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

Progressive Knowledge-Guided Large Language Model Framework for Bearing Fault Diagnosis

Vibration-based bearing fault diagnosis requires resolving three interrelated measurement challenges, including the trade-off between global statistical feature efficiency and local transient signal fidelity, insufficient traceability of measurement features to underlying fault physics, and ineffective multi-source measurement information fusion across diagnostic scales. This paper presents a progressive physics-guided multi-scale vibration signal processing framework that addresses all three challenges within a unified diagnostic pipeline. An 81-dimensional measurement descriptor, derived from bearing kinematic theory and characteristic defect frequencies, establishes a physically traceable feature space enabling real-time fault screening at approximately 20 ms per sample. A fault-adaptive signal segmentation mechanism then directs analytical attention toward fault-relevant waveform regions guided by physics-based priors, without manual feature engineering. Structured fault mechanism knowledge is further encoded implicitly in model parameters during training, enabling autonomous multi-scale measurement fusion without external knowledge dependencies at inference. Validated on four public benchmark datasets under diverse operating conditions, the framework achieves 98.49% diagnostic accuracy with a 12.6-fold reduction in computational cost relative to signal-level baselines. Interpretability analysis confirms that diagnostic feature activations align with established bearing fault mechanics, supporting measurement traceability in safety-critical industrial systems.

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

CoIRL-AD: Collaborative-Competitive Imitation-Reinforcement Learning in Latent World Models for Autonomous Driving

End-to-end autonomous driving models trained with imitation learning (IL) often generalize poorly, particularly in long-tail scenarios where expert demonstrations are sparse. Reinforcement learning (RL) can provide complementary task-level supervision, but applying RL to real-world autonomous driving is challenging in offline settings without interactive simulators, where datasets are dominated by expert actions and provide limited behavioral diversity. We propose CoIRL-AD, a competitive dual-policy framework that integrates IL and RL under a unified offline training regime. CoIRL-AD decouples imitation and reward optimization into separate actors to alleviate objective conflicts, uses imagined future rollouts for long-horizon reward estimation, and introduces a competition mechanism that selectively transfers beneficial behaviors while keeping RL anchored to expert-like driving. Experiments on the nuScenes benchmark show that CoIRL-AD consistently improves robustness over strong IL-based baselines, with especially large gains in cross-city generalization and long-tail scenarios. Code is available at: https://github.com/SEU-zxj/CoIRL-AD.

03.
arXiv (CS.CL) 2026-06-12

HyPE: Category-Aware Hypergraph Encoding with Persistent Edge Embeddings for Persona-Grounded Dialogue

Persona-grounded dialogue systems aim to produce responses consistent with a speaker's persona, yet existing methods treat personas as a flat set of sentences and fail to model the high-order relations among persona attributes-e.g., that several persona sentences share a topical category. We propose HyPE (Hypergraph Persona Encoder), a framework that (i) analyzes each persona-bearing text as a (Core, Expression, Sentiment, Category) quadruple, and (ii) organizes persona elements into a hypergraph whose hyperedges are induced by shared category labels. An HyperGCN hypergraph neural network propagates this structure into a persona summary vector and a soft-memory bank that condition the response generator. We further propose Persistent Edge Embeddings (PEE), lightweight per-category learnable priors fused into the HyperGCN message-passing step. On PersonaChat under greedy decoding, HyPE consistently outperforms sentence-level pooling baselines across GPT-2, LLaMA-3.2-3B, and Qwen2.5-3B backbones by demonstrating that structured hyperedge-level persona encoding provides a transferable advantage across model scales.

