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

Mind-Studio: Executable World Models with Lookahead Evaluation for Partially Observable Games

arXiv:2606.16070v1 Announce Type: new Abstract: World-model synthesis aims to turn interaction experience into an internal model of environment dynamics. Existing symbolic approaches often fit observed transitions or mixtures of local rules, but they do not produce a complete executable program that can run independently of the real environment. We present Mind-Studio, a framework that synthesizes executable pygame-style world models from state-action-next-state trajectories using large language models. Mind-Studio combines entropy-selected traces with a lightweight game skill file containing object, action, and static scene information extracted from screenshots. We evaluate synthesis quality with a K-step lookahead fidelity protocol that compares generated world-model rollouts against Real-ALE rollouts from the same state. On Montezuma's Revenge, Mind-Studio improves chosen-action next-state prediction from 0.3% for PoE-World to 48.7% while verifying 5 of 8 subgoals; across Alien, Assault, and Skiing, it achieves stronger branch-level fidelity than prior learned lookahead sources.

02.
bioRxiv (Bioinfo) 2026-06-14

Prediction of parsimonious and temporally sensitive sets of cell fate engineering transcription factors with IMCell

Transcription factor (TF) cocktails used in cell identity reprogramming protocols have largely been developed from experimental approaches. A handful of computational approaches have been reported, though have not been widely adopted by the scientific community. To standardize their use and assess their performance, we built CompForce, a platform that integrates these tools. Using CompForce, we found that existing computational methods offer modest improvements over differential expression on both synthetic and literature-curated data, and that their lackluster and inconsistent performance could be attributed to a reliance on local centrality metrics. To improve upon these methods, we developed IMCell, a prediction method that is inspired by the influence maximization problem. Unlike existing tools, IMCell returns optimized TF sets rather than ranked TF lists. We demonstrate that IMCell vastly out-performs existing tools, and further extend it to dynamic, stepwise contexts. The tools presented here are available in the R packages CompForce and IMCell.

04.
arXiv (quant-ph) 2026-06-16

Semiclassical Gravity Efficiently Solves $\mathsf{NP}$-Complete Problems

arXiv:2606.14806v1 Announce Type: cross Abstract: Assuming the gravitational field is classical and that it couples to quantum fields via the semiclassical Einstein field equations, we show that the weak-field dynamics of a massive and non-relativistic qubit can in principle be used to solve an $\mathsf{NP}$-complete problem in polynomial time. We attribute this vast computational power to the non-linear dynamics afforded by the semiclassical Einstein field equations. Consequently, the above two assumptions entail a violation of the Physical Extended Church–Turing Thesis, which we regard as evidence for the quantization of gravity.

05.
arXiv (quant-ph) 2026-06-16

Influence of the Electron's Anomalous Magnetic Dipole Moment on High-Atomic-Number Atoms

arXiv:2606.15995v1 Announce Type: new Abstract: Super-heavy atoms ($Z > 100$) are usually studied in the context of the so-called ``Quantum Electrodynamics of Strong Fields''. In this theory the problem of the singularity in the electron energy whenever $Z > 137$ is overcome. This is done by considering the finite size of the nucleus and leads to interesting phenomena, such as the spontaneous production of positrons. Here, we show that taking into account the contribution from the Anomalous Magnetic Dipole Moment of the electron (by means of an effective theory), within a point-nucleus model, is a sufficient condition to obtain regular wave functions and physically acceptable energy values for $Z > 137$.

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

Safe Exploration via Policy Priors

arXiv:2601.19612v3 Announce Type: replace-cross Abstract: Safe exploration is a key requirement for reinforcement learning (RL) agents to learn and adapt online, beyond controlled (e.g. simulated) environments. In this work, we tackle this challenge by utilizing suboptimal yet conservative policies (e.g., obtained from offline data or simulators) as priors. Our approach, SOOPER, uses probabilistic dynamics models to optimistically explore, yet pessimistically fall back to the conservative policy prior if needed. We prove that SOOPER guarantees safety throughout learning, and establish convergence to an optimal policy by bounding its cumulative regret. Extensive experiments on key safe RL benchmarks and real-world hardware demonstrate that SOOPER is scalable, outperforms the state-of-the-art and validate our theoretical guarantees in practice.

