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

From Benchmarks to Skills: Low-Rank Factors for LLM Evaluation

作者:
Aviya Maimon↗Amir DN Cohen↗Gal Vishne↗Shauli Ravfogel↗Reut Tsarfaty↗

Current evaluations of large language models (LLMs) rely heavily on a growing collection of benchmarks and on aggregate benchmark scores, yet it remains unclear what this comparison actually captures, and what these scores reveal about models' underlying capabilities. Here, we propose a new paradigm for LLM evaluation, by asking whether benchmark performance reflects many independent abilities, or rather relies on a small number of shared dimensions. To answer this, we apply Factor Analysis (FA) to a massive performance matrix of LLMs versus benchmarks \((60\times44)\) revealing an intrinsically low-rank structure of that matrix. That is, a small number of latent factors captures most of the structure in the full task space. This low-rank geometry reveals substantial redundancy across existing tasks and explains why many benchmarks appear to be measuring overlapping abilities. We further show that these latent factors correspond to coherent, skill-like, dimensions of LLM behavior. Leveraging this latent skill-space, we deliver three practical tools for LLM evaluation and downstream users: (i)~identifying redundant tasks, (ii)~profiling new models using a small subset of tasks, and (iii)~selecting models aligned with desired skill profiles. Our method provides a solid alternative to the de-facto standard of a single aggregate score, and establishes an interpretable and practical framework for understanding and benchmarking LLM core capabilities.

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03.
arXiv (math.PR) 2026-06-11

Asymptotic analysis of the finite predictor for fractional Gaussian noise

作者:
P. Chigansky↗M. Kleptsyna↗

arXiv:2504.01562v2 Announce Type: replace-cross Abstract: This paper proposes a new approach to the asymptotic analysis of the finite predictor for stationary sequences. Our method yields the exact asymptotics of both the relative prediction error and the partial correlation coefficients. The underlying assumptions are analytic in nature, making the approach applicable to processes with long-range dependence. The ARMA-type process driven by fractional Gaussian noise (fGn), which had previously remained elusive, is used as a case study.

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

Before You Think: System 0, AI-Mediated Cognition and Cognitive Colonization

作者:
Marianna Bergamaschi Ganapini↗Massimo Chiriatti↗Enrico Panai↗Giuseppe Riva↗

arXiv:2606.13658v1 Announce Type: new Abstract: This paper examines three recent frameworks for understanding the cognitive and epistemic consequences of artificial intelligence: Tri-System Theory, Thinkframes, and System 0. It argues that while the first two capture important dimensions of AI's influence on individual reasoning and collective epistemic practices, System 0 occupies a theoretically distinctive position that neither can fully replicate. The paper introduces the concept of cognitive colonization, according to which AI systems can embed external interests within the architecture of the self in ways that are difficult for users to perceive. Because such systems are already widely deployed, understanding these invisible forms of influence is an urgent philosophical and practical task.

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05.
arXiv (quant-ph) 2026-06-12

Squeezing Enhancement in Lossy Multi-Path Atom Interferometers

作者:
Julian G\"unther↗Jan-Niclas Kirsten-Siem{\ss}↗Naceur Gaaloul↗Klemens Hammerer↗

arXiv:2409.04091v3 Announce Type: replace Abstract: This paper explores the sensitivity gains afforded by spin-squeezed states in atom interferometry, in particular using Bragg diffraction. We introduce a generalised input-output formalism that accurately describes realistic, non-unitary interferometers, including losses due to velocity selectivity and scattering into undesired momentum states. This formalism is applied to evaluate the performance of one-axis twisted spin-squeezed states in improving phase sensitivity. Our results show that by carefully optimising the parameters of the Bragg beam splitters and controlling the degree of squeezing, it is possible to improve the sensitivity of the interferometer by several dB with respect to the standard quantum limit despite realistic levels of losses in light pulse operations. However, the analysis also highlights the challenges associated with achieving these improvements in practice, most notably the impact of finite temperature on the benefits of entanglement. The results suggest ways of optimising interferometric setups to exploit quantum entanglement under realistic conditions, thereby contributing to advances in precision metrology with atom interferometers.