04.
arXiv (CS.CV) 2026-06-16

Region-Adaptive Sampling for Diffusion Transformers

Diffusion models (DMs) have become the leading choice for generative tasks across diverse domains. However, their reliance on multiple sequential forward passes significantly limits real-time performance. Previous acceleration methods have primarily focused on reducing the number of sampling steps or reusing intermediate results, failing to leverage variations across spatial regions within the image due to the constraints of convolutional U-Net structures. By harnessing the flexibility of Diffusion Transformers (DiTs) in handling variable number of tokens, we introduce RAS, a novel, training-free sampling strategy that dynamically assigns different sampling ratios to regions within an image based on the focus of the DiT model. Our key observation is that during each sampling step, the model concentrates on semantically meaningful regions, and these areas of focus exhibit strong continuity across consecutive steps. Leveraging this insight, RAS updates only the regions currently in focus, while other regions are updated using cached noise from the previous step. The model's focus is determined based on the output from the preceding step, capitalizing on the temporal consistency we observed. We evaluate RAS on Stable Diffusion 3 and Lumina-Next-T2I, achieving speedups up to 2.36x and 2.51x, respectively, with minimal degradation in generation quality. Additionally, a user study reveals that RAS delivers comparable qualities under human evaluation while achieving a 1.6x speedup. Our approach makes a significant step towards more efficient diffusion transformers, enhancing their potential for real-time applications.

05.
arXiv (CS.CL) 2026-06-24

Poster: Exploring the Limits of Audio-Based Detection of Turkish Phone Call Scams

Scam phone calls exploit vulnerable communities worldwide, yet research on detection has focused almost exclusively on English and other high-resource languages. In low-resource settings such as Turkish, detection is especially difficult, as annotated data is scarce and technological defenses remain limited. This research investigates how large language models (LLMs) can support scam detection in Turkish by introducing the first public multi-modal dataset of 100 aligned audio-transcript pairs of scam and benign conversations. We evaluate seven LLMs spanning three model families: Gemini 2.5 (Flash, Flash-Lite, Pro), GPT-4o, and Qwen (Max, Plus, Turbo), under three input conditions: raw audio, automatic speech-to-text transcripts, and transcripts refined by a native speaker. Our results suggest that transcript-based inputs consistently outperform direct audio processing, while human-corrected and uncorrected transcripts perform comparably. By centering a low-resource language and real world threat, this work highlights the urgent need for culturally and linguistically inclusive AI safety research and more robust multi-modal systems for fraud prevention.

06.
Nature (Science) 2026-06-09

Don’t compete, collaborate: why collective funding applications are the future

Authors:

Scientists with disparate expertise writing grants together can identify knowledge gaps and drive progress — but systems must change to incentivize them. Scientists with disparate expertise writing grants together can identify knowledge gaps and drive progress — but systems must change to incentivize them.

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

From Overload to Convergence: Supporting Multi-Issue Human-AI Negotiation with Bayesian Visualization

arXiv:2603.22766v2 Announce Type: replace-cross Abstract: As AI systems increasingly mediate negotiations, understanding how the number of negotiated issues impacts human performance is crucial for maintaining human agency. We designed a human-AI negotiation case study in a realistic property rental scenario, varying the number of negotiated issues; empirical findings show that without support, performance stays stable up to three issues but declines as additional issues increase cognitive load. To address this, we introduce a novel uncertainty-based visualization driven by Bayesian estimation of agreement probability. It shows how the space of mutually acceptable agreements narrows as negotiation progresses, helping users identify promising options. In a within-subjects experiment (N=32), it improved human outcomes and efficiency, preserved human control, and avoided redistributing value. Our findings surface practical limits on the complexity people can manage in human-AI negotiation, advance theory on human performance in complex negotiations, and offer validated design guidance for interactive systems.

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

Model Graph Inductive Learning for Knowledge Graph Completion

arXiv:2606.16509v1 Announce Type: new Abstract: Link prediction in knowledge graphs fundamentally depends on the quality of learned embeddings for entities and relations. However, most existing methods derive these embeddings by aggregating only the local neighborhood of each entity, neglecting the global structure of the knowledge graph. This limited view prevents models from capturing higher-level structural patterns that are essential for accurate and generalizable link prediction. To address these limitations, we introduce Model Graph Inductive Learning (MGIL), a framework that constructs a model graph by clustering entities based on the similarity of their incoming and outgoing relational structures or their entity types. A GNN is then applied to this model graph to produce embeddings that capture the global view of the knowledge graph. These embeddings subsequently serve as high-quality initial features %embeddings for the original knowledge graph, replacing random initialization and leading to more stable and expressive representations. Extensive experiments on standard and recently proposed inductive benchmarks demonstrate that MGIL achieves state-of-the-art or highly competitive performance in inductive link prediction, highlighting its effectiveness across diverse graph settings.

