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

A Bifurcation Theory Framework for Gradient Descent on the Edge of Stability

Authors:

arXiv:2606.15551v1 Announce Type: new Abstract: The Edge of Stability (EoS) phenomenon, where gradient descent operates with sharpness exceeding the classical convergence threshold yet the loss decreases over long timescales, is ubiquitous in modern deep learning but remains poorly understood in realistic settings. Prior rigorous analyses have been largely confined to scalar or low-dimensional losses with specific structural forms. In this work, we develop a bifurcation theory framework for gradient descent on the edge of stability that applies directly to overparameterized neural networks. By decomposing the training dynamics into components normal and tangent to the manifold of minimizers, we show that stable EoS training arises from a flip bifurcation in the normal direction, governed by the sign of the first Lyapunov coefficient, while the tangent dynamics drift toward regions of decreasing sharpness. Under mild spectral and geometric assumptions on the loss landscape, we prove convergence to the minimizing manifold when training at the EoS threshold. As a corollary, we recover and unify prior results: we show that the product-stability condition of Gan (2026) is an instance of our framework.

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

SAGE: Retain-Aware Post-Hoc Sanitization of Final Unlearning Vector

arXiv:2606.18309v1 Announce Type: cross Abstract: Large Language Model (LLM) unlearning aims to remove undesirable knowledge or behaviors while preserving retained capabilities. Current unlearning methods all involve a trade-off between unlearning and retention. We have found that the retention activation bias can also be used to quantify the damage an unlearning method inflicts on retention, without considering the specific implementation of the unlearning process. This allows us to restore retention performance for any unlearning method using a post-hoc approach. Therefore, we propose a complementary post-hoc setting to sanitize the final update vector without rerunning the original unlearning pipeline. In this setting, we design SAGE, Spectral Activation-GEometry Sanitization, a source-agnostic correction for final unlearning updates. SAGE collects real module inputs from a small retain proxy, extracts their dominant activation geometry, and solves a source-anchored optimization objective in closed form, which suppresses update components aligned with high-energy retained directions while preserving the source method's forgetting carrier. Across multiple unlearning methods, model scales, and benchmarks, SAGE consistently relieves the retain-forget trade-off, identifying post-hoc sanitization of final vectors as a practical and underexplored axis for machine unlearning.

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

MorphStrata: Layer-Specific Perturbations for Generating Morphence Students in Time-Series Moving Target Defense

arXiv:2606.17435v1 Announce Type: new Abstract: Time-series forecasting models remain vulnerable to gradient-based adversarial attacks while existing defense mechanisms typically incur a trade-off in robustness for bounded response and compute cost. The problem is pronounced in Moving Target Defense where maintaining multiple randomized model instances substantially exacerbates the training overhead. In this work, we introduce MorphStrata, a student generation strategy with selective, layer-specific stochastic noise injection that extends the traditional Morphence defense. MorphStrata uses a Transformer backbone as the teacher and perturbs randomly selected architectural blocks to create structured heterogeneity across student models in response to varied data distributions and threat models. We evaluate against vanilla Transformer and Morphence backbones on a suite of benchmarks including the Jena Climate, Electricity Load Diagrams, and Appliances Energy Prediction using FGSM, BIM and PGD attacks across multiple attack strengths. Across datasets and attack regimes, the proposed ensemble maintains comparable adversarial RMSE. Specifically, for high entropy, periodic datasets as in the case of the AEP data, MorphStrata achieves the lowest RMSE across all attacks and perturbation budgets, improving over the static baseline by up to 24.11% and 97.97% under FGSM and BIM respectively at an epsilon value of 0.5 over 30 randomized trials. Targeting the layers to generate MorphStrata students accounts for less than 1% increase in train-times over the Morphence MTD baseline for most of the experiments, while accounting for double digit gains in adversarial RMSE reduction. We also observe a positive correlation between higher pairwise L2 distance (among generated students) and overall defense effectiveness. In summary, MorphStrata maintains adversarial robustness as an MTD defense at marginal cost deltas when compared to existing baselines.

