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01.
arXiv (CS.CV) 2026-06-16

A Multi-Center Benchmark for Abdominal Disease Diagnosis and Report Generation from Non-Contrast CT

Multiphasic contrast-enhanced CT (CECT) is widely used for abdominal lesion characterization, yet it carries inherent risks of contrast-induced nephropathy, escalates acquisition burden, and heavily contributes to radiologist workload. To address these challenges, we introduce a novel multi-center benchmark for multi-organ abdominal disease diagnosis and automated radiology report generation, which learns to synthesize contrast-enhanced findings from single-phase non-contrast CT (NCCT). To support this, we curated a large-scale dataset of paired NCCT-CECT studies and their corresponding contrast-enhanced radiology reports from two centers, partitioned into internal sets and an external validation cohort. Under a unified evaluation protocol, we benchmarked five contemporary deep learning architectures encompassing chest-specific, abdomen-specific, and general-purpose multimodal domains. Extensive experiments demonstrate that NCCT retains diagnostic signals, achieving an average multi-organ AUC of 69.1% on the internal cohort and 63.1% on the external cohort, respectively. By releasing this dataset and standardized benchmark publicly, this study aims to catalyze future research into safer, resource-efficient, and globally accessible contrast-free abdominal imaging workflows. Code is available at: https://github.com/xmed-lab/TriALS-Report.

02.
arXiv (CS.CL) 2026-06-24

Societal Alignment Frameworks Can Improve LLM Alignment

Recent progress in large language models (LLMs) has focused on producing responses that meet human expectations and align with shared values - a process coined alignment. However, aligning LLMs remains challenging due to the inherent disconnect between the complexity of human values and the narrow nature of the technological approaches designed to address them. Current alignment methods often lead to misspecified objectives, reflecting the broader issue of incomplete contracts, the impracticality of specifying a contract between a model developer, and the model that accounts for every scenario in LLM alignment. In this paper, we argue that improving LLM alignment requires incorporating insights from societal alignment frameworks, including social, economic, and contractual alignment, and discuss potential solutions drawn from these domains. Given the role of uncertainty within societal alignment frameworks, we then investigate how it manifests in LLM alignment. We end our discussion by offering an alternative view on LLM alignment, framing the underspecified nature of its objectives as an opportunity rather than perfect their specification. Beyond technical improvements in LLM alignment, we discuss the need for participatory alignment interface designs.

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

Half a Link can Be Enough to Predict a Whole Link: Understanding Generalization in Knowledge Graph Foundation Models

arXiv:2606.18001v1 Announce Type: new Abstract: Knowledge graph (KG) foundation models (KGFMs) are zero-shot generalizers: trained once, they can predict links on unseen graphs without retraining. However, understanding when and how they can robustly generalize across KGs is still an open question. In this paper, we shed some light on their generalization mechanisms highlighting how their performance on unseen KGs is not uniform when it comes to partially seen links, which we call half-links. In fact, we show that to predict a test triple $(h,r,t)$ it might suffice in practice to have observed the half-link $(h,r)$ or $(r,t)$ in the inference graph. This yields a taxonomy of four scenarios when combinations of these half-links are observed or not. In a rigorous stratified analysis over these scenarios, we reveal that SoTA KGFMs use seen half links for predictions, while unseen half-links pose different challenges. As such, our finer-grained taxonomy can be a diagnostic protocol for robust KGFM generalization and highlights where novel KGFMs can improve.

