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01.
PLOS Medicine 2026-05-22

Differences in tuberculosis prevalence by sex in low- and middle-income countries over 1993–2025: A systematic review and meta-analysis

by Nicole A. Swartwood, Nanki Singh, Seyed Alireza Mortazavi, Melike Hazal Can, Hening Cui, Do Kyung Ryuk, Peter MacPherson, Katherine C. Horton, Nicolas A. Menzies Background Global and national initiatives to combat tuberculosis (TB) have expanded over recent years. Despite this, the TB burden remains high in some population groups, with men recognized as having elevated TB risks. Summary measures of sex differences in TB prevalence were last estimated in 2016. Since then, many additional prevalence surveys have been conducted, including in the highest TB burden countries. We conducted a systematic review of sex-stratified TB prevalence survey data published over 1993–2025, to provide updated estimates of male-to-female (M:F) TB prevalence ratios and determine whether sex-related disparities in TB burden have closed over time. Methods and findings We identified surveys reporting community-representative, sex-stratified estimates of pulmonary TB prevalence in low- and middle-income countries (LMICs), including surveys from an earlier review (covering January 1993–March 2016) and a new systematic review (covering 1st December 2015–13th October 2025). This review was prospectively registered with PROSPERO (CRD42024503853) and included searches of PubMed, Embase, Global Health, the Cochrane Library, Africa Index Medicus, LILACS, and SciELO. We extracted data on bacteriologically confirmed and smear-positive TB prevalence among adults (aged ≥ 15 years), stratified by sex. Risk of bias was evaluated using eight criteria specific to prevalence surveys. We fit multi-level Bayesian regression models with study- and country-level random effects to estimate the M:F ratio of TB prevalence (male prevalence divided by female prevalence), overall and for key subgroups. In meta-regression analyses, we estimated how prevalence ratios varied over time and according to known TB risk factors and TB case definitions.We identified 10,124 publications and extracted data from 100 eligible studies representing 102 unique prevalence surveys and 4,658,310 participants (45.6% male) in 33 LMICs. TB prevalence was higher in men than women in 90/102 of the included surveys, with a pooled M:F prevalence ratio of 2.02 (95% credible interval (CrI): 1.71, 2.34) for bacteriologically confirmed TB and 2.38 (95% CrI: 1.91, 2.90) for smear-positive TB. Time trend analyses showed a 2.0% (95% CrI: −0.2, 4.5%) average annual change in the M:F ratio of bacteriologically confirmed TB over the study period. The M:F prevalence ratio was estimated to be higher for countries with greater excess HIV prevalence among men, and countries with greater gender equity (as measured by the United Nation’s Gender Development Index). The estimated M:F prevalence ratio was also higher for surveys that did not restrict testing to individuals reporting TB symptoms. Study limitations include heterogeneity in survey methods and definitions, as well as limited data from the Americas, Eastern Mediterranean, and Europe WHO world regions and post-COVID-19 period. Conclusions Men in LMICs consistently experience TB at a higher prevalence than women. Time trend estimates are uncertain, but consistent with widening sex differences in TB prevalence over the last three decades, despite efforts to address the risk factors underlying this excess TB burden.

02.
arXiv (CS.AI) 2026-06-16

Input-Dependent Fisher Information for Local Sensitivity Analysis of Medical Image Classifiers

arXiv:2606.16362v1 Announce Type: cross Abstract: Deep neural networks have achieved strong performance in medical image classification, but often work like black-box. Commonly used post-hoc interpretation methods often provide heuristic visualizations whose relationship to the classifier's predictive distribution is indirect. This work introduces a local sensitivity analysis framework based on the input-dependent Fisher Information Matrix (iFIM) of a trained classifier. The iFIM characterizes how the classifier's predictive distribution changes under infinitesimal perturbations of the input image. By using a Gram-matrix formulation, the nonzero eigenspectrum of the iFIM can be recovered without explicitly forming the full image-dimensional Fisher matrix. The leading iFIM eigenspace is then used to project an input image into a high local-sensitivity component and its orthogonal component. These components provide a model-intrinsic description of local predictive sensitivity, rather than a conventional pixel-wise attribution heatmap or a causal segmentation of task-relevant anatomy. The framework is evaluated on controlled and clinical medical image classification tasks using multiple classifier architectures. Perturbation-based experiments show that high-sensitivity iFIM components are more strongly coupled to changes in predictive confidence and classification performance than lower-sensitivity complementary components. The results support the iFIM framework as a principled tool for analyzing local decision sensitivity and for complementing existing attribution-based interpretability methods in medical imaging.

