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

When Does Routing Become Interpretable? Causal Probes on Block Attention Residuals

Authors:

arXiv:2606.13168v1 Announce Type: new Abstract: Block Attention Residuals (Block AttnRes) by replace fixed additive residuals with a learned softmax over earlier depth-source representations, surfacing cross-layer routing as an inspectable tensor in the forward pass. This is a tempting interpretability target: information flow normally inferred indirectly is now directly observable. We ask whether such exposure suffices for mechanistic interpretation. We probe two same-scale ($0.6$B) Block AttnRes checkpoints under identical routing-ablation interventions: a vanilla Qwen3 inference-wrapped through a deterministic recency-bias schedule that the codebase admits as a routing-equivalent loading path, and a Block AttnRes Qwen3 trained from scratch with routing as part of optimisation. The wrapped baseline's routing weights are content-independent and reproduce the schedule's analytic prediction. The trained AttnRes checkpoint instead exhibits three localised routing motifs: an embedding-source pathway through early-layer MLP, a current-state pathway through early-layer attention and MLP, and an older-history pathway through late-layer attention. Beyond this stratification, we find a sharp dissociation between average routing mass and causal importance: in both sublayers, the largest mass slice is not the largest causal contribution, and one source family carries appreciable mass with no detectable causal role under intervention. Architectural exposure of routing is therefore necessary but not sufficient for mechanistic interpretation: structured depth routing emerges only when routing has been part of training, and even then, descriptive routing summaries should be treated as candidate hypotheses to be tested by causal interventions, not as evidence of mechanism in their own right.

02.
PLOS Computational Biology 2026-06-05

A multiscale, Bayesian inference approach to augment mechanistic models of cell signaling with machine-learning predictions of binding affinity

by Holly A. Huber, Stacey D. Finley Computational models in systems biology are often underdetermined—that is, there is little data relative to the complexity and size of the model. This lack of data is primarily due to limits in our ability to observe specific biological systems and restricts the utility of computational models. To reduce this uncertainty, recent methods have explored augmenting parameter inference of systems biology models with predictions from machine learning models. Such approaches expand the pool of data that is applicable for the inference problem. Here, we explore augmenting the parameter inference of intracellular signaling models. We choose to investigate signaling because experimental measurements of the variables of interest, protein dynamics, are still quite limited. To investigate, we propose a novel, multiscale, Bayesian inference approach that augments traditional signaling data with predictions of binding affinity. These predictions are generated using a machine learning pipeline with measurements of amino acid sequence, from the Universal Protein Resource, or protein structure, from the Protein Data Bank, as inputs. We find that we can successfully integrate these measurements into the inference problem using our novel framework. Excitingly, this integration significantly improves the parameter estimates of signaling models. We demonstrate that how much this improvement impacts predictions of signaling depends on the sensitivity of the prediction to perturbations in the parameter values. Overall, the framework we establish here improves the parameter inference of intracellular signaling models by successfully bridging data on protein sequence and structure with systems-level signaling.

03.
arXiv (CS.AI) 2026-06-12

Structured Testbench Generation for LLM-Driven HDL Design and Verification-Oriented Data Curation

arXiv:2606.12983v1 Announce Type: new Abstract: Automated testbench generation has become a critical bottleneck in large language model (LLM)-driven Register Transfer Level (RTL) workflows, where large numbers of candidate designs must be verified rapidly and reliably. Existing prompt-based approaches treat testbench generation as unconstrained code synthesis, yielding stochastic outputs with high token cost, low reproducibility, and insufficient coverage. To address this gap, we present STG, a Structured Testbench Generation framework that exploits the inherent structure of hardware designs to generate deterministic testbenches. As a direct verification tool, STG runs 720x faster than an iterative LLM-based testbench generation flow and higher rate of successful compilation, achieves higher coverage, and reduces false-pass verdicts on incorrect DUTs. STG also helps identify errors in RTL generation benchmarks by exposing faulty benchmark testbenches. As a data curation engine, it is 11x faster than LLM-based filtering on a single CPU core with 127x less energy, and the resulting distilled models provide state-of-the-art performance in our multi-benchmark evaluation. As a test-time scaling oracle, it reduces node count by 14-47\%. Our models are available at https://huggingface.co/collections/AS-SiliconMind/siliconmind-v12.