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

SpatialAvatar-0: High-Quality 4D Head Avatar with Multi-Stage Reconstruction

High-quality 4D head avatars from one or a few source portraits are central to telepresence, AR/VR, and digital-human interaction. 3D Gaussian Splatting (3DGS) has emerged as the dominant representation, with two complementary regimes (generalizable feed-forward predictors and per-subject refiners) maturing in parallel. However, existing feed-forward predictors are trained on a single dataset family with a hard-coded source count, inheriting the corresponding domain bias. Per-subject refiners require 300K–600K iterations and rely on adaptive densification that destroys upstream Gaussian layouts, preventing the two regimes from sharing a representation end-to-end. To bridge both regimes we propose SpatialAvatar-0 on a shared FLAME-mesh-bound Gaussian representation: a feed-forward generator with a parameter-free K-source mean-pool and a monocular-temporal to multi-view-spatial two-phase schedule that anchors against identity-prior collapse onto the smaller multi-view set. We further introduce a 10K-iter layout-preserving per-subject refinement loop that freezes the FLAME-binding and Gaussian count and replaces densification with a three-component anti-spike regularization. On VFHQ/HDTF cross-domain zero-shot we surpass the in-domain leader GAGAvatar by +1.5 dB PSNR despite never training on either test domain, and on the SplattingAvatar monocular benchmark we lead every reported metric, surpassing the 300K-iter GeoAvatar by +1.3 dB PSNR at up to 60x shorter per-subject schedule than common SOTA baselines. Website: https://spatialwalk.github.io/SpatialAvatar-0.

05.
arXiv (CS.AI) 2026-06-16

Emergent Strategic Reasoning Risks in AI: A Taxonomy-Driven Evaluation Framework

arXiv:2604.22119v2 Announce Type: replace Abstract: As reasoning capacity and deployment scope grow in tandem, large language models (LLMs) gain the capacity to engage in behaviors that serve their own objectives, a class of risks we term Emergent Strategic Reasoning Risks (ESRRs). These include, but are not limited to, deception (intentionally misleading users or evaluators), evaluation gaming (strategically manipulating performance during safety testing), and reward hacking (exploiting misspecified objectives). Systematically understanding and benchmarking these risks remains an open challenge. To address this gap, we introduce ESRRSim, a taxonomy-driven agentic framework for automated behavioral risk evaluation. We construct an extensible risk taxonomy of 7 categories, which is decomposed into 20 subcategories. ESRRSim generates evaluation scenarios designed to elicit faithful reasoning, paired with dual rubrics assessing both model responses and reasoning traces, in a judge-agnostic and scalable architecture. Evaluation across 11 reasoning LLMs reveals substantial variation in risk profiles (detection rates ranging 14.45%-72.72%), with dramatic generational improvements suggesting models may increasingly recognize and adapt to evaluation contexts.

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

HeatKV: Head-tuned KV-cache Compression for Visual Autoregressive Modeling

Visual Autoregressive (VAR) models have recently demonstrated impressive image generation quality while maintaining low latency. However, they suffer from severe KV-cache memory constraints, often requiring gigabytes of memory per generated image. We introduce HeatKV, a novel compression method that adapts cache allocation in each head based on its attention to previously generated scales. Using a small offline calibration set, the attention heads are ranked according to their attention scores over prior scales. Based on this ranking, we construct a static pruning schedule tailored to a given memory budget. Applied to the Infinity-2B model, HeatKV achieves $2 \times$ higher compression ratio in memory allocation for KV cache compared to existing methods, while maintaining similar or better image fidelity, prompt alignment and human perception score. Our method achieves a new state-of-the-art (SOTA) for VAR model KV-cache compression, showcasing the effectiveness of fine-grained, head-specific cache allocation. Code and calibration script available at https://github.com/arm-research/heatkv.

07.
arXiv (CS.CL) 2026-06-16

GePBench: Evaluating Fundamental Geometric Perception for Multimodal Large Language Models

Geometric shapes play important roles in both physical world and human cognition. While multimodal large language models (MLLMs) have made significant advancements in visual understanding, their abilities to recognize geometric shapes and their spatial relationships, which we term geometric perception, are not explicitly and systematically explored. To address this gap, we introduce GePBench, a novel benchmark specifically designed to assess the geometric perception capabilities of MLLMs. Our extensive evaluations reveal that even the current state-of-the-art MLLMs exhibit significant deficiencies in geometric perception tasks. Furthermore, we show that models trained with GePBench data demonstrate considerable improvements on a wide range of downstream tasks, highlighting the critical role of geometric perception in enabling advanced multimodal applications. Our code and datasets are available at \href{https://github.com/Changhao-Xiang/GePBench}{https://github.com/Changhao-Xiang/GePBench}.

