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01.
arXiv (CS.CV) 2026-06-25

Expresso-AI: Explainable Video-Based Deep Learning Models for Depression Diagnosis

Given the widespread prevalence of depression and its consequential impact on individuals and society, it is crucial to obtain objective measures for early diagnosis and intervention. As a multidisciplinary topic, these objective measures should be interpretable and accessible to health care professionals, ensuring effective collaboration and treatment planning in the realm of mental health care. Even though current automated depression diagnosis approaches improved over the last decade, a critical gap exists as they often lack affect-specificity and interpretability, limiting their practical application and potential impact on mental health care. In particular, interpretability from temporal activities from videos when deep models are used is not fully explored. In this study, we present a novel framework for analyzing Deep Neural Networks' decisions when trained on facial videos, specifically focusing on automatic depression severity diagnosis. By fine-tuning Deep Convolutional Neural Networks (DCNN) pre-trained on Action Recognition datasets on depression severity facial videos from AVEC depression dataset, our framework is able to interpret the model's saliency maps by examining face regions and temporal expression semantics. Our approach generates both visual and quantitative explanations for the model's decisions, providing greater insight into its reasoning. In addition to this interpretability, our video-based modeling has improved upon previous single-face benchmarks for visual depression diagnosis, resulting in enhanced predictive performance. Overall, our work demonstrates the successful development of a framework capable of generating hypotheses from a facial model's decisions while simultaneously improving depression's predictive capabilities.

02.
arXiv (quant-ph) 2026-06-16

Quantum Nonlocal Games on Graph Ensembles

arXiv:2606.16784v1 Announce Type: new Abstract: Quantum entanglement is one of the most striking discoveries in all of science. This effect allows, for instance, two spatially separated agents to coordinate their actions, without communication, to an extent that is both counter-intuitive, and provably impossible by any other physical means. A recently discovered example is that of mobile agents (players) performing spatial coordination tasks such as rendezvous, where the agents aim to meet on a network without communication. Until now, demonstrations of this advantage have relied on highly idealized conditions: agents are assumed to have complete knowledge of the topography, and experiments have been restricted to simulations using data generated by qubits within a single quantum processor. Here we address both limitations by developing a theory for graph ensembles that capture topographical uncertainty and by experimentally demonstrating the advantage in rendezvous scenarios between physically separated ion-trap systems with access to remote entanglement. Moreover, we simulate a broader set of problems on superconducting hardware. Surprisingly, when players are given the ability to gather more local information the quantum advantage increases – a feat impossible by classical means. Our findings establish a concrete route toward practical quantum advantages in motion coordination problems. More broadly, they point to a new way of using portable quantum devices to enhance collective decision-making in uncertain environments.

03.
arXiv (CS.CL) 2026-06-17

LVLMs and Humans Ground Differently in Referential Communication

For generative AI agents to partner effectively with human users, the ability to accurately predict human intent is critical. But this ability to collaborate remains limited by a critical deficit: an inability to model common ground. We present a referential communication experiment with a factorial design involving director-matcher pairs (human-human, human-AI, AI-human, and AI-AI) that interact with multiple turns in repeated rounds to match pictures of objects not associated with any obvious lexicalized labels. We show that LVLMs cannot interactively generate and resolve referring expressions in a way that enables smooth communication, a crucial skill that underlies human language use. We release our corpus of 356 dialogues (89 pairs over 4 rounds each) along with the online pipeline for data collection and the tools for analyzing accuracy, efficiency, and lexical overlap.

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

MIDS: Detecting Stealthy Masquerade and Tampering Attacks on CAN Bus via Bidirectional Mamba

arXiv:2606.18599v1 Announce Type: cross Abstract: The Controller Area Network (CAN) protocol is the primary communication standard for Electronic Control Units (ECUs) in modern vehicles, but its lack of encryption and authentication exposes it to a range of security threats. Existing intrusion detection systems are largely tuned to fabrication-style attacks (DoS, fuzzing, ID spoofing realised by frame injection), in which detection signals such as per-ID inter-arrival statistics are readily available. We instead address the harder masquerade setting[b37], in which an internal adversary substitutes a legitimate frame in-situ at its original transmission slot, preserving traffic periodicity and rendering traffic-statistic defences ineffective. We propose the Mamba Intrusion Detection System (MIDS), an innovative dual-stream framework that processes CAN identifiers and payloads in parallel and reconstructs their joint temporal semantics through bidirectional selective state-space modelling. To evaluate MIDS, we collected over 100 million CAN frames from a physical Tesla Model 3 across three driving regimes and synthesised 54 masquerade attack variants spanning ID-only, data-only, and combined modifications. MIDS attains an F1 of 96.94\% on this dataset, exceeding the strongest reproducible baseline by more than 8 percentage points, while sustaining a 1.147~ms single-window inference latency – ample headroom for real-time onboard deployment. To verify generalisation, we further evaluate MIDS on four public benchmarks (ROAD, CrySyS, OTIDS, CT\&T) covering both masquerade and injection scenarios; MIDS attains F1 from 93.70\% to 99.61\%, outperforming the strongest of eight reproduced baselines by up to 13.94 percentage points under a unified 5-fold protocol.