07.
arXiv (CS.AI) 2026-06-15

CARE: Controlling LLM-Generated Policies through Auditable Review of Evidence in Scientific Experimentation

arXiv:2606.14581v1 Announce Type: cross Abstract: Granting LLMs direct control over costly, irreversible scientific experiments leads to unsafe exploration and unstable performance, but discarding LLM creativity entirely sacrifices significant optimization potential. We introduce CARE (Controlling LLM-Generated Policies through Auditable Review of Evidence in Scientific Experimentation), an auditable controller for high-throughput experimentation (HTE) optimization that keeps a non-LLM incumbent optimizer as the default action path while using LLMs to revise challenger ranking policies. Before each outcome is revealed, a public-evidence intervention gate compares the challenger with the incumbent. It authorizes the challenger's selection only when the evidence available before selection supports the change, with the decision recorded in the audit log. CARE outperforms all other evaluated methods on Minerva/Olympus and ChemLex benchmarks, with final-best improving from 80.0 to 88.5 on Minerva/Olympus and from 83.9 to 92.1 on ChemLex, relative to the public incumbent. Our experiments indicate that LLM self-evolution is more reliable when it expands the proposal space under an auditable controller, rather than directly choosing experiments.

08.
arXiv (CS.CL) 2026-06-15

The Culture Funnel: You Can't Align What isn't in the Data

Current cultural alignment approaches focus on inference-time interventions, assuming models already contain sufficient cultural knowledge. We argue modern LLM pipelines suffer from a cultural data funnel. Using a multidimensional tagging framework across pretraining, fine-tuning, alignment, and reasoning datasets, we show explicit cultural signals decline sharply during post-training, while geographically concentrated, task-specialized data dominates. Multilinguality enhances geographic diversity of cultural knowledge but does not ensure balanced representation. Our tags improve downstream cultural benchmark performance, demonstrating that advances require shifting focus in training data pipelines. To facilitate future research, we release our culturally tagged dataset with 5.6M samples at https://huggingface.co/datasets/CohereLabs/CultureMarkers.

09.
arXiv (CS.AI) 2026-06-16

Sample from What You See: Visuomotor Policy Learning via Diffusion Bridge with Observation-Embedded Stochastic Differential Equation

arXiv:2512.07212v3 Announce Type: replace Abstract: Imitation learning with diffusion models has advanced robotic control by capturing the multi-modal action distributions. However, existing methods typically treat observations only as high-level conditions to the denoising network, rather than integrating them into the stochastic dynamics of the diffusion process itself. As a result, the sampling is forced to begin from random noise, weakening the coupling between perception and control and often yielding suboptimal performance. We propose BridgePolicy, a generative visuomotor policy that directly integrates observations into the stochastic dynamics via a diffusion-bridge formulation. By constructing an observation-informed trajectory, BridgePolicy enables sampling to start from a rich and informative prior rather than random noise, substantially improving precision and reliability in control. A key difficulty is that diffusion bridge normally connects distributions of matched dimensionality, while robotic observations are heterogeneous and not naturally aligned with actions. To overcome this, we introduce a semantic aligner to unify the visual and state inputs and align the observations with action representations, making diffusion bridge applicable to heterogeneous robot data. Extensive experiments across 52 simulation tasks on three benchmarks and 5 real-world tasks demonstrate that BridgePolicy consistently outperforms state-of-the-art generative policies. Our code is available at https://jianghcsr.github.io/BridgePolicy_page/.

