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

AgenticRec: A Recommendation-Oriented Agentic Framework with Progressive Tool-Integrated Reasoning Optimization

arXiv:2603.21613v2 Announce Type: replace-cross Abstract: Recommender agents built on Large Language Models offer a promising paradigm for personalized recommendation. However, existing agents typically suffer from a misalignment between their tool-integrated reasoning trajectories and recommendation feedback, limiting their ability to distinguish fine-grained user preferences. To address these challenges, we propose AgenticRec, an agentic recommendation framework that formulates recommendation as a tool-integrated reasoning process over a recommendation-oriented tool suite. Built upon this framework, we further develop a dedicated two-stage training paradigm tailored for recommender agents. In the first stage, we introduce Recommendation-Oriented Trajectory Activation, optimize the agentic recommendation ability under implicit feedback. In the second stage, Progressive Preference Refinement further refines the agent through bidirectional preference reasoning over self-bootstrapped hard pairs, progressively sharpening preference boundaries. Theoretical analysis and extensive experiments demonstrate the effectiveness of AgenticRec. Our code is available at https://anonymous.4open.science/r/AgenticRec-FB16.

02.
arXiv (CS.CV) 2026-06-11

MARIC: Multi-Agent Reasoning for Image Classification

Image classification has traditionally relied on parameter-intensive model training, requiring large-scale annotated datasets and extensive fine tuning to achieve competitive performance. While recent vision language models (VLMs) alleviate some of these constraints, they remain limited by their reliance on single pass representations, often failing to capture complementary aspects of visual content. In this paper, we introduce Multi Agent based Reasoning for Image Classification (MARIC), a multi agent framework that reformulates image classification as a collaborative reasoning process. MARIC first utilizes an Outliner Agent to analyze the global theme of the image and generate targeted prompts. Based on these prompts, three Aspect Agents extract fine grained descriptions along distinct visual dimensions. Finally, a Reasoning Agent synthesizes these complementary outputs through integrated reflection step, producing a unified representation for classification. By explicitly decomposing the task into multiple perspectives and encouraging reflective synthesis, MARIC mitigates the shortcomings of both parameter-heavy training and monolithic VLM reasoning. Experiments on 4 diverse image classification benchmark datasets demonstrate that MARIC significantly outperforms baselines, highlighting the effectiveness of multi-agent visual reasoning for robust and interpretable image classification.

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

CMIP-Forge: An Agentic System that Retrieves, Computes, and Self-Reviews Climate Science

arXiv:2606.17076v1 Announce Type: cross Abstract: The Coupled Model Intercomparison Project Phase 6 (CMIP6) has generated thousands of peer-reviewed publications documenting model configurations, evaluation procedures, emergent constraints, and projection uncertainties. As the community transitions toward CMIP7, efficiently extracting and operationalizing this unstructured knowledge alongside live data analysis represents a critical bottleneck. Here we present CMIP-Forge, a hybrid retrieval-augmented generation (RAG) and autonomous analysis system that bridges the gap between scientific literature and Earth System Grid Federation (ESGF) data archives. The system pairs a curated corpus of 6,581 CMIP6-related open-access publications (101,828 indexed chunks) with an agentic pipeline in which a tool-augmented worker plans and executes Python workflows over live climate data, while a panel of independent reviewer models audits its methodology end to end. CMIP-Forge introduces a multi-layered Defense-in-Depth architecture that enforces physical and methodological invariants through executable mechanisms: Abstract Syntax Tree (AST) static analysis, audited scientific primitives, and an autonomous adversarial peer-review protocol. We demonstrate the system's capabilities through end-to-end autonomous research pipelines spanning atmospheric teleconnections, ocean dynamics, regional extremes, and global warming projections. An agentic analysis system grounded in peer-reviewed literature, constrained by automated code guardrails, and audited by an independent adversarial review loop can complete complex climate-research workflows autonomously. The same experiments expose concrete failure modes of the review loop (sycophantic regression, REVISE verdicts that are never resolved, and the submission of stub code for review), each diagnosable from the immutable telemetry and provenance record released with the article.

