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01.
medRxiv (Medicine) 2026-06-24

Genetically Proxied Interleukin-6 Inhibition and Cancer Risk: A Multi-Ancestry Drug-Target Mendelian Randomization Study of Hepatocellular Carcinoma and Colorectal Cancer

Authors:
Ranjha↗M. M. A↗Munir↗

Background: Interleukin-6 (IL-6) signalling drives chronic inflammation and is therapeutically targeted by tocilizumab, an approved IL-6 receptor inhibitor. Whether genetically proxied lifelong IL-6 inhibition causally influences the risk of hepatocellular carcinoma (HCC) or colorectal cancer (CRC) remains unanswered. Prior single-variant estimates from pooled observational data are methodologically limited and may reflect confounding. Methods: A two-sample drug-target Mendelian randomization (MR) study was conducted. Four independent cis-acting protein quantitative trait loci (pQTL) variants within the IL6 and IL6R gene loci (rs2228145, rs4129267, rs7529229, rs1800795) were selected as genetic instruments , with F-statistics ranging from 32.3 to 120.5, confirming instrument strength. Outcome data were obtained from four independent genome-wide association studies: HCC from BioBank Japan (BBJ; 1,866 cases, 195,745 controls), HCC from FinnGen Release 10 (674 cases, 218,118 controls), CRC from a European meta-analysis (19,948 cases, 12,124 controls), and CRC from BBJ (7,062 cases, 195,745 controls). Causal estimates were derived using inverse variance weighted (IVW) regression as the primary method, with MR-Egger and weighted median analyses as sensitivity methods. Cochran Q statistics assessed heterogeneity and MR-Egger intercept testing assessed directional pleiotropy. Results: Genetically proxied IL-6 inhibition showed no significant causal effect on HCC risk in East Asian populations (IVW odds ratio [OR] 0.997, 95% confidence interval [CI] 0.903 to 1.101, p=0.953) or European populations (IVW OR 0.984, 95% CI 0.802 to 1.208, p=0.880). Similarly, no causal effect was observed on CRC risk in European populations (IVW OR 1.015, 95% CI 0.957 to 1.075, p=0.623) or East Asian populations (IVW OR 0.999, 95% CI 0.948 to 1.052, p=0.971). Sensitivity analyses confirmed the absence of directional pleiotropy and heterogeneity across all four analyses. Leave-one-out analyses demonstrated that no single instrument drove the null findings. Conclusions: Genetically proxied IL-6 receptor inhibition, modelling the therapeutic effect of tocilizumab, showed no causal effect on HCC or CRC risk across four independent cohorts and two ancestries. These findings do not support a role for IL-6 pathway inhibition in the prevention of these cancers and provide reassuring genetic safety evidence regarding cancer risk in patients receiving tocilizumab. Larger HCC-specific GWAS are needed to definitively evaluate modest effects in this cancer type.

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02.
arXiv (CS.CL) 2026-06-18

From Sparse Features to Trustworthy Proxies: Certifying SAE-Based Interpretability

Authors:
Dibyanayan Bandyopadhyay↗Asif Ekbal↗

Sparse autoencoders (SAEs) are increasingly used to extract interpretable features from language models (LMs), yet a central question remains: when can an SAE-based explanation be treated as a faithful view of an underlying frozen LM We study this through a post-hoc generalization framework that certifies the LM via a sparse proxy, obtained by replacing a native hidden activation with its pretrained SAE reconstruction. Our framework derives an upper bound on the base model's expected risk using four measurable quantities: proxy risk, SAE reconstruction gap, concept-pool mismatch, and sparse complexity. We interpret this certificate as an operational criterion for explanatory faithfulness. In particular, a non-vacuous bound indicates that the extracted sparse features retain meaningful predictive information, while small reconstruction and mismatch errors indicate that the proxy remains behaviorally close to the original model. Empirically, we show that the bound becomes non-vacuous on GPT-2 Small, Gemma-2B, and Llama-3-8B at practical sample sizes. A detailed layerwise analysis of Llama-3-8B reveals a strong depth dependence, with later layers becoming much easier to certify, associated with both stronger local fidelity and weaker downstream error amplification. Finally, through feature-shuffling ablations, we show that the decomposition distinguishes genuine semantic alignment from mere statistical sparsity, providing a useful diagnostic for when SAE-based explanations become less reliable.