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

Robust Regularized Policy Iteration under Transition Uncertainty

arXiv:2603.09344v3 Announce Type: replace Abstract: Offline reinforcement learning (RL) enables data-efficient and safe policy learning without online exploration, but its performance often degrades under distribution shift. The learned policy may visit out-of-distribution state-action pairs where value estimates and learned dynamics are unreliable. To address policy-induced extrapolation and transition uncertainty in a unified framework, we formulate offline RL as robust policy optimization, treating the transition kernel as a decision variable within an uncertainty set and optimizing the policy against the worst-case dynamics. We propose Robust Regularized Policy Iteration (RRPI), which replaces the intractable max-min bilevel objective with a tractable KL-regularized surrogate and derives an efficient policy iteration procedure based on a robust regularized Bellman operator. We provide theoretical guarantees by showing that the proposed operator is a $\gamma$-contraction and that iteratively updating the surrogate yields monotonic improvement of the original robust objective with convergence. Experiments on D4RL benchmarks demonstrate that RRPI achieves strong average performance, outperforming recent baselines including percentile-based methods on the majority of environments while remaining competitive on the rest. Moreover, RRPI exhibits robust performance by aligning lower $Q$-values with high epistemic uncertainty, which prevents the policy from executing unreliable out-of-distribution actions.

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

A Systematic Evaluation of Large Language Models for PTSD Severity Estimation: The Role of Contextual Knowledge and Modeling Strategies

Large language models (LLMs) are increasingly being used in a zero-shot (generative) fashion to assess mental health conditions, yet we have limited knowledge on what factors affect their accuracy. In this study, we use a clinical dataset of natural language narratives and self-reported PTSD severity scores from 1,437 individuals to comprehensively evaluate the performance of 11 state-of-the-art LLMs. To understand the factors affecting model's assessment accuracy, we systematically varied (i) contextual knowledge prompted to the models like subscale definitions, distribution summary, and interview questions, and (ii) modeling strategies including zero-shot vs few shot, amount of reasoning effort, model sizes, structured subscales vs direct scalar prediction, output rescaling and nine ensemble methods. Our findings indicate that (a) LLMs are most accurate when provided with detailed construct definitions and context of the narrative, even exceeding human raters agreement with self-reported scores; (b) increased reasoning effort leads to better estimation accuracy; (c) performance of open-weight models (Llama, DeepSeek) plateaus beyond 70B parameters while closed-weight (gpt-o3-mini, gpt-5) alternatives improve with newer generations; and (d) best performance is achieved when ensembling a supervised model with the zero-shot LLMs. Beyond agreement with self-reports, LLMs' estimates discriminated PTSD severity from depression, anxiety, and alcohol use, and prospectively predicted future mental healthcare expenditure. Together, these results suggest that contextual knowledge and modeling strategies meaningfully affect accuracy and clinical utility of LLM-based assessments of PTSD severity.

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

TEDD: Robust Detection of Unstable Temporal Features

arXiv:2606.12643v1 Announce Type: new Abstract: When working with real-world temporal data, it is common to encounter features whose distribution is changing over time. The naive employment of Machine Learning models on this unstable data might lead to rapidly degrading performance, especially if the new distribution is much different from what was previously seen during training. In order to cope with this problem, it is critical to automatically identify features that are changing over time. With these features detected, data scientists and other practitioners will be able to mitigate the issue (for instance, by applying data transformations), deploying more robust models that retain high performance for longer periods of time. In this paper, we describe which temporal changes a feature should not suffer from, and propose TEDD, a technique to a) identify when a dataset might lead to an unstable Machine Learning model and b) automatically detect which features cause such lack of robustness. In order to achieve it, we leverage a regression model to highlight which features contribute to a good prediction of an instance's timestamp. We compare our approach to other methods in real and synthetic data, testing their detection capability on all simple change patterns. We show that our method: detects all types of basic changes, both for numerical and categorical features; can detect multivariate drifts; returns a comparable value measuring the amount of change of each feature; requires no parameter tuning; and is scalable both on number of features and instances of the dataset.