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

Context-Aware Hierarchical Bayesian Modeling of IVF Laboratory Environmental Conditions

arXiv:2606.20459v1 Announce Type: new Abstract: IVF pregnancy rates are routinely modeled using patient-level variables, while high-resolution laboratory environmental data remain underutilized. We show that this is a missed opportunity. Rather than relying on raw sensor averages, we engineer 55 context-aware temporal features, including rolling thermal stability, simultaneous temperature-humidity adherence, peak stress duration, and post-stress recovery speed, that capture the dynamics of incubator microenvironments. On 61 weeks of data from an Asian IVF clinic, these features reduce cross-validated prediction error to 1.27%, compared to 3-5% for raw averages. We then train a hierarchical Bayesian Beta regression model that shares environmental effects across an Asian and a Northern European clinic via partial pooling, while preserving site-specific baselines. On held-out data from the Northern European clinic, the model achieves R2 = 0.86 and a 64% error reduction for the 35-39 age group over a naive baseline, demonstrating that structured environmental monitoring contains clinically meaningful, transferable signal.

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

p-PSO: A Penalized Particle Swarm Optimization Technique for Finding D-Optimal Designs with Mixed Factors in Generalized Linear Models

arXiv:2606.15962v1 Announce Type: cross Abstract: Finding D-optimal designs for generalized linear models (GLMs) is challenging due to the dependence of the Fisher information matrix on unknown parameters and the lack of closed-form solutions, particularly when input factors include both discrete and continuous variables. Although classical algorithms and recent metaheuristic approaches have offered partial solutions, there remains a need for robust and computationally efficient methods. In this paper, we propose a penalized Particle Swarm Optimization (PSO) approach, named $p$-PSO. Here we introduce a new, general-purpose penalty formulation for constrained optimization and demonstrate its effectiveness in optimal design problems. The formulation is algorithm-agnostic and applicable to a broad class of black-box optimization methods. Results show that the method is highly efficient, with its primary contribution being a penalty formulation that enables the direct use of an off-the-shelf PSO algorithm and extends naturally to more general constrained optimization tasks.

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

PRISMR: Overcoming Parse Collapse in Multimodal Listwise Ranking via Parameterized Representation Internalization

arXiv:2606.12942v1 Announce Type: new Abstract: Generative listwise ranking with Large Multimodal Models (LMMs) aims to capture global list context in a single forward pass, but its effectiveness degrades in long-context multimodal scenarios. We identify a recurring failure mode, parse collapse, where the autoregressive decoder produces fluent yet incomplete rankings by silently omitting candidates and terminating early. This failure stems from limited context utilization rather than simple formatting mistakes, making prompt engineering and constrained decoding insufficient. We propose PRISMR (Parameterized Representation Internalization for Semantic Multimodal Ranking), a framework that replaces transient in-context list processing with parametric structural conditioning. PRISMR uses a lightweight hypernetwork to encode multimodal candidates in parallel and generate item-specific LoRA weights, which are synthesized into an instance-specific adapter for a LMM. This paradigm enables more robust internalization of list structure while preserving the base model. We further introduce a large-scale multimodal review-ranking benchmark for evaluation. Experiments demonstrate that PRISMR substantially reduces parse collapse, improves listwise ranking performance, and transfers effectively across domains and instruction-tuned backbones.

07.
Nature (Science) 2026-06-17

These ‘master’ proteins protect us from deadly mutations — and could inspire new drugs

Authors:

Biology has clever ways to mask the effects of potentially harmful gene mutations. Scientists are investigating how this ‘buffering’ works — and how to exploit it. Biology has clever ways to mask the effects of potentially harmful gene mutations. Scientists are investigating how this ‘buffering’ works — and how to exploit it.