04.
medRxiv (Medicine) 2026-06-22

Effectiveness of Stress Management to Reduce Stress Eating for Women: A Systematic Review and Meta-analysis of Intervention Studies

Objective: This systematic review and meta-analysis examined 1) the effects of stress management interventions on changes in stress eating for women, and 2) the longevity of these effects, by summarizing and assessing evidence from controlled and non-equivalent pretest-posttest intervention studies. Method: Five databases (PsycINFO, PubMed, Medline, Web of Science, CINAHL), existing sources, and grey literature were searched (February - June 2025). Studies that assessed stress eating or emotional eating, included a stress management intervention, and comprised at least 70% women were included. The primary outcome was reduction in stress eating. Data were pooled in meta-analyses using multi-level random-effects models and subset by follow-up period. Risk of bias was assessed via funnel plots and sensitivity analyses. Results: Sixty studies with 119 effect size estimates were included in the primary analysis. Pooled estimates indicated that stress management interventions significantly reduced stress eating (Hedges g = -0.4174, p < 0.001), with pre-post designs having larger effects than controlled trials. Subgroup analyses of follow-up periods found small effects in the short-term (before 3 months; Hedges g = -0.4202, p < 0.0001) and moderate effects for mid-term (3-6 months; Hedges g = -0.5886, p < 0.0001). Effects beyond 6 months were small and nonsignificant (Hedges g = -0.4370, p = 0.0660). Conclusion and Relevance: Stress management interventions appear to be effective for reducing stress eating for women, suggesting the potential to incorporate stress management in interventions targeting obesity. Effects may be only sustained 6 months post-intervention, suggesting the need for strategies to bolster long-term effectiveness.

05.
arXiv (CS.AI) 2026-06-19

Creativity Reconsidered: Generative AI and the Problem of Intentional Agency

arXiv:2601.15797v2 Announce Type: replace Abstract: Many theorists maintain that conscious intentional agency is a necessary condition of creativity. We argue that this requirement, which we call the Intentional Agency Condition (IAC), should be abandoned. We motivate this by highlighting the problems this criterion encounters in the face of recent advances in generative AI, which is ostensibly creative despite being incapable of intentional agency. We present two corpus analyses to illustrate the rapidly increasing tendency of people to predicate creativity to generative AI. In response to this predicament, theorists of creativity have proposed a range of conflicting solutions, which we critically evaluate. We find that none of these satisfyingly resolves the initial predicament, and we therefore propose a novel approach. Our claim is that ascriptions of creativity are dependent on what we call creative ability. This solution explains why intentional agency is important for judgements of creativity, without being a necessary condition. Our approach thereby accommodates AI creativity without dismissing the intuition that perceived intentions are of key importance for ascriptions of creativity.

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

Dimension-Free Convergence of Discrete Diffusion Models: Adjoint Equations Induce the Right Space

arXiv:2605.17232v2 Announce Type: replace Abstract: Discrete diffusion has become a leading framework for generative modeling in various applications including language, vision, and biology. Existing convergence theory, however, exhibits fundamental limitations. KL-based analyses diverge under singular priors such as the masked distribution, while bounds in total variation (TV) depend on the state space size $S$ and become vacuous for modern language tasks, where vocabularies contain hundreds of thousands of tokens. We develop a unified adjoint-equation-based framework that establishes dimension-free convergence guarantees in any integral probability metric (IPM). To the best of our knowledge, our bounds are the first to be entirely free of $S$ and applicable to both masked and uniform priors. Importantly, our theory relies only on a single standard rate-matrix regularity assumption and applies to general priors. Five novel techniques drive our improvements: working in the space of observables via adjoint equations rather than directly with probability measures, a regularity analysis that yields bounds on any IPM, a coupling argument that removes $S$-dependence under uniform transitions, and score-marginal cancellation and exit-routing techniques that remove $S$-dependence under masked transitions. Our framework thus sharply departs from prior analyses and avoids the shortcomings of pathspace-KL and existing TV-based approaches. Beyond convergence bounds, our framework provides a versatile toolkit for further theoretical study of discrete diffusion models, including principled choices of loss functions and dimension-free step complexity.