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03.
arXiv (CS.LG) 2026-06-16

Elastic ODYN: Differentiable Optimization for Infeasible Control and Learning in Robotics

Authors:
Aristotelis Papatheodorou↗Jose Rojas↗Ioannis Havoutis↗Carlos Mastalli↗

arXiv:2606.16564v1 Announce Type: cross Abstract: Robotic systems routinely encounter conflicting objectives, modeling errors, and degenerate contact conditions that render quadratic programs (QPs) infeasible. Yet most optimization solvers and differentiable QP layers assume feasibility, leading to numerical failures, unstable gradients, or solver breakdown when constraints cannot be simultaneously satisfied. We present Elastic ODYN, a primal–dual non-interior-point QP solver that handles infeasibility through smooth squared-$\ell_2$ elastic relaxations. The resulting formulation remains well posed under ill-conditioning and degeneracy, supports warm starting, and converges to closest-to-feasible solutions when no feasible point exists. A lightweight refinement stage recovers physically meaningful dual variables from the elastic solution. Building on this framework, we develop Elastic OdynLayer, a differentiable QP layer with stable gradients under infeasibility, and Elastic OdynSQP, an infeasibility-aware SQP method that resolves inconsistent subproblems and intrinsically infeasible optimal control tasks through selective constraint relaxation. We evaluate the framework on benchmark QPs, singular contact mechanics, differentiable parameter identification, and quadrupedal and humanoid trajectory optimization. Across all settings, Elastic ODYN consistently outperforms state-of-the-art elastic QP solvers in robustness, warm-start performance, and convergence reliability, enabling optimization, simulation, control, and learning beyond the feasibility assumptions of existing methods.

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

Harnessing cortical geometry, wiring, and function as inductive biases for recurrent neural networks

Authors:
Mo Shakiba↗Rana Rokni↗Mohammad Mohammadi↗Nima Dehghani↗

arXiv:2606.14975v1 Announce Type: cross Abstract: How the wiring and functional organization of cortex shape recurrent computation remains a central question in both neuroscience and machine learning. Here, we leverage data released through the Machine Intelligence from Cortical Networks (MICrONS) program–a functional connectomics resource spanning multiple areas of mouse visual cortex, in which dense calcium imaging is co-registered with high-resolution electron microscopy reconstruction from the same animal–to build biologically grounded recurrent neural networks. Using neuronal spatial coordinates, anatomical connectivity, and function-derived relationships from nearly 12,000 coregistered excitatory neurons, we initialize recurrent weights and impose communication-aware spatial constraints during learning. Across three cognitive decision-making tasks, networks constrained by cortical structure and function consistently outperform baseline and partially constrained models. Functional weight initialization provides the largest gain, while real spatial embedding yields robust additional improvements across conditions. These biologically grounded networks also develop low-entropy, modular, and small-world organization, and retain strong performance even when recurrence is restricted to positive weights. Together, our results show that the machinery of cortex–its geometry, wiring, and functional structure–can be harnessed as a powerful inductive basis for building recurrent networks that learn more effectively while converging toward key organizational principles of biological computation.

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

ComputeFHE: A Privacy-Preserving General-Purpose Computation Library

Authors:
Faris Serdar Tasel↗Efe Ciftci↗

Fully Homomorphic Encryption (FHE) enables computations to be performed directly on encrypted data while preserving data confidentiality. However, its practical applications remain limited by high computational costs and development complexity. This paper presents ComputeFHE, an open-source C++ library that facilitates the development of privacy-preserving applications based on the TFHE cryptosystem. The library provides encrypted integer and fixed-point data types together with arithmetic, logical, comparison, conditional, and oblivious array-access operations which allow developers to implement algorithms using a familiar imperative programming paradigm. ComputeFHE supports both conventional TFHE arithmetic based on standard two-input logic gates and an optimized Arithmetic Logic Unit (ALU) architecture utilizing FHE-friendly logic primitives. Experimental results demonstrate significant reductions in the number of required bootstrapping operations, achieving performance improvements of up to 3.9x for selected operations. In addition, the library includes a simulation mode that enables testing, debugging, and complexity analysis without performing actual cryptographic computations while providing circuit complexity and bootstrapping costs. Built on top of OpenFHE, ComputeFHE offers a practical and accessible framework for developing and evaluating privacy-preserving algorithms and applications.