08.
arXiv (quant-ph) 2026-06-16

Fast and high-fidelity transfer of edge states via dynamical control of topological phases and effects of dissipation

arXiv:2505.16606v2 Announce Type: replace-cross Abstract: Topological edge states are robust against symmetry-preserving perturbations and noise, making them promising for quantum information and computation, particularly in topological quantum computation through the braiding operations of Majorana quasiparticles. Realizing these applications requires fast and high-fidelity dynamic control of edge states. In this work, we theoretically propose a high-fidelity protocol for transferring topological edge states by dynamically moving a domain wall between two regions with different topological numbers in one dimension. This protocol fundamentally relies on Lorentz invariance and relativistic effects, because moving the domain wall at a constant speed is described by a mass term with the uniform linear motion in the Dirac equation. We demonstrate the effectiveness of our protocol in transferring edge states with high fidelity using a one-dimensional quantum walk with two internal states, which is feasible with current experimental technology. We also investigate how bit-flip and dephasing dissipation to the environment affect transfer efficiency. Remarkably, bit (dephasing) dissipation does not affect the fidelity at the slow (fast) transfer limit, which can be explained by the relativistic effects on the edge states.

09.
arXiv (CS.CV) 2026-06-16

LIBERO-Occ: Evaluating and Improving Vision-Language-Action Models under Scene-Induced Occlusion via Viewpoint Imagination

Vision-Language-Action (VLA) models achieve strong performance on standard manipulation benchmarks, but most evaluations assume that task-relevant objects are fully visible. This assumption often fails in realistic settings, where occlusion makes manipulation partially observable. In this paper, we study scene-induced occlusion as a fundamental challenge for VLA models and introduce LIBERO-Occ, an occlusion-oriented extension of LIBERO. Experiments show that state-of-the-art VLAs suffer substantial performance degradation under occlusion. To address this issue, we propose Viewpoint Imagination (VIM), which generates a complementary view from an occluded primary observation and conditions action prediction on both observed and imagined evidence. VIM improves robustness across task suites, occlusion types, and severity levels without requiring additional cameras at deployment time, suggesting that viewpoint imagination is an promising mechanism for perception completion in partially observable manipulation. Our benchmark and corresponding code are available at: \href{https://github.com/litsh/Libero-Occ}{https://github.com/litsh/Libero-Occ}.

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

S3OD: Towards Generalizable Salient Object Detection with Synthetic Data

Salient object detection exemplifies data-bounded tasks where expensive pixel-precise annotations force separate model training for related subtasks like DIS and HR-SOD. We present a method that dramatically improves generalization through large-scale synthetic data generation and ambiguity-aware architecture. We introduce S3OD, a dataset of over 139,000 high-resolution images created through our multi-modal diffusion pipeline that extracts labels from diffusion and DINO-v3 features. The iterative generation framework prioritizes challenging categories based on model performance. We propose a streamlined multi-mask decoder that handles the inherent ambiguity in salient object detection by predicting multiple valid interpretations. Models trained only on synthetic data achieve 20-50% error reduction in cross-dataset generalization, while fine-tuned versions reach state-of-the-art performance across DIS and HR-SOD benchmarks.

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

SMT-AD: a scalable quantum-inspired anomaly detection approach

arXiv:2604.06265v2 Announce Type: replace Abstract: Quantum-inspired tensor networks algorithms have shown to be effective and efficient models for machine learning tasks, including anomaly detection. Here, we propose a highly parallelizable quantum-inspired approach which we call SMT-AD from Superposition of Multiresolution Tensors for Anomaly Detection. It is based upon the superposition of bond-dimension-1 matrix product operators to transform the input data with Fourier-assisted feature embedding, where the number of learnable parameters grows linearly with feature size, embedding resolutions, and the number of additional components in the matrix product operators structure. We demonstrate successful anomaly detection when applied to standard datasets, including credit card transactions, and find that, even with minimal configurations, it achieves competitive performance against established anomaly detection baselines. Furthermore, it provides a straightforward way to reduce the weight of the model and even improve the performance by highlighting the most relevant input features.