07.
arXiv (CS.AI) 2026-06-12

Prism: Cost-Efficient Multi-LLM Serving via GPU Memory Ballooning

arXiv:2505.04021v3 Announce Type: replace-cross Abstract: Inference providers must maintain availability for many LLMs, including low-volume but essential models, making resource efficiency increasingly important as token prices fall. Analysis of production traces reveals a dynamic bursty-group pattern in which sets of models become active together and shift over time; existing space- and time-sharing approaches lack principled mechanisms to adapt to this variability, forcing trade-offs between SLO adherence and efficiency. We observe that elastic memory allocation can unify spatial and temporal sharing. Based on this insight, we have developed Prism, a memory-centric LLM co-serving framework that applies memory ballooning to reclaim memory across models and support both forms of sharing under a single scheme. Prism's balloon driver, referred to as kvcached, has been open-sourced at https://github.com/ovg-project/kvcached, and deployed in production environments across 10K+ GPUs.

08.
medRxiv (Medicine) 2026-06-17

Reverse engineering of motor unit discharge in multiple sclerosis reveals heterogeneity of voluntary motor commands

Central nervous system injury causes motor deficits through derangement of excitatory, inhibitory, and/or neuromodulatory inputs to motoneurons, the three fundamental components of motor commands. Typically, study of pathologic neural control in humans is restricted to only one of the three. Chardon et al. (2024) presented a fundamentally new approach to comprehensively study all components by reverse engineering motor unit firing patterns. We apply their framework to motor unit firing patterns from 89 people with multiple sclerosis (MS) and 34 controls to study excitatory, inhibitory, and neuromodulatory contributions to pathologic motor output. Disruptions to all components are plausible in MS, a disease hallmarked by heterogeneity in nearly all aspects. Accordingly, we found abnormalities in MS for all three components. Notably, neuromodulation included both high and low extremes. Our results suggest that pathophysiology of motor commands in MS varies among patients, a finding fundamentally different from other studied populations showing relative consistency.

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

Weaving Multi-Source Evidence for Biomedical Reasoning: The BioMedHop Benchmark and BioWeave Framework

Biomedical question answering (QA) increasingly requires reasoning over interacting entities, where supporting evidence is scattered across biomedical knowledge graphs, literature documents, and web-accessible resources. However, existing biomedical QA benchmarks mainly focus on exam-style knowledge, literature comprehension, or short-range multi-hop inference, leaving source-conditioned graph reasoning and evidence topology construction underexplored. To fill this gap, we introduce BioMedHop, a multi-source graph-grounded benchmark for evaluating biomedical reasoning over structured evidence topologies. BioMedHop contains 10,045 instances across KG, document, web, and hybrid evidence settings, covering shared-neighbor matching, intersection reasoning, path-based reasoning, and counting, with option-based, open-ended, and numeric count renderings. To support this benchmark, we further propose BioWeave, a source-aware reasoning framework that retrieves biomedical KG paths, gathers supporting clues from documents and web sources, assembles them into a unified evidence graph, and verifies answers through entity-level evidence support. Comprehensive experiments show that BioWeave achieves the best overall performance among compared methods on BioMedHop, outperforming the strong hybrid baseline ToG-2 by 10.5% in the overall average. Moreover, BioWeave consistently improves different LLM backbones and enables smaller models, such as Qwen3-4B, to achieve reasoning performance comparable to GPT-4-Turbo.

