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01.
arXiv (CS.AI) 2026-06-12

MP3: Multi-Period Pattern Pre-training forSpatio-Temporal Forecasting

arXiv:2606.13119v1 Announce Type: cross Abstract: Spatio-Temporal forecasting is crucial in diverse fields, such as transportation, climate, and energy. Urban spatio-temporal data exhibits temporal mirage: similar short-window inputs have divergent future trends, and vice versa. Existing spatio-temporal graph neural networks (STGNNs) cannot effectively identify such mirages. We argue that the core reason lies in the short-window inputs that have incomplete period observation, heterogeneous global spatial correlation, and cross-period superposition causality. To bridge this gap, we develop a novel Multi- Period Pattern Pre-training (MP3), a plug-and-play pre-training plugin for distinguishing temporal mirages. MP3 presents two core innovations: (1) The multi-period pattern learning is designed to learn multi-period patterns from long time series. Specifically, multi-period temporal modeling leverages edge convolution to identify different multi-period patterns. Multi-period spatial modeling uses a bottleneck project and a global memory bank to capture heterogeneous global spatial relations efficiently. Cross-period pattern interaction employs a causality-enhanced Transformer to capture dependencies across different period patterns. (2) This plugin can seamlessly integrate into existing STGNN backbones to strengthen their forecasting performance. The experiment on five STGNN baselines across five real-world datasets (including a large-scale dataset CA) verify the effectiveness, superior scalability and strong adaptability of MP3, which brings consistent and robust performance improvements across all evaluated baselines. On average, MP3 reduces the MAE 4.7% and the RMSE 5.0%. The code can be available at https://github.com/YAN-outlook/MP3.

02.
arXiv (CS.LG) 2026-06-11

Breaking the Ice: Analyzing Cold Start Latency in vLLM

arXiv:2606.07362v2 Announce Type: replace Abstract: As scalable inference services become popular, the cold start latency of an inference engine becomes important. Today, vLLM has evolved into the de facto inference engine of choice for many inference workloads. Although popular, due to its complexity and rapid evolution, there has not been a systematic study of its startup latency. With major architectural innovations such as the V1 API and the introduction of torch.compile, this paper presents the first detailed performance characterization of vLLM startup latency. We break down the startup process into six foundational steps and demonstrate that it is predominantly CPU bound. Each step exhibits consistent and interpretable scaling trends with respect to model-level and system-level parameters, enabling fine-grained attribution of latency sources. Building on these insights, we develop a lightweight analytical model that accurately predicts vLLM startup latency for a given hardware configuration, providing actionable guidance for resource planning in large-scale inference environments. All benchmarking datasets, analysis tools, and prediction scripts are open sourced at https://github.com/upb-cn/vllm-startup-profiler.

03.
arXiv (CS.AI) 2026-06-19

Science Earth: Towards A Planet-Scale Operating System for AI-Native Scientific Discovery

arXiv:2606.01316v2 Announce Type: replace Abstract: Scientific discovery demands intelligence, perseverance, and serendipity across vast search spaces. Today, top scientific capabilities remain siloed–one AI system for biological analysis, another for clinical reasoning, mathematical derivation, or materials simulation–and no pre-designed team can anticipate every skill a question will need. Science Earth is a planet-scale scientific runtime in which any capability–a simulation cluster, a wet-lab robot, a proof engine, a single-cell pipeline–can connect to any other, with collaboration structure emerging from the question itself. Its underlying EACN protocol lets capabilities discover one another, negotiate task ownership, and adjudicate across incompatible evidentiary standards without prior knowledge of who will meet whom. This shifts the organizing challenge from workflow design to open-ended connectivity. Two runs validate this under structurally distinct conditions. In a trans-Pacific higher-order Kuramoto synchronization study, agents identified and corrected a closure-ratio assumption in Ott-Antonsen analytic theory that fails outside the Lorentzian limit, within thirty minutes. In an eight-agent single-cell run on the 4.88M-cell Kang 2024 pan-cancer atlas, heterogeneous capabilities coupled over a 64.9-hour window with one structural external instruction, producing three new result layers and anchoring findings against an independent wet-lab study on an adjacent CCR8- TIGIT+ Treg subset. These cases are a first empirical reading, not a benchmark sweep. They show that when AI capabilities are truly connectable and coordination emerges from the problem, scientific reasoning becomes a distributed, self-correcting process–a step towards scaling AI-native discovery to the planet.

