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01.
Nature Medicine 2026-06-22

<b>PROTEUS trial heralds perioperative therapy for prostate cancer</b>

Perioperative androgen-deprivation therapy plus apalutamide could represent a new treatment option for patients with high-risk, localized prostate cancer. Perioperative androgen-deprivation therapy plus apalutamide could represent a new treatment option for patients with high-risk, localized prostate cancer.

02.
arXiv (CS.AI) 2026-06-12

OCOO-T : A Simple and Scalable Virtual Cell Model for Transcriptional Perturbation Response Prediction

arXiv:2606.12838v1 Announce Type: cross Abstract: Predicting single-cell transcriptional responses to genetic, chemical and cytokine perturbations is a fundamental challenge in computational biology and AI Virtual Cell (AIVC) modeling, with direct implications for drug discovery and the elucidation of gene regulatory networks. Existing approaches often rely on auxiliary cell-state encoders, hierarchical variational autoencoders, dedicated Transformer encoder-decoder modules, or gene-interaction priors to compress high-dimensional expression profiles into latent representations. While effective, these designs increase architectural complexity and may limit scalability and generalizability. This paper introduces OCOO-T, a minimalist flow-matching-based AIVC model for transcriptional perturbation response prediction. OCOO-T utilizes a vanilla Transformer stack that operates directly on continuous gene expression profiles and formulates perturbation response prediction as a continuous-time denoising process. Perturbation embeddings, dosage information, and cell-line/cell-type specificity are integrated through adaptive layer normalization and in-context tokens. Comprehensive evaluations on Tahoe100M, Replogle, and PBMC benchmarks demonstrate that OCOO-T achieves state-of-the-art performance across diverse perturbations and cell types while effectively scaling to long transcriptional profiles through patching and depatching of cellular contexts. By leveraging the simplicity of Transformer-based denoising for single-cell omics, OCOO-T provides an effective and scalable framework for in-silico cellular simulation.

03.
arXiv (CS.AI) 2026-06-16

AL-GNN: Privacy-Preserving and Replay-Free Continual Graph Learning via Analytic Learning

arXiv:2512.18295v2 Announce Type: replace-cross Abstract: Continual graph learning (CGL) aims to enable graph neural networks to incrementally learn from a stream of graph structured data without forgetting previously acquired knowledge. Existing methods particularly those based on experience replay typically store and revisit past graph data to mitigate catastrophic forgetting. However, these approaches pose significant limitations, including privacy concerns, inefficiency. In this work, we propose AL GNN, a novel framework for continual graph learning that eliminates the need for backpropagation and replay buffers. Instead, AL GNN leverages principles from analytic learning theory to formulate learning as a recursive least squares optimization process. It maintains and updates model knowledge analytically through closed form classifier updates and a regularized feature autocorrelation matrix. This design enables efficient one pass training for each task, and inherently preserves data privacy by avoiding historical sample storage. Extensive experiments on multiple dynamic graph classification benchmarks demonstrate that AL GNN achieves competitive or superior performance compared to existing methods. For instance, it improves average performance by 10% on CoraFull and reduces forgetting by over 30% on Reddit, while also reducing training time by nearly 50% due to its backpropagation free design.

04.
arXiv (CS.AI) 2026-06-15

A Multi-Agent AI System for Automated High School Transcript Processing: Collaborative Document Analysis at Scale

arXiv:2606.13916v1 Announce Type: new Abstract: Each year, college admissions offices face an overwhelming challenge: processing millions of high school transcripts, each with unique formats, grading systems, and layouts. This manual process creates operational bottlenecks that delay admissions decisions and consume valuable resources. We present a transformative solution through a multi-agent AI system where specialized agents collaborate to automatically process diverse transcript formats through intelligent coordination and communication. Our multi-agent architecture consists of three specialized agents-a Pattern Recognition Agent for format-specific parsing, a Semantic Analysis Agent for natural language understanding, and a Vision Intelligence Agent for multimodal document analysis-coordinated by an Orchestration Agent that manages agent communication and result reconciliation. Our key innovation lies in agent-based quality control using GPA extraction as a coordination signal, ensuring reliable agent collaboration and preventing critical information loss. When evaluated on 40 real world transcripts from high schools across 13 U.S. states, our agent system successfully processed every document, achieving 96.7% accuracy compared to expert manual review while maintaining practical processing speeds of 45 seconds per transcript. This work demonstrates how multi-agent coordination can solve complex document processing challenges, offering institutions a scalable, collaborative AI solution that preserves accuracy while dramatically reducing processing time.