05.
arXiv (quant-ph) 2026-06-15

Fulde-Ferrell superfluids in an asymmetric three-component Fermi Gas

arXiv:2602.24006v2 Announce Type: replace-cross Abstract: An asymmetric three-component Fermi gas, featuring Raman-induced spin-orbit coupling between the first and second components and contact interaction only between the first and third components, introduces both spin-orbit coupling and population imbalance-two mechanisms known to stabilize the Fulde-Ferrell superfluids.We systematically study Fulde-Ferrell superfluids in an asymmetric three-component Fermi gas { in two dimensions and at zero temperature} by finding the global minima of the thermodynamic potential. We reveal a new class of composite Fulde-Ferrell superfluids that emerges when strong spin-orbit coupling generates a double-well structure in momentum space within the lower spin-orbit-coupled band. The key features of these composite superfluids are identified.

06.
arXiv (CS.AI) 2026-06-25

Beyond Shapley: Efficient Computation of Asymmetric Shapley Values

arXiv:2606.25103v1 Announce Type: new Abstract: We address the problem of explainability in machine learning models through feature attribution methods. In particular, we consider a variant of Shapley values known as Asymmetric Shapley Values (ASV), which enables the incorporation of causal knowledge into model-agnostic explanations through the use of a causal graph. We show that in certain contexts in which the computation of SHAP is $\#P$-hard, the exact computation of ASV can be done in polynomial time. To extend this algorithmic result, we introduce a notion of equivalence classes over the topological orderings of the underlying causal graph, which is useful to reduce the time to compute ASV. In particular, we present a polynomial-time algorithm (in the number of equivalence classes) to compute it whenever the causal graph is a rooted directed tree. Finally, we develop an algorithm for approximating ASV in arbitrary causal DAGs which relies on a procedure to sample topological orderings uniformly at random. To implement this sampling mechanism we leverage known algorithms as well as simpler alternatives. Our experimental results demonstrate the practical viability of the proposed approach in realistic causal structures.

07.
arXiv (CS.AI) 2026-06-24

A Unified Framework for Runtime Verification and Model-Based Diagnosis in LOLA

arXiv:2606.23720v1 Announce Type: cross Abstract: We present an integrated framework that unifies runtime verification and model-based diagnosis within the stream specification language LOLA. By encoding system descriptions, component health states, and observations into a single stream-based formalism, the approach enables continuous, online fault localization directly alongside fault detection, without requiring separate toolchains. The framework supports both time-invariant and transient faults, and naturally accommodates nondeterministic observations.

08.
arXiv (CS.AI) 2026-06-12

A Zero-shot Generalized Graph Anomaly Detection Framework via Node Reconstruction

arXiv:2606.12673v1 Announce Type: cross Abstract: Cross-domain graph anomaly detection (GAD) aims to identify abnormal nodes in unseen target graphs, showing strong potential in real-world applications with heterogeneous graph data. However, existing methods often depend on dataset-specific feature semantics and structural patterns, which limits their ability to generalize across different domains. To address this challenge, we propose AlignGAD, a zero-shot generalized graph anomaly detection framework. Our framework is built upon three key components: a Global Unification Module that aligns heterogeneous node features and normalizes graph signals in the spectral domain; a Clustering Module that constructs cluster-aware graph views to capture group-level abnormal patterns; and a Node Discrepancy Scoring Module that measures reconstruction discrepancy and aggregates anomaly evidence from different graph views. Experiments on multiple real-world datasets demonstrate the effectiveness of AlignGAD under the zero-shot GAD setting.