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

MVEB: Massive Video Embedding Benchmark

We introduce the Massive Video Embedding Benchmark (MVEB), a 23-task benchmark for video embeddings spanning classification, zero-shot classification, clustering, pair classification, retrieval, and video-centric question answering. We evaluate 33 models and find that no single model dominates: MLLM-based embeddings lead on classification, clustering, pair classification, and QA; multimodal binding leads on retrieval and zero-shot classification; generative MLLMs without contrastive adaptation collapse on cross-modal tasks. Paired video-only vs. audio+video evaluations show that audio's contribution depends on dataset annotation provenance: audio helps when labels were produced from both modalities and hurts when they were produced from visuals alone, a six-point gap consistent across model families. MVEB is derived from MVEB+, a 184-task pool, and is designed to maintain task diversity while reducing evaluation cost. It integrates into the MTEB ecosystem for unified evaluation across text, image, audio, and video. We release MVEB and all 184 tasks along with code and a leaderboard at https://github.com/embeddings-benchmark/mteb.

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

Sonar-TS: Search-Then-Verify Natural Language Querying for Time Series Databases

Natural Language Querying for Time Series Databases (NLQ4TSDB) aims to assist non-expert users retrieve meaningful events, intervals, and summaries from massive temporal records. However, existing Text-to-SQL methods are not designed for continuous morphological intents such as shapes or anomalies, while time series models struggle to handle ultra-long histories. To address these challenges, we propose Sonar-TS, a neuro-symbolic framework that tackles NLQ4TSDB via a Search-Then-Verify pipeline. Analogous to active sonar, it utilizes a feature index to ping candidate windows via SQL, followed by generated Python programs to lock on and verify candidates against raw signals. To enable effective evaluation, we introduce NLQTSBench, the first large-scale benchmark designed for NLQ over TSDB-scale histories. Our experiments highlight the unique challenges within this domain and demonstrate that Sonar-TS effectively navigates complex temporal queries where traditional methods fail. This work presents the first systematic study of NLQ4TSDB, offering a general framework and evaluation standard to facilitate future research.

12.
arXiv (CS.AI) 2026-06-15

Closing the Reflection Gap: A Free Calibration Bonus for Agentic RL

作者:

arXiv:2606.14211v1 Announce Type: new Abstract: LLMs are increasingly deployed as agents that interact with external environments and observe feedback such as execution results, error messages, and tool outputs. A well-functioning agent should be able to leverage this feedback to accurately assess its own performance. Yet we find a persistent reflection gap: LLM agents tend to mis-assess their own outputs after observing concrete environment feedback – even for questions they correctly answered – and standard RL barely helps due to a credit-assignment mismatch. To close this gap, we propose RefGRPO, a simple yet effective fix that augments standard RL algorithms with two key ingredients: a free calibration bonus computed by contrasting the agent's own reflection with the actual outcome (requiring no additional reward model, LLM judge, or external annotation), and a dynamic schedule on its coefficient. Compared to standard RL baselines, our method simultaneously improves reflection calibration (e.g., reduces underconfidence rate $44.4\% \to 7.7\%$) and task accuracy (e.g., $75.1\% \to 76.5\%$) on text-to-SQL across five benchmarks. The resulting calibrated reflection turns the agent into its own verifier grounded in environment feedback, which further enables (i) better self-improvement that uses reflections as pseudo-rewards without outcome supervision, and (ii) more effective test-time selective prediction by committing only to rollouts flagged as correct.