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

AsFT: Anchoring Safety During LLM Fine-Tuning Within Narrow Safety Basin

arXiv:2506.08473v4 Announce Type: replace Abstract: Fine-tuning large language models (LLMs) improves performance but introduces critical safety vulnerabilities: even minimal harmful data can severely compromise safety measures. We observe that perturbations orthogonal to the alignment direction - defined by weight differences between aligned (safe) and unaligned models - rapidly compromise model safety. In contrast, updates along the alignment direction largely preserve it, revealing the parameter space as a "narrow safety basin". To address this, we propose AsFT (Anchoring Safety in Fine-Tuning) to maintain safety by explicitly constraining update directions during fine-tuning. By penalizing updates orthogonal to the alignment direction, AsFT effectively constrains the model within the "narrow safety basin," thus preserving its inherent safety. Extensive experiments on multiple datasets and models show that AsFT reduces harmful behaviors by up to 7.60%, improves task performance by 3.44%, and consistently outperforms existing methods across multiple tasks.

13.
medRxiv (Medicine) 2026-06-22

Evidence-guided AI regularization for suicidal ideation prediction in pediatric bipolar disorder

Background: Suicide prediction models in psychiatry often rely on purely data-driven feature selection, which can produce unstable and clinically opaque predictor sets in modest-sized samples. We developed Evidence-Based AI LASSO (EBAL), an evidence-guided regularization framework that incorporates curated clinical evidence into feature-specific penalty factors for interpretable prediction. Methods: Baseline data from 136 youth with confirmed bipolar spectrum disorder in the Greater Houston Area Bipolar Registry were analyzed using 20 candidate clinical predictors. Forty higher-level evidence documents on suicidality and related predictor domains were curated through a structured evidence synthesis workflow and indexed as an auditable evidence corpus. An open-weight large language model assigned feature-specific penalty factors using a prespecified scoring rubric, and these penalties were used to fit a weighted LASSO model. EBAL was compared with a standard evidence-agnostic LASSO using nested leave-one-out cross-validation. Results: For suicidal ideation, EBAL achieved an AUROC of 0.768, balanced accuracy of 0.757, sensitivity of 0.758, and specificity of 0.757. The standard LASSO achieved an AUROC of 0.760 and balanced accuracy of 0.715. EBAL improved balanced accuracy (+0.042, p=0.010) and Matthews correlation coefficient (+0.079, p=0.010), while retaining fewer stable predictors than standard LASSO (11/20 vs 18/20). The strongest positive predictors were current depressed mood, duration of mood disorder illness, and comorbid generalized anxiety disorder. For suicidal behavior, both models performed near chance and retained all candidate predictors. Limitations: The study was cross-sectional, single-site, and modest in sample size, with no external validation cohort. Conclusions: EBAL produced a sparser and more clinically coherent model for suicidal ideation in pediatric bipolar disorder, but did not improve prediction of suicidal behavior. These findings support evidence-guided regularization as a transparent strategy for aligning psychiatric prediction models with prior clinical knowledge while preserving interpretability.