05.
medRxiv (Medicine) 2026-06-16

Non-invasive Detection of Fasciculation Using Surface EMG with a Wavelet-Based Analytical Method (DEWCS)

Objective: Needle electromyography (nEMG) is essential for diagnosing neuromuscular disorders but is invasive and often painful. We employed single-channel bipolar surface EMG (sEMG) analyzed with a novel wavelet-based analytical approach, Detecting and Extracting Elemental Wave Components based on a Wavelet Coefficient Set (DEWCS) and investigated whether fasciculation-related activity could be identified. Methods: In this prospective study, 28 patients undergoing nEMG for suspected neuromuscular disorders and 13 healthy controls were included. Resting-state sEMG was recorded from selected muscles using single-channel bipolar active electrodes at a high sampling rate. DEWCS was used to extract indices reflecting fast- and slow-type motor unit (MU)-related activity. These standardized indices were evaluated against nEMG-detected fasciculation potentials using generalized estimating equation logistic regression to account for within-subject clustering. Diagnostic performance was assessed by receiver operating characteristic analysis. Results: A total of 67 muscles from 38 participants were analyzed. Indices of fast- and slow-type MU-related activity were significantly associated with fasciculation potentials (slow: OR 5.10, p = 0.0041; fast: OR 2.38, p = 0.0162). The combined model showed excellent discrimination (area under the curve = 0.97), outperforming either index alone. Muscle region had no significant effect. Conclusions: A single-channel bipolar sEMG setup combined with DEWCS detected fasciculation-related activity with promising accuracy. This method may serve as a non-invasive surrogate marker of lower motor neuron involvement. Further validation in larger cohorts is warranted. Significance: This non-invasive sEMG approach may help detect fasciculation-related activity and complement nEMG in neuromuscular diagnostics.

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

Toward quantum-noise-limited interferometric measurements of optical nonlinearity in vacuum

arXiv:2602.10896v2 Announce Type: replace-cross Abstract: Quantum Electrodynamics predicts that the vacuum must behave as a nonlinear optical medium: the vacuum optical index should increase when it is stressed by intense electromagnetic fields. The DeLLight (Deflection of Light by Light) project aims to measure it by using intense and ultra-short laser pulses. The experiment uses a Sagnac interferometer to amplify the tiny deflection signal of a low-intensity probe pulse crossing the vacuum refractive-index gradient produced by an external high-intensity pump pulse. The measurement of the amplified signal by a CCD camera requires a high spatial resolution, which is limited by the ultimate quantum noise of the CCD. However, interferometric phase noise induced by the mechanical vibrations of the interferometer is also amplified and degrades spatial resolution. To overcome this, we propose a new method named High-Frequency Phase Noise Suppression (HFPNS), based on the addition of a delayed replica (5 ns) of the probe pulse. The delayed pulse, which is not affected by the pump but is subject to the same vibration noise, enables offline subtraction of correlated phase noise. In this work, we present an experimental proof-of-concept on a prototype interferometer operating with a limited amplification factor ($\mathcal{A}\simeq25$), about 10 times smaller than the required value of the final experiment. We have succeeded in reducing phase noise by a factor of 40, resulting in a residual noise level 2.3 times higher than the expected quantum noise. The residual noise is linked to delay-line instabilities and incident beam pointing fluctuations present during these tests. This result validates HFPNS as a robust method for future quantum-noise-limited interferometric measurements of vacuum optical nonlinearity, though additional stabilization and higher interferometric amplification are still needed.

