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01.
medRxiv (Medicine) 2026-06-19

Fine-Tuning SAM2 for Coronary Artery Segmentation in X-Ray Fluoroscopy

作者:

SAM2 (Meta, 2024) provides a strong starting point for segmentation, but given the unique challenges in medical imaging (noise from patient movement, the projection-based nature of X-ray fluoroscopy, and low contrast between vessels and background), direct application is difficult. We fine-tune MedSAM2 on annotated coronary angiograms and apply it to video data for point-of-care use. On the ARCADE validation set (200 images), the fine-tuned model achieves Dice 0.767 compared to 0.033 zero-shot. On 10 fluoroscopic video studies from CoronaryDominance, it tracks vessels coherently and avoids falsely segmenting ribs, stents, and bypass grafts in 9 of 10 studies. Code is available at https://github.com/elakiyasivakumar/SAM2-Coronary-Angiography-VA and the fine-tuned checkpoint at https://huggingface.co/Elakiya17/CA-SAM2.

02.
PLOS Computational Biology 2026-06-04

CIPHER: An end-to-end framework for designing optimized aggregated spatial transcriptomics experiments

by Zachary Hemminger, Haley De Ocampo, Fangming Xie, Zhiqian Zhai, Jingyi Jessica Li, Roy Wollman Motivation Most imaging-based spatial transcriptomics methods measure individual genes, which limits scalability and typically requires integration with scRNA-seq to recover full cellular states. Recent approaches such as CISI, FISHnCHIPs, and ATLAS address this limitation by measuring aggregate transcriptional signatures, where multiple genes are pooled into each channel to increase throughput. While aggregate measurements improve scalability, they shift the problem from gene selection to feature design. For effective integration with scRNA-seq, these signatures must be not only discriminative in transcriptional space but also straightforward to measure, with balanced signal, sufficient dynamic range, and robustness to experimental noise. By optimizing decoding accuracy in isolation, existing methods leave substantial performance on the table. Results We present CIPHER (Cell Identity Projection using Hybridization Encoding Rules), a neural-network framework that jointly optimizes the experimental encoding matrix, i.e., the way that genes are aggregated to signatures, and the downstream cell embedding. CIPHER integrates the physical limits of imaging assays directly into its loss function, shaping the latent space to maximize discriminability while maintaining robustness to measurement noise and signal constraints. Using a large-scale mouse brain scRNA-seq reference, we show that CIPHER-designed encodings yield latent spaces with improved cell-type separability, uniform signal utilization, and greater resilience to hybridization variability, resulting in higher decoding accuracy from both simulated and experimental data. Conclusion CIPHER formulates aggregate signature design as a joint optimization problem over decoding accuracy and experimental measurability. This enables systematic, scRNA-seq-aligned feature design for scalable spatial transcriptomics based on aggregate measurements. Availability Code and documentation are available at https://github.com/wollmanlab/Design/.

03.
medRxiv (Medicine) 2026-06-11

Conversational Speech for Respiratory Triage in Primary Care: A Pilot Study

作者:

Background. Respiratory complaints account for a substantial share of adult ambulatory care visits, and triaging them accurately has direct consequences for antibiotic stewardship and pathogen-specific therapy. Prior work has investigated voice as a triage signal, but that literature is dominated by single-condition detection from scripted speech in crowdsourced or controlled clinical settings and has not been evaluated at primary care scale on conversational ambient audio. Methods. A dataset of 514,377 ambient-recorded primary care visits from 379,225 adult patients at a US clinic network was used, with per-visit clinically assigned ICD-10 diagnosis codes and de-identified demographic and geographic metadata. Patient audio was extracted from each doctor-patient conversation, and spectral, voice quality, and prosodic features were computed. Eleven binary classification tasks were defined, aligned with a respiratory triage cascade (e.g., acute respiratory versus acute non-respiratory illness, and lower versus upper respiratory tract infection). An acoustic model (feed-forward network) was trained independently for each task using patient-stratified five-fold cross-validation and evaluated on a held-out test set. Each task's model was also compared against six non-acoustic baselines using a single demographic, geographic, or temporal variable. The 11 trained classifiers were composed into a hierarchical cascade and illustrated as case studies on selected patients. Results. Test-set AUC across the 11 tasks ranged from 0.602 (95% CI: 0.588-0.614) to 0.745 (95% CI: 0.742-0.748), with a mean expected calibration error of 0.018. Six of eleven binaries outperformed all confounder baselines. Four binaries showed median within-stratum AUC of 0.62-0.70 when the confounder was held fixed, indicating acoustic discrimination beyond what the confounder alone explains. The exception was the pneumonia versus non-pneumonia lower respiratory tract infection binary, which failed against the patient-city confounder baseline, plausibly reflecting a clinic-level difference in ICD-10 coding. Conclusion. Conversational primary care audio carries acoustic signal that discriminates clinically meaningful respiratory contrasts. Absolute performance is moderate, but the conditions are stricter than prior work: conversational speech and differential-diagnosis contrasts among sick patients. This pilot study is a baseline for voice-based clinical AI moving beyond sick-versus-healthy detection toward differential-diagnosis panels and a proof-of-concept for hierarchical reasoning.