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

Task-guided cross-subject latent alignment: a multi-encoder-decoder VAE

arXiv:2606.15989v1 Announce Type: cross Abstract: Aligning neural activity across subjects offers the promise of discovering shared computational principles and generalizable decoders. However, traditional alignment methods require shared stimuli across subjects, a constraint that limits applicability to naturalistic paradigms with limited or non-overlapping data. We introduce a Multi-Encoder-Decoder Variational Autoencoder (MED-VAE) that achieves cross-subject alignment without shared stimuli by anchoring representations to a common scaffold provided by a pretrained ANN. Using the Natural Scenes Dataset, we show that MED-VAE creates common latent spaces with superior semantic organisation, achieving higher cross-subject alignment than common methods while maintaining robust generalisation to held-out stimuli where traditional methods degrade. Reconstructing from these common spaces back to each subject's original neural space, MED-VAE preserves equal stimulus-driven signal in its cross-subject latent space. Finally, we show that this superior alignment directly enables cross-subject neural prediction, as demonstrated via cross-subject image decoding. In summary, we introduce a framework to identify generalisable common subspaces for cross-subject predictions and downstream tasks, demonstrated here for visual cortex responses to static images.

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

The algebra of Krom logic programs

arXiv:2606.15719v1 Announce Type: cross Abstract: This paper investigates the algebraic structure of Krom logic programs, consisting only of facts and rules with at most one body atom. We show that sequential composition endows the class of Krom programs with a natural monoid structure and that this structure admits rich algebraic extensions to Krom seminearrings, Krom quemirings, Krom-Conway seminearrings, and Krom-Conway omegaseminearrings. Furthermore, we establish explicit generating sets and canonical decompositions, study the associated ${}^\omega$-operator, characterize the Kleene star in graph-theoretic terms, and relate finite Krom monoids to transformation monoids and finite-state automata. These results provide new connections between logic programming, algebraic automata theory, and algebraic graph theory.

15.
arXiv (CS.LG) 2026-06-11

Scaling Laws of Global Weather Models

arXiv:2602.22962v2 Announce Type: replace Abstract: Data-driven models are revolutionizing weather forecasting. To optimize training efficiency and model performance, this paper analyzes empirical scaling laws within this domain. We investigate the relationship between model performance (validation loss) and three key factors: model size ($N$), dataset size ($D$), and compute budget ($C$). Across a range of models, we find that Aurora exhibits the strongest data-scaling behavior: increasing the training dataset by 10x reduces validation loss by up to 3.2x. GraphCast demonstrates the highest parameter efficiency, yet suffers from limited hardware utilization. Our compute-optimal analysis indicates that, under fixed compute budgets, allocating resources to more total training data yields greater performance gains than increasing model size. Furthermore, we analyze model shape and uncover scaling behaviors that differ fundamentally from those observed in language models: weather forecasting models consistently favor increased width over depth. These findings suggest that future weather models should prioritize wider architectures and larger effective training datasets to maximize predictive performance.

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

Regression Language Models for Code

We study code-to-metric regression: predicting numeric outcomes of code executions, a challenging task due to the open-ended nature of programming languages. While prior methods have resorted to heavy and domain-specific feature engineering, we show that a single unified Regression Language Model (RLM) using a frozen LLM encoder can simultaneously predict directly from text, (i) the memory footprint of code across multiple high-level languages such as Python and C++, (ii) the latency of Triton GPU kernels, and (iii) the accuracy and speed of trained neural networks represented in ONNX. In particular, a relatively small 300M parameter RLM based on T5Gemma, obtains >0.9 Spearman-rank on competitive programming submissions from APPS, and a single unified model achieves >0.5 average Spearman-rank across 24 different programming languages from CodeNet. Furthermore, the RLM can obtain the highest average Kendall-Tau of 0.46 on five classic NAS design spaces previously dominated by graph neural networks, and simultaneously predict architecture latencies on numerous hardware platforms.