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

Gaussian Spatial Priors for Anatomy-Aware Object Detection in Surgical Videos

Authors:
Yunfan Li↗Artem Shmelev↗Himanshu Gupta↗

Detecting anatomical structures in surgical video is essential for intraoperative safety frameworks such as the Critical View of Myopectineal Orifice (CVMPO) in inguinal hernia repair. While prominent structures like the Cooper's Ligament and Triangle of Doom are reliably detected by standard methods, smaller structures such as the epigastric vessels remain challenging due to their visual ambiguity and intermittent visibility. We observe that the spatial relationship between structures is anatomically constrained, and propose a Gaussian Spatial Prior (GSP) module that encodes this relationship as a compact, parametric bias injected into the self-attention of a DAB-DETR decoder. The prior is computed offline from training annotations as a small set of frozen Gaussian parameters and recomputed at each decoder layer using the iteratively refined reference points. On a dataset of inguinal hernia repair videos with 5-fold cross-validation, GSP improves dependent class detection by $+33.5\%$ ($AP_{50}$) over DAB-DETR and $+53.9\%$ over YOLOv26, while also improving anchor detection by $+6.0\%$. These gains are statistically significant across all folds ($p=0.012$, paired $t-$test).

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

Can In-Context Learning Support Intrinsic Curiosity?

Authors:
Eric Elmoznino↗Sangnie Bhardwaj↗Johannes von Oswald↗Rajai Nasser↗Blaise Ag\"uera y Arcas↗Jo\~ao Sacramento↗Rif A. Saurous↗Guillaume Lajoie↗

arXiv:2606.19476v1 Announce Type: cross Abstract: Effective machine learning depends not only on how we model data, but also on what data we choose to collect. While large sequence models have revolutionized data modeling, the problem of automated data selection, or "intrinsic curiosity", remains a significant challenge. Classic approaches incentivize exploration by rewarding an agent based on its "learning progress", which measures how much a newly acquired observation improves a world model's predictive ability. However, evaluating these rewards traditionally requires expensive inner loops of gradient descent updates within each trajectory, rendering them computationally impractical at scale. In this work, we investigate whether the emergent in-context learning (ICL) capabilities of sequence models can eliminate this bottleneck by serving as immediate, update-free world models. Specifically, we evaluate whether an exploration policy can be trained to maximize learning progress, using solely the prediction errors and counterfactual context manipulations of an in-context learner. We first prove that in general Markov decision processes, this is in fact impossible in an unbiased way: the resulting intrinsic rewards either suffer from nuisance terms that bias their estimation of true learning progress, or they cannot be implemented using an in-context learner's prediction errors. Conversely, we prove a positive result for a broad subclass of non-temporal settings, encompassing active learning and Bayesian Experimental Design: here, ICL-derived rewards successfully bound and asymptotically converge to the true learning progress. We corroborate our theory with controlled experiments across continuous and symbolic environments, demonstrating that our ICL-driven framework successfully trains curious data-collection policies that explore optimally.

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08.
arXiv (CS.AI) 2026-06-19

The Hidden Evolution of Disguised Visual Context inside the VLM

Authors:
Wish Suharitdamrong↗Tony Alex↗Muhammad Awais↗Sara Atito↗

arXiv:2606.20077v1 Announce Type: cross Abstract: Visual tokens enter Large Language Models (LLMs) as raw, foreign signals. How they are transformed into meaningful representations and interact with the language space depends entirely on the integration architecture. Whether by treating visual tokens as in-context prompts within the input sequence or injecting them directly into the LLM's intermediate layers. A controlled comparison and understanding of how these architectural choices affect visual information and its internal transformation to integrate with the LLM remains underexplored. We provide a fair comparison by evaluating in-context and layer-wise injection VLM integration paradigms under identical training conditions across single image, multi-image, and video benchmarks. In doing so, we uncover a hidden evolution where visual tokens enter the LLM as disguised visual context, raw representations lacking linguistic structure, but are progressively reshaped depending on the integration paradigm, each capturing fundamentally different frequency characteristics of the visual signal. We show that this evolution inside the LLM determines what visual features the VLM can utilize effectively, how visual representations align with the language space, and ultimately how each paradigm performs across different tasks. We further demonstrate that attention allocation alone is insufficient, and that performance is driven by the quality of visual representations at each layer.