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

Continual Self-Improvement with Lightweight Experiential Latent Memories

arXiv:2606.17803v1 Announce Type: new Abstract: Large language models achieve strong reasoning performance by scaling inference-time compute, yet remain fundamentally stateless, discarding the rich, self-produced reasoning traces generated during this process. We investigate whether models can instead learn online from this experience, converting transient computation (reasoning traces) into persistent reusable knowledge, and without external supervision or access to future data. We show that In-Context Learning (ICL) over raw reasoning traces fails to generalize, reflecting a fundamental limitation of token-level reuse: individual traces lack the abstraction needed for transfer, even after refinement (e.g. self-reflection). In contrast, drawing inspiration from recent works on unsupervised reinforcement learning, we find that lightweight per-instance training with self-generated test-time signals (majority voting) as rewards yields substantial gains, often surpassing full-dataset offline training, motivating a shift from raw traces to learned latent representations. Building on this insight, we propose an online method that distills inference-time compute spent on encountered problems into compact modular latent memories capturing the underlying reasoning structure. These memories are stored and retrieved for future inputs, enabling continual improvement while avoiding catastrophic forgetting through modular design. Importantly, our method is highly efficient, parametrized as extremely lightweight soft prompt memories (~0.001% of model parameters) and trained with only a few gradient steps, yet achieving performance competitive with full parametric updates and offline training. Across challenging mathematical reasoning benchmarks, our approach significantly outperforms zero-shot and raw data ICL baselines, while transferring effectively across datasets.

04.
arXiv (CS.LG) 2026-06-19

Beyond Averaging in John Ellipsoid Approximation: High-Accuracy Algorithms in the Leverage-Score Model

arXiv:2606.20082v1 Announce Type: cross Abstract: The John ellipsoid of a symmetric polytope $P=\{\mathbf{x}\in\mathbb{R}^d:\|\mathbf{A}\mathbf{x}\|_\infty\le1\}$, $\mathbf{A}\in\mathbb{R}^{n\times d}$, is computed by a long line of leverage-score algorithms, from Cohen, Cousins, Lee and Yang (COLT 2019) to its successors [WY24, CLS+25], all reaching a $(1+\varepsilon)$-approximation in $\Theta(\varepsilon^{-1}\log(n/d))$ iterations. We separate this complexity into three costs the modern line conflates (certification, identification, and accuracy) and locate the historical $\varepsilon^{-1}$ in the first alone. In the equivalent D-optimal-design form $\min_{\mathbf{p}\in\Delta_n}-\log\det(\sum_i p_i\mathbf{a}_i\mathbf{a}_i^\top)$, the leverage-score oracle is exactly the first-order oracle and the $(1+\varepsilon)$-John guarantee the Frank-Wolfe gap $g(\mathbf{p})\le\varepsilon d$; through this dictionary the costs come apart. The $\varepsilon^{-1}$ is a certification artifact: the uniform average of the iterates, the certificate used throughout the line, has gap exactly $\Theta(1/T)$, however cheap each iteration is made. Pointed instead at the last iterate the same oracle is fast: a warm-started accelerated method reaches the guarantee in $C(\mathbf{A})+O(\sqrt{\kappa}\log(1/\varepsilon))$ queries after an $\varepsilon$-independent setup $C(\mathbf{A})$, and once the optimal face is identified the facial problem is an unconstrained self-concordant minimization whose Hessian the oracle recovers exactly, so damped Newton needs only $O(\log\log(1/\varepsilon))$ steps, for a total of $C(\mathbf{A})+O(d^2\log\log(1/\varepsilon))$ queries. The accuracy dependence is thus doubly logarithmic after an $\varepsilon$-independent, condition-dependent setup; the open problem is the remaining identification cost (a condition-free bound on reaching the optimal face) and lower bounds. Accuracy is not the obstruction.

