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

VISTA: An End-to-End Benchmark for Visual Spec-to-Web-App Coding Agents

We present VISTA (VIsual Spec-To-App Benchmark), a benchmark for evaluating the end-to-end web-app generation capabilities of LLM-based agents. Unlike prior code generation benchmarks that focus on algorithmic tasks, VISTA targets realistic UI-centric development, where agents must produce functional, visually coherent applications from underspecified inputs. We define five prompt-information conditions that vary along two axes, visual/structural fidelity and stack constraint: (1) text only with free stack choice, (2) text with reference screenshots under three specified stacks, (3) text with reference screenshots under free stack choice, (4) text with screenshots and pruned Figma structure under a single specified stack, and (5) text with screenshots and pruned Figma structure under free stack choice. To enable robust evaluation, each page in the benchmark is manually annotated with interactive UI components and around three visual anchor points, addressing the well-known limitations of script-based testing tools such as Playwright in open-ended code generation settings. Evaluation combines DOM-grounded reference matching, behavior-specific browser tests, and CLIP-based visual similarity, jointly measuring structural alignment, behavioral completeness, and overall visual fidelity. We use VISTA to assess four agent systems drawn from two model families and two harnesses, finding that visual fidelity and functional correctness are partially decoupled across both input conditions and agents, and that agent editing style varies sharply but is largely orthogonal to task quality. VISTA establishes a rigorous and reproducible foundation for advancing agent-based software engineering research.

02.
arXiv (CS.LG) 2026-06-16

Sobolev Approximation by Fixed-Size Neural Networks with Arbitrary Accuracy

arXiv:2606.16975v1 Announce Type: cross Abstract: In this work, we investigate new activation functions for achieving arbitrary-accuracy Sobolev approximation by fixed-size neural networks. We first show that any function in $W^{2,\infty}((a,b)^d)$ can be approximated with arbitrary accuracy, measured in the $W^{1,\infty}$-norm, by a fixed-size neural network using the Elementary Universal Activation Function ($\mathrm{EUAF}$). To extend this result to $W^{s,\infty}((a,b)^d)$ for $s\in\mathbb{N}$, we introduce a smooth activation $\mathrm{DUAF}_{\infty}$ from the family of Differentiable Universal Activation Functions ($\mathrm{DUAF}_n$). We prove that any function in $W^{s,\infty}((a,b)^d)$ can be approximated with arbitrary accuracy in the $W^{s-1,\infty}$-norm by a fixed-size $\mathrm{DUAF}_{\infty}$-activated network. We further construct sigmoidal variants $\widetilde{\mathrm{DUAF}}_n$ and show that, for every $1\leq s\leq n$, fixed-size $\widetilde{\mathrm{DUAF}}_n$-activated networks still approximate any $f\in W^{s,\infty}((a,b)^d)$ with arbitrary accuracy in the $W^{s-1,\infty}$-norm. In all these results, the width and depth bounds are computed explicitly, and the proposed activations are elementary.

03.
arXiv (CS.CL) 2026-06-15

Cross-Dataset Bloom Question Classification: Supervised Models and Prompted LLMs

Automatic Bloom's taxonomy classification of assessment questions can substantially reduce instructor workload, but labeling is subjective and teacher-dependent. Prior machine learning (ML) and deep learning (DL) approaches reported strong within-dataset results, yet were rarely evaluated in cross-dataset settings, leaving real-world generalizability unclear; meanwhile, LLM effectiveness for Bloom question classification has not been systematically studied. We evaluated the cross-dataset generalization of existing ML/DL methods and assessed LLMs with multiple prompting strategies on five datasets; the best prompting strategy combined in-context examples with course-specific action verbs. Supervised ML/DL models degraded substantially on unseen datasets, whereas LLMs were more stable, suggesting a robust alternative across diverse educational contexts. Based on the best prompting strategy, we also presented a lightweight UI that supports instructors in automatically classifying large question banks; a usability study indicated low workload and high usability.