07.
arXiv (CS.CL) 2026-06-17

Prompt Perturbation for Reliable LLM Evaluation over Comparison Graphs

Evaluating large language models (LLMs) is important for understanding their capabilities, comparing competing systems, and supporting the deployment of reliable models in practice. For open-ended tasks, pairwise evaluation has become a popular paradigm, in which two responses to the same prompt are compared and the resulting judgments are aggregated into an overall ranking. A central challenge of this paradigm is intransitivity: the induced comparison outcomes may fail to support any coherent global ranking. For example, one may observe cyclic preferences such as $A \succ B \succ C \succ A$, or inconsistencies involving ties such as $A \equiv B\equiv C\neq A$. Such contradictions make the resulting leaderboard unstable and challenging to interpret. In this paper, we propose a prompt perturbation framework for improving the consistency of pairwise LLM evaluation. Our approach generates perturbed variants of each prompt, uses the resulting comparison graphs to identify and filter out structurally inconsistent comparison patterns, and then applies standard ranking methods to the filtered comparisons. A key feature of the proposed framework is that graph-level structural consistency is incorporated explicitly into the evaluation pipeline before ranking aggregation. This provides a simple and principled way to reduce cyclic inconsistencies and improve the reliability of LLM rankings.

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

LLM-as-an-Investigator: Evidence-First Reasoning for Robust Interactive Problem Diagnosis

arXiv:2606.13220v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly used as interactive assistants for technical problem solving. However, when users provide incomplete descriptions or plausible but unverified explanations, LLMs may prematurely align with these assumptions and propose solutions before collecting sufficient evidence. We refer to this behavior as user-driven sycophancy: the tendency of an LLM to reinforce a user-provided hypothesis instead of testing alternative explanations. This paper introduces LLM-as-an-Investigator, an evidence-first agentic AI methodology for robust problem diagnosis. The approach is implemented through a Solution Investigator Agent, which estimates the ambiguity of an initial problem description, generates candidate hypotheses, asks targeted clarification questions, and updates hypothesis probabilities after each answer. Rather than producing an immediate response, the agent continues the investigation until the evidence makes one candidate explanation stronger than the alternatives. To evaluate the approach, we build a benchmark from solved technical forum threads in mechanical, electrical, and hydraulic domains. We use a three-agent evaluation pipeline in which a Problem-Solution Extractor Agent converts solved threads into structured cases, a Ground-Truth Evaluator Agent simulates the user while hiding the known solution, and the tested assistant attempts to recover the solution through dialogue. The experiments compare standard assistants, reasoning-oriented LLMs, and the proposed investigator-based model across LLM backbones. In addition to diagnostic accuracy, we analyze how standard assistants follow misleading user hypotheses in diagnostic cases. The results show that the proposed approach identifies the problem more accurately than direct prompting and reasoning-only baselines, while its evidence-first protocol helps reduce user-induced conversational bias.

09.
arXiv (CS.CL) 2026-06-12

Select to Think: Unlocking SLM Potential with Local Sufficiency

Small language models (SLMs) offer efficient deployment, yet they often lag behind their larger counterparts (LLMs) in reasoning. Existing remedies either invoke an LLM at points of reasoning divergence, incurring substantial latency and cost, or rely on standard distillation, which is limited by the SLM's capacity to accurately mimic the LLM's complex generative distribution. We address this dilemma by identifying local sufficiency: at divergence points, the LLM's preferred token often resides within the SLM's top-K next-token predictions, even when failing to emerge as the SLM top-1 choice. We therefore propose Select to Think (S2T), which reframes the LLM's role from open-ended generation to selection among the SLM's proposals, simplifying the supervision signal to discrete candidate rankings. Leveraging this, we introduce S2T-Local, which distills the selection logic into the SLM, empowering it to perform autonomous re-ranking without inference-time LLM dependency. Empirically, a 1.5B SLM's top-8 candidates contain the 32B LLM's choice with a 95% hit rate, and S2T-Local improves the 1.5B SLM's Math Avg. over greedy decoding by 24.1% relative gain, matching the efficacy of 8-path self-consistency with single-trajectory efficiency.

