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01.
medRxiv (Medicine) 2026-06-22

UKBAnalytica: an integrated R package for scalable phenotyping and reproducible epidemiological analysis within the UK Biobank Research Analysis Platform

作者:

UK Biobank provides longitudinal health-related data for approximately 500,000 participants, and its Research Analysis Platform (RAP) has shifted large-scale analyses toward secure cloud-based computation. However, many existing tools address only specific steps of the analytical workflow, leaving a need for an integrated framework that connects multi-source disease phenotyping, survival-ready cohort construction, and downstream analysis on the RAP. Here, we present UKBAnalytica, an extensible R package for scalable phenotyping and integrated analysis of UK Biobank data within the RAP environment. It currently includes 52 predefined baseline variables and a built-in library of 331 curated disease definitions. These definitions are based on multiple UK Biobank data sources, including ICD-10, ICD-9, self-reported conditions, death registry records, algorithmically defined outcomes, and OPCS-4 procedure codes. UKBAnalytica distinguishes prevalent and incident cases, constructs follow-up time, generates analysis-ready survival datasets, and summarizes participant flow. Beyond phenotype construction, UKBAnalytica provides integrated modules for epidemiological analysis, omics analysis, and machine-learning-based modeling and interpretation. By linking endpoint definition with downstream modeling under a consistent data structure, UKBAnalytica reduces repetitive scripting and improves analytical transparency. Furthermore, we demonstrate the package's practical utility through a case study on chronic obstructive pulmonary disease (COPD) proteomics. The findings align closely with previously reported conclusions, underscoring the robustness and reliability of our analytical framework. This phenotype-centered framework complements existing UK Biobank tools and facilitates reproducible RAP-based biomedical research. UKBAnalytica is freely available at https://github.com/Hinna0818/UKBAnalytica.

02.
arXiv (quant-ph) 2026-06-12

Characterizing the functional role of quantum coherence in energy transfer

arXiv:2606.13404v1 Announce Type: new Abstract: Quantum coherence is understood to play a role in excitation energy transfer in open quantum systems, yet a quantitative approach to assessing its influence on the transfer process is still missing. Using Nakajima-Zwanzig projection operators, we derive a general memory kernel identity that enables us to characterize and quantify the impact of coherence in the eigenenergy basis on a generalized rate of energy transfer. Applying our approach to the electronic dynamics of a dimer coupled to a structured phonon bath, we demonstrate how quantum coherence acts to modulate energy transfer.

03.
Science (Express) 2026-05-07

Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design | Science

作者: 未知作者

A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.

05.
medRxiv (Medicine) 2026-06-15

Population-scale genomics reveals divergent pathogenicity of variant classes across paralogous collagen IV genes

Monoallelic pathogenic or likely pathogenic variants in COL4A3 and COL4A4 occur in approximately 1 in 106 individuals, yet whether these paralogous genes confer equivalent pathogenicity for the same variant classes has not been tested at population scale. Using whole-genome sequencing data from the UK Biobank (UKB; n = 500,000), with replication in the All of Us Research Program (n = 414,000), we performed per-variant association testing, gene-based collapsing analyses and phenome-wide association studies (PheWAS) across haematuria, proteinuria and chronic kidney disease. We identified 64 COL4A3 and 92 COL4A4 rare variants significantly associated with haematuria or proteinuria, generating a quantitative allelic series for clinical variant interpretation. Glycine substitutions within collagenous domains conferred similar risks in both genes. In contrast, truncating and non-collagenous domain (NC1) missense variants were strongly associated with haematuria and proteinuria in COL4A4 carriers but showed substantially attenuated or absent associations in COL4A3 carriers despite comparable carrier frequencies and predicted pathogenicity scores. These findings were independently replicated in All of Us. Genome-wide association analysis identified the COL4A3/COL4A4 locus as the dominant genetic determinant of haematuria, with the signal attributable to the aggregate effects of rare coding variants and no evidence of independent common variant or trans-acting modifier effects. These findings demonstrate substantial gene-specific differences in tolerance to truncating and NC1 variants between COL4A3 and COL4A4, challenging assumptions of equivalent pathogenicity across paralogous collagen IV genes. Gene identity and not variant class alone, should inform risk stratification, variant interpretation and genetic counselling in individuals carrying collagen IV risk genotypes.