04.
arXiv (CS.CV) 2026-06-19

MeshPad: Interactive Sketch-Conditioned Artist-Reminiscent Mesh Generation and Editing

We introduce MeshPad, a generative approach that creates 3D meshes from sketch inputs. Building on recent advances in artist-reminiscent triangle mesh generation, our approach addresses the need for interactive mesh creation. To this end, we focus on enabling consistent edits by decomposing editing into 'deletion' of regions of a mesh, followed by 'addition' of new mesh geometry. Both operations are invoked by simple user edits of a sketch image, facilitating an iterative content creation process and enabling the construction of complex 3D meshes. Our approach is based on a triangle sequence-based mesh representation, exploiting a large Transformer model for mesh triangle addition and deletion. In order to perform edits interactively, we introduce a vertex-aligned speculative prediction strategy on top of our additive mesh generator. This speculator predicts multiple output tokens corresponding to a vertex, thus significantly reducing the computational cost of inference and accelerating the editing process, making it possible to execute each editing step in only a few seconds. Comprehensive experiments demonstrate that MeshPad outperforms state-of-the-art sketch-conditioned mesh generation methods, achieving more than 22% mesh quality improvement in Chamfer distance, and being preferred by 90% of participants in perceptual evaluations.

05.
arXiv (math.PR) 2026-06-18

On a class of reflected McKean-Vlasov Stochastic Differential Equations with jumps

arXiv:2606.18433v1 Announce Type: new Abstract: This paper investigates a class of reflected McKean-Vlasov Stochastic Differential Equations driven by both Brownian motion and a compensated Poisson random measure. We establish the existence and uniqueness of solutions and provide moments estimates for the state processes.

07.
medRxiv (Medicine) 2026-06-17

Macrophage-targeted glucocorticoid prodrug resolves acute inflammation while preserving HPA axis function: mechanistic, preclinical, and Phase II/III clinical evidence

Glucocorticoids (GCs) remain the fastest-acting anti-inflammatory agents but are constrained by systemic exposure that suppresses the hypothalamic pituitary adrenal (HPA) axis, silences adaptive immunity, and drives chronic toxicities. Chronic inflammatory diseases are sustained by long-lived CD206+ macrophages containing immune-resistant pathogenic material not cleared physiologically. We developed 101-PGC-005 ('005), a macrophage-targeted type 1a dexamethasone prodrug engineered for low-affinity, recycling-compatible uptake via CD206, with intracellular release triggered by acidic endosomes. We evaluated '005 in mechanistic assays, pathogen-diverse preclinical models, three human pharmacokinetic (PK) studies, and an adaptive-design randomized Phase II/III trial in 309 hospitalized patients with moderate COVID-19. In two completed Phase I human studies, a first-in-human dose-escalation and repeated-dose study and a dedicated single/multiple-dose PK and safety study; '005 circulated as intact prodrug with rapid systemic clearance (Tmax ~0.5 h; terminal half-life ~1.9 h), with no measurable free dexamethasone after single dosing and only low, clinically non-significant free dexamethasone after repeated dosing, and intact prodrug recovered unchanged in urine. Morning cortisol and ACTH were preserved after 30 mg once daily for three consecutive days (1.5 times the intended therapeutic dose). A cerebrospinal fluid PK study is evaluating central-compartment penetration. In the Phase II/III trial, powered for non-inferiority, conducted across six sites in India under GCP with Ministry of Health approval and independent DSMB oversight; '005 (20 mg IV daily for 3 days) was superior to dexamethasone (6 mg IV daily for 3 -10 days) on the primary endpoint of time to > a 2-point improvement on the WHO ordinal scale (HR 2.31; 95% CI 1.83-2.93; p < 0.0001; median 3 vs. 4 days). '005 was also superior on viral clearance (HR 1.47; 95% CI 1.17-1.84; p = 0.0001), hospital discharge rate, SpO2; recovery, and fever resolution. Zero patients in the '005 arm received investigator-initiated corticosteroid supplementation despite protocol allowance. All 309 randomized patients completed the study (ITT = per-protocol). Safety profiles were equivalent (TEAEs 54.8% vs 54.5%; p = 0.958), with no Grade 3+ events, SAEs, deaths, or discontinuations in either arm. Mechanistically, '005 delivered dual benefit: acute debulking of inflammatory macrophages and selective depletion of chronically activated pathology-sustaining macrophages, while preserving CXCL10 antiviral signaling and physiologic HPA control. Critically, HPA preservation is not merely a safety feature, it is a core efficacy mechanism: by clearing the pathogenic macrophage burden that was overriding HPA regulation, '005 restores the conditions for endogenous cortisol to resume its pulsatile, demand-responsive anti-inflammatory role across all GR-expressing cells, lymphocytes, endothelial cells, neurons, and newly differentiated macrophages, that '005 itself cannot reach. These findings support regulatory-grade evidence for macrophage-targeted corticosteroid therapy and provide the foundation for further development across acute inflammatory indications (sepsis, viral pneumonia, cytokine-release syndromes) and chronic macrophage-driven diseases (atherosclerosis, metabolic steatohepatitis, neurodegeneration, tumor-associated macrophages).

