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

LingxiDiagBench: A Multi-Agent Framework for Benchmarking LLMs in Chinese Psychiatric Consultation and Diagnosis

Mental disorders are highly prevalent worldwide, but the shortage of psychiatrists and the inherent subjectivity of interview-based diagnosis create substantial barriers to timely and consistent mental-health assessment. Progress in AI-assisted psychiatric diagnosis is constrained by the absence of benchmarks that simultaneously provide realistic patient simulation, clinician-verified diagnostic labels, and support for dynamic multi-turn consultation. We present LingxiDiagBench, a large-scale multi-agent benchmark that evaluates LLMs on both static diagnostic inference and dynamic multi-turn psychiatric consultation in Chinese. At its core is LingxiDiag-16K, a dataset of 16,000 EMR-aligned synthetic consultation dialogues designed to reproduce real clinical demographic and diagnostic distributions across 12 ICD-10 psychiatric categories. Through extensive experiments across state-of-the-art LLMs, we establish key findings: (1) although LLMs achieve high accuracy on binary depression–anxiety classification (up to 92.3%), performance deteriorates substantially for depression–anxiety comorbidity recognition (43.0%) and 12-way differential diagnosis (28.5%); (2) dynamic consultation often underperforms static evaluation, indicating that ineffective information-gathering strategies significantly impair downstream diagnostic reasoning; (3) consultation quality assessed by LLM-as-a-Judge shows only moderate correlation with diagnostic accuracy, suggesting that well-structured questioning alone does not ensure correct diagnostic decisions. We release LingxiDiag-16K and the full evaluation framework to support reproducible research at https://github.com/Lingxi-mental-health/LingxiDiagBench.

02.
arXiv (CS.AI) 2026-06-17

Know Thy Reasoner: Not All Language Models Explore Alike

arXiv:2604.10827v2 Announce Type: replace Abstract: Compute scaling for LLM reasoning trades off exploring solution approaches (breadth) against refining promising ones (depth), yet why a given trade-off works, and why it often fails to transfer across models, remains unclear. We argue that the optimal strategy depends on the model's diversity profile, the spread of probability mass across solution approaches, and that this must be characterized before any exploration strategy is adopted. We formalize this with a framework decomposing reasoning uncertainty, deriving when depth-based refinement outperforms parallel sampling, and validate it across three model families at both inference and training. Our central finding is that the diversity regime dictates the strategy: low-diversity aligned models benefit from depth-based refinement with lightweight intrinsic signals, whereas high-diversity base models are often harmed by it, and instead need breadth or stronger signals to compensate.

03.
arXiv (CS.AI) 2026-06-18

A Convex Route to Thermoelasticity: Learning Internal Energy and Dissipation

arXiv:2603.28707v3 Announce Type: replace-cross Abstract: We present a physics-based neural network framework for the discovery of constitutive models in fully coupled thermomechanics. In contrast to classical formulations based on the Helmholtz energy, we adopt the internal energy and a dissipation potential as primary constitutive functions, expressed in terms of deformation and entropy. This choice avoids the need to enforce mixed convexity–concavity conditions and facilitates a consistent incorporation of thermodynamic principles. In this contribution, we focus on materials without preferred directions or internal variables. While the formulation is posed in terms of entropy, the temperature is treated as the independent observable, and the entropy is inferred internally through the constitutive relation, enabling thermodynamically consistent modeling without requiring entropy data. Thermodynamic admissibility of the networks is guaranteed by construction. The internal energy and dissipation potential are represented by input convex neural networks, ensuring convexity and compliance with the second law. Objectivity, material symmetry, and normalization are embedded directly into the architecture through invariant-based representations and zero-anchored formulations. We demonstrate the performance of the proposed framework on synthetic and experimental datasets, including purely thermal problems and fully coupled thermomechanical responses of soft tissues and filled rubbers. The results show that the learned models accurately capture the underlying constitutive behavior. All code, data, and trained models are made publicly available via https://doi.org/10.5281/zenodo.19248596.