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

Language-Guided Abstraction for Visual Reasoning

The Abstraction and Reasoning Corpus (ARC) is viewed as a critical avenue to Artificial General Intelligence (AGI), as it enables models to learn abstract transformation rules from few-shot examples and then generalize to new tasks. However, prevalent ARC methodology is either pure language or vision-only (i.e., VARC). The former depends heavily on LLMs, consuming billions of parameters. The latter often struggles to capture high-level semantics, leading to overfitting on pixel-level patterns. To bridge this gap, we propose L-VARC, a novel framework that enhances visual reasoning via a language-guided Learning Using Privileged Information (LUPI) branch. Specifically, we design a Semantic Compression Module by feeding a unified, task-agnostic prompt into DeepSeek-V3. In this way, the raw LARC (a crowd-sourced language description dataset) can be substantially refined and structured, fitting with the context length constraint of standard text encoders (e.g., CLIP). Moreover, we design a Cross-Attention Projector to align visual features with semantic embeddings, aiming to guide the training of the ARC model. Notably, the LUPI branch is taken in the training process and will be discarded during inference, thereby yielding a lightweight model with a mere 18 million parameters. Extensive experiments demonstrate that our L-VARC effectively leverages linguistic priors to boost visual reasoning and outperforms state-of-the-art. Ablation studies further confirm the contribution of the two new designs towards the L-VARC framework. The code is available at https://github.com/GZHU-DVL/L-VARC.

05.
arXiv (CS.CL) 2026-06-11

The Periodic Table of LLM Reasoning: A Structured Survey of Reasoning Paradigms, Methods, and Failure Modes

Large Language Models (LLMs) have achieved strong performance across natural language processing tasks, yet reliable reasoning remains an open challenge. Although modern LLMs show progress in structured inference, multi-step problem solving, and contextual understanding, their reasoning behavior is often inconsistent and sensitive to prompting strategies, task design, and model scale. This survey provides a systematic analysis of more than 300 recent papers from arXiv, Semantic Scholar, Google Scholar, Papers with Code, and the ACL Anthology to examine how reasoning capabilities emerge in LLMs and where they fail. We make three main contributions. First, we introduce a structured taxonomy of LLM reasoning research, covering Chain-of-Thought reasoning, multi-hop reasoning, mathematical reasoning, common sense reasoning, visual and temporal reasoning, code and algorithmic reasoning, retrieval-augmented reasoning, tool-augmented and agentic reasoning, and reinforcement learning-based reasoning. Second, we analyze methodological trends across these paradigms, including prompting methods, model architectures, training objectives, reward modeling, and evaluation benchmarks. Third, we synthesize recurring limitations and failure modes, such as reasoning hallucinations, brittle multi-step inference, weak causal abstraction, and poor cross-domain generalization. By organizing a rapidly expanding literature, this survey offers a unified view of the current capabilities and limitations of reasoning in LLMs. We also identify emerging research directions, including meta-reasoning, self-evolving reasoning frameworks, multimodal reasoning, and socially grounded reasoning. Overall, this work aims to serve as a reference for developing more robust, interpretable, and generalizable reasoning systems in future language models.

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

Nonslop: A Gamified Experiment in Human-AI Collaborative Writing

arXiv:2606.12350v1 Announce Type: new Abstract: The rapid proliferation of large language models (LLMs) raises critical questions about human creativity and individual expression in an era of AI-assisted creation. When do humans adopt AI suggestions, and what are the implications for individual voice? This study examines these questions through a gamified writing exercise where 74 participants (214 responses) replied to prompts while AI-generated word suggestions were available as they wrote. The game simulates a dystopian future in which an AI is attempting to learn from what remains of human individuality, and disincentivizes AI-like writing. In doing so, it attempts to create conditions that reveal authentic user preferences rather than default behaviors, such as accepting a readily available AI-generated suggestion. Note that this is a deliberate inversion of the "helpful assistant" design pattern; the system is explicitly forbidding you from accepting AI suggestions. We analyze user behavior patterns across different task types, user behaviors, and response characteristics to understand the factors influencing human-AI interaction in creative tasks. The study focuses on when users choose to maintain creative autonomy versus violating the rules of the game and accepting AI assistance. It also explores how these choices relate to response patterns, task characteristics, and user behavior. This gamified approach offers both a framework for studying authentic human-AI interaction and a provocative lens for understanding the tension between efficiency and authenticity in AI-augmented creativity.