05.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

Authors:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

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

S4oP: Operator-level Pruning of Structured State Space Models for Resource-Constrained Devices

arXiv:2606.18096v1 Announce Type: cross Abstract: Structured State Space Models (SSMs), including the S4 and S4D architectures, have recently emerged as powerful alternatives to attention-based models for capturing long-range dependencies in sequential data. Despite their strong empirical performance, deploying these models in time- and resource-constrained settings remains challenging due to their computational and memory demands. In this paper, we propose a novel incremental, operator-level pruning approach for S4- and S4D-based models that significantly reduces inference cost while preserving predictive performance. To the best of our knowledge, this is the first work to systematically investigate structured operator pruning for SSMs. Our method progressively prunes model operators by interleaving structured masking with fine-tuning, while jointly monitoring accuracy and inference latency. We implement this approach within a unified training and evaluation framework that enables systematic exploration of efficiency-accuracy trade-offs. Experiments across multiple benchmark datasets show that pruning up to 70% of the model operators preserves the performance of the original models in most cases, while substantially reducing inference latency. These results demonstrate that structured operator pruning is an effective and previously unexplored strategy for improving the efficiency of SSMs and facilitate their deployment in practical, resource-constrained scenarios.

07.
bioRxiv (Bioinfo) 2026-06-12

ProMiSE: Protein Multi-State Evaluation Benchmark in Biological Contexts

Proteins are inherently dynamic, with biological functions often emerging from transitions between multiple conformational states. While recent breakthroughs have largely addressed the static structure prediction problem, no systematic benchmark exists to demonstrate how well current models capture functionally relevant dynamics. We introduce ProMiSE, the first benchmark that provides both a dataset and an evaluation scheme, based on native biological assemblies and integrating major conformational change mechanisms - intrinsic, ligand-induced, and protein-induced - within a single curated dataset. We conducted a comprehensive evaluation of state-of-the-art structure prediction models, including AlphaFold3 and recent generative approaches. Our findings reveal that current models exhibit a limited ability to sample intrinsic multi-states and are often insensitive to biological context in induced scenarios. Internal representation analysis suggests that training-data exposure can shift predictions toward dominant conformational states over alternative biologically relevant states, primarily at the structure module. In contrast, results from BioEmu indicate that reducing decoding-stage bias can substantially improve multi-state sampling without major changes to upstream pair representations.

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

ProductConsistency: Improving Product Identity Preservation in Instruction-Based Image Editing via SFT and RL

Recent advances in instruction-based image editing have enabled models to perform complex visual edits from natural language instructions. However, in product-centric scenarios where preserving product features, branding, and textual elements are critical, current open and closed source models often struggle to maintain this fine-grained object identity. This issue is further compounded by the lack of datasets for instruction-based product image editing with text fidelity constraints, leaving it largely treated as an implicit capability of instruction-based image editing models. In this work, we introduce the ProductConsistency dataset which is designed to improve product-centric image editing. Our approach includes a supervised fine-tuning (SFT) dataset of 87k samples for product editing, a reinforcement learning (RL) dataset with 869 unique product images, and a new benchmark dataset, the ProductConsistency Benchmark, to allow rigorous and standardized evaluation of editing models. To guide RL training, we propose a Cyclic Consistency reward that enforces semantic preservation of product identity by using caption similarity between the original product description and captions generated from the edited image. We fine-tune both Qwen-Image-Edit-2511 and Flux.1-Kontext-dev using our dataset and demonstrate consistent improvements over baseline models in OCR and Perceptual metrics, and MLLM-based evaluations as well, indicating stronger product consistency, text rendering, and overall visual quality; with the Qwen-Image-Edit-2511 model achieving a 5x reduction in the character error rate. The code and pipeline is available at https://anonymous.4open.science/r/ProductConsistency-6FCC/README.md