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

Truncated Wigner dynamics of biclique quantum spin glasses

Authors:

arXiv:2606.20187v1 Announce Type: cross Abstract: Quantum spin glasses are often considered testbeds for studying quantum optimization algorithms and as such have been the subject of various quantum advantage claims. Here we investigate the near adiabatic dynamics of biclique quantum spin glasses within the (discrete) truncated Wigner approximation (TWA). Benchmarks on small systems show that TWA recovers sample-to-sample fluctuations of the Edwards-Anderson order parameter, over a wide range of annealing times, with increasing fidelity when the system size increases. We extract critical exponents from the Binder cumulant in line with theoretical expectations, reproducing recent quantum experiments. The computational cost of the method is minimal and it can easily be applied to tens of thousands of qubits.

15.
arXiv (CS.LG) 2026-06-25

Two Stages of Folding: Convergent Mechanisms in AI Protein Folding Trunks

arXiv:2602.06020v3 Announce Type: replace Abstract: How do protein structure prediction models fold proteins? We investigate this question through causal interventions on the folding trunks of ESMFold, OpenFold, and Boltz-1. Across all three models, we find a shared two-stage computational structure. In the first stage, early blocks initialize pairwise biochemical signals: features like charge propagate from sequence into pairwise representations through architecture-specific pathways. In the second stage, late blocks develop pairwise spatial features: distance and contact information accumulate in the pairwise representation. We verify these mechanisms causally by showing that steering charge and distance features induces predictable structural changes. Furthermore, these representations are functionally interchangeable: pairwise states can be linearly aligned and substituted across models. Together, these results suggest that folding trunks with different architectures, inputs, and training procedures converge on a shared representational organization for mapping sequence chemistry into spatial geometry.

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

Learning universal approximations for partial differential equations with Physics-Informed Broad Learning System

arXiv:2606.19754v1 Announce Type: new Abstract: Partial differential equations (PDEs) play a central role in modeling complex physical, biological, and engineering systems. While traditional numerical solvers are robust, they often incur prohibitive computational costs due to mesh dependencies, whereas recent Physics-Informed Neural Networks (PINNs) offer a mesh-free alternative but frequently suffer from slow convergence and optimization instability. To bridge this gap, this article proposes the Physics-Informed Broad Learning System (PIBLS), a novel backpropagation-free framework that reformulates PDE solving as a direct least-squares optimization. We improved an algorithm within this framework to handle nonlinear PDEs efficiently and provide a rigorous mathematical proof establishing the universal approximation property of PIBLS for these equations. Experiments on linear and nonlinear PDEs demonstrate that PIBLS is one to three orders of magnitude faster than conventional PINNs while achieving significantly higher solution accuracy. This framework provides a computationally efficient paradigm for scientific machine learning, offering a practical, high-speed alternative for real-time simulation and design optimization tasks.

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

Retrievable Gradients: Continual Post-Training Without Cumulative Weight Drift

Continual post-training enables models to absorb emerging knowledge after deployment, but repeatedly updating shared parameters can accumulate weight drift, potentially causing catastrophic forgetting and degrading general capabilities. Retrieval-augmented generation avoids such parameter drift, yet often lacks the depth of parametric knowledge integration. In this paper, we propose ReGrad (Retrievable Gradients), a new paradigm that treats gradients as retrievable units of knowledge. ReGrad pre-computes document-specific gradients offline, stores them in an indexed Gradient Bank, and retrieves only query-relevant gradients at inference time for temporary weight adaptation. However, raw language-modeling gradients are optimized for token-level document reconstruction rather than for query-driven knowledge use. We therefore introduce a bi-level meta-learning objective that reshapes document-derived gradients into generalizable adaptation signals for downstream tasks. Experiments across general and domain-specific settings show that \textsc{ReGrad} outperforms CPT and RAG baselines, enabling scalable and reversible parametric knowledge injection without accumulating weight drift.