08.
arXiv (CS.AI) 2026-06-24

The Measurable Majority

arXiv:2606.23853v1 Announce Type: cross Abstract: This paper studies strict majority reasoning in finite electorates using so-called $social decision frames$: finite sets of voters equipped with distinguished families of coalitions interpreted as those voting blocs evaluated to form a strict majority. A coherence criterion for qualitative majority judgments is identified and shown to give an exact characterization for representability of strict majorities by finitely additive measures. In addition, a minimal natural logic for reasoning about strict majorities is shown to be sound and complete. These developments motivate examination of associated combinatorial questions concerning incoherence in finite families of sets; partial results and a conjecture are given. Finally, the results of this paper are applied to correct a classical representation theorem for weak qualitative probability structures due to Patrick Suppes and to establish a May-type characterization for ordinary strict majority rule for social decision frames.

09.
arXiv (CS.AI) 2026-06-17

Discrete Autoregressive Transformer for Generative Mechanism Synthesis

arXiv:2606.17409v1 Announce Type: cross Abstract: Planar path synthesis requires mechanisms whose coupler curves match a prescribed trajectory; the mapping from curve to linkage is inherently one-to-many across four-, six-, and eight-bar topologies. We address this design problem with simulation-grounded evaluation on a curated corpus of over one million mechanisms, reporting Chamfer distance and dynamic time warping after forward kinematics and geometric alignment. We formulate synthesis as conditional autoregressive sequence modeling: joint coordinates are uniformly quantized to tokens and generated by a decoder-only transformer with a variational-autoencoder (VAE) latent of the target curve and an explicit mechanism-type token. Training combines token cross-entropy with a Gaussian-smoothed bin auxiliary loss that respects ordinal structure among bins. At inference, a bounded latent-noise schedule decodes all mechanism types at each noise level; we retain the top five candidates by geometric error, yielding diverse accurate families without dataset lookup. On held-out tests, aggregate mean Chamfer distance is $0.0132$ and mean dynamic time warping is $0.153$; a latent $k$-nearest-neighbor baseline that conditions on training-set neighbor latents in VAE space achieves matched-topology mean Chamfer distance $0.0071$ and mean dynamic time warping $0.117$ using the same decoder.

10.
arXiv (CS.CL) 2026-06-16

Adapting Reinforcement Learning with Chain-of-Thought Supervision for Explainable Detection of Hateful and Propagandistic Memes

Hateful and propagandistic memes exploit the interplay between images and text to convey harmful intent that neither modality reveals alone. Although thinking-based multimodal large language models (MLLMs) have advanced vision-language understanding, their application to meme content moderation remains underexplored. We propose a reinforcement learning-based post-training method that improves classification performance and reference-based explanation quality in thinking-based MLLMs via task-specific rewards and Group Relative Policy Optimization (GRPO). Concretely, we (i) conduct a systematic empirical study of off-the-shelf MLLMs for hateful and propagandistic meme understanding across English and Arabic benchmarks, (ii) extend existing meme datasets with weakly supervised chain-of-thought (CoT) rationales via distillation and multi-LLM fine-grained propaganda annotations, (iii) introduce a GRPO-based objective with thinking-length regularization that jointly optimizes classification accuracy and explanation quality, and (iv) investigate self-supervised GRPO on unlabeled memes using consensus-based pseudo-labels. Experiments on the Hateful Memes and ArMeme benchmarks show that our approach improves over previously reported results on FHM accuracy (up to +2.1%, from 79.9% to 82.0%) and on ArMeme macro-F1 (up to +7.6 points, from 0.536 to 0.612 with explanations; +6.1 compared to the original ArMeme benchmark), while also generating natural-language explanations. On ArMeme, sequence-classification baselines remain stronger in terms of raw accuracy, whereas our approach provides more balanced per-class performance along with explanations. We publicly release our code, data extensions, and evaluation resources.

