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01.
arXiv (CS.CL) 2026-06-19

Beyond the GUI Paradigm: Do Mobile Agents Need the Phone Screen?

Recent advances in mobile agents are dominated by the GUI paradigm, in which agents perceive UI information and emit screen interactions. However, mobile platforms also expose a command-line interface (CLI) that provides direct access to device services and data. We argue CLI deserves first-class consideration alongside GUI. We evaluate three coding agents (Claude Code, Terminus-2, mini-swe-agent) across four model APIs on AndroidWorld and MobileWorld without any mobile-specific post-training, comparing against three reproducible GUI baselines (GUI-Owl-1.5-32B, MAI-UI, Qwen3-VL-32B). Claude Code (Opus 4.7) reaches 71.8\% and 51.9\%, outperforming every reproducible GUI baseline (69.3/68.1/57.8\% on AndroidWorld; 43.2/26.3/13.3\% on MobileWorld), while every other CLI configuration remains competitive. To establish the paradigm's ceiling, we provide oracle CLI solutions that reach 88.8\% on AndroidWorld (103/116 tasks CLI-solvable) and 86.3\% on MobileWorld (101/117 tasks CLI-solvable), indicating substantial room for future improvement. To cover everyday user intents beyond the GUI scope, we introduce the CLI-Advantage Task Suite, comprising 45 templates across five categories: bulk operations, multi-condition filtering, aggregation, cross-app workflows, and hidden device state. Every CLI agent outperforms every GUI baseline in all five categories, with substantially fewer steps per task (10.7 vs.\ 18.6). To support future research on mobile CLI agents, we will open-source agent implementations, oracle solutions, the CLI-Advantage suite, and evaluation infrastructure.

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

sebis at CRF Filling 2026: A Two-Stage Local LLM Pipeline for Medical CRF Filling

The extraction of structured clinical information from unstructured EHR notes is a persistent bottleneck in healthcare informatics. While large language models (LLMs) offer high performance, their deployment in clinical settings is hindered by privacy risks, inference costs, and the tendency to hallucinate beyond textual evidence. We address these challenges for the CL4Health 2026 Case Report Form (CRF) filling task by proposing a fully local, domain-adapted pipeline using the MedGemma-27B model. Our two-stage architecture, which separates binary presence classification from value extraction, enforces strict adherence to textual evidence and ensures deterministic outputs for negated, uncertain, or unknown states. By leveraging item-specific, few-shot in-context learning without external API calls or fine-tuning, our approach achieves a macro-F1 score of 0.55 on the official English test track. This result secures second place among all locally-hosted, open-source submissions. Our work demonstrates that privacy-preserving, on-premise LLM pipelines can achieve near-competitive performance with proprietary frontier models, providing a practical, data-sovereign framework for clinical NLP.

03.
arXiv (CS.LG) 2026-06-18

Towards Anomaly Detection on Relational Data

arXiv:2606.18621v1 Announce Type: new Abstract: Relational databases are widely used for managing structured data in real-world systems. Detecting anomalies from such relational data is crucial for identifying fraud, risks, and abnormal behaviors, yet remains under-explored. The key challenges lie in the intrinsic complexity of relational data: multi-table attributes are high-dimensional and heterogeneous, making sparse abnormal clues easy to overwhelm by normal or irrelevant information; and anomalies may further manifest as abnormal connection patterns across different foreign-key relations, which existing tabular and graph anomaly detection methods are ill-suited to capture. To address them, we propose RelAD, a reconstruction-based framework that captures anomalies from both attribute and relational edge reconstruction. RelAD contains two core modules: conditional sparse-gated attribute reconstruction, which suppresses redundant multi-table attributes and emphasizes abnormal semantic blocks, and dual-view multi-relational edge reconstruction, which detects relation-specific abnormal connections from both intrinsic and behavioral entity profiles. The resulting attribute and relational signals are integrated through a lightweight fusion module to produce the final anomaly score. We further construct 6 benchmark datasets with systematic anomalies, on which extensive experiments show that RelAD consistently outperforms other baselines while achieving competitive efficiency.

