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01.
medRxiv (Medicine) 2026-06-15

Routine use of oral iron for people with heart failure and iron deficiency in primary care; retrospective cohort study

Aims: Iron deficiency is common among people with heart failure and associated with morbidity and mortality. While intravenous iron improves clinical outcomes, oral iron continues to be prescribed in routine practice despite limited evidence of benefit. Methods: We completed a retrospective primary care cohort study (2016 to 2021) to investigate the proportion of people with an incident diagnosis of heart failure who had iron deficiency identified (defined as ferritin

02.
arXiv (quant-ph) 2026-06-11

Quantum Correlation Hierarchy and Teleportation in Dephased Hydrogen Hyperfine System

arXiv:2606.11731v1 Announce Type: new Abstract: We study the dynamics of quantum correlations in the hydrogen hyperfine spin system subject to Markovian phase noise. Treating the electron and proton spin degrees of freedom as an open two-qubit system governed by an isotropic hyperfine Hamiltonian and local dephasing, we obtain the exact time-dependent density matrix and derive analytical expressions for the full X-state family. We compute concurrence($C$), trace-distance measurement-induced nonlocality (Trace MIN–$\mathcal{N}_1$), and average steering coherence (ASC) in closed form and establish their strict ordering $ C(t)\leq \mathcal{N}_1(t)\leq \mathrm{ASC}(t) $ at all times. Entanglement is identified as the most fragile resource, undergoing sudden death at a finite time. Trace MIN exhibits dephasing-immune freezing for states with nonzero population imbalance, while ASC is the most robust quantity, persisting longest in every scenario studied.We additionally demonstrate that the dephased thermal hyperfine state serves as a resource for quantum teleportation, deriving a closed-form expression for the average fidelity and establishing that the teleportation advantage window coincides exactly with the entanglement survival interval, $\mathcal{F}_A > 2/3 \Longleftrightarrow \mathcal{C} > 0$, for the full X-state family with maximally mixed marginals. We identify four distinct dynamical regimes and map all three correlation measures onto directly measurable Pauli spin correlators, enabling experimental reconstruction of the full hierarchy without full state tomography.

03.
medRxiv (Medicine) 2026-06-25

Performance of Cardiovascular Polygenic Risk Scores in Carotid Stenosis Identification

Background: Clinically significant carotid stenosis remains a major cause of ischemic stroke (IS), yet prediction of disease progression is limited. Polygenic risk scores (PRSs) for coronary artery disease (CAD) and peripheral artery disease (PAD) have demonstrated associations with atherosclerosis burden and major cardiovascular disease (CVD) events, but whether these insights extend to carotid stenosis is unclear. We evaluated the association and discriminative performance of validated PRSs for CAD, PAD, IS, and carotid intima-media thickness (cIMT) with carotid stenosis. Methods: Carotid stenosis was identified in genotyped Mass General Brigham Biobank participants using validated ICD- and CPT-based phenotyping algorithms. Logistic regression adjusted for age, sex, and 10 ancestry principal components assessed PRS associations. Incremental discrimination was evaluated using changes in Harrell's C-statistic. Results: Compared with 52,636 controls, 670 participants with carotid stenosis were more frequently male (61.5% vs 44.1%), older (70.8 SD 9.0 vs 53.4 SD 17.2 years), and more likely to be European (95.7% vs 84.1%). The IS (OR 1.31, 95% CI 1.21?1.41), CAD (OR 1.62, 95% CI 1.50?1.75), and PAD (OR 1.66, 95% CI 1.54?1.80) PRSs were each associated with carotid stenosis (all p

04.
arXiv (quant-ph) 2026-06-11

A saturation-absorption rubidium magnetometer with multilevel optical Bloch-equation modeling for intermediate-to-high fields