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

Scalable and Interpretable Representation Alignment with Ordinal Similarity

arXiv:2606.16379v1 Announce Type: new Abstract: Evaluating representation similarity is fundamental to representation learning. However, existing metrics suffer from significant limitations: they lack interpretability due to shifting baselines, lack robustness to outliers, and are computationally intractable for large datasets, forcing reliance on heuristic approximations. To address this, we develop an ordinal-similarity framework, instantiated by the Triplet (TSI) and Quadruplet (QSI) Similarity Indices, which measure alignment by quantifying the consistency of ordinal relationships. We theoretically demonstrate this formulation is inherently interpretable, robust to outliers, and computationally efficient. Finally, we establish a formal equivalence between TSI and local neighborhood alignment, measured by Mutual Nearest Neighbors. Empirically, we validate these properties and show that ordinal similarity offers a scalable approach to measuring alignment, enabling practitioners to better understand and design representations.

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

AI Economist Agent: An Agentic Framework for Model-Grounded Economic Analysis with RAG, Knowledge Graphs, and Large Language Models

Authors:

arXiv:2606.20041v1 Announce Type: cross Abstract: We propose a model-grounded RAG-based AI economist with an agentic framework for economic scenario analysis using large language models (LLMs) and knowledge graphs. While LLMs can generate fluent economic narratives, economists are often required to make economic claims grounded by economic theory and real-world data. Based on this motivation, this study proposes an RAG-based AI economist, which utilizes knowledge graphs including economic data and theory and LLM-based agents to plan the analysis, retrieve relevant evidence, select appropriate models, and generate reports. In our framework, we do not produce quantitative claims directly with the language model alone; instead, we generate narratives grounded in explicit model-based computations and linked to the retrieved evidence via AI agents. We refer to our framework as an AI economist agent. We evaluate the AI economist agent in two applications: economist report generation for U.S. inflation persistence and Federal Reserve policy, and bank stress-test narrative generation for U.S. commercial real estate refinancing stress. The results illustrate how grounding the generated reports improves their economic coherence and traceability.

14.
arXiv (CS.CL) 2026-06-16

On Defining Erasure Harms for NLP

The deployment of NLP systems has raised concerns about harms they might produce, including representational harms. Recent literature has begun to conceptualize and measure one such harm, the harm of erasure. Nevertheless, the field lacks a clear and cohesive conceptual foundation for identifying and measuring erasure. Existing conceptualizations of erasure are often broad – making it difficult to identify what is needed to establish and measure erasure – or else specific to particular settings – facilitating measurement for those settings but potentially challenging to adapt to other settings. To address this gap, we develop and propose a structured definition of erasure that clarifies what components are necessary for establishing whether erasure has occurred, which practitioners need to explicitly articulate and operationalize in order to measure erasure.

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

Modelling magnetic material properties with uncertainty-aware neural networks

arXiv:2606.11870v1 Announce Type: cross Abstract: Machine learning is increasingly applied to accelerate the discovery of novel materials by exploring large compositional and structural design spaces. Yet, the scarcity of high-quality data and the frequent need for out-of-distribution prediction introduce substantial uncertainty, making the assessment of model reliability essential. In this work, we investigate uncertainty quantification as a means to evaluate model confidence in the context of permanent magnet research. In a first study, we benchmark classical and modern machine learning models for predicting intrinsic magnetic properties, focusing on the quality of their uncertainty estimates. We apply Gaussian negative log-likelihood loss and dropout-based Bayesian approximation as practical strategies for estimating predictive uncertainty. In a second study, we transfer these architectural features for uncertainty estimation to a more complex task: predicting coercivity from microstructural information using a graph neural network. Together, these studies demonstrate that uncertainty quantification not only enhances the trustworthiness of predictions but is also transferable across different modeling tasks.