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

Reliable Neural-Codec Text-to-Speech by ASR Self-Verification and Distillation: Near-Zero Catastrophic Failures Across Models and Codecs

arXiv:2606.18323v1 Announce Type: cross Abstract: Open autoregressive neural-codec text-to-speech (TTS) models sound excellent on typical inputs yet suffer stochastic catastrophic failures: on a meaningful fraction of utterances they emit silence, terminate early, or collapse into repetitive or hallucinated content. We show this failure mode is cheap to remove. Under a single format-robust metric (a catastrophic-failure rate via an ASR round-trip), best-of-N ASR self-verification drives failures to near-zero: no observed failures remain by N=2 on a standard corpus (LibriSpeech) and by N=4 on a hard prompt set. This is not an artifact of one model: the reduction replicates across four open codec-TTS systems and three neural codecs (XCodec2, SNAC, Mimi), reaching the near-zero floor by N=2 on three of the four. We then make the fix free at inference time by distilling the self-verified behaviour into the model, which recovers much of the robustness in single-shot decoding, closing ~52-58% of the failure mass on hard inputs at no test-time cost. The distillation gain concentrates where it is needed (hard inputs); on already-reliable prose there is no headroom and no detectable change. A controlled comparison adds a clean negative: offline direct preference optimization (DPO/IPO) does not beat plain supervised distillation, and an online iterative variant is promising but not statistically separable at our evaluation size. We report honestly the one model that resists (a larger Llasa where scale did not obviously help) and a rare-word capability ceiling that no self-distillation method overcomes

11.
bioRxiv (Bioinfo) 2026-06-11

TifBERT: a self-supervised foundation model for normalization-robust bulk RNA-seq representation learning

Bulk RNA sequencing remains central to translational genomics, yet foundation-model development has largely focused on single-cell data. Existing transformer approaches for bulk RNA-seq often rely on expression discretization, numerical reconstruction, external gene embeddings, or restricted gene sets, limiting robustness across normalization schemes and cohorts. Here, we introduce TifBERT, a self-supervised framework for full-transcriptome bulk RNA-seq representation learning. TifBERT converts each unordered expression profile into a sample-specific gene sequence using term frequency-inverse document frequency (TF-IDF) ordering, prioritizing genes that are both highly expressed within a sample and selectively expressed across the cohort. It is then pretrained using masked gene modeling, predicting gene identities from transcriptomic context rather than reconstructing expression values. Pretrained on harmonized TCGA Pan-Cancer data spanning five RNA-seq normalization schemes, TifBERT learns contextual representations across approximately 10,000 genes without expression binning, landmark-gene restriction, or external biological embeddings. Across 33 TCGA cancer types, TifBERT achieved 90.83% accuracy, 0.996 macro AUC-ROC, and 0.903 MCC. It also captured pathway-level biology, achieving mean sample-wise and pathway-wise Pearson correlations of 0.754 and 0.762 across 1,387 PARADIGM pathway activities. Independent evaluation on GTEx healthy tissues showed preservation of tissue-level transcriptomic structure without retraining. In comparison with existing models, TifBERT achieves competitive subtype discrimination with substantially greater stability and produces markedly richer embedding geometry (effective rank 95.6 versus 6.3), without requiring expression discretization or in-distribution pretraining exposure. Together, TifBERT provides a scalable, normalization-independent foundation model for reusable bulk transcriptomic representation learning

12.
arXiv (CS.LG) 2026-06-11

Visualizing LLM Latent Space Geometry Through Dimensionality Reduction

arXiv:2511.21594v3 Announce Type: replace Abstract: Large language models (LLMs) achieve state-of-the-art results across many natural language tasks, but their internal mechanisms remain difficult to interpret. In this work, we extract, process, and visualize latent state geometries in Transformer-based language models through dimensionality reduction. We capture layerwise activations at multiple points within Transformer blocks and enable systematic analysis through Principal Component Analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP). We demonstrate experiments on GPT-2 and LLaMa models, where we uncover interesting geometric patterns in latent space. Notably, we identify a clear separation between attention and MLP component outputs across intermediate layers, a pattern not documented in prior work to our knowledge. We also characterize the high norm of latent states at the initial sequence position and visualize the layerwise evolution of latent states. Additionally, we demonstrate the high-dimensional helical structure of GPT-2's positional embeddings and the sequence-wise geometric patterns in LLaMa. We make our code available at https://github.com/Vainateya/Feature_Geometry_Visualization. A better formatted blog-post with identical content is available at https://iclr-blogposts.github.io/2026/blog/2026/vis-llm-latent-geometry/.