arXiv:2601.09115v2 Announce Type: replace Abstract: We present SASHMAG (Saturated Absorption Spectroscopy High-field MAGnetometer), an atomic sensor designed for precision magnetic-field measurements in the intermediate-to-high field regime ($>0.2\,T$) using Rubidium-87 ($^{87}Rb$). The sensor operates in the hyperfine Paschen-Back regime, where the hyperfine and Zeeman interactions decouple, and utilizes counter-propagating pump-probe configuration in Faraday geometry to resolve isolated, Doppler-free Zeeman transitions. To interpret the resulting spectra in this strongly field-dependent regime, we developed a comprehensive multilevel optical Bloch-equation model solved explicitly in the uncoupled $\ket{m_I, m_J}$ basis, capturing state mixing and nonlinear saturation dynamics. This model reproduces measured spectra at sub-Doppler resolution and is consistent with analytical expectations for power broadening and thermal Doppler scaling. Magnetic field estimation is performed using a physics-constrained optimization routine that infers the magnetic field by minimizing the residual between experimentally extracted line centers and calculated transition frequencies from the field-dependent Hamiltonian. We demonstrate magnetic field retrieval from $0.2\,T$ to $0.4\,T$ with a precision of $\pm 0.0017 \,T$). Furthermore, the validated simulation establishes a foundation for generating synthetic training datasets, paving the way for autonomous, Machine Learning-enhanced magnetometry in applications ranging from MRI to fusion reactors.

05.
arXiv (CS.AI) 2026-06-24

A global log for medical AI

arXiv:2510.04033v2 Announce Type: replace Abstract: Modern computer systems rely on syslog, a universal protocol that records critical events across heterogeneous infrastructure. Medicine's rapidly growing AI stack has no equivalent. As medicine deploys AI tools at scale, there is no standard way to record how, when, by whom, and for whom these models are used. Without such records, it is difficult to measure real-world performance and outcomes, detect adverse events, or identify bias and dataset drift. Here we introduce MedLog, a protocol for event-level logging of medical AI. Each time an AI model interacts with a human, another algorithm, or an automated workflow, MedLog creates a record. Each record contains nine core fields: header, model, user, target, inputs, artifacts, outputs, outcomes, and feedback. We apply MedLog across four deployments in the US, Switzerland, and Vietnam: ICU deterioration prediction, tetanus progression monitoring from wearable signals, automated sepsis quality reporting, and patient attendance prediction. MedLog records capture model behavior, workflow interactions, and downstream outcomes, including AI performance degradation during severe weather events in patient attendance prediction and increased laboratory testing after ICU deterioration alerts. MedLog limits the data footprint through risk-based sampling, lifecycle-aware retention policies, and write-behind caching, enabling deployment in low-resource settings. It also supports detailed traces for complex, agentic, or multi-stage workflows, creating a foundation for continuous monitoring, auditing, and improvement of medical AI.

06.
medRxiv (Medicine) 2026-06-17

Perceptions of aging well among older adults with heart failure: insights from a qualitative study

Background: Heart failure (HF) is a prevalent and often debilitating cardiovascular condition among older adults, frequently accompanied by multimorbidity, functional limitations, and the need to age in place. Traditional models of successful aging emphasize disease absence and preserved function, yet most individuals with HF live with ongoing symptoms and chronic health challenges. How older adults with HF define aging well, particularly across different socioeconomic contexts, remains underexplored. Objectives: To explore how older adults with HF conceptualize aging well and to identify perceived facilitators and barriers across more and less resourced New York City neighborhoods. Methods: We conducted semi-structured interviews with 20 adults diagnosed with HF residing in Manhattan and Brooklyn neighborhoods classified by 2019 United States Census data. Interviews were guided by Rowe and Kahn's model. Transcripts were analyzed using an inductive-deductive thematic approach and interpreted in alignment with the Healthy People 2030 framework. Results: Participants had a mean age of 69 years; 50% identified as Black and 50% were women. Despite functional limitations, 65% reported aging well. Five themes emerged: maintaining physical function, maintaining cognitive function, sustaining social relationships, avoiding pain, and promoting overall well-being. Avoiding pain and promoting well-being extended beyond traditional models. Neighborhood context shaped priorities, with financial stability emphasized in more affluent areas and social cohesion prioritized in less affluent communities. Conclusions: Older adults with HF frequently perceive themselves as aging well despite chronic illness, reframing successful aging beyond disease avoidance. These findings support a patient-centered, place-informed model of aging well with implications for healthcare delivery and policy.