04.
arXiv (CS.AI) 2026-06-16

OSGuard: A Benchmark for Safety in Computer-Use Agents

arXiv:2606.15034v1 Announce Type: new Abstract: Computer-use agents are increasingly evaluated by whether they complete realistic desktop and web tasks. However, task success alone can miss failures in which an agent reaches the nominal goal through an unsafe shortcut. We introduce OSGuard, a dual-granularity benchmark suite for evaluating safety in computer-use agents under benign, unchanged user instructions. OSGuard contains an action-level benchmark for local guardrail decisions and a risk-augmented execution suite for end-to-end evaluation. The action-level benchmark consists of contextualized proposed actions labeled as allowed, unrelated, or unsafe, each judged relative to the original instruction and current interface state. The execution suite contains manually constructed OSWorld-derived task variants in which the original task remains achievable, but the environment is modified to introduce latent hazards such as destructive overwrites, etc. Each variant is paired with augmented evaluators that retain the original task-success criterion while adding explicit state-based safety invariants, allowing us to distinguish safe completions from unsafe completions that satisfy the nominal task objective. Our experimental results on OSGuard show that current multimodal guardrails can perform well on isolated action judgments, while risk-augmented execution exposes remaining gaps between local oversight and reliable end-to-end safety. This dual-granularity design enables more precise diagnosis of whether models can both recognize unsafe proposed actions and improve full-task safety when deployed as guardrails.

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

The Proxy Knows Too Much: Sealing LLM API Routers with Attested TEEs

arXiv:2606.16358v1 Announce Type: cross Abstract: Agents increasingly access large language models (LLMs) through API routers. A router terminates the client's transport-layer security session and opens a separate upstream session, so it holds the full interaction in plaintext. This makes the router an application-layer man-in-the-middle: it can rewrite agent tool calls, swap dependencies for typosquatted packages, trigger attacks only under audit-evading conditions, and passively exfiltrate secrets. Existing client-side defenses are evadable. We propose AEGIS, a provider-transparent attested API router whose data path is a client-verified faithful passthrough. AEGISconfines plaintext handling to a small hardware-enclave component while leaving authentication, scheduling, accounting, and management on the untrusted host. The client verifies the enclave before releasing plaintext. The host can neither read nor alter the interaction, and plaintext leaves only toward destinations fixed by the measured image. We show that all four malicious-router attack classes succeed against a plaintext-access baseline and are blocked by AEGIS, including adaptive tests against the same boundary. The trusted path is $851$ lines, carries three provider-native APIs without conversion, and completes every request under real-provider workload and concurrency. In a seeded audit pilot, two commodity coding agents find eight and ten of ten planted invariant violations. The local relay overhead is about six milliseconds per request.

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

When Lower Privileges Suffice: Investigating Over-Privileged Tool Selection in LLM Agents

As LLM agents increasingly select tools autonomously, their choices among tools with different privileges become safety-relevant. However, prior tool-selection studies focus on safety-agnostic metadata preferences, leaving privilege-sensitive choices underexplored. To address this gap, we study over-privileged tool selection, in which an agent selects or escalates to a higher-privilege tool despite a sufficient lower-privilege alternative. We introduce ToolPrivBench to evaluate whether agents choose higher-privilege tools despite sufficient lower-privilege alternatives, measuring both initial selection and escalation after transient tool failures. Across eight domains and five recurring risk patterns, we find that over-privileged tool selection is common among mainstream LLM agents and is further amplified by transient failures. We further find that general safety alignment does not reliably transfer to least-privilege tool choice, while prompt-level controls provide only limited mitigation under transient failures. We therefore introduce a privilege-aware post-training defense that teaches agents to prefer sufficient lower-privilege tools and escalate only when necessary. Our mitigation experiments show that this defense substantially reduces unnecessary high-privilege tool use while preserving general capabilities.