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

SICI: A Semantic-Pragmatic Complexity Index Reveals Regime Shifts in LLM Stance Detection

Prompt-based LLMs are increasingly used for stance detection, but harder examples are not always repaired by clearer instructions, reasoning prompts, retrieval, or debate. We introduce SICI (Stance Inference Complexity Index), a seven-dimensional diagnostic measure of the semantic-pragmatic burden imposed by a target–text pair. Across SemEval-2016 and VAST, SICI predicts LLM accuracy better than surface proxies and shows substantial cross-scorer reliability ($\alpha=0.771$). More importantly, LLM errors change regime as SICI increases: low-complexity examples invite over-attribution, especially Against predictions; intermediate examples form an unstable boundary; and high-complexity examples rapidly concentrate on None. This phase-transition-like structure persists across GPT-3.5, GPT-4o-mini, DeepSeek-V3, and GPT-4o, although stronger models move the boundaries. A 15-method intervention study further shows that prompting, retrieval, and debate often shift models along the attribution–abstention axis rather than removing the high-complexity bottleneck.

08.
Nature (Science) 2026-06-09

People are turning to AI chatbots to plug gaps in health information

A systematic assessment of health-related queries to a chatbot powered by artificial intelligence highlights shortfalls in health-care provision and the responsibilities of AI companies. A systematic assessment of health-related queries to a chatbot powered by artificial intelligence highlights shortfalls in health-care provision and the responsibilities of AI companies.

09.
Nature (Science) 2026-06-19

Daily briefing: Human detritus remakes geology

Authors:

What, exactly, is a rock? Plus, a stem-cell success for a severe autoimmune disease and evidence that ‘AI deskilling’ is real. Researchers have tracked the electrical activity of individual brain cells during conversation in real time. Plus, the history of GPS and a cross-species transplant that could reveal clues about the origin of animals.

10.
arXiv (CS.CL) 2026-06-16

Free Energy Heuristics: Fast-And-Frugal Cognition as Active Inference Under Uncertain Precision

Authors:

Chain-of-thought (CoT) improves large language models' performance in math and symbolic reasoning. But on planning, contested ethics, and tasks where the model cannot check itself, more reasoning makes things worse. Both effects are documented; what has been missing is a principled account of which property decides the outcome. We argue it is meta-uncertainty: how unsure the model is about the reliability of its own evidence. When that uncertainty is high, extra reasoning stops adding signal and starts manufacturing false confidence. We prove that the policy minimizing expected free energy under uncertain precision stops integrating cues after a finite number of high-validity ones when the precision prior is heavy-tailed (Theorem 2.6.1), and under a Descending Dominance condition, is sample-wise identical to take-the-best (Theorem 2.7.4). Fast-and-frugal heuristics and active inference are, then, two descriptions of the same computation. The prediction is that on high-meta-uncertainty items, longer CoT should degrade accuracy. We score the regime per item (simulate-and-recover rho > 0.96), build FEH-79, a benchmark of Knightian frames with matched controls, and run a pre-registered study across seven models (five open-weight 3B-32B, two frontier), five CoT lengths, and 7,875 responses. The gate, fixed before any data, required a negative interaction with posterior probability above 0.95 and an accuracy drop of more than 6 points. It held. The high-regime drop is 17.3 points (95% CI [7.7, 25.5]); matched items with definite answers show no cost. The effect is regime-dependent: decisive in capable mid-to-large models, directional in the two frontier systems, absent-to-reversed in the weakest. The framework answers when CoT helps and unifies the Bayesian and fast-and-frugal traditions: less-is-more effects are evidence about the meta-uncertainty regime, not against Bayesian cognition.

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

ARTEMIS: Agent-guided Reliability-aware Temporal Mask Evolution for Imperfectly Supervised Video Polyp Segmentation