10.
arXiv (math.PR) 2026-06-15

Scaling limits of multitype Bienaymé trees

arXiv:2507.23241v2 Announce Type: replace Abstract: We consider critical multitype Bienaymé trees that are either irreducible or possess a critical irreducible component with attached subcritical components. These trees are studied under two distinct conditioning frameworks: first, conditioning on the value of a linear combination of the numbers of vertices of given types; and second, conditioning on the precise number of vertices belonging to a selected subset of types. We prove that, under a finite exponential moment condition, the scaling limit as the tree size tends to infinity is given by the Brownian Continuum Random Tree. Additionally, we establish strong nonasymptotic tail bounds for the height of such trees. Our main tools include a flattening operation applied to multitype trees and sharp estimates regarding the structure of monotype trees with a given sequence of degrees.

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

Neural Additive and Basis Models with Feature Selection and Interactions

arXiv:2606.19850v1 Announce Type: cross Abstract: Deep neural networks (DNNs) exhibit attractive performance in various fields but often suffer from low interpretability. The neural additive model (NAM) and its variant called the neural basis model (NBM) use neural networks (NNs) as nonlinear shape functions in generalized additive models (GAMs). Both models are highly interpretable and exhibit good performance and flexibility for NN training. NAM and NBM can provide and visualize the contribution of each feature to the prediction owing to GAM-based architectures. However, when using two-input NNs to consider feature interactions or when applying them to high-dimensional datasets, training NAM and NBM becomes intractable due to the increase in the computational resources required. This paper proposes incorporating the feature selection mechanism into NAM and NBM to resolve computational bottlenecks. We introduce the feature selection layer in both models and update the selection weights during training. Our method is simple and can reduce computational costs and model sizes compared to vanilla NAM and NBM. In addition, it enables us to use two-input NNs even in high-dimensional datasets and capture feature interactions. We demonstrate that the proposed models are computationally efficient compared to vanilla NAM and NBM, and they exhibit better or comparable performance with state-of-the-art GAMs.

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

On the Position Bias of On-Policy Distillation

arXiv:2606.22600v2 Announce Type: replace-cross Abstract: On-Policy Distillation (OPD) improves the learning efficiency of standard reinforcement learning through dense, token-level supervision from teachers. In the standard KL objective of OPD, token-level losses are uniformly averaged, implying equal weights for all tokens. However, we discover that not all tokens are created equal: as student rollouts grow longer, they deviate further from the teacher's distribution, leading to degraded supervision quality at later positions. As a result, OPD using only the first 30% of tokens can perform comparably to using all tokens, whereas OPD using only the last 30% of tokens barely learns anything. In this work, we provide a principled understanding of this issue through the lens of constrained optimization. Based on these insights, we derive Importance-Weighted On-Policy Distillation (IW-OPD), in which the weight assigned to each token depends on the accumulated discrepancy between the student's and teacher's distributions, naturally upweighting earlier tokens and downweighting later ones with larger deviations. We show that IW-OPD converges significantly faster than OPD, with better learning efficiency, and achieves better final performance than standard OPD in both same-size and cross-scale settings, improving performance up to 6.9 points on AIME-2025.

13.
medRxiv (Medicine) 2026-06-11

Neighborhood socioeconomic status associated with post-stroke cognitive impairment: a retrospective cohort study

Background: Late complications after stroke (LCAS), including cognitive symptoms, impact quality of life and recovery. It is not known if neighborhood-level measures of socioeconomic status (SES) influence LCAS. This study assessed associations between SES measures, including neighborhood income inequality (Gini) and area deprivation index (ADI), and cognitive symptoms after acute ischemic stroke (AIS) in a hospital leveraging active surveillance of LCAS. Methods: This retrospective cohort study included 512 patients hospitalized with AIS at Tufts Medical Center with subsequent follow-up (between zero and three months or between three and twelve months) in the Stroke Clinic from 1/1/2018 - 12/31/2022. Using ZIP code data, patients were characterized as low Gini (low inequality) and high ADI (high deprivation) (Gini = 5) by state medians. These variables were combined, indicating patients who were living in both a low Gini and high ADI neighborhood to evaluate the effects of living in a homogeneously deprived area. There were 206 and 281 patients in the low Gini and high ADI groups respectively. 140 patients lived in a low Gini and high ADI neighborhood. The multivariable logistic analysis assessed the likelihood of cognitive symptoms, adjusting for age, race, ethnicity, sex, NIH Stroke Scale (NIHSS), thrombolysis, active LCAS surveillance, poverty, and ADI-Gini combination. Results: There were no associations between high ADI (OR: 1.03, 95% CI: 0.67 ? 1.57) or low Gini (OR: 1.74, 95% CI: 0.98 ? 3.07) alone and cognitive symptoms after AIS. However, the combined variable demonstrated increased likelihood of cognitive symptoms in the high ADI-low Gini group (OR: 1.82, 95% CI: 1.08 ? 3.06). Conclusions: This study suggests that individuals living in homogeneously deprived neighborhoods report higher likelihood of cognitive symptoms after AIS. Further studies with increased power are needed to investigate the underlying causes of these disparities and to develop interventions to reduce these complications.