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

Principled RL for Flow Matching Emerges from the Chunk-level Policy Optimization

Recent Progress in post-training flow matching for text-to-image (T2I) generation with Group Relative Policy Optimization (GRPO) has demonstrated strong potential. However, it is hindered by a critical limitation: inaccurate advantage attribution. In this work, we argue that aggregating consecutive steps into a coherent 'chunk' and shifting the policy optimization paradigm from GRPO's step level to the chunk level can effectively mitigate the negative impact of this issue. Building on this insight, we propose Group Chunking Policy Optimization (GCPO), the first chunk-level reinforcement learning approach for post-training flow matching. Extensive experiments demonstrate that GCPO achieves superior performance on both standard T2I benchmarks and preference alignment, with up to 43% relative gains over GRPO, highlighting the promise of chunk-level policy optimization. The code is available on https://github.com/xingzhejun/GCPO.

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

PURe: A Plug-and-Play Product-Unit Residual Module for Vision Networks

Modern vision networks are dominated by additive local transformations, whereas explicit multiplicative local interactions remain underexplored. Product units offer a direct approach to modeling such interactions, but their use in deep architectures has been limited by optimization instability. In this work, we propose PURe, a Product-Unit Residual Module for deep vision networks. PURe is built around a 2D Product Unit with a real-valued log-domain formulation that makes multiplicative local aggregation practical within deep residual hierarchies. The resulting module serves as a drop-in replacement for native residual units. We instantiate PURe in residual CNNs for image classification and in 2D residual encoder-decoder networks for slice-based segmentation on volumetric CT data. Across Galaxy10 DECaLS, ImageNet, and CIFAR-10, PURe consistently improves residual CNNs and yields a more favorable accuracy-parameter trade-off, allowing moderately deep models to match or surpass substantially deeper ResNet baselines with much smaller parameter budgets. On the AMOS benchmark, PURe also improves slice-based CT segmentation under 3D case-level evaluation. These results show that explicit multiplicative local interaction is a practical and effective design primitive for deep residual vision networks.

08.
arXiv (CS.CV) 2026-06-18

FlowObject: Flow Steering for Bridging Generative Priors and Reconstruction Fidelity

Recovering complete 3D representations of objects from few casual image captures remains a significant challenge. Recent 3D generative models, particularly those based on Flow-Matching (FM), can synthesize high-quality textured assets; however, they often suffer from ''synthetic bias'' where learned priors override observational evidence, alongside a lack of alignment with the observed instance. Conversely, optimization-based methods like 3D Gaussian Splatting (3DGS) provide high fidelity on visible surfaces but fail to reason about unobserved geometry. In this paper, we present FlowObject, a framework that reformulates sparse-view 3D reconstruction as a training-free, guided inverse problem. Our approach applies a dual-space guidance strategy to steer the Ordinary Differential Equation (ODE) trajectory of a flow-matching model, enabling the completion of unseen regions through learned generative priors while enforcing strict consistency with real-world observations. By integrating a 3DGS refinement stage, FlowObject further bridges the gap between ''synthetic-looking'' generative outputs and photorealistic reconstructions. Comprehensive benchmarks on synthetic and real-world datasets demonstrate that current state-of-the-art methods often struggle to achieve geometric completeness and observational consistency simultaneously, especially under severe occlusions. In contrast, our method significantly outperforms state-of-the-art generative models and optimization-based frameworks in both geometric completeness and view-dependent appearance fidelity.

09.
arXiv (CS.CL) 2026-06-11

AI Coding Agents Can Reproduce Social Science Findings

Recent anecdotal evidence suggests that AI coding agents can reproduce published findings when provided with original data and code; yet systematic evaluation across social sciences remains limited. Existing evaluation benchmarks are insufficient, either small or conflate agent performance with problems in the reproduction materials themselves, such as code that fails to execute correctly. Here we introduce SocSci-Repro-Bench, a benchmark of 221 tasks spanning four disciplines and 13 substantive domains, constructed from studies whose results are either fully reproducible with available materials or demonstrably non-reproducible due to missing data, allowing us to isolate agents' reproduction capacity. Evaluating two frontier coding agents, Claude Code and Codex, we find that both can reproduce a large share of social science findings, with Claude Code substantially outperforming Codex. These reproduction rates considerably exceed those previously reported for general-purpose LLM-based agents on comparable reproducibility benchmarks. Both agents also perform strongly on a reasoning task requiring identification of underlying research questions, and additional analyses suggest that results are not primarily driven by memorization. Providing the original paper PDF alongside replication materials modestly improves performance but introduces bias on tasks where reproduction is impossible. We also show that agents can be nudged toward confirmatory specification search through subtle prompt framing. Together, these findings suggest that at least some frontier coding agents can serve as reliable executors of computational workflows while underscoring the need for careful benchmarking and prompt design as AI systems assume larger roles in scientific production.