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

Robustness without Wrinkles: Parallel Simulation and Robust MPC for Certified Deformable Manipulation

作者:
Wei-Chen Li↗Jeffrey Fang↗Sasanka Polisetti↗Yuexi Song↗Glen Chou↗

arXiv:2606.14188v1 Announce Type: cross Abstract: We present CORD-SLS, a real-time control method for safe deformable object manipulation, with a focus on ropes and cloth. At its core is a GPU-parallel differentiable simulator with contact smoothing which enables efficient gradient-based planning through intermittent contact. To robustly satisfy constraints under model and sensing uncertainty, we develop a real-time, GPU-parallel output-feedback robust model predictive control (MPC) algorithm that plans with this simulator. We further show that the simulator accelerates model-based RL for training neural manipulation policies. To improve real-world robustness, we use conformal prediction to calibrate visual-feedback and perception-error bounds for MPC, producing reachable tubes that enable high-probability safe control. We evaluate CORD-SLS on high-dimensional, contact-rich rope and cloth manipulation tasks in simulation and hardware, including obstacle avoidance, routing, folding, and smoothing. Across settings, CORD-SLS achieves millisecond-speed planning, exceeding baselines in safety, speed, and task success.

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07.
arXiv (CS.LG) 2026-06-16

DAL: A Practical Prior-Free Black-Box Framework for Piecewise Stationary Bandits

作者:
Argyrios Gerogiannis↗Yu-Han Huang↗Subhonmesh Bose↗Venugopal V. Veeravalli↗

arXiv:2501.19401v5 Announce Type: replace Abstract: We introduce a practical, black-box framework termed Detection Augmented Learning (DAL) for the problem of piecewise stationary bandits without knowledge of the underlying non-stationarity. DAL accepts any stationary bandit algorithm with order-optimal regret as input and augments it with a change detector, enabling applicability to all common bandit variants. Extensive experimentation demonstrates that DAL consistently surpasses all state-of-the-art methods across diverse non-stationary scenarios, including synthetic benchmarks and real-world datasets, underscoring its versatility and scalability. We provide theoretical insights into DAL's strong empirical performance, complemented by thorough empirical validation.

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08.
arXiv (CS.LG) 2026-06-11

Urban Heat MiniCubes: An AI-Ready dataset for urban heat research

作者:
Jonathan Starfeldt↗Maria J. Molina↗Alexander Kerr↗Adam Yang↗Thomas R. H. Holmes↗Christopher R. Hain↗

arXiv:2606.11534v1 Announce Type: cross Abstract: Urban heat is amplified by impermeable surfaces and heterogeneous built environments, yet street-level variability remains difficult to quantify because multi-sensor observations are rarely available in consistent, analysis-ready form at the necessary spatiotemporal scales. We present "Urban Heat MiniCubes," a publicly available, FAIR-oriented dataset designed for machine learning applications in urban heat research. The dataset provides harmonized 90 x 90 km gridded data cubes for 48 cities in the Western Hemisphere spanning 2022-2023, with variables reprojected and collocated to a common grid to reduce preprocessing (e.g., reprojection, resampling, and spatiotemporal alignment). Urban Heat MiniCubes includes two complementary modalities: (i) higher-spatial-resolution, lower-frequency observations from Landsat 8/9 (e.g., surface reflectances) and Sentinel-1 (e.g., synthetic aperture radar backscatter), and (ii) higher-temporal-frequency, coarser observations from GOES-R (e.g., longwave infrared brightness temperatures) and a microwave land surface temperature product. We document variables and metadata and provide technical assessment using inter-variable analyses and autoencoder-based reconstruction-error summaries across pixel classes (e.g., water and cloud). Potential use cases and limitations are also discussed.

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09.
arXiv (CS.LG) 2026-06-19

Towards Modality-imbalanced Federated Graph Learning: A Data Synthesis-based Approach