08.
arXiv (CS.LG) 2026-06-12

Scalable anomaly detection via a univariate Christoffel function

arXiv:2606.12483v1 Announce Type: new Abstract: Anomaly detection plays a critical role in identifying unusual patterns across domains such as fraud detection, network intrusion, and system fault diagnosis. Recently, Christoffel function-based methods, rooted in polynomial optimization, have emerged as promising alternatives to deep learning due to their strong mathematical foundations and computational frugality. However, their practical applicability is hindered by the need to invert a matrix whose size grows exponentially with the data dimension, rendering the method intractable even for moderate-dimensional datasets. This paper addresses the dimensionality limitations of Christoffel function-based anomaly detection while preserving its key theoretical properties, i.e., the on-off support dichotomy behavior and the accurate support shape capture. We introduce UCF, a univariate Christoffel function which is based on the squared distance between the query point and the support points. Extensive experiments on the ADBench benchmark demonstrate that UCF consistently outperforms 14 state-of-the-art baselines in terms of Average Precision. By resolving the scalability bottleneck of the Christoffel Function, this work expands the toolkit of anomaly detection methods with a robust, theoretically grounded, and universally applicable approach.

09.
arXiv (CS.CL) 2026-06-24

The $\mathbf{P}$-Completeness of Inverted Index Traversal: On the Complexity of Evaluating Boolean Query DAGs

作者:

Modern AI agents increasingly rely on search infrastructure to execute complex, neuro-symbolic reasoning workflows. These workflows often compile into deeply nested, non-monotonic Boolean queries over text fields. However, standard query evaluation strategies over inverted indices face severe theoretical limits when handling these structures. Stateful iterator models (Document-at-a-Time) are structurally bounded by $NC^1$ formula evaluation, suffering a worst-case $O(2^{|Q|})$ exponential blowup in query complexity when unrolling re-convergent logic. Conversely, recursive materialization models (Term-at-a-Time) incur an $\Omega(|U|)$ space complexity penalty (the Universal Scan) when evaluating logical negation over the document universe. In this paper, we establish the theoretical boundaries of executing complex logic natively over an inverted index. We formalize a retrieval language ($\mathcal{L}_R$) based on Directed Acyclic Graphs (DAGs) and prove that its evaluation problem is strictly $\mathbf{P$-Complete}. To make evaluation tractable, we introduce \texttt{ComputePN}, a deterministic, sparsity-aware evaluation algorithm. By decoupling logical negation from universe-scale materialization via a novel Positive-Negative dual representation, and utilizing native DAG memoization, \texttt{ComputePN} strictly bounds evaluation time to $O(|Q| \cdot |U_{\mathit{active}}|)$. This approach successfully evaluates $\mathbf{P}$-Complete queries natively over the index, avoiding both the combinatorial tree-expansion bottleneck and the universal scan penalty, laying the formal foundation for computational retrieval.

10.
arXiv (math.PR) 2026-06-18

Kemeny's constant minimization for reversible Markov chains via structure-preserving perturbations

arXiv:2510.24679v4 Announce Type: replace-cross Abstract: Kemeny's constant measures the efficiency of a Markov chain in traversing its states. We investigate whether structure-preserving perturbations to the transition probabilities of a reversible Markov chain can improve its connectivity while maintaining a fixed stationary distribution. Although the minimum achievable value for Kemeny's constant can be estimated, the required perturbations may be infeasible. We reformulate the problem as an optimization task, focusing on solution existence and efficient algorithms, with an emphasis on the problem of minimizing Kemeny's constant under sparsity constraints.