09.
arXiv (CS.CV) 2026-06-24

Learning Ego-Centric BEV Representations from a Perspective-Privileged View: Cross-View Supervision for Online HD Map Construction

Bird's-eye-view (BEV) representations derived from multi-camera input have become a central interface for online high-definition (HD) map construction. However, most approaches rely solely on ego-centric supervision, requiring large-scale scene structure to be inferred from incomplete observations, occlusions, and diminishing information density at long range, where perspective effects and spatial sparsity hinder consistent structural reasoning. We introduce Cross-View Supervision (CVS), a representation learning paradigm that transfers geometric and topological priors from an ego-aligned overhead perspective into camera-based BEV encoders. Rather than adding auxiliary semantic losses, CVS aligns representations in a shared BEV feature space and distills globally consistent structural knowledge from a perspective-privileged teacher into the ego-centric backbone. This supervision enhances structural coherence without modifying the inference architecture or requiring overhead input at test time. Experiments on nuScenes using ego-aligned aerial imagery from the AID4AD cross-view extension demonstrate consistent improvements over StreamMapNet while maintaining identical camera-only inference. CVS yields +3.9mAP in the standard $60\times30\,\mathrm{m}$ region and +9.9mAP in the extended $100\times50\,\mathrm{m}$ setting, corresponding to a 44% relative gain at long range. These results highlight perspective-privileged structural supervision as a promising training principle for improving BEV representation learning in HD map construction.

10.
arXiv (CS.LG) 2026-06-25

How Modular Is a Frontier Mixture-of-Experts? A Pre-registered Causal Test in Which Apparent Expert Modularity Mostly Dissolves

arXiv:2606.25092v1 Announce Type: new Abstract: Sparse Mixture-of-Experts (MoE) models route each token to a few of many experts, inviting the hypothesis that experts form functional modules tied to capabilities or languages. We test this causally on Command A+, a frontier open-weights MoE (218B total / 25B active; 128 experts, 8 active, +1 shared). We build a routing-mass atlas, pre-register six family-to-axis hypotheses before any intervention, and ablate each family at inference time against a size-matched random-expert null, measuring whether it selectively breaks its own axis (worst off-target effect at most one third of on-target). Crucially, we test the same families under four metrics and a held-out, independent-corpus run with bootstrap confidence intervals. Our finding is cautionary: robust functional modularity is rare and measurement-dependent. Of six pre-registered families, only one, the Arabic-language family, is a clean selective module that survives an independent corpus and a conservative statistical bar (1/6; a more permissive pre-registered point rule admits 3/6, but that count is threshold-sensitive). Every other family has a real causal effect yet fails selectivity, and its apparent modularity flips with the measurement: with the corpus, the metric, and the statistical bar. A positive control on Qwen3-30B-A3B recovers its published disjoint structure, confirming the method detects modularity when present. The verdict reproduces on the un-quantized BF16 model, ruling out a 4-bit quantization artifact. We conclude that ablation-based modularity verdicts are not safe unless the corpus, metric, and statistical bar are controlled. We release the atlas and ablation data.

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

EvoTrainer: Co-Evolving LLM Policies and Training Harnesses for Autonomous Agentic Reinforcement Learning

arXiv:2606.03108v2 Announce Type: replace Abstract: Autonomous LLM training is often framed as recipe search, which leaves the training harness largely static. This limitation sharpens in agentic RL, where shifting bottlenecks and scalar rewards mask diverse failure modes. We introduce EvoTrainer, an autonomous training framework that co-evolves LLM policies and training-side harnesses through empirical feedback: it diagnoses rollout-level evidence, revises diagnostics, backtests interventions, and accumulates reusable skills. Evaluated on mathematical reasoning, competitive-programming code generation, and repository-level software engineering, EvoTrainer matches or exceeds the human-engineered RL references under the same data, codebase, and evaluation protocol, with the largest gain on long-horizon agentic SWE. Trajectory analyses show that retained strategies diverge across domains, evolving diagnostics prevent invalid high-scoring branches from being promoted, and reusable skills shape later search. Autonomous LLM RL should move beyond recipe search toward joint evolution of policies and the training harnesses that interpret them.

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

GRACE: Gated Refinement for Accurate Causal Edge Discovery in High-Dimensional Time Series