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

Mask-Morph Graph U-Net: A Generalisable Mesh-Based Surrogate for Crashworthiness Field Prediction under Large Geometric Variation

Authors:
Haoran Li↗Tobias Lehrer↗Yingxue Zhao↗Haosu Zhou↗Philipp Stocker↗Tobias Pfaff↗Marcus Wagner↗Nan Li↗

arXiv:2605.15231v2 Announce Type: replace Abstract: Nonlinear finite element crash simulations are accurate but computationally expensive, limiting their use in iterative design optimisation. Machine-learning surrogate models based on graph neural networks (GNNs) offer a faster alternative. Message-passing GNNs are widely used for mesh simulation, and their shared node and edge update functions are relatively generalisable across varying graph structures. By contrast, non-shareable edge-specific aggregation layers can capture nonlinear relationships more accurately but usually require fixed graph connectivity, which limits generalisability. This paper presents Mask-Morph Graph U-Net (MMGUNet), a practical approach to addressing the limitation of hierarchical Graph U-Net architectures that use edge-specific downsampling and upsampling layers. Fixed coarse graph connectivity is required for edge-specific layers. To retain this while improving spatial correspondence, the proposed method morphs the coarsened graph hierarchy to each input mesh using feature-aligned barycentric parameterisation before constructing cross-graph edges. It further applies node masking during supervised pretraining, followed by parameter-efficient fine-tuning in which high-parameter edge-specific layers are frozen. The proposed approach is evaluated in in-distribution, out-of-distribution, and cross-component transfer settings using mean Euclidean distance and maximum intrusion percentage error. Results show that coarse-graph morphing improves test accuracy relative to a fixed-coarse-graph baseline, while masked supervised pretraining reduces the train-test discrepancy and improves data efficiency during transfer. The proposed model also achieves lower prediction error compared with external baselines. These results demonstrate a practical route toward reusable, data-efficient mesh-based surrogate modelling for crashworthiness design exploration.

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10.
arXiv (CS.CV) 2026-06-15

OmniVideo-100K: A Dataset for Audio-Visual Reasoning through Structured Scripts and Evidence Chains

Authors:
Xinyue Cai↗Chaoyou Fu↗Yi-Fan Zhang↗Ran He↗Caifeng Shan↗

Current automated pipelines for audio-visual Question Answering (QA) generally adopt a ``video-caption-QA'' paradigm. However, these methods typically segment videos into short clips and generate separate descriptions for audio and visual modalities. This decoupled processing severs inherent associations between sounds and their visual sources, while independent clip processing often causes inconsistent descriptions of the same entity across segments. Furthermore, coupling long-text comprehension and QA synthesis into a single step often restricts models to localized events, yielding questions lacking long-term temporal connections and deep cross-modal reasoning. To address these issues, we propose an automated data engine featuring two mechanisms: (1) Entity-Anchored Video Scripting transforms videos into structured scripts, comprising summaries, main entity lists, and segment-wise audio-visual descriptions. The entity list serves as a global prior to ensure cross-segment referential consistency and reconstruct audio-visual associations. (2) Clue-Guided QA Generation prompts models to first mine cross-segment, multimodal clues from the script, and subsequently generate QA pairs based on these high-value clues. Leveraging this pipeline, we construct the instruction-tuning dataset OmniVideo-100K and a human-verified test set, OmniVideo-Test. Fine-tuning VITA-1.5, Qwen2.5-Omni-7B and Qwen3-Omni-30B on OmniVideo-100K yields performance gains of up to 20.59% on OmniVideo-Test, demonstrating strong generalization (up to 12.64% improvements) across established benchmarks like Daily-Omni and JointAVBench.

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

Agentic Framework for Deep Learning workload migration via In-Context Learning

Authors:
Qiyue Liang↗Steven Ingram↗George Vanica↗Andi Gavrilescu↗Newfel Harrat↗Hassan Sipra↗Sethuraman Sankaran↗

arXiv:2606.15994v1 Announce Type: new Abstract: Translating deep learning models from PyTorch's flexible, object-oriented design to JAX's functional, stateless setup is usually a manual and error-prone task. Automated migration is challenging because Large Language Models (LLMs) struggle with strict and dynamic API alignment and are prone to mistakes for exacting operations. We propose a fully autonomous system that combines In-Context Learning (ICL) with oracle-driven self-debugging. First, we curated an ICL context that serves as a strict reference for idiomatic JAX styling and test case generation. Second, instead of depending on the LLM to deduce mathematical outputs, we run the source PyTorch modules to get their actual dynamic tensor states. This creates an unchangeable execution oracle. We then use an autonomous agentic loop to synthesize tests based on the oracle data. The test cases are executed repeatedly, and the traceback is sent back to the LLM for self-correction. Ablations show that combining ICL references with oracle grounding and self-debugging greatly outperforms pure instructional and basic agentic baselines. This improvement does not add an excessive computational overhead. Our lightweight pipeline achieves 91% numerical equivalence (compared to baseline: 9%, instruction + self-debugging: 27%) on neural modules, providing a highly reliable, scalable blueprint for cross-framework migration. This has been validated across several state-of-the-art models including SAM (segment anything), T5, Code Whisper amongst others showing high numerical equivalency. Code: https://github.com/AI-Hypercomputer/accelerator-agents/tree/main/MaxCode