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

CAP: Towards PPG Universal Representation Learning with Patient-level Supervision

arXiv:2606.15284v1 Announce Type: cross Abstract: Photoplethysmography (PPG) plays a central role in wearable health monitoring and clinical decision support. Yet existing approaches to universal PPG representation learning largely focus on signal-level objectives and often overlook patient-level health context, which limits generalization to complex clinical tasks and heterogeneous cohorts. To address this gap, we construct a large-scale paired PPG-EHR multimodal dataset by distilling fragmented medical histories and clinical records into cohesive, patient-level electronic health records (EHR). Building on this resource, we propose Clinical Anchored Pretraining for PPG (CAP). During pretraining, CAP performs cross-modal contrastive alignment that anchors PPG representations to patient-level clinical semantics, guiding the encoder beyond waveform fitting toward modeling consistency in a patient's overall physiological state. During downstream adaptation, the pretrained PPG encoder provides clinically grounded representations that strengthen inductive bias and improve robustness and transferability. Experiments demonstrate that CAP consistently outperforms strong baselines on four diverse downstream tasks. CAP achieves a particularly large gain on respiratory rate prediction (up to +87.6% relative improvement over the state-of-the-art baseline) and delivers an average relative +26.7% across all tasks. We further enhance the interpretability of our approach through comprehensive analyses, including ablations and multiple complementary visualizations of the learned representations. The code for our experiments is available at: https://github.com/gody123gody/CAP .

08.
arXiv (CS.LG) 2026-06-16

Contrastive Regularization for Accent-Robust ASR

arXiv:2605.03297v2 Announce Type: replace-cross Abstract: ASR systems based on self-supervised acoustic pretraining and CTC fine-tuning achieve strong performance on native speech but remain sensitive to accent variability. We investigate supervised contrastive learning (SupCon) as a lightweight, accent-invariant auxiliary objective for CTC fine-tuning. An utterance-level contrastive loss regularizes encoder representations without architectural modification or explicit accent supervision. Experiments on the L2-ARCTIC benchmark show consistent WER reductions across multiple pretrained encoders, with up to 25 – 29\% relative reduction under unseen-accent evaluation. Analysis using within-transcript cosine dispersion indicates that SupCon promotes more compact and stable representation geometry under accent variability. Overall, SupCon provides an effective and model-agnostic regularization strategy for improving accent robustness.

09.
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.

10.
arXiv (CS.CL) 2026-06-17

Moderating Illicit Online Image Promotion for Unsafe User-Generated Content Games Using Large Vision-Language Models

Online user generated content games (UGCGs) are increasingly popular among children and adolescents for social interaction and more creative online entertainment. However, they pose a heightened risk of exposure to explicit content, raising growing concerns for the online safety of children and adolescents. Despite these concerns, few studies have addressed the issue of illicit image-based promotions of unsafe UGCGs on social media, which can inadvertently attract young users. This challenge arises from the difficulty of obtaining comprehensive training data for UGCG images and the unique nature of these images, which differ from traditional unsafe content. In this work, we take the first step towards studying the threat of illicit promotions of unsafe UGCGs. We collect a real-world dataset comprising 2,924 images that display diverse sexually explicit and violent content used to promote UGCGs by their game creators. Our in-depth studies reveal a new understanding of this problem and the urgent need for automatically flagging illicit UGCG promotions. We additionally create a cutting-edge system, UGCG-Guard, designed to aid social media platforms in effectively identifying images used for illicit UGCG promotions. This system leverages recently introduced large vision-language models (VLMs) and employs a novel conditional prompting strategy for zero-shot domain adaptation, along with chain-of-thought (CoT) reasoning for contextual identification. UGCG-Guard achieves outstanding results, with an accuracy rate of 94% in detecting these images used for the illicit promotion of such games in real-world scenarios.

