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01.
arXiv (CS.CV) 2026-06-17

Edit3DGS: Unified Framework for Dynamic Head Editing via 2D Instruction-Guided Diffusion and 3D Gaussian Splatting

We present Edit3DGS, a unified framework for dynamic 3D head editing that integrates 2D instruction-guided diffusion with 3D Gaussian splatting. Unlike prior approaches that separately address frame-based edits or static 3D reconstruction, our method couples semantic controllability in the image domain with photorealistic, temporally consistent 3D representations. Given an input video, editable facial regions are masked and modified using a text-conditioned diffusion model to support fine-grained operations such as expression transformation, attribute modification, and appearance refinement. The edited frames are then aggregated through 3D Gaussian splatting to produce a coherent, high-fidelity avatar that preserves both identity and motion dynamics. To enforce consistency, Edit3DGS incorporates multi-view batch editing and lightweight inpainting strategies that recover lost expressions across timesteps. Experimental results demonstrate that our framework enables controllable, artifact-free head editing with smooth temporal transitions, offering practical applications in virtual avatars, immersive communication, film production, and interactive media.

02.
arXiv (CS.LG) 2026-06-18

Knockoffs-based False Discovery Rate Control and Simplification for Deep Neural Networks

arXiv:2606.04404v2 Announce Type: replace-cross Abstract: The deep neural network is a widely used framework in machine learning that has been widely applied in various fields. However, deep neural networks often involve a large number of parameters and inputs, many of which may be irrelevant to the goal or true output. These parameters and input variables not only increase computational complexity, but also contribute to additional computational cost. One solution to this problem is knockoff methods, which have proven successful in controlling false discovery rates in high-dimensional regression. Building on the knockoff methods and using the regularised neural network, this paper proposes three variable screening methods under the condition of controlling false discovery rates: one layer filter, multiple layers filter, and variable weight aggregation filter. In comparison with existing algorithms, we find that our algorithms show satisfactory performance.

03.
arXiv (CS.AI) 2026-06-15

History of the Muddy Children Puzzle

arXiv:2606.13703v1 Announce Type: new Abstract: The Muddy Children Puzzle is a puzzle about knowledge and ignorance that has been inspiring for the development of epistemic logic. Who came up with it first? This is unclear. We trace the origin of the Muddy Children Puzzle through logical and literary publications over the past two centuries. The puzzle inspired a numerous variations such as involving numbers or coloured hats. We also present a novel hats puzzle involving self-reference.

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

Externalizing Research Synthesis and Validation in AI Scientists through a Research Harness

arXiv:2606.18874v1 Announce Type: new Abstract: AI systems can increasingly automate scientific workflows, but the reasoning that links prior evidence, generated ideas, experiments and final claims often remains implicit inside model inference. Here we introduce Xcientist, a research harness that externalizes research synthesis and experimental validation into inspectable, contract-governed processes. Xcientist organizes literature evidence, idea states, implementation plans, ablation records and repair traces as persistent research artifacts, so that generated mechanisms can be grounded, executed, tested and revised without losing their evidential basis. We identify claim drift as a failure mode of automated research, where runnable artifacts no longer support the mechanism originally claimed. Across training-free memory systems, graph-structured traffic forecasting and multi-scale physics-informed neural networks, Xcientist preserves traceable trajectories from problem formulation to mechanism design, validation and bounded revision. These results suggest that AI scientists should be evaluated not only by their final artifacts, but by whether their synthesis and validation processes remain attributable, inspectable and scientifically accountable.