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

Rethinking Text-to-Image as Semantic-Aware Data Augmentation for Indoor Scene Recognition

Authors:
Trong-Vu Hoang↗Quang-Binh Nguyen↗Dinh-Khoi Vo↗Hoai-Danh Vo↗Minh-Triet Tran↗Trung-Nghia Le↗

In the realm of computer vision, indoor image recognition presents challenges due to the intricate interplay of lighting conditions, occlusions, and diverse object arrangements within confined spaces. To address the lacks of training indoor images, we introduce a novel approach leveraging Stable Diffusion (SD) for the generation of synthetic images, which serve as a powerful data augmentation tool. The utilization of SD offers a principled framework for synthesizing diverse and realistic indoor scenes, thereby enriching the training data pool for robust indoor image recognition models. Experimental findings on the MIT Indoor Scene dataset reveal the potential of our proposed approach in enhancing the training of deep models when authentic data is limited. Furthermore, to prevent the misuse of SD synthetic images, we introduce a counter measure based on DIffusion Reconstruction Error (DIRE). The powerful DIRE presentation enables training robust classifiers only using lightweight deep models. Experiments show that our approach can perfectly recognize SD generated images with the accuracy of 100% using MobilenetV3.

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

Recognizing and Reconstructing a Multi-Unit Floor Plan

Authors:
Lukas Kratochvila↗Gijs de Jong↗Monique Arkesteijn↗Simon Bilik↗Tomas Zemcik↗Karel Horak↗Jan S. Rellermeyer↗

Digital twins have a major potential to form a significant part of urban management in emergency planning, as they allow more efficient designing of the escape routes, better orientation in exceptional situations, and faster rescue intervention. Nevertheless, creating the twins still remains a largely manual effort, due to a lack of 3D-representations, which are available only in limited amounts for some new buildings. Thus, in this paper we aim to synthesize 3D information from commonly available 2D architectural floor plans. We propose two novel pixel-wise segmentation methods based on the MDA-Unet and MACU-Net architectures with improved skip connections, an attention mechanism, and a training objective together with a reconstruction part of the pipeline, which vectorizes the segmented plans to create a 3D model. The proposed methods are compared with two other state-of-the-art techniques and several benchmark datasets. On the commonly used CubiCasa benchmark dataset, our methods have achieved the mean F1 score of 0.86 over five examined classes, outperforming the other pixel-wise approaches tested. We have also made our code publicly available to support research in the field.

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

LatticeBridge: Rare-Event Sequential Inference for Faithful Structured Sequence Synthesis

Authors:
Faruk Alpay↗Bugra Kilictas↗

Structured sequence generation often requires a model to satisfy several input-derived constraints in a single output. Standard decoding methods may assign high probability to fluent continuations while placing low mass on continuations that realize all required anchors jointly. We study this regime as a rare-event sequential inference problem. LatticeBridge combines a compact prefix language model, instance-compiled surface automata, and a twisted sequential Monte Carlo (SMC) decoder with resampling, multilevel splitting, and a source-support proposal term derived from instance-provided phrases. The constraint representation is compiled from each input instance and does not rely on manually curated lexical classes. On 2,610 attainable validation tasks spanning CommonGen, E2E NLG, and WikiBio, the particle decoder improves exact anchor satisfaction and mean anchor coverage over greedy, beam-filtered, and best-of-k ancestral baselines under a shared proposal model. Since exact anchor satisfaction alone does not rule out unsupported attribute substitutions, the evaluation reports required-anchor coverage, source coverage, source-intrusion diagnostics, overlap, runtime, and particle statistics jointly. The benchmark characterizes the faithfulness-overlap-latency frontier under a fixed proposal model.