17.
arXiv (CS.AI) 2026-06-18

Maturing Markov Decision Processes: Decision Making under Increasing Information and Shrinking Action Sets

arXiv:2606.18820v1 Announce Type: cross Abstract: Sequential decision problems often exhibit an asymmetric evolution of information and decision flexibility: as a decision cycle unfolds, the agent receives richer information while feasible actions expire due to operational cutoffs, commitments, or resource constraints. Standard MDP formulations typically flatten this structure into stage-dependent state descriptions and action masks, thereby obscuring the nested information–action asymmetry that determines which decisions are urgent and which can be deferred. We introduce Maturing Markov Decision Processes (MMDPs), a formulation built around this information–action asymmetry. We characterize one of its key consequences through an expiring-action priority principle, which identifies the actions that must be resolved before the next stage. Motivated by this structure, we develop a structure-aware reinforcement learning framework with stage-aware policy design, expiring-action abstraction, and search-augmented learning with distillation. Experiments on a controlled multi-supplier replenishment problem, simplified cash-management environments of increasing complexity, and a production-scale simulator show that explicitly modeling this asymmetry improves learning efficiency and becomes increasingly valuable as decision problems scale.

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

EPIG: Emotion-Based Prompting for Personalised Image Generation

arXiv:2606.13247v1 Announce Type: new Abstract: Text-to-image diffusion models have achieved impressive results in synthesizing high-quality images from natural language prompts. However, commonly used prompting strategies remain relatively generic, limiting the model's ability to accurately express emotional intent and nuanced affective attributes. This work proposes EPIG, a method that enhances emotional expressiveness at the prompt level prior to image generation. Grounded in psychologically informed emotion representations (valence-arousal) and leveraging structured, role-aware prompt enrichment, EPIG enriches emotion-related components of prompts without modifying or retraining the image generation backbone. The resulting emotion-aware prompts guide the generative process toward more emotionally coherent visual outputs, with particular effectiveness in controlling arousal. EPIG is lightweight, training-free, and well suited for resource-constrained and personalized image generation scenarios. Experimental results on a benchmark of 10 diverse prompts show that EPIG reduces mean arousal error compared to strong baselines, including naive insertion and LLM-based prompt expansion, with reductions of 14% and 12%, respectively. These improvements are statistically significant. EPIG also preserves valence alignment and semantic consistency, as measured by CLIPScore and supported by ablation studies. The effect is more pronounced on prompts containing explicit subjects such as humans, children, or animals, where the reduction reaches 17%, highlighting the subject-sensitive behavior of the proposed method.

19.
arXiv (math.PR) 2026-06-12

Counterintuitive problems in discrete probability

arXiv:2606.07516v2 Announce Type: replace Abstract: This manuscript contains a collection of counterintuitive problems in discrete probability, together with detailed solutions. The dataset was constructed as part of a broader research project investigating the capabilities of the latest-generation Large Language Models (LLMs) in solving discrete probability problems, in order to assess whether LLMs tend to make systematic reasoning errors associated with known cognitive biases. The problems collected here are specifically designed to challenge heuristic reasoning strategies that often lead to intuitively appealing but mathematically incorrect conclusions. The dataset combines several types of problems. Some are adapted from classical probabilistic paradoxes and cognitive-bias literature, while others originate from recreational mathematics sources or were developed by ourselves following similar principles. The primary purpose of this document is to provide a transparent and publicly accessible reference for the problems used in our experimental evaluation of language models, as well as providing detailed human-made solutions. At the same time, we believe that this collection may also prove useful for future research on probabilistic reasoning, cognitive biases, and the evaluation of reasoning capabilities in artificial intelligence systems.

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

Fusing Stylometric and Embedding Systems to Estimate Authorship Likelihood Ratios in Japanese

The likelihood ratio framework is widely recognized as the logically and legally sound basis for evidential analysis across forensic sciences, and its importance is increasingly acknowledged in analyses of authorship in textual evidence. To date, however, its application has been confined to English-language texts. Meanwhile, authorship attribution has traditionally relied on a diverse array of stylometric features, even as the rise of pre-trained large language models enables new contextual-embedding approaches. Combining these diverse approaches through fusion promises enhanced performance, yet it has not been applied to integrate stylometric-feature systems with embedding-based systems within the likelihood ratio paradigm. This study is the first to apply likelihood ratio-based forensic text comparison to Japanese digital texts, using ~1,000-character excerpts from blogs, to 1) evaluate system performance and likelihood ratio magnitudes and 2) assess the impact of fusing stylometric-feature systems with embedding-based systems. The results demonstrate that the fused system maintains excellent calibration while 1) increasing consistent-with-fact likelihood ratio magnitudes; 2) decreasing contrary-to-fact likelihood ratio magnitudes and 3) improving overall discriminability. The best-performing fusion achieved a log-likelihood-ratio cost of 0.32484, illustrating both the feasibility of likelihood ratio framework for Japanese and the benefits of fusion across heterogeneous systems.

