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01.
arXiv (CS.AI) 2026-06-15

Securing the Future of IoMT in the Post-Quantum Era: An Edge-Native Federated Learning Approach

arXiv:2606.14515v1 Announce Type: cross Abstract: Internet of Medical Things (IoMT) devices operate under strict resource constraints while handling highly sensitive health data, making security and privacy critical concerns. Federated learning (FL) further complicates this landscape, as model updates exchanged during training may unintentionally expose private medical information. Emerging quantum computing capabilities threaten the long-term viability of conventional lightweight cryptographic mechanisms, motivating the integration of Post-Quantum Cryptography (PQC) into IoMT systems. This article discusses key enabling technologies for quantum-resilient IoMT, including post-quantum key establishment, lightweight encryption, and edge-native orchestration. We propose a scalable Kubernetes-based framework that integrates PQC into FL-enabled IoMT environments and validate it on a Raspberry Pi testbed. Results demonstrate that distributed cryptographic processing significantly reduces latency compared to sequential designs while maintaining feasible resource overhead. The primary contribution of this work lies in the design and validation of a secure orchestration and communication framework for FL-enabled IoMT systems. We conclude by outlining future directions toward energy-aware architectures, intelligent security optimization, and resilient next-generation Intelligent Internet of Medical Things (IIoMT) ecosystems.

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

Categorical Robustness Assessment for Machine Learning based Network Intrusion Detection Systems

arXiv:2606.12075v1 Announce Type: cross Abstract: Network Intrusion Detection Systems (NIDS) heavily utlize Machine Learning (ML) but ML models can be manipulated via adversarial attacks. These attacks add carefully crafted perturbations to network traffic data that leads to misclassifications. While prior work has demonstrated adversarial vulnerabilities in isolated settings, systematic cross-architecture as well as class and category of attack based comparisons under controlled attack conditions remain limited, leaving practitioners without clear guidance on which models to deploy in adversarial environments. This paper asks a simple question: what type of classifier architectures actually hold up when attackers try to manipulate the systems? We put three popular architectures through their paces: a 1D Convolutional Neural Network, a Long Short-Term Memory (LSTM) network, and a Random Forest (RF) ensemble. Using the ACI-IoT-2023 dataset (over 1.2 million samples spanning 12 attack types), we subject each model with FGSM and PGD adversarial attacks, which apply gradient-based perturbations in normalized feature space consistent with established adversarial ML evaluation protocols, at perturbation budgets ranging from $\epsilon=0.01$ to $\epsilon=0.1$. Surprisingly, Random Forest achieved near-perfect baseline accuracy (99.98\%), yet collapsed catastrophically under attack, dropping 73 percentage points at the smallest perturbation we tested. CNN, on the other hand, retained 95.5\% accuracy at $\epsilon=0.01$ and degraded gracefully as perturbations increased. LSTM fell somewhere in between. These findings flip the conventional wisdom where high baseline accuracy means nothing if a model shatters at the first sign of adversarial pressure. For practitioners deploying intrusion detection in adversarial environments, we recommend CNN-based architectures and provide scenario-specific deployment guidance.

03.
arXiv (CS.AI) 2026-06-18

PSyGenTAB: A Privacy-Preserving Framework for Synthetic Clinical Tabular Data Generation via Constrained Optimization

arXiv:2606.18518v1 Announce Type: cross Abstract: The development of medical AI is constrained by limited access to high-quality clinical data due to institutional silos and strict privacy regulations such as HIPAA and GDPR. Synthetic data generation offers a potential solution, but existing methods lack principled mechanisms to explicitly manage the privacy-utility trade-off, often degrading clinically meaningful patterns or risking patient re-identification. We present PSyGenTAB, a privacy-preserving generative framework that formulates synthetic healthcare data generation as a constrained optimization problem solved using the Augmented Lagrangian Method. By embedding configurable privacy constraints directly into model training, PSyGenTAB enforces minimum privacy thresholds while maximizing clinical data utility. Across multiple clinically motivated benchmarks, PSyGenTAB preserves inter-feature clinical relationships and minority-class diagnostic patterns essential for reliable health AI. Downstream evaluation using Train-on-Synthetic, Test-on-Real and Train-on-Real, Test-on-Synthetic protocols shows that models trained on synthetic data achieve performance comparable to those trained on real patient records. Privacy auditing further demonstrates reduced exact record reproduction and strong resilience to membership inference attacks. These results establish PSyGenTAB as a principled framework for balancing privacy protection and clinical utility in synthetic healthcare data, supporting secure cross-institutional AI development.