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

Towards One-for-All Anomaly Detection for Tabular Data

arXiv:2603.14407v2 Announce Type: replace Abstract: Tabular anomaly detection (TAD) aims to identify samples that deviate from the majority in tabular data and is critical in many real-world applications. However, existing methods follow a ``one model for one dataset (OFO)'' paradigm, which relies on dataset-specific training and thus incurs high computational cost and yields limited generalization to unseen domains. To address these limitations, we propose OFA-TAD, a generalist one-for-all (OFA) TAD framework that only requires one-time training on multiple source datasets and can generalize to unseen datasets from diverse domains on-the-fly. To realize one-for-all tabular anomaly detection, OFA-TAD extracts neighbor-distance patterns as transferable cues, and introduces multi-view neighbor-distance representations from multiple transformation-induced metric spaces to mitigate the transformation sensitivity of distance profiles. To adaptively combine multi-view distance evidence, a Mixture-of-Experts (MoE) scoring network is employed for view-specific anomaly scoring and entropy-regularized gated fusion, with a multi-strategy anomaly synthesis mechanism to support training under the one-class constraint. Extensive experiments on 34 datasets from 14 domains demonstrate that OFA-TAD achieves superior anomaly detection performance and strong cross-domain generalizability under the strict OFA setting. The source code is available at https://github.com/Shiy-Li/OFA-TAD.

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

SAG: SQL-Retrieval Augmented Generation with Query-Time Dynamic Hyperedges

Retrieval-Augmented Generation (RAG) offers an effective approach for large language models to access external knowledge. However, existing methods rely on dense similarity retrieval and face inherent limitations in handling structured constraints and multi-hop reasoning. Incorporating knowledge graphs partially alleviates these issues, but at the cost of semantic fragmentation, high maintenance overhead, and difficult incremental updates. This paper introduces SAG (SQLRetrieval Augmented Generation), a structured architecture for retrieval and agent systems. Instead of pre-building a global static graph, SAG converts each chunk into one semantically complete event and a set of indexing entities, then uses SQL join queries to dynamically link events that share entities into local hyperedges,constructing, at query time, a dynamically instantiated local index structure. This design avoids the need for global graph rebuilding and ongoing maintenance; the system naturally supports incremental writes, concurrent processing, and continuous scaling through its reliance on standard database infrastructure. Across HotpotQA, 2WikiMultiHop, and MuSiQue, three standard multi-hop benchmarks,SAG achieves the best results on 8 out of 9 Recall@K metrics, reaching 80.0% Recall@5 on MuSiQue, the benchmark with the highest multi-hop reasoning demands.SAG has also been deployed at a production scale of hundreds of millions of data items, with online retrieval latency kept within seconds. Project site and code are available at https://github.com/Zleap-AI/SAG-Benchmark.

11.
arXiv (quant-ph) 2026-06-16

Quantum Nonlocal Games on Graph Ensembles

arXiv:2606.16784v1 Announce Type: new Abstract: Quantum entanglement is one of the most striking discoveries in all of science. This effect allows, for instance, two spatially separated agents to coordinate their actions, without communication, to an extent that is both counter-intuitive, and provably impossible by any other physical means. A recently discovered example is that of mobile agents (players) performing spatial coordination tasks such as rendezvous, where the agents aim to meet on a network without communication. Until now, demonstrations of this advantage have relied on highly idealized conditions: agents are assumed to have complete knowledge of the topography, and experiments have been restricted to simulations using data generated by qubits within a single quantum processor. Here we address both limitations by developing a theory for graph ensembles that capture topographical uncertainty and by experimentally demonstrating the advantage in rendezvous scenarios between physically separated ion-trap systems with access to remote entanglement. Moreover, we simulate a broader set of problems on superconducting hardware. Surprisingly, when players are given the ability to gather more local information the quantum advantage increases – a feat impossible by classical means. Our findings establish a concrete route toward practical quantum advantages in motion coordination problems. More broadly, they point to a new way of using portable quantum devices to enhance collective decision-making in uncertain environments.