04.
arXiv (CS.CV) 2026-06-11

DIRECT: When and Where Should You Allocate Test-Time Compute in Embodied Planners?

Vision-Language Models (VLMs) are increasingly deployed as high-level planners for embodied agents, with an emerging strategy of scaling test-time compute to improve capability. However, we observe that doing so increases latency, token usage, and FLOPs while yielding uneven, often diminishing gains in downstream success, limiting where embodied agents can be deployed. We argue that choosing when and where to spend test-time compute is central to bringing frontier performance to the real world. We introduce DIRECT, a routing framework that uses multimodal scene context to allocate compute per prompt, improving the success–cost Pareto frontier over fixed model selection. Across three dominant scaling axes, namely chain-of-thought depth, model size, and memory history, our experiments on VLABench and RoboMME show that test-time compute is not a uniform lever: different axes yield qualitatively distinct capability gains. We validate these insights on a physical Franka arm in a DROID setup spanning zero-shot manipulation and long-horizon chaining, where our router matches or exceeds a stronger model's success rate at up to 65% lower average latency. Ultimately, our results show that naively scaling test-time compute is wasteful, and that DIRECT can provide frontier-level embodied planning in robotic systems at a fraction of the cost. Project page can be found at jadee-dao.github.io/direct/.

05.
arXiv (CS.AI) 2026-06-16

SorryDB: Can AI Provers Complete Real-World Lean Theorems?

arXiv:2603.02668v2 Announce Type: replace Abstract: We present SorryDB, a dynamically-updating benchmark of open Lean tasks drawn from 78 real world formalization projects on GitHub. Unlike existing static benchmarks, often composed of competition problems, hillclimbing the SorryDB benchmark will yield tools that are aligned to the community needs, more usable by mathematicians, and more capable of understanding complex dependencies. Moreover, by providing a continuously updated stream of tasks, SorryDB mitigates test-set contamination and offers a robust metric for an agent's ability to contribute to novel formal mathematics projects. We evaluate a collection of approaches, including generalist large language models, agentic approaches, and specialized symbolic provers, over a selected snapshot of 1000 tasks from SorryDB. We show that current approaches are complementary: even though an agentic approach based on Gemini Flash is the most performant, it is not strictly better than other off-the-shelf large-language models, specialized provers, or even a curated list of Lean tactics.

06.
bioRxiv (Bioinfo) 2026-06-11

An AI-Powered Trisomy 21 Research Assistant

Down syndrome, caused by trisomy 21, increases the risk of diverse co-occurring conditions. With more than 34,000 related publications indexed in PubMed as of early 2026, keeping pace with this expanding literature is challenging. While general-purpose large language models are widely used for information retrieval, they often rely on broad training data rather than specific evidence. Retrieval-augmented generation (RAG) improves rigor and reliability of responses by linking model outputs to source texts. In research, source texts are peer-reviewed articles. Standard implementations treat all manuscript sections equally, allowing background text to rank as highly as experimental results. To focus model outputs on experimentally supported responses, we developed the T21 Research Assistant, a section-aware RAG system that prioritizes Results sections to ground responses in primary experimental evidence. The system draws exclusively from 1,789 open-access Down syndrome publications from PubMed Central, including 327 NIH INCLUDE-funded studies, and uses a multistage pipeline for query validation, retrieval, reranking, synthesis, and citation verification. Built on NVIDIA Nemotron models, it generates structured, cited responses. Evaluation using expert-curated questions demonstrated strong performance, achieving a BERTScore F1 of 0.712 and recall of 0.758, comparable to or exceeding leading proprietary and open-source models. T21 Research Assistant is available at: https://bioinformatics.cuanschutz.edu/t21-res-assi/