04.
medRxiv (Medicine) 2026-06-22

Use of the Pharmacy First service in England in the first 12 months: geographic variation and health system context

Objectives: The Pharmacy First (PF) service was introduced across England from 31 January 2024 to expand the clinical role of community pharmacies and improve access to primary care. This paper describes use of PF in its first 12 months, in terms of uptake, access routes, consultation outcomes, geographic variations, service costs and antimicrobial supply. Methods: A descriptive analysis of all PF consultations submitted for payment to NHS Business Services Authority in England between 31 January 2024 and 31 January 2025. Pharmacy-level consultation data were linked to national data on population, location and pharmacy characteristics. PF use was examined using population-standardised consultation rates and consultations per pharmacy. Results: During the first year of implementation, 2,205,731 PF consultations were recorded as delivered across 11,349 pharmacies, with payment of GBP123 million to pharmacies. Uptake increased steadily over time. Most consultations were for acute sore throat (33%) and uncomplicated urinary tract infection (27%), with corresponding antibiotics, phenoxymethylpenicillin and nitrofurantoin being the most supplied. Most people self-referred (74%) into the service, with 95% of consultations managed without onward referral. Substantial geographic variation was observed. Northern regions had higher use based on the eligible population. The South East and Midlands had higher activity per pharmacy. London showed a distinct pattern, with higher self-referral into the service, lower medication supply and higher referral to other healthcare services. Higher consultation volume was weakly associated with pharmacy characteristics, including opening hours, pharmacy type and retail setting, and local context, in terms of socio-economic and geographic factors. Conclusions: PF had immediate uptake and is operating primarily as a direct-access model for common acute conditions. Findings suggest that PF is contributing to improved access to care and may shift demand away from general practice. However, the service uptake appears to be shaped by geographic location, proximity to other healthcare services and pharmacy characteristics.

05.
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.

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

Agents' Last Exam

Recent AI systems have achieved strong results on a wide range of benchmarks, yet these gains have not translated into economically meaningful deployment across many professional domains. We argue that this gap is largely an evaluation problem: widely used benchmarks lack sustained performance measurement on real and economically valuable workflows. This paper introduces Agents' Last Exam (ALE), a benchmark designed to evaluate AI agents on long horizon, economically valuable, real world tasks with verifiable outcomes. Developed in collaboration with 250+ industry experts, ALE covers non-physical industries defined with reference to O*NET / SOC 2018 (the U.S. federal occupational taxonomy). It is organized around a task taxonomy with 55 sub fields grouped into 13 industry clusters covering 1K+ tasks. Current results show that the hardest tier remains far from saturated: across mainstream harness and backbone configurations, the average full pass rate is below 1%. ALE is designed as a living benchmark: its task pool grows continuously as new workflows and industries are onboarded. More broadly, ALE is intended not merely as another leaderboard, but as an instrument for closing the gap between benchmark success and GDP relevant impact.