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

Green AI Carbon Optimizer: Carbon-Efficient Training Location Recommendation and Global AI Energy Demand Forecasting

arXiv:2606.14707v1 Announce Type: cross Abstract: AI training and deployment consume substantial electricity, but carbon outcomes remain weakly integrated into routine model development decisions. This paper presents Green AI Carbon Optimizer with two primary contributions: (i) a carbon aware cloud region recommendation method for training workloads, and (ii) a power law forecasting pipeline for global AI energy demand. For location recommendation, we combine regional grid carbon intensity, renewable share, and data center Power Usage Effectiveness (PUE) into a unified scoring model across 100+ regions from major cloud providers. For a reference workload (8*A100, 100h), estimated emissions in our sampled regions range from 7.74kg to 272.00kg CO2. Selecting the best region instead of the worst corresponds to a 97.2% reduction relative to the worst case. Ablation shows that ranking by renewable share alone can select regions with higher CO2 emissions than rankings that include grid carbon intensity. For forecasting, we fit a power law relation between parameter count and training energy using 26 anchor models. We combine this fit with scenario assumptions on model growth, hardware efficiency, and training frequency, and evaluate sensitivity to inference ratio and ecosystem scaling. Across scenarios, projected 2030 demand ranges from 7TWh to 1,436TWh under the stated assumptions, highlighting the importance of deployment choices, model scaling discipline, and transparent energy reporting.

22.
arXiv (CS.AI) 2026-06-15

tap: A File-Based Protocol for Heterogeneous LLM Agent Collaboration

作者:

arXiv:2606.14445v1 Announce Type: cross Abstract: Existing multi-agent software development systems have proposed many forms of agent collaboration, including role-based collaboration and automated code review. However, many systems assume a common runtime, a central conversation server, or the same API family. Under these assumptions, LLM agents from different vendors cannot easily exchange messages directly from their own execution environments while dividing development and review work on a shared codebase. This paper presents tap, a file-based collaboration protocol that allows Claude (Anthropic) and Codex (OpenAI) to collaborate on one codebase without shared memory or an identical runtime. The core of tap is a file-first design that preserves markdown files with metadata as original messages, combines a file inspection path (file communication, Tier 1) with real-time notification paths for Claude and Codex (real-time communication, Tier 2), and isolates work through separate git worktrees. Even if real-time notification fails or a receiver restarts, the message file remains available and the same content can be inspected again. In a 27-day, 37-generation self-applied operation where tap was used to develop and review itself, we collected 209 tap-related pull requests and 717 operational artifacts. An analysis of 375 review artifacts showed that the share of reviews recording at least one defect or requested change was 69.8% for heterogeneous model pairs and 53.1% for homogeneous model pairs. These results show that tap, which combines file-based message preservation with real-time notification, operates in a real production repository, and that combining heterogeneous models and execution environments can broaden review perspectives. tap is distributed as the open-source npm package @hua-labs/tap (v0.5.2).