11.
medRxiv (Medicine) 2026-06-19

Reassessing Instrument Strength in Two-Sample Mendelian Randomization Analysis

Mendelian randomization (MR) analysis is widely used to estimate causal relationships between risk factors and outcomes of interest. Two-sample MR approaches have gained increasing attention in genetic epidemiology due to the growing availability of Genome-Wide Association Study (GWAS) summary statistics from public databases. A critical step in two-sample MR is the selection of genetic variants as instrumental variables (IVs). Although genome-wide significant variants are typically preferred, the inclusion of variants with weaker association p-values is considered, as they may potentially improve power through an increased instrument number of instruments, while they may introduce weak instrument bias and attenuate effect estimates towards the null. Our simulation results show that even modest levels of pleiotropy substantially increase the variability of causal effect estimates, while the inclusion of weak IVs does not substantially affect the direction and variability of causal effect estimates in most cases. In real data analyses, we used two released versions of FinnGen GWAS summary statistics with different sample sizes as exposure GWASs to assess the influence of weak IVs. Here, the inclusion of IVs with higher exposure-association p-values resulted in weakened estimated effect sizes, particularly when the exposure GWAS sample size was small. These findings suggest that incorporating weak IVs is reasonable when the exposure GWAS sample size is large, but it poses a risk of falsely concluding null associations when the exposure GWAS sample size is small.

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

scLLM-DSC: LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering for Single-Cell RNA Sequencing

arXiv:2606.13007v1 Announce Type: cross Abstract: Clustering is fundamental to scRNA-seq analysis, serving as a cornerstone for identifying cell populations and resolving tissue heterogeneity. However, existing methods focus on mining numerical statistical patterns, suffering from semantic agnosticism by neglecting the intrinsic biological functions encoded by genes. While Large Language Models (LLMs) offer promising semantic capabilities, their direct adaptation to cell clustering is hindered by the structural mismatch between generative pre-training objectives and discriminative downstream tasks. To bridge this gap, we propose scLLM-DSC, a novel LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering framework. Diverging from data-driven paradigms, scLLM-DSC establishes a semantically-grounded representation by synergizing two views: a Knowledge-Driven Semantic View derived from NCBI gene priors and contextualized Cell2Sentence embeddings, and a Structure-Aware Topological View extracted via a graph-guided encoder. Crucially, we introduce a cross-modal contrastive alignment mechanism to enforce consistency between biological semantics and transcriptomic features within a unified latent space. Extensive benchmarks demonstrate that scLLM-DSC significantly outperforms eleven state-of-the-art baselines in clustering accuracy.

13.
Nature (Science) 2026-06-24

Genetic technologies to enhance crop nutritional value under climate change

At present, more than 700 million people live with caloric hunger, and more than two billion suffer from micronutrient deficiencies, known as ‘hidden hunger’. From an agricultural viewpoint, three major objectives need to be worked towards simultaneously to achieve zero hunger (the United Nations Sustainable Development Goal 2): (1) enhanced yield; (2) higher vitamin and mineral density to sustain recommended daily intake (multi-biofortification); and (3) enhanced climate-change resilience. Although the Green Revolution increased global calorie production, it exacerbated hidden hunger by prioritizing high yield over nutritional quality. Stress from global climate change has been shown to reduce the densities of several micronutrients. CRISPR–Cas, which allows genome editing with extremely high precision, has emerged as a groundbreaking breeding technology that has already been adopted by many countries. Here we examine how CRISPR–Cas-based approaches could be used to achieve biofortification targets by enhancing micronutrient densities to the levels necessary to alleviate dietary vitamin and mineral deficiencies. Given the limited time frame available to achieve zero hunger, we argue that CRISPR–Cas technologies should be combined with metabolic engineering based on transformation and other technologies. We also consider untapped resources beyond metabolic pathways and current CRISPR–Cas methodologies to address one of the most important societal issues of the twenty-first century. This Review reflects on the joint power of genetic technologies, including untapped CRISPR–Cas techniques to combat hidden hunger and improve crop resilience, and argues in favour of their combined use to overcome these societal challenges.