arXiv:2606.23880v1 Announce Type: new Abstract: From climate teleconnections to gene regulation, modern time-series datasets encompass tens or hundreds of interacting variables, making causal discovery increasingly challenging. Constraint-based methods offer statistical rigor but their nonlinear CI tests are infeasible at scale, while score-based alternatives avoid CI testing but require arbitrary thresholds to binarize continuous edge scores. We propose GRACE ($G$ated $R$efinement for $A$ccurate $C$ausal $E$dge discovery), which refines constraint-based discovery using Hard Concrete gates with $L_0$ regularization: each candidate edge has an independent gate whose values concentrate near 0 or 1, yielding a clean bimodal separation that makes the binary decision robust, unlike the narrow, overlapping score distributions produced by $L_1$ and attention-based methods. A fast linear CI skeleton provides high-recall candidates; a single gated model then prunes false positives by learning which edges genuinely improve prediction, with automatic regularization adapted to problem dimensions and skeleton density. Systematic experiments on synthetic benchmarks, spanning diverse graph topologies (scale-free, Erdős-R'enyi, small-world) and dimensionalities up to $d=100$, show that GRACE substantially improves F1 over its base CI method while maintaining high precision, and outperforms attention-based and score-based alternatives. GRACE matches or exceeds expensive nonlinear CI tests at a fraction of the cost ($75\times$ faster). On a real-world river flow dataset, where rainfall confounders, variable propagation lags, and distributional shifts violate standard assumptions, a temporal bootstrap variant of GRACE recovers 9 of 11 causal edges along the Elbe River with only 1 false positive ($F_1 = 0.86$, AUROC${} = 0.99$), reducing the skeleton's 106 false positives by 99%.

13.
arXiv (quant-ph) 2026-06-25

High-sensitivity and high-resolution collaborative determination of birefringence coefficient using weak measurement

arXiv:2504.15571v2 Announce Type: replace-cross Abstract: Precise nanofilm birefringence characterization is essential for high-sensitivity polarization response and strong anti-interference detection in photodetectors. We present a high-sensitivity and high-resolution birefringence coefficient determination system for nm-level membranes based on weak measurement, addressing the sensitivity-resolution trade-off. A tunable bandwidth light source is exploited to achieve simultaneous and complementary measurements of momentum (P-pointer) and intensity (I-pointer), enabling calibration-free operation across various bandwidths, and to realize high-precision phase difference monitoring of the measured membranes. This method maps the birefringence effect to a weak-value amplified signal of spectral shift and light intensity. The optimal resolution, achieved at a spectral width of 6 nm, is $1.12 \times 10^{-8}$ RIU, while the optimal sensitivity is achieved when the light source is a narrow-linewidth coherent laser, reaching 4710 mV/RIU. The linear range of the system covers a broad birefringence coefficient range for crystals, from $10^{-6}$ to 0.1. Furthermore, the auxiliary optical path eliminates substrate interference, achieving a detection limit of birefringence coefficient as low as $10^{-8}$ RIU. This approach, characterized by high precision, high sensitivity, and strong robustness, provides an effective solution for the detection of optical nano-thin membrane parameters.

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

RetailBench: Benchmarking long horizon reasoning and coherent decision making of LLM agents in realistic retail environments

arXiv:2606.15862v1 Announce Type: new Abstract: Large language model (LLM) agents have made rapid progress on short-horizon, well-scoped tasks, yet their ability to sustain coherent decisions in dynamic long-horizon environments remains uncertain. We introduce RetailBench, a data-grounded simulation benchmark for evaluating tool-using LLM agents in single-store supermarket operation. RetailBench models retail management as a partially observable decision process and is designed to support thousand-day-scale simulations. In this environment, agents must manage pricing, replenishment, supplier selection, shelf assortment, inventory aging, customer feedback, external events, and cash-flow constraints. We evaluate seven contemporary LLMs under representative agent frameworks over a 180-day evaluation horizon and compare them with a privileged oracle policy. Results show substantial variation across models: only a small subset survives the full evaluation horizon, and even the strongest LLM runs remain substantially behind the oracle policy in final net worth and sales outcomes. Behavioral analysis attributes these gaps to incomplete evidence acquisition, surface-level decision making, and the lack of a consistent long-horizon policy. RetailBench provides a controlled testbed for studying reliable autonomy in economically grounded long-horizon decision-making.

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

Human genetic evidence is associated with drug approval across therapeutic areas: an observational analysis of 26,278 target-disease pairs with temporal validation and feature ablation