13.
arXiv (CS.CL) 2026-06-15

C2-Faith: Benchmarking LLM Judges for Causal and Coverage Faithfulness in Chain-of-Thought Reasoning

Large language models (LLMs) are increasingly used as judges of chain-of-thought (CoT) reasoning, yet it remains unclear whether they can reliably assess process faithfulness rather than merely answer plausibility. We introduce C2-Faith, a benchmark built from PRM800K that explicitly decomposes faithfulness into two complementary dimensions: causality (whether each step logically follows from prior context) and coverage (whether essential intermediate inferences are present). Using controlled perturbations, we construct examples with known causal error positions by replacing a single step with a logically inconsistent variant, and with controlled coverage deletions at varying rates, enabling direct measurement against reference labels. We evaluate three frontier LLM judges across three tasks: binary causal detection, causal step localization, and coverage scoring. Our results reveal that judge reliability is highly task-dependent, with no single model dominating across settings. While models often detect that an error exists, they struggle to accurately localize it, indicating a substantial gap between detection and attribution. Moreover, all judges systematically overestimate reasoning completeness, assigning high coverage scores even when substantial portions of intermediate reasoning are missing. These findings expose fundamental limitations of LLM judges in process-level evaluation and highlight the need for more reliable and calibrated methods when using LLMs to assess reasoning quality.

14.
arXiv (CS.AI) 2026-06-12

Mental-R1: Aligning LLM Reasoning for Mental Health Assessment

arXiv:2606.13176v1 Announce Type: new Abstract: Mental health problems such as anxiety, depression, and suicide remain urgent global challenges, where timely and accurate assessment is critical for effective intervention. Recently, large language models have been explored for mental health assessment. However, existing general-purpose post-training methods do not align with the cognitive processes of human assessment, which may lead to unreliable reasoning outcomes. To bridge this gap, we propose Cognitive Relative Policy Optimization (CRPO), a reinforcement learning framework tailored for the mental health domain. CRPO extends group relative policy optimization by integrating stage-dependent uncertainty modeling into the policy optimization process. Specifically, we introduce a stage-wise entropy regularization mechanism that encourages broad exploration in early reasoning phases and progressively enforces confident decision-making in later stages, mimicking the human cognitive shift from uncertainty to certainty. In addition, inspired by cognitive appraisal theory, we formalize cognitive reasoning stages, thereby guiding theory-grounded interpretable inference. Experiments on 8 mental health datasets show that CRPO achieves an average improvement of 10.4 percentage points in weighted F1-score over the best reinforcement learning baseline. Furthermore, the CRPO-trained model Mental-R1 demonstrates clear advantages compared with existing large language models on reasoning-intensive cases, suggesting that CRPO enhances reasoning capabilities for mental health assessment.

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

T2MM: An LLM Supported Architecture For Inquiry-Based Modeling

Model Construction is a foundational practice in science learning that relies on visualization and interactivity. Large Language Models, increasingly augmented with multimodal capabilities, have been integrated in education contexts to support learning. However, these tools lack visual interactivity that is required by some learning contexts. We introduce Text to Multimodal Model (T2MM), a robust, dynamic LLM supported architecture that assists in model construction within the open inquiry ecology-based modeling software Virtual Experimental Research Assistant (VERA). T2MM accounts for the current context of the learner's model and creates interactive models, rather than static images, enabling the model to remain responsive to manual adjustment. To measure technical feasibility, we evaluate T2MM through a custom procedurally generated dataset of natural language learner modeling requests and target models within the VERA system. T2MM outperforms a baseline model generation architecture implemented through LLM-supported full code generation, common in the literature, across all measured success metrics. Our contribution not only outlines LLM integration into a inquiry-based learning modeling tool, but also describes a possible architecture through which more interactive multimodal LLM tools can be created.