14.
arXiv (CS.CV) 2026-06-18

Native Active Perception as Reasoning for Omni-Modal Understanding

Passive models for long video understanding typically rely on a "watch-it-all" paradigm, processing frames uniformly regardless of query difficulty, causing computational cost to grow with video duration. Although interactive frameworks have emerged, they often rely on global pre-scanning, and their context cost still scales with video length. We propose OmniAgent, the first native omni-modal agent that formulates video understanding as a POMDP-based iterative Observation-Thought-Action cycle. OmniAgent executes on-demand actions to selectively distill audio-visual cues into a persistent textual memory, effectively decoupling reasoning complexity from raw video duration. To operationalize this, we introduce (1) Agentic Supervised Fine-Tuning to bootstrap native active perception via best-of-N trajectory synthesis with dual-stage quality control, and (2) Agentic Reinforcement Learning with TAURA (Turn-aware Adaptive Uncertainty Rescaled Advantage), which leverages turn-level entropy to steer credit assignment toward pivotal discovery turns. Crucially, OmniAgent exhibits positive test-time scaling, where performance improves as the number of reasoning turns increases, validating the efficacy of active perception. Empirical results across ten benchmarks (e.g., VideoMME, LVBench) demonstrate that OmniAgent achieves state-of-the-art performance among open-source models. Notably, on LVBench, our 7B agent outperforms the 10$\times$ larger Qwen2.5-VL-72B (50.5% vs. 47.3%).

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

Direct Fisher Score Estimation for Likelihood Maximization

arXiv:2506.06542v2 Announce Type: replace-cross Abstract: We study the problem of likelihood maximization when the likelihood function is intractable but model simulations are readily available. We propose a sequential, gradient-based optimization method that directly models the Fisher score based on a local score matching technique which uses simulations from a localized region around each parameter iterate. By employing a linear parameterization to the surrogate score model, our technique admits a closed-form, least-squares solution. This approach yields a fast, flexible, and efficient approximation to the Fisher score, effectively smoothing the likelihood objective and mitigating the challenges posed by complex likelihood landscapes. We provide theoretical guarantees for our score estimator, including bounds on the bias introduced by the smoothing. Empirical results on a range of synthetic and real-world problems demonstrate the superior performance of our method compared to existing benchmarks.

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

Real vs. Complex Spectral Bases for Neural Operators: The Role of Green's Function Alignment

arXiv:2606.24851v1 Announce Type: new Abstract: Fourier Neural Operators (FNO) learn solution operators of partial differential equations by parameterizing global convolutions in the complex Fourier domain. For real-valued PDE solutions, the complex FFT carries representational redundancy through conjugate symmetry. We introduce the Hartley Neural Operator (HNO), the exact real-valued mirror of FNO: it replaces the FFT with the purely real Discrete Hartley Transform and learns a single real multiplier per retained spectral mode, with no complex arithmetic. Because the real Hartley spectrum is not halved by conjugate symmetry, HNO retains twice as many frequency corners as FNO but one real weight where FNO carries a complex pair, so the two operators are iso-parametric at equal width and differ only in spectral basis. Our central thesis is that the best basis is a property of the operator. Self-adjoint elliptic operators (Poisson, biharmonic) have real, symmetric Green's functions that the real Hartley multiplier diagonalizes exactly, and HNO is favored there. Time-dependent operators carry phase, from oscillation in the wave equation to transport in advection, Burgers, and Navier-Stokes, which a real diagonal multiplier cannot represent, so FNO is favored there, and increasingly so with the operator's phase content, leaving the phaseless heat equation as the borderline case. Training both operators identically and benchmarking across PDE classes, initial-condition families, and boundary conditions, we find an elliptic-versus-time-dependent split that is monotone in operator phase content and matches the Green's-function theory we develop. Rather than a universal winner, our findings give a predictive rule: match the spectral basis to the symmetry of the solution operator.