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

A Conservation Law for Equilibrium Propagation and Coupled Learning

arXiv:2606.15444v1 Announce Type: cross Abstract: In this paper we show that the physical learning methods known as coupled learning (CL) and equilibrium propagation (EP) conserve a mass-like quantity in the trainable parameters in the continuous-time, small-nudging limit. We prove that this conservation holds in a broad range of physically relevant settings. We then show that the conservation law constrains the training dynamics in a way that makes convergence reliable in important settings for linear circuits. We conclude by discussing some practical implications of this conservation law.

17.
PLOS Computational Biology 2026-06-01

Histology-informed spatial domain identification through multi-view graph convolutional networks

Authors:

by Huihui Zhang, Jiaxing Chang, Zirong Li, Yue Sun, Pinli Hu, Haoxiu Wang, Hang Yang, Yonglin Ren, Xingtan Zhang, Zehua Chen, Kok Wai Wong, Haojing Shao Identifying spatial domains is crucial in spatial transcriptomics, yet effectively integrating gene expression, spatial location, and histology remains challenging. We present STESH, a Spatial Transcriptomics clustering method that combines Expression, Spatial information and Histology. STESH extracts histological features using a convolutional neural network and generates expression, histology, spatial, and collaborative convolution modules for a multi-view graph convolutional network with a decoder and attention mechanism. We evaluated STESH on multiple tissue types and technology platforms. STESH consistently outperformed ten state-of-the-art methods, achieving superior clustering accuracy with the highest scores in adjusted Rand index, normalized mutual information, and Fowlkes-Mallows index.

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

SA-VIS: Sparse frame Annotations for training Video Instance Segmentation

Recent online video instance segmentation (VIS) methods have achieved impressive results, thus becoming the preferred approach to segment instances in videos. Despite the resurgence of impressive single image models, the online (or semi-online) VIS approaches outperform single-image models (e.g., based on SAM) by using long sequences of densely annotated frames during training. However,such a training setup of VIS is expensive in the sense of compute as well as dense annotations required. In order to solve these major flaws, we argue that the effective modeling of the instances and their evolution in videos do not require densely annotated frames. To that end, we propose a simple and effective module, called Past-frames Feature Propagation (PFP) which aggregates low-dimensional features from the image encoder of multiple frames. This simple low-compute module provides tremendous learning capability in using sparse video frame labels for end-to-end training. Combined with a light-weight frame-specific Instance Queries, our Sparse frame Annotation VIS (SA-VIS) significantly improves performance over its baseline. Most interestingly, our simple design that avoids complexities effectively bridges the gap in accuracy between training on sparsely and densely annotated video sequences. This translates to a mere 0.4% drop in performance of SA-VIS when using annotations for only 1/5 of the images in the dataset. Empirically, SA-VIS shows strong improvements over the baseline on YouTube-VIS 2019/2021/2022 and Occluded VIS (OVIS) and an over 1% improvement in AP on the state-of-the-art in a limited annotations scenario.

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

Charge-Conjugation Violation and Population Asymmetry in Bipartite Fermionic Lattices

arXiv:2606.06138v2 Announce Type: replace-cross Abstract: Charge conjugation violation (CCV) is a central concept in particle physics and appears also for quasiparticles in quantum many-body systems, which typically relies on an embedded external symmetry breaking to the underlying system. An open question is how an intrinsic CCV mechanism could emerge and what its macroscopic consequences would be. We establish sublattice kinks in bipartite fermionic lattices as a concrete setup showing intrinsic CCV. The intrinsic CCV of the sublattice kink is based on the graph-topological nature of the underlying Hamiltonian, with no explicit symmetry breaking taking place. It leads to a population asymmetry of different configurations and imprints a hidden leaf-like structure in the eigenenergy spectrum. The population asymmetry also leads to an imbalanced sublattice-kink production triggered by the vacuum-instability in the quench dynamics. Our work demonstrates the graph topology as the microscopic origin of intrinsic CCV, with the population asymmetry as the macroscopic consequence, of which the proposed setup is highly amenable to experimental implementation via cold-atom quantum simulators.