04.
arXiv (CS.CV) 2026-06-12

Navigating Gigapixel Pathology Images with Large Multimodal Models

Recent advances in large multimodal models have allowed for the development of interactive chat models that can converse and reason about pathology whole-slide images (WSIs). However, existing slide-level chat systems are often highly specialized, typically compressing WSIs into fixed slide-level embeddings or relying on multi-component pipelines, which can lose multi-scale detail and limit generalizability beyond the target task. We present GIANT (Gigapixel Image Agent for Navigating Tissue), a simple, training-free approach that lets general-purpose multimodal models navigate WSIs on their own, iteratively selecting multi-magnification crops and aggregating evidence over time. To evaluate generalizability in WSI question answering and to promote reproducibility, we introduce MultiPathQA, a benchmark suite spanning five clinical challenges and 934 questions over 868 unique WSIs. This includes a new set of 128 pathologist-authored multiple-choice questions designed to mirror real diagnostic search and multi-scale reasoning. Using GPT-5, GIANT outperforms models specialized for pathology question answering, achieving state-of-the-art performance on four out of five benchmarks.

05.
medRxiv (Medicine) 2026-06-15

ICD-10 Code Ambiguity Obscures Treatment-Eligible Adults with Spinal Muscular Atrophy: A Single-Center Chart Review and Patient Outreach Study

Background. Three disease-modifying therapies (DMTs) for spinal muscular atrophy (SMA) have been approved since 2016, yet many adults remain untreated. Identifying them depends on ICD-10 codes that capture SMA but do not reliably distinguish it from other related conditions. We examined, in one U.S. health system, both patients' engagement with therapy and the accuracy of the codes used to find them. Methods. We conducted a retrospective chart review of adults in an academic health system identified by SMA-associated ICD-10 codes, with manual adjudication of diagnosis and DMT status. Confirmed SMA-positive, DMT-naive patients were invited to a structured telephone interview on treatment awareness and barriers. Results. Of 60 charts, 22 (36.7%; 95% CI 25.6-49.3%) were appropriately coded for SMA or a related disorder; only 16 (26.7%) had molecularly confirmed SMA. The other 38 (63.3%) were miscoded, spanning spinal and bulbar muscular atrophy, asymptomatic carriers, prenatal screening, and conditions unrelated to SMA. Ten of the 16 confirmed patients (62.5%) were DMT-naive; one was interviewed, one declined, and eight could not be reached. The non-response is itself a finding: the patients least visible to administrative data are the hardest to reach. Conclusions. ICD-10 ambiguity is a barrier to treatment access in adult SMA, as is loss to follow-up. We make two recommendations: continuous documentation-coding alignment that uses natural language processing to verify the genetic precondition, and type-specific SMA codes (subcodes for Types 0-4) anchored on molecular SMN1 confirmation. Together these would support cohort identification, outreach, and evidence generation without adding to clinician burden.

06.
bioRxiv (Bioinfo) 2026-06-17

Beyond phylogeny: Genome-wide DNA sequence patterns suggest DNA physical properties associated with thermal adaptation in extremophile microbes

Temperature is a fundamental constraint on biological systems, yet how it is reflected in genome sequence organization remains unclear. Here, we show that genome-wide distributions of short DNA sequences contain a robust signal of thermal adaptation that is largely independent of phylogeny. Using Structural Topic Modelling (STM), a machine-learning approach for identifying groups of co-occurring sequence motifs, we analyze canonical 6-mer and 9-mer frequency profiles of bacterial and archaeal genome proxies (randomly sampled genomic regions) and identify motif families systematically associated with thermophiles and psychrophiles. In bacterial thermophiles, the identified motif families are dominated by highly specific, overrepresented and co-occurring C- and G-stacked hexamers, and a distinct family of CG-periodic hexamers recurring across multiple temperature comparisons. In contrast, bacterial psychrophile-associated motifs are dominated by low-complexity A-, T-, and AT-run hexamers. Thermophilic archaea generally exhibit a distinct CTAG-centred hexamer family, suggesting that different domains may adapt to similar environmental constraints through different sequence-level solutions. However, this domain-level contrast is not absolute: in a targeted analysis of two thermophilic bacterium–archaeon pairs, we find unusually similar frequencies of all the STM-identified thermophile-associated hexamer families, suggesting that shared high-temperature environments can, in specific cases, partially override phylogenetic divergence. Notably, the identified motif families constitute only a small and highly selective subset of the vast space of possible G+C-rich or A+T-rich sequences. This indicates that thermal adaptation is associated with specific sequence architectures rather than broad shifts in nucleotide composition. Accordingly, the observed signal cannot be explained by overall base composition alone, but instead arises from structured combinations and positional arrangements of nucleotides within short sequence contexts. Related motif families are recovered at both k=6 and k=9, indicating that the signal reflects systematic shifts in genome-wide sequence organization rather than isolated sequence motifs. These patterns are consistent with known sequence-dependent DNA physical properties documented in biochemical and biophysical studies, including differences in base-stacking interactions and conformational flexibility. Together, our results suggest that genome-wide sequence organization reflects sequence-dependent DNA physical properties associated with thermal adaptation, revealing a previously underappreciated physical layer of genomic information beyond phylogenetic history.