04.
arXiv (CS.CV) 2026-06-18

Semantic Robustness Certification for Vision-Language Models

Vision-language models (VLMs) are now widely used in downstream tasks. However, real-world applications often expose VLMs to distribution shifts induced by semantic variation (e.g., shape, size, and style). Robustness certification determines if a model's prediction changes when transformations are applied to its input. While most certification frameworks study geometric or pixel-level transformations over inputs, this work proposes a novel framework that enables certifying VLM robustness under semantic-level transformations. Leveraging the open-vocabulary capability of VLMs, we use text prompts as semantic proxies to construct transformations parameterized by an extent that controls the degree of semantic variation. By characterizing the VLM decision boundary in closed form, our framework quantitatively certifies extent intervals for which the predicted class remains unchanged under the semantic transformation. Our framework is the first to certify VLM robustness under semantic-level variations without requiring additional data for each variation, making it practical to apply. Experiments on both synthetic and real-world data show that our framework enables certifying robustness under diverse semantic variations across scenarios.

05.
medRxiv (Medicine) 2026-06-15

Wellbeing After Stroke-2 (WAterS-2): a feasibility study with process evaluation exploring inclusive, accessible, online psychological support after stroke

Objectives: Explore feasibility and acceptability of upskilling a workforce to deliver a co-developed intervention, based on Acceptance and Commitment Therapy (ACT), to support psychological adjustment post-stroke targeting underserved groups. Design: Multi-site, single-arm feasibility study with embedded mixed-methods process evaluation (ISRCTN17628580). Setting: Four NHS community stroke services across England. Participants: 1. Stroke survivors [≥]18 years of age, [≥]4 months post-stroke, reporting psychological difficulties adjusting to stroke, able to consent and access remote group sessions in English; 2. Group facilitators from NHS stroke services, not ACT specialists. Intervention: WAterS-2: an eight-session, remotely-delivered ACT-informed group intervention. Outcome measures: Recruitment, fidelity, safety, acceptability and perceived value were assessed using fidelity checklists, post-intervention surveys and semi-structured interviews with stroke survivors and facilitators. Clinical outcomes including mood (HADS), wellbeing (ONS4), psychological flexibility (AAQ-ABI), measured post-group and three-months later. Results: Nineteen stroke survivors recruited (mean 9.6 months post-stroke; n=5 (26%) minoritised ethnicities; n=10 (52%) with aphasia). Thirteen facilitators - including two peer support workers - delivered the intervention with fidelity following structured training across four services. Drop-out was low (2/19; 11%); with 15 (79%) attending [≥]5/8 sessions. Remote data collection was feasible (79% follow-up completion), with no adverse events recorded. Acceptability was high: survivors valued peer connection, grounding and mindfulness practices. ACT metaphors were helpful for some but challenging for others, including some with aphasia. Online delivery was suitable but limited informal connection. Facilitators reported increased capability, incorporating ACT skills into routine care. NHS workforce pressures and geographically-constrained referral pathways limited recruitment reach. Conclusions: WAterS-2 is feasible, safe, acceptable and inclusive. A mixed workforce, including NHS peer support workers, can be upskilled to deliver with fidelity. Inclusion of underserved groups is achievable but requires active strategies beyond standard NHS referral routes. Findings inform a provisional logic model and a future pragmatic trial.

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

SkillChain: Closing the Loop on Skill Evolution for Image-Based E-Commerce AI Assistants

Image-based AI assistants are now deployed at production scale on e-commerce platforms, where a single uploaded image can trigger fundamentally different user intents: product search, style recommendation, visual encyclopedia, or utility tool calls, each demanding its own response format, tool invocation, and domain knowledge. Without per-intent behavioral constraints, LLM-based systems conflate these heterogeneous modes and fall short of domain quality standards, while the breadth and dynamism of the intent space render manual engineering infeasible. To address this, we present SkillChain, which closes the production feedback loop on Skill evolution, automating the lifecycle of Skills through three stages: Skill Creator for bootstrapping from task specs and trajectories, Route Optimizer for routing alignment, and Body Refiner for iterative Skill Body refinement via dual-path LLM-Judge evaluation. Deployed on a production-scale e-commerce image assistant, SkillChain substantially improves aggregate response quality, with the strongest gains on structural compliance and content quality; a one-week online A/B experiment further confirms significant gains in user engagement, content consumption, and long-term retention.