作者:
Zhengyu Wu↗Hongchao Qin↗Xunkai Li↗Zekai Chen↗Rong-Hua Li↗Guoren Wang↗

arXiv:2606.20382v1 Announce Type: new Abstract: MultiModal Federated Graph Learning (MM-FGL) offers a natural collaborative training paradigm, but its practical deployment is challenged by two granularities of modality imbalance. Client-level imbalance occurs when certain clients lack entire modalities, while node-level imbalance occurs when individual nodes exhibit missing visual or textual attributes. While several relevant studies exist, our investigation reveals that they predominantly target graph-agnostic or centralized scenarios, rendering them difficult to adapt directly. To address these challenges, we formalize modality-imbalanced MM-FGL as an implicit graph-aware latent semantic representation synthesis problem. This paradigm recovers missing modal semantics directly within the representation space, thereby maximizing alignment with the original data's semantic distribution and mitigating the high variance induced by missing modalities. To this end, we propose FedMGS (Federated Modality-aware Graph Synthesis), which integrates three core components. The availability-aware graph encoder prevents missing modalities from contaminating local structural propagation. The prototype-guided latent semantic synthesizer establishes cross-client semantic anchors for unavailable modalities. The reliability-calibrated semantic fusion mechanism regulates the impact of recovered latent representations prior to predictive readout. Extensive experiments on four tasks show that FedMGS consistently outperforms competitive baselines with gains up to 17.41% with best efficiency-performance tradeoff.

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10.
arXiv (CS.CV) 2026-06-12

Amnesia: A Stealthy Replay Attack on Continual Learning Dreams

作者:
Ahmed Sharshar↗Naveen Kumar Kummari↗Mohsen Guizani↗

Continual learning (CL) models often use experience replay to reduce catastrophic forgetting, but their robustness to replay sampling interference remains underexplored. Existing CL attacks alter inputs or training pipelines (poisoning/backdoors) and rarely include explicit auditable constraints, limiting realism. Here, auditability means a monitor can verify compliance from sampler-visible telemetry - e.g., logged replay index/label statistics - by checking that the realized replay class histogram stays close to a nominal baseline and that replay rate is unchanged per batch and/or over a rolling window. We study a limited-privilege insider who controls only replay index selection, not pixels, labels, or model parameters, while staying within auditable limits such as queue priorities. We introduce Amnesia, a replay composition attack that maximizes degradation under two budgets: a visibility budget delta bounding the TV/KL divergence from a nominal class histogram p0, and a mass budget f fixing the replay rate. Amnesia has two steps: (i) compute lightweight class utilities, such as EMA loss or confidence, to tilt p0 toward harmful classes; and (ii) project the tilt back into the delta-ball using efficient KL (exponential tilt) or TV (balanced mass redistribution) optimizers. A windowed scheduler enforces rolling audits. Across challenging CL benchmarks and strong replay baselines, Amnesia consistently lowers final accuracy (ACC) and worsens backward transfer (-BWT). The KL variant delivers high impact while remaining largely undetected under multiple audit schemes, including per-batch and rolling-window checks. The TV variant is more damaging but easier to detect, especially under tight per-class constraints. These results expose index-only replay control as a practical, auditable threat surface in CL systems and establish a principled impact-visibility trade-off.

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

Why SWAVE May Not Be All You Need:A Concept-Evolution Retrospective on Complex-Valued Recurrent Language Models

作者:
Ramprasath Ganesaraja↗Swathika N↗Sahil Dilip Panse↗

arXiv:2606.18324v1 Announce Type: cross Abstract: SWave is a complex-valued recurrent language model (169.26M parameters, D=384, L=16, T=2048) trained on FineWeb-Edu using 2xH100 NVL. It was designed around three founding premises: that representing language as complex waves rather than real-valued numbers enables richer information encoding; that a Cayley-parameterised unitary transition provides a mathematical guarantee against state decay or explosion; and that a hidden state which rotates rather than shrinks preserves signal integrity over arbitrarily long contexts. The core of SWave evolved substantially across three development phases. The Resonance Head was found to structurally admit imaginary-channel collapse as a global loss minimum (a failure mode we term cos-domination collapse) and was superseded by an untied head with independent real and imaginary embedding tables from the Phase-Associative Memory (PAM) architecture. This resolved the degenerate minimum and enabled stable 200,000-step training (best-step PPL 22.0 at step 89,861). ComplexNorm and the Wave Propagation Scan proved load-bearing throughout all three phases and were retained to the final architecture. ProtectGatedScan was reframed as a structural prior rather than a learned behaviour. The four multi-scale retention concepts showed no measurable improvement under controlled evaluation and were found non-load-bearing. The ComplexGatedUnit was superseded by a real-valued squared-ReLU channel mixer with fewer parameters. The auxiliary training objectives showed no benefit once structural constraints were resolved. The investigation yields a formal characterisation of cos-domination collapse, a parallel scan with a log-space backward pass for numerical stability, six transferable engineering principles for complex-valued recurrent training, and a plan-to-code traceability methodology for catching structural divergences that conventional test suites miss.

