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

Unified Multimodal Model for Brain MRI Imputation and Understanding

Multimodal large language models (MLLMs) hold great potential for medicine, as they inherit knowledge from LLM and allow multiple data modalities to be integrated, analysed and interpreted in natural language. However, the field of medical MLLMs is constrained by non-trivial challenges, notably the scarcity of high-quality training data and the frequent occurrence of missing data in the real-world clinical setting. Here, we propose a novel unified multimodal model, UniBrain, for brain magnetic resonance image (MRI) analysis. To address potential missing brain MRI modalities, we employ a unified training strategy to perform joint imaging modality imputation and brain image understanding. During training, an interleaved and description-enriched data flow is constructed to train the model in an autoregressive manner, enabling medical reasoning with generated multimodal data. A self-alignment strategy is introduced to leverage dense image embeddings to learn fine-grained anatomical features without requiring detailed image captions. Furthermore, we propose a dynamic hidden state mechanism to alleviate the exposure bias during long-context multimodal inference. Extensive experiments on multi-disease brain MRI dataset demonstrate that UniBrain achieves high performance for brain image imputation, understanding, and disease diagnosis under various extents of modality incompleteness.

02.
PLOS Computational Biology 2026-06-22

<i>HoloBio</i>: A holographic microscopy tool for quantitative biological analysis

作者:

by Waira Mona, Maria J. Gil-Herrera, Emanuel Mazo, Daniel Córdoba, Sofia Obando-Vasquez, Maria J. Lopera, Rene Restrepo, Carlos Trujillo, Ana Doblas, Raul Castaneda Holographic imaging in microscopy enables label-free quantitative information of biological specimens and has found applications across a wide range of biomedical studies, from cell morphology to particle dynamics; yet its widespread adoption is often limited by the lack of accessible and standardized analysis software. We present HoloBio, an open-source, Python-based graphical user interface developed to address this issue. This software offers two primary operational modes: a Real-Time mode that enables live processing of holograms at video frame rates, and an Offline mode designed for post-processing previously recorded holograms. HoloBio is compatible with holograms recorded using both lens-based and lensless systems, supporting off-axis architectures in telecentric and non-telecentric configurations, as well as slightly off-axis and in-line optical setups. The software incorporates tools for cell tracking, phase profiling, thickness estimation, and morphological analysis, including cell counting and object area quantification. HoloBio is designed to be accessible for users without coding expertise, offering a reproducible, high-throughput environment tailored for researchers in biology, biophotonics, and biomedical imaging.

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

Test-Time Adaptation in Optical Coherence Tomography Using Trajectory-Aligned Time-Independent Flow

Optical coherence tomography (OCT) is essential in ophthalmology, but inconsistent image quality especially in low-cost devices hinders automated analysis. To address this, we introduce a flow-matching-based test-time adaptation method that generates high-quality surrogate images from noisy inputs. Typically, domain gaps between test and training data cause pixel distribution mismatches during the denoising process. We overcome this by matching the test image's histogram to synthetic reference trajectories, successfully aligning the input with expected distributions. Additionally, we remove the network's time conditioning to account for slight deviations in real-world noise distributions. Our approach achieves state-of-the-art performance in segmenting critical biomarkers for two stages of Age-related Macular Degeneration (AMD). Code is available: https://github.com/Veit21/tta-flow.

04.
arXiv (CS.CL) 2026-06-17

ALAS: An Automatic Latent Alignment Score for Audio Language Models

Large Language Models (LLMs) are extended into Speech-LLMs, and the quality of the audio–text alignment they learn affects most downstream Spoken Language Understanding (SLU) behavior. Yet despite a growth of fusion strategies, there is no standard way to measure how well a Speech-LLM internally binds audio frames to text tokens. We introduce ALAS (Automatic Latent Alignment Score), a model and task-agnostic metric that probes the LLM's per-layer hidden states, scoring the cross-modal cosine similarity between audio and text representations against a Whisper-derived reference. ALAS needs only a frozen forward pass and an off-the-shelf ASR reference, with no training or fitted classifier, and is calibrated to an interpretable uniform baseline comparable across tasks. Applying ALAS to four open-source Speech-LLMs (AF3, Qwen2-Audio, Qwen-Omni, SALMONN) across emotion recognition (IEMOCAP), open-ended SQA (LibriSQA), and multi-choice audio understanding (MMAU-speech), we find that the depth and strength of alignment reflect each model's audio-encoder design and the acoustic-versus-semantic demands of the task, and that ALAS tracks but does not duplicate task accuracy, exposing models that score well without genuinely grounding in the audio. We release ALAS as an open-source library so that practitioners can probe their own Speech-LLMs or try it on new tasks.