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

Wasserstein Equilibrium Decoding for Reliable Medical Visual Question Answering

Small vision-language models (2-8B) are well-suited for clinical deployment due to privacy constraints, limited connectivity, and low-latency requirements favouring on-device or on-premise inference. However, their limited capacity exacerbates the generation of plausible but incorrect outputs. We extend game-theoretic decoding, previously restricted to text-only, closed-ended NLP tasks, to vision-language models for open-ended Medical VQA. We introduce a semantically aware Wasserstein stopping criterion that replaces lexical order matching, enabling convergence based on semantic consensus among near-synonymous candidate answers and avoiding unnecessary iterations caused by clinically equivalent ranking swaps. On VQA-RAD and PathVQA, we obtain consistent, statistically significant improvements over greedy and discriminative baselines. On VQA-RAD, we improve Qwen3-VL-2B by +3.5 percentage points (p < 0.01), surpassing the greedy 4B model, with similar trends at larger scales. On PathVQA, Gemma-3-4B with BDG matches MedGemma-4B under greedy decoding despite no domain-specific fine-tuning. At accuracy parity with classic BDG, the Wasserstein criterion reduces average convergence iterations by approximately 20%, improving inference efficiency while preserving the game-theoretic equilibrium behaviour. Code is available at https://github.com/luca-hagen/ Wasserstein-BDG-medical-VQA.

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

Overcoming Labelled Data Scarcity for Defect Classification in Scanning Tunneling Microscopy

arXiv:2506.01678v2 Announce Type: replace-cross Abstract: Scanning tunnelling microscopy (STM) is a powerful technique for imaging surfaces with atomic resolution, providing insight into physical and chemical processes at the level of single atoms and molecules. A regular task of STM image analysis is the identification and labelling of features of interest against a uniform background. Performing this manually is a labour-intensive task, requiring significant human effort. To reduce this burden, we propose an automated approach to the segmentation of STM images that uses both few-shot learning and unsupervised learning. Our technique offers greater flexibility compared to previous supervised methods; it removes the requirement for large manually annotated datasets and is thus easier to adapt to an unseen surface while still maintaining a high accuracy. We demonstrate the effectiveness of our approach by using it to recognise atomic features on three distinct surfaces: Si(001), Ge(001), and TiO$_2$(110), including adsorbed AsH$_3$ molecules on the silicon and germanium surfaces. Our model exhibits strong generalisation capabilities, and following initial training, can be adapted to unseen surfaces with as few as one additional labelled data point. This work is a significant step towards efficient and material-agnostic, automatic segmentation of STM images.

09.
arXiv (CS.LG) 2026-06-17

From Drift to Coherence: Stabilizing Beliefs in LLMs

arXiv:2606.17832v1 Announce Type: new Abstract: Large language models (LLMs) are often hypothesized to perform implicit Bayesian inference, yet a key coherence condition, the martingale property of predictive beliefs, has been shown to fail in controlled synthetic in-context learning settings. We revisit this question in a more typical usage regime: generic multiple-choice question answering. Exploiting the discrete answer space, we compute exact predictive distributions and study belief dynamics induced by autoregressive answer resampling. We introduce prompted predictive resampling (PPR), where an LLM generates a sequence of answers to the same question. Empirically, PPR reveals early-stage belief drift, indicating martingale violations. However, after sufficient resampling steps, the belief process self-stabilizes and converges to a coherent predictive distribution. Based on this observation, we further propose (i) a seed-answer prompting strategy to accelerate stabilization, and (ii) a self-consistency loss that amortizes early-stage drift into the model via fine-tuning. Experiments on multiple-choice QA benchmarks show that our methods substantially reduce belief drift and improve predictive coherence without sacrificing accuracy.