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

Building Customer Support AI Agents at 100M-User Scale: An Evaluation-Driven Framework

The rapid rise in LLM capabilities has made AI agents increasingly viable across a broad range of tasks. Among the most promising applications is building production-ready customer-facing agents, a challenge that demands coordinated excellence in evaluation methodology, context engineering, training, and online measurement. Yet these critical pillars are typically developed in isolation, creating blind spots that only surface after deployment. In this paper, we present a unified framework that bridges offline development with online impact for customer support AI agents at Nubank, a company with 100M+ users. Our approach integrates several key components: (1) structured context engineering tailored to customer support agents, (2) systematic human-in-the-loop prompt iteration, (3) rigorous LLM judge evaluation with measured inter-rater agreement and GEPA optimization for consistency, and (4) ideation-to-production validation. A central insight is that evaluation-pipeline quality directly determines iteration velocity. We present results from five production deployments spanning distinct domains: card delivery, debt management, credit-limit support, card management, and product explanation. These deployments deliver consistent customer-satisfaction gains while substantially accelerating iteration. In our card-delivery deployment, large-scale A/B testing yields a 37 percentage-point improvement in AI transactional Net Promoter Score and a 29 percentage-point gain in self-service rate over prior agent variants, alongside a strong correlation between offline simulation metrics and online outcomes, demonstrating that eval-driven development reliably predicts production impact. On most use cases, AI satisfaction reaches within a few percentage points of expert human agents.

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

Transformer-Guided Graph Attention for Direct Cardiac Mesh Reconstruction: A Structural Digital Twin Framework

Building patient-specific cardiac models sits at the heart of precision cardiology, yet getting those models into clinical use keeps running into the same wall: mesh generation is slow, messy, and frustrating. The standard workflow – segmenting the image, running Marching Cubes, and then manually cleaning up the result – is time-consuming, inconsistent across operators, and demands specialist knowledge most clinical teams do not have. We take a fundamentally different approach. Instead of treating segmentation and mesh generation as two separate problems, we train a single end-to-end network that goes directly from a raw 3D medical image to a smooth, simulation-ready cardiac surface mesh. The core is a 3D Swin Transformer encoder-decoder that extracts volumetric features from CT or MRI volumes, paired with a Graph Attention Network (GAT) head that iteratively deforms a template mesh to fit the patient's cardiac boundary. We tested on the MM-WHS 2017 benchmark using both CT and MRI. Segmentation scores were competitive (Dice of 0.84 on CT, 0.83 on MRI), but the primary focus is mesh quality: mean Chamfer distance of 1.8 mm, with 95th-percentile surface distance below 5 mm. Every mesh is produced in a single forward pass – no Marching Cubes, no smoothing filters, no manual cleanup. We argue that for cardiac digital twin pipelines, geometric fidelity and topological correctness matter more than pixel-level Dice scores. By removing the post-processing bottleneck, this approach makes patient-specific cardiac simulation substantially more accessible for clinical use.

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

BadScientist: Can a Research Agent Write Convincing but Unsound Papers that Fool LLM Reviewers?

arXiv:2510.18003v2 Announce Type: replace-cross Abstract: The convergence of LLM-powered research assistants and AI-based peer review systems creates a critical vulnerability: fully automated publication loops where AI-generated research is evaluated by AI reviewers without human oversight. We investigate this through BadScientist, a framework that evaluates whether fabrication-oriented paper generation agents can deceive multi-model LLM review systems. Our generator employs presentation-manipulation strategies requiring no real experiments. We develop a rigorous evaluation framework with formal error guarantees (concentration bounds and calibration analysis), calibrated on real data. Our results reveal systematic vulnerabilities: fabricated papers achieve acceptance rates up to . Critically, we identify concern-acceptance conflict – reviewers frequently flag integrity issues yet assign acceptance-level scores. Our mitigation strategies show only marginal improvements, with detection accuracy barely exceeding random chance. Despite provably sound aggregation mathematics, integrity checking systematically fails, exposing fundamental limitations in current AI-driven review systems and underscoring the urgent need for defense-in-depth safeguards in scientific publishing.