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

Beyond Case Law: Evaluating Structure-Aware Retrieval and Safety in Statute-Centric Legal QA

arXiv:2604.06173v2 Announce Type: replace-cross Abstract: Legal QA benchmarks have predominantly focused on case law, overlooking the unique challenges of statute-centric regulatory reasoning. In statutory domains, relevant evidence is distributed across hierarchically linked documents, creating a statutory retrieval gap where conventional retrievers fail and models often hallucinate under incomplete context. We introduce SearchFireSafety, a structure- and safety-aware benchmark for statute-centric legal QA. Instantiated on fire-safety regulations as a representative case, the benchmark evaluates whether models can retrieve hierarchically fragmented evidence and safely abstain when statutory context is insufficient. SearchFireSafety adopts a dual-source evaluation framework combining real-world questions that require citation-aware retrieval and synthetic partial-context scenarios that stress-test hallucination and refusal behavior. Experiments across multiple large language models show that graph-guided retrieval substantially improves performance, but also reveal a critical safety trade-off: domain-adapted models are more likely to hallucinate when key statutory evidence is missing. Our findings highlight the need for benchmarks that jointly evaluate hierarchical retrieval and model safety in statute-centric regulatory settings.

13.
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.

14.
arXiv (CS.CL) 2026-06-16

DRA-GRPO: Your GRPO Needs to Know Diverse Reasoning Paths for Mathematical Reasoning

Post-training LLMs with Reinforcement Learning, specifically Group Relative Policy Optimization (GRPO), has emerged as a paradigm for enhancing mathematical reasoning. However, standard GRPO relies on scalar correctness rewards that are often non-injective with respect to semantic content: distinct reasoning paths receive identical rewards. This leads to a Diversity-Quality Inconsistency, where the policy collapses into a narrow set of dominant modes while ignoring equally valid but structurally novel strategies. To bridge this gap, we propose Diversity-aware Reward Adjustment (DRA), a theoretically grounded framework that calibrates the reward signal using the semantic density of sampled groups. By leveraging Submodular Mutual Information (SMI), DRA implements an Inverse Propensity Scoring (IPS) mechanism that effectively de-biases the gradient estimation. This creates a repulsive force against redundancy, driving the policy to achieve better coverage of the high-reward landscape. Our method is plug-and-play and integrates seamlessly with GRPO variants. Empirical evaluations on five math benchmarks demonstrate that DRA-GRPO consistently outperforms strong baselines, achieving an average accuracy of 58.2% on DeepSeek-R1-Distill-Qwen-1.5B with only 7,000 training samples and $55 cost, highlighting the critical role of diversity calibration in data-efficient alignment. The code is available at https://github.com/xiwenc1/DRA-GRPO.

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

Consensus-based Agentic Large Language Model Framework for Harmonized Tariff Schedule Code Classification

arXiv:2606.16987v1 Announce Type: new Abstract: Accurate Harmonized Tariff Schedule (HTS) code classification is essential for customs clearance, duty assessment, trade statistics, and regulatory compliance in maritime logistics. However, exact HTS classification remains challenging because product descriptions are often short, incomplete, or ambiguous, while correct classification depends on hierarchical tariff structures, legal notes, and jurisdiction-specific rules. This paper proposes an agentic large language model (LLM) framework for Canadian 10-digit HTS code classification in smart-port and maritime logistics environments. The framework integrates multi-agent information retrieval, semantic retrieval over official tariff documents, evidence-grounded reasoning, consensus-based validation, element-wise voting across hierarchical code components, confidence estimation, and human-in-the-loop escalation. We evaluate the framework on a private dataset of 3,300 domain-expert-labeled product records collected from logistics and delivery contexts. Experimental results show that exact 10-digit classification remains difficult even for advanced LLMs, with performance decreasing from coarse chapter-level prediction to fine-grained tariff and statistical suffix assignment. These findings demonstrate the need for evidence-grounded, uncertainty-aware, and human-centered classification workflows rather than fully autonomous single-step prediction. The proposed framework supports more interpretable, accountable, and compliance-oriented HTS classification for maritime logistics and smart-port operations. Our code is available at https://github.com/Analytics-Everywhere-Lab/hts.