07.
arXiv (quant-ph) 2026-06-16

Benchmarking Quantum Computers via Protocols, Comparing IBM's Heron vs IBM's Eagle

arXiv:2603.04377v3 Announce Type: replace Abstract: As quantum computing hardware rapidly advances, objectively evaluating the capabilities and error rates of new processors remains a critical challenge for the field. A clear and realistic understanding of current quantum performance is essential for guiding research priorities and driving meaningful progress. In this work, we apply and extend a protocol-based benchmarking methodology (Meirom, Mor, Weinstein Arxiv 2505.12441) that utilizes well-defined \underline{quantumness} thresholds. By evaluating performance at protocol level rather than the gate level, this approach provides a transparent and intuitive assessment of whether specific quantum processors, or isolated sub-chips within them, can demonstrate a practical quantum advantage. To illustrate the utility of this method, we compare two generations of IBM quantum computers: the older Eagle architecture and the newer Heron architecture. Our findings reveal the genuine operational strengths and limitations of these devices, demonstrating substantial performance improvements in the newer Heron generation. This work was made possible by IBM Quantum policies that enable independent and objective assessment of its quantum computers and sub-chips. We strongly encourage other companies to emulate the independent qubit availability and the fair pricing that allow researchers to perform such assessments.

08.
arXiv (CS.LG) 2026-06-17

Predictive Analytics in E-Commerce for CustomerBehavior Forecasting using hybrid Ret-DNN withXGBoost Model

arXiv:2606.17931v1 Announce Type: new Abstract: In recent years, electronic (E) commerce services have rapidly increased in the daily lives of people, which helpsthem to purchase products online. However, retail platforms have struggled to understand customer behavior and make it difficult to predict their future purchases. To overcome these challenges, this study proposes a hybrid Retail Deep NeuralNetwork (Ret-DNN) with an Extreme Gradient Boosting(XGBoost) model for capturing temporal features and tabular dynamics of retail data. First, data were sourced from a UnitedKingdom (UK)-based online retailer that contains transactions with almost 500,000 records. Then, the collected data were pre-processed using a series of techniques, such as data cleaning, outlier handling, temporal feature extraction, feature encoding, and z-score normalization, to ensure that the data were ready for model training and testing. Subsequently, the preprocessed data were fed into the Ret-DNN model, which acts as a feature extractor to understand the complete context of customer transactions. Further, the extracted data were fed as input into the XGBoost model, which predicted the final output as the purchase probability of customers. Finally, the proposed Ret-DNN XGBoost model achieved better results by attaining aMean Absolute Error (MAE) 0.2193 when compared to the existing Ret-DNN model. Keywords: Customer behavior forecasting, extreme gradientboosting, electronic commerce, predictive analytic, retail deepneural networks.

09.
medRxiv (Medicine) 2026-06-24

Rare protein-coding variation and the genetic architecture of height in >1.4 million individuals

Highly heritable, polygenic, and easily measured, adult height has long been the model trait in human genetics. While the landscape of height-associated common genetic variation has been studied extensively, rare variation remains relatively unexplored. Using rare protein-altering variants in a discovery set of 826,066 exomes, we identify 207 height-associated genes - 98% of which replicate in an additional 624,567 individuals. The rarest and most deleterious class of variation, singleton (frequency

10.
arXiv (CS.CL) 2026-06-11

Neural FOXP2 – Language Specific Neuron Steering for Targeted Language Improvement in LLMs

LLMs are multilingual by training, yet their lingua franca is often English, reflecting English language dominance in pretraining. Other languages remain in parametric memory but are systematically suppressed. We argue that language defaultness is governed by a sparse, low-rank control circuit, language neurons, that can be mechanistically isolated and safely steered. We introduce Neural FOXP2, that makes a chosen language (Hindi or Spanish) primary in a model by steering language-specific neurons. Neural FOXP2 proceeds in three stages: (i) Localize: We train per-layer SAEs so each activation decomposes into a small set of active feature components. For every feature, we quantify English vs. Hindi/Spanish selectivity overall logit-mass lift toward the target-language token set. Tracing the top-ranked features back to their strongest contributing units yields a compact language-neuron set. (ii) Steering directions: We localize controllable language-shift geometry via a spectral low-rank analysis. For each layer, we build English to target activation-difference matrices and perform layerwise SVD to extract the dominant singular directions governing language change. The eigengap and effective-rank spectra identify a compact steering subspace and an empirically chosen intervention window (where these directions are strongest and most stable). (iii) Steer: We apply a signed, sparse activation shift targeted to the language neurons. Concretely, within low to mid layers we add a positive steering along the target-language dominant directions and a compensating negative shift toward the null space for the English neurons, yielding controllable target-language defaultness.