07.
arXiv (CS.AI) 2026-06-19

PrototypeNAS: Rapid Design of Deep Neural Networks for Microcontroller Units

arXiv:2603.15106v2 Announce Type: replace Abstract: Enabling efficient deep neural network (DNN) inference on edge devices with different hardware constraints is a challenging task that typically requires DNN architectures to be specialized for each device separately. To avoid the huge manual effort, one can use neural architecture search (NAS). However, many existing NAS methods are resource-intensive and time-consuming because they require the training of many different DNNs from scratch. Furthermore, they do not take the resource constraints of the target system into account. To address these shortcomings, we propose PrototypeNAS, a zero-shot NAS method to accelerate and automate the selection, compression, and specialization of DNNs to different target microcontroller units (MCUs). We propose a novel three-step search method that decouples DNN design and specialization from DNN training for a given target platform. First, we present a novel search space that not only cuts out smaller DNNs from a single large architecture, but instead combines the structural optimization of multiple architecture types, as well as optimization of their pruning and quantization configurations. Second, we explore the use of an ensemble of zero-shot proxies during optimization instead of a single one. Third, we propose the use of Hypervolume subset selection to distill DNN architectures from the Pareto front of the multi-objective optimization that represent the most meaningful tradeoffs between accuracy and FLOPs. We evaluate the effectiveness of PrototypeNAS on 12 different datasets in three different tasks: image classification, time series classification, and object detection. Our results demonstrate that PrototypeNAS is able to identify DNN models within minutes that are small enough to be deployed on off-the-shelf MCUs and still achieve accuracies comparable to the performance of large DNN models.

08.
arXiv (CS.CV) 2026-06-19

Current World Models Lack a Persistent State Core

World models are increasingly regarded as a decisive step toward artificial general intelligence, yet modeling the physical world demands more than rendering convincing frames on demand: it requires an internal world state that keeps evolving over time, decoupled from observation, so that objects endure and events run to their conclusions whether or not a camera is watching, much as the moon holds to its orbit when no one is looking. This requirement is a blind spot of existing benchmarks, which reward surface properties such as fidelity, motion, and camera controllability while never asking whether a generated world keeps evolving once it is unobserved. We introduce WRBench, the first systematic diagnostic benchmark that treats camera motion as an intervention on observability and resolves evaluation into a human-calibrated chain that asks whether the camera executes the requested interaction, whether the scene stays continuous and identifiable while in view, and whether a returning target remains consistent with the event that was set in motion. Across 9{,}600 videos from 23 models spanning four control paradigms, one finding proves stubborn: current systems maintain the observed world as a tracking shot, resuming a returning target in the state at which it was abandoned rather than advancing the event while it went unseen. Because this failure recurs across control paradigms, model families, and increments of scale, robust world-state evolution does not follow from cleaner imagery, tighter control, richer geometric priors, or sheer parameter count We therefore argue that the stability of the physical state kernel and the consistency of worldlines under viewpoint intervention should become first-class objectives of world-model design, so that a world model captures how the world will unfold rather than how the next frame appears.