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

Bridging Spatial And Frequency Views For Disaster Assessment: Benefits And Limitations

Rapid assessment of building damage from satellite imagery is essential for effective disaster response and recovery. While most deep learning methods rely on spatial-domain features, frequency-domain representations can capture complementary structural cues such as debris patterns and collapse-induced textures. This study presents a controlled comparison of spatial-domain, frequency-domain, and dual-domain deep learning approaches for multi-class building damage classification using post-disaster imagery from the xView2 (xBD) dataset. To ensure fairness, all models are built on an EfficientNet-B0 backbone and trained under identical settings, differing only in their input representations and fusion strategies. Performance is evaluated using accuracy, macro F1-score, per-class metrics, and confusion matrices. Results show that dual-domain models provide measurable improvements over single-domain approaches. The dual spatial configuration achieves the highest test accuracy (0.4688) and lowest loss, while the spatial-only model attains the best macro F1-score (0.4254), indicating more balanced class performance. In contrast, frequency-only models perform worst and exhibit overfitting, suggesting limited generalization. Despite these gains, all models struggle to detect subtle damage levels, particularly the Minor class, due to class imbalance and fine-grained visual ambiguity. While dual-domain approaches improve detection of severe damage, challenges remain. These findings highlight the benefits and limitations of hybrid representations and motivate future work on data balancing, advanced fusion, and regularization.

17.
bioRxiv (Bioinfo) 2026-06-16

Super Learner Ensemble Modeling of CPTAC Proteomic Data for Survival Prediction in Head and Neck Squamous Cell Carcinoma

Survival analysis in head and neck squamous cell carcinoma (HNSCC) is traditionally performed using Cox proportional hazards models, alongside some exploration into black-box machine learning methods. The Super Learner (SL) algorithm addresses this model selection dilemma by combining diverse candidate algorithms into a weighted ensemble to perform comparably to the best candidate method. This study evaluates the performance of SL in HNSCC. Proteomic features as well as clinical covariates from 96 CPTAC HNSCC samples were modeled with three candidate algorithms (Cox LASSO, Cox Ridge, and Random Survival Forest) as well as the ensemble SL method. Models were optimized via Uno's time-dependent Concordance Index (C-index) and tested at 1- and 3-year time horizons using 2000 bootstrap resamples. The Cox Ridge regression model achieved the highest predictive accuracy among the four total methods. However, the SL demonstrated stable performance over both time horizons (1-year C-index: 0.985; 3-year C-index: 0.960). Variable importance analysis of the Cox Ridge model successfully identified malignant proteins (ATR, MAML1, MIEN1) alongside novel potential prognostic indicators (ZNF800, KERA). This analysis emphasizes the statistical necessity for larger cohorts for ensemble learning, while providing a benchmark of proteomic indicators in HNSCC.

18.
Nature (Science) 2026-06-17

Molecular basis of polyadenylated RNA fate determination in the nucleus

Authors:

Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs1,2, which are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, including protein-coding RNPs, are exported to the cytoplasm, whereas transcripts within non-functional pA+ RNPs are degraded in the nucleus1–4. How cells distinguish these opposing fates remains unknown. The DExD-box ATPase UAP56 (also known as DDX39B) is a central component of functional pA+ RNPs, and promotes their docking to the nuclear pore complex-anchored TREX-25,6, which triggers transcript release from UAP56 to facilitate export7. Here we reveal that the poly(A) tail exosome targeting (PAXT) connection8 binds a TREX-2-like module, which releases pA+ RNAs from UAP56 for decay by the nuclear exosome. The core of this module consists of a LENG8–PCID2–SEM1 trimer, which we show is structurally and biochemically equivalent to the central GANP–PCID2–SEM1 trimer of TREX-2. Mutagenesis and transcriptomic data demonstrate that the nuclear fate of pA+ RNPs is governed by the contending actions of nucleoplasmic PAXT and nuclear pore complex-associated TREX-2, which interpret RNA-bound UAP56 as a signal for RNA decay or export, respectively. As RNA targets of PAXT are generally short and intron-poor, we propose an overall model for pA+ RNP fate determination whereby the distinct sub-nuclear localizations of PAXT and TREX-2 govern the degradation of short non-functional pA+ RNAs while allowing export of their longer and functional counterparts. Biochemical, structural and cell biological analyses reveal that UAP56 (DDX39B) assembles with a TREX-2–like module that redirects non-functional polyadenylated RNAs from export to degradation.