05.
arXiv (CS.LG) 2026-06-12

Robust State-Conditional Feature-Weighted Jump Models for Temporal Clustering

arXiv:2606.13146v1 Announce Type: cross Abstract: We propose a robust feature-weighted jump model for time-dependent clustering. A penalty is used to encourage smoothness of transitions over time, while robustness is achieved through the use of a Tukey's biweight loss function. An additional parameter controls the variability of feature weights across states, allowing the model to assign state-specific relevance to each feature. We illustrate in simulation how the method accurately recovers the true cluster sequence and reliably identifies relevant features, outperforming competing approaches, particularly in the presence of outliers. We conclude with two empirical applications, one on the number of conflict-related homicides in Kosovo in the period 1998-2000, and another on macroeconomic performance of twelve European countries in the period 1949-2024.

07.
arXiv (CS.LG) 2026-06-15

Cluster LOCO: Feature Importance For Interpreting Clusters

arXiv:2606.14592v1 Announce Type: cross Abstract: Clustering is widely used for exploratory analysis and scientific discovery, driving insights from market segmentation to biological data analysis, but its outputs can be difficult to interpret, audit, and reproduce as modern datasets become increasingly large and complex. Reliable use of clustering requires understanding which features drive the discovered structure, yet feature-level explanations for clustering remain scarce compared with methods in supervised learning. Furthermore, existing clustering feature importance scores are often tied to specific algorithms and data assumptions. To address these challenges, we propose Cluster LOCO (Leave-One-Covariate-Out), a family of model-agnostic feature importance scores for clustering. Cluster LOCO is built on feature occlusion and clustering generalizability, defined as whether cluster labels learned on one subset of the data can be accurately predicted on held-out samples. For any chosen clustering algorithm, Cluster LOCO quantifies a feature's importance by measuring how much its removal degrades generalizability. We first introduce Cluster LOCO-Split, which relies on data splitting, and then extend it to Cluster LOCO-MP, a minipatch ensemble-based version designed for large-scale data. Across synthetic simulations and an application to cell-type discovery in single-cell transcriptomics, we show that Cluster LOCO more reliably recovers informative features than existing clustering feature importance methods.

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

Show the Signal, Hide the Noise: Spectral Forcing for Pixel-Space Diffusion

Pixel-space diffusion models are trained on full-bandwidth noisy images, yet the useful signal available to the denoiser is strongly frequency dependent. Under rectified-flow diffusion and natural-image power-law spectra, the per-band data-to-noise contour $k^{*}(t) = (1-t)^{-2/\alpha}$ separates a signal-bearing low-frequency region from a noise-dominated high-frequency region at each time $t$. We show that this implicit coarse-to-fine structure is not merely descriptive: it induces a capacity-allocation problem. A standard pixel-space denoiser must discover the moving bandwidth boundary internally and can spend computation on frequency-time regions where the optimal prediction collapses to deterministic baselines rather than data-distribution modeling. To make this boundary explicit, we introduce Spectral Forcing, a parameter-free, time-conditional 2D-DCT low-pass operator applied to the noisy input before the patch embedder. Its cutoff expands monotonically with the diffusion time and becomes the identity at the data endpoint. Through controlled synthetic experiments, we identify the regime in which the operator is beneficial: coarse patch tokenization and data whose high-frequency content is predominantly noise rather than essential signal. On ImageNet-256 with JiT-700M/32, Spectral Forcing consistently improves both FID and Inception Score across different training epochs, demonstrating robust gains throughout training; at finer tokenization, the spectral forcing is still competitive. We further insert the unchanged operator into SenseNova-U1, a unified text-to-image model, where it improves DPG-Bench and GenEval, showing that the input-side spectral prior transfers beyond class-conditional generation. These results suggest a route to capacity-efficient pixel-space diffusion by showing the signal and hiding the noise.

