach makes a significant step towards more efficient diffusion transformers, enhancing their potential for real-time applications.

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

Semantic Robustness Certification for Vision-Language Models

Vision-language models (VLMs) are now widely used in downstream tasks. However, real-world applications often expose VLMs to distribution shifts induced by semantic variation (e.g., shape, size, and style). Robustness certification determines if a model's prediction changes when transformations are applied to its input. While most certification frameworks study geometric or pixel-level transformations over inputs, this work proposes a novel framework that enables certifying VLM robustness under semantic-level transformations. Leveraging the open-vocabulary capability of VLMs, we use text prompts as semantic proxies to construct transformations parameterized by an extent that controls the degree of semantic variation. By characterizing the VLM decision boundary in closed form, our framework quantitatively certifies extent intervals for which the predicted class remains unchanged under the semantic transformation. Our framework is the first to certify VLM robustness under semantic-level variations without requiring additional data for each variation, making it practical to apply. Experiments on both synthetic and real-world data show that our framework enables certifying robustness under diverse semantic variations across scenarios.

14.
Nature (Science) 2026-06-17

Mapping the neuronal building blocks of human language with language models

作者:

Humans can convey new and highly diverse information through language. This ability to form and combine words into elaborate phrases and sentences enables us to express inexhaustible meanings and is fundamental to human cognition1–5. However, understanding the microscopic&nbsp;cellular building blocks and cortical landscape that precisely&nbsp;underlie human language has remained a challenge. Here we used wide-scale single-neuronal recordings combined with natural language processing models to identify fine-grained linguistic representations across the human frontotemporal cortex during language production. We find that, whereas certain neurons represented the detailed grammatical relationships between words or their parts of speech, others tracked the sentences’ higher-order syntactic structure, their phrase transitions and sequence. Collectively, these neurons reliably captured the words’ syntactic and semantic properties but also dynamically incorporated their specific sentence contexts, therefore&nbsp;enabling them to encode information combinatorially and at highly granular levels of detail. We show how these cell populations were locally organized and how their microscale representations differed from that of their wider field potential patterns. We also show how these neurons were distributed broadly across the frontotemporal cortex, but how their ability to encode linguistic information was left-lateralized and varied between&nbsp;cortical regions. Together, these findings identify some of the most basic cellular building blocks by which linguistic information is encoded in humans and begin to define the cortical landscape of language at a combined micro (cellular), meso (local population) and macro (regional) scale. Wide-scale recordings reveal neurons in&nbsp;the human brain that encode&nbsp;fundamental components of language such as&nbsp;the grammatical relationships between words, their parts of speech and the&nbsp;higher-order syntactic structure&nbsp;of phrases and sentences.

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

Free Heavy-Tailed Lunch for Muon: A Theoretical Justification of Empirical Success

arXiv:2606.14560v1 Announce Type: cross Abstract: Non-Euclidean optimisation methods with matrix-valued updates, such as Muon and Scion, have recently shown strong empirical performance for training Transformer models, yet their theoretical advantages over Euclidean methods remain poorly understood. We address this gap in the heavy-tailed non-convex regime, where stochastic gradients have bounded $p$-th central moments, $p \in (1,2]$. We show that certain non-Euclidean methods achieve optimal sample complexity under stronger stationarity measures, while Euclidean methods incur additional dimension-dependent costs. As a consequence, for $m \times n$ matrices, Muon finds an $\varepsilon$-stationary point in nuclear norm within $\mathcal{O}\left(\min\{m, n\} \frac{\Delta_1 L}{\varepsilon^2} \left(\frac \sigma \varepsilon \right)^{\frac p {p-1}}\right)$ samples, absorbing heavy-tailed noise without extra dimension dependence, unlike Euclidean methods. We further prove this sample complexity, including its dimension dependence, is optimal for all first-order methods under nuclear-norm stationarity. Experiments on large language models support our theory. Surprisingly, our results suggest that other Schatten geometries beyond the spectral geometry of Muon can perform competitively in certain settings.