Genetic evidence is enriched among approved drug targets: in an observational analysis of 26,278 target-disease pairs from Open Targets and ChEMBL, targets with any genetic association had a 3.25-fold higher approval rate than those without (OR = 3.25, 95% CI 2.79-3.79, p = 1.91e-42). A target-level analysis accounting for non-independence of pairs sharing the same gene gave OR = 2.79 (bootstrap 95% CI 2.22-3.53); the oncology pair-level OR of 6.72 attenuates to 2.71 at the target level, illustrating how non-independence inflates area-specific estimates. The enrichment replicated in post-2015 approvals (OR = 3.51, p = 1.72e-8). Feature ablation across six evidence types revealed that literature mining alone accounts for most classifier performance (AUPRC = 0.099 versus 0.109 for all features), consistent with temporal leakage from post-approval publications. Excluding literature, remaining evidence types retain above-baseline signal (AUPRC = 0.084, 1.63x baseline). Sensitivity analyses bracket the pair-level OR between 3.25 and 4.93. Genetic evidence alone yields only a 1.0-percentage-point absolute AUPRC gain and the best model has poor calibration; the classifier has limited practical predictive value. We catalogue 1,433 genetically supported Phase 1/2 pairs as a hypothesis-generating resource. All findings are observational.

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

LiFT: Local Search via Linear Programming for Overfitting-Controlled Transformers

This paper proposes a Linear Programming (LP)-based local search framework for fine-tuning pretrained transformer models with explicit control against overfitting. The approach formulates transformer fine-tuning as a bilevel optimization-based regularization problem, in which model parameters and regularization hyperparameters are jointly updated. Information collected during initial warm-up iterations, including validation gradients and training Hessian information, is used to construct a local descent direction by solving an LP that minimizes a scaled directional derivative while preserving training optimality. This validation-aware descent direction enables focused local updates of both parameters and regularization hyperparameters, reducing overfitting without requiring repeated full retraining cycles. The resulting method, termed Linear Programming-based Fine-Tuning (LiFT) for transformers, differs from conventional fine-tuning by systematically identifying task-specific updates rather than relying on heuristic or grid-based hyperparameter selection. Experiments on GPT-2 Small fine-tuned on WikiText-2 demonstrate that LiFT enables effective adaptation through selective tuning of transformer blocks and regularization parameters, yielding consistent improvements in test perplexity across multiple layer configurations and regularization settings, with particularly pronounced gains in overfitting-prone scenarios. Beyond empirical performance, LiFT establishes a principled connection between transformer fine-tuning, bilevel optimization, local search, and regularization theory.

17.
medRxiv (Medicine) 2026-06-16

Cardiac positronium lifetime in human PET: a reproducible right-left ventricular contrast that is not explained by blood oxygenation

Background. Ortho-positronium (o-Ps) lifetime, now measurable in vivo on long-axial-field-of-view (LAFOV) PET/CT, has been proposed as a biomarker of tissue oxygenation and hypoxia. Because o-Ps lifetime is dominated by tissue free-volume structure while the oxygen- specific contribution is small, whether an in-vivo lifetime contrast reflects oxygenation rather than anatomy is an open, identifiability-limited question. Aim. To test the oxygenation hypothesis directly using the heart's natural arterial/venous oxygenation contrast, with a built-in anatomical control. Methods. We re-analysed a public [82Rb]Cl human cardiac LAFOV PET/CT dataset (5.30 x 10^8 evaluated three-photon events). Per-compartment o-Ps lifetimes were extracted with a background-plus-two-component exponentially-modified-Gaussian (EMG) model. The list-mode to image mapping and right/left ventricle (RV/LV) identity were established lifetime-free (the mapping reproduces the provider's reconstructed image at block-correlation 0.998 and wins a joint multi-organ alignment panel). We applied a confound battery: registration stress test, blood-core vs wall, lung-air and wall-myocardium partial-volume, tissue density; and a structure/position-matched control (pulmonary artery, deoxygenated, vs aorta, oxygenated). An isotope-matched 82Rb uniform-quartz reference bounded the instrument's positional behaviour. All results were produced by two independent analysis pipelines. Results. RV o-Ps lifetime exceeded LV by delta tau = +0.304 ns (RV 1.700 +/- 0.172, LV 1.396 +/- 0.130 ns; about 1.4 sigma), in the oxygen-expected direction; the contrast was stable across +/-16 mm registration perturbation (sign preserved in 100% of 342 shifts) and resided in the blood core, not the wall. However, the matched-vessel control was null: pulmonary artery minus aorta = -0.011 +/- 0.344 ns. Lung-air and wall-myocardium partial-volume were disfavoured, and the effect fell within the isotope-matched 82Rb instrumental positional envelope (about 0.1-0.35 ns over 40 mm in uniform material). Conclusion. On this single subject, the cardiac o-Ps lifetime contrast does not provide a clean readout of blood oxygenation: an oxygenation effect of the observed (about 0.3 ns) magnitude is ruled out by the matched control, while a small physiological effect cannot be excluded. We provide a reusable confound-control battery for evaluating future in-vivo o-Ps oxygenation claims. Multi-subject replication with anatomy decoupled from oxygenation is required.