Imperfectly supervised video polyp segmentation (VPS) aims to learn dense, temporally consistent masks from inexpensive supervision, including weak annotations (points, scribbles) and semi-supervision with few densely labeled frames. This setting is clinically valuable but challenging due to weak contrast, ambiguous boundaries, motion blur, and specular highlights, compounded by sparse pixel-level guidance. While SAM2 can generate dense masks from sparse inputs, direct pseudo-labeling often yields geometry-degraded masks with boundary leakage, underutilizes temporal consistency, and ignores reliability. To address these issues, we propose ARTEMIS, a unified framework for imperfectly supervised VPS driven by agent-guided reliability-aware temporal mask evolution. ARTEMIS initializes coarse masks from available supervision: SAM2 converts points/scribbles, while dense labels serve as reliable anchors. A debate-and-judge vision-language agent selects reliable temporal anchors under weak supervision, which are propagated bidirectionally with SAM2 to refine unreliable or unlabeled frames. Finally, ARTEMIS trains the segmenter using temporal reliability-aware robust learning, incorporating reliability-guided reference selection, a Reference Prototype Transport Module, and reliability-aware robust loss. These components assess mask reliability, evolve anchors over time, transport target identity across frames, and down-weight noisy supervision instead of discarding difficult samples. Experiments on SUN-SEG and CVC-ClinicDB-612 under scribble, point, and limited-label settings demonstrate that ARTEMIS achieves state-of-the-art performance. Code will be released at https://github.com/wangtong627/ARTEMIS.

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

DPRM: A Plug-in Doob h transform-induced Token-Ordering Module for Diffusion Language Models

arXiv:2604.24357v2 Announce Type: replace-cross Abstract: Diffusion language models generate without a fixed left-to-right order, leaving token ordering as a central algorithmic choice. Existing systems mainly use random masking or confidence-driven ordering, which respectively suffer from train–test mismatch and myopic exploration. We introduce DPRM (Doob -transform Process Reward Model), a plug-in token-ordering module that keeps the host architecture, denoising objective and supervision unchanged, and modifies only the ordering policy. DPRM starts from confidence-driven ordering and gradually shifts to process-reward-guided ordering through online estimates. We characterize the exact DPRM policy as a reward-tilted Gibbs reveal law, prove convergence of its stagewise Soft-BoN approximation, show that the online bucketized controller tracks the exact DPRM score at empirical-Bernstein rates, and establish a sample-complexity advantage under tractable optimization assumptions. Across nine hosts covering language reasoning, test-time scaling, protein, single-cell, molecular, DNA, text-to-image generation, and VQA, DPRM order variants improve several language, DNA, and multimodal settings while also identifying boundary cases where confidence-only ordering or task-specific utilities are preferable. Code is available at: https://github.com/DakeBU/DPRM-DLLM

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

Schrödinger's Navigator: Imagining an Ensemble of Futures for Zero-Shot Object Navigation

Zero-shot object navigation (ZSON) requires robots to find target objects in unseen environments without task-specific fine-tuning or pre-built maps, a key capability for general-purpose service robots. Yet methods that perform well in simulation often degrade in cluttered real-world scenes with severe occlusion and latent hazards, where large unseen regions make single-scene inference brittle and unsafe. We propose Schrödinger's Navigator, a belief-aware framework that reasons at inference time over multiple trajectory-conditioned imagined 3D futures. Given candidate paths, a trajectory-conditioned 3D world model predicts hypothetical observations and maintains a superposition of plausible scene realizations rather than committing to one map. An adaptive occluder-aware sampler directs imagination to uncertainty-critical regions, while a Future-Aware Value Map (FAVM) aggregates imagined futures for robust, proactive action selection. Experiments in simulation and on a physical Go2 quadruped show that Schrödinger's Navigator outperforms strong ZSON baselines, improving hidden-target discovery and risk-aware waypoint selection in occlusion-heavy navigation scenarios. These results highlight imagined 3D futures as a scalable and generalizable strategy for zero-shot navigation in uncertain real-world environments.

14.
arXiv (quant-ph) 2026-06-19

Application and quantum properties of superpositions of oppositely squeezed states

arXiv:2511.03204v2 Announce Type: replace Abstract: We show that superpositions of oppositely squeezed states – non-Gaussian Schr{\"{o}}dinger-cat-like states – exhibit enhanced nonclassical features and provide an entanglement advantage in the small-squeezing regime. These states possess photon-number structures distinct from conventional coherent-state cat states, and we analyze their Wigner functions and the entanglement generated when they are injected into a 50-50 beam splitter. As a practical application, we demonstrate that they enable a high-quality heralded single-photon source whose second-order intensity correlation function is smaller than that obtained from a pure two-mode squeezed vacuum state. We further propose a linear-optical heralding scheme that approximates these superpositions without requiring strong Kerr nonlinearities. Our results indicate that the superposition of oppositely squeezed states is a promising non-Gaussian resource for quantum information processing, particularly for single-photon generation.