18.
medRxiv (Medicine) 2026-06-16

Physiological Aging of the Respiratory System (PARS): from development to application

Background: Aging has a critical role in lung changes and the outcome of lung disease. Several lung aging equations have been proposed to measure deviation from physiological aging of the respiratory system. In this study, we aimed to develop a single measure of accelerated lung aging and show its application as a measure of lung aging. Method: We used a pre-bronchodilator pulmonary function test (PFT) from NHANES adult participants recruited from 2007 to 2011. We applied Klemera-Dubal Method (KDM) to four PFT measurements, FEV1, FVC, FEF25-75, and PEF, to calculate a measure of lung biological aging. Physiological Aging of the Respiratory System (PARS) was calculated from the residual method vs. chronological age. We tested the construct validity of PARS by measuring its association with risk factors of lung health. The prognostic validity was measured using a survival analysis. Sampling weights were applied to all analyses. Results: In 14,123 adult participants, the mean (SD) of accelerated lung age (PARS) was 0 (8.2) years. Participants with a history of asthma and emphysema had 4- and 10-year higher PARS. Cigarette smoking, lower socioeconomic status, black race, higher serum cadmium, and lower serum selenium and magnesium were associated with higher PARS. During 116 months of follow-up, PARS was associated with a higher mortality (HR = 1.06, 95%CI: 1.05-1.07 per year). Females with higher PARS had a higher risk of death (P for interaction < 0.001). Results were consistent across different subgroups and sensitivity analyses. Conclusion: PARS is a noninvasive lung aging marker and can be applied as a single measure of lung accelerated aging in the adult population. Its strong construct and predictive validity support its future application among different populations with and without lung disease.

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

CoRe: A Continuously Reward-Finetuned LLM Query Rewriter for Multi-Stage Context-Aware Relevance in Web-Scale Video Search

LLM-based query rewriters in production face a tension: the training reward must reflect how the rewrite is consumed by the production ranker, yet the training procedure must be cheap enough to support continuous redeployment as data drifts. We present CoRe (Context Relevance), such a system, redeployed weekly for over five months in a major short-video search engine. Our reward uses the deployed multimodal relevance model as its source and a multiplicative ratio form mirroring the production fusion algebra, closing the simulation-production gap that offline reward proxies leave open. A semi-online Mixed Preference Optimization loop makes this reward affordable at multi-million-instance weekly scale: a DPO-style pairwise objective restricts the gradient pass to a small top-k/bottom-k subset of sampled trajectories, and a phase structure reduces trainer/inference-server parameter syncs from per-step to per-phase. An automated promotion gate over reward-like and stability metrics detected and recovered from a real reward-hacking incident in production. Rewriter output is consumed as parallel relevance signals at recall, rawrank, and finerank without displacing the original signals, bounding rewriter-failure blast radius. Online A/B from two sequential production launches, first deploying the rewriter at finerank, then extending consumption to recall and rawrank, delivers statistically significant reductions in change-query rate on rewrite-impacted queries, with all headline relevance and engagement metrics moving in the expected direction.

20.
arXiv (CS.AI) 2026-06-19

SoftSkill: Behavioral Compression for Contextual Adaptation

arXiv:2606.20333v1 Announce Type: new Abstract: Agent skills are commonly deployed as natural-language Markdown files that encode answer policies, evidence-use habits, and task procedures. These files are readable and portable, but they are consumed indirectly: for each task instance, a frozen language model must translate a long textual artifact into generation-time behavior. This paper asks whether a natural-language skill can instead initialize a compact continuous context object, refined by a trainable soft delta while the base model remains frozen. We propose SoftSkill, a frozen-backbone method that tunes such soft skills with next-token prediction and deploys them as latent behavioral priors at inference time. In our main single-round setting, a length-32 SoftSkill prefix on Qwen3.5-4B improves over no-skill prompting by 8.3 points on SearchQA, 42.1 points on LiveMath, and 1.3 points on DocVQA. Relative to SkillOpt, SoftSkill improves accuracy by 5.2 points on SearchQA and 12.5 points on LiveMath, while replacing hundreds to thousands of Markdown skill tokens with a few virtual tokens. We further study agentic execution as a harder boundary case, where sparse trajectory imitation provides useful signal but does not yet robustly compress long-horizon procedural behavior. More broadly, the results suggest that some task skills are better treated not as additional Markdown to be reinterpreted at inference time, but as compact latent controls over how a frozen model enters the task.