09.
arXiv (quant-ph) 2026-06-11

Fast Adiabatic Quantum Gates via Hyperfine Intermediate States

arXiv:2606.11655v1 Announce Type: new Abstract: The appeal of adiabatic quantum computing lies in its intrinsic robustness against various technical imperfections, making it attractive for many quantum information applications. However, it faces a fundamental challenge: accelerating the adiabatic operations while preserving adiabaticity within the qubit coherence time. In this article, we propose an electromagnetically induced transparency-based adiabatic CNOT gate protocol which harnesses atomic hyperfine intermediate states (HISs) to speed up the adiabatic evolution. The HISs, naturally-existed in two-photon transitions, often need to be suppressed due to their significant decay errors. In contrast, this paper introduces a novel method that utilizes appropriately chosen HISs not only to enhance the adiabaticity in STAY pathway but also to accelerate the population transfer in TRANSFER pathway. Through pulse optimization, we achieve adiabatic gate fidelities exceeding 0.9991 within 0.3903 {\mu}s in realistic Cs atomic setups. To demonstrate the generality of protocol we further assess the impact of decays from multiple HIS and extend our model to arbitrary number of states, providing a practical route toward fast and robust adiabatic quantum gates in Rydberg-atom platforms.

10.
medRxiv (Medicine) 2026-06-22

T Cell Receptor repertoire analysis reveals antigenic convergence and immunotherapeutic opportunities in Prostate Cancer

Background: The T-cell receptor {beta} (TCR{beta}) repertoire reflects antigen-driven adaptive immune responses and provides insight into tumor-immune interaction. In prostate cancer (PCa), the immunosuppressive tumor microenvironment limits effective T-cell activation, and the antigenic drivers shaping intratumoral TCR repertoires remains poorly defined. This study aimed to characterize matched tumor and peripheral TCR{beta} repertoires from treatment-naive PCa patients and to identify shared clonotypes and antigenic specificities associated with disease severity. Methods: Next-generation sequencing was used to profile TCR{beta} repertoires from matched tumor biopsies and peripheral blood mononuclear cells obtained from treatment-naive PCa patients. Repertoires clonality, diversity, and was assessed using established metrics. Antigenic convergence was evaluated using GLIPH2 to identify shared CDR3{beta} motifs and predicted tumor-associated antigen (TAA) recognition, followed by functional validation using IFN-{gamma} ELISpot and T-cell expansion assays. Results: Tumor-derived TCR{beta} repertoires displayed reduced richness and increased clonality compared with peripheral blood mononuclear cells, consistent with local antigen-driven expansion. High-grade tumors demonstrated greater interpatient clonotype sharing and motif-level convergence, indicative of recognition of common TAAs. GLIPH2 analysis associated expanded clonotypes with epitopes derived from prostate-specific G-protein coupled receptor (PSGR), prostate-specific membrane antigen (PSMA), and prostate-specific antigen (PSA). Functional validation confirmed that peptide pools containing PSGR- and PSMA-derived epitopes induced IFN-{gamma} production and antigen-specific T-cell proliferation in vitro. Conclusions: These findings reveal an oligoclonal, antigen-driven intratumoral TCR{beta} landscape and identify PSGR and PSMA as immunogenic, potentially actionable targets. Integration of TCR profiling with antigen discovery pipelines may support the development of TCR-based biomarkers and precision immunotherapeutic strategies in prostate cancer.

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

Not all Jensen-Shannon Divergence Estimators are Equal

arXiv:2606.16411v1 Announce Type: new Abstract: The Jensen-Shannon divergence is widely reported as a scalar measure of fidelity for synthetic tabular data. Yet, in practice, it is estimated from finite samples using protocols that are often underspecified. This creates a measurement problem. Although the population divergence is well defined, the empirical value depends on the estimator family, sampling protocol, calibration, dimensionality, and class balance. We show that different protocols can yield non-comparable values: marginal-based estimators ignore dependencies in the joint distribution and can severely underestimate divergence, while classifier-based estimators capture joint structure but exhibit strong estimator dependence. We systematically study this behavior across controlled settings with reference divergences and real-world synthetic tabular benchmarks. Our analysis reveals dependence blindness in marginal estimators, prior-shift bias under class imbalance, and estimator sensitivity in high dimensions. To address prior shift, we derive a closed-form posterior correction for classifier-based Jensen-Shannon estimation. Our results show that empirical Jensen-Shannon divergence values are inherently protocol-dependent, making explicit specification of the estimation procedure necessary for meaningful comparison. We provide practical guidelines and an open-source tool for estimator-aware Jensen-Shannon evaluation.