23.
arXiv (math.PR) 2026-06-16

Sharp connectivity bounds for the vacant set of random interlacements

arXiv:2504.02777v2 Announce Type: replace Abstract: We consider percolation of the vacant set of random interlacements at intensity $u$ in dimensions three and higher, and derive lower bounds on the truncated two-point function for all values of $u>0$. These bounds are sharp up to principal exponential order for all $u$ in dimension three and all $u \neq u_\ast$ in higher dimensions, where $u_*$ refers to the critical parameter of the model, and they match the upper bounds derived in the article arXiv:2503.14497. In dimension three, our results further imply that the truncated two-point function grows at large distances $x$ at a rate that depends on $x$ only through its Euclidean norm, which offers a glimpse of the expected (Euclidean) invariance of the scaling limit at criticality. The rate function is atypical, it incurs a logarithmic correction and comes with an explicit pre-factor that converges to $0$ as the parameter $u$ approaches the critical point $u_*$ from either side. A particular challenge stems from the combined effects of lack of monotonicity due to the truncation in the super-critical phase, and the precise (rotationally invariant) controls we seek, that measure the effects of a certain "harmonic humpback" function. Among others, their derivation relies on rather fine estimates for hitting probabilities of the random walk in arbitrary direction $e$, which witness this invariance at the discrete level, and preclude straightforward applications of projection arguments.

24.
arXiv (CS.LG) 2026-06-19

3D-DLP: Self-Supervised 3D Object-Centric Scene Representation Learning

arXiv:2606.19451v1 Announce Type: new Abstract: We introduce 3D-DLP, a self-supervised object-centric representation learning model that decomposes scene-level RGB-D or voxel observations into a set of 3D latent particles. Building on the Deep Latent Particles (DLP) framework, each particle encodes disentangled attributes, including 3D keypoint position, bounding box dimensions, and appearance features, and represents a distinct entity in the scene. The model learns interpretable per-particle segmentation maps through an end-to-end self-supervised reconstruction objective. We demonstrate on both simulated and real-world datasets that the learned latent space is interpretable and controllable: by manipulating particle positions and decoding, we can generate novel scene configurations. Furthermore, we show that leveraging these compact 3D latent particles for downstream robotic manipulation improves performance over baselines that either lack explicit 3D information or rely on memory-intensive dense 3D inputs without object-centric structure. Code and videos are available at https://eubooks3003.github.io/3d-dlp.

25.
medRxiv (Medicine) 2026-06-12

Heterogeneity of Treatment Effect of Aspirin and Clinically Significant Bleeding in Older Adults

Aim: The global population of older adults is growing, and older age is linked to higher bleeding risk. Although guidelines discourage aspirin for primary prevention in healthy older adults due to bleeding harms outweighing benefits, many continue taking it without a clear indication. It remains unclear whether all older adults face uniform aspirin-related bleeding risk or if certain subgroups are more vulnerable. Methods: We analyzed data from 19,114 ASPREE trial participants to develop machine learning models using 116 baseline variables. Random forest (RF) and random survival forest (RSF) models predicted 5-year bleeding risk, and participants were stratified into low, intermediate, and high-risk groups based on the 20th and 80th percentiles of predicted risk. We assessed heterogeneity of treatment effect (HTE) by testing treatment-by-risk group interactions on the relative scale using Fine-Gray models, and on the absolute scale using observed 5-year cumulative incidence rates. Results: Over a median follow-up of 4.7 years, 626 major bleeding events occurred. The RF model had moderate discrimination (AUC = 0.65, 95% CI: 0.63-0.67) and good calibration (Brier = 0.032, 95% CI: 0.029-0.034). Statistically significant HTE was observed on the relative scale, with the greatest relative increase in bleeding risk seen in the low-risk group (subdistribution hazard ratio = 2.26, 95% CI: 1.27-4.01). On the absolute scale, low-risk participants experienced higher bleeding with aspirin (absolute risk difference (ARD) = 1.17%, 95% CI: 0.37-1.95), but heterogeneity in ARDs was not statistically significant (Cochran's Q p > 0.45). Similar findings were observed when using the RSF model. Conclusion: Participants at lowest baseline bleeding risk experienced the greatest relative increase in bleeding risk with aspirin therapy. We found statistically significant heterogeneity in treatment effects on the relative but not absolute scale. These findings support an individualized, risk-based approach to aspirin therapy decision-making in older adults.