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

Gaussian Process Prior Variational Autoencoder for Endoscopic Videos

Endoscopic video analysis is essential for gastrointestinal diagnosis and computer-assisted interventions, but video sequences are routinely degraded by specular reflections, motion artifacts, and missing frames. These transient corruptions can distract clinicians, reduce image interpretability, and disrupt downstream tasks such as 3D reconstruction and navigation. Effective restoration therefore requires methods that exploit temporal continuity rather than treating frames in isolation. We introduce a Gaussian Process Prior Variational Autoencoder (GPVAE) framework for endoscopic video restoration that replaces the standard factorized latent prior with a temporal Gaussian process prior, enabling interpolation of missing frames with uncertainty-aware reconstruction. The framework combines endoscopy-specific encoders, including a convolutional EndoVAE backbone and pretrained Vision Transformer encoders from GastroNet-5M, with two scalable GP approximations: Hierarchical Prior Approximation (HPA) and Sparse Precision Approximation (SPA). Specular reflections are handled using a DUCKNet-based masking pipeline that excludes corrupted pixels from the reconstruction objective. On the C3VDv2 colonoscopy dataset, the best GPVAE variants reduced image reconstruction RMSE by 21.9\% on average, and by up to 26.1\%, relative to matched VAE baselines. Downstream trajectory RMSE was reduced by 12.7\% on average across classical visual odometry and a pretrained PoseNet, at an average increase of 27.3\% in training time per epoch. Finally, the GP posterior provides per-frame uncertainty estimates that reflect temporal support and offer a confidence signal for restored frames.

08.
arXiv (CS.AI) 2026-06-16

Controlled Dynamics Attractor Transformer

arXiv:2606.15207v1 Announce Type: cross Abstract: Transformer architectures have dramatically advanced representation learning and inference in deep models through self-attention mechanisms. In parallel,associative memory (AM) frameworks map representations onto energy landscapes, offering interpretable retrieval mechanisms. However, their continuous-time inference dynamics lack the biological plausibility of classical Continuous Attractor Neural Networks (CANNs). To bridge this gap, we propose Controlled Dynamics Attractor Transformer (CDAT), which couples a mixture von Mises-Fisher (Mo-vMF) attention energy with a Hopfield refinement energy, while augmenting energy descent with a CANN-inspired excitation-inhibition modulation. CDAT instantiates a topology-constrained dynamical system whose couplings encode relational structure among tokens, thereby linking attractor-style dynamics to modern energy-based attention. We further provide a constructive dissipation analysis to formally establish their controlled inference dynamics. Benefiting from these robust and structured dynamics, CDAT achieves state-of-the-art performance across multiple benchmarks in graph anomaly detection and graph classification.