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

CCKS: Consensus-based Communication and Knowledge Sharing

arXiv:2606.12281v1 Announce Type: cross Abstract: In Decentralized Training and Decentralized Execution (DTDE) for cooperative Multi-Agent Reinforcement Learning (MARL), action-advising-based knowledge sharing promotes interpretable and scalable cooperation among agents. However, current action advising approaches often adhere too much to the teacher's guidance without evaluating teacher-student compatibility, which causes excessive advising, suboptimal stability, and degraded performance. To overcome these challenges, this paper presents a Consensus-based Communication and Knowledge Sharing (CCKS) framework, which allows agents to adopt recommendations based on consensus-derived constraints and to follow the teacher's instructions more smartly. This mechanism enables agents to balance exploration and learning from experienced teachers, improving overall performance. The key is the consensus model construction, for which we propose to employ contrastive learning to construct consensus models based on local observations in the agents' training phase. In action selection, agents score and choose actions based on consensus and shared knowledge. Designed as a plug-and-play solution, CCKS integrates seamlessly with existing DTDE algorithms. Experiments conducted in the Google Research Football environment and the complex StarCraft II Multi-Agent Challenge demonstrate that the integration with CCKS significantly improves cooperation efficiency, learning speed, and overall performance compared with current DTDE baselines. The code is available at https://github.com/yuanxpy/CCKS.

17.
arXiv (CS.LG) 2026-06-11

REACH: Interpretability-Driven Feature Identification and Architecture Compression for Multi-Channel Vehicular Channel Estimation

arXiv:2606.11857v1 Announce Type: cross Abstract: Multi-channel mixed-SNR training improves out-of-distribution (OOD) generalisation of deep learning channel estimators for IEEE 802.11p vehicular communications, yet the internal mechanism responsible for this remains unexplained. This work presents REACH (Relevance-based Explanation and Architectural Compression for cHannel estimators), a gradient-based interpretability framework that operates at two levels. Input-level attribution identifies a subset of time-frequency features consistently relevant across all evaluated channel conditions, enabling input dimensionality reduction with minimal performance loss. Filter-level attribution reveals a near-universal internal representation, providing a representational account of the observed OOD generalisation. Guided by the resulting filter taxonomy, relevance-guided architecture compression substantially reduces both the number of parameters and the number of floating-point operations (FLOPs) with sub-1 dB normalised mean square error (NMSE) degradation, and OOD generalisation degrades more slowly than within-distribution accuracy under increasing compression.

18.
Science (Express) 2026-04-16

Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) are widespread bacterial anti-phage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6 Å resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.

19.
arXiv (CS.LG) 2026-06-11

Flow Matching with In-Context Priors for Out-of-Distribution Brain Dynamics

arXiv:2606.11833v1 Announce Type: new Abstract: Flow matching and diffusion models enable conditional generation across domains ranging from images to proteins, with recent extensions to out-of-distribution contexts. Yet generative models of neural time series have largely remained restricted to categorical conditioning, precluding compositional and zero-shot generalization. In this work, we propose a per-timestep conditioned diffusion transformer for generating realistic fMRI brain dynamics during unseen cognitive tasks by injecting both compositional language and optional spatial priors in-context. Such zero-shot generation could enable counterfactual neuroscience by supporting in-silico design and evaluation of novel cognitive experiments before empirical validation. Leveraging this model, we evaluate across hundreds of held-out task conditions and characterize predictive performance in relation to the training manifold. From language alone, the model recovers region-specific recruitment across tasks and held-out spatial activation patterns. Spatial priors, when available, complement the text pathway by anchoring generation in regions of task space where language alone degrades, while retaining the compositional structure needed for counterfactual task specification. To our knowledge this is the first generative model of whole-cortex fMRI dynamics for unseen cognitive tasks, advancing counterfactual neuroscience and data-driven experimental design.