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15.
arXiv (CS.AI) 2026-06-12

Rarity-Gated Context Conditioning for Offline Imitation Learning-Based Maritime Anomaly Detection

Authors:
Yongmin Kim↗ByeongHoon Jeon↗Sungil Kim↗

arXiv:2606.13311v1 Announce Type: cross Abstract: Contextual anomaly detection aims to identify abnormal behavior conditional on context variables, but practical deployments often face highly imbalanced context distributions where rare regimes can be critical information. Under such frequency bias, context-conditioned models can produce unstable decisions and excessive false alarms in rare contexts. We propose Rarity-Gated Feature-wise Linear Modulation (RGFiLM), a rarity-aware conditioning module that combines feature-wise modulation (i.e., context-conditioned scaling and shifting of hidden features) with a gate controlled by a data-driven rarity score. The rarity score is estimated from the empirical distribution of context variables and regulates how strongly context modulates intermediate representations: the gate becomes more decisive under rare contexts while remaining conservative under frequent contexts. We evaluate RGFiLM on maritime trajectory anomaly detection using AIS motion sequences with ERA5 environmental context in an environment-sensitive detour scenario. When instantiated in a sequential anomaly scoring pipeline, RGFiLM achieves the best mean F1–False Positive Rate (FPR) trade-off among the compared context-agnostic and context-conditioned methods. These results suggest that explicitly accounting for context rarity is an effective approach for reducing false alarms in context-sensitive anomaly detection.

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

Categorical Prior Lock-in: Why In-Context Learning Fails for Structured Data

Authors:
Antonio Pelusi↗Stefano Braghin↗Alberto Trombetta↗

arXiv:2606.11961v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly used as conditional generators for structured data, relying on in-context learning (ICL) to adapt to new distributions without parameter updates. We investigate the limits of ICL for structured generation under distribution mismatch, using high-cardinality tabular data as a controlled test case, and identify a structural failure mode we term categorical prior lock-in: the inability of ICL to update the model's prior over token distributions inherited from pre-training. Across two 7B-parameter open-weight models, ICL improves numerical fidelity with additional examples but exhibits a sharp ceiling on categorical distributions, failing to reproduce rare classes entirely. Parameter-efficient fine-tuning (LoRA) overcomes these limitations but introduces measurable memorization risk and, in some cases, destabilizes structured output generation, highlighting a fundamental trade-off between adaptability and privacy.

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17.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

Authors:
Eger↗S. J↗Lopez↗Gomez Navarro↗L. F↗Pena-Tauber↗Cochran↗J. N↗Hiatt↗S. M↗Gelvez↗Garcia-Garcia↗…

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

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18.
Nature (Science) 2026-06-10

Mutation-dependent responses to sleep and exercise in clonal haematopoiesis

Authors:
Teresa Gerhardt↗

Clonal haematopoiesis (CH) activates inflammation and increases the risk of atherosclerosis1,2. Whether lifestyle alters CH clone expansion or the phenotypic programming of CH mutant cells, thereby affecting atherosclerosis, is unknown. Here, in humans and mice and across mutations in Jak2, Tet2, Trp53 and Dnmt3a, we demonstrate mutation-dependent responses to sleep and exercise in CH and show that mutant cells are uniquely sensitive to lifestyle. In two human datasets, moderate-to-vigorous physical activity was associated with lower prevalence of non-DNMT3A-driven CH. In atherogenic mice with Jak2V617F or Tet2 loss of function (LOF), but not Trp53 LOF or Dnmt3aR878H CH, uninterrupted sleep or exercise curtails clone expansion. In CH with the Jak2V617F mutation, sleep and exercise reduces clone expansion by selectively reprogramming mutant, but not cohabitant wild type, haematopoietic progenitor cells towards antiproliferative and metabolically healthy phenotypes by tempering bone marrow macrophage–haematopoietic progenitor cell IL-1β signalling. Sleep or exercise also lessens Jak2V617F-driven, Tet2 LOF-driven and Trp53 LOF-driven, but not Dnmt3aR878H-driven, atherosclerosis by locally reprogramming mutant vascular macrophages, independent of peripheral clone dynamics. In Jak2V617F, but not adjacent wild type, aortic macrophages, uninterrupted sleep blunts CLEC4E-dependent inflammasome activation, consequently diminishing lesions. Exercise, meanwhile, activates PAC1+ neurons in the locus coeruleus, raising the levels of peripheral noradrenaline, which signals through adrenergic receptor β2 (ADRβ2) whose expression is preserved by exercise in Jak2V617F, but not cohabitant wild type, aortic macrophages, selectively repressing their inflammatory programming and atherosclerosis. Our findings establish that healthy lifestyles gene-specifically diminish CH and selectively reprogram mutant haematopoietic progenitor cells and macrophages to maintain cardiovascular health. Sleep and exercise can slow clonal haematopoiesis and limit mutant cell-driven atherosclerosis.