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

Machine-learned particle flow as a foundation model for collider physics

作者:
Farouk Mokhtar↗Joosep Pata↗Michael Kagan↗Javier Duarte↗

arXiv:2606.14373v1 Announce Type: cross Abstract: The workflow from particle collision to physics analysis passes through a series of reconstruction steps that are traditionally modular and disconnected, with no shared representation linking low-level detector data to high-level analysis tasks. We show that casting event reconstruction as a machine learning problem naturally produces such a shared representation. We repurpose a machine learning model trained for particle-flow reconstruction (MLPF) to perform three distinct analysis tasks: jet flavor identification, jet energy regression, and missing momentum regression. By appending the per-particle latent representations learned during reconstruction as additional input features, we substantially improve over baselines that use kinematic features alone. We further demonstrate that a single linear layer trained using only the latent representations achieves competitive performance against state-of-the-art baseline architectures, and outperforms the baseline for missing momentum regression with approximately 35 times fewer parameters. These results demonstrate that the latent representations learned during reconstruction encode essential physics information needed for downstream analysis, establishing MLPF as a foundation model and offering a concrete step toward an end-to-end pipeline from detector data to physics analysis.

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

SorryDB: Can AI Provers Complete Real-World Lean Theorems?

作者:
Austin Letson↗Leopoldo Sarra↗Auguste Poiroux↗Oliver Dressler↗Paul Lezeau↗Dhyan Aranha↗Frederick Pu↗Aaron Hill↗Miguel Corredera Hidalgo↗Julian Berman↗George Tsoukalas↗Lenny Taelman↗…

arXiv:2603.02668v2 Announce Type: replace Abstract: We present SorryDB, a dynamically-updating benchmark of open Lean tasks drawn from 78 real world formalization projects on GitHub. Unlike existing static benchmarks, often composed of competition problems, hillclimbing the SorryDB benchmark will yield tools that are aligned to the community needs, more usable by mathematicians, and more capable of understanding complex dependencies. Moreover, by providing a continuously updated stream of tasks, SorryDB mitigates test-set contamination and offers a robust metric for an agent's ability to contribute to novel formal mathematics projects. We evaluate a collection of approaches, including generalist large language models, agentic approaches, and specialized symbolic provers, over a selected snapshot of 1000 tasks from SorryDB. We show that current approaches are complementary: even though an agentic approach based on Gemini Flash is the most performant, it is not strictly better than other off-the-shelf large-language models, specialized provers, or even a curated list of Lean tactics.

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

X-OPD: Cross-Modal On-Policy Distillation for Capability Alignment in Speech LLMs

作者:
Di Cao↗Dongjie Fu↗Hai Yu↗Siqi Zheng↗Xu Tan↗Tao Jin↗

While the shift from cascaded dialogue systems to end-to-end (E2E) speech Large Language Models (LLMs) improves latency and paralinguistic modeling, E2E models often exhibit a significant performance degradation compared to their text-based counterparts. The standard Supervised Fine-Tuning (SFT) and Reinforcement Learning (RL) training methods fail to close this gap. To address this, we propose X-OPD, a novel Cross-Modal On-Policy Distillation framework designed to systematically align the capabilities of Speech LLMs to their text-based counterparts. X-OPD enables the Speech LLM to explore its own distribution via on-policy rollouts, where a text-based teacher model evaluates these trajectories and provides token-level feedback, effectively distilling teacher's capabilities into student's multi-modal representations. Extensive experiments across multiple benchmarks demonstrate that X-OPD significantly narrows the gap in complex tasks while preserving the model's inherent capabilities.