07.
arXiv (CS.CV) 2026-06-18

Quantile Transfer for Reliable Operating Point Selection in Visual Place Recognition

Visual Place Recognition (VPR) is a key component for localisation in Global Navigation Satellite System (GNSS)-denied environments, but its performance critically depends on selecting an image matching threshold (operating point) that balances precision and recall. Thresholds are typically hand-tuned offline for a specific environment and fixed during deployment, leading to degraded performance under environmental change. We propose a method that automatically selects the operating point of a VPR system to maximise recall at 100% precision. The method uses a small calibration traversal with known correspondences and transfers thresholds to deployment via quantile normalisation of similarity score distributions. This quantile transfer ensures that thresholds remain stable across calibration sizes and query subsets. Experiments with seven state-of-the-art VPR techniques across five benchmark datasets demonstrate that our proposed approach consistently outperforms existing baselines, enabling the underlying VPR technique to operate at 100% precision in approximately twice as many deployment scenarios (median improvement), while retrieving up to 29% more correct matches at that precision. The method eliminates manual tuning by adapting to new environments and generalising across operating conditions. Our code is available at https://github.com/DhyeyR-007/Quantile-Transfer-for-Reliable-VPR.

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

Feature-preserving Latent-EnKF for Data Assimilation of Flows with Shocks

arXiv:2606.12559v1 Announce Type: cross Abstract: The ensemble Kalman filter (EnKF) is widely adopted for sequential data assimilation, but fails for solutions with discontinuities, such as shocks in compressible flows. Uncertainty in shock location induces multimodal ensemble statistics that violate the Gaussian assumptions underlying the EnKF, producing large-scale spurious oscillations in the analysis state. We introduce a feature-preserving latent-EnKF that performs the ensemble update in a learned low-dimensional latent space, where shock and flow features admit a smooth manifold representation, thereby preserving sharp features during EnKF analysis. The updated latent state is mapped back to physical state through a shared decoder for all ensemble members. The algorithm eliminates the member-specific ordered training and positivity flooring used in prior approaches. Numerical experiments on a Sod shock tube and Mach 2 shock interaction with a 2D cylinder, using sparse and noisy observations, show accurate feature recovery of shocks and contact discontinuities without spurious oscillations.

09.
arXiv (CS.LG) 2026-06-19

MolGraphBench: A Benchmark of GNN Architectures for Molecular Regression Tasks

arXiv:2602.20573v3 Announce Type: replace Abstract: Molecules are often represented as SMILES strings, which can be readily converted to hand-crafted descriptors or fingerprints (FP) for molecular property prediction. Research has demonstrated that SMILES can be converted to molecular graphs $G = (V, E)$, with atoms as nodes $(V)$ and bonds as edges $(E)$. These molecular graphs can subsequently be used to train graph neural networks (GNN) models. Despite the recent surge in application of GNN (existing and novel architectures) for molecular property prediction, a rigorous benchmark is still lacking. We propose MolGraphBench, a comprehensive benchmark of four commonly used GNN models for molecular property prediction. Benchmarking results demonstrate graph convolutional network (GCN) and graph isomorphism networks (GIN) as the optimal GNN architectures for molecular graph regression tasks, based on absolute performance, training efficiency, transfer learning and prediction quality. The study also indicates the non-complementary nature of molecular fingerprints in the fusion (GNN-FP) framework. Furthermore, our GNN models achieved performance superior or comparable performance to current state-of-the-art GNN baselines across three datasets (GCN with RMSE of $0.518$ on B3DB, GIN-FP with RMSE of $1.022$ on FreeSolv and GIN with MAE of $63.783$ on RT datasets). Findings from this study indicate that type of GNN-layer, should be treated as a tunable hyperparameter rather than a fixed design choice to achieve superior performance.

10.
arXiv (quant-ph) 2026-06-25

Rounding Almost Commuting Hamiltonians

arXiv:2605.26096v2 Announce Type: replace Abstract: Commuting Hamiltonians lie at the boundary between classical constraint satisfaction and quantum many-body physics, exhibiting rich quantum structure while remaining more tractable than general noncommuting models. In contrast, physical Hamiltonians are rarely exactly commuting, which naturally motivates the study of almost commuting Hamiltonians. Despite their relevance, the implications of approximate commutation are only poorly understood. In this work, we show how to efficiently approximate any almost commuting $2$-local qubit Hamiltonian by a commuting one: we give a new locality-preserving algorithmic rounding technique that maps any $2$-local Hamiltonian $H=\sum_{i=1}^m h_i$ with $\|[h_i,h_j]\| \leq \epsilon$ to a nearby Hamiltonian $\hat{H}$ whose terms pair-wise commute, and which is within overall distance $\|H-\hat{H}\| = O(m\,\epsilon^{1/6})$. As a consequence, we show that $\delta$-approximations to the ground energy for $\epsilon$-almost commuting $2$-local qubit Hamiltonians lie in $\mathsf{NP}$ when $\delta \gg m\epsilon^{1/6}$, extending the classical containment well beyond the commuting setting. Finally, we present two applications of our rounding framework: Gibbs sampling and fast Hamiltonian simulation for almost commuting systems.