15.
arXiv (CS.CL) 2026-06-18

LLM Compression by Block Removal with Constrained Binary Optimization

In this paper, we formulate the compression of large language models (LLMs) by optimally deleting transformer blocks (``block removal'') as a constrained binary optimization (CBO) problem that can be mapped to a physical system (Ising glass), whose energies are a strong proxy for downstream model performance. This formulation enables an efficient ranking of a large number of candidate block-removal configurations yielding many high-quality, non-trivial solutions beyond those only removing consecutive regions. Our method performs strongly in the deep compression regime, such as for 50% compression of Llama-3.3-70B-Instruct, where we achieve an almost 23 percentage point increase on the MMLU benchmark compared to other state-of-the-art (SOTA) block-removal methods. For lighter compression, it performs on par with those methods across several benchmarks for Llama-3.1-8B-Instruct, Qwen3-14B (both before and after retraining), as well as Llama-3.3-70B-Instruct. The approach is computationally efficient and requires only forward and backward passes on a calibration dataset for a few active parameters. Additionally, we demonstrate that using good heuristic solvers for the CBO problem provides solutions that perform well on downstream tasks in negligible runtime when it is unfeasible to solve the problem exactly. The method can be readily applied to any architecture. We illustrate this generality on the recent NVIDIA-Nemotron-3-Nano-30B-A3B-FP8 model, which exhibits a highly inhomogeneous and challenging block structure, and where we outperform SOTA for AIME25 and GPQA when removing either 2 attention layers or 3 mixture-of-experts layers.

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

Cross-Layer Discrete Concept Discovery for Interpreting Language Models

Interpreting language models remains challenging due to the existence of residual stream, which linearly mixes and duplicates features across adjacent layers, causing single-layer analyses to miss this cross-layer structure. Cross-layer sparse autoencoders (SAEs) address layer mixing but operate in continuous space, where concepts split across many neurons without clear boundaries. We introduce Cross-Layer Vector Quantized-Variational Autoencoder (CLVQ-VAE), a novel framework which maps representations from a lower layer to a higher layer through a discrete vector-quantization bottleneck, collapsing duplicated residual-stream features into compact, interpretable concept vectors. Our approach combines top-k temperature-based sampling with exponential moving average (EMA) codebook updates, providing controlled exploration of the discrete latent space while maintaining codebook diversity. Across both encoder- and decoder-based models on ERASER-Movie, Jigsaw, and AGNews, CLVQ-VAE outperforms clustering, single-layer vector quantized-variational autoencoder (VQ-VAE), and sparse autoencoder (SAE) baselines across three evaluation axes: removing identified concepts drops model accuracy by up to 93%, LLM judges rank our concepts first in 66.7% of comparisons, and human annotators recover model predictions from our visualizations with 78% accuracy versus 54% for clustering.

17.
arXiv (CS.CV) 2026-06-18

Global Offshore Wind Infrastructure: Deployment and Operational Dynamics from Dense Sentinel-1 Time Series

The offshore wind energy sector is expanding rapidly, increasing the need for independent, high-temporal-resolution monitoring of infrastructure deployment and operation at global scale. While Earth Observation based offshore wind infrastructure mapping has matured for spatial localization, existing open datasets lack temporally dense and semantically fine-grained information on construction and operational dynamics. We introduce a global Sentinel-1 synthetic aperture radar (SAR) time series data corpus that resolves deployment and operational phases of offshore wind infrastructure from 2016Q1 to 2025Q1. Building on an updated object detection workflow, we compile 15,606 time series at detected infrastructure locations, with overall 14,840,637 events as analysis-ready 1D SAR backscatter profiles, one profile per Sentinel-1 acquisition and location. To enable direct use and benchmarking, we release (i) the analysis ready 1D SAR profiles, (ii) event-level baseline semantic labels generated by a rule-based classifier, and (iii) an expert-annotated benchmark dataset of 553 time series with 328,657 event labels. The baseline classifier achieves a macro F1 score of 0.84 in event-wise evaluation and an area under the collapsed edit similarity-quality threshold curve (AUC) of 0.785, indicating temporal coherence. We demonstrate that the resulting corpus supports global-scale analyses of deployment dynamics, the identification of differences in regional deployment patterns, vessel interactions, and operational events, and provides a reference for developing and comparing time series classification methods for offshore wind infrastructure monitoring.