09.
arXiv (CS.CL) 2026-06-18

GrowthHacker: Automated Off-Policy Evaluation Optimization Using Code-Modifying LLM Agents

With data-driven development now widely adopted, online A/B testing is an established method for measuring the effects of new technologies. However, deploying online experiments demands resources for design, implementation, and deployment, and may negatively impact users (e.g., unsafe or unethical outcomes) while requiring weeks of data collection. To address this, the growing research area of off-policy evaluation (OPE), or offline A/B testing, assesses new technologies offline using previously collected logged data. OPE is also a fundamental problem in reinforcement learning and is important where online testing is expensive or risky, such as healthcare, recommender systems, education, and robotics. Despite advances in code-generation large language models (LLMs) and agentic workflows, little is known about whether and how LLMs and LLM-based agents can automatically optimize OPE implementations. We propose GrowthHacker, a benchmark that evaluates baseline LLMs and LLM-based agents on large-scale public datasets. GrowthHacker autonomously and iteratively modifies code, runs OPE, and uses the metrics to guide subsequent optimization. We evaluate methods on Open Bandit Pipeline (OBP) and Scope-RL, and develop a two_agent framework that addresses limitations of existing frameworks while reducing complexity. Across both libraries, two_agent shows the highest reliability (98.1%-100% success rate) and positive-outcome rate (78%), with a median improvement of 4.4% among positive outcomes; CrewAI achieves the highest average improvement (37.9%) and is the only framework with zero extreme-value failures. AutoGen and Default each reach 65% positive-outcome rates. These results establish the feasibility of using LLM-based agents as automated "growth hackers" to continuously improve OPE systems, with implications for scaling data-driven decision-making where manual optimization is expensive.

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

Correcting Sensor-Induced Distribution Drift with Wasserstein Adversarial Learning

arXiv:2606.18561v1 Announce Type: cross Abstract: The quality of recorded data depends on the stability of the sensor system that acquires it. Sensor motion and aging can degrade the performance and stability of downstream data-driven methods. We present a Wasserstein-GAN-inspired approach for unsupervised inference of physically interpretable transformation parameters that map a changed detector response distribution back to a nominal reference distribution. In contrast to standard generative modeling, the generator is used as a learnable calibration transformation whose trainable weights represent the sought parameters, while the critic provides a distributional distance signal via the Wasserstein objective. We validate the approach on a tracking-detector toy model with controlled layer shifts and demonstrate its application on high-granularity Geant4-simulated calorimeter data with cell-wise aging effects. The method recovers aging coefficients for individual cells with correlation to ground truth and improves agreement between calibrated and reference energy-sum distributions, while exhibiting the expected degradation at increasing channel-to-channel noise levels. These results indicate that adversarial distribution matching can serve as a data-driven component of calibration strategies in settings where direct labels for degradation parameters are unavailable.

11.
arXiv (CS.LG) 2026-06-16

FlowRL: A Taxonomy and Modular Framework for Reinforcement Learning with Diffusion Policies

arXiv:2603.27450v2 Announce Type: replace Abstract: Thanks to their remarkable flexibility, diffusion models and flow models have emerged as promising candidates for policy representation. However, efficient reinforcement learning (RL) upon these policies remains a challenge due to the lack of explicit log-probabilities for vanilla policy gradient estimators. While numerous attempts have been proposed to address this, the field lacks a unified perspective to reconcile these seemingly disparate methods, thus hampering ongoing development. In this paper, we bridge this gap by introducing a comprehensive taxonomy for RL algorithms with diffusion/flow policies. To support reproducibility and agile prototyping, we introduce a modular, JAX-based open-source codebase that leverages JIT-compilation for high-throughput training. Finally, we provide systematic and standardized benchmarks across Gym-Locomotion, DeepMind Control Suite, and IsaacLab, offering a rigorous side-by-side comparison of diffusion-based methods and guidance for practitioners to choose proper algorithms based on the application. Our work establishes a clear foundation for understanding and algorithm design, a high-efficiency toolkit for future research in the field, and an algorithmic guideline for practitioners in generative models and robotics. Our code is available at https://github.com/typoverflow/flow-rl.