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

Beyond Perplexity: UTF-8 Validity in Byte-aware Language Models

作者:
Sangwhan Moon↗Daisuke Oba↗Youmi Ma↗Tatsuya Hiraoka↗Naoaki Okazaki↗

Byte-level tokenization enables language models to handle any Unicode input, but models can generate invalid UTF-8 sequences when encountering rare or unseen characters. We investigate the relationship between training scale and UTF-8 generation reliability with a 355M parameter model trained on 80B tokens from a balanced multilingual corpus of English, Japanese, Korean, and Chinese. We introduce multiple evaluation protocols that isolate UTF-8 structural validity from language modeling. UTF-8 validity convergence lags perplexity by a roughly a factor of two: perplexity stabilizes after 2.1B tokens, but UTF-8 validity requires 4.2B tokens. In context-free generation, rare characters achieve higher structural validity than common characters, suggesting over-specialization of frequent character representations. Through experiments, we observed that reliable UTF-8 generation is a distinct capability requiring evaluation beyond perplexity.

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18.
arXiv (quant-ph) 2026-06-17

Average entropy of Bogoliubov-Kubo-Mori random state ensemble

作者:
Sohail↗Lu Wei↗

arXiv:2606.17960v1 Announce Type: cross Abstract: Random states play a foundational role in different branches of modern quantum science. In this work, we study a recently proposed random state ensemble induced from von Neumann entropy through the Bogoliubov-Kubo-Mori (BKM) metric. In particular, we derive an exact yet explicit formula of average entanglement entropy over BKM ensemble. In obtaining the formula, we only make use of properties of normalization constant of the ensemble in the absence of its correlation kernel, contrary to average entropy computation of other ensembles. This new framework paves the way for calculating higher-order cumulants of BKM ensemble beyond the average.

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

Direct Fisher Score Estimation for Likelihood Maximization

作者:
Sherman Khoo↗Yakun Wang↗Song Liu↗Mark Beaumont↗

arXiv:2506.06542v2 Announce Type: replace-cross Abstract: We study the problem of likelihood maximization when the likelihood function is intractable but model simulations are readily available. We propose a sequential, gradient-based optimization method that directly models the Fisher score based on a local score matching technique which uses simulations from a localized region around each parameter iterate. By employing a linear parameterization to the surrogate score model, our technique admits a closed-form, least-squares solution. This approach yields a fast, flexible, and efficient approximation to the Fisher score, effectively smoothing the likelihood objective and mitigating the challenges posed by complex likelihood landscapes. We provide theoretical guarantees for our score estimator, including bounds on the bias introduced by the smoothing. Empirical results on a range of synthetic and real-world problems demonstrate the superior performance of our method compared to existing benchmarks.

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20.
arXiv (CS.CV) 2026-06-15

Rethinking One-Step Image Editing through ChordEdit: Reproduction, Simplification, and New Insights

作者:
Minghan Li↗Jeremy Moebel↗Mengyu Wang↗

One-step image editing is important for making text-guided editing fast, practical, and easy to deploy, but its underlying mechanism is still not fully understood. We revisit ChordEdit through reproduction, ablation, and simplification. Our analysis shows that a) the chord window $\delta$ largely acts as an effective timestep shift from $t$ to $t - \delta$; b) chord transport acts on high-noise images and mainly performs low-frequency semantic editing; and c) proximal alignment acts on low-noise images and complements it by adding high-frequency target details. In this view, ChordEdit naturally decomposes editing into a coarse low-frequency transport stage and a fine high-frequency alignment stage. These findings suggest a path toward prompt-conditioned dynamic timestep selection for adaptive image editing. All code and results can be found at \href{https://github.com/Harvard-AI-and-Robotics-Lab/ChordEdit-Reproduction}{link}.

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21.
arXiv (CS.CV) 2026-06-16

Gen-VCoT: Generative Visual Chain-of-Thought Reasoning via Diffusion-Based RGB Intermediate Representations

作者:
Zhiqiang Zhou↗Junliang Dai↗Xu ling↗

Multimodal large language models (MLLMs) excel at visual reasoning but rely on text-based chain-of-thought (CoT), lacking interpretable visual intermediates. Existing methods use opaque tokens or external tools, missing key properties. We propose Gen-VCoT, a framework using expert vision models to generate RGB images as reasoning intermediates. It has three stages: visual grounding (SAM segmentation), geometric reasoning (Marigold depth maps), and semantic reasoning (Qwen2-VL integration). An adaptive router selects reasoning depth. Evaluations show Gen-VCoT improves spatial (25% better) and depth (50% better) questions, but may hurt simple factual queries. Text CoT outperforms visual intermediates on CLEVR (91.2% vs 62.5%), showing task-dependent optimal representations. Gen-VCoT establishes a new paradigm for interpretable multimodal reasoning.