11.
arXiv (CS.AI) 2026-06-16

Auditing Reward Hackability in Code RL Training Environments

arXiv:2606.16062v1 Announce Type: new Abstract: We measure the rate at which code RL environments accept incorrect solutions as correct. On a 49-task sample of SWE-bench Verified, 28.5% of tasks have test suites weak enough that a Docker-verified incorrect patch passes them. On 20 R2E-Gym tasks across 6 repositories, the same pipeline at single-shot exploit generation yields 25.0%. A random-effects meta-analysis over 134 frontier model submissions to SWE-bench Verified finds, within the same human-rated difficulty stratum, model Pass@1 is +14.14 percentage points higher on flagged-hackable tasks than on robust ones (95% CI [+11.80, +16.48]; one-sided p < 10^-6; I^2 = 0%; 123 of 134 models positive). We then describe a procedure for hardening the broken tasks. An inline LLM judge with a Docker gold-sanity gate runs each generated test against the gold solution before the judge is consulted. On the 11 broken tasks in the audit, the gate flags 65 of 105 decisive LLM-generated tests as failing on the gold patch itself, a 61.9% per-augmentation defect rate the LLM judge alone misses. With diversity-biased retry, the loop converges 9 of 11 tasks to a gated upgrade.

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

Succeeding at Scale: Enterprise Retrieval Benchmark Construction and Index-Preserving Query Adaptation for Multi-Tenant Search

Large-scale multi-tenant retrieval systems generate extensive query logs but lack curated relevance labels for effective domain adaptation, resulting in substantial underutilized "dark data." This challenge is compounded by the high cost of model updates, as jointly fine-tuning query and document encoders requires full corpus re-indexing, which is impractical in multi-tenant settings with thousands of isolated indices. We introduce DevRev-Search, a passage retrieval benchmark for technical customer support built via a fully automated pipeline. Candidate generation uses fusion across diverse sparse and dense retrievers, followed by an LLM-as-a-Judge for consistency filtering and relevance labeling. We further study and systematically evaluate index-preserving query-only adaptation strategies that fine-tune only the query-encoder while keeping the document indices fixed. Experiments on DevRev-Search, SciFact, and FiQA-2018 show that parameter-efficient fine-tuning of the query encoder delivers a remarkable quality-efficiency trade-off, enabling scalable and practical enterprise multi-tenant retrieval.

13.
medRxiv (Medicine) 2026-06-11

Ferritin across long-term conditions in England: cross-sectional primary care study

Background Iron deficiency (ID) is a readily treatable condition once identified. Ferritin is the primary diagnostic marker, but cut-offs vary and inflammation complicates interpretation in patients with long-term conditions (LTCs). Aim To describe ferritin distribution and the prevalence of threshold-defined low ferritin in adults with and without LTCs in primary care. Design and setting Cross-sectional observational study using routinely collected electronic health records from a national primary care database in England (1st January 2015 to 31st December 2021). Method Adults with >1 ferritin test in Clinical Practice Research Datalink (CPRD) Aurum were included. LTCs were identified using validated primary-care code lists. Outcomes included ferritin distribution and threshold-defined ID prevalence using World Health Organization (WHO) (

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

Bayesian 3D Steerable CNNs: Enabling Equivariance and Uncertainty Quantification Simultaneously

arXiv:2606.15479v1 Announce Type: cross Abstract: Steerable convolutional neural networks (Steerable-CNNs) guarantee SE(3)-equivariance by parameterizing kernels as linear combinations of steerable basis functions, but their deterministic nature precludes uncertainty quantification - limiting their use in settings where confidence estimates are essential. We propose a Bayesian Steerable-CNN that places posterior distributions over the basis coefficients, yielding stochastic kernels while preserving equivariance exactly. The loss function of the model is obtained via variational inference and minimized by Bayes-by-Backpropagation. The framework admits a decomposition of predictive uncertainty into epistemic and aleatoric components. Empirically, the model attains competitive classification accuracy alongside an expected calibration error of 0.0263 and outperforms its deterministic counterpart by up to 6.17% under distributional shift induced by additive Gaussian noise. Furthermore, we leverage the model's uncertainty estimates to enhance its performance significantly, achieving a notable gain - approximately 4% higher accuracy across 84% of the test dataset. A statistically significant negative correlation between epistemic uncertainty and prediction error confirms that the learned posterior variance is semantically meaningful. The framework unifies Bayesian uncertainty quantification with the inductive bias of equivariant CNNs.