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

AI-Driven Framework for Adaptive Water Network Management with Proof-of-Concept Implementation: Addressing Non-Revenue Water in Jordan

arXiv:2606.15709v1 Announce Type: new Abstract: Jordan faces severe water scarcity with 50\% of water produced is lost to leakage, theft and metering issues also known as non-revenue water (NRW). Traditional reactive approaches have proven insufficient for sustained NRW reduction. This paper proposes an intelligent framework integrating EPANET hydraulic modeling, digital twin technology, SCADA systems, and large language model (LLM)-based AI agents for continuous network monitoring and adaptive decision-making. The system combines real-time data streams with physics-based simulation to detect anomalies, employing retrieval-augmented generation (RAG) for policy interpretation and function calling for network control. A proof-of-concept implementation validates technical feasibility using EPYT with offline LLMs (llama3.1:8b via Ollama) on a 1,164-junction Amman district network. The system demonstrates automated hydraulic simulation, flow-based anomaly detection aligned with water distribution zone (DZ) practice, and AI-generated health reports with response times under 2 minutes and zero API costs. Burst detection relies on local flow anomaly analysis: a 30.1~L/s simulated leak produces measurable flow redistribution in 15 pipes, flagging a 15-junction cluster that localises the burst – confirming alignment with water distribution zone (DZ) monitoring practice. The framework accommodates Jordan's intermittent supply patterns and limited automation through phased implementation, offering a scalable pathway for water-scarce regions to leverage intelligent automation for NRW reduction and operational efficiency.

13.
medRxiv (Medicine) 2026-06-22

Leishmaniasis on YouTube: a critical appraisal of the quality, reliability, and transparency of educational content

Background: Leishmaniasis is a neglected tropical disease of significant global public health importance, for which accurate information is essential to support prevention and early care-seeking, particularly in endemic, resource-limited settings. YouTube is a widely used source of health information, but the quality and reliability of leishmaniasis-related content have not been evaluated. We aimed to assess the quality, reliability, and transparency of English-language YouTube videos on leishmaniasis. Methods: We conducted a cross-sectional analysis of YouTube videos retrieved via the YouTube Data API on 15 June 2026 using the terms "leishmaniasis," "cutaneous leishmaniasis," and "visceral leishmaniasis." After applying eligibility criteria and screening the 150 most-viewed eligible videos, 48 videos were included. Two reviewers independently assessed each video using the modified DISCERN (mDISCERN) tool, the Global Quality Score (GQS), and the JAMA benchmark criteria, with disagreements resolved by consensus. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC), and associations were examined using Spearman's rank correlation. Results: Of 402 videos retrieved, 48 met the inclusion criteria. The median GQS was 3.00 (IQR 2.00-4.00) and median mDISCERN was 3.00 (IQR 2.38-4.50), indicating moderate quality and reliability, while the median JAMA score was 2.00 (IQR 1.00-2.00), reflecting limited transparency; no video met all four JAMA criteria. The overwhelming majority of videos (47/48, 97.9%) were of professional or institutional origin. Inter-rater agreement was good to excellent (ICC 0.883 for GQS, 0.896 for mDISCERN, 1.000 for JAMA). The instruments were strongly inter-correlated (mDISCERN-GQS rho = 0.841, p < 0.001). Quality scores did not correlate positively with views, likes, or video duration; comments correlated weakly and negatively with mDISCERN (rho = -0.337, p = 0.031) and JAMA (rho = -0.381, p = 0.014). Conclusions: YouTube videos on leishmaniasis are of moderate quality and reliability but limited transparency, and are produced almost exclusively by professional sources. Video popularity, length, and age were not indicators of quality. There is a need for experts and institutions to produce clearly authored, well-sourced, and transparent educational content on this neglected tropical disease.