10.
arXiv (CS.LG) 2026-06-24

Project Ariadne: Prompt-Conditioned Route Generation for Synthesis Planning

arXiv:2606.24184v1 Announce Type: new Abstract: Retrosynthetic planning seeks to connect a target molecule to commercially available starting materials through a multistep route. Classical planners construct such routes by iteratively applying single-step reaction models within a search procedure; constrained variants often require specialized algorithms or architectural changes. Direct route generation reframes retrosynthesis as sequence generation, but existing direct-generation methods still train separate models for different planning specifications. We introduce Ariadne, a decoder-only route generator that represents the target, optional constraints, and route in one prompt-completion sequence. On the RetroCast/PaRoutes mkt-cnv-160 benchmark family, one 24-layer checkpoint follows route-depth and required-starting-material prompts: adding the corresponding prompt fields raises Solv-0 by 13.7 points for depth constraints and 31.2 points for required-leaf constraints. Ariadne also improves over DESP, a bidirectional search planner, on required-leaf Top-10 and Solv-0 in 24 GPU-minutes versus 6.8 GPU-hours. On standard reconstruction, Ariadne is comparable to DMS Explorer XL at about half the reported inference time. Across additional target-only benchmarks, Ariadne's clearest gains are on route-holdout reconstruction, whereas AiZynthFinder MCTS remains stronger on several Solv-0 comparisons. These results extend sequence generation from specialist retrosynthesis models to prompt-conditioned structural route generation. We release the codebase and training scripts to support further work, but do not introduce Tier-1–3 route checkers; those remain the main bottleneck before models of this kind can become useful to experimental chemists.

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

Ex-Omni: Enabling 3D Facial Animation Generation for Omni-modal Large Language Models

Omni-modal large language models (OLLMs) aim to unify multimodal understanding and generation, yet extending them to jointly produce speech and 3D facial animation remains largely unexplored despite its importance for natural human-computer interaction. A key challenge is the mismatch between the discrete semantic reasoning of LLMs and the dense temporal dynamics required for 3D facial motion. We propose Expressive Omni (Ex-Omni), an open-source model that augments OLLMs with native speech-accompanied 3D facial animation. Ex-Omni decouples semantic reasoning from temporal generation through a blendshape-aware speech unit generator and a blendshape decoder, where speech units provide temporal scaffolding and hidden speech representations carry facially relevant cues. We further introduce a unified token-as-query gated fusion (TQGF) mechanism for controlled semantic injection, as well as InstructS2SF-1200K, a dataset consisting of 1200K samples for pre-training. Extensive experiments show that Ex-Omni maintains competitive speech understanding and generation ability while achieving better audio-visual synchronization and lower face-generation latency than cascaded pipelines.

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

Towards Responsibly Non-Compliant Machines

arXiv:2606.12147v1 Announce Type: new Abstract: We consider the problem of engineering autonomous intelligent agents that are capable to responsibly not comply with user requests. We argue that machine non-compliance comes in many different forms, and sketch the issues we should pursue on the road of accomplishing responsibly non-compliant intelligent machines. We anchor responsible non-compliance in justifications for task refusal, pathways to override the non-compliance, as well as careful tracking of security risks and liability transfers.

13.
arXiv (CS.CV) 2026-06-24

Multilevel Stochastic Plug-and-Play for Sparse-View CT Reconstruction

Sparse-view computed tomography (SVCT) reduces radiation exposure and acquisition time, but the limited number of projection views makes the reconstruction problem severely ill-posed and leads to streak artifacts when analytical methods are used. Plug-and-Play (PnP) methods provide an effective way to combine data fidelity with learned image priors, while stochastic PnP methods further improve robustness by matching the denoiser input distribution through re-noising. However, these methods often require many iterations to converge, which limits their practical efficiency. In this work, we propose a multilevel (ML) stochastic PnP method for SVCT that accelerates stochastic PnP reconstruction. We highlight that, in the stochastic setting, directly enforcing prior coherence across levels would require accurately estimating fine-level prior gradients through multiple denoiser function evaluations, which substantially increases the computational cost. Motivated by this observation, we perform the multilevel steps in multiresolution analysis (MRA) approximation spaces. This choice is supported by the structure of the wavelet decomposition, which causes the prior-coherence correction to vanish in expectation, thereby avoiding costly estimation of fine-level stochastic prior gradients for the coarse-level corrections. Experiments on SVCT reconstruction show that our method, called Multilevel Stochastic Plug-and-Play (ML-SPnP), achieves reconstruction quality comparable to state-of-the-art methods while substantially reducing runtime.