13.
medRxiv (Medicine) 2026-06-22

Anterior-superior hypothalamic enlargement as specific marker in episodic migraine: converging evidence from an independent discovery-replication design

Background: Growing evidence implicates the hypothalamus as a key structure in migraine pathophysiology; however, our understanding of its precise role and of the specific nuclei involved remains limited. We combined MRI data from our laboratory with publicly available MRI datasets from OpenNeuro to examine hypothalamic subunit volumes in episodic migraine and assess the specificity of these alterations relative to chronic pain conditions. Methods: Structural MRI combined with an automated atlas-based segmentation algorithm and a discovery-replication design was employed to investigate cross-sectional volumetric differences across 5 bilateral hypothalamic subunits in two independent migraine cohorts: DS1-MIG (DS1-MIG-base, n = 111 patients, n = 35 controls) and DS2-MIG (n = 27 patients, n = 31 controls). The adjusted volumes were compared between groups using MANOVA as an omnibus test, followed by Welch t-tests to test univariate follow-up. Longitudinal volumetric changes were additionally assessed in DS1-MIG participants with available follow-up scans using linear mixed models. To assess the specificity of findings to migraine, the same pipeline was applied to two chronic pain datasets, one including patients with fibromyalgia (DS-FM, n = 33 patients, n = 33 controls) and the other including patients with trigeminal neuralgia (n = 119 patients, n = 55 controls). Results: MANOVA revealed significant multivariate group differences in the discovery and replication migraine cohorts (DS1-MIG-base: = .006; DS2-MIG: = .008). Follow-up univariate analyses identified a consistent enlargement of the left anterior-superior subunit across both cohorts (FDR = .023 in DS1-MIG-base and FDR = .046 in DS2-MIG), representing the only cross-cohort replication finding. Beyond this shared signature, DS2-MIG exhibited additional significant enlargements of the right anterior-inferior and right tubular-inferior subunits. Longitudinal analyses in DS1-MIG showed that hypothalamic subunit volumes remained broadly stable over time within both migraine patients and control participants. No significant volumetric alterations were detected in the fibromyalgia or trigeminal neuralgia cohorts, either in multivariate or univariate analyses, underscoring migraine-specific findings. Conclusions: These findings provide evidence for subunit-specific hypothalamic structural alterations in migraine localized in the left anterior hypothalamic subunit. The stability of these differences over time and their absence in other chronic pain conditions suggest a migraine-specific structural organisation of hypothalamic circuitry.

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

Out-of-Distribution (OOD) Detectors for Open-Set RF Fingerprinting

arXiv:2606.12718v1 Announce Type: new Abstract: Radio-frequency (RF) fingerprinting systems must operate in open-world environments where signals from unknown transmitters and temporal drift introduce distribution shift at test time. Out-of-distribution (OOD) detection provides a natural framework for this problem, yet its application to RF fingerprinting (RFF) remains limited. A key barrier to their adoption is that most OOD detectors require auxiliary OOD data for parameter tuning, an assumption that is difficult to satisfy in RF environments where representative OOD data is impractical to collect. In this work, we introduce a promising set of OOD detection methods from the machine learning literature to open-set RFF domain. We present these methods within a unified mathematical framework based on information theory, which is a natural framework for communication systems. Our framework allows for the systematic analysis of methods and development of new methods. We further demonstrate the applicability of recent work on tuning OOD detectors without given OOD tuning data for open-set RFF. We evaluate on the POWDER RF fingerprinting dataset, showing that detectors tuned without any given OOD data achieve performance comparable to baselines with access to true OOD tuning data and greatly out-perform baseline approaches without access to true OOD tuning data, showcasing the practical viability for the RFF problem.

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

Predicting Immune Biomarkers with MultiModal Mixture-of-Expert Pathology Foundation Models Empowers Precision Oncology