05.
medRxiv (Medicine) 2026-06-11

Polygenic risk scores associate with asthma phenotypes and proteomic analyses implicate IL1R1 in two family-based studies

Despite its high prevalence and the discovery of hundreds of genetic associations, the genetic determinants and heterogeneous manifestations of asthma remain incompletely understood. Incorporating polygenic risk scores (PRS) into asthma research offers a powerful approach to quantify inherited susceptibility, refine risk profiles, and advance mechanistic understanding of disease development. For this study, we leveraged whole-genome sequencing (WGS) data from two family-based cohorts of childhood asthma - the Genetics of Asthma in Costa Rica Study (GACRS) and the Childhood Asthma Management Program (CAMP) - to examine the transmission profiles of externally derived asthma PRS and their associations with clinical phenotypes in children with asthma. To further elucidate molecular mechanisms, we integrated large-scale external genome-wide association study (GWAS) summary statistics and genetic prediction models of protein abundance in a two-step proteome-wide association study (PWAS) of asthma. Our findings provide robust evidence supporting the validity of externally derived asthma PRS (asthma PRS association p-value p={10}^{-24} [GACRS and CAMP trios combined] for the Global Biobank Meta-analysis Initiative [GBMI]) and reveal consistent associations with spirometry measures and atopy markers across both studies, as 13 of 21 traits (62%) were significantly associated with the GBMI-PRS in the meta-analysis after multiple-testing correction. Moreover, the results of the integrative proteomic analysis implicate IL-1 signaling in the etiology of asthma, reinforcing the candidacy of IL1R1 antagonists for drug repurposing.

06.
PLOS Computational Biology 2026-06-04

Cell differentiation can underpin the reproducibility of morphogenesis

by Dominic K. Devlin, Austen R. D. Ganley, Nobuto Takeuchi Morphogenesis of complex body shapes is reproducible despite the noise inherent in the underlying morphogenetic processes. However, how these morphogenetic processes work together to achieve this reproducibility remains unclear. Here, we ask how this reproducibility is achieved by evolving complex morphologies in a multi-scale, computational model. Each morphology consists of a population of cells on a two-dimensional grid using the Cellular Potts Model framework. Each cell contains a genome that encodes a gene regulatory network, morphogens for cell-cell signalling, and proteins that determine cell behaviours. By repeatedly simulating our model with different initial conditions under selection for shape complexity, we obtained a “zoo” of evolved morphologies. We find that these evolved, complex morphologies are reproducible in a sizeable fraction of simulations, despite no direct selection for reproducibility. We show that high reproducibility is caused by spatially segregating moving cells that “shape” morphologies from stationary cells that “maintain” morphologies during morphogenesis. Strikingly, most highly reproducible morphologies also evolved cell differentiation, where proliferative, moving progenitor cells irreversibly differentiate into non-dividing, stationary differentiated cells at tissue boundaries. These results suggest that cell differentiation observed in natural development plays a fundamental role in morphogenesis in addition to the production of specialised cell types. This previously unrecognised role of cell differentiation has major implications for our understanding of how morphologies are generated and regenerated.

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

ESBMC-PLC: Formal Verification of IEC 61131-3 Ladder Diagram Programs Using SMT-Based Model Checking

PLCs execute safety-critical programs across industrial sectors. The dominant PLC notation, ladder diagram (LD) per IEC 61131-3, remains absent from formal verification: SMT-based model checkers cannot process LD's rung-and-coil graphics. This paper presents ESBMC-PLC, the first open-source formal verifier with native LD support (PLCopen XML format), implemented as a new ESBMC frontend. ESBMC-PLC translates LD rungs to GOTO IR, models the PLC scan cycle as a while(true) loop with nondeterministic inputs, and checks safety properties via SMT-based bounded model checking or k-induction. A five-property YAML language (mutual_exclusion, invariant, absence, response, reachability) avoids temporal logic. A survey of 22 studies (2020-2026) identifies four research gaps; ESBMC-PLC closes two of them. Evaluation on 13 benchmarks (6 domains, 3 sources - including deployed CONTROLLINO PLCs and MathWorks Simulink PLC Coder) shows correct classification across 61 properties: all 9 author-constructed programs (Categories A/B) as expected, all 4 vendor programs (Category C) correctly unlabeled, with 8 bugs found (actionable counterexamples), 7 unbounded k-induction proofs, all runs under 60ms on Apple Silicon. Feature comparison with PLCverif shows that ESBMC-PLC is the only open-source tool that combines native LD, k-induction, and SMT bit-vector semantics.