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

Displacement Is Not Direction: Evaluating Fidelity Metrics for Quantized LLM Deployment

Fidelity metrics, such as per-token KL divergence (KLD) against a high-precision reference, are often used in practice as low-cost proxies for benchmark quality. We test this practice on a 28-quant cohort of Qwen3.6-35B-A3B and a 41-quant cohort of Devstral-Small-2-24B, evaluated across a suite of downstream benchmarks. We find that KLD is strongly correlated with benchmark score over the full cohort ($\rho=-0.72$ on Qwen and $\rho=-0.86$ on Devstral, both with $p

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

Metacognitive Myopia in Large Language Models

Large Language Models (LLMs) exhibit potentially harmful biases that reinforce culturally embedded stereotypes, influence moral judgments, or amplify positive evaluations of majority groups. We propose metacognitive myopia as a cognitive-ecological framework accounting for a conglomerate of established and emerging LLM biases. Our theoretical framework posits that biased samples in the information environment cause five symptoms of metacognitive myopia in LLMs: integration of invalid embeddings, susceptibility to redundant information, neglect of base rates in conditional computation, decision rules based on frequency, and inappropriate higher-order statistical inference for nested data structures. Moreover, it posits that the two main components of metacognition, monitoring and control, could account for these five symptoms. Accordingly, we further outline how monitoring and control could be approximated technically, for instance, through hidden parallel reasoning histories that allow interactive LLMs to evaluate risks of myopic inference before generating overt responses. Our theoretical framework provides a novel perspective on flawed human-machine interactions and agentic AI and raises significant ethical concerns regarding the implementation of LLMs in organizational structures and high-stakes decisions.

21.
arXiv (quant-ph) 2026-06-16

Linear algebra at exponential scale via tensor network dimension reduction

arXiv:2606.15350v1 Announce Type: cross Abstract: Many problems in modern scientific computing are challenging because of a curse of dimension, where their mathematical formulation involves objects whose dimension is exponential in the nominal "size" of the problem. Tensor networks can provide a compact representation for exponentially large vectors and matrices that arise in applications, but these representations do not always lead to reliable algorithms. This paper develops and analyzes techniques for randomized dimension reduction of tensor network data. These techniques support a suite of efficient algorithms for provably solving exponential-scale linear algebra problems, including trace estimation and eigenvalue approximation. The paper includes several stylized illustrations from quantum many-body physics with ambient dimension up to $2^{200}$.

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

SHIFT: Semantic Harmonization via Index-side Feature Transformation for Multilingual Information Retrieval

arXiv:2606.18801v1 Announce Type: cross Abstract: With the rapid expansion of massive multilingual corpora, Multilingual Information Retrieval (MLIR) has emerged as a critical technology for global information access. MLIR enables users to retrieve semantically relevant documents from multilingual text collections using a single-language query. However, recent multilingual dense retrieval models often exhibit a strong preference for documents in the same language as the query. This leads to severe language bias, where top-ranked results are dominated by documents of specific languages, even when documents in other languages contain more semantically relevant information. To address this issue, we propose SHIFT, a training-free method applicable in the indexing stage. Specifically, SHIFT utilizes parallel translation pairs to estimate a relative language vector for each target language with respect to a source language. Subsequently, SHIFT corrects the language-specific offset by subtracting this relative language vector from document embeddings during indexing. Our comprehensive evaluation across four MLIR benchmarks and diverse dense retrieval models confirms that SHIFT can effectively mitigate language bias and enhance MLIR performance.