Predicting immune biomarkers associated with the tumor immune microenvironment (TIME) is critical for advancing precision oncology, yet existing approaches are largely limited to single image modalities and suffer from insufficient resolution and incomplete utilization of complementary clinical and biological information. Here we introduce MixTIME, a multimodal foundation model that leverages a mixture-of-experts (MoE) architecture to integrate pathology foundation models trained across distinct modalities: image only (UNIv2), image text (CONCHv1.5), and image transcriptomic (STPath) representations for pixel-level and slide-level prediction of multiplex immunofluorescence (mIF) protein expression from hematoxylin and eosin (HE) whole-slide images. MixTIME employs a learnable router to dynamically weight expert contributions and is trained with a distribution- and tendency-aware loss function. Benchmarked on two datasets of different scales, MixTIME achieves state-of-the-art performance across 17 protein markers as measured by correlation metrics. The predicted mIF profiles substantially enhance downstream tasks, including spatial domain identification, survival prediction, and AI-assisted pathology report generation validated by expert pathologists from multiple institutes across the world. Furthermore, MixTIME enables longitudinal tracking of protein expression dynamics across clinical time points and reveals protein gene interaction patterns linked to drug resistance and immune suppression in tumor microenvironments. Collectively, MixTIME provides a scalable framework for multimodal biomarker discovery and clinical translation in computational pathology.

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

Fair Cognitive Impairment Detection Through Unlearning

Mild Cognitive Impairment (MCI) is a medical condition characterized by a noticeable decline in memory, language, or thinking abilities. MCI detection from spontaneous speech is promising for scalable screening. However, learned models often exploit demographic cues correlated with labels, resulting in a large performance gap across subgroups. We present a multimodal framework that combines (i) cross-model fusion between modalities (speech, text, and image), and (ii) unlearning using gradient reversal that discourages the shared embedding from encoding task-irrelevant demographic attributes. Evaluated on the multilingual benchmarks TAUKADIAL and PREPARE, our method outperforms the state-of-the-art multilingual and multimodal baseline in MCI classification while substantially reducing the performance gap across patient subgroups (sex and language). We further analyze transfer across datasets, showing that demographic unlearning helps learn more robust representations for MCI detection.

17.
arXiv (CS.CV) 2026-06-16

Decoupled Object-Centric Video Understanding for Generating Robotic Manipulation Commands

Translating video demonstrations into executable robot commands remains challenging because existing methods often fail to identify which objects are functionally involved in the demonstrated action. As a result, they may generate commands that are linguistically plausible but operationally ambiguous. We propose an object-centric video understanding framework that decouples action recognition from object identification to generate precise, grammar-free manipulation commands. Our approach integrates Temporal Shift Modules (TSM) for efficient spatio-temporal action classification with a novel Object Selection algorithm that identifies task-relevant objects through trajectory-based role classification, blur detection, and overlap minimization. The selected objects are then processed by Vision-Language Models (VLMs) for robust category recognition and zero-shot generalization. Evaluated on a modified Something-Something V2 dataset, our method achieves 86.79\% action classification accuracy and BLEU-4 scores of 0.337 on standard objects and 0.261 on novel objects. These results improve over the strongest task-specific baseline by 80.2\% and 143.9\%, respectively. Larger gains are observed in METEOR and CIDEr, reaching 157.9\% and 171.7\% on novel objects. Across all semantic metrics, our approach consistently outperforms task-specific methods and remains competitive with, or surpasses, large general-purpose VLMs while retaining a modular, object-centric design.

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

Beyond Global Replanning: Hierarchical Recovery for Cross-Device Agent Systems

Real-world computer-use tasks often span multiple applications and devices, requiring agents to coordinate heterogeneous environments under dynamic runtime failures. Existing multi-device agent systems support task decomposition and cross-device assignment, but recovery remains largely coarse-grained: when execution fails, they typically retry the same strategy, reassign the subtask, or revise the global plan, without systematically modeling the device-local strategy space. This limits their ability to distinguish failures that can be repaired within the current device from those that require cross-device replanning. We propose H-RePlan, a hierarchical replanning framework for multi-device agents with unified API–CLI–GUI execution. H-RePlan equips each device with interchangeable execution strategies and separates device-local strategy recovery from orchestrator-level global replanning through a compact cross-layer failure abstraction. To evaluate this capability, we introduce HeraBench, a fault-injected benchmark that constructs cross-device workflows over Linux and Android devices and injects strategy- and device-level failures. Experiments show that H-RePlan substantially outperforms single-strategy and coarse-grained multi-device baselines, achieving higher completion, instruction adherence, and perfect-pass rates while reducing the token cost required for reliable end-to-end success. These results demonstrate that scope-aware hierarchical recovery is essential for robust multi-device agent execution.