18.
arXiv (CS.AI) 2026-06-17

A Unified Framework for Context-Aware and Relation-Aware Graph Retrieval-Augmented Generation

arXiv:2606.18075v1 Announce Type: new Abstract: Retrieval-Augmented Generation (RAG) has emerged as a paradigm for enhancing large language models (LLMs) with external knowledge, yet existing graph-based methods face a fundamental limitation: entity-centric and chunk-centric approaches operate on representations anchored to original text without true knowledge fusion. While entity-centric methods connect logically related content and chunk-centric methods preserve context, both retrieve information separately through similarity search, missing emergent understanding from their synthesis. In this paper, we propose HyGRAG, a hierarchical graph RAG framework that transcends source documents by addressing three core challenges: constructing summaries that genuinely integrate contextual and relational information, leveraging these synthesized representations to access emergent knowledge during retrieval, and efficiently updating hierarchical structures for dynamic corpora. Specifically, we design hierarchical index structures over hybrid graphs with both chunk and entity nodes, then iteratively cluster them and generate LLM-based summaries. Then, we design context and relation-aware retrieval that searches across all abstraction levels while expanding through community membership. Moreover, we enable dynamic knowledge update through attachment-based algorithms with only local re-summarization. Experimental results show that HyGRAG improves the average accuracy of multi-hop reasoning tasks by 9.7%, while maintaining reasonable efficiency.

19.
arXiv (CS.CV) 2026-06-16

CoMNeT: A MedNeXt-CorrDiff Framework for Volumetric Brain Tumor Segmentation

Accurate brain tumor segmentation from multiparametric magnetic resonance imaging (MRI) is critical for treatment planning, response assessment, and quantitative neuro-oncology research. However, automated segmentation remains a difficult task in computer vision because of variation in tumor appearance and MRI protocols across patient scans. Moreover, clinically important regions such as enhancing tumor (ET) and tumor core (TC) are often small relative to the full brain volume, furthering increasing the difficulty of achieving high voxel-level precision. In this paper, we show that combining a modern 3D convolutional segmentation model with corrective diffusion-based refinement and ensembling improves volumetric glioma segmentation on the UTSW-Glioma dataset. We propose CoMNeT, a MedNeXt-CorrDiff framework that uses four MRI modalities as input and predicts ET, TC, and whole tumor (WT) regions for automated brain tumor segmentation. MedNeXt is used as the primary segmentation model with Global Response Normalization for feature learning, while CorrDiff is trained as a postprocessing residual refinement method to correct errors in the probability maps before final thresholding. Using five-fold cross-validation, CoMNeT achieved the highest Dice score for most tumor regions, with ET, TC, WT, and average Dice scores of 0.7543 +/- 0.0261, 0.6806 +/- 0.0166, 0.9049 +/- 0.0128, and 0.7798 +/- 0.0184, respectively. CoMNeT outperformed two selected baseline models: SegResNet (0.7555 +/- 0.0190 average Dice) and standalone MedNeXt (0.7697 +/- 0.0154 average Dice). Our findings support the use of corrective diffusion and fold-level probability ensembling as practical additions to existing state-of-the-art 3D convolutional models for automated glioma segmentation.

20.
medRxiv (Medicine) 2026-06-11

Population-scale detection of methylation outliers from long-read genome sequencing

Background: Aberrant DNA methylation can mediate the functional effects of rare genetic variation and contribute to imprinting disorders, repeat expansion diseases, and other pathogenic regulatory mechanisms. Long-read sequencing technologies now enable genome-wide detection of CpG methylation alongside genetic variation from a single assay. However, methods for systematic identification and interpretation of methylation outliers from long-read sequencing data remain limited. Methods: We developed METAFORA, a computational workflow for detecting methylation outlier regions from PacBio and Oxford Nanopore long-read sequencing data. METAFORA constructs population-level methylation references, segments the genome into correlated CpG blocks, infers technical and biological sources of variation through hidden factor estimation, models uncertainty due to variable depth sequencing, and computes covariate-adjusted methylation outlier scores for individual samples. We applied METAFORA across large long-read sequencing cohorts and integrated methylation outliers with multi-omic data. METAFORA is implemented as a snakemake workflow available at https://github.com/tjense25/METAFORA. Results: METAFORA identified methylation outlier regions associated with rare structural variants, tandem repeat expansions, and imprinting abnormalities. We found outlier regions were enriched for molecular outliers across transcriptomic and chromatin accessibility datasets, supporting their functional relevance in gene regulation. In a representative case, METAFORA identified an imprinting defect affecting the GNAS locus associated with an STX16 deletion. Conclusions: METAFORA enables scalable detection and interpretation of methylation outliers from long-read sequencing data and provides a framework for integrating epigenetic outliers with genomic and multi-omic analyses. These approaches may improve interpretation of rare regulatory variation and support discovery of clinically relevant epigenetic abnormalities in genomic medicine.