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

LAUKIN: A Multi-jurisdictional Common Law Contract Dataset

Multinational companies increasingly require cross-jurisdictional contract review, yet existing legal NLP datasets are largely restricted to a single jurisdiction. We introduce LAUKIN (Legal equivalence dataset of Australia, UK, and INdia), a dataset of clause pairs (AU-UK, UK-IN, IN-AU) labelled for boolean legal equivalence. We develop a novel multi-stage retrieval and reranking pipeline to construct the initial clause pair mapping, with a subset of clause pairs subsequently annotated by legal experts as Equivalent or Not Equivalent. The dataset comprises 14,727 clause pairs from 204 contracts across 8 agreement types, of which 3,000 are manually labelled: 900 train, 600 dev, and 1,500 test. We evaluate 12 models across 4 techniques, achieving a best macro-F1 of 65.11%, establishing LAUKIN as a challenging benchmark. Results reveal that, despite shared legal heritage, drafting conventions diverge significantly across jurisdictions, making cross-jurisdictional equivalence classification non-trivial. LAUKIN also includes 11,727 unlabelled training pairs to support future semi-supervised learning research in legal NLP.

12.
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) (

13.
arXiv (CS.CL) 2026-06-16

MAWARITH: A Dataset and Benchmark for Legal Inheritance Reasoning with LLMs

Islamic inheritance law is challenging for large language models because solving inheritance cases requires complex, structured, multi-step reasoning and the correct application of juristic rules to compute heirs' shares. We introduce MAWARITH, a large-scale annotated dataset of 12,500 Arabic inheritance cases for training and evaluating models on the full reasoning chain: (i) identifying eligible heirs, (ii) applying blocking (\d{hajb}) and allocation rules, and (iii) computing exact inheritance shares. To the best of our knowledge, MAWARITH is the first Arabic corpus and benchmark designed for end-to-end Islamic inheritance reasoning. Unlike prior datasets that restrict inheritance case solving to multiple-choice questions, MAWARITH supports the full reasoning chain and provides step-by-step solutions with justifications grounded in classical juristic sources and established inheritance rules, as well as exact share calculations. This enables models to learn how to generate detailed, step-by-step responses to user queries that reflect real-world Islamic inheritance cases. To evaluate models beyond final-answer accuracy, we propose MIR-E (Mawarith Inheritance Reasoning Evaluation), a weighted multi-stage metric that scores key reasoning stages and captures error propagation across the pipeline. We evaluate six large language models in a zero-shot setting. A commercial model achieves about 90\%, whereas all evaluated open-source models remain below 50\%. Our error analysis identifies recurring failure patterns, including scenario misinterpretation, errors in heir identification, errors in share allocation, and missing or incorrect application of key inheritance rules such as \textquotesingle awl and radd. The MAWARITH dataset is publicly available at https://gitlab.com/nlpresearcher/mawarith.

14.
medRxiv (Medicine) 2026-06-16

Utilising Artificial Intelligence to Identify Ventricular Tachycardia Ablation Targets in Sinus Rhythm