14.
arXiv (CS.AI) 2026-06-19

Science Earth: Towards A Planet-Scale Operating System for AI-Native Scientific Discovery

arXiv:2606.01316v2 Announce Type: replace Abstract: Scientific discovery demands intelligence, perseverance, and serendipity across vast search spaces. Today, top scientific capabilities remain siloed–one AI system for biological analysis, another for clinical reasoning, mathematical derivation, or materials simulation–and no pre-designed team can anticipate every skill a question will need. Science Earth is a planet-scale scientific runtime in which any capability–a simulation cluster, a wet-lab robot, a proof engine, a single-cell pipeline–can connect to any other, with collaboration structure emerging from the question itself. Its underlying EACN protocol lets capabilities discover one another, negotiate task ownership, and adjudicate across incompatible evidentiary standards without prior knowledge of who will meet whom. This shifts the organizing challenge from workflow design to open-ended connectivity. Two runs validate this under structurally distinct conditions. In a trans-Pacific higher-order Kuramoto synchronization study, agents identified and corrected a closure-ratio assumption in Ott-Antonsen analytic theory that fails outside the Lorentzian limit, within thirty minutes. In an eight-agent single-cell run on the 4.88M-cell Kang 2024 pan-cancer atlas, heterogeneous capabilities coupled over a 64.9-hour window with one structural external instruction, producing three new result layers and anchoring findings against an independent wet-lab study on an adjacent CCR8- TIGIT+ Treg subset. These cases are a first empirical reading, not a benchmark sweep. They show that when AI capabilities are truly connectable and coordination emerges from the problem, scientific reasoning becomes a distributed, self-correcting process–a step towards scaling AI-native discovery to the planet.

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

SpikeDecoder: Realizing the GPT Architecture with Spiking Neural Networks

arXiv:2606.12287v1 Announce Type: cross Abstract: The Transformer architecture is widely regarded as the most powerful tool for natural language processing, but due to a high number of complex operations, it inherently faces the issue of high energy consumption. To address this issue, we consider Spiking Neural Networks (SNNs), which are an energy-efficient alternative to conventional Artificial Neural Networks (ANNs) due to their naturally event-driven approach to processing information. However, this inherently makes them difficult to train. Often, many SNN-based models circumvent this issue by converting pre-trained ANNs. More recently, attempts have been made to design directly trainable SNN-based adaptations of the Transformer model structure. Although the results showed great promise, the application field was computer vision. Moreover, the proposed model incorporates only encoder blocks. In this paper, we propose SpikeDecoder, a fully SNN-based implementation of the Transformer decoder block, for applications in natural language processing. In a series of experiments, we analyze the impact of exchanging different blocks of the ANN model with spike-based alternatives to identify trade-offs and significant sources of performance loss. We further investigate the role of residual connections and the selection of SNN-compatible normalization techniques. Besides the work on the model architecture, we formulate and compare different embedding methods to project text data into spikes. Finally, we demonstrate that our proposed SNN-based decoder block reduces the theoretical energy consumption by 87% to 93% compared to the ANN baseline.

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

HACMatch Semi-Supervised Rotation Regression with Hardness-Aware Curriculum Pseudo Labeling

Regressing 3D rotations of objects from 2D images is a crucial yet challenging task, with broad applications in autonomous driving, virtual reality, and robotic control. Existing rotation regression models often rely on large amounts of labeled data for training or require additional information beyond 2D images, such as point clouds or CAD models. Therefore, exploring semi-supervised rotation regression using only a limited number of labeled 2D images is highly valuable. While recent work FisherMatch introduces semi-supervised learning to rotation regression, it suffers from rigid entropy-based pseudo-label filtering that fails to effectively distinguish between reliable and unreliable unlabeled samples. To address this limitation, we propose a hardness-aware curriculum learning framework that dynamically selects pseudo-labeled samples based on their difficulty, progressing from easy to complex examples. We introduce both multi-stage and adaptive curriculum strategies to replace fixed-threshold filtering with more flexible, hardness-aware mechanisms. Additionally, we present a novel structured data augmentation strategy specifically tailored for rotation estimation, which assembles composite images from augmented patches to introduce feature diversity while preserving critical geometric integrity. Comprehensive experiments on PASCAL3D+ and ObjectNet3D demonstrate that our method outperforms existing supervised and semi-supervised baselines, particularly in low-data regimes, validating the effectiveness of our curriculum learning framework and structured augmentation approach.