16.
arXiv (CS.AI) 2026-06-15

Hybrid Open-Ended Tri-Evolution Makes Better Deep Researcher

arXiv:2606.13710v1 Announce Type: new Abstract: Deep research and agent evolution serve as de-facto tasks for AI agents in real-world applications toward artificial general intelligence. The former enables autonomous retrieval and integration of information in open-ended environments to tackle open-ended research tasks, yet it is constrained by the static parametric deep research capabilities of agent systems. The latter allows agents to autonomously interact with the environment to gain experiences that evolve model capabilities. However, its effectiveness has been widely validated only on verifiable tasks with standard answers, leaving a gap with open-ended research tasks. To bridge these two critical tasks, we propose the Hybrid Open-Ended Tri-Evolution (HOTE) framework, which leverages hybrid-mode reinforcement learning to facilitate the collaborative evolution of a proposer, solver and judge based on web-scale knowledge, moving toward autonomous evolving agents in open-ended tasks and environments. Extensive experiments on three long-form deep research benchmarks demonstrate that the 8B model trained via HOTE surpasses the strongest static open 8-32B models as well as those trained by state-of-the-art deep research training methods with less time overhead, and further verify that the evolution of all three modules in HOTE is indispensable.

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

Understanding helpfulness and harmless tension in reward models

Reward models are a key component of reinforcement learning from human feedback (RLHF), aligning language models toward both helpful and harmless behaviour. However, the internal mechanisms underlying these objectives and their conflicts remain poorly understood. We study alignment tension in reward models trained under helpfulness-only, harmlessness-only, and mixed-objective settings. We find that mixed-objective models often underperform single-objective models, indicating interference between objectives. Using activation-based methods, we identify neurons associated with each objective and study their functional roles via targeted ablations. We find that these neurons causally support their corresponding objectives while often negatively affecting the opposing one. We find that a substantial proportion of neurons are shared between helpfulness and harmlessness, and that these shared neurons exert a disproportionate influence on model behaviour, contributing to alignment tension. Additionally, our results provide insights and mechanistic interpretation into how alignment objectives are represented in reward models and why multi-objective alignment remains challenging, motivating future work on disentangled and controllable alignment methods.

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

Deterministic Policy Gradient for Learning Equilibrium in Time-Inconsistent Control Problems

arXiv:2606.11798v1 Announce Type: cross Abstract: In this paper, we develop a continuous-time model-free reinforcement learning algorithm to learn deterministic equilibrium policies in general time-inconsistent control problems. Utilizing the extended Hamilton-Jacobi-Bellman system, we recast the original time-inconsistent problem into an equivalent two-stage problem. In the first stage, for given auxiliary functions, we employ the deterministic policy gradient approach to learn an optimal policy in an auxiliary time-consistent control problem. In the second stage, given the updated policy, we exploit the inner fixed point iterations and some martingale characterizations to learn the auxiliary functions. As a theoretical contribution, we provide some mild model assumptions and establish the convergence of inner fixed point iterations. By repeating this actor-critic style of iterations across two stages, our algorithm aims to learn the equilibrium under different sources of time-inconsistency in a unified manner. The superior effectiveness of the proposed algorithm are illustrated in two classical financial applications with time-inconsistency: mean-variance portfolio management and optimal tracking portfolio under non-exponential discounting.

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

Explaining Attention with Program Synthesis

arXiv:2606.19317v1 Announce Type: cross Abstract: A longstanding goal of research on interpretable deep learning is to replace opaque neural computations with human-meaningful symbolic descriptions. In this paper, we propose an approach for approximating the behavior of components of deep networks with executable programs. We focus on attention heads in transformer language models. For a given head, we first compute its associated attention matrices on a collection of randomly selected training examples. Next, we prompt a pre-trained language model with a summary of these matrices, and instruct it to generate a set of Python programs that can reproduce the associated attention patterns given only text from the input sentence. Finally, we re-rank programs according to how well our final set of programs predict behavior on held-out inputs. We demonstrate that a set of fewer than 1,000 such generated programs can reproduce the attention patterns of heads in GPT-2, TinyLlama-1.1B, and Llama-3B, achieving an average Intersection-over-Union similarity above 75% on TinyStories. Moreover, the best-fit programs can replace neural attention heads without substantially affecting model behavior: replacing 25% of attention heads with programmatic surrogates across the three models incurs only a 16% average perplexity increase, while maintaining performance on a variety of downstream question answering benchmarks. This work contributes a scalable pipeline for reverse-engineering attention heads in transformer models using human-readable, executable code, advancing a path toward symbolic transparency in neural models.