11.
arXiv (CS.CL) 2026-06-18

EARS: Explanatory Abstention for Reliable Sub-Agent Modeling in Large-scale Multi-Agent Systems

In large-scale enterprise settings, centralized multi-agent systems (MAS) are increasingly adopted, in which a coordinator delegates user requests to lightweight, domain-specialized sub-agents. While this architecture improves modularity, scalability, and cost efficiency, its reliability depends not only on accurate routing but also on sub-agents' ability to calibrate their responses to capability constraints. In particular, sub-agents built on smaller fine-tuned models often struggle with such calibration, leading them to over-answer ambiguous, underspecified, misrouted, or unsupported requests and produce hallucinated outputs instead of actionable feedback. To address this challenge, we present EARS (Explanatory Abstention for Reliable Sub-Agent Modeling), a production-oriented framework that reframes sub-agent abstention as an inter-agent communication protocol: a sub-agent does not merely abstain, but exposes an actionable failure state to the coordinator. EARS curates human-agent interaction data using an ensemble of calibrated LLM-as-a-Judge models, producing structured abstention labels and rationales under a taxonomy of sub-agent failure modes. These data are used to fine-tune sub-agents to detect failure conditions and return rationales for coordinator-level clarification, rerouting, or fallback. We evaluate EARS in a large-scale production e-commerce assistant supporting enterprise business intelligence workflows. EARS improves the overall response pass rate from 68.5% to 78.9%, demonstrating that sub-agent-side explanatory abstention improves MAS reliability.

12.
arXiv (CS.CL) 2026-06-24

MorfFlex: Handling Rich Morphology

We present MorfFlex, a morphological dictionary architecture suitable for languages with extensive regularity in both inflection and derivation. As the primary example of MorfFlex in use we introduce MorfFlex CZ, a morphological dictionary of Czech. It is distributed as a simple, unstructured list of triplets, however, its manually maintained, unpublished source files and conversion scripts encode a sophisticated system of inflectional and derivational patterns. These patterns dramatically reduce the otherwise enormous size of the dictionary, which currently contains over 100 million wordforms and more than 1 million lemmas. The MorfFlex CZ dictionary serves as an essential resource for ensuring the consistency of manual morphological annotation in the Prague Dependency Treebanks and underpins state-of-the-art automatic tools such as MorphoDiTa. In this paper, we focus on: (i) presenting an effective method for managing the rich morphological system within the dictionary, and (ii) demonstrating the utility of such a language resource for maintaining annotation consistency in corpora and supporting the development of advanced NLP applications.

13.
arXiv (CS.AI) 2026-06-19

Wisdom of Committee: Diverse Distillation from Large Foundation Models and Domain Experts

arXiv:2402.14035v4 Announce Type: replace-cross Abstract: Knowledge distillation from foundation models to compact domain models is challenging due to substantial gaps in capacity, architecture, and modality. For example, in our experiments, distilling from a 76M-parameter language model to a 2M-parameter recommender closes less than 40% of the performance gap between the undistilled student and the teacher. We show that introducing domain-specific experts – which share the student's architectural characteristics – alongside the foundation model as a diverse teacher committee significantly improves transfer. However, standard multi-teacher methods fail to exploit this diversity: naively combining heterogeneous teachers can degrade performance below single-teacher distillation. To address this, we propose DiverseDistill, an interactive distillation framework that employs a learnable Question-Answer mechanism to generate teacher-conditioned queries and align heterogeneous teacher outputs into the student's representation space. Unlike methods requiring gradient-based co-optimization or architectural modification of teachers, DiverseDistill operates with frozen teachers using only forward-pass inference through their intermediate layers: no parameter updates, no co-training, and no architectural surgery. A dynamic teacher importance mechanism further reduces training cost by filtering low-relevance teachers per sample (e.g., ~30% fewer forward passes with no quality loss for recommendation tasks), while the entire Distillation Module is discarded after training, adding zero inference overhead. Evaluations on recommendation (38x compression) and vision (3.6x compression) tasks demonstrate that DiverseDistill recovers 73-114% of the teacher-student performance gap, consistently outperforming all single- and multi-teacher baselines.