17.
arXiv (math.PR) 2026-06-16

Malliavin Calculus for the stochastic Cahn-Hilliard equation driven by fractional noise

arXiv:2601.10490v2 Announce Type: replace Abstract: The stochastic partial differential equation analyzed in this work is the Cahn-Hilliard equation perturbed by an additive fractional white noise (fractional in time and white in space). We work in the case of one spatial dimension and apply Malliavin calculus to investigate the existence of a density for the stochastic solution $u$. In particular, we show that $u$ admits continuous paths almost surely and construct a localizing sequence through which we prove that its Malliavin derivative exists locally, and that its law is absolutely continuous with respect to the Lebesgue measure on $\bf R$, establishing thus that a density exists. A key contribution of this work is the analysis of the stochastic integral appearing in the mild formulation: we derive sharp estimates for the expectation of the $p$-th power ($p \geq 2$) of the $L^{\infty}(D)$-norm of this stochastic integral as well as for the integral involving the $L^{\infty}(D)$-norm of the operator associated with the kernel appearing in the integral representation of the fractional noise, all of which are essential for this study.

18.
arXiv (CS.AI) 2026-06-12

Mapping AI Programs in the U.S: A Status Report from Early 2026 and an Analysis of AI Majors and Minors

arXiv:2606.12428v1 Announce Type: cross Abstract: We present a report on the status of undergraduate Artificial Intelligence (AI) programs in the United States in Spring 2026. In so doing, we 1) describe our scraping and mapping tools, which dynamically update to track the state of AI education in the U.S., and 2) create a historic record at a time of great upheaval. The tool we developed, available at https://cicmap.ai, detects, scrapes, and displays data from more than 350 undergraduate AI programs–majors, minors, concentrations, and certificates–at 4-year universities. Our tool searched over 560 institutions to locate these programs, a sample that represents 86\% of all undergraduate Computer Science (CS) graduates in the U.S. This tool allows prospective students, guidance counselors, administrators, and faculty to easily access AI program requirements and is designed to continually update as new programs emerge. To the best of our knowledge, this survey represents the most comprehensive snapshot of the state of AI programs in the U.S. to date. With this work we offer three important contributions: 1) a record of AI programs in the U.S. at a time of great upheaval; 2) a tool to explore AI programs and their requirements; and 3) an analysis of the courses required for 66 AI majors and 87 AI minors. Our analysis of majors and minors shows great variability in the size and the requirements of these degrees, but we note two takeaways. First, not all majors require a general AI course, but if they don't, they do require a Machine Learning (ML) course. Second, while more than a third of majors require an Ethics in AI course, just under a quarter of AI minors do.

19.
medRxiv (Medicine) 2026-06-15

Using wastewater surveillance to explore community-level dietary intake in sewered and non-sewered sanitation systems in Malawi, Africa

Wastewater can be used to measure biomarkers that reflect population-level dietary intake and diversity; however, how this approach may apply in a low-income country remains a knowledge gap. This study aims to evaluate whether select dietary-related metabolites can be detected in wastewater and environmental surveillance (WES) samples from both sewered and non-sewered sanitation systems in Malawi, Africa. Fourteen WES samples were collected and analyzed from two university campuses in Mzuzu and Thyolo, Malawi. Four targets were analyzed: N-methyl-2-pyridone-5-carboxamide (2PY; a biomarker of vitamin B3), 4-pyridoxic acid (4-PA; a biomarker of vitamin B6), as well as enterodiol and enterolactone (biomarkers of dietary fiber and polyphenol consumption). An 18-question survey, paired spatiotemporally with the WES measurements, assessed self-reported daily dietary intake, food insecurity, and nutrient deficiency symptoms among 500 respondents. Among the 14 WES samples, 2PY, 4-PA, and enterolactone were detected, while enterodiol was not detected above the method limit (

20.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

作者:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue&nbsp;degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