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

Limited Marginal Benefit of Reasoning-Heavy LLM Deployment in ESG Narrative Scoring: A 4-Model Consensus Study on Japanese Listed Firms

arXiv:2606.13693v1 Announce Type: cross Abstract: Automated scoring of ESG narrative disclosures with large language models (LLMs) is gaining traction, yet whether reasoning-heavy frontier models add value commensurate with their cost remains empirically unsettled. We evaluate this question on a corpus of ten Japanese listed firms across three rubric axes – quantitative targets, progress-tracking infrastructure, and external-standard alignment – using a four-model consensus design that combines a reasoning-on frontier model with three reasoning-off contemporaries. Across 120 firm x axis x model scores, the pooled mean absolute deviation between the reasoning-on model and each reasoning-off counterpart is 0.38 on a 5-point scale; only 2% of pairwise comparisons reach a two-point deviation, and none exceeds two points. Per-firm cost accounting shows the reasoning-on arm alone costs roughly 5.6x as much as the three-provider reasoning-off ensemble, for outcomes that differ only within small margins. We conclude that in span-based ESG narrative scoring, reasoning-heavy deployment does not materially improve outcomes relative to reasoning-off consensus, while substantially increasing operational cost. We discuss implications for cost-effective ESG auto-scoring pipelines and LLM deployment governance in applied accountability settings. An earlier version of this work is available on SSRN (Abstract ID 6683303).

10.
arXiv (CS.CV) 2026-06-19

Can Agents Distinguish Visually Hard-to-Separate Diseases in a Zero-Shot Setting? A Pilot Study

The rapid progress of multimodal large language models (MLLMs) has led to increasing interest in agent-based systems. While most prior work in medical imaging concentrates on automating routine clinical workflows, we study an underexplored yet clinically significant setting: distinguishing visually hard-to-separate diseases in a zero-shot setting. We benchmark representative agents on two imaging-only proxy diagnostic tasks, (1) melanoma vs. atypical nevus and (2) pulmonary edema vs. pneumonia, where visual features are highly confounded despite substantial differences in clinical management. We introduce a multi-agent framework based on contrastive adjudication. Experimental results show improved diagnostic performance (an 11-percentage-point gain in accuracy on dermoscopy data) and reduced unsupported claims on qualitative samples, although overall performance remains insufficient for clinical deployment. We acknowledge the inherent uncertainty in human annotations and the absence of clinical context, which further limit the translation to real-world settings. Within this controlled setting, this pilot study provides preliminary insights into zero-shot agent performance in visually confounded scenarios.

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

TINNs: Time-Induced Neural Networks for Solving Time-Dependent PDEs

arXiv:2601.20361v2 Announce Type: replace Abstract: Physics-informed neural networks (PINNs) solve time-dependent partial differential equations (PDEs) by learning a mesh-free, differentiable solution that can be evaluated anywhere in space and time. However, standard space-time PINNs take time as an input but reuse a single network with shared weights across all times, forcing the same features to represent markedly different dynamics. This coupling degrades error performance and can destabilize training when enforcing PDE, boundary, and initial constraints jointly. We propose Time-Induced Neural Networks (TINNs), a novel architecture that parameterizes the network weights as a learned function of time, allowing the effective spatial representation to evolve over time while maintaining shared structure. The resulting formulation naturally yields a nonlinear least-squares problem, which we optimize efficiently using a Levenberg-Marquardt method. Experiments on various time-dependent PDEs show up to 4 times improved relative error and 10 times faster convergence compared to PINNs and strong baselines.

12.
medRxiv (Medicine) 2026-06-15

Repurposing cardiovascular disease risk models to predict incident and co-occurring cardiovascular, cardiometabolic and neurocognitive outcomes.