14.
arXiv (CS.CV) 2026-06-24

MambaRaw: Selective State Space Modeling for Efficient 4K Raw Image Reconstruction

In-camera JPEG previews are ubiquitous in raw image formats and provide an sRGB reference at negligible storage cost. Although existing metadata-based reconstruction frameworks can exploit this side information when recovering raw images, their context models often become computationally expensive especially at high resolution, eg, 4K raw image, given that attention mechanisms scale quadratically with feature maps, hindering its practical application. To address these limitations, we propose MambaRaw, a JPEG-conditioned metadata-based raw image reconstruction framework that uses State Space Models (SSMs) to estimate entropy parameters efficiently. Our key contribution comprises a Spatial-Energy Coupled Context Modeling mechanism with two lightweight modules: (1) TileMambaBlock, which performs Mamba-style selective scanning only on information-dense tiles to improve the efficiency; and (2) Energy-Aware Refinement (EAR), an identity-initialized residual module that enhance feature representation to match the long-tail energy distribution of raw signals. Extensive experiments on three camera datasets (Sony, Olympus, Samsung) show consistent improvements over strong metadata-based baselines and set a new state of the art for JPEG-guided raw reconstruction with great efficiency. Notably, at low metadata bitrates, MambaRaw increases PSNR by 1.2–1.4 dB and reduces end-to-end coding latency by about 9%. Code is released at https://github.com/Peizeli1/MambaRaw.

15.
arXiv (quant-ph) 2026-06-12

Theoretical Study for Generating Optical GKP State via a Single-Photon-Added Squeezed Vacuum

arXiv:2606.12467v1 Announce Type: new Abstract: A theoretical framework is developed to analyze the generation of the optical GKP state using a single-photon-added squeezed vacuum. This state, defined by the squeezing parameter $r$, is injected into a 50:50 beam splitter, and the optical GKP state is obtained through conditional measurement at one output port. The single-photon-added squeezed vacuum is especially prominent in this context because it provides a simpler and more experimentally accessible ingredient than Schrodinger cat states, while conditional measurement ensures projection onto a state that closely approximates the finite-energy GKP form. Fidelity is employed to quantify this closeness, and the analysis demonstrates that the scheme achieves a maximum fidelity of 85% at a squeezing level of $3.76 \ dB$. This performance surpasses approaches based on squeezed optical odd Schrodinger cat states, underscoring the single-photon-added squeezed vacuum as a practical and effective pathway toward fault-tolerant photonic quantum computing.

16.
arXiv (quant-ph) 2026-06-15

Stab-QRAM: A Clifford-Only Quantum Oracle for Affine Boolean Data

arXiv:2509.26494v3 Announce Type: replace Abstract: Oracle-based quantum algorithms require coherent evaluation of classical functions on superposed inputs, and in fault-tolerant architectures this cost is dominated by non-Clifford gates: generic lookup constructions incur $T$-counts that grow with the data size. Here we show that affine Boolean functions $f(\mathbf{x})=A\mathbf{x}+\mathbf{b}$ over $\mathbb{F}_2$ – the algebraic core of parity checks, linear feedback shift registers, and cipher linear layers – are exactly the functions admitting computational-basis-preserving Clifford oracles, and we develop this correspondence into Stab-QRAM, a compiler mapping a specification $(A,\mathbf{b})$ to an ancilla-free circuit of CNOT and $X$ gates with zero $T$-count. Via K\"{o}nig's edge-coloring theorem, the compiled schedule provably attains the minimum depth for its gate set. Case studies spanning Simon-type oracles, block-encodings of $X$-type coset operators, and syndrome extraction for CSS codes show one compiler serving the algorithm, primitive, and error-correction layers of the quantum stack.

17.
arXiv (quant-ph) 2026-06-24

Universality beyond the Kibble-Zurek mechanism in the condensation of coherently coupled Bose gases

arXiv:2606.24864v1 Announce Type: cross Abstract: We study the universal spatial statistics of point-like topological defects formed during the nonequilibrium condensation of a coherently coupled Bose gas using the stochastic projected Gross-Pitaevskii equation. The symmetry-breaking transition is driven by a linear quench of the chemical potential, leading to stochastic vortex nucleation in the individual condensate components. When the two components are considered together, these elementary defects may combine across components to emerge as composite topological defects known as full quantum vortices. Beyond the mean defect density predicted by the Kibble-Zurek mechanism (KZM), we investigate the spatial organization of both the elementary and composite defects and show that their positions are well described by a Poisson point process, revealing a universal stochastic geometry. This universality is further described through Voronoi tessellation, whose cell-area statistics follow Poisson-Voronoi predictions. We also introduce the spatial form factor for characterizing the vortex configurations and demonstrate the emergence of a characteristic dip-ramp-plateau structure. Our results establish universal stochastic geometry of topological defects beyond conventional Kibble-Zurek scaling and identify it as a fundamental feature of nonequilibrium condensation in coherently coupled Bose gases.