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

PhononBench:A Large-Scale Phonon-Based Benchmark for Dynamical Stability in Crystal Generation

arXiv:2512.21227v3 Announce Type: replace-cross Abstract: In recent years, generative artificial intelligence has made significant advances in the design of crystalline materials, giving rise to approaches based on graph neural networks, diffusion models, and large language models. Existing evaluations commonly follow the stability-uniqueness-novelty (S.U.N.) framework, where stability is primarily assessed using thermodynamic criteria, which do not fully capture the dynamical stability essential for a material's practical existence. Dynamical stability is a key determinant of whether a material can be synthesized and persist, with phonon spectrum calculations serving as the standard for its evaluation. However, the high computational cost of such calculations has prevented large-scale assessment of dynamical stability in generated crystals. In this work, we introduce PhononBench, the first large-scale benchmark for dynamical stability in AI-generated crystals. Leveraging the recently developed MatterSim interatomic potential, which achieves density-functional-theory (DFT)-level accuracy in phonon predictions across more than 10,000 materials, PhononBench enables efficient phonon calculations and dynamical-stability analysis for 133,838 crystal structures generated by 7 leading crystal generation models. PhononBench reveals a widespread limitation of current generative models: unless otherwise specified, all reported dynamical-stability metrics are evaluated at a phonon-frequency threshold of -0.1 THz, with the average dynamical-stability rate across all generated structures being only 32.15%, and the top-performing model, MatterGen, reaching just 45.05%.In addition, we identify 32,995 crystal structures that are phonon-stable across the entire Brillouin zone under a strict threshold of -0.001 THz. In addition, a web-based service is accessible at http://phononbench.cn/, enabling minute-level ultra-fast phonon predictions.

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

Judging Against the Reference: Uncovering Knowledge-Driven Failures in LLM-Judges on QA Evaluation

While large language models (LLMs) are increasingly used as automatic judges for question answering (QA) and other reference-conditioned evaluation tasks, little is known about their ability to adhere to a provided reference. We identify a critical failure mode of such reference-based LLM QA evaluation: when the provided reference conflicts with the judge model's parametric knowledge, the resulting scores become unreliable, substantially degrading evaluation fidelity. To study this phenomenon systematically, we introduce a controlled swapped-reference QA framework that induces reference-belief conflicts. Specifically, we replace the reference answer with an incorrect entity and construct diverse pairings of original and swapped references with correspondingly aligned candidate answers. Surprisingly, grading reliability drops sharply under swapped references across a broad set of judge models. We empirically show that this vulnerability is driven by judges' over-reliance on parametric knowledge, leading judges to disregard the given reference under conflict. Finally, we find that this failure persists under common prompt-based mitigation strategies, highlighting a fundamental limitation of LLM-as-a-judge evaluation and motivating reference-based protocols that enforce stronger adherence to the provided reference.

20.
medRxiv (Medicine) 2026-06-18

Plasma proteomics reveals clinical and mechanistic heterogeneity among individuals who develop coronary artery disease

BACKGROUND: Individuals who develop coronary artery disease (CAD) are clinically and mechanistically heterogeneous, and understanding this variation is crucial for precise risk stratification and tailored interventions. However, the molecular mechanisms that connect these two kinds of heterogeneity remain unclear, limiting progress toward biologically grounded risk stratification and targeted interventions. Here, we investigated the heterogeneity of individuals who develop CAD by leveraging plasma proteomic signatures, placed individuals along continuous metabolic gradients and revealed the molecular programs underlying these patterns, thereby linking mechanistic variation to clinical heterogeneity. METHODS AND RESULTS: From 42,803 UK Biobank participants, including 3,713 individuals who developed CAD within 10 years (incident CAD), we first identified a 320-protein panel from 2,923 baseline proteins that improved prediction of incident CAD beyond clinical risk scores. Using reverse graph embedding, we reduced the proteomic data to two dimensions and mapped each incident case onto the resulting two-dimensional latent proteomic space. These proteomic dimensions show significant associations with cardiometabolic and kidney-related clinical markers. The patterns were replicated in the EPIC-Norfolk study. Phenome-wide Cox regression analyses further linked these proteomic dimensions to 10-year incidence rates for various diseases, including type 2 diabetes, obesity, and chronic kidney disease (CKD). Furthermore, adding the proteomic dimensions to clinical variable-based Cox regression model improved prediction of 10-year incidence of CKD and other diseases, demonstrating the value of proteomic dimensions beyond conventional clinical risk factors. Moreover, individuals with prevalent CAD (diagnosed before proteomic sampling) exhibited high, metabolically adverse dimension values, indicating that these axes capture cumulative metabolic burden. Pathway enrichment analyses implicated altered extracellular matrix organization and immune programs among the proteins contributing to the proteomic dimensions. CONCLUSIONS: Our findings demonstrate that plasma proteomic signatures can dissect the heterogeneity of individuals who develop CAD in continuous phenotypic gradients, improve prediction of CAD and comorbidities, and map underlying biological mechanisms.