20.
medRxiv (Medicine) 2026-06-17

A multistate model of frailty progression after severe infections in adults >=65 years in England: a matched-cohort study

Background Evidence on frailty progression following severe infections is limited. We compared rates of transition to greater frailty or death between adults with and without severe infection in England. Methods We conducted a matched-cohort study among adults aged [&ge;]65 years (1,452,117: median age 76 years, 45% male) in Clinical Practice Research Datalink Aurum (2006-2019). Adults with severe infection (hospitalised primarily due to infection) were matched on calendar time to individuals without severe infection on age, sex, and primary care practice. The admission date was used as index date and same was assigned to matched unexposed adults. We measured frailty using Electronic Frailty Index, a proportion of 36 health deficits in validated categories (Fit 0-0.12, Mild >0.12-0.24, Moderate >0.24-0.36, Severe >0.36). In a time-varying Markov multistate model, we focused on forward transitions from baseline or intermediate frailty states to higher states or death. For each transition, we used Cox regression to estimate cause-specific transition hazard ratios (HR) with 95% confidence intervals (CIs), comparing adults with and without severe infection. We adjusted for baseline frailty score, age, sex, deprivation, harmful alcohol use, smoking, and primary care infection history 5 years before index date. We estimated state occupancy probabilities, and expected length of stay (ELOS) in each state at year five among adults with and without severe infection. We explored effect modification by infection type. Results Across all transitions, severe infection was associated with higher adjusted hazards of transitioning to worsening frailty or death, HR, 95% CI: (fit to: mild[1.56, 1.54-1.58], moderate[2.51, 1.79-3.51], death[4.57, 4.50-4.65]; mild to: moderate[1.52, 1.50-1.53], severe[1.90, 1.43-2.52], death[2.67, 2.64-2.70]; moderate to: severe[1.40, 1.38-1.42], death[1.87, 1.85-1.90]; severe to death[1.48, 1.46-1.50]). Transition hazard ratios were strongest for lower respiratory tract infections, followed by sepsis, urinary tract infections, meningitis/encephalitis, gastroenteritis, and skin and soft tissue infections. At five years, adults with severe infection had higher probabilities of transitioning to greater frailty or death across all transitions and lower ELOS in each frailty state than those without severe infection. Interpretation Severe infections may accelerate frailty deterioration in older age. Prevention through vaccination, early detection, and prompt management may help mitigate this decline.

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

Do We Still Need Humans in the Loop? Comparing Human and LLM Annotation in Active Learning for Hostility Detection

Instruction-tuned LLMs can annotate thousands of instances at low cost. This raises two questions for active learning (AL): can LLM labels replace human labels within the AL loop, and does AL remain necessary when entire corpora can be cheaply labeled? We investigate both on a new dataset of 277,902 German political TikTok comments (25,974 LLM-labeled, 5,000 human-annotated), comparing LLM and human annotation across seven conditions, four encoders, and 10 random seeds. Under a two-question interface that mirrors the human annotation task, LLM annotation at scale outperforms human-supervised classifiers at roughly one-tenth the cost (\$28 for GPT-5.2 Batch API vs. \$316 for Prolific). The advantage holds for both a closed-source (GPT-5.2) and an open-weight (Qwen3.5-122B-10B) LLM, is robust under soft-label evaluation, and is unlocked specifically by the two-question decomposition; a holistic single-prompt baseline only ties with human supervision. AL provides no reliable advantage over random sampling under either LLM annotator. However, error structure varies sharply: only GPT-5.2 under the two-question interface produces classifiers with near-human FP/FN balance, while other LLM variants over-flag border-control and economic competition discourse. We release the dataset and code.

22.
arXiv (CS.CV) 2026-06-18

Would you still call this Dax? Novel Visual References in VLMs and Humans

Vision-language models (VLMs), like human learners, are frequently exposed to new visual concepts, but how they map novel visual references to language after exposure remains largely underexplored, particularly when those references contradict prior knowledge from pre-training. To study this, we present the Novel Visual References Dataset (NVRD): 19,176 images spanning 90 visual concepts across different levels of visual novelty, each with up to 20 increasingly perturbed versions of the original object to probe generalization. Unlike prior work on visual augmentations of familiar concepts, NVRD comprises entirely novel, open-ended stimuli constructed from scratch, mirroring how humans encounter genuinely new concepts. We evaluate 3 open- and 2 closed-source models alongside 2,400 human judgments for direct human-model comparison, and find that (i) models struggle to acquire novel concepts in-context when they contradict prior knowledge, and (ii) while models and humans show correlated sensitivity to visual perturbations, models significantly overgeneralize, extending learned labels to stimuli that humans reject. We contribute NVRD as a corpus and benchmark for research on visual concept learning in both humans and machines.