14.
arXiv (CS.AI) 2026-06-11

The Art of Interrogation: Consistency Amplifies Factuality in Spatial Reasoning

arXiv:2606.11918v1 Announce Type: new Abstract: Current Large Reasoning Models (LRMs) exhibit remarkable general capabilities but significantly underperform in spatial reasoning tasks. Existing approaches treat this gap as a knowledge deficit, relying on supervised fine-tuning (SFT) to ingest labeled spatial data from external vision sources or synthetic engines. In contrast, we argue that for many tasks, spatial reasoning capabilities are already present in pre-trained LRMs but require alignment through logical coherence under geometric 2D and 3D constraints. In this work, we propose a self-supervised reinforcement learning (RL) framework that targets the internal reasoning process without requiring ground-truth annotations. By formalizing the notion of consistency verifiers – reward functions that check for geometric and semantic consistency under transformations – we demonstrate that models can improve their spatial reasoning abilities. We use both image transformations, like flipping, and textual transformations, like swapping the order of objects in the question, and propose a new optimal transport-based RL strategy, OT-GRPO, which is a minimal-matching variant of group relative policy optimization tailored to pairwise verifiers. We show that this label-free consistency training approaches the accuracy of models trained with ground-truth supervision and achieves similar generalization across diverse tasks and data domains.

15.
bioRxiv (Bioinfo) 2026-06-18

A data-driven rediscovery of the specificity-conferring code of adenylation domains in nonribosomal peptide synthetases

Nonribosomal peptide synthetases (NRPSs) are large modular enzymes that assemble structurally diverse peptides, many of pharmacological importance, including antibiotics and immunosuppressants. Within each NRPS module, the adenylation (A) domain selects the substrate to be incorporated, a choice governed by a small set of residues lining the binding pocket. For two decades, computational prediction of A-domain substrate specificity has relied on residue sets - most prominently the Stachelhaus code and the 34-residue "8 Angstrom code" - that were defined by spatial proximity to the substrate rather than by demonstrated predictive value. Here we revisit which residues govern substrate specificity from a purely data-driven perspective. We assembled a non-redundant dataset of 5,366 A-domain sequences (4,693 bacterial and 673 fungal) and used information-theoretic measures to rank alignment positions by their statistical association with substrate identity, without restricting candidate positions to any predefined structural shell. This procedure yielded two compact, kingdom-specific codes: IG15B (15 positions) for bacterial and IG13F (13 positions) for fungal A-domains. Both match or exceed the predictive accuracy of the 34-residue 8 Angstrom code while using fewer than half its positions, and both independently recover the majority of the classical Stachelhaus positions. Notably, our analysis identifies four positions (242, 280, 281, and 284) that lie outside all conventional codes yet carry non-redundant specificity information and co-localize with classical determinants on two helices flanking the binding pocket. These positions provide new candidate sites for the rational engineering of A-domain specificity.

16.
arXiv (CS.LG) 2026-06-24

A Robust Model-Based Approach for Continuous-Time Policy Evaluation with Unknown Lévy Process Dynamics

arXiv:2504.01482v3 Announce Type: replace-cross Abstract: This paper develops a model-based framework for continuous-time policy evaluation (CTPE) in reinforcement learning, incorporating both Brownian and Lévy noise to model stochastic dynamics influenced by rare and extreme events. Our approach formulates the policy evaluation problem as solving a partial integro-differential equation (PIDE) for the value function with unknown coefficients. A key challenge in this setting is accurately recovering the unknown coefficients in the stochastic dynamics, particularly when driven by Lévy processes with heavy tail effects. To address this, we propose a robust numerical approach that effectively handles both unbiased and censored trajectory datasets. This method combines maximum likelihood estimation with an iterative tail correction mechanism, improving the stability and accuracy of coefficient recovery. Additionally, we establish a theoretical bound for the policy evaluation error based on coefficient recovery error. Through numerical experiments, including a real-data BTC price experiment, we demonstrate the effectiveness and robustness of our method in recovering heavy-tailed Lévy dynamics and verify the theoretical error analysis in policy evaluation.