19.
arXiv (CS.CL) 2026-06-19

Connect the Dots: Training LLMs for Long-Lifecycle Agents with Cross-Domain Generalization Via Reinforcement Learning

This work presents a general framework for training large language models (LLMs) to "Connect the Dots" (CoD), a meta-capability required by long-lifecycle agents: as an LLM-based AI agent gets deployed in an environment, it solves a long sequence of tasks while continuously exploring the environment, learning from its own experiences, and iteratively self-updating its context about the environment, thereby achieving progressively better performance on future tasks conditioned on the updated context. Major components of the CoD framework include: (1) algorithm design and infrastructure for end-to-end reinforcement learning (RL) with long rollout sequences interleaving solve-task and update-context episodes; (2) tasks and environments for incentivizing and eliciting the targeted meta-capability in LLMs during training, as well as for faithfully measuring progress during evaluation. We present proof-of-concept implementations of the CoD framework, including a GRPO-style RL algorithm with fine-grained credit assignment, as well as tasks and environments tailored to the targeted meta-capability (rather than domain-specific LLM capabilities or standard task-by-task RL). Empirical results validate the efficacy of end-to-end RL training in the CoD setting, and demonstrate the potential for out-of-distribution generalization – within the training domains, across different domains, and from CoD to Ralph-loop settings – of the elicited meta-capability. Our investigation of CoD connects several lines of prior works, and opens up new opportunities for advancing LLMs and AI agents. To facilitate further research and applications, we release our implementations at \url{https://github.com/agentscope-ai/Trinity-RFT/tree/research/cod/examples/research_cod}.

20.
arXiv (CS.LG) 2026-06-16

Descriptive versus Regulatory Uncertainty in Bounded Predictive Systems

arXiv:2605.18909v2 Announce Type: replace Abstract: Any system that models the world under finite representational capacity must compress; any compression entails a prior; and the prior is the system's bias. What has not been established is whether uncertainty participates in the dynamics governing future behavior, or merely describes the output distribution without consequence. We introduce a structural distinction between descriptive uncertainty, which does not recursively modulate the system's policy, and regulatory uncertainty, which directly enters the optimization landscape and drives persistent adaptive restructuring. We prove formally that current transformer architectures are confined to descriptive uncertainty at inference. We ground this in thermodynamics via Landauer's principle: for uncertainty to be regulatory, epistemic error must cost real energy; in a decoupled system, hallucinations and correct derivations dissipate identical energy. We test this empirically across three locally-deployed language models (3B, 8B, 70B parameters). Token-level Shannon entropy is statistically invariant across tasks spanning pattern retrieval, causal operator application, and out-of-distribution causal generalization in all three models (all pairwise p >= 0.568; within-model ranges 0.011-0.028 nats), while task accuracy varies substantially across the same conditions (0%-100%). Entropy and accuracy are orthogonal. The decoupling is scale-invariant: larger models achieve higher accuracy but identical entropy flatness. This structural incapacity is not resolvable by additional parameters or training data. Genuine epistemic grounding requires physical coupling between thermodynamic substrate state and information processing cost.

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

NanoQuant: Efficient Sub-1-Bit Quantization of Large Language Models

arXiv:2602.06694v3 Announce Type: replace Abstract: Weight-only quantization has become a standard approach for efficiently serving large language models (LLMs). However, existing methods fail to efficiently compress models to binary (1-bit) levels, as they either require large amounts of data and compute or incur additional storage. In this work, we propose NanoQuant, the first post-training quantization (PTQ) method to compress LLMs to both binary and sub-1-bit levels. NanoQuant formulates quantization as a low-rank binary factorization problem, and compresses full-precision weights to low-rank binary matrices and scales. Specifically, it utilizes an efficient alternating direction method of multipliers (ADMM) solver to precisely initialize latent binary matrices and scales, and then tunes the initialized parameters through a block and model reconstruction process. Consequently, NanoQuant establishes a new Pareto frontier in low-memory post-training quantization, and enables sub-1-bit compression. NanoQuant makes large-scale deployment feasible on consumer hardware. For example, it compresses Llama2-70B by 25.8$\times$ in just 13 hours on a single H100, enabling a 70B model to operate on a consumer 8 GB GPU. Code is available at https://github.com/SamsungLabs/NanoQuant.