Background and Aims: Machine learning has shown potential in predicting ablation targets for ventricular tachycardia (VT) in an animal model. This study progresses to externally validating deep learning approaches for human data. Methods: The development and external validation dataset included 21 and 13 patients, respectively, with structural VT undergoing catheter ablation. In the development datasets, electrophysiological studies were conducted using the AdvisorTM HD grid (EnsiteTM X), while both CARTO and Ensite Precision were used in the validation dataset. In each patient, VT ablation targets were defined as mapping points within 8 mm of VT isthmuses. Three advanced machine learning models were trained using cardiac mapping data acquired in both omnipolar and unipolar configurations during sinus rhythm and ventricular pacing. Discrimination was evaluated using nested leave-one-out cross-validation at patient level. Results: Overall, graph convolutional networks (GCNs), which integrate intracardiac signal waveforms with three-dimensional electroanatomical geometries, achieved the highest performance, with optimal results obtained from unipolar electrograms acquired in sinus rhythm (median AUC 0.793, sensitivity 83.6%, specificity 69.0%). This may be partly explained by the inclusion of repolarization dynamics in unipolar electrograms and the higher point density of sinus rhythm maps. Comparable performance was observed in the external dataset. Conclusion: This study demonstrates that graph convolutional networks applied to sinus rhythm EGM waveforms collected during substrate mapping can localise critical components of VT re-entry circuits. This approach has potential to provide fast and accurate ablation guidance without the need to induce and map VT, improving safety and efficacy of VT catheter ablation.

15.
arXiv (CS.AI) 2026-06-18

Benchmarking Action Spaces in Reinforcement Learning for Vision-based Robotic Manipulation

arXiv:2606.18594v1 Announce Type: cross Abstract: In real-world reinforcement learning (RL), the choice of action space can play a key role in shaping motion smoothness, safety, and overall task performance. In this study, we evaluate pose increment, pose velocity, joint position increment, and joint velocity across two vision-based manipulation tasks: object picking and pushing. We train policies in simulation and deploy them to the real world using sim-to-real transfer. We find that action-space representation indeed significantly affects sim-to-real performance. In particular, we find that the joint velocity action space is best for the vision-based picking and pushing tasks in terms of smoothness and final task performance. We also provide practical guidance for RL practitioners in choosing action spaces for both simulation and real-world experiments.

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

A complexity theory for non-local quantum computation

arXiv:2505.23893v2 Announce Type: replace Abstract: Non-local quantum computation (NLQC) replaces a local interaction between two systems with a single round of communication and shared entanglement. Despite many partial results, it is known that a characterization of entanglement cost in at least certain NLQC tasks would imply significant breakthroughs in complexity theory. Here, we avoid these obstructions and take an indirect approach to understanding resource requirements in NLQC, which mimics the approach used by complexity theorists: we study the relative hardness of different NLQC tasks by identifying resource efficient reductions between them. Most significantly, we prove that $f$-measure and $f$-route, the two best studied NLQC tasks, are in fact equivalent under $O(1)$ overhead reductions. This result simplifies many existing proofs in the literature and extends several new properties to $f$-measure. For instance, we obtain sub-exponential upper bounds on $f$-measure for all functions, and efficient protocols for functions in the complexity class $\mathsf{Mod}_k\mathsf{L}$. Beyond this, we study a number of other examples of NLQC tasks and their relationships.

17.
medRxiv (Medicine) 2026-06-23

Timing of S. aureus-related mortality in a large randomized clinical trial: Implications for future study design

Background: Longer follow-up periods in clinical trials for S. aureus bacteremia (SAB) may capture unrelated deaths, adding random noise that risks biasing trial results towards the null. Objective: To evaluate the timing and infection-relatedness of deaths within a large SAB clinical trial platform. Design: Blinded duplicate adjudication of trial deaths using a modified 7-point Likert-Scale. A third reviewer settled disagreements. Setting: 37 Canadian hospitals participating in the S. aureus Network Adaptive Platform (SNAP) Trial. Participants: 1515 adult patients recruited to SNAP between February 2022 and May 2026. Measurements: Timing and relatedness of 90-day deaths categorized as at least possibly SAB-related not likely to be SAB-related. Optimal follow-up cut-off was determined using Youden's index and graphically. Results: 247 deaths occurred; 97 (39.3%) were adjudicated as at least possibly SAB-related and 150 (60.7%) as not likely related. For probably/definitely related deaths, interrater agreement was 85.0% (Gwet's AC 0.73, substantial); for at least possibly related, it was 77.3% (Gwet's AC 0.55, moderate). Median survival was significantly shorter for SAB-related deaths (12 vs. 30.5 days; difference: 19 days earlier, 95% CI: 12-26, p