17.
arXiv (math.PR) 2026-06-16

Plateau Gaps of Poisson Correctors Encode Metastable Reaction Rates

arXiv:2606.14789v1 Announce Type: cross Abstract: Metastable reaction rates are commonly inferred from transition-state fluxes, mean first-passage times, or fitted kinetic models. We show that they are directly encoded in the plateau gap of an occupation-time Poisson corrector. For a centered basin-occupation observable, the Poisson corrector develops metastable plateaus in the reactant and product basins, and their separation determines the forward and backward transition rates. This construction requires only the generator, stationary measure, and metastable partition, and therefore does not rely on a predefined transition-state surface. In overdamped and underdamped double-well dynamics, the plateau-gap rate recovers the Kramers, Grote-Hynes, and Pollak-Grabert-Hänggi hierarchy. The same corrector-martingale decomposition yields a reactive-noise density, revealing where stochastic forcing contributes to transitions in configuration or phase space. Thus, reaction rates and their fluctuation sources emerge from a single corrector field.

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

The Degeneracy Distillery

arXiv:2606.23838v1 Announce Type: new Abstract: When two or more parameters or labels produce similar data, they are degenerate, or hard to distinguish. Degeneracies render both label prediction and inverse problems difficult, since both machine learning algorithms and probabilistic samplers rely on the distinguishability of data and its gradients with respect to parameters. However, identifying degeneracies in physical models or real-world datasets can be elucidating about the choice of model or the underlying process that produces the data. We present the degeneracy distillery, a method that (1) detects and (2) resolves degenerate parameter combinations (a) automatically and (b) symbolically, from parameter-data (or parameter-simulation) pairs alone, through estimation and flattening of the Fisher information matrix. By exploring the information geometry of the likelihood, we characterize degeneracies as an intrinsic property of the physical model, requiring no realised data observation. We demonstrate our approach on a range of synthetic and real-world problems, discovering symbolic coordinate transformations that identify the combinations of parameters of a model which yield independent effects on the data. The resulting coordinates flatten the Fisher information in expectation globally, in contrast to posterior-based methods that flatten only at a single point, and substantially reduce the simulation budget required for downstream neural posterior estimation. In test cases we require up to $10\times$ fewer simulations for posterior estimation at matched validation calibration whilst simultaneously gaining physical insight on the system.

19.
arXiv (CS.AI) 2026-06-12

EpiBench: Verifiable Evaluation of AI Agents on Epigenomics Analysis

arXiv:2606.13602v1 Announce Type: new Abstract: We introduce EpiBench, a verifiable benchmark for short-horizon epigenomics analysis. EpiBench evaluates whether agents can make well-defined analysis decisions from realistic workflow states and return deterministically gradable answers. The benchmark includes 106 evaluations across CUT\&Tag/CUT\&RUN, ATAC-seq, ChIP-seq, and DNA methylation workflows. Across 5,088 valid trajectories from 16 model-harness pairs, no system passed a majority of attempts: GPT-5.5 / Pi led at 45.0\% (143/318 attempts; 95\% confidence interval (CI), 36.3–53.7), followed by GPT-5.5 / OpenAI Codex at 39.9\% (127/318 attempts; 95\% CI, 31.6–48.3). Claude Opus 4.8 Max / Pi and GPT-5.4 / Pi each passed 39.0\% (124/318 attempts; 95\% CI, 30.2–47.8 and 31.0–47.0, respectively). Performance varies across assay types, and many failed runs still contain parts of the correct answer. Agents often found the right files and computed useful intermediate results, but failed when the task required deeper, assay-specific scientific judgment.