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

LapidaryEngine: Fully Conversational Crystal Generation

arXiv:2606.14215v1 Announce Type: new Abstract: The emergence of Large Language Models (LLMs) has inspired the vision of generating bespoke crystal materials directly from natural-language instructions, enabling users to design materials through intuitive, conversational interaction. Existing text-to-crystal generative models represent important early steps toward this goal, but they suffer from two critical limitations: (i) restricted input formats that require highly structured descriptions (e.g., chemical formulas), and (ii) one-directional generation, where models can map text to crystal but cannot perform the inverse. These limitations prevent fully conversational workflows and hinder alignment with users' inherently ambiguous and evolving desiderata. We address these challenges with LapidaryEngine, the first model to support fully conversational crystal generation. LapidaryEngine accepts free-form natural-language requests and performs iterative refinement and editing in a dialogue-like manner. The key innovation is a pivot representation, a third, intermediate form that enables bidirectional translation between text and crystal structures despite the absence of direct paired datasets. Leveraging this pivot allows robust interpretation of user feedback and precise structural control. We demonstrate LapidaryEngine across diverse tasks, including insulator discovery, stability optimization, compositional modification, and structural editing, showcasing its ability to align generated materials with user intent in an interactive manner.

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

HilDA: Hierarchical Distillation with Diffusion for Advancing Self-Supervised LiDAR Pre-trainin

arXiv:2606.20189v1 Announce Type: cross Abstract: Leveraging Vision Foundation Models (VFMs) for camera-to-LiDAR knowledge distillation offers a promising solution to the scarcity of annotated data needed to represent the immense geometric and kinematic diversity of real-world autonomous driving (AD). However, current approaches typically treat VFMs as black-box teachers, relying exclusively on frame-wise feature similarity. Consequently, they do not fully exploit the teacher's layer-wise semantic structure and global context, as well as the rich spatiotemporal information inherent in LiDAR sequences. We propose HilDA, a self-supervised pretraining framework for LiDAR backbones that better captures the semantic what and geometric where needed for driving tasks. HilDA combines hierarchical distillation comprising multi-layer distillation for progressive semantic alignment and global context distillation for scene-level semantics, with a temporal occupancy diffusion objective promoting spatiotemporal consistency. Models pre-trained with HilDA achieve state-of-the-art results on cross-modal distillation benchmarks and outperform models trained via prior distillation approaches on 3D object detection, scene flow, and semantic occupancy prediction. Code available at: https://maxiuw.github.io/hilda.

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

RQUL-UIE: Revitalizing Quality-Unstable Labels for Underwater Image Enhancement via In-Dataset Self-Supervision

Underwater Image Enhancement (UIE) is essential for mitigating degradations caused by water medium. Although learning-based methods have advanced significantly, most rely on paired datasets with unstable label quality, which bottlenecks model performance. This paper proposes a diffusion-based, in-dataset self-supervised learning strategy designed to exploit the quality distribution of training labels. Specifically, we evaluate label quality via semantic perception embeddings from a pre-trained diffusion model in a training-free manner. These quality scores are subsequently quantized into noise-level indices, guiding a multi-step denoising process for level-wise supervision. This mechanism prevents low-quality labels from degrading the model while maximizing their utility during training. Furthermore, a Fourier-based refinement network is incorporated to explicitly reconstruct high-frequency components. Extensive evaluations demonstrate that our method consistently outperforms SOTA approaches in restoration quality. The code and pre-trained model will be available once accepted in link.