Background: Cardiovascular disease (CVD), cardiometabolic and neurocognitive conditions share risk factors and frequently co-occur. We evaluated whether four established CVD risk prediction models (QRISK3, PCE, SCORE2, SCORE2-OP) can be repurposed to predict 10-year risk of these conditions and their co-occurrence with CVD. Methods: The models were recalibrated using 20% of the UK Biobank (UKB) and evaluated in the remaining 80%. We performed external validation using data from Clinical Practice Research Datalink (CPRD) Aurum, assessing model discrimination (c-statistics) and calibration (intercept and slope). We used permuted feature importance to determine the influence of each individual predictor in the models. Results: Depending on the model, the c-statistics for incident CVD ranged from 0.71 to 0.74 in the UKB test set (16,137 events). Discrimination was equal to or higher than CVD when evaluated against non-traditional CVD outcomes: 0.74 to 0.77 for heart failure (3,471 events), 0.72 to 0.73 for atrial fibrillation (9,213 events), 0.73 to 0.75 for peripheral arterial disease (1,927 events) and 0.80 to 0.82 for abdominal aortic aneurysm (595 events). For the multimorbidity endpoints, model discrimination ranged from 0.74 for the composite of CVD and T2DM (SCORE2-OP) to 0.83 for the composite of CVD and dementia or Parkinson's disease (QRISK3). When considering the onset of any cardiovascular, cardiometabolic, or neurocognitive outcome discrimination ranged from 0.71 to 0.72. The repurposed models slightly underestimated the predicted risk in the CPRD compared to the UKB: average difference in calibration intercept was at most -0.64. After age and sex, smoking status and systolic blood pressure contributed most to model predictions. Conclusions: Repurposed CVD models can be used to identify 10-year risk of many CVD-related conditions and their multimorbidity. These may be used to support risk-based approaches to prevention and screening. The repurposed models have been made available at: https://repurposed-cvd-risk-models.shinyapps.io/cvd_cmd_dementia_app/ Keywords: Risk prediction; cardiovascular disease; cardiometabolic disease; dementia; disease prevention.

13.
Nature (Science) 2026-06-08

Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding

作者:

Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in ~40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging. Here, we programmed CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage activities3,4, to selectively kill cancer cells by targeting cancer-specific transcripts. This approach limits cell growth by inducing trans shredding of chromatin, triggering DNA damage responses and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides a new approach to precision disease treatments for undruggable targets.

14.
medRxiv (Medicine) 2026-06-22

Clinical-grade Cuffless Blood Pressure Monitoring via Deep-tissue Diffuse Speckle Pulsatile Flowmetry

Blood pressure (BP) is a vital sign which is measured to diagnose and manage hypertension. However, current methods to measure BP use inflatable cuffs which cause discomfort and limit the frequency at which measurements can be made, or intra-arterial catheters which are invasive and pose infection risks. Here, we propose and evaluate the use of Diffuse Speckle Pulsatile Flowmetry (DSPF) as a cuffless BP measurement method to address these limitations. DSPF is a laser speckle-based technique which simultaneously records blood flow rate and blood volume (i.e. photoplethysmography or PPG) signals from relatively deep vascular tissue. Using information from these signals, we studied DSPFs effectiveness in measuring systolic BP (SBP) and diastolic BP (DBP) through an outpatient study in which 133 patients were recruited, and in measuring beat-to-beat BP waveforms through an inpatient study in which two patients were recruited. In the outpatient study, the DSPF method was able to achieve mean absolute errors (MAEs) of 4.17 mmHg and 2.42 mmHg for SBP and DBP respectively compared to conventional cuff-based methods. It was also able to fulfil the requirements of the AAMI/ESH/ISO 81060-2:2018 standard for BP measurement devices and attain an "A" grade according to the British Hypertension Society grading scheme. For the inpatient study, it produced BP waveforms which had MAEs of 2.35 mmHg and 3.06 mmHg compared to arterial-line measurements for the two patients, respectively. Compared to PPG which has been studied more extensively as a cuffless BP measurement method, we found through ablation studies that DSPF was able to reach significantly lower MAEs and hence better accuracies. DSPF augments the performance of PPG-only methods by leveraging additional information from the blood flow rate signal, and we therefore find it to be a superior cuffless BP measurement method which can potentially be used in outpatient, inpatient, and remote settings.

15.
arXiv (CS.AI) 2026-06-19

Global Ease of Living Index: a machine learning framework for longitudinal analysis of major economies

arXiv:2502.06866v3 Announce Type: replace-cross Abstract: The drastic changes in the global economy, geopolitical conditions, and disruptions such as the COVID-19 pandemic have impacted the cost of living and quality of life. It is essential to comprehend the long-term implications of the cost of living and quality of life in major economies. A transparent and comprehensive living index must include multiple dimensions of living conditions. In this study, we present an approach to quantifying the quality of life through the Global Ease of Living Index that combines various socio-economic and infrastructural factors into a single composite score. Our index utilises economic indicators that define living standards, which could help in targeted interventions to improve specific areas. We present a machine learning framework to address missing data for certain economic indicators in specific countries. We then curate and update the data and use a dimensionality reduction approach (Principal Component Analysis and Factor Analysis) to create the Ease of Living Index for major economies since 1970. Our work significantly adds to the literature by offering a practical tool for policymakers to identify areas needing improvement, such as healthcare systems, employment opportunities, and public safety. Our approach with open data and code can be easily reproduced and applied to various contexts, providing transparency and accessibility for ongoing research and policy development in quality-of-life assessment.