08.
arXiv (CS.AI) 2026-06-11

INFRAMIND: Infrastructure-Aware Multi-Agent Orchestration

arXiv:2606.11440v1 Announce Type: new Abstract: Existing multi-agent LLM orchestration methods, ranging from brute-force ensembles to learned routers, select models and topologies based on task and model features. However, these methods do not consider the runtime state of the serving infrastructure. On shared GPU clusters under concurrent load, this infrastructure blindness causes systematic resource underutilization: preferred models accumulate deep request queues while equally capable alternatives sit idle. In multi-agent pipelines, where each query triggers multiple sequential model calls, these delays then compound across every downstream step. Closing this gap is challenging because the relevant infrastructure signals (queue depths, KV-cache pressure, latencies) are dynamic and noisy, and they must drive three different decisions: planning, per-step routing, and scheduling. We introduce INFRAMIND, a framework that makes the entire multi-agent stack infrastructure-aware. An infra-aware planner conditions topology and role selection on real-time system load and remaining budget, biasing toward simpler graphs under congestion and richer ones at low load. An infra-aware executor then observes per-model queue depths, cache utilization, and response latencies at each agent step to decide which model to call and how deeply to reason; a budget-aware scheduler further reorders each model's queue so that urgent requests are served first. Cast as a hierarchical constrained MDP and solved end-to-end via reinforcement learning, the system learns to balance quality against latency automatically. Across five benchmarks, INFRAMIND delivers up to +7.6 pp accuracy over the prior baseline at low load with up to 7x lower latency, and sustains up to 99.9% SLO compliance under high load where every baseline drops below 50%.

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

Z-Plane Neural Networks: Bounded Geometric Activation Replaces ReLU and LayerNorm

arXiv:2606.15669v1 Announce Type: cross Abstract: Modern deep neural networks rely on Euclidean scalar activations (e.g., ReLU) and global normalization techniques (e.g., LayerNorm) to prevent gradient instability in deep architectures. However, these mechanisms inherently cause dead neurons, discard critical directional information, and destroy the orthogonality of feature representations. Inspired by the frequency-modulation transmission of biological axons, we propose the Z-Plane Neural Network, which maps hidden states into 2D phasor bundles on a hypersphere. We introduce a novel geometric activation function, Radial Bounding($\mathbf{x} / \max(1, \|\mathbf{x}\|_2)$), which limits the energy magnitude while preserving the phase (direction). We demonstrate mathematically that this isotropic activation maintains 1-Lipschitz continuity and prevents gradient vanishing by preserving tangential gradients. Empirically, a 100-layer Z-Plane Multi-Layer Perceptron (MLP)-entirely devoid of ReLU and LayerNorm-successfully converges on the MNIST dataset with 98.34% accuracy and absolute numerical stability, proving that bounded geometric activation alone is sufficient for stable deep learning.

10.
arXiv (quant-ph) 2026-06-12

Measuring Control-Plane Openness in Near-Term Quantum Computing: A Rubric, Its Validation, and an Application to Thirteen Vendor Stacks