15.
arXiv (CS.AI) 2026-06-19

HilDA: Hierarchical Distillation with Diffusion for Advancing Self-Supervised LiDAR Pre-trainin

arXiv:2606.20189v1 Announce Type: cross Abstract: Leveraging Vision Foundation Models (VFMs) for camera-to-LiDAR knowledge distillation offers a promising solution to the scarcity of annotated data needed to represent the immense geometric and kinematic diversity of real-world autonomous driving (AD). However, current approaches typically treat VFMs as black-box teachers, relying exclusively on frame-wise feature similarity. Consequently, they do not fully exploit the teacher's layer-wise semantic structure and global context, as well as the rich spatiotemporal information inherent in LiDAR sequences. We propose HilDA, a self-supervised pretraining framework for LiDAR backbones that better captures the semantic what and geometric where needed for driving tasks. HilDA combines hierarchical distillation comprising multi-layer distillation for progressive semantic alignment and global context distillation for scene-level semantics, with a temporal occupancy diffusion objective promoting spatiotemporal consistency. Models pre-trained with HilDA achieve state-of-the-art results on cross-modal distillation benchmarks and outperform models trained via prior distillation approaches on 3D object detection, scene flow, and semantic occupancy prediction. Code available at: https://maxiuw.github.io/hilda.

16.
medRxiv (Medicine) 2026-06-15

Iron deficiency testing among people with incident heart failure in primary care

Background: Given around 50% of people with heart failure have a degree of iron deficiency, guidelines recommend screening. It is uncertain to what extent this is done in primary care and whether testing is equitable. Aim: To report the proportion of people with incident heart failure who undergo a ferritin test within 12 months. Design and setting: Retrospective primary care cohort study using Clinical Practice Research Datalink Aurum data, between 2016 and 2021. Methods: We report the proportion of adults with an incident diagnosis of heart failure who received a ferritin test within 12 months. Multivariable logistic regression was used to examine the odds of testing based on key demographic covariates and co-morbidities. Results: Among 105,749 individuals with an incident diagnosis of heart failure (mean age 71.6 years, SD 14.3), only 35,688 (33.7%) received a ferritin test within the subsequent year. Increasing age (odds ratio 1.25 per 10-year increase, 95% CI: 1.24-1.27), female sex (male sex OR 0.86, 0.84-0.89) and Asian ethnicity (OR 1.70, 1.59-1.80) were all associated with increased odds of testing as were diagnoses of coeliac disease (OR 1.86, 1.58-2.21), type 1 diabetes (OR 1.82, 1.51-2.19) and cirrhosis (OR 1.64, 1.43-1.87). There was geographic variation in testing, even in adjusted analyses. Conclusion: In a large primary care dataset, two thirds of people with incident heart failure did not receive a ferritin test for iron deficiency within a year of diagnosis demonstrating a gap in current practice and an opportunity for improvements in service delivery.

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

ThinkJEPA: Empowering Latent World Models with Large Vision-Language Reasoning Model

Recent progress in latent world models (e.g., V-JEPA2) has shown promising capability in forecasting future world states from video observations. Nevertheless, dense prediction from a short observation window limits temporal context and can bias predictors toward local, low-level extrapolation, making it difficult to capture long-horizon semantics and reducing downstream utility. Vision–language models (VLMs), in contrast, provide strong semantic grounding and general knowledge by reasoning over uniformly sampled frames, but they are not ideal as standalone dense predictors due to compute-driven sparse sampling, a language-output bottleneck that compresses fine-grained interaction states into text-oriented representations, and a data-regime mismatch when adapting to small action-conditioned datasets. We propose a VLM-guided JEPA-style latent world modeling framework that combines dense-frame dynamics modeling with long-horizon semantic guidance via a dual-temporal pathway: a dense JEPA branch for fine-grained motion and interaction cues, and a uniformly sampled VLM thinker branch with a larger temporal stride for knowledge-rich guidance. To transfer the VLM's progressive reasoning signals effectively, we introduce a hierarchical pyramid representation extraction module that aggregates multi-layer VLM representations into guidance features compatible with latent prediction. Experiments on hand-manipulation trajectory prediction show that our method outperforms both a strong VLM-only baseline and a JEPA-predictor baseline, and yields more robust long-horizon rollout behavior.