14.
arXiv (CS.LG) 2026-06-15

NeST: Neuron Selective Tuning for LLM Safety

arXiv:2602.16835v2 Announce Type: replace-cross Abstract: Safety alignment is essential for the responsible deployment of Large Language Models (LLMs). Yet, existing approaches often rely on heavyweight fine-tuning that is costly to update, audit, and maintain across model families. Full fine-tuning incurs substantial computational and storage overhead, while parameter-efficient methods, e.g., Low-Rank Adaptation (LoRA), trade efficiency for inconsistent safety gains and sensitivity to design choices. Safety intervention mechanisms reduce unsafe outputs without modifying model weights, but do not directly shape or preserve the internal representations that govern safety behavior. We present NeST, a Neuron-Selective Tuning framework for efficient post-hoc safety alignment. NeST identifies safety-relevant feed-forward neurons via activation probing on vanilla harmful and benign prompts, clusters neurons with similar activation profiles, and trains shared cluster-level updates while freezing the rest of the model. Importantly, NeST is trained only on vanilla malicious prompts, without using jailbreak-specific attack data, yet generalizes robustly to diverse jailbreaks. The learned updates are then folded into the original weights, incurring no inference-time overhead. Evaluated on 14 open-weight language and multimodal models, NeST outperforms lightweight baselines and approaches full fine-tuning robustness with significantly fewer trainable parameters. On text-only models, NeST reduces average jailbreak attack success rate from 44.5% to 1.1% while training only 0.4M parameters on average. Across multimodal settings, it reduces ASR from 55.3% to 1.1%, and for downstream fine-tuned variants, it restores safety by reducing ASR from 53.8% to 0.8%. These results show that robust, maintainable safety alignment can be achieved by concentrating adaptation on localized, functionally coherent safety structures.

15.
arXiv (CS.CL) 2026-06-24

Prague Dependency Treebank – Consolidated 2.0: Enriching a Complex Annotation Scheme

The Prague Dependency Treebank framework is unique in its attempt to systematically include and link different layers of language, including a meaning representation with several types of inter-sentential phenomena, especially coreference and discourse relations. We present its second consolidated version (PDT-C 2.0), which concludes almost 30-years long project of sustained development of the resource to a uniformly and coherently annotated, genre-diversified, almost 4 million token language resource of Czech language, with accompanying fully compatible lexicons. In addition to continuous linguistic research, the richly linguistically annotated corpus is also widely used in international comparisons of the development of traditional and novel NLP tools as well as in conversions into other formalisms. The corpus and the trained parsers are available under the CC BY-NC-SA licence.

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

Detecting basis-dependent hardware errors through spatio-temporal quantum steering