arXiv:2605.15233v2 Announce Type: replace Abstract: Public access to pulse-level and control-electronics interfaces in commercial quantum computing has bifurcated. This paper proposes a six-axis rubric for measuring control-plane openness, the layer between gate-level circuit specification and physical control electronics, defined operationally so that the same evidence produces the same grade across vendors. The rubric is validated three ways: a blinded re-grading pass, thirty-nine days after the evidence cutoff, that tests whether the cited evidence and the level definitions alone reproduce the recorded grades; a boundary-case methodology that fixes where each level begins and ends; and a published grading protocol that lets others reproduce and contest any cell. We establish that the rubric measures change rather than describing a snapshot by comparing the catalog against the documented control plane before the February 2025 removal of pulse-level access from IBM hardware, and reporting the cells that moved. The rubric is applied to thirteen commercial vendors across superconducting, trapped-ion, neutral-atom, and photonic modalities as of May 1, 2026, as its first application, and one of the three harms the rubric is designed to detect is demonstrated through a reproduction-access audit of five pre-2025 IBM Qiskit Pulse experiments against the access available on current hardware, carried through to a client-side structural port of the audit's selected target to Rigetti Quil-T. The catalog ships as a separate machine-readable artifact under CC-BY-4.0 with per-cell source URLs (https://doi.org/10.5281/zenodo.20163276). The catalog readings will change as vendor policies shift; the rubric is the contribution that survives them.

11.
arXiv (CS.AI) 2026-06-19

Towards Engineering Scaling Laws with Pretraining Data Composition

arXiv:2606.19781v1 Announce Type: cross Abstract: Neural scaling laws describe how model performance improves as a power law in compute, model size, and dataset size. While well-established for large language models, these relationships are emerging for large models in particle physics. As with language, empirical studies show that the performance scales as a power law. However, unlike natural language or image domains, fundamental physics has high-fidelity simulators that produce synthetic data cheaply. This favors scaling regimes where additional data is cheaper than additional parameters, and allows the pretraining dataset itself to be engineered to influence the scaling. For the task of classifying hadronic jets produced in collisions of high-energy particle beams, we show that the scaling behavior can be engineered towards requiring more data rather than larger models by inclusion of pretraining data which is more diverse and better aligned with the downstream classification task.

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

DYNA-PRUNER: Input-Adaptive Data-Model Co-Pruning for Efficient and Scalable Spatio-Temporal Media Prediction

Spatio-temporal prediction supports radar/satellite nowcasting and city-scale traffic monitoring, but modern models are often too expensive for real-time deployment. This stems from a mismatch between dense computation and strong input-dependent redundancy (e.g., calm seas or clear skies). To enable automated, resource-aware architecture optimization in scalable media analysis, we propose Dyna-Pruner, an end-to-end framework for input-dependent co-pruning of data and model structure. A shared-importance synchronization mechanism generates coupled masks that prune redundant regions and their corresponding computational units (e.g., convolutional filters), yielding per-sample sparse sub-networks at inference time. Experiments on WeatherBench, SEVIR, and TaxiBJ show seamless integration with CNN, RNN, and Transformer backbones, reducing FLOPs by up to $70\%$ and achieving a $2.5\times$ speedup on NVIDIA Jetson AGX Orin with negligible accuracy loss ($

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

Reassessing High-Performing LLMs on Polish Medical Exams: True Competence or Bias-Driven Performance?

Large language models (LLMs) in medicine are mainly evaluated using multiple-choice question answering (MCQA), which can overestimate real clinical ability due to guessing strategies and answer biases. To address these limitations, we introduce an expanded and more challenging benchmark based on Polish medical exams, adding over 15,000 questions, two new domains, and four structural modifications that reduce MCQA-specific artifacts and better test reasoning. We evaluate 21 LLMs and show that evaluation design strongly affects results. Under our harder setup, the best model (Qwen3.5-122B) drops by 28.4 and 31 pp on English and Polish exams, respectively. Despite low evidence of data contamination, standard MCQA scores do not reliably reflect true medical competence. To facilitate further research, we make our benchmark publicly available.