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

Latent Space Reinforcement Learning for Inverse Material Estimation in Food Fracture Simulation

Realistic visual simulation of food manipulation requires accurate material parameters, yet these are difficult to measure directly and vary across the heterogeneous regions of a single food item. We address the inverse problem of estimating material parameters from a target description of fracture behavior in a non-differentiable continuum damage mechanics simulator. Using orange peeling as a test case, we train a neural surrogate on 2,000 forward simulations and compare Covariance Matrix Adaptation Evolution Strategy (CMA-ES, a gradient-free evolutionary optimizer) with Proximal Policy Optimization (PPO, a reinforcement learning algorithm) across the original 9-dimensional parameter space and two learned 4-dimensional latent representations. Since different oranges have different material properties, a practical inverse system must handle arbitrary targets without retraining. We train a goal-conditioned PPO policy that learns a general inverse mapping: given any target description of peeling behavior, the policy produces a material parameter estimate in a single forward pass (8 surrogate evaluations, approximately 10ms). Operating in a normalizing flow latent space with a shared surrogate evaluator, the goal-conditioned policy achieves 0.642 actual recovery when validated through the simulator, outperforming the original parameter space by 23%. A warm-start extension that initializes CMA-ES refinement from the policy's output further improves recovery to 0.828 with 540 evaluations. These findings provide a practical framework for inverse food physics and lay groundwork for vision-driven material identification from video observations of food manipulation.

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

CORA: Analyzing and bridging thinking-answer gap in Multimodal RLVR via Consistency-Oriented Reasoning Alignment

Reinforcement learning with verifiable rewards (RLVR) has successfully elicited the reasoning capabilities of large language models, motivating its extension to multimodal scenarios. Existing methods primarily focus on improving the visual coverage of reasoning traces and mitigating visual hallucinations, but underestimate the semantic inconsistency between the reasoning process and the final answer. In this paper, we delve into thinking-answer inconsistency in RLVR for large vision-language models (LVLMs), showing thorough analyses of rollouts collected throughout Group Relative Policy Optimization (GRPO) training process and post-RLVR evaluation outputs that this issue persists during training and remains present during inference. Motivated by the analysis, we propose Consistency-Oriented Reasoning Alignment (CORA), which introduces thinking-answer semantic consistency into RLVR through a lightweight plug-and-play consistency reward model, and further incorporates Hybrid Reward Advantage Splitting (HRAS) to stably coordinate task and consistency optimization. Extensive experiments across representative multimodal reasoning benchmarks and mainstream LVLMs show that CORA improves task performance while effectively mitigating thinking-answer inconsistency, leading to more faithful reasoning traces.

18.
arXiv (CS.CV) 2026-06-16

Question-Aware Evidence Ledgers for Video Relational Reasoning

The VRR-QA challenge evaluates visual relational reasoning in videos, where answers often depend on implicit spatial relations, event boundaries, target identity, and dialogue context rather than a single salient frame. We present a test-time reasoning pipeline built around a strong GPT-5.5 video QA solver and a set of question-aware evidence ledgers. The initial solver answers each question from a uniform video representation, while routed ledgers are prompted to make the required targets, count units, reference frames, and temporal or spatial scope explicit for counting, spatial, endpoint, viewpoint, and dialogue reasoning. External tools such as open-vocabulary detection, depth cues, pair crops, ASR, and scene-graph ledgers are used only as evidence sources. A conservative gate keeps the current answer unless independent evidence uniquely supports a different option. The final evidence-gated pipeline achieves 92.95% overall accuracy and 93.79% macro accuracy on the challenge test split.