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

Range-Aware Bayesian Optimization for Discovering Diverse Designs within Target Property Windows

arXiv:2606.11574v1 Announce Type: new Abstract: In many materials and product design problems, desirable candidates exhibit properties that fall within an acceptable range rather than achieve a single optimum. Recovering multiple, distinct solutions that satisfy such specifications is also practically valuable, as some candidates may be preferred for reasons of cost, processability, or robustness that are difficult to encode directly in an objective function. Here, we develop a range-aware Bayesian optimization (BO) framework in which the acquisition function directly scores the posterior probability that a candidate satisfies a target range. The framework naturally extends to parallel pursuit of multiple distinct specifications over a shared candidate space. Across benchmark tasks, range-aware acquisition consistently recovers larger and more diverse sets of valid designs than standard BO baselines and recent goal-seeking methods. Its utility is further demonstrated in two practically motivated design case studies involving optimizing reaction conditions for polymer synthesis and sequence-defined oligomer discovery for prescribed optical absorption bands, supported by quantum chemical calculations. These results suggest that range-aware BO can provide a practical and sample-efficient foundation for specification-driven design, particularly when design flexibility and solution diversity are important considerations.

24.
arXiv (CS.CV) 2026-06-15

PhysVLA: Towards Physically-Grounded VLA for Embodied Robotic Manipulation

Vision-Language-Action (VLA) models excel at mapping visual inputs and natural language instructions directly to robotic control policies. However, because they are trained primarily to fit behavioural demonstration data, they do not explicitly enforce fundamental physical principles such as rigid-body dynamics or contact constraints. This exposes a critical physics gap: standard temporal smoothing applied on top of single-step or chunked VLAs trades trajectory quality for added failures that short-term memory cannot resolve. To bridge this gap, we introduce PhysVLA (Physics-VLA), a plug-and-play, inference-time framework designed to wrap any frozen VLA backbone without retraining, fine-tuning, or weight access, with less than 1 ms of overhead per control step. PhysVLA intercepts the predicted control action, captures only the simulator or system state, and applies a dual-layered correction: (i) a phase-aware finite-state machine that structures discrete task segments (approach, grasp, transport, and place), and (ii) a selective Euler-Lagrange gate that activates only when a dynamics oracle detects kinodynamic inconsistency. Evaluated across OpenVLA, OpenVLA-OFT, Force-VLA, and Generalist-VLA on LIBERO-Spatial with a 7-DoF Franka Panda, the framework delivers absolute success rate increases of up to 17% and stability increases of up to 19% with no per-task regressions, improves trajectory efficiency by up to 15% across all four backbones, and shows up to a 10x improvement in trajectory jerk robustness on a Robosuite Lift cross-simulator sweep. We further validate the framework on a real Agilex Piper arm with a pick-and-place task, confirming that PhysVLA transfers to physical hardware without retraining, with success-rate improvements of up to 50%, establishing physical awareness as a composable, backbone-agnostic runtime module.

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arXiv (CS.AI) 2026-06-16

Looking Is Not Picking: An Attention-Segment Account of Tool-Selection Failures in LLM Agents

Authors:

arXiv:2606.16364v1 Announce Type: new Abstract: LLM agents mis-call tools, and the natural guess is that the model failed to see the right tool in a crowded harness. We show the opposite through a lens concurrent work sets aside – the model's attention to labeled tool-definition segments. On real BFCL failures, by per-candidate attention argmax the model attends most to the correct tool 80% of the time (vs. 21% chance), and the gold is the under-attended segment on only 10%: it looks at the right tool and still picks wrong. This directly refutes the intuitive "crowded-harness / lost-in-the-middle" explanation: the failure is at the decision readout, not the harness, and we pin it there three ways. (1) Input vs. readout: repairing the prompt (reordering or duplicating the gold tool) recovers