15.
arXiv (quant-ph) 2026-06-12

Proper and improper mixed states serve as different prior beliefs for quantum state retrodiction

arXiv:2502.10030v2 Announce Type: replace Abstract: A mixed quantum state can be taken as capturing an unspecified form of ignorance; or as describing the lack of knowledge about the true pure state of the system ("proper mixture"); or as arising from entanglement with another system that has been disregarded ("improper mixture"). These different views yield identical density matrices and therefore identical predictions for future measurements. But when used as prior beliefs for inferring the past state from later observations ("retrodiction"), they lead to different updated beliefs. This is a purely quantum feature of Bayesian agency. Based on this observation, we establish a framework for retrodicting on any quantum belief and we prove a necessary and sufficient condition for the equivalence of beliefs. We also illustrate how these differences have operational consequences in quantum state recovery.

16.
arXiv (quant-ph) 2026-06-19

Effective Faraday interaction between light and Helium-3 nuclear spins in a multi-pass cell

arXiv:2606.20328v1 Announce Type: new Abstract: Helium-3 nuclear spins form an exceptionally stable quantum system with extremely long coherence time, offering exciting opportunities for quantum technologies. In particular, nuclear spin-squeezed states promise enhanced precision for sensing tasks and tests of new physics. A central challenge for all these applications is the realization of a controllable light-nuclear spin interface. Here we experimentally demonstrate such an interface by exploiting metastability-exchange collisions in a low-pressure helium-3 gas cell at room temperature. A radio-frequency discharge produces a small population of metastable atoms that both enables efficient optical pumping and mediates an effective Faraday interaction between the collective nuclear spin and an optical probe. We quantitatively characterize the strength of this interaction as a function of the nuclear polarization, applied magnetic field, and probe-beam parameters. Moreover, we show that using a multi-pass cell enhances this interaction by effectively increasing the optical depth. Extrapolating to a tenfold increase of the probe power used in the present experiment, we project a measurement-induced squeezing rate of 0.52 s$^{-1}$. Our results provide a practical pathway for optical access to helium-3 nuclear spins and open prospects for generating long-lived, macroscopic nuclear spin-squeezed states for quantum metrology.

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

Posterior Twins: Distributional Behavioral Simulation for Enterprise Decisions

Authors:

arXiv:2606.16415v1 Announce Type: new Abstract: Enterprise behavioral simulation requires more than producing a plausible response. Many decisions depend on the shape of a population under a proposed action: which segments accept, defect, hesitate, or move into risk-sensitive states. This paper introduces Posterior Twins, a memory-grounded digital-twin approach that represents likely behavior as an updated distribution under a specific decision context. We evaluate a family of Twinning Labs behavioral-model operating points on a 226-example held-out behavioral-response benchmark and report both modal accuracy and Wasserstein-1 distance. The results show that modal accuracy and distributional fidelity identify different operating regimes. TL-Twin Alpha achieves the lowest observed Wasserstein-1 distance in the reported result set ($W_1 = 1.16$), while TL-Twin Delta and TL-Twin Gamma provide balanced operating points near the modal-accuracy frontier. The paper frames these results as a systems result: governed memory, behavioral model routing, scenario orchestration, distributional aggregation, and auditability are necessary for turning simulated behavior into reusable enterprise decision evidence.

18.
Nature (Science) 2026-06-08

GPR15-guided CD8<sup>+</sup> T regulatory cells control intestinal inflammation

Authors:

Inflammatory bowel disease (IBD) causes chronic suffering from gastrointestinal inflammation and dysfunction that can progress to colon cancer1,2. The disease prevalence is increasing and there is an urgent need to better understand its pathogenic mechanisms to improve treatment. We show that GPR15, a G protein-coupled receptor (GPCR) expressed in immune cells and previously described as an entry co-factor for human and simian immunodeficiency viruses3, is a marker and homing receptor for a subset of intramucosal GPR15-guided regulatory CD8+ T lymphocytes (CD8+ TIGR). Deleterious GPR15 gene variants in humans cause defective homing of CD8+ TIGR and are associated with severe early-onset IBD. Moreover, CD8+ TIGR cells are reduced in the intestinal mucosa of sporadic IBD patients. In mice, GPR15 deficiency impairs colonic homing of CD8+ TIGR cells, leading to accumulation of inflammatory macrophages and increased susceptibility to colitis. CD8+ TIGR cells potently kill macrophages activated by intestinal damage or disease using Fas ligand (FasL) and TNF-related weak inducer of apoptosis (TWEAK). The identification of CD8+ TIGR cells yields new insights into organ-specific immune regulation and potential therapeutics for IBD.