19.
Nature (Science) 2026-06-10

Structural basis for chaperone-guided assembly of RNA-induced silencing complex

The RNA-induced silencing complex (RISC), comprising an Argonaute (AGO) protein and a small RNA, is the central effector in RNA silencing. Small RNAs are loaded onto AGO as bulky duplexes in an HSP70- and HSP90-dependent process1–3, but the molecular mechanism remains poorly understood. Here we identify the human AGO–HSP90–p23 complex, which captures AGO in an RNA-free state, termed the AGO maturation complex (AMC). The purified AMC enables RNA loading and AGO folding, faithfully recapitulating de novo RISC assembly. Using cryogenic electron microscopy, we determined the structure of AMC bound to a microRNA duplex. In contrast to its conformation in the RISC, AGO adopts a highly open conformation in the AMC: the N domain and the RNA-binding module (PAZ–MID–PIWI) are fully detached and anchored to opposite sides of the HSP90 dimer, connected solely by the unfolded L1 linker. This arrangement exposes a positively charged cleft that accommodates an RNA duplex. AGO folding is facilitated by a small RNA duplex containing a 5′-terminal phosphate—but not by single-stranded RNAs—revealing a role for the RNA duplex as a chaperone-like cofactor that directs AGO domain assembly. These findings elucidate the RISC assembly mechanism and establish the AMC as a molecular tool for probing optimal RNA features and chemical modifications for the rational design of small interfering RNA therapeutics. Our study also sheds light on how chaperones, together with ligands, can guide the folding of client proteins. Structures of the AGO maturation complex reveal how chaperones and an RNA duplex drive assembly of the RNA-induced silencing complex.

20.
arXiv (CS.CV) 2026-06-17

PhaseWin: An Efficient Search Algorithm for Faithful Visual Attribution

Visual attribution is a fundamental tool for interpreting modern vision and vision-language models, particularly when their decisions must be inspected, diagnosed, or audited. Its goal is to explain how a model's decision depends on local regions of the visual input, typically by assigning an importance ordering over candidate image regions. Given an image partitioned into $n$ regions, faithful attribution can be cast as an ordered subset-search problem, in which progressively inserting the selected regions should recover the target model response as early as possible. Exhaustive search over region subsets incurs exponential cost, while the widely used greedy search still requires a quadratic number of model evaluations, because every selection step rescores all remaining candidates. We propose PhaseWin, an efficient subset-search algorithm for faithful visual attribution. PhaseWin reorganizes greedy region selection into a phased window-search procedure: rather than re-evaluating the full candidate set at every step, it alternates between global candidate screening, adaptive pruning, and localized window refinement, while preserving the essential region-ranking behavior of greedy search. We analyze PhaseWin under monotone evidence-accumulation conditions and show that, under feature-level structural assumptions, it attains controllable linear evaluation complexity together with near-greedy faithfulness guarantees. Extensive experiments on image classification, object detection, visual grounding, and image captioning show that, among all compared attribution methods, PhaseWin reaches high faithfulness with the fewest forward passes, empirically realizing the predicted reduction from $O(n^2)$ to $O(n)$. The code is available at https://github.com/Qihuai27/phasewin-va.

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

MBABench: Evaluating LLM Agents on End-to-End Spreadsheet Tasks in Finance

arXiv:2605.22664v3 Announce Type: replace Abstract: LLM agents are increasingly expected to carry out end-to-end workflows, producing complete artifacts from high-level user instructions. To meet enterprise needs, frontier AI labs have developed agents that can construct entire spreadsheets from scratch. This is especially relevant in finance, where core workflows such as financial modeling, forecasting, and scenario analysis are commonly conducted through spreadsheets. Yet, existing spreadsheet benchmarks do not measure this advanced capability, focusing instead on question-answering or single-formula edits. To address this gap, we provide one of the first evaluations of agents on end-to-end spreadsheet tasks, focusing on economically critical financial workflows such as modeling and scenario analysis. Since deliverables therein are routinely reviewed and revised by multiple stakeholders, judging their quality necessarily involves high-level criteria such as readability or ease of modification. To reflect the multidimensional nature of solution quality, we develop an evaluation taxonomy comprising three dimensions: Accuracy, Formula, and Format, each comprising fine-grained criteria that reflect professional standards. The Claude family leads the benchmark and produces the most professional-looking outputs in our qualitative review, but even the strongest agents frequently fall short of professional finance standards and degrade sharply as the difficulty increases beyond a few chained calculations. This suggests that current agents are not yet able to reliably produce professional-quality spreadsheets at the level of complexity real-world workflows demand.