20.
arXiv (quant-ph) 2026-06-17

Universal Design and Physical Applications of Non-Uniform Cellular Automata on Translationally Invariant Lattices

arXiv:2605.13379v2 Announce Type: replace Abstract: Motivated by recent theoretical and experimental advances, hyperbolic lattices have emerged as a paradigmatic setting in which geometry becomes an active organizing principle of quantum systems. Their negative curvature, exponential volume growth, and non-Abelian translation symmetry make them fundamentally distinct from Euclidean lattices and give rise to rich geometry-dependent physics, but also hinder the direct application of well-established analytical and computational approaches originally developed for physical systems defined on Euclidean lattices. To establish a unified framework for geometry-dependent physics on Euclidean and hyperbolic lattices, we develop higher-order non-uniform cellular automata (NUCA) as a local-to-global construction for translationally invariant regular lattices. This construction derives geometry-dependent update rules through a lattice-deforming procedure that embeds hyperbolic lattices into a Euclidean square lattice, thereby encoding hyperbolic geometry while preserving physical locality. It thus provides a systematic route toward quantum and classical physics on hyperbolic lattices. We demonstrate the framework in three applications ranging from quantum many-body physics to non-equilibrium statistical physics. First, on the hyperbolic $\{5,4\}$ lattice, a linear NUCA generates exactly solvable subsystem symmetry-protected topological (SSPT) models and spontaneous subsystem symmetry-breaking models. Second, as a quantum generalization, we construct non-uniform Clifford quantum cellular automata (CQCA) for the hyperbolic cluster state. Third, we formulate a probabilistic NUCA for directed percolation (DP) on the hyperbolic lattice.

21.
medRxiv (Medicine) 2026-06-22

Assessment of adaptive functioning in Angelman syndrome using the Vineland Adaptive Behavior Scales, Third Edition

Purpose: This study examined longitudinal trajectories of adaptive functioning in 331 individuals with Angelman syndrome (AS) using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) and examined differences by molecular subtype. Methods: A total of 331 individuals (156 females, 47%) with genetically confirmed AS (ages 6 months to 52 years) were assessed between 2018 and 2025, including 207 with a deletion subtype, 63 with uniparental disomy or imprinting defect, and 61 with a UBE3A point mutation. Growth scale values were analyzed using linear mixed-effects models with log2-transformed age. Results: Individuals with deletion subtypes demonstrated significantly lower adaptive functioning across domains compared to those with non-deletion subtypes. Adaptive skills across all Vineland-3 subdomains increased nonlinearly with age, showing faster growth early in life that slowed over time, with largely parallel trajectories across subtypes. Conclusion: Individuals with AS demonstrate slow but steady growth in adaptive functioning that continues into adulthood, with progress varying by molecular subtype. These findings provide updated natural history benchmarks and demonstrate the utility of the Vineland-3 for clinical trials.

22.
bioRxiv (Bioinfo) 2026-06-17

An Integrated Framework for Transcriptomic Characterization and Lorentzian Hyperbolic Visualization of a High-Risk Topological Branch in Alzheimer's Disease