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

Clifford disentanglers for entanglement reduction in molecular electronic structure simulations

arXiv:2606.12056v1 Announce Type: new Abstract: Entanglement is a key bottleneck limiting the efficiency of tensor-network and quantum simulations of molecular electronic structures. Here, we systematically assess and extend Clifford disentanglers as a structure-preserving approach to entanglement reduction: they can modify the entanglement structure of qubit wavefunctions while retaining the Pauli-string form of qubit Hamiltonians. To enable a practical search over Clifford transformations, we classify Clifford operators by their action on the Schmidt spectrum across a bipartition, reducing the two- and four-qubit search spaces to 20 and 91392 representatives, respectively. Embedded in an iterative Clifford-augmented matrix product state framework, these transformations reduce the energy errors at fixed bond dimension for the molecular test cases studied and mitigate the dependence on orbital orderings and fermion-to-qubit mappings. We further show that Clifford disentanglers can also benefit quantum simulations such as the shallow-circuit variational quantum eigensolver calculations. Together, these results establish Clifford disentanglers as a useful structure-preserving entanglement-engineering tool for tensor-network and quantum simulations of molecular electronic structure, while also clarifying their correlation dependence and motivating future developments.

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

Position: Generative Engine Optimization Creates Underexamined Risks, Governance Must Target Concentration, Disclosure, and Academic Blind Spots

arXiv:2606.12439v1 Announce Type: cross Abstract: Large language model (LLM) answer engines are increasingly used for information seeking, shifting visibility from ranked lists to synthesized answers. This enables Generative Engine Optimization (GEO), which targets LLM answer engines' evidence pool and generation. We analyze the search engine optimization (SEO) to GEO transition to identify two risks: (i) concentrated influence from low contestability and system sensitivity, and (ii) undisclosed commercial influence embedded in evidence and reasoning. We then formalize a general GEO pipeline to locate where optimization acts and compare academic and industry practices, revealing a third risk: (iii) academic-industry blind spots driven by visibility and evaluation asymmetries between offline setups and deployed systems. This position argues the need for answer-level governance and measurement: stronger contestability, high-precision disclosure, black-box auditing of material influence, and deployment-aligned metrics for exposure persistence.

13.
arXiv (quant-ph) 2026-06-19

Computing noise-canceling observables via Pauli propagation

arXiv:2606.20441v1 Announce Type: new Abstract: The pursuit of quantum advantage is driving the co-evolution of quantum processors and classical simulation methods. Despite advances in scale and quality, the accuracy of quantum simulation is ultimately limited by error rates and sampling overheads. Similarly, while classical simulation methods such as Pauli propagation have made remarkable progress, their accuracy is ultimately limited by the exponential growth of operator paths and the truncations needed to control memory and runtime. Here we show that these complementary limitations can be mitigated by embedding Pauli propagation within a hybrid error-mitigation framework that reduces quantum sampling overhead while achieving lower truncation errors with fewer classical resources than traditional Pauli propagation alone. In this framework, a target observable is classically propagated through noise-canceling inverse channels, producing a modified observable that is measured directly on a quantum processor. We prototype two implementations and benchmark their performance numerically on canonical models that challenge traditional Pauli propagation. We also perform experiments on a quantum processor using 56 superconducting qubits, revealing the tradeoffs of their respective truncation strategies. These results illustrate how classical and quantum resources can be orchestrated to extend observable estimation beyond the limits of either approach alone, providing a foundation for quantum-centric supercomputing and future demonstrations of quantum advantage.

14.
arXiv (quant-ph) 2026-06-19

Optimal Shadow Estimation with Minimal Measurement Settings

arXiv:2606.20003v1 Announce Type: new Abstract: Shadow estimation is a powerful framework for predicting quantum properties from randomized measurements. While $3$-design protocols achieve optimal worst-case performance, the minimal number of measurement bases required for such optimality has remained open. Here we prove that $\Theta(d^2)$ measurement bases are both necessary and sufficient for worst-case optimal shadow estimation and construct an explicit basis family. In stark contrast, any state $2$-design already suffices for average-case optimality: the mean squared shadow norm of normalized observables is bounded by a universal constant, and we prove strong concentration for Haar-random states, yielding constant sample complexity for generic pure-state fidelity estimation. Easily implementable $2$-designs – from mutually unbiased bases, cyclic measurements, or shallow $\mathcal{O}(\log n)$-depth circuits – enable optimal average-case protocols with remarkably simple measurement strategies. Our results establish a fundamental complexity separation: worst-case estimation requires $\Theta(d^2)$ bases, whereas average-case performance requires only $\Theta(d)$ bases, with broad implications for quantum information theory and near-term experiments.