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

The Mathematics of AI Winters: The mathematical Taxonomy of Paradigm Fragility in AI Winter

arXiv:2606.12610v1 Announce Type: new Abstract: Two major periods of reduced funding and confidence in artificial intelligence research, commonly called the first and second AI winters, are usually explained through engineering failure, commercial disappointment, and inflated expectations. This article develops a complementary thesis: that the dominant paradigms of those periods also met genuine formal barriers, including limitations of representation, optimisation, computational complexity, statistical learnability, and high-dimensional approximation. The contribution is synthetic rather than archival. We do not claim that particular theorems mechanically caused the winters; rather, we show that several central disappointments of early AI were aligned with mathematically precise bottlenecks. We analyse these bottlenecks through the perceptron impossibility results of Minsky and Papert, the complexity-theoretic hardness of exact neural-network training established by Blum and Rivest, minimax rates for nonparametric estimation in high dimension due to Stone, vanishing-gradient analyses by Hochreiter and by Bengio and collaborators, and classical statistical learning theory in the tradition of Vapnik and Chervonenkis, Valiant, and Blumer and collaborators. We then relate these barriers to the later breakthroughs that mitigated, rather than eliminated, them.

13.
arXiv (CS.CV) 2026-06-16

MAF: Multimodal Adaptive Few-shot Prompting for Sentiment Analysis with MLLMs

作者:

Multimodal large language models (MLLMs) have demonstrated remarkable capabilities in understanding complex multimodal content. However, their performance in sentiment analysis exhibits acute sensitivity to prompt design, rendering static, uniformly applied prompts inherently suboptimal for capturing the nuanced multimodal cues that vary across inputs. To address this limitation, we propose a Multimodal Adaptive Few-Shot Prompting (MAF) framework, which dynamically retrieves and integrates query-relevant demonstrations to elicit the sentiment reasoning capabilities of MLLMs in a context-sensitive manner. MAF constructs a demonstration retrieval module that holistically encodes facial expressions, scene context, and textual semantics, with a lip movement amplitude detection mechanism introduced for accurate speaker identification in multi-person scenarios. Departing from conventional fixed-weight fusion, a lightweight coefficient generation network is trained to output query-conditioned fusion weights in real time, enabling weighted aggregation of multimodal similarity scores to retrieve the top-K most informative demonstrations. Prediction stability is further enhanced through majority voting over multiple candidate outputs generated by the MLLM. Extensive experiments on public benchmark datasets demonstrate that MAF achieves substantial and consistent performance improvements over the corresponding backbone variants and remains competitive with strong multimodal sentiment-analysis baselines.

14.
arXiv (CS.CV) 2026-06-19

HumanScale: Egocentric Human Video Can Outperform Real-Robot Data for Embodied Pretraining

Embodied foundation models are expected to benefit from data scaling like large language models, but face a much tighter data bottleneck. Teleoperated real-robot trajectories remain the dominant pretraining source due to their precise action supervision and embodiment alignment, yet their scalability is limited by high collection cost, acquisition difficulty, and low behavioral and environmental diversity. These limitations have sparked interest in egocentric human video as a scalable, substantially lower-cost, and more diverse alternative for embodied model pretraining. However, its effectiveness compared to teleoperated real-robot data remains underexplored. To address this question, we conduct a systematic study comparing egocentric human video and teleoperated real-robot trajectories as pretraining data sources for embodied foundation models, under fixed post-training and validation protocols. Surprisingly, we find that egocentric data, when processed through a carefully designed filtering and labeling pipeline, is not merely a viable substitute for model pretraining but can lead to superior performance. With the same amount of pretraining data, models pretrained on egocentric data achieve a 24% lower validation loss on real-robot action prediction, as well as 52.5% and 90% higher success rates on in-distribution and out-of-distribution real-robot task execution, respectively. This finding verifies a scalable paradigm for embodied foundation models: pretrain on egocentric human video to learn diverse world representations, then adapt with a small amount of labeled real-robot data for action-space alignment. We hope this study encourages broader exploration of egocentric data and offers guidance for data quality assessment before costly robot data collection.