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

Real-Time Execution with Autoregressive Policies

arXiv:2606.13355v1 Announce Type: cross Abstract: Real-time execution, enabled by asynchronous inference that ensures both smooth action trajectories and fast reactivity, is critical for realistic deployments of large-scale Vision-Language-Action models. However, recent work on real-time execution primarily focuses on variants of diffusion policies, even though it is more critical for autoregressive policies given their slower rollout speed in synchronous inference. In contrast, we demonstrate that autoregressive policies can achieve real-time execution by adjusting the tokenization horizon and applying constrained decoding, thereby guaranteeing strict latency bounds that enable multi-trajectory decoding to maximize performance. Across simulated and real-world environments, we find that the autoregressive policy consistently outperforms its equivalent-level flow-matching policy counterpart while achieving significantly improved task completion speeds from synchronous inference. Coupled with the inherent advantages of autoregressive policies, such as faster convergence and better generalizability in instruction-following, these results confirm that autoregressive policies can remain a competitive policy type supporting real-time execution.

20.
arXiv (CS.LG) 2026-06-12

Adjusted Cup-Product Neural Layer

arXiv:2606.13568v1 Announce Type: new Abstract: Many important observables in physics and geometry are cup products of cochains. The adjusted cup product neural layer has been introduced in this paper. It is a neural primitive that hard wires the cup product with an adjustment term from higher gauge theory. This creates a readout that is gauge invariant by design. Their main theoretical result shows that on a closed cycle the output relies entirely on the adjustment coefficient. Setting this coefficient to zero removes the output completely regardless of other parameters. Thus the adjustment is the only source of gauge invariant signal. They prove this observable is a nonzero quadratic form and is exactly invariant under one and two gauge transformations.

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

OCOO-T : A Simple and Scalable Virtual Cell Model for Transcriptional Perturbation Response Prediction

arXiv:2606.12838v1 Announce Type: cross Abstract: Predicting single-cell transcriptional responses to genetic, chemical and cytokine perturbations is a fundamental challenge in computational biology and AI Virtual Cell (AIVC) modeling, with direct implications for drug discovery and the elucidation of gene regulatory networks. Existing approaches often rely on auxiliary cell-state encoders, hierarchical variational autoencoders, dedicated Transformer encoder-decoder modules, or gene-interaction priors to compress high-dimensional expression profiles into latent representations. While effective, these designs increase architectural complexity and may limit scalability and generalizability. This paper introduces OCOO-T, a minimalist flow-matching-based AIVC model for transcriptional perturbation response prediction. OCOO-T utilizes a vanilla Transformer stack that operates directly on continuous gene expression profiles and formulates perturbation response prediction as a continuous-time denoising process. Perturbation embeddings, dosage information, and cell-line/cell-type specificity are integrated through adaptive layer normalization and in-context tokens. Comprehensive evaluations on Tahoe100M, Replogle, and PBMC benchmarks demonstrate that OCOO-T achieves state-of-the-art performance across diverse perturbations and cell types while effectively scaling to long transcriptional profiles through patching and depatching of cellular contexts. By leveraging the simplicity of Transformer-based denoising for single-cell omics, OCOO-T provides an effective and scalable framework for in-silico cellular simulation.