15.
bioRxiv (Bioinfo) 2026-06-12

ProMiSE: Protein Multi-State Evaluation Benchmark in Biological Contexts

Proteins are inherently dynamic, with biological functions often emerging from transitions between multiple conformational states. While recent breakthroughs have largely addressed the static structure prediction problem, no systematic benchmark exists to demonstrate how well current models capture functionally relevant dynamics. We introduce ProMiSE, the first benchmark that provides both a dataset and an evaluation scheme, based on native biological assemblies and integrating major conformational change mechanisms - intrinsic, ligand-induced, and protein-induced - within a single curated dataset. We conducted a comprehensive evaluation of state-of-the-art structure prediction models, including AlphaFold3 and recent generative approaches. Our findings reveal that current models exhibit a limited ability to sample intrinsic multi-states and are often insensitive to biological context in induced scenarios. Internal representation analysis suggests that training-data exposure can shift predictions toward dominant conformational states over alternative biologically relevant states, primarily at the structure module. In contrast, results from BioEmu indicate that reducing decoding-stage bias can substantially improve multi-state sampling without major changes to upstream pair representations.

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

HadBalance: A Plug-and-Play Unified Global Geometric Prior Framework for Generalizable Biomedical Segmentation

Precise biomedical image segmentation is crucial for clinical diagnosis. Geometric cues (e.g., boundary, shape, and topology) can improve structural consistency, yet most are task-specific and lack a unified geometric foundation that generalizes across organs and modalities. We are motivated by the observation that several medical segmentation targets can be approximated as globally near-convex shapes. A convex region is one in which any two interior points can be connected by a line segment entirely contained within the region. In practice, medical targets may exhibit small local concavities or boundary irregularities; we refer to such globally convex-like shapes as near-convex. Motivated by this, we derive Hadwiger Shape Priors from Hadwiger's theorem as an interpretable global regularizer using three 2D measures: area A, perimeter P, and Euler characteristic chi, enabling transfer across organs and modalities. However, because medical datasets are shape-heterogeneous, enforcing near-convex priors uniformly can over-regularize non-convex anatomy with significant concavities, washing out concavities and fine details and degrading segmentation accuracy. To address this challenge, we propose Conflict-Aware Objective Balancing (CAOB), which integrates shape priors with segmentation in a gradient-aware manner. For each prior, CAOB removes only the gradient component that conflicts with segmentation while preserving the remaining aligned component, and adaptively regulates objective influences to prevent prior dominance. This enables stable use of shape priors on shape-heterogeneous data without erasing genuine concavities or fine structural details. We call this plug-and-play framework HadBalance.

17.
arXiv (math.PR) 2026-06-15

Stationary measures for higher spin vertex models on a strip

作者:

arXiv:2309.04897v2 Announce Type: replace-cross Abstract: We introduce a higher spin vertex model on a strip with fused vertex weights. This model can be regarded as a generalization of both the unfused six-vertex model on a strip arXiv:2212.09111 and an 'integrable two-step Floquet dynamics' model introduced in arXiv:1711.08884. We solve for the stationary measure using a fused version of the matrix product ansatz and then characterize it in terms of the Askey-Wilson process. Using this characterization, we obtain the limits of the mean density along an arbitrary down-right path. It turns out that all these models share a common phase diagram, which, after an appropriate mapping, matches the phase diagram of open ASEP. This provides evidence for the universality of this phase diagram.

18.
arXiv (quant-ph) 2026-06-11

Time-Frequency Grid States for Reconstruction and Correction of Channel-Induced Distortion in Entangled Photons

arXiv:2606.12216v1 Announce Type: new Abstract: Characterization of time-frequency (TF) quantum states requires reliable reconstruction of their TF distributions. However, imperfect transmission or measurement channels can distort reconstructed joint spectral intensities (JSIs), especially when the underlying perturbation mechanism is unknown. Here, we experimentally demonstrate a reconstruction and correction framework that uses a TF grid state as an intrinsic frequency-domain reference. By analyzing the displacement of the grid points, a Gaussian process regression model is employed to reconstruct a correction mapping for the nonlinear coordinate deformation without assuming a prior physical model of the distortion. The learned mapping reduces the residual coordinate deviation of the TF grid state by approximately a factor of 11 and, when applied to an independent frequency-entangled test state, improves the Gaussian-shape fidelity from 76.2\% to 90.0\%. These results establish TF grid states as practical metrological resources for diagnosing and correcting distortions in TF quantum systems, providing a pathway toward distortion-resilient quantum communication and high-dimensional quantum information processing.