23.
bioRxiv (Bioinfo) 2026-06-16

RetroMol: Parsing a shared encoding from natural products and their biosynthetic gene clusters

Natural products such as polyketides and nonribosomal peptides (NRPs) are important sources of bioactive compounds, including many antibiotics. Many of them are assembled by modular enzyme complexes and further modified and diversified by tailoring reactions encoded by biosynthetic gene clusters (BGCs). Although natural products and their coding BGCs describe different data modalities of the same biochemical process, a unified language to jointly describe their biochemistry is lacking. Here we introduce a sequence-based representation of the core biosynthesis of modular natural products, which we call primary sequences, that bridges chemical structures and BGCs. We also present RetroMol, an algorithm that parses either natural product structures or their encoding BGCs into their primary sequences of natural product building blocks. RetroMol allows for similarity scoring between natural products and BGCs, enabling the retrieval of compounds, BGCs, and a combination of the two, based on their biosynthetic similarity. This can, for instance, be used to retrieve biosynthetically similar but structurally dissimilar compounds, or link natural products to candidate coding BGCs in large experimental datasets. We demonstrate the latter by rediscovering the nocardichelin B BGC as a proof of principle. We also exemplify the utility of biosynthetic similarity by showing various pairs of biosynthetically similar compounds with low structural similarity. Together, these results establish primary sequences as a shared biosynthetic encoding for natural product comparison and BGC prioritization.

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

Surpassing Scale by Efficiency: A Compact 135M Parameter Foundational LLM Natively Adapted for the Bangla Language

While the NLP landscape is dominated by multi-billion parameter architectures, their deployment in low-resource, non-Latin scripts remains computationally prohibitive for edge configurations, mobile systems, and decentralized local hardware. This paper presents bangla-smollm-135m, a highly compact 135-million parameter decoder-only foundational model engineered explicitly for high-efficiency language modeling in the Bangla script. By leveraging a deterministic intersect-and-append token merging strategy between TituLLMs and SmolLM2-135M, the model overcomes subword script fragmentation without destabilizing early pretrained parameter states. In zero-shot multi-task benchmark evaluations (PIQA_bn, OpenBookQA_bn, CommonsenseQA_bn, and Bangla_MMLU), bangla-smollm-135m matches or outperforms models twice its size (Gemma-3-270m) and achieves parity with models in the 1B parameter tier. The model is available at rnnandi/bangla-smollm-135m

25.
arXiv (CS.AI) 2026-06-11

Improving Generalization and Data Efficiency with Diffusion in Offline Multi-agent RL

arXiv:2307.01472v2 Announce Type: replace Abstract: We present a novel Diffusion Offline Multi-agent Model (DOM2) for offline Multi-Agent Reinforcement Learning (MARL). Different from existing algorithms that rely mainly on conservatism in policy design, DOM2 enhances policy expressiveness and diversity based on diffusion model. Specifically, we incorporate a diffusion model into the policy network and propose a trajectory-based data-reweighting scheme in training. These key ingredients significantly improve algorithm robustness against environment changes and achieve significant improvements in performance, generalization and data-efficiency. Our extensive experimental results demonstrate that DOM2 outperforms existing state-of-the-art methods in all multi-agent particle and multi-agent MuJoCo environments, and generalizes significantly better to shifted environments {(in $28$ out of $30$ settings evaluated)} thanks to its high expressiveness and diversity. Moreover, DOM2 is ultra data efficient and requires no more than $5\%$ data for achieving the same performance compared to existing algorithms (a $20\times$ improvement in data efficiency).