Alzheimer's disease (AD) is a highly heterogeneous brain disorder in which molecular alterations vary across brain regions, disease stages, and patient subgroups. This study introduces an integrated analytical framework for characterizing transcriptomic variation associated with a high-risk topological branch, which was identified based on Lorentz distance in postmortem Brodmann area 36 samples from the Mount Sinai Brain Bank cohort, where over 70% of samples were in Braak stages V-VI. The framework integrates weighted gene co-expression network analysis, repeated stability-based differential expression analysis, network-level gene filtering, Gene Ontology enrichment, and nested stratified cross-validation to evaluate whether topological branch-associated genes capture biologically meaningful signals and carry predictive information for high-Braak group status. The identified gene sets were functionally enriched for neuronal development, neuron projection organization, synaptic signaling, vesicle fusion, and regulated synaptic release, suggesting that the high-risk topological branch reflects biologically relevant transcriptomic programs linked to neurodegenerative progression. Nested cross-validation further showed that the selected genes achieved measurable internal predictive performance for distinguishing high-Braak samples. As a second methodological contribution, we introduced a Lorentzian hyperbolic variant of t-distributed stochastic neighbor embedding (Lorentz t-SNE) to explore latent non-Euclidean structure in transcriptomic data. This method embeds samples in hyperbolic space, providing an alternative to Euclidean embeddings for representing hierarchical or nonlinear structures. Compared with conventional Euclidean embeddings, the proposed Lorentz t-SNE revealed a more localized organization of high-Braak samples. Together, these results demonstrate the utility of the proposed analytical framework and Lorentz t-SNE for investigating heterogeneous, potentially non-Euclidean organization in AD transcriptomes.

23.
arXiv (CS.AI) 2026-06-16

PH-KAN: Port-Hamiltonian Kolmogorov-Arnold Network

arXiv:2606.14708v1 Announce Type: cross Abstract: Data-driven machine learning approaches have become increasingly attractive for nonlinear system identification, but standard models often fail to preserve the underlying physical structure and remain difficult to interpret, especially when no analytical model is available. In this context, port-Hamiltonian (pH) models provide a natural physics-informed representation. However, when these models are parameterized with standard multilayer perceptrons (MLPs), the learned constitutive components often remain poorly interpretable. In this paper, we propose a structure-preserving identification framework for nonlinear port-Hamiltonian systems based on Kolmogorov-Arnold Networks (KANs). The proposed PH-KAN model parameterizes the interconnection matrix, dissipation matrix, Hamiltonian, and input mapping using dedicated KAN blocks, while enforcing the port-Hamiltonian constraints by construction. This yields constitutive representations in which the nonlinear functions defining the identified pH components can be explicitly inspected, leading to a more interpretable model than with standard MLP-based parameterizations.

24.
arXiv (CS.CL) 2026-06-11

Pre-AF 13: An Interpretable Atrial Fibrillation Risk Score Mined from Discharge Reports

Background. Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and a major determinant of prognosis. Established AF risk scores rely on factors (older age, hypertension) nearly ubiquitous among patients with cardiovascular disease (CVD), offering limited stratification in this high-risk group. Most target long-term (5-10 year) rather than medium-term prediction. We developed interpretable ML models predicting AF risk over a 24-month and entire follow-up horizon in CVD patients using routinely collected hospital data. Methods. Single-center retrospective study of electronic health records from the National Research Cardiology Center (Russia) for patients aged >=18 with CVD but without pre-existing AF, hospitalized more than once between January 2012 and May 2019. A custom NLP pipeline transformed unstructured discharge reports into 73 structured features, combining a rule-based parser with transformer-based NER. Using LightAutoML we built a full model (73 features), a simple model (reduced subset), and a linear model for a bedside risk score. Performance was assessed by ROC AUC, compared with CHARGE-AF, C2HEST, MHS, and HAVOC, and interpreted via SHAP. Results. Of 80,576 records from 45,000 patients, 17,562 met inclusion criteria; 1,438 (8.19%) developed AF. The full model reached ROC AUC 0.735 (24-month) and 0.696 (entire follow-up); the simple model was nearly identical (0.725, 0.696). All non-linear models outperformed the four clinical risk scores (ROC AUC 0.53-0.64). The simple model uses 13 features and is named Pre-AF 13. SHAP identified age and left atrial volume as dominant predictors. A linear risk score (Pre-AF 9) stratified observed 24-month AF incidence from ~7% to 36%. Conclusion. Interpretable ML models built from routinely collected EHR data identify high-AF-risk CVD patients, outperforming established clinical risk scores.

25.
Nature (Science) 2026-06-10

Gene ancestries reveal diverse microbial associations during eukaryogenesis

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