20.
bioRxiv (Bioinfo) 2026-06-11

Revealing trajectories of multi-modal voxel-level changes in neurodegenerative diseases using latent event mapping

Neurodegenerative diseases are driven by pathological mechanisms that can be indirectly measured in vivo using multi-modal neuroimaging. However, current computational methods that aim to reconstruct trajectories of voxel-level changes in the brain are either not computationally scalable or fully interpretable, limiting their ability to reveal associations between disease progression and underlying mechanisms. Here we introduce Latent Event Mapping (LEMING), a generative unsupervised modelling technique that learns a latent map of disease events along a common pseudo-timeline of events. We apply LEMING to amyloid PET and structural MRI data from the Alzheimer's Disease Neuroimaging Initiative to reveal the first voxel-level trajectories of events in Alzheimer's disease. Notably, we show how LEMING can provide new insights into progression-dependent disease mechanisms. We find that acetylcholine receptor density is significantly positively associated with both late-stage amyloid and atrophy events, suggesting that either these receptors are targeted later in disease progression, or that amyloid does not play an active role. This has strong implications for therapeutics that target acetylcholine receptors, particularly for early-stage intervention strategies.

21.
arXiv (CS.AI) 2026-06-19

A Systematic Evaluation of Black-Box Uncertainty Estimation Methods for Large Language Models

arXiv:2606.19868v1 Announce Type: new Abstract: Although large language models (LLMs) have shown strong capabilities across a wide range of tasks, their outputs often remain unreliable and may contain hallucinations, making uncertainty estimation (UE) essential for building trustworthy LLMs. In practice, many mainstream LLMs are only accessible through restricted APIs, where internal signals such as logits and hidden states are unavailable, making black-box UE especially important. However, existing work on black-box UE for LLMs remains fragmented in methodology and lacks a unified empirical comparison. To address this gap, we present a systematic review of black-box UE methods and organize them into five categories: verbalization-based, sampling-based, explanation-based, multi-agent, and hybrid methods. We further build a unified evaluation framework and benchmark 24 representative methods across 4 models and 4 dataset settings. Our results show that no single method consistently dominates across all settings. Nevertheless, methods that reason over and compare candidates in the answer space are generally effective, and hybrid methods that combine multiple uncertainty signals perform well under most conditions. By releasing the benchmark data and a unified evaluation framework, we aim to facilitate reproducible comparisons and support future research, while our empirical findings provide practical guidance for developing future black-box UE methods for LLMs.

22.
arXiv (CS.CV) 2026-06-18

Performance Gap Analysis between Latin and Arabic Scripts HTR

Recent studies have shown that handwritten text recognition (HTR) systems perform worse on Arabic-script datasets than on Latin-script data. However, the reasons for this gap are still not well understood due to the lack of controlled comparisons. In this work, we present a comprehensive study of Arabic and Latin scripts HTR using a unified CRNN model for line-level HTR across nine datasets (including KHATT (Arabic), Muharaf (Arabic), NUST-UHWR (Urdu), PHTD (Persian), IAM (English), READ-2016 (German), and others) and di ferent training sizes (K in {100, 500, 1000, 2000, ..., Kfull}). Our results show the performance gap remains: it is large in low-resource settings, decreases with more data, but remains even at full scale, with a consistent difference of 5-7 CER points. We show that annotation quality matters, as many datasets contain labeling errors. Cleaning reduces error rates and narrows the gap, but does not eliminate it. In addition, we find that a fixed number of training samples provides less effective coverage in Arabic due to higher visual variability, requiring more data to learn similar representations. We compare recognition across datasets in terms of the number of text lines and the number of characters, showing an equivalence trade-off. We compare character frequency distributions across scripts and show that Arabic is significantly more heavy-tailed than Latin. Our error analysis reveals that around 30 percent of substitution errors in Arabic datasets (e.g., KHATT) are caused by confusion between visually similar characters, compared to about 15 percent in Latin-script datasets such as IAM.