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22.
arXiv (CS.LG) 2026-06-17

Randomized Midpoint Method for Log-Concave Sampling under Constraints

作者:
Yifeng Yu↗Shijie Zhang↗Lu Yu↗

arXiv:2405.15379v3 Announce Type: replace-cross Abstract: In this paper, we study the problem of sampling from log-concave distributions supported on convex and compact sets, with a particular focus on the randomized midpoint discretization of both overdamped and kinetic Langevin diffusions in constrained domains. We revisit the proximal framework for handling constraints through projection operators and develop a more general formulation that encompasses Euclidean, Bregman, and Gauge projections. The resulting smooth approximation allows a unified and tractable analysis of Langevin algorithms and their variants under constraints. Within this framework, we establish convergence guarantees in Wasserstein-$q$ $(q\geqslant 1)$ distances between the smooth surrogate and the target distribution. We further derive complementary lower bounds, showing that the results are near-optimal in order. Building upon this tight approximation analysis, we obtain new convergence guarantees for the randomized midpoint Langevin algorithms and refined bounds for both vanilla and kinetic Langevin Monte Carlo methods under constraints, thereby advancing the theoretical understanding of constrained diffusion-based sampling.

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23.
bioRxiv (Bioinfo) 2026-06-10

Folding the unfoldable 2: using AlphaFold and ESMFold to explore spurious proteins

作者:
Orr↗A. K↗Bateman↗

Motivation: Spurious protein sequences, resulting from gene prediction errors, theoretically should not yield folded structures. AlphaFold2 was previously shown to predict short spurious sequences with high pLDDT scores and was therefore unlikely to distinguish between real proteins and spurious proteins which are usually short. We evaluate whether newer structure prediction methods (ESMFold and AlphaFold3) similarly predict short sequences with high pLDDT or if they better discriminate between spurious and real proteins. Results: All three structure prediction methods (ESMFold, AlphaFold2, and AlphaFold3) predict short spurious sequences from AntiFam with unexpectedly high pLDDT scores, however the discrimination between spurious and real proteins improves beyond 100 amino acids. By analysing sequences with disparate pTM and pLDDT scores, we identified two likely spurious shadow ORFs in Swiss-Prot and one potentially non-spurious AntiFam entry. Using the structure prediction scores, we developed a Gaussian Process Model and evaluated its performance on AlphaFold DB, identifying potential spurious proteins at scale. While limited on its own, this model can increase confidence in spurious protein identification when combined with other methods.

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

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

作者:
Xingyu Tan↗Shiyuan Liu↗Xiaoyang Wang↗Qing Liu↗Xiwei Xu↗Xin Yuan↗Liming Zhu↗Wenjie Zhang↗

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

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25.
medRxiv (Medicine) 2026-06-22

Panel-level multilocus methylation quantification in native cell-free DNA by PCR-compatible sequential enzymatic processing

作者:
Vaquer↗C. C↗Wetten↗P. A↗Garcia Samartino↗Rodriguez↗J. D↗Manzino↗N. R↗Perez Ravier↗Angeloni↗A. R↗…

DNA methylation is informative for liquid biopsy, but low template abundance, distributed methylation signals and workflow complexity limit implementation. Here we present Delta-HLD, a PCR-compatible methylation assay platform that quantifies methylation directly in native DNA through sequential hybridization, ligation and methylation-sensitive digestion. The assay co-reports methylation-dependent signals from multiple loci through a shared amplification architecture, generating a single panel-level PCR readout. We established the chemistry, optimized panel size and composition through model-guided experiments, and implemented the assay as a triplex qPCR workflow with per-sample internal process controls. Plasma proof-of-concept analyses showed discriminatory signal in CRC and proof-of-concept transferability to hepatocellular carcinoma. Additional platelet-retaining experiments identified a strategy to increase recovery of analyzable circulating templates while reducing genomic DNA recognition. Delta-HLD provides a compact PCR-compatible framework for low-input methylation analysis without base conversion.

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