18.
arXiv (quant-ph) 2026-06-12

New bounds on private simultaneous quantum message passing

arXiv:2606.12557v1 Announce Type: new Abstract: In the private simultaneous message (PSM) setting, $k$ players obtain inputs $x_i\in\{0,1\}^n$ and then each send messages to a referee, who should learn $f(x_1,...,x_k)$ but no other information about $(x_1,...,x_k)$. The PSM setting was introduced as a minimal model for secure multiparty computation and has connections to Boolean function complexity. In the quantum setting, PSM has been related to non-local quantum computation (NLQC). The communication and correlation cost of implementing PSM remains poorly understood. Here, we give new upper and lower bounds on the (quantum) PSM model. For lower bounds, we show: 1) Nečiporuk's measure lower bounds the entanglement required for $k$-player quantum PSM with perfect correctness. This leads to quadratic lower bounds for explicit functions. 2) The rank of the communication matrix of $f(x_1,x_2)$ lower bounds 2-player quantum PSM with perfect privacy but imperfect correctness. This implies a previously unknown lower bound on classical PSM with imperfect correctness. When allowing quantum communication and shared entanglement, these are the first lower bounds on quantum PSM that make use of the privacy condition. For upper bounds, we show: 1) Letting $s$ be the size of a quantum circuit computing $f$, $d_f$ be the circuit depth, $k$ the number of players, $n$ the number of bits received by each player, and $\epsilon$ a correctness parameter, we obtain $\mathsf{PSM}_k^*(f) \leq (kn +s) \cdot \log^{O(d_f)}(s/\epsilon)$. 2) The square of the Fourier 1 norm of $f$, $\Vert \hat{f}\Vert_1^2$, upper bounds the classical PSM complexity, $\mathsf{PSM}(f)\leq O(\Vert \hat{f} \Vert^2_1)$. In proving the first upper bound, we generalize existing $T$-depth based techniques for NLQC from $2$ to $k\geq 2$ parties, and consider cases where the Clifford layers are restricted to having small light cones.

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

QIAS 2026: Overview of the Shared Task on Islamic Inheritance Reasoning

This paper presents a comprehensive overview of the QIAS 2026 shared task, organized as part of the OSACT7 Workshop and co-located with LREC 2026. The shared task was designed to evaluate the ability of large language models to perform complex reasoning in the religious and legal domain of Islamic inheritance. Unlike conventional question-answering benchmarks, QIAS 2026 focuses on end-to-end reasoning from natural language cases, requiring systems to perform the full inheritance calculation process, from identifying the eligible heirs to assigning the correct share to each beneficiary. To support this evaluation, the task was based on the MAWARITH benchmark, a dataset of $12{,}500$ Arabic inheritance cases annotated with intermediate reasoning steps and final answers. System submissions were evaluated using MIR-E, a multi-step metric that measures performance across the main stages of inheritance reasoning. A total of $16$ teams participated in the shared task, investigating a range of approaches, including prompting-based methods, retrieval-augmented generation, and fine-tuning strategies. The results show that Islamic inheritance remains a highly challenging benchmark for current language models, especially in stages that require precise legal interpretation and structured numerical reasoning. This overview summarizes the task design, dataset, evaluation framework, participating systems, and main results.

20.
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.

21.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

22.
medRxiv (Medicine) 2026-06-19

Performance of family history-based colorectal cancer screening criteria by race and age at diagnosis in the Disparities and Cancer Epidemiology (DANCE) study