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19.
arXiv (quant-ph) 2026-06-24

Biophysical EPR Using Superconducting Resonators

Authors:
Austin R. Gamble Jarvi↗Hamid R. Mohebbi↗Ishit Raval↗Omari Culzac↗Jack Erickson↗Sameh Hegazy↗Don Carkner↗Andrew Wiles↗David G. Cory↗Troy W. Borneman↗

arXiv:2606.23952v1 Announce Type: new Abstract: We present innovations that enable the use of superconducting resonators for high sensitivity, high bandwidth pulsed electron paramagnetic resonance (EPR) measurements on biologically relevant samples with enhanced stability and throughput. A custom-built X-band pulsed EPR spectrometer with AWG and digital IF capability generated by an FPGA was used to control a novel patterned thin film planar superconducting microstrip resonator capable of generating Rabi fields sufficient to achieve 6 ns pi/2 Gaussian pulses using a 100 W solid-state HPA. The system allows automated sequential calibration, measurement, and analysis of five 3.5 uL samples contained in a sample cartridge. Performance was validated through measurements of double electron-electron resonance (DEER) distances in a variety of spin-labeled protein samples with biologically relevant concentrations, including measurements below 10 uM. The results enable broadening the scope of applications for both superconducting resonators and the use of EPR in biotechnology.

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20.
arXiv (CS.AI) 2026-06-16

StyleShield: Exposing the Fragility of AIGC Detectors through Continuous Controllable Style Transfer

Authors:
Guantian Zheng↗

arXiv:2605.00924v2 Announce Type: replace-cross Abstract: AI-generated content (AIGC) detectors are increasingly deployed in high-stakes settings such as academic integrity screening, yet their reliability rests on a fundamental paradox: as language models are trained on human-written corpora, the statistical boundary between AI and human writing will inevitably dissolve as models improve. Commercial incentives have further distorted this landscape – detection services and "de-AIification" tools often operate within the same supply chain, replacing evaluation of content quality with judgment of content origin. We present StyleShield, the first flow matching framework for conditional text style transfer, operating directly in continuous token embedding space via a DiT backbone with zero-initialized cross-attention adapters conditioned on frozen Qwen-7B representations. At inference, we adapt the SDEdit paradigm from image synthesis to text embeddings, with a single parameter gamma providing smooth continuous control over the evasion-preservation trade-off. On a multi-domain Chinese benchmark, StyleShield achieves 94.6% evasion against the training detector and >=99% against three unseen detectors, maintaining 0.928 semantic similarity. We further introduce RateAudit, a document-level scheduling algorithm that demonstrates detection-rate verdicts can be set to arbitrary values, directly questioning the reliability of score-based evaluation.

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

Task-Adaptive Parameter-Efficient Fine-Tuning for Weather Foundation Models

Authors:
Shilei Cao↗Hehai Lin↗Jiashun Cheng↗Yang Liu↗Guowen Li↗Xuehe Wang↗Juepeng Zheng↗Haoyuan Liang↗Meng Jin↗Chengwei Qin↗Hong Cheng↗Haohuan Fu↗…

arXiv:2509.22020v2 Announce Type: replace Abstract: While recent advances in machine learning have equipped Weather Foundation Models (WFMs) with substantial generalization capabilities across diverse downstream tasks, the escalating computational requirements associated with their expanding scale increasingly hinder practical deployment. Current Parameter-Efficient Fine-Tuning (PEFT) methods, designed for vision or language tasks, fail to address the unique challenges of weather downstream tasks, such as variable heterogeneity, resolution diversity, and spatiotemporal coverage variations, leading to suboptimal performance when applied to WFMs. To bridge this gap, we introduce WeatherPEFT, a novel PEFT framework for WFMs incorporating two synergistic innovations. First, during the forward pass, Task-Adaptive Dynamic Prompting (TADP) dynamically injects the embedding weights within the encoder to the input tokens of the pre-trained backbone via internal and external pattern extraction, enabling context-aware feature recalibration for specific downstream tasks. Furthermore, during backpropagation, Stochastic Fisher-Guided Adaptive Selection (SFAS) not only leverages Fisher information to identify and update the most task-critical parameters, thereby preserving invariant pre-trained knowledge, but also introduces randomness to stabilize the selection. We demonstrate the effectiveness and efficiency of WeatherPEFT on three downstream tasks, where existing PEFT methods show significant gaps versus Full-Tuning, and WeatherPEFT achieves performance parity with Full-Tuning using fewer trainable parameters. The code of this work is available at https://github.com/ShileiCao/WeatherPEFT.