22.
arXiv (CS.LG) 2026-06-19

The Representational Limit of Scalar Interactions: An Interventional Decomposition

arXiv:2606.19410v1 Announce Type: cross Abstract: Signed pairwise interaction scores fundamentally conflate uniqueness (U), redundancy (R), and synergy (S). We prove this on a minimal 3-way XOR structural causal model: faithful indices such as Shapley-Taylor return zero per pair, whereas projective indices such as Shapley Interaction spread the third-order effect into pair scalars that conflate the three mechanisms. We introduce Stochastic Hi-Fi, a post-hoc, retraining-free predictability decomposition that estimates per-feature U/R/S profiles by interventional masked inference. The estimator provides exact interventional semantics, finite-sample Monte Carlo bounds, strict variance reduction from coupled diamond sampling, and uniform finite-vocabulary convergence. Across tabular SCMs, Stochastic Hi-Fi recovers structure missed by scalar baselines (up to 411x larger interaction-magnitude recovery ratios). It also separates redundant and synergistic heads in the GPT-2 IOI circuit. On NIH ChestX-ray14, Stochastic Hi-Fi matches GradCAM on Pointing Game and improves substantially on Deletion AUC.

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

Question-Aware Evidence Ledgers for Video Relational Reasoning

The VRR-QA challenge evaluates visual relational reasoning in videos, where answers often depend on implicit spatial relations, event boundaries, target identity, and dialogue context rather than a single salient frame. We present a test-time reasoning pipeline built around a strong GPT-5.5 video QA solver and a set of question-aware evidence ledgers. The initial solver answers each question from a uniform video representation, while routed ledgers are prompted to make the required targets, count units, reference frames, and temporal or spatial scope explicit for counting, spatial, endpoint, viewpoint, and dialogue reasoning. External tools such as open-vocabulary detection, depth cues, pair crops, ASR, and scene-graph ledgers are used only as evidence sources. A conservative gate keeps the current answer unless independent evidence uniquely supports a different option. The final evidence-gated pipeline achieves 92.95% overall accuracy and 93.79% macro accuracy on the challenge test split.

24.
arXiv (CS.CL) 2026-06-17

Smarter edits? Post-editing with error highlights and translation suggestions

As MT quality increases, interest in enhanced post-editing features such as QE-derived error highlights is growing, yet evidence for their usefulness remains limited. In this work, we explore the usefulness of LLM-derived error highlights and correction suggestions based on automatic post-editing (APE). We conduct a study where professional translators (En-Nl) post-edit translations using APE error highlights and correction suggestions and compare productivity, quality and user experience to regular PE and PE with QE-derived highlights. While no condition yielded productivity or quality gains compared to regular PE, APE highlights were better received than QE-derived highlights, and correction suggestions improved overall user experience.

25.
medRxiv (Medicine) 2026-06-16

MRMU: A New Paradigm for Mendelian Randomization by Accounting for Measured Covariates and Unmeasured Confounders

Mendelian randomization (MR) is a powerful approach for causal inference, however, its reliability is frequently compromised by unadjusted covariates and unmeasured confounders, such as unmeasured pleiotropy and sample structure. To address these challenges, we introduce MRMU, a novel paradigm for the MR framework. Unlike traditional single-variable or multivariable MR methods, MRMU selects instrumental variables only from the exposure of interest and estimates one exposure effect at a time, while jointly accounting for measured covariates and unmeasured confounders. This design improves the reliability of MR analyses. In simulations and real data, MRMU achieved better type I error control, higher statistical power, and more accurate effect estimation than existing MR methods. Applying to coronary artery disease (CAD), MRMU identified robust cardiometabolic risk factors, including LDL-C, APOB, systolic blood pressure, body mass index, and smoking initiation, with consistent evidence across multiple CAD datasets. In contrast, traits such as HDL-C, height, and educational attainment, which were found to be significant by existing MR methods, were no longer supported by MRMU. MRMU further supported blood pressure-related traits, rather than lipid traits, as the more relevant pathway linking urate to CAD. Finally, by integrating large-scale plasma proteomics data, MRMU identified candidate CAD drug targets beyond established HMGCR- and PCSK9-related pathways, highlighting its utility for therapeutic target prioritization.