20.
arXiv (CS.AI) 2026-06-15

SpheriCity: Designing Trustworthy Conversational AI for Sustainability Decision Support

arXiv:2606.13854v1 Announce Type: cross Abstract: We present SpheriCity, an expert-grounded conversational prototype designed to support trustworthy knowledge sensemaking from sustainability reports. City-level circularity assessment reports contain rich information about materials, infrastructure, and policy interventions, yet their length and heterogeneous structure make cross-document synthesis and comparison difficult for practitioners and researchers working on circular economy initiatives. While large language models (LLM) promise faster knowledge access and synthesis, their opaque reasoning, hallucinations, and lack of source transparency introduce risks for trust and interpretability, and require verification in high-stakes sustainability contexts. SpheriCity addresses these challenges through a provenance-first conversational agent that foregrounds evidence traceability, structured synthesis, and interaction scaffolds to support exploratory querying and cross-document synthesis across sustainability reports. We conducted a formative expert review with six sustainability experts using representative queries spanning cross-city comparison, policy summarization, and recommendation-oriented tasks. Experts evaluated responses across dimensions and provided qualitative reflections on the system's usefulness for sustainability knowledge work. Our results reveal that transparent sourcing, contextual explanation, interpretability, and alignment with expert workflow strongly shape expert trust and judgments of system usefulness. This work contributes (1) a conversational prototype for sustainability knowledge sensemaking, (2) an expert-grounded evaluation framework for assessing AI responses in high-stakes knowledge domains, and (3) design insights into how provenance, uncertainty communication, and integration in workflow influence expert users' trust in AI assistance for sustainability decision support.

21.
bioRxiv (Bioinfo) 2026-06-12

DNA Compression with Genomic Language Models: Tokenization, Benchmarking, and an Information-Content Map

Lossless compression and probabilistic sequence modeling are two faces of the same coin: a model that assigns high probability to a sequence can encode it in few bits via arithmetic coding. We exploit this duality to evaluate genomic language models as compressors of DNA, using compression primarily as an objective probe of generative sequence modeling rather than as a deployable storage system. We release DNAGPT2, a family of ten GPT-2-small models pretrained for one epoch on a single A40 using the DNABERT2 multi-species corpus that differ only in byte-pair encoding vocabulary size. Coupled with arithmetic coding, the best model reaches 1.47 bits per base (bpb) on the T2T human genome, fourth in the Cobilab compression benchmark and ahead of every general-purpose compressor. Our results suggest that NLP-style tokenization choices may be suboptimal for DNA: a 32-token BPE vocabulary compresses better than larger vocabularies. We also find that, in this benchmark, published long-context genomic LMs underperform a much shorter-context BPE GPT-2; we discuss in Section 5 that this is not a controlled context-length ablation, since the compared models also differ in architecture, training data, parameter count, and tokenization. Finally, we compute a per-nucleotide information-content map of the human genome and show that exons, introns, intergenic regions, and Alu repeats have statistically distinct information profiles.

22.
Science (Express) 2026-06-11

Laser phase plate improves structure determination of small proteins by cryo-EM | Science

Authors: Unknown Author

Phase plates can in principle overcome the poor image contrast in electron cryo–microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous designs have been unstable and compromised the high-resolution signal. They have thus been unable to surpass results achieved by standard cryo-EM. Here, we show that the laser phase plate (LPP), installed in a custom, modern Titan Krios microscope, enhances the resolution in single-particle reconstruction of small proteins by improving specimen-motion correction, recovery of information from the early frames, as well as particle visualization, 3D classification, and alignment. These advances use standard defocus ranges and reconstruction procedures, but open the door to LPP-tailored protocols offering further improvements by leveraging the LPP demonstrated here.