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22.
arXiv (quant-ph) 2026-06-16

Non-Gaussian Phase Transition and Cascade of Instabilities in the Dissipative Quantum Rabi Model

Authors:
Mingyu Kang↗Yikang Zhang↗Kenneth R. Brown↗Thomas Barthel↗

arXiv:2507.07092v3 Announce Type: replace Abstract: The open quantum Rabi model describes a two-level system coupled to a harmonic oscillator. A Gaussian phase transition for the nonequilibrium steady states has been predicted when the bosonic mode is soft and subject to damping. We show that oscillator dephasing is a relevant perturbation, which leads to a non-Gaussian phase transition and an intriguing cascade of instabilities for $k$-th order bosonic operators, as well as a jump in the steady-state qubit polarization. For the soft-mode limit, the equations of motion form a closed hierarchy and spectral properties can be efficiently studied. To this purpose, we establish a fruitful connection to non-Hermitian Hamiltonians. The results for the phase diagram, stability boundaries, and relevant observables are based on mean-field analysis, exact diagonalization, perturbation theory, and Keldysh field theory.

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23.
medRxiv (Medicine) 2026-06-16

Cross-sectional study of the association between depressive symptoms and attentional bias to emotional stimuli in patients with acute stroke: Study protocol

Authors:
Yamashita↗Takizawa↗Koizumi↗Hamaguchi↗

Post-stroke depression affects approximately 30% of patients after stroke and is associated with delayed recovery in activities of daily living, reduced rehabilitation effectiveness, and poorer quality of life. Attentional bias modification may provide a low-burden, nonpharmacological approach for patients in the acute phase of stroke. However, before such an intervention can be implemented in clinical practice, it is necessary to clarify whether attentional bias is present in patients with acute stroke and depressive symptoms, whether cognitive function influences the manifestation of this bias, and which task and stimulus formats are most appropriate for assessment. This multicenter, cross-sectional observational study will enroll patients with acute stroke between 7-30 days after stroke onset. Depressive symptoms will be assessed using the depression subscale of the Hospital Anxiety and Depression Scale. Attentional bias will be measured under four task conditions based on the dot-probe task and the cue-target task, using face and word stimuli. Secondary assessments will include cognitive function, anxiety symptoms, activities of daily living, health-related quality of life, and clinical background variables. The aims of this study are to investigate the association between depressive symptoms and attentional bias in patients with acute stroke, compare attentional bias characteristics across task and stimulus types, and examine the potential influence of cognitive function on this association. The findings are expected to provide an empirical basis for designing future attentional bias modification protocols targeting post-stroke depression in the acute phase. This study has been registered with the UMIN Clinical Trials Registry (UMIN000059166).

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

ParaPairAudioBench: Paralinguistic Pairwise Audio Benchmark for LALM-as-a-Judge

Authors:
Jisu Jeon↗Seungyeon Jwa↗Joosung Lee↗Jinhyeon Kim↗Woojin Chung↗Hwiyeol Jo↗Jeonghoon Kim↗Jonghyun Choi↗Soyoon Kim↗

Large Audio-Language Models (LALMs) have been widely used as judge models for the automatic evaluation of generated speech. However, prior approaches predominantly focus on holistic naturalness, leaving fine-grained paralinguistic distinctions underexplored. We introduce ParaPairAudioBench, a pairwise benchmark of 5,175 audio pairs across five paralinguistic dimensions: Style, Rate, Emphasis, Age, and Gender. Our experiments show that current LALM judges still lag behind human judgments by 32%p on average and exhibit severe calibration failures, particularly in Tie cases where the correct decision is to abstain. To further analyze lexical versus acoustic reliance, the benchmark includes both same-transcript and cross-transcript conditions. ParaPairAudioBench enables multi-dimensional, calibration-aware assessment of the reliability of LALM-as-a-Judge for paralinguistic speech evaluation.

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25.
arXiv (CS.CV) 2026-06-16

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

Authors:
Tianqi Chen↗Jun Hou↗Yinchi Zhou↗James S. Duncan↗Chi Liu↗Bo Zhou↗

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

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