18.
medRxiv (Medicine) 2026-06-22

The direct economic impact of surgical non-response in orthopaedic hip, knee, and spine surgery for osteoarthritis: a cost-utility analysis

Background Annually, nearly 2 million hip, knee, and spinal inpatient surgeries are performed in Canada and the US for osteoarthritis (OA), costing over $37 billion in hospital expenditures. However, 15-30% of patients experience limited or no improvement, resulting in poor value for money. This study evaluated the one-year cost-utility of joint and spine procedures for OA by comparing non-responders to responders, considering various responder definitions. Methods Individual micro-costing data were collected for 1,175 elective hip, knee, and spine patients enrolled in the Longitudinal Evaluation in the Arthritis Program - Osteoarthritis (LEAP-OA) between 2014 and 2018. Quality-adjusted life years (QALYs) were derived using the SF-6D utility index. One-year incremental cost-utility ratios (ICURs) were calculated from the hospital perspective. Results Responder rates varied by definition, ranging from 78%-94% for hip replacements, 64%-90% for knee replacements, 60%-64% for spine fusions, and 50%-68% for spine decompressions. Corresponding ICURs were: $45,956-$51,773/QALY for responders versus $108,593-$485,762/QALY for non-responders for hip replacements; $54,831-$71,151/QALY for responders versus $200,486-$1,203,596/QALY for non-responders for knee replacements; $65,980-$74,422/QALY for responders versus $262,039-$729,686/QALY for non-responders for spine fusions; and $29,947-$42,168/QALY for responders versus $63,195-$662,586/QALY for non-responders for spine decompressions. Conclusions While surgical response rates were highly dependent on the responder definition, ICURs for non-responders were significantly higher than those for responders across all definitions. Beyond the negative impact on patients, there is a compelling economic argument for investment in improved pre-operative identification of patients at risk of surgical non-response. Such efforts could enable more personalized, value-based care pathways and reduce the provision of low-value surgical interventions.

19.
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

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

Alternate loss functions and regression models that achieve robustness to outliers by modulating the learning rate

arXiv:2606.22068v2 Announce Type: replace-cross Abstract: Most real-world datasets used for training supervised learning models are contaminated with noisy data and outliers leading to large prediction errors. This paper proposes a new approach for achieving robustness where the learning rate is modulated by a factor that is sensitive to outliers. In this approach a reduction of the learning rate is shown to be achieved by using alternate loss functions that are infinitely differentiable, strictly convex or quasiconvex and more closely approximate the absolute error than Huber and log-cosh losses. A comparison of the performance of regression models trained with different loss functions on a wide variety of benchmarks and datasets is presented to demonstrate the superior performance of the Square Root Loss (SRL) and Smooth Mean Absolute Error (SMAE) losses proposed in this paper. Two new robust linear regression models are presented. Highly vectorized robust parameter update formulae that take advantage of modern GPUs for both stochastic and batch gradient descent are presented.

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

One Probe Won't Catch Them All: Towards Targeted Deception Detection

arXiv:2602.01425v2 Announce Type: replace Abstract: Linear probes are a promising approach for monitoring AI systems for deceptive behaviour. Previous work has shown that a linear classifier trained on a contrastive instruction pair and a simple dataset can achieve good performance. However, these probes exhibit notable failures even in straightforward scenarios, including spurious correlations and false positives on non-deceptive responses. In this paper, we demonstrate that deception detection is inherently heterogeneous: while a single universal probe achieves modest improvements (+0.032 AUC), post-hoc oracle analysis reveals substantially higher potential (+0.108 AUC) when probes are matched to specific deception types, and synthetic validation experiments suggest this ceiling is achievable a priori when the deception type is known in advance. Our findings reveal that instruction pairs capture deceptive intent rather than content-specific patterns, explaining why prompt choice dominates probe performance (70.6% of variance). Given this heterogeneity, we conclude that organizations should define their specific threat models and deploy appropriately matched probes rather than seeking a universal deception detector.