21.
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.

22.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

23.
Nature (Science) 2026-06-24

Epiblast diversification and blood formation in a human pregastrula

Authors:

The incipient stage of gastrulation in human, when the primitive streak is about to emerge, represents a critical yet underexplored period. Here we present the high-resolution spatial transcriptomic landscape of a human embryo at Carnegie stage 6 (approximately 13–14 days post-conception), a stage at which primitive streak remains invisible and gastrulation-derived mesodermal/endodermal progenitors are not yet transcriptomically detected. We identified an anterior visceral endoderm-like hypoblast population, as well as a trifurcated developmental trajectory of the epiblast, progressing towards the amnion, primitive streak and node/prechordal plate/notochord (axial mesoderm) at subsequent developmental stages1–3. Furthermore, our findings challenge the existing paradigms by revealing that primitive haematopoiesis, involving three blood lineages, initiates in human yolk sac before gastrulation, earlier than previously recognized2,4–7, and that the first blood cells arise from the extra-embryonic mesoderm with a hypoblast rather than epiblast origin. Notably, we identified two spatial zones, each consisting of molecularly distinct yolk sac endoderm and extra-embryonic mesoderm populations, that respectively facilitated the generation of erythro-megakaryocytic lineages and myeloid precursors. These findings provide insights into the onset of gastrulation and the earliest blood formation in humans, with profound implications for advancing stem cell-derived human embryo models and in vitro blood regeneration. High-resolution spatial transcriptome analysis of a human embryo at Carnegie stage 6 reveals three distinct developmental trajectories from the epiblast towards amnion, primitive streak and axial mesoderm, and detects the&nbsp;initiation of haematopoiesis before gastrulation, originating from hypoblast rather than epiblast.

24.
arXiv (CS.CL) 2026-06-11

Semantic Grading of Written Answers in Low-Resource Language Bangla Using a Fine-Tuned Lightweight Language Model

Bangla is among the world's most widely spoken languages, yet it remains underserved in educational NLP research. In many remote and rural regions, access to qualified subject teachers is limited, and written answers are consequently graded largely by hand, restricting timely and consistent feedback. Automatic assessment is challenging because semantically correct responses can vary substantially in surface form. We present a bilingual (Bangla-English) evaluation system designed for low-resource educational settings that prioritizes semantic correctness over lexical overlap. Our approach fine-tunes a lightweight language model to grade each response using the question, reference answer, and student answer, producing a numeric score and concise, context-grounded feedback suitable for classroom deployment. We also construct a synthetic bilingual dataset to enable controlled training and evaluation. Across proprietary and open-source LLMs evaluated under a unified protocol, our QLoRA-tuned Qwen3-8B confirms consistent improvement by producing the most leakage-resistant feedback (RoRa = 0.819) in synthetic evaluation and the strongest agreement with human scores (rho = 0.936, MAE = 0.725) in a dedicated human study.

25.
arXiv (CS.CL) 2026-06-15

Optimizing the Cost-Quality Tradeoff of Agentic Theorem Provers in Lean

Large language models (LLMs) are increasingly used in workflows for generating formal proofs in Lean. These workflows often decompose problems into smaller lemmas, sample many proof attempts, and use compiler feedback to guide search. However, they can be prohibitively expensive, often spending substantial compute on attempts that ultimately fail. In this work, we address this problem with an action routing agent that consists of a data plane and a control plane. The data plane generates natural-language lemma decompositions, formalizes them in Lean, and samples proof attempts for the resulting theorem and lemma targets. The control plane observes previous failed Lean attempts, estimates both the likelihood of success and cost of another attempt, and decides whether to continue proving the current target or restart from a new breakdown. On a subset of PutnamBench, our agent decreases the cost by $28.9\%$ over a fixed-step baseline on average, preserving performance while using substantially less compute. These results suggest that failed Lean trajectories provide actionable signals for cost-aware resource allocation in agentic theorem proving.