23.
arXiv (CS.CL) 2026-06-11

Multi-task Learning is Not Enough: Representational Entanglement in Dual-output Second Language Speech Recognition

Second-language (L2) speech recognition often requires transcriptions of pronunciations and intended meanings. Multi-task learning (MTL) is a natural approach because it assumes that shared representations benefit both outputs. However, this paper shows that this assumption does not hold across Korean and English. MTL improves meaning but degrades surface transcription, especially in English, where the degradation scales with surface-meaning divergence measured by Levenshtein edit distance. Encoder analysis links these patterns to encoder-level entanglement, with Korean preserving distinct task representations while English produces nearly identical ones. Cross-task decoder analysis shows that the meaning dual-output decoder adapts with a unique representation, while the surface dual-output decoder remains constrained by the encoder. These findings motivate the design of MTL frameworks that mitigate encoder-level entanglement to reduce surface degradation in dual-output L2 automatic speech recognition.

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

Guiding Federated Graph Recommendation with LLM-encoded knowledge

arXiv:2606.15277v1 Announce Type: cross Abstract: Graph-based recommender systems are highly effective at extracting collaborative signals from user–item interactions, and federated learning (FL) allows these models to be trained while preserving user privacy. However, aggregating graph representations across distributed, non-IID clients remains a challenge; structural embeddings learned locally often misalign, and naive averaging fails to capture meaningful cross-client relationships. Most existing federated graph methods rely exclusively on structural aggregation, neglecting the rich, global semantic context available in large language models (LLMs). In this paper, we propose a novel framework that uses LLM-encoded knowledge to guide federated graph recommendation. Specifically, clients learn structural representations from local graphs while simultaneously summarizing their typical interaction patterns into compact semantic vectors via a frozen LLM. The central server then uses these LLM-encoded semantic signals to discover related preference patterns across clients, guiding the selective aggregation of their structural representations. This enables semantically informed cross-client collaboration without exposing raw data. Extensive experiments on standard benchmarks show that guiding structural alignment with LLM-encoded knowledge consistently improves recommendation accuracy over existing federated graph baselines.

25.
medRxiv (Medicine) 2026-06-15

Quantitative Gait Categorization in Parkinson's Disease with and without Freezing of Gait

Background: Freezing of gait (FOG) is a disabling and often underrecognized feature of Parkinsons disease (PD). Objective gait analysis may improve characterization of this motor symptom. Objective: To compare quantitative 3D gait parameters in PD with FOG (PDF) and PD without FOG (PDNF) in a routine clinical cohort. Methods: We retrospectively analyzed a sequential sample of 180 patients with PD referred for motion analysis between 2020 and 2024. All patients underwent 3D motion capture in the off-medication state. Eighteen gait outcomes spanning pace, rhythm, postural control, variability, and asymmetry domains were derived from steady-state walking tasks. FOG status was determined using physician documentation and Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS-UPDRS) items. Group differences between PDF (n=99) and PDNF (n=81) were evaluated using independent samples t-tests, with outcomes adjusted for disease duration and corrected for multiple comparisons. A secondary analysis among PDF compared those in Hoehn and Yahr (H&Y) stage [&ge;]III to those in H&Y [&le;]II. Results: PDF had longer disease duration, higher OFF MDS-UPDRS III scores, and higher Hoehn and Yahr stage than PDNF but were similar in age and sex. After adjusting for disease duration and multiplicity, PDF demonstrated reduced step length, stride length, and forward velocity, and greater cadence variability, while most postural control, and asymmetry measures were comparable between groups. Among PDF, advanced H&Y stage was associated with impaired pace and rhythm, similar to previous reports among PD in general. Conclusion: In this large, sequential, clinically referred cohort, FOG was associated with more advanced PD and specific impairments in pace and gait variability. These findings support comprehensive 3D gait analysis as an objective tool to better delineate FOG-related gait abnormalities and identify features that may predict FOG, informing targeted interventions.