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

Tackling GNARLy Problems: Graph Neural Algorithmic Reasoning Reimagined through Reinforcement Learning

arXiv:2509.18930v3 Announce Type: replace-cross Abstract: Neural algorithmic reasoning (NAR) is a paradigm that trains neural networks to execute classic algorithms by supervised learning. Despite its successes, important limitations remain: inability to construct valid solutions without post-processing and to reason about multiple correct ones, poor performance on combinatorial NP-hard problems, and inapplicability to problems for which strong algorithms are not yet known. To address these limitations, we reframe the problem of learning algorithm trajectories as a Markov decision process, which imposes structure on the solution construction procedure and unlocks the powerful tools of imitation and reinforcement learning (RL). We propose the GNARL framework, encompassing the methodology to translate problem formulations from NAR to RL and a learning architecture suitable for a wide range of graph-based problems. We achieve very high graph accuracy results on several CLRS-30 problems, performance matching or exceeding much narrower NAR approaches for NP-hard problems and, remarkably, applicability even when lacking an expert algorithm.

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

LLM Jaggedness Unlocks Scientific Creativity

arXiv:2605.10574v3 Announce Type: replace Abstract: As artificial intelligence advances, models are not improving uniformly. Instead, progress unfolds in a jagged fashion, with capabilities growing unevenly across tasks, domains, and model scales. In this work, we examine this dynamic jaggedness through the lens of scientific idea generation. We introduce SciAidanBench, a benchmark of open-ended scientific questions designed to measure the scientific creativity of large language models (LLMs). Given a scientific question, models are asked to generate as many unique and coherent ideas as possible, with the total number of valid responses serving as a proxy for creative potential. Evaluating 19 base models across 8 providers (30 total variants including reasoning versions), we find that jaggedness manifests both across models and within models. First, in a cross-task comparison between general and scientific creativity, improvements in general creativity do not translate uniformly to scientific creativity, revealing divergent capability profiles across models. Second, at the prompt level, stronger models do not improve uniformly; instead, they exhibit high variability, with bursts of creativity on some questions and limited performance on others. Third, at the domain level, individual models display uneven strengths across scientific subfields, reflecting fragmented internal capability profiles. Finally, we show that this jaggedness can be harnessed. We explore mechanisms of inference-time compute, knowledge pooling, and brainstorming to combine models effectively and construct meta-model ensembles that outperform any single model. Our results position jaggedness not as a limitation, but as a resource, a structural feature of AI progress that, when understood and leveraged, can amplify LLM-driven scientific creativity.

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

Focus When Necessary: Adaptive Routing and Collaborative Grounding for Training-Free Visual Grounding

While Multimodal Large Language Models (MLLMs) excel in cross-modal reasoning, they often struggle to perceive fine-grained details in complex high-resolution images. Recent training-free methods address this through image scaling and localized cropping. However, applying these manipulations indiscriminately introduces computational redundancy for simple queries and can degrade accuracy by truncating essential global context or introducing irrelevant background noise. To this end, we propose LazyMCoT, a dynamic and training-free framework that adaptively allocates visual grounding efforts based on sample difficulty. The framework features an Adaptive Routing mechanism that evaluates predictive uncertainty using first-token statistics from a single forward pass. This efficiently bypasses confident cases while ensuring the recall of difficult samples via conformal calibration. For these challenging cases, a Collaborative Grounding module integrates the inherent cross-modal attention of the model with an external visual expert through a two-stage refinement process. This refinement process generates a precise localized display to recover small or occluded targets. Extensive experiments across diverse benchmarks demonstrate that LazyMCoT rivals training-based approaches by simultaneously improving reasoning accuracy and reducing average inference latency. Our code is availble at https://github.com/TencentBAC/LazyMCoT.