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

Rotation-Invariant Spherical Watermarking via Third-Order SO(3) Representation Coupling

Reliable watermarking of panoramic imagery is fundamentally challenged by arbitrary 3D rotations. As panoramas are defined on the sphere, they naturally transform under the action of $SO(3)$, rendering conventional planar representations and augmentation-based robustness strategies inadequate and devoid of theoretical guarantees. To address this, we formulate panoramas as spherical signals and leverage $SO(3)$ representation theory to derive provably rotation-invariant descriptors. While spherical harmonic coefficients transform equivariantly under rotations, the natural invariant constructions are typically limited to zeroth-order statistics which eliminate directional information and severely constrain embedding capacity. In this work, we introduce a principled third-order invariant construction by coupling higher-order $SO(3)$ irreducible representations via tensor products and projecting onto the trivial representation. This yields a spherical invariant bispectrum that preserves phase information while remaining strictly rotation-invariant. Leveraging this property, we embed watermarks into higher-order spherical harmonic coefficients and recover them from invariant bispectral scalars, enabling reliable extraction under arbitrary 3D rotations. We provide a theoretical proof of $SO(3)$ invariance for it and demonstrate experimentally its near-perfect robustness to continuous rotations while maintaining high visual fidelity.

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

Quality Over Clicks: Iterative Reinforcement Learning for Early-Stage E-Commerce Query Suggestion

Existing dialogue systems rely on query suggestion to enhance user engagement. Recent approaches mainly optimize generative models using click-through rate (CTR) models to align with user preferences. However, these methods are less effective in early-stage deployment scenarios, where click feedback is sparse and insufficient for training a reliable CTR model. To bridge this gap, we propose QualEQS, a quality-first iterative reinforcement learning framework for e-commerce query suggestion. We formalize actionable suggestion quality along three dimensions that directly affect downstream usability: answerability, factuality, and information gain. To continuously improve from online traffic without click supervision, we further propose group-level disagreement among candidate suggestions to identify ambiguous query contexts and mine hard training cases for iterative refinement. We also introduce EQS-Benchmark, a dataset of 16,949 real-world e-commerce queries for offline training and evaluation. Experiments show that our quality-based offline metrics correlate strongly with online performance, providing a practical evaluation recipe for sparse-feedback deployment. In both offline and online settings, QualEQS consistently outperforms strong baselines, yielding a 6.81% improvement in online ChatPV in a real-world enterprise-level conversational shopping assistant system.

25.
medRxiv (Medicine) 2026-06-12

An integrative multi-omics framework identifies epigenetic dysregulation of HAND2 as a potential primary driver of impaired enteric neural crest cell differentiation in Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital neurodevelopmental disorder characterized by segmental aganglionosis due to impaired developmental processes of enteric neural crest cells (NCCs). Despite being the leading genetic cause of functional intestinal obstruction in early childhood, HSCR represents a paradigmatic challenge in precision medicine: its multifactorial etiology, complex gene-environment interactions and limited resolution of single-modality analyses have long hindered mechanistic understanding and therapeutic translation. Here, we applied an integrative multi-omics approach combining genetic, phenotypic, epigenomic and transcriptomic analyses of matched ganglionic and aganglionic formalin-fixed paraffin-embedded (FFPE) patient tissues, complemented by patient-specific in vitro models. Beyond established genetic contributors, our integrative approach reveals novel regulatory pathways predominantly affecting enteric NCC differentiation, with convergent evidence pointing to epigenetic dysregulation as a primary disease mechanism. Notably, we identified over 1,300 differentially methylated positions between ganglionic and aganglionic FFPE samples, with HAND2 emerging as a key candidate due to multiple hypermethylated sites and consistently reduced expression levels in aganglionic tissues and in vitro models, suggesting a potential role in HSCR pathophysiology. We propose that our multi-omics approach offers a powerful and comprehensive framework for dissecting disease mechanisms. Beyond advancing biological understanding, this strategy holds promise for paving the way for molecularly informed patient stratification and supporting the development of personalized treatment and postoperative management strategies.