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

Towards CONUS-Wide ML-Augmented Conceptually-Interpretable Modeling of Catchment-Scale Precipitation-Storage-Runoff Dynamics

arXiv:2510.02605v2 Announce Type: replace Abstract: While many modern studies are dedicated to ML-based large-sample hydrologic modeling, these efforts have not necessarily translated into predictive improvements that are grounded in enhanced physical-conceptual understanding. Here, we report on a CONUS-wide large-sample study (spanning diverse hydro-geo-climatic conditions) using ML-augmented physically-interpretable catchment-scale models of varying complexity based in the Mass-Conserving Perceptron (MCP). Results were evaluated using attribute masks such as snow regime, forest cover, and climate zone. Our results indicate the importance of selecting model architectures of appropriate model complexity based on how process dominance varies with hydrological regime. Benchmark comparisons show that physically-interpretable mass-conserving MCP-based models can achieve performance comparable to data-based models based in the Long Short-Term Memory network (LSTM) architecture. Overall, this study highlights the potential of a theory-informed, physically grounded approach to large-sample hydrology, with emphasis on mechanistic understanding and the development of parsimonious and interpretable model architectures, thereby laying the foundation for future models of everywhere that architecturally encode information about spatially- and temporally-varying process dominance.

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

OpenThoughts-Agent: Data Recipes for Agentic Models

arXiv:2606.24855v1 Announce Type: new Abstract: Agentic language models dramatically expand the applications of AI yet little is publicly known about how to curate training data for broadly capable agents. Existing open efforts such as SWE-Smith, SERA, and Nemotron-Terminal typically target a single benchmark, leaving open the question of how to train models that generalize across diverse agentic tasks. The OpenThoughts-Agent (OT-Agent) project addresses this gap with a fully open data curation pipeline for training agentic models. We conduct more than 100 controlled ablation experiments to systematically investigate each stage of the pipeline, yielding insights on the importance of task sources and diversity. We then assemble a training set of 100K examples from our pipeline and fine-tune Qwen3-32B on this dataset, which yields an average accuracy of 44.8% across seven agentic benchmarks and a 3.9 percentage point improvement over the strongest existing open data agentic model (Nemotron-Terminal-32B, 40.9%). Moreover, our training data exhibits strong scaling properties, outperforming alternative open datasets at every training set size in compute-controlled comparisons. We publicly release our training sets, data pipeline, experimental data, and models at openthoughts.ai to support future open research on agentic model training.

25.
arXiv (CS.CL) 2026-06-19

Benchmarking Local LLMs for Natural-Language-to-SQL Querying in Biopharmaceutical Manufacturing: An Empirical Benchmark on Consumer-Grade Hardware

Biopharmaceutical manufacturing organizations operate under regulatory frameworks such as FDA guidance, EU Good Manufacturing Practice (GMP), and the EU AI Act, which can restrict the use of cloud-based artificial intelligence systems. Locally deployed large language models (LLMs) offer a privacy-preserving alternative, but their suitability for pharmaceutical manufacturing tasks remains underexplored. This study evaluates four open-source LLMs (Qwen 2.5 Coder 7B, Llama 3.1 8B, Mistral 7B, and Meditron 7B) deployed locally via Ollama for natural-language-to-SQL generation over a pharmaceutical manufacturing database. A FastAPI-based evaluation platform, PharmaBatchDB AI, was developed using a synthetic Microsoft SQL Server database containing approximately 63,000 records across Batch, Manufacturing Execution System (MES), and Clean-In-Place (CIP) modules. Models were benchmarked on 60 domain-specific natural-language questions using metrics including SQL extraction rate, SQL compliance, factual consistency, ROUGE-L, hallucination rate, throughput, and latency. Qwen 2.5 Coder 7B, Llama 3.1 8B, and Mistral 7B generated SQL for all evaluation tasks, while Meditron 7B failed on nearly all tasks due to context-window limitations and poor SQL generation capability. Llama 3.1 8B achieved the highest SQL compliance, whereas Qwen 2.5 Coder 7B achieved the strongest overall text similarity and factual consistency. Performance differences between the two leading models were not statistically significant. The results show that code-tuned general-purpose LLMs outperform a domain-specific biomedical model on structured query generation for pharmaceutical manufacturing data. Although fully local, GxP-aligned NLQ systems are feasible on consumer hardware, current performance levels still require human oversight and downstream validation for regulated use.