15.
arXiv (math.PR) 2026-06-11

Percolation phase transition on planar spin systems

arXiv:2105.13314v2 Announce Type: replace Abstract: In this article we study the continuity and sharpness of the phase transition for percolation models defined on top of planar spin systems. The two examples that we treat in detail concern the Glauber dynamics for the Ising model and a Dynamic Bootstrap process. For both of these models we prove that their phase transition is continuous and sharp, providing also quantitative estimates on the two point connectivity. The techniques that we develop in this work can be applied to a variety of different percolation models based on spin-flip dynamics. We also discuss some of the problems that can be tackled in a similar fashion.

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

Identifiable Markov Switching Models with Instantaneous Effects and Exponential Families

arXiv:2606.02231v2 Announce Type: replace-cross Abstract: Temporal systems often exhibit non-stationary behaviour, such as seasonal climate variation or glucose fluctuations in patients with type-1 diabetes. One way to model non-stationarity is through discrete latent regimes, i.e., stationary segments of time. Such systems induce a Markov Switching Model (MSM), a class of Hidden Markov Models with autoregressive dependencies among latent regimes and observed variables. Identifying latent regimes is challenging in the presence of frequent regime switches and nonlinear and non-Gaussian dynamics, particularly when there are instantaneous effects between the variables, e.g., due to slow rates of measurements. In this work, we establish the identifiability of both latent regimes and regime-dependent causal structures under temporal regime dependencies, nonlinear lagged and instantaneous effects, and independent noise from the exponential family. Our identifiability theory subsumes non-temporal mixtures of causal models. Furthermore, we introduce FlowMSM, a regime detection framework that can be paired with any stationary causal discovery method to recover regime-dependent causal structures. Experiments on synthetic benchmarks and a financial economics dataset demonstrate the effectiveness of our approach to detect latent regimes and discover causal structures from non-stationary time series.

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

HoloRec: Holistic Encoding and Interleaved Reasoning for Generative Recommendation

arXiv:2606.15331v1 Announce Type: cross Abstract: Generative recommendation models that formulate the task as sequence generation overcome the objective fragmentation problem of traditional cascade architectures, yet existing approaches still suffer from flat semantic representations lacking hierarchical structure for multi-step reasoning and an externally constructed chain-of-thought (CoT) that requires expensive annotations and remains disconnected from the generation objective. We propose HoloRec, an endogenous chain-of-thought recommendation mechanism that unifies representation, reasoning, and generation by constructing a hierarchical semantic encoding matrix via multi-granularity nested residual quantization optimized by a holistic reconstruction loss. HoloRec supports two inference modes: a non-thinking mode that uses lightweight multi-granularity supervised alignment for fast prediction, and a thinking mode that employs an interleaved reasoning scheme to generate CoT steps on the fly, directly embedding reasoning into the generation process without external data. Experiments on multiple public recommendation datasets demonstrate that HoloRec consistently outperforms baselines, with especially significant gains in sparse scenarios, and the thinking mode achieves better accuracy than the non-thinking mode with only modest inference overhead.

18.
medRxiv (Medicine) 2026-06-22

Survival differences and artemisinin resistance in severe malaria among HIV coinfected patients: data from Mozambique

Abstract Background Malaria remains a significant cause of morbidity and mortality, especially in sub-Saharan Africa, where rates of HIV coinfection are high. This study aimed to determine whether Plasmodium falciparum malaria treatment outcomes and rates of antimalarial resistance markers differ according to HIV serostatus in Mozambique. Methodology We conducted an observational study of non-pregnant adults, with and without HIV coinfection, admitted to the Hospital Central de Maputo for treatment of severe malaria. Plasmodium falciparum DNA was extracted from whole blood and sequenced to identify single-nucleotide polymorphisms. Statistical analyses to compare clinical outcomes and rates of nonsynonymous mutations in genes associated with drug resistance were performed in R version 4.2. Results We recruited 149 study participants aged between 18-62 years, 72 (48.3%) were female, and 59 (39.6%) were infected with HIV. Comparing clinical outcomes, we found a significant difference in anemia (hemoglobin