arXiv:2606.16451v1 Announce Type: new Abstract: Spatio-temporal quantum steering provides a framework for benchmarking the nonclassicality of general quantum state transfer processes. A central diagnostic is the no-signaling-in-time (NSIT) condition, whose violation can indicate basis-dependent hardware errors. However, finite measurement statistics may also yield apparent violations, thereby obscuring the detection of basis-dependent hardware errors. To address this, we construct a statistical hypothesis test under the null hypothesis that NSIT violations arise solely from statistical fluctuations. Combining the statistical properties of NSIT violation under the null hypothesis with Chebyshev's inequality, we obtain a distribution-free upper bound on the $p$-value without parametric assumptions. We apply this method to two examples. For a single-qubit state-transfer experiment on a superconducting processor, we observe several instances that the NSIT violation is observed and the null hypothesis is simultaneously rejected by a small $p$-value, providing statistical evidence of basis-dependent hardware errors. For a seven-qubit Hayden-Preskill teleportation protocol on IonQ devices, the null hypothesis is also rejected even when the average fidelity exceeds the classical threshold, while the associated nonclassicality measure vanishes. Our results highlight the necessity of statistical hypothesis testing for detecting basis-dependent errors in near-term quantum devices.

17.
arXiv (CS.CV) 2026-06-12

CPAM: Context-Preserving Adaptive Manipulation for Zero-Shot Real Image Editing

Editing natural images using textual descriptions in text-to-image diffusion models remains a significant challenge, particularly in achieving consistent generation and handling complex, non-rigid objects. Existing methods often struggle to preserve textures and identity, require extensive fine-tuning, and exhibit limitations in editing specific spatial regions or objects while retaining background details. This paper proposes Context-Preserving Adaptive Manipulation (CPAM), a novel zero-shot framework for complicated, non-rigid real image editing. Specifically, we propose a preservation adaptation module that adjusts self-attention mechanisms to preserve and independently control the object and background effectively. This ensures that the objects' shapes, textures, and identities are maintained while keeping the background undistorted during the editing process using the mask guidance technique. Additionally, we develop a localized extraction module to mitigate the interference with the non-desired modified regions during conditioning in cross-attention mechanisms. We also introduce various mask-guidance strategies to facilitate diverse image manipulation tasks in a simple manner. CPAM can be seamlessly integrated with multiple diffusion backbones, including SD1.5, SD2.1, and SDXL, demonstrating strong generalization across different model architectures. Extensive experiments on our newly constructed Image Manipulation BenchmArk (IMBA), a robust benchmark dataset specifically designed for real image editing, demonstrate that our proposed method is the preferred choice among human raters, outperforming existing state-of-the-art editing techniques. The source code and data will be publicly released at the project page: https://vdkhoi20.github.io/CPAM

18.
arXiv (CS.AI) 2026-06-24

FLUX3D: High-Fidelity 3D Gaussian Generation with Diffusion-Aligned Sparse Representation

arXiv:2606.24874v1 Announce Type: cross Abstract: Sparse voxel representation has emerged as a scalable foundation for image-to-3D Gaussian Splatting (3DGS) generation, yet current methods struggle to preserve high-frequency visual details of input images due to two structural bottlenecks. First, they adopt discriminative 2D features optimized for semantic abstraction to construct sparse voxel latents, which suppress reconstructive cues and induce a representation bottleneck. Second, in the generation stage, standard diffusion transformers lack effective mechanisms to align dense 2D image tokens with sparse 3D voxel latents, resulting in a cross-modal correspondence bottleneck. To address these issues, we propose FLUX3D, a scalable image-to-3DGS framework that boosts both representation learning and cross-modal alignment during generation. We first revisit 2D feature selection for sparse-voxel-based 3D representation learning, propose Diffusion-Aligned Structured Latents (DA-SLAT) and couple it with a decoder-only architecture to improve 3DGS reconstruction fidelity. We also design a sparse-structure-aware diffusion framework, which integrates the Sparse-structure Multimodal Diffusion Transformer (SMDiT) and Modal-Aware Rotary Positional Embedding (MARoPE) to achieve geometry-agnostic 2D-3D alignment. Extensive benchmark experiments demonstrate that FLUX3D yields substantial improvements in appearance fidelity and significantly outperforms all state-of-the-art (SOTA) methods in generating high-quality 3DGS assets.