21.
arXiv (CS.AI) 2026-06-18

RODS: Reward-Driven Online Data Synthesis for Multi-Turn Tool-Use Agents

arXiv:2606.19047v1 Announce Type: new Abstract: Multi-turn tool-use RL is bottlenecked by the rapid depletion of informative samples in static datasets. We observe that the gradient signal in GRPO concentrates on tasks with the highest rollout reward variance, a consequence of the Popoviciu upper bound. Consequently, samples near the agent's capability boundary – where successes and failures are roughly balanced – contribute disproportionately large policy gradients. As training progresses, this boundary continuously shifts, which gradually depletes the pool of informative samples in a static dataset. We propose RODS (Reward-driven Online Data Synthesis) to resolve this depletion. RODS closes the loop between RL training and data generation by repurposing the progress reward variance as a practical, zero-cost boundary detector that requires no extra inference beyond the rollouts already computed for training. It continuously identifies such boundary samples, synthesizes new multi-turn variants matching their structural complexity (e.g., API topology and dependency depth) via a skill-aligned resampling pipeline, and manages a dynamic replay buffer that co-evolves with the policy. Starting from 400 human seeds and maintaining an active training pool of ~800 samples, RODS achieves comparable performance to a 17K-sample offline pipeline while requiring roughly 20x fewer trajectories, and improves over fixed-data RL and environment augmentation in our controlled setting.

22.
medRxiv (Medicine) 2026-06-16

Language fMRI lateralization success and head motion in pediatric epilepsy patients with ADHD, and improvements based on fMRI task training

Introduction Language functional MRI (fMRI) is a valuable tool for presurgical planning in epilepsy. Functional MRI can be challenging in children, and head motion can compromise its utility. The candidacy of patients with ADHD for fMRI is sometimes queried regarding concerns about possible head motion. In 2020, we implemented an fMRI task training program, via telehealth and/or mock MRI. We aimed to determine whether training increased language lateralisation success and/or reduced head motion in all patients, and in those with ADHD. We also aimed to determine whether patients with ADHD exhibited more head motion during fMRI than those without ADHD. Methods We retrospectively identified 223 epilepsy (85%) and other neurosurgery patients, (241 scans including repeats) with language fMRI at Royal Children's Hospital, Melbourne, Australia, 2016-2024. There were 24 individuals with ADHD listed in the Electronic Medical Record, five of whom had diagnoses of both ADHD and autism; and nine with autism. Language lateralisation success was determined by clinician description recorded as left/right/bilateral in the medical record. 99 patients were provided the training including fMRI task practise. Head motion was quantified by maximum Framewise Displacement (FDmax; mm). Results ADHD was associated with lower language lateralisation success. Training was associated with greater language lateralisation success, across all patients, and in those with ADHD. Regarding ADHD and head motion, outliers in FDmax were seen in 5 young patients with ADHD. Data were trimmed to allow separate investigation of FDmax for the sample with and without extremes of head motion. In untrimmed data, FDmax was significantly higher in patients with ADHD than in those without. In trimmed data, FDmax was on average lower in patients with ADHD than those without, however this was not statistically supported. Regarding training and head motion, across all patients, FDmax was significantly lower for scans with training than without. In patients with ADHD, FDmax was on average lower for scans with training, however training was not associated with FDmax. Conclusions Language fMRI training was associated with higher language lateralization success, particularly in patients with ADHD. Training was associated with reduced head motion across all patients. Although some young patients with ADHD had substantial head motion, most in our sample did not move more than those without ADHD. We conclude that the training program increases success of language fMRI, and that an ADHD diagnosis should not be a contraindication to language fMRI.

23.
bioRxiv (Bioinfo) 2026-06-12

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.

25.
arXiv (CS.CL) 2026-06-12

LAUKIN: A Multi-jurisdictional Common Law Contract Dataset

Multinational companies increasingly require cross-jurisdictional contract review, yet existing legal NLP datasets are largely restricted to a single jurisdiction. We introduce LAUKIN (Legal equivalence dataset of Australia, UK, and INdia), a dataset of clause pairs (AU-UK, UK-IN, IN-AU) labelled for boolean legal equivalence. We develop a novel multi-stage retrieval and reranking pipeline to construct the initial clause pair mapping, with a subset of clause pairs subsequently annotated by legal experts as Equivalent or Not Equivalent. The dataset comprises 14,727 clause pairs from 204 contracts across 8 agreement types, of which 3,000 are manually labelled: 900 train, 600 dev, and 1,500 test. We evaluate 12 models across 4 techniques, achieving a best macro-F1 of 65.11%, establishing LAUKIN as a challenging benchmark. Results reveal that, despite shared legal heritage, drafting conventions diverge significantly across jurisdictions, making cross-jurisdictional equivalence classification non-trivial. LAUKIN also includes 11,727 unlabelled training pairs to support future semi-supervised learning research in legal NLP.