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

Embodied-BenchClaw: An Autonomous Multi-Agent System for Embodied Spatial Intelligence Benchmark Construction

arXiv:2606.11909v1 Announce Type: new Abstract: Benchmarks are essential for evaluating embodied spatial intelligence, yet their construction is labor-intensive, hard to reuse, and difficult to maintain. Existing embodied benchmarks are often static and may quickly become saturated as models improve, limiting their ability to distinguish new capabilities. We propose Embodied-BenchClaw, an autonomous agentic system for constructing embodied spatial intelligence benchmarks. Given a user-specified evaluation intent, Embodied-BenchClaw automatically produces a complete and continually updatable benchmark package through a five-stage pipeline: intent blueprinting, data collection, structuring and cleaning, benchmark synthesis, and evaluation reporting. The pipeline is coordinated by three agents for planning, construction, and evaluation. To improve reusability and reliability, Embodied-BenchClaw introduces an extensible Skill Library and process quality control, enabling benchmark construction to be composable, verifiable, and repairable. We instantiate multiple benchmarks covering indoor spatial reasoning, outdoor spatial reasoning, robotic manipulation, quadruped robot navigation, UAV/aerial-view understanding, and static benchmark enhancement. These benchmarks span diverse embodied carriers, data sources, and spatial capabilities. Experiments with human evaluation, judge-based assessment, consistency checks, cost analysis, and ablations show that Embodied-BenchClaw can construct verifiable, executable, maintainable, and diagnostically useful embodied spatial benchmarks with reduced manual effort.

20.
medRxiv (Medicine) 2026-06-11

Long-term Penetrance of Disease Variants in Genes Prioritized for Genomic Newborn Screening: Evidence from Adult Biobanks

Importance: Genomic newborn screening (gNBS) is a potential public health intervention, but its positive predictive value (PPV) remains uncertain. Estimating the prevalence and penetrance of pathogenic and likely pathogenic (P/LP) variants in genes prioritized for screening may clarify the long-term PPV and clinical utility of gNBS. Objective: To compare ICD-based ascertainment, electronic medical record (EMR) review, and clinical assessment of genetic disorders in adults with P/LP variants in 54 genes prioritized for gNBS. Design: Two-cohort observational study with EMR review and clinical assessment in the hospital-based cohort. Setting: The U.K. Biobank (UKB) and Mass General Brigham Biobank (MGBB). Participants: 451,877 adults from the UKB and 53,371 from the MGBB, all with exome sequencing data. Exposures: P/LP variants in 54 genes prioritized through expert consensus for gNBS, in genotypes consistent with each gene's inheritance pattern. Main outcomes and measures: The primary outcome was the absolute difference in the proportion of MGBB participants identified as affected by ICD versus EMR ascertainment. Secondary outcomes included findings from clinical assessments of undiagnosed MGBB participants, corrected UKB penetrance estimates, and extrapolation to U.S.. annual birth cohorts and living adults. Results: P/LP variants were identified in 665 UKB participants (0.15%) and 82 MGBB participants (0.15%), approximately 1 in 650. In MGBB, EMR review revealed that 58/82 individuals (70.7%) were undiagnosed, although 25 of 58 (43.1%) had documented symptoms. Disease-associated ICD codes were found in 39.0% (32/82) of participants, whereas EMR review identified symptoms in 59.8% (49/82, McNemar P

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

Strategic PAC Learnability via Geometric Definability

arXiv:2605.13426v3 Announce Type: replace Abstract: Strategic classification studies learning settings in which individuals can modify their features, at a cost, in order to influence the classifier's decision. A central question is how the sample complexity of the induced (strategic) hypothesis class depends on the complexities of the underlying hypothesis class and the cost structure governing feasible manipulations. Prior work has shown that in several natural settings, such as linear classifiers with norm costs, the induced complexity can be controlled. We begin by showing that such guarantees fail in general - even in simple cases: there exist hypothesis classes of VC dimension $1$ on the real line such that, even under the simplest interval neighborhoods, the induced class has infinite VC dimension. Thus, strategic behavior can turn an easy learning problem into a non-learnable one. To overcome this, we introduce structure via a geometric definability assumption: both the hypothesis class and the cost-induced neighborhood relation can be defined by first-order formulas over $\mathbb{R}_{\mathtt{exp}}$. Intuitively, this means that hypotheses and costs can be described using arithmetic operations, exponentiation, logarithms, and comparisons. This captures a broad range of natural classes and cost functions, including $\ell_p$ distances, Wasserstein distance, and information-theoretic divergences. Under this assumption, we prove that learnability is preserved, with sample complexity controlled by the complexity of the defining formulas.