21.
arXiv (CS.CL) 2026-06-24

A P\={a}ninian Foundation for Indic Language Processing

More than a billion people communicate in Indic languages, yet the natural language processing infrastructure serving them remains fragmented and underdeveloped. The cause is structural: the field organizes its tools and benchmarks around individual languages or small subsets of genealogical language families, building separate analyzers, parsers, and datasets for each language and starting over for the next. This overlooks a deep regularity. Through more than two millennia of convergence around Sanskrit, Indic languages came to share a morphosyntactic architecture formalized in P\={a}nini's grammar, the Ast\={a}dhy\={a}y\={i}. This cuts across genealogical lines, uniting languages through a common framework. We argue that this P\={a}ninian framework supplies a unifying computational architecture the field has lacked, and that benchmarks grounded explicitly in it would make Indic language systems more accurate, more data-efficient, and more transferable, effectively merging many apparently disparate and sparse Indic language resources into a single high-resource metalanguage bedrock. We propose a four-part benchmark suite to render this shared architecture explicit, measurable, and ready to be leveraged for practical applications. Moreover, we underscore the question it raises for interpretability research: whether neural models trained on these languages come to represent P\={a}nini's categories on their own.

22.
Nature Medicine 2026-06-08

Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

Authors:

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0–IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60–1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.

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

Evaluating Local Explainability Metrics for Machine Learning Models on Tabular Data

arXiv:2605.27618v2 Announce Type: replace Abstract: Despite the wide use of explainability techniques to attempt to understand the behavior of Artificial Intelligence (AI), the generated explanations may not always be reliable. An explanation can appear plausible to humans but fail to capture the internal reasoning of a model, particularly when dealing with complex tabular data. This paper studies the trustworthiness of local explainability techniques when applied to complex tabular classification tasks, considering evaluated metrics for three main properties: faithfulness to the model's predictions, robustness to input data variations, and complexity of the explanation itself. A benchmark was performed for Local Interpretable Model-Agnostic Explanations (LIME), Kernel SHapley Additive exPlanations (SHAP), and Feature Ablation techniques, across 32 datasets and different types of machine learning models. Model performance ranges were analyzed to identify two groups: consensus-correct, which are samples that all models predicted correctly, and consensus-wrong, samples that all models predicted incorrectly. The obtained results demonstrate that that the explanations are not always correlated with a model's predictive performance. Instead, dataset complexity and feature distributions seem to be the main factors affecting explanation quality and reliability.

24.
Nature (Science) 2026-06-17

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

Authors:

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

25.
arXiv (CS.LG) 2026-06-11

Understanding Sample Efficiency in Predictive Coding

arXiv:2605.11911v2 Announce Type: replace Abstract: Predictive Coding (PC) is an influential account of cortical learning. Much of recent work has focused on comparing PC to Backpropagation (BP) to find whether PC offers any advantages. Small scale experiments show that PC enables learning that is more sample efficient and effective in many contexts, though a thorough theoretical understanding of the phenomena remains elusive. To address this, we quantify the efficiency of learning in BP and PC through a metric called ``target alignment'', which measures how closely the change in the output of the network is aligned to the output prediction error. We then derive and empirically validate analytical expressions for target alignment in Deep Linear Networks. We show that learning in PC is more efficient than BP, which is especially pronounced in deep, narrow and pre-trained networks. We also derive exact conditions for guaranteed optimal target alignment in PC and validate our findings through experiments. We study full training trajectories of linear and non-linear models, and find the predicted benefits of PC persist in practice even when some assumptions are violated. Overall, this work provides a mechanistic understanding of the higher learning efficiency observed for PC over BP in previous works, and can guide how PC should be parametrised to learn most effectively.