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

Harsher on Male? Evaluating LLMs on Gender-Asymmetric Moral Framing Across Diverse Conflict Scenarios

Existing studies on gender bias in LLMs have largely focused on stereotypes, occupational associations, or explicit harmful outputs. In this work, we ask whether LLMs apply consistent response standards to the same negative behavior under matched male-actor and female-actor conditions. We introduce GAMA-Bench, a gender-mirrored benchmark of 1,298 scenarios covering intimate relationship and public social conflicts. It constructs gender-neutral misconduct templates through controlled grids and cross-model review, then compiles them into paired first-person prompts with matched actor-gender and role-reference variations. We further design a structured response-framing protocol to measure how models allocate punishment, empathy, escalation, instruction, and blame. Experiments on 10 representative LLMs reveal a consistent male-disadvantaging asymmetry: male actors receive more punitive, escalatory, and blame-centered framing, whereas female actors receive more therapeutic and empathy-oriented framing for the same misconduct. Further analyses show that this pattern persists across model families, scenario tracks, model scale, and explicit thinking-style reasoning. The official code is available at https://github.com/xufeiqiong/GAMA-Bench.

20.
Nature (Science) 2026-06-10

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

作者:

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.

21.
arXiv (CS.AI) 2026-06-12

scLLM-DSC: LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering for Single-Cell RNA Sequencing

arXiv:2606.13007v1 Announce Type: cross Abstract: Clustering is fundamental to scRNA-seq analysis, serving as a cornerstone for identifying cell populations and resolving tissue heterogeneity. However, existing methods focus on mining numerical statistical patterns, suffering from semantic agnosticism by neglecting the intrinsic biological functions encoded by genes. While Large Language Models (LLMs) offer promising semantic capabilities, their direct adaptation to cell clustering is hindered by the structural mismatch between generative pre-training objectives and discriminative downstream tasks. To bridge this gap, we propose scLLM-DSC, a novel LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering framework. Diverging from data-driven paradigms, scLLM-DSC establishes a semantically-grounded representation by synergizing two views: a Knowledge-Driven Semantic View derived from NCBI gene priors and contextualized Cell2Sentence embeddings, and a Structure-Aware Topological View extracted via a graph-guided encoder. Crucially, we introduce a cross-modal contrastive alignment mechanism to enforce consistency between biological semantics and transcriptomic features within a unified latent space. Extensive benchmarks demonstrate that scLLM-DSC significantly outperforms eleven state-of-the-art baselines in clustering accuracy.

22.
arXiv (CS.LG) 2026-06-16

Active Learning with Low-Rank Structure for Data Selection

arXiv:2606.16045v1 Announce Type: new Abstract: In the data selection problem, the objective is to choose a small, representative subset of data that can be used to efficiently train a machine learning model. Sener and Savarese [ICLR 2018] showed that, given an embedding representation of the data and suitable geometric assumptions, heuristics based on $k$-center clustering can be used to perform data selection. This perspective was further explored by Axiotis et. al. [ICML 2024], who proposed a data selection approach based on $k$-means clustering and sensitivity sampling. However, these methods rely on the assumption that the dataset exhibits intrinsic geometric structure that can be effectively captured by clustering, whereas many modern datasets instead possess global algebraic structure that is better exploited by low-rank approximation or principal component analysis. In this paper, we introduce a new data selection framework based on low-rank approximation and residual-based sampling, formulated through the lens of row subset selection and loss-preserving coreset construction. Given an embedding representation of the data satisfying mild regularity conditions, which can be interpreted as algebraic or angular notions of Lipschitz continuity, we show that it is possible to select a weighted subset of $\tilde{O}\left(k + \frac{1}{\varepsilon^2}\right)$ data points whose average loss approximates the average loss over the full dataset within a $(1+\varepsilon)$ relative error, up to an additive $\varepsilon \Phi_k$ term, where $\Phi_k$ denotes the optimal rank-$k$ approximation cost of the embedding matrix. We complement these theoretical guarantees with empirical evaluations, demonstrating that on a range of real-world datasets, our data selection approach achieves improved performance over prior strategies based on uniform sampling or clustering-based sensitivity sampling.