22.
arXiv (quant-ph) 2026-06-16

Quantum Illumination with Symmetry-Constrained Random Unitaries

arXiv:2606.15586v1 Announce Type: new Abstract: Quantum illumination provides a quantum advantage in detecting weakly reflecting objects embedded in a noisy environment, even when environmental noise destroys most of the initial entanglement. We investigate this advantage using Haar-random probe states constrained to symmetry-resolved subspaces. Employing tools from quantum channel discrimination and asymptotic hypothesis testing, we derive the discrimination exponents associated with Haar-random probe ensembles and identify the role of symmetry in determining their performance. We show that typical states drawn from fixed-charge sectors achieve the same asymptotic quantum-illumination advantage as maximally entangled probes. In particular, we show that the effective thermal-noise suppression and the corresponding Chernoff exponent are governed by the dimension of the accessible symmetry sector. Our results reveal that the operational resource underlying quantum illumination can be generalized from fine-tuned structure of a specific probe state to the existence of a large symmetry-protected correlation subspace. These findings establish a direct connection between quantum illumination, symmetry-resolved typicality, and quantum channel discrimination, and demonstrate that near-optimal quantum hypothesis testing resources can emerge naturally from generic many-body quantum states constrained by conservation laws.

23.
arXiv (math.PR) 2026-06-15

Boltzmann-Like Occupation of Nonequilibrium Steady States on Dense Networks

arXiv:2606.14542v1 Announce Type: cross Abstract: A central problem in statistical physics is to extend the Boltzmann distribution to nonequilibrium steady states (NESS). We prove that NESS on large dense networks have Boltzmann-like occupation despite extensive entropy production. We further show that the active-matter heuristic of "low rattling" is asymptotically exact. Intuitively, these NESS spend a greater fraction of their time in states they leave more slowly. This explanation extends to the broader class of "equiaccessible" steady states, which play a role in our analysis akin to that of equilibrium in linear response.

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

Your Mouse and Eyes Secretly Leak Your Preference: LLM Alignment using Implicit Feedback from Users

To align a Large Language Model (LLM), most existing methods collect explicit human feedback and train a reward model to predict the human preference based on the response text. These existing methods have two key limitations. First, the users rarely provide explicit feedback for LLM responses, which makes the high-quality preference annotation expensive to collect. Second, the methods do not leverage implicit human feedback, which has proven vital to the economic moats of Internet giants. To quantify the value of implicit feedback, we build a new dataset called IFLLM, which collects 1336 multi-turn questions from the 59 Mechanical Turk workers, their mouse trajectories, and eye gazing points to the LLMs' responses from their webcams. IFLLM shows that the users have very diverse types of gazing behavior and mouse trajectories. Our reward model based on the implicit user feedback boosts the accuracy of the text-based reward model from 55% to 64% and nearly triples the relative response quality improvements after applying the DPO to eight LLMs, demonstrating the value of implicit feedback in the wild. Our data collection website, dataset, and codes can be found at https://github.com/themehulpatwari/llm-implicit-feedback/.

25.
arXiv (quant-ph) 2026-06-11

Robust Mixed-State Cluster States and Spurious Topological Entanglement Negativity

arXiv:2504.16165v2 Announce Type: replace Abstract: We investigate 1D and 2D cluster states under local decoherence to assess the robustness of their mixed-state subsystem symmetry-protected topological (SSPT) order. By exactly computing fidelity correlators via dimensional reduction of effective statistical mechanics models, we pinpoint the critical error rate for strong-to-weak spontaneous breaking of strong subsystem symmetry. Without resorting to the replica trick, we demonstrate that mixed-state SSPT order remains remarkably robust up to the maximal decoherence rate when noise respects strong subsystem symmetry. Furthermore, we propose that the mixed-state SSPT order can be detected by a constant correction to the area-law scaling of entanglement negativity, termed spurious topological entanglement negativity. This also highlights that topological entanglement negativity, a widely used diagnostic for mixed-state topological order, is generally not invariant under finite-depth quantum channels.