21.
PLOS Medicine 2026-05-20

Brain morphology in Anorexia Nervosa and its subtypes: A multi-cohort study of individual participant data

by Fabio Bernardoni, Dominic Arold, Luis Schoppik, Klaas Bahnsen, Ruiyang Ge, Clara Moreau, Lasse Bang, Federico D’Agata, Giovanni Abbate-Daga, Christian K. Tamnes, Iain Campbell, Owen O’Daly, Ulrike Schmidt, Guido Frank, Stefanie Horndasch, Andreas Hess, Arnd Dörfler, Hans-Christoph Friederich, Joe Simon, Angela Favaro, Luca Lavagnino, Christina E. Wierenga, Amanda Bischoff-Grethe, Amy E. Miles, Allan Kaplan, Aristotle Voineskos, Paul A. M. Smeets, Annemarie A. van Elburg, Unna Danner, Sophia I. Thomopoulos, Laura Berner, Neda Jahanshad, Sophia Frangou, Joseph A. King, Paul Thompson, Stefan Ehrlich Background In a recent coordinated meta-analysis of neuroimaging data, we reported gray matter (GM) alterations in acutely underweight patients with anorexia nervosa (AN). Here, we extend these findings by examining individual variation in brain structure within AN, individual-level differentiation between AN and healthy controls (HC), and differences between AN subtypes, with potential relevance for understanding clinical heterogeneity. Methods and findings We analyzed individual-level data from 11 international sites in the ENIGMA Eating Disorders Working Group, including 570 female participants with AN and 739 HC. We examined cortical thickness, cortical surface area and subcortical volumes in AN versus HC using three complementary approaches: (i) group-level differences in a mega-analysis correcting for age effects, (ii) frequencies of extreme deviations (infra-/supranormal; z  1.96) based on normative reference models by the CentileBrain Initiative, and (iii) individual-level classification performance using machine learning. The same analytic framework was applied to compare AN restricting versus binge-eating/purging subtype, additionally correcting for BMI effects.Mega-analyses reinforced previous meta-analytic findings of pronounced and widespread GM deficits in AN compared to HC. Normative modelling revealed that the frequency of infranormal z-scores (23/68 cortical thickness, 13/14 subcortical volume metrics) and supranormal z-scores (35/68 cortical thickness, 17/68 cortical surface area metrics) was significantly higher in AN than expected based on reference data. Individuals with AN could be reliably differentiated from HC using machine-learning classifiers (ROC–AUC = 0.75–0.81). In contrast, neither group-level differences nor frequency of extreme z-scores differed between AN subtypes, and individuals with different subtypes could not be reliably differentiated from each other. Importantly, the observational design cannot distinguish neurobiological differences related to AN from the effects of starvation or low BMI in the AN versus HC analyses. The lack of differences between subtypes does not exclude brain structural differences between AN subtypes that might be detectable with other modalities or analytic approaches. Conclusion Using a mega-analytic approach, we confirm widespread GM deficits in AN, show that these alterations are (in some patients) extreme, and demonstrate that they enable robust classification with superior performance compared to most MRI-based psychiatric classification studies. The absence of differences between AN subtypes may reflect shared neurobiology, though other imaging modalities may reveal distinctions beyond brain structure.