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

Speaking the Language of Science: Toward a General-Purpose Generative Foundation Model for the Natural Sciences

In this report, we present LOGOS (Language Of Generative Objects in Science), a scientific generative language model that unifies heterogeneous tasks across the natural sciences within a single autoregressive framework based on a shared scientific grammar. It encodes diverse scientific objects and their spatial interactions as token sequences over a common vocabulary. By representing spatial contact and constraint patterns as discrete tokens, the model captures complex structural interactions in a purely sequential manner, without relying on explicit coordinates or geometric neural networks. This unified representation enables a wide range of downstream tasks to be formulated consistently as next-token prediction in the same grammar space, creating strong alignment between continued multi-domain pre-training and downstream objectives. Across diverse tasks, LOGOS consistently matches or outperforms domain-specific baselines, providing preliminary evidence for the feasibility of "one model fits all" in the natural sciences. We train LOGOS models at different scales (1B, 3B, and 8B parameters) and find a consistent positive correlation between model size and performance. This suggests that the future of AI for Science (AI4S) may not lie in building an independent technical stack that is separated from large language models (LLMs). Instead, it may depend on deeply aligning scientific foundation models with LLMs through shared architectures, shared training paradigms, and shared inference infrastructure, so that LLMs can truly become a new entry point for AI4S. We release the model weights and associated resources to facilitate further research.

21.
bioRxiv (Bioinfo) 2026-06-22

Benchmarking cell type annotation in spatial transcriptomics: resolving cellular hierarchies, biological fidelity, and dynamic cell states

Spatial transcriptomics enables the quantification of gene expression within its native tissue context, providing unprecedented insight into tissue architecture, cellular ecosystems, and local cell-cell interactions at regional and single-cell resolution. Accurate cell type annotation is a critical prerequisite for interpreting these data and is often the first and most essential step in downstream analysis. Despite rapid advances in computational methods, cell type annotation remains challenging and frequently requires extensive expert-driven manual curation based on marker-gene expression, spatial context, and prior biological knowledge. While early approaches relied primarily on transcriptional similarity, newer methods increasingly incorporate spatial information, histological features, and multimodal data to improve annotation accuracy. Nevertheless, reliable annotation remains difficult when biological interpretation requires fine-grained subtype resolution, particularly for platforms with limited gene panels, tissues undergoing dynamic cellular state transitions, and studies in which reference and query datasets differ substantially in biological context or technical modality. Here, we present a systematic benchmark of 20 state-of-the-art cell type annotation methods across four spatial transcriptomics datasets spanning diverse technologies, experimental conditions, cell numbers, and gene panel sizes. Importantly, all benchmark datasets contain expert-curated cell type labels, including well-resolved cell populations and subtype annotations, providing high-quality biological ground truth for evaluation. The benchmark encompasses both reference-based and reference-free methods representing a broad range of computational frameworks. Performance was assessed using conventional classification metrics, including accuracy and F1-based measures, together with structure-aware metrics that evaluate both cell-level annotation accuracy and preservation of higher-order biological organization. Across datasets, annotation performance varied substantially according to tissue context, reference-query similarity, and annotation granularity. Fine-grained subtype annotation and recovery of rare cell populations remained challenging for many methods, particularly in datasets capturing injury, repair, developmental, and regenerative processes characterized by continuous cellular state transitions. Notably, high classification accuracy did not necessarily correspond to preservation of global cellular relationships or biologically coherent downstream pathway and gene-set enrichment analyses. Overall, scANVI, Seurat, and TACCO consistently ranked among the top-performing methods, although their relative advantages were context dependent. Together, our results provide a comprehensive assessment of current annotation strategies for spatial transcriptomics and offer practical guidance for selecting methods that best align with specific biological questions, dataset characteristics, and analytical priorities.