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

Cross-Silo De-Anonymization Under Local Differential Privacy: Threat Model, Phase Transition, and Coordination Necessity

arXiv:2606.16763v1 Announce Type: cross Abstract: When a person's records appear in k independent data silos, each protected by (epsilon, delta)-differential privacy, standard composition yields a valid (k*epsilon, k*delta)-DP guarantee for the joint output. This worst-case bound, however, does not answer the concrete inference question: at what k can an adversary actually identify a target person? This paper develops the information-theoretic framework needed to answer that question. We introduce cross-silo person-level DP (XSP-DP), a Pufferfish-style privacy notion whose adjacency relation captures all records of a single person across all silos simultaneously, and verify that the standard basic composition bound carries over to this adjacency model. Within this framework we prove that de-anonymization undergoes a phase transition at k* = Theta(log n / epsilon^2) (population size n, per-silo RR parameter epsilon): a Fano lower bound shows any estimator fails for k > k*. An explicit XOR + randomized-response construction demonstrates information synergy: each silo's output is individually uninformative about the target, yet the joint mutual information is strictly positive. For non-coordinated binary randomized-response mechanisms, we prove that de-anonymization is inevitable once k exceeds the threshold, establishing that cross-silo coordination is necessary. These results provide a baseline threat model and Theta-level threshold for cross-silo inference attacks under local DP.

21.
medRxiv (Medicine) 2026-06-15

Bidirectional associations between cannabis use, oddball performance, and P3 event-related potential

Importance: Cannabis use remains prevalent in youth despite concerns regarding its potential impact on cognitive function. Unraveling whether the association between cannabis use and cognition is partially due to preexisting differences or primarily related to use is vital to understanding underlying mechanisms. Objective: To estimate the longitudinal association between cannabis initiation and cognitive trajectories, indexed by task performance and P3 event-related potential (ERP), and to estimate whether baseline cognition is associated with cannabis initiation. Design: Data were analyzed from the ongoing longitudinal Collaborative Study on the Genetics of Alcoholism (COGA) cohort, which was followed up approximately every 2-5 years from 2004 to 2025. Setting: 6 sites across the United States. Participants: Adolescent and young adult offspring of past COGA participants and control families who reported on their cannabis use and who had Visual Oddball (VOP) performance and P3 ERP data (N=4814; 52.4% female, 68.4% white) were grouped based on the timing of cognitive data collection relative to cannabis initiation into Pre-onset (n=2,449; [&ge;]1 assessment) and Post-onset (n=998; [&ge;]3 assessments) subsamples. Main Outcomes and Measures: VOP measures include performance accuracy (%), reaction times (ms), and P3 amplitude (V) and latency (ms) during target trials. Cannabis measures included lifetime use of cannabis (i.e., ever used) and age at first use. Results: High P3 amplitude, and prolonged P3 latency and reaction time were associated with a reduced hazard of cannabis initiation (All Hazards Ratio, [H.R.s]< 0.91, p's

22.
medRxiv (Medicine) 2026-06-17

Characterizing the genetic basis of Cardio-Renal-Metabolic multimorbidity using multivariate genomic modelling

Cardio-renal-metabolic multimorbidity (CRMM) encompasses interrelated conditions affecting the heart, kidneys, and metabolic systems. Although the genetics of individual components are well studied, their shared architecture remains unclear. Here, we performed the largest multi-ancestry multivariate GWAS of CRMM across seven biobanks, including individuals of European (EUR; neff = 353,130), African (AFR; neff = 75,436), and East Asian (EAS; neff = 164,373) ancestry. We identified 287 lead loci in EUR, 30 in AFR, and 202 in EAS. Cross-ancestry analyses revealed ancestry-specific signals and 24 shared loci mapping to FTO and TCF7L2. Drug-repurposing highlighted candidates used for type 2 diabetes and hypertension. Mendelian randomization supported causal links with diverse diseases, while polygenic risk scores showed improved prediction across ancestries. Collectively, these findings advance understanding of CRMM genetics and inform precision medicine.