22.
arXiv (CS.LG) 2026-06-18

Shrinkage priors for Bayesian Substitute Confounders

arXiv:2606.18535v1 Announce Type: cross Abstract: Multi-cause observational studies contain information about unmeasured confounding through the dependence structure among causes. However, literal imputation of the unobserved confounder is often more complex than learning a lower-dimensional substitute score that preserves the shared assignment variation needed for stable causal adjustment. The deconfounder (Wang and Blei, 2019) and related substitute confounder methods exploit this idea, but flexible assignment models can fit the joint distribution of the causes while producing scores that over-encode the treatment vector, collapse overlap, or capture single-cause variation. We develop a Bayesian factor assignment framework for learning sparse substitute confounders that retain coarse multi-cause dependence with shrinkage priors. The theory is stated at the level of posterior concentration, factor score contraction, and overlap-preserving assignment geometry and therefore does not rely on a particular shrinkage prior. Under these conditions, the proposed regression-adjusted estimators are consistent for mean potential outcomes when the corresponding latent variable identification assumptions hold. Shrinkage priors provide a natural tool for latent structural learning: they favour low-dimensional factors supported by multiple causes, discourage effectively single-cause factors, and induce an ordering of the latent factors through progressive shrinkage. Synthetic experiments illustrate the roles of signal strength, outcome validity, and geometry-aware regularization. In an Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline analysis, sparse substitute scores recover much of the adjustment obtained by directly conditioning on invasive cerebrospinal-fluid biomarkers, while collapse diagnostics identify when fitted factors reduce to individual observed measurements.

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

Protein Design with Agent Rosetta: A Case Study for Specialized Scientific Agents

arXiv:2603.15952v2 Announce Type: replace Abstract: Large language models (LLMs) are capable of emulating reasoning and using tools, creating opportunities for autonomous agents that execute complex scientific tasks. Protein design provides a natural testbed: although machine learning (ML) methods achieve strong results, these are largely restricted to canonical amino acids and narrow objectives, leaving unfilled need for a generalist tool for broad design pipelines. We introduce Agent Rosetta, an LLM agent paired with a structured environment for operating Rosetta, the leading physics-based heteropolymer design software, capable of modeling non-canonical building blocks and geometries. Agent Rosetta iteratively refines designs to achieve user-defined objectives, combining LLM reasoning with Rosetta's generality. We evaluate Agent Rosetta on design with canonical amino acids, matching specialized models and expert baselines, and with non-canonical residues – where ML approaches fail – achieving comparable performance. Critically, prompt engineering alone often fails to generate Rosetta actions, demonstrating that environment design is essential for integrating LLM agents with specialized software. Our results show that properly designed environments enable LLM agents to make scientific software accessible while matching specialized tools and human experts.

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

NoContactNoWorries: Estimating Contact through Vision and Proprioception for In-Hand Dexterous Manipulation

arXiv:2606.24450v1 Announce Type: cross Abstract: Perceiving physical contact is fundamental to dexterous manipulation. While robots often rely on dedicated hardware tactile sensors, humans exhibit a remarkable ability to infer contact by integrating visual information with an innate sense of their body's pose and movement. Inspired by this embodied perceptual skill, we investigate whether a robot can learn to infer contact from vision, an approach that also offers a scalable alternative to tactile hardware specifically for binary contact estimation, which faces practical challenges in cost, fragility, and integration. We present NoContactNoWorries, a transformer-based multimodal framework that fuses RGB-D vision with the robot's proprioception to infer binary contact states as a pseudo-tactile signal for hand-object interactions. We validate by training a single contact prediction model on multiple objects and show that the inferred contact signal supports downstream reinforcement learning agents for in-hand object reorientation, generalizing to novel objects. Experiments in both simulation and on a real-world robot validate our approach, highlighting the feasibility of inferring contact from vision and proprioception. Project Page: https://soham2560.github.io/no-contact-no-worries/

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

Trusted Uncertainty in Large Language Models: A Unified Framework for Confidence Calibration and Risk-Controlled Refusal

Deployed language models must decide not only what to answer but also when not to answer. We present UniCR, a unified framework that turns heterogeneous uncertainty evidence including sequence likelihoods, self-consistency dispersion, retrieval compatibility, and tool or verifier feedback into a calibrated probability of correctness and then enforces a user-specified error budget via principled refusal. UniCR learns a lightweight calibration head with temperature scaling and proper scoring, supports API-only models through black-box features, and offers distribution-free guarantees using conformal risk control. For long-form generation, we align confidence with semantic fidelity by supervising on atomic factuality scores derived from retrieved evidence, reducing confident hallucinations while preserving coverage. Experiments on short-form QA, code generation with execution tests, and retrieval-augmented long-form QA show consistent improvements in calibration metrics, lower area under the risk-coverage curve, and higher coverage at fixed risk compared to entropy or logit thresholds, post-hoc calibrators, and end-to-end selective baselines. Analyses reveal that evidence contradiction, semantic dispersion, and tool inconsistency are the dominant drivers of abstention, yielding informative user-facing refusal messages. The result is a portable recipe of evidence fusion to calibrated probability to risk-controlled decision that improves trustworthiness without fine-tuning the base model and remains valid under distribution shift.