22.
arXiv (CS.LG) 2026-06-16

Learning Hybrid Biophysical Neuron Models with Neural ODEs

arXiv:2606.16693v1 Announce Type: cross Abstract: Biophysical neuron models link measurements of neural activity to underlying cellular mechanisms. Yet, a central challenge is that the kinetics of many ion channels are poorly characterized, and practical simplifications – omitting channels or reducing morphological detail – introduce systematic gaps between model and biology. Bridging these gaps requires approaches that can flexibly discover unmodeled dynamics while preserving mechanistic interpretability. Here, we introduce a hybrid modeling framework that embeds neural ordinary differential equations into conductance-based biophysical models to capture unknown currents or mis-specified channel kinetics. By parameterizing the neural ODE in terms of voltage-dependent steady-state and time-constant functions, we recover interpretable gating dynamics directly from voltage recordings without assuming a functional form. We show that the hybrid model fits the gating kinetics of 2400 ion channel models and recovers unknown gating dynamics from single current-clamp recordings, generalizing to out-of-distribution stimulus regimes under realistic inputs and parameter misspecification. We also use our method to reduce a multicompartment model of a cortical neuron into a single-compartment hybrid model with a learned axial current, yielding up to an order of magnitude lower computational cost. Together, our results establish a plug-and-play framework for selectively replacing unknown components of conductance-based models with neural ODEs while preserving their mechanistic structure.

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

GRACE: Step-Level Benchmark for Faithful Reasoning over Context

Many reasoning tasks require models to reason over input context, from document-grounded question answering to rule-based deduction. Chain-of-Thought (CoT) prompting produces traces that appear transparent, yet individual steps can silently deviate from the source evidence, even when the final answer is correct. Existing methods detect hallucinations at the response level but fail to identify where in the chain a failure occurs or what type it is. We introduce GRACE, the first human-annotated step-level faithfulness benchmark with a data-driven error taxonomy for context-grounded textual reasoning. GRACE covers CoT traces from 10 models across 4 source datasets, with each step annotated for faithfulness, error category, and natural language explanation. A data-driven taxonomy, discovered bottom-up via unsupervised clustering, organizes failures into two tracks: GRACE-Inference (deductive errors) and GRACE-Grounding (factual grounding errors), with four categories each. The evaluation set is human-annotated and challenging by design. Our experiments reveal substantial headroom for current models. In addition, integrating step-level faithfulness signals into reinforcement learning pipelines improves both downstream accuracy and reasoning reliability.

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

A Training-Free Mixture-of-Agents Framework for Multi-Document Summarization using LLMs and Knowledge Graphs

Multi-Document Summarization (MDS) plays a critical role in distilling essential information from collections of textual data. Existing approaches often struggle to capture complex inter-document relationships, rely heavily on large amounts of labeled data for supervised training, or exhibit limited generalization across domains and languages. To address these limitations, we present a training-free mixture-of-agents framework for MDS that leverages the complementary strengths of large language models (LLMs) and knowledge graphs. Our approach decomposes summarization into specialized agent tasks: extractive selection, knowledge-aware abstraction, and iterative refinement, each operating without task-specific fine-tuning. We unify their outputs using a multi-perspective consistency mechanism guided by LLMs. Experiments across four datasets in English and Vietnamese demonstrate state-of-the-art or competitive performance, validating the effectiveness and adaptability of our modular design.

25.
arXiv (quant-ph) 2026-06-15

On-site interactions in quantum thermal machines: efficiency, rectification and entanglement beyond local and global master equations

arXiv:2606.14593v1 Announce Type: new Abstract: Advances in experimental techniques have opened new routes for harnessing non-equilibrium dynamics in mesoscopic quantum systems. In this context, we study the impact of on-site interactions on the transport properties of a continuous quantum thermal machine composed of two coupled oscillators connected to two thermal reservoirs. In the weak system-reservoir coupling regime, where a long-standing debate concerns which reduced description should be preferred, we first show that the Redfield master equation (RME) provides an accurate and unifying framework that interpolates between two well-known limits: the local and global master equations. By relying on the Hierarchy of Pure States (HOPS), a numerically exact stochastic method, we then explore the full parameter space and show that interactions can be leveraged to tune the efficiency of the thermal machine at high temperatures (while leaving it essentially unchanged at low temperatures), induce non-reciprocal transport under asymmetric reservoir couplings, and generate steady-state entanglement within the junction. We derive expressions for system-bath correlators, such as heat and particle currents, consistently across different frameworks. Our work features on-site interactions to enhance the versatility of quantum thermodynamic junctions and clarifies the role of non-Markovianity and non-linearities in quantum transport.