23.
arXiv (CS.CL) 2026-06-16

Calibrated Triage, Not Autonomy: Confidence Estimation for Medical Vision-Language Models

A vision-language model can answer a question about a medical image fluently and confidently while barely using the image, leaning instead on language priors. In medicine this is the failure that matters most, because the answer looks trustworthy and is not, and the only protection is a confidence score reliable enough to tell the system when to abstain. We ask a deployment question rather than an accuracy one: how much imaging work a model can safely handle alone, and which confidence signal makes that possible. We evaluate seven confidence estimators across five open-weight LVLMs and three medical visual-question-answering datasets spanning broad clinical imaging, radiology, and pathology, with every probe trained only on natural images and applied without adaptation. Recast as bounded selective prediction (automate a case only when confidence clears a threshold, defer the rest), the comparison is cautionary. The standard metrics are poor guides: discrimination barely separates the methods, and the weak calibration of a cheap self-report is cheaply removed by off-domain temperature scaling without changing deployable yield. What distinguishes a usable estimator is the high-confidence region a clinician acts on: the weakest baselines are confidently wrong on 41 to 45 percent of their errors against 1 to 4 percent for the best probe, and no estimator is reliably best across domains or models. Safe handoff is governed at two levels: base-model competence sets a ceiling, so a well-calibrated score recovers roughly a third of radiology cases at a 20 percent error tolerance but almost none of pathology; the confidence layer then decides how much of that ceiling is reachable. The usable role today is calibrated triage, not autonomy: automate the cases a calibrated score marks safe, route the rest to a clinician. We release all outputs, correctness judgments, and confidence scores, with code.

24.
arXiv (quant-ph) 2026-06-15

Merged amplitude encoding for Chebyshev quantum Kolmogorov–Arnold networks: trading qubits for circuit executions

arXiv:2603.02818v3 Announce Type: replace Abstract: Quantum Kolmogorov–Arnold networks based on Chebyshev polynomials (CCQKAN) evaluate each edge activation function as a quantum inner product, creating a trade-off between qubit count and the number of circuit executions per forward pass. We introduce merged amplitude encoding, a technique that packs the element-wise products of all $n$ input-edge vectors for a given output node into a single amplitude state, reducing circuit executions by a factor of $n$ at a cost of only 1–2 additional qubits relative to the sequential baseline. The merged and original circuits compute the same mathematical quantity exactly; the open question is whether they remain equally trainable within a gradient-based optimization loop. We address this question through numerical experiments on 10 network configurations under ideal, finite-shot, and noisy simulation conditions, comparing original, parameter-transferred, and independently initialized merged circuits over 16 random seeds. Wilcoxon signed-rank tests show no significant difference between the independently initialized merged circuit and the original ($p > 0.05$ in 28 of 30 comparisons), while parameter transfer yields significantly lower loss under ideal conditions ($p < 0.001$ in 9 of 10 configurations). On 10-class digit classification with the $8\times8$ MNIST dataset using a one-vs-all strategy, original and merged circuits achieve comparable test accuracies of 53–78\% with no significant difference in any configuration. These results provide empirical evidence that merged amplitude encoding preserves trainability under the simulation conditions tested.

25.
Nature Biotechnology 2026-06-19

Optimized R2 retroelement complexes for DNA insertion into plant genomes

Traditional approaches for DNA insertion into plant genomes using Agrobacterium tumefaciens result in random integration. Newer genetic engineering methods based on nucleases, prime editors, transposases and recombinases extend capabilities but remain constrained with low efficiencies, off-target integration or limited payload size. Here we adapt the avian Taeniopygia guttata R2 protein (R2Tg) for targeted DNA insertion into plant genomes by engineering R2Tg expression cassettes and RNA payloads carrying intron-disrupted reporters, with optimized ribosomal DNA homology arms and untranslated regions. In Arabidopsis thaliana protoplasts, Nicotiana benthamiana leaves and Solanum lycopersicum seedlings, our R2Tg editor system achieves targeted insertion of full-length payloads ranging from 2.2 kb to 5 kb. In Nicotiana benthamiana leaves, integration occurs, on average, at 1 copy per genome, which is 30 times more efficient than that achieved by Cas9 homology-directed repair. This work establishes an R2Tg ribonucleoprotein platform for targeted DNA insertion into plant genomes, using a multicopy genomic safe-harbor site to enable efficient addition of multikilobase genes. R2 retrotransposons are used to integrate DNA into plant and crop 25S ribosomal DNA sites.