18.
arXiv (CS.CV) 2026-06-19

DiffMath: Symbol- and Graph-Aware Latent Diffusion Transformer for Handwritten Mathematical Expression Generation

Handwritten Mathematical Expression Generation (HMEG) is challenging due to the complex two-dimensional layouts and long-range structural dependencies of mathematical expressions. Existing methods typically rely on explicit spatial supervision, such as symbol-level bounding boxes, which incurs high annotation costs and limits scalability. In this work, we propose DiffMath, a symbol- and graph-aware latent diffusion framework that leverages the hierarchical structure inherent in LaTeX as a structural prior, eliminating the need for positional supervision. First, we design a Relational Abstract Syntax Tree (RelAST), a generation-oriented representation that distills MathML trees into compact triplet sequences [S, R, D], where each token directly encodes a symbol identity, spatial relation, or nesting depth. Second, we introduce MathVAE, which learns structure-preserving latent representations through symbol-aware and relation-aware perceptual regularization, ensuring that the latent space captures both character semantics and spatial topology. Third, MathDiT performs conditional denoising in this structured latent space, further guided by a global symbol-count prior via Adaptive Layer Normalization (AdaLN) to improve structural coherence. Experiments show that DiffMath produces structurally consistent handwritten expressions, achieves superior performance over existing methods, and improves the accuracy of downstream OCR models through synthetic data augmentation.

19.
arXiv (CS.CV) 2026-06-24

Stochastic Signed Distance Processes

Multi-view surface reconstruction is a core problem in computer vision. One prominent line of work represents the surface implicitly as a signed distance field (SDF), optimizing it based on the photometric loss between rendered and observed pixel colors. These approaches typically employ SDF-based volume rendering to obtain a differentiable relaxation of discontinuous visibility along rays, thereby reducing reliance on silhouette supervision. In this paper, we reformulate SDF-based volume rendering as probabilistic surface rendering, where each pixel color is modeled as a mixture distribution induced by the random first ray-surface intersection. To this end, we introduce Stochastic Signed Distance Processes (SSDP), which model the SDF along each ray as a stochastic process, inducing a first-passage-time distribution for each ray. We then derive the first-passage probability for each sampling interval based on Bayesian filtering, together with its practical approximation for parallel rendering. We further show that NeuS, an existing SDF-based volume rendering method, arises as a special case of our formulation. Experiments on the DTU and MobileBrick datasets demonstrate that our method outperforms baselines in both surface reconstruction and uncertainty quantification, supporting the effectiveness of our first-passage formulation. Our code is available at https://github.com/skmhrk1209/SSDP.

20.
arXiv (CS.CV) 2026-06-25

GroundSet: A Cadastral-Grounded Dataset for Spatial Understanding with Vector Data

Precise spatial understanding in Earth Observation is essential for translating raw aerial imagery into actionable insights for critical applications like urban planning, environmental monitoring and disaster management. However, Multimodal Large Language Models exhibit critical deficiencies in fine-grained spatial understanding within Remote Sensing, primarily due to a reliance on limited or repurposed legacy datasets. To bridge this gap, we introduce a large-scale dataset grounded in verifiable cadastral vector data, comprising 3.8 million annotated objects across 510k high-resolution images with 135 granular semantic categories. We validate this resource through a comprehensive instruction-tuning benchmark spanning seven spatial reasoning tasks. Our evaluation establishes a robust baseline using a standard LLaVA architecture. We show that while current RS-specialized and commercial models (e.g., Gemini) struggle in zero-shot settings, high-fidelity supervision effectively bridges this gap, enabling standard architectures to master fine-grained spatial grounding without complex architectural modifications.

21.
bioRxiv (Bioinfo) 2026-06-14

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

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

22.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

23.
arXiv (CS.CL) 2026-06-15

LLMs Contain Multitudes: How Deployment Context Reshapes Model-Level Preferences and Values