22.
medRxiv (Medicine) 2026-06-18

Effectiveness and Safety of Bempedoic Acid Across Clinically Relevant Subgroups: Insights from the CLEAR Taiwan Study

Background Despite available lipid-lowering therapies (LLT), many patients fail to achieve low-density lipoprotein cholesterol (LDL-C) targets. This gap persists across clinically relevant subgroups. Bempedoic acid has demonstrated effective LDL-C lowering with a favorable safety profile in the CLEAR Taiwan study; however, its effects across subgroups in Asian populations remains limited. Methods The phase IV CLEAR Taiwan study (NCT06925100) enrolled patients with inadequately controlled hypercholesterolemia who received bempedoic acid for 12 weeks in addition to background LLT. This analysis evaluated changes in lipid parameters, high-sensitivity C-reactive protein (hsCRP), and safety outcomes in clinically relevant subgroups, including cardiovascular risk, diabetes, age, statin tolerance, and sex. Results A total of 180 patients were included. Bempedoic acid achieved significant LDL-C reductions in all subgroups. Numerically greater LDL-C reductions were observed in primary prevention, statin-intolerant, younger (< 65 years), and female patients, while comparable reductions were observed across diabetes status. Reductions in non-high-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B were consistent with LDL-C findings. Significant decreases in hsCRP were observed in all subgroups, with numerically greater reductions in patients aged < 65 years and those without diabetes. Bempedoic acid was well tolerated, with a low incidence of adverse events and no new safety signals identified. Changes in liver enzymes, renal function, and uric acid were minimal within subgroups. Conclusion Subgroup analyses from the CLEAR Taiwan study demonstrate consistent efficacy and safety of bempedoic acid across clinically relevant subgroups and support its use as a flexible option to address residual gaps in lipid management.

23.
arXiv (CS.CV) 2026-06-12

VISA: VLM-Guided Instance Semantic Auditing for 3D Occupancy World Models

Semantic 3D occupancy provides a voxelized world state for autonomous driving and robot decision making, but object and rare-class errors can affect free-space interpretation, collision checking, and temporal state propagation. We show that a common VLM strategy, aligning 3D voxel or object features with crop-caption embeddings, improves text-space similarity without reliably improving closed-set occupancy mIoU. Motivated by this mismatch, we propose VISA, a training-time semantic auditing approach for existing occupancy world models. VISA queries an offline VLM on a representative crop of each physical object instance, obtains a structured audit with class hypotheses, plausible confusions, reliability, attributes, and evidence, and propagates it along the object track. The audit is grounded to matched 3D object voxels and distilled into semantic logits through reliability-weighted taxonomy, attribute-factor, and scene-level audit graph losses, while inference remains unchanged and requires no VLM. On nuScenes, averaged across three runs, VISA improves OccWorld from 19.06 to 20.05 mIoU and GaussianWorld from 21.36 to 21.91 mIoU; on GaussianWorld, object mIoU improves from 18.18 to 19.16 and rare-class mIoU from 15.60 to 16.79. These results suggest that VLMs are better suited to closed-set occupancy as reliability-aware semantic auditors than as generic caption-embedding targets.

24.
arXiv (CS.CL) 2026-06-18

RECOM: A Validity Discrimination Tradeoff in Automatic Metrics for Open Ended Reddit Question Answering

Automatic metrics are the default for evaluating LLM-generated text, yet a metric is quietly asked to do two jobs: tell genuine content alignment from surface coincidence (validity), and tell a better system from a worse one (discriminative power). On open-ended, opinion-driven question answering, the two are in tension. We introduce RECOM (Reddit Evaluation for Correspondence of Models), a contamination-free evaluation dataset of 15,000 r/AskReddit questions (September 2025), each paired with its authentic community replies, which postdate every evaluated model's training cutoff. Scoring five open-source LLMs (7–10B) against every reply each metric paired with a random-derangement noise floor we find that no metric does both jobs well. Cosine similarity separates real from random answers (Cohen's $d \approx 2$) but cannot rank the five models ($|d| < 0.1$); BERTScore precision appears to rank the models (raw $|d|$ up to 0.63), but once response length is controlled this collapses to $|d| = 0.09$ and its validity is weak ($d \approx 0.8$, versus cosine's $\approx 2$). Because every metric scores the same outputs, this validity–discrimination tradeoff is a property of the metrics, not the models, and we argue it stems from representation design. Three independent LLM judges reproduce the validity gap and likewise separate the five models only weakly. We recommend reporting metrics on both axes, with an explicit random-baseline floor. RECOM is publicly available at https://anonymous.4open.science/r/recom-D4B0

25.
Nature (Science) 2026-06-18

Daily briefing: The brain builds a sentence neuron by neuron

作者:

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. 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.