23.
arXiv (quant-ph) 2026-06-15

Certifying Macroscopic Quantum Mechanics via Hypothesis Testing with Finite Data

arXiv:2506.22092v2 Announce Type: replace Abstract: We address the challenge of certifying quantum behavior with single macroscopic massive particles, subject to decoherence and finite data. We propose a hypothesis testing framework that distinguishes between classical and quantum mechanics based on position measurements. While interference pattern visibility in single-particle quantum superposition experiments has been commonly used as a sufficient criterion to falsify classical mechanics, we show that, from a hypothesis testing perspective, it is neither necessary nor efficient. Focusing on recent proposals to prepare macroscopic superposition states of levitated nanoparticles, we show that the likelihood ratio test – which leverages differences across the entire probability distribution – provides an exponential reduction in measurements needed to reach a given confidence level. These results generalize to a broad class of quantum states, and offer a principled, efficient method to falsify classical mechanics in interference experiments, relaxing the experimental constraints faced by current efforts to test quantum mechanics at the macroscopic scale.

24.
arXiv (CS.AI) 2026-06-12

Competition and Diversity in Generative AI

arXiv:2412.08610v3 Announce Type: replace-cross Abstract: Recent evidence, both in the lab and in the wild, suggests that the use of generative artificial intelligence reduces the diversity of content produced. The use of the same or similar AI models appears to lead to more homogeneous behavior. Our work begins with the observation that there is a force pushing in the opposite direction: competition. When producers compete with one another (e.g., for customers or attention), they are incentivized to create novel or unique content. We explore the impact competition has on both content diversity and overall social welfare. Through a formal game-theoretic model, we show that competitive markets select for diverse AI models, mitigating monoculture. We further show that a generative AI model that performs well in isolation (i.e., according to a benchmark) may fail to provide value in a competitive market. Our results highlight the importance of evaluating generative AI models across the breadth of their output distributions, particularly when they will be deployed in competitive environments. We validate our results empirically by using language models to play Scattergories, a word game in which players are rewarded for answers that are both correct and unique. Overall, our results suggest that homogenization due to generative AI is unlikely to persist in competitive markets, and instead, competition in downstream markets may drive diversification in AI model development.

25.
arXiv (CS.CV) 2026-06-12

VISTA: Video Interaction Spatio-Temporal Analysis Benchmark

Existing benchmarks for Vision-Language Models (VLMs) primarily evaluate spatio-temporal understanding on simple single-action videos, closed attribute sets and restricted entity types, failing to capture the freeform, multi-action interactions between diverse entities which characterize real-world video understanding. Furthermore, the lack of a systematic framework for analyzing model failures across complementary spatio-temporal axes hinders comprehensive evaluation. To address these gaps, we introduce VISTA, a Video Interaction Spatio-Temporal Analysis benchmark designed for open-set, multi-entity and multi-action spatio-temporal understanding in VLMs. VISTA decomposes videos into interpretable entities, their associated actions, and relational dynamics, enabling multi-axis diagnostics and unified assessment of relational, spatial, and temporal understanding. Our benchmark integrates multiple datasets into a single interaction-aware taxonomy and comprises ~12K curated video-query pairs spanning diverse scenes and complexities. We systematically evaluate 11 state-of-the-art VLMs on VISTA, and break down aggregate performance across our taxonomy to reveal shortcomings and pronounced spatio-temporal biases obscured by traditional metrics. By providing detailed, taxonomy-driven diagnostics on a challenging dataset, VISTA offers a nuanced framework to guide advances in model design, pretraining strategies, and evaluation protocols. Overall, VISTA is the first, large-scale, interaction-aware diagnostic benchmark for spatio-temporal understanding in VLMs.