Large language models (LLMs) are increasingly characterised in recent evaluation work as having stable, model-level preference and value systems. However, accompanying robustness checks are limited to incidental prompt perturbations such as syntax variation and option reordering. This leaves open whether the measured properties survive when the surrounding task context changes, as it does in most real deployments. We test this directly across two established pairwise paradigms: ranking country preferences and eliciting utility judgements. In both, we make the deployment context – the high-level task the model is performing while making concrete value-dependent choices – our controlled variable, varied across framings such as writing a Reddit post or a news article. Across five LLMs and over 1.2M pairwise decisions, deployment context produces variation far larger than prompt paraphrasing and temperature controls. In country preference rankings over 15 countries, context induces widespread, statistically significant rank shifts; the aggregate Global North favouritism reported in prior work is itself context-dependent, with each model's bias shifting systematically across contexts. In utility elicitation over 50 outcomes, broad cross-category ordering is preserved, but fine-grained rankings within domains vary substantially, and cardinal exchange rates between outcomes (e.g. how many lives in one region equal one in another) shift by a factor of 2.47 at the median. Reported model-level preferences and utilities are therefore better understood as context-conditioned measurements than fixed model-level properties: safety guarantees obtained under one framing provide limited assurance in another.

24.
medRxiv (Medicine) 2026-06-17

Clinical Study Protocol of the 'Biomarkers of Severity of COVID-19 Patients' (BIOMARCOVID) Project

Introduction The coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems worldwide, in certain areas exceeding hospital capacities and human resources. This has underscored the importance of having better tools to predict the outcome of potentially severe respiratory infections such as SARS-CoV-2. Predicting COVID-19 severity may allow physicians to better manage ICU beds and increase the chances of patient survival through appropriate management. During the toughest months of the pandemic, most physicians tried to identify patients that might develop severe forms based primarily on clinical features on admission (e.g., BMI, age). In this context, significant research has focused on identifying comorbidities, clinical manifestations, and routine blood biomarkers to predict disease severity. However, despite the demonstrated value of untargeted metabolomics in assessing severity, limited data exist on its use for identifying novel metabolite biomarkers that could improve both the sensitivity and specificity of outcome prediction. Our goal is to identify metabolite biomarkers that could enhance the predictive accuracy of standard medical biology data and clinical parameters. Methods and analysis This is a retrospective, observational, monocentric cohort study conducted at the Centre Hospitalier Universitaire Grenoble Alpes (CHUGA). The maximum number of eligible patients admitted for PCR-confirmed COVID-19 between March and December 2020 will be included. Severity outcome is defined using the WHO 10-category ordinal scale (mild: categories 4-5; severe: >5). Blood samples were collected within 48 hours of admission and analyzed for 62 routine blood tests and untargeted multiplatform LC-MS/MS metabolomics across four national platforms. Statistical analysis will include logistic regression with variable selection for the primary aim, and multi-block chemometric integration of clinical, biological, and metabolomics data as a secondary aim. Ethics and dissemination A study steering committee has been formed to ensure the accuracy of the collected data by thoroughly reviewing it prior to the data lock. All aspects of the study comply with ethical standards, including approval by the CHUGA institutional review board and adherence to CNIL Reference Methodology MR004 for the protection of participants' rights, privacy, and confidentiality. This study is registered on the French Health Data Hub (number F20210218154851). Results will be disseminated through peer-reviewed publications, presentations at national and international scientific and clinical conferences, and reports shared with key healthcare system stakeholders.

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

Privacy-Preserving Federated Autoencoder for ECG Anomaly Detection on Edge Devices

arXiv:2606.11556v1 Announce Type: cross Abstract: Continuous electrocardiography (ECG) monitoring could surface rhythm abnormalities before they escalate into cardiovascular events. However, a deployable system must satisfy three requirements simultaneously: legal-grade privacy (GDPR, HIPAA), real-time inference on constrained edge hardware, and detection quality under non-IID cross-hospital data. We design and evaluate an end-to-end federated system addressing all three for unsupervised 12-lead ECG anomaly detection on PTB-XL dataset, combining three autoencoder families (VanillaAE, ConvAE, VAE), Flower-based federated averaging (FedAvg) across ten simulated hospitals, client-side differentially private SGD (DP-SGD) with a Rényi-DP accountant, and 8-bit integer (INT8) post-training quantization with Raspberry Pi 4 benchmarking. Our main contributions are: an empirical characterization of how these mechanisms compose, practical DP-specific recommendations, and technical and security insights for a clinically sensitive setting. Federated learning matches or exceeds the centralized baseline across all architectures (ConvAE federated area under the ROC curve, AUROC, $0.782$), and an $\varepsilon$ sweep identifies $\varepsilon=4$ as the recommended clinical operating point. INT8 quantization roughly halves model size and cuts Pi 4 latency by up to $44%$ with $