Importance: Family history (FH) and age are the primary criteria employed for early colorectal cancer (CRC) risk stratification. We evaluated how well these criteria identify individuals diagnosed with CRC across age and racial groups. Objective: To evaluate the performance of FH and age based screening criteria for identifying individuals with CRC, with attention to differences by race and age at diagnosis. Design, Setting, and Participants: This case control and case only analysis used data from the Disparities and Cancer Epidemiology (DANCE) cohort, a population based study of invasive CRC cases diagnosed from 2013 to 2022, recruited through the Metropolitan Detroit Cancer Surveillance System and the Louisiana Tumor Registry. Analyses included 1,158 non-Hispanic Black (NHB) and non-Hispanic White (NHW) CRC cases and 1,434 cancer-free controls from the Inflammation Health and Lung Epidemiology (INHALE) study, enrolled from the same Detroit catchment area. Data were analyzed in 2025. Exposures: Self reported cancer FH among first-degree (FD) relatives and grandparents, summarized into three FH-based screening criteria: at least one FD relative with CRC (colon early-screening criterion), any FH of Lynch syndrome related cancers, and meeting NCCN criteria for Lynch syndrome genetic testing. Main Outcomes and Measures: Proportion of cases meeting each FH based screening criterion stratified by race and age at diagnosis (

23.
arXiv (CS.AI) 2026-06-24

Impatient Bandits: Optimizing for the Long-Term Without Delay

arXiv:2501.07761v2 Announce Type: replace-cross Abstract: Increasingly, recommender systems are tasked with improving users' long-term satisfaction. In this context, we study a content exploration task, which we formalize as a bandit problem with delayed rewards. There is an apparent trade-off in choosing the learning signal: waiting for the full reward to become available might take several weeks, slowing the rate of learning, whereas using short-term proxy rewards reflects the actual long-term goal only imperfectly. First, we develop a predictive model of delayed rewards that incorporates all information obtained to date. Rewards as well as shorter-term surrogate outcomes are combined through a Bayesian filter to obtain a probabilistic belief. Second, we devise a bandit algorithm that quickly learns to identify content aligned with long-term success using this new predictive model. We prove a regret bound for our algorithm that depends on the Value of Progressive Feedback, an information-theoretic metric that captures the quality of short-term leading indicators that are observed prior to the long-term reward. We apply our approach to a podcast recommendation problem, where we seek to recommend shows that users engage with repeatedly over two months. We empirically validate that our approach significantly outperforms methods that optimize for short-term proxies or rely solely on delayed rewards, as demonstrated by an A/B test in a recommendation system that serves hundreds of millions of users.

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

State-Grounded Multi-Agent Synthetic Data Generation for Tool-Augmented LLMs

Training tool-augmented LLM agents requires large corpora of multi-turn, tool-grounded conversational data that is expensive to annotate, privacy-constrained in production settings, and largely absent from public datasets. We present StateGen, a synthetic data generation platform that produces scored, reasoning-trace-rich training conversations by orchestrating a four-role LLM loop: a persona-conditioned user simulator, an agent under test, a state-grounded tool simulator, and a multi-axis LLM judge. The key architectural contribution is an authoritative state manager that maintains a structured world-state object across turns, enforcing a backend-is-truth invariant that eliminates the dominant class of tool-call hallucinations by construction. StateGen extends naturally to hierarchical multi-agent settings by declaring sub-agents as tools, all sharing a single state object. We report results on 64,698 evaluated conversations across three production corpora: tool-call hallucination scores reach 9.66/10, the system supports persona-driven variation via a 23-dimensional trait vector, and a cleanly separated train and golden evaluation set split confirms the data is not memorization bait (per-criterion gap analysis). Comparison with eight external systems shows that no single publicly available platform combines multi-turn generation, state-grounded tool simulation, hierarchical multi-agent support, and built-in judge scoring.

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

Think Fast: Estimating No-CoT Task-Completion Time Horizons of Frontier AI Models

arXiv:2606.07157v2 Announce Type: replace Abstract: Many efforts to ensure frontier AI models are safe rely on monitoring their chain-of-thought (CoT) reasoning. If models become able to perform sufficiently complex reasoning internally, without explicit thinking tokens, this would undermine such oversight. We measure how well frontier models reason without CoT across a suite of over 30,000 questions spanning 43 benchmarks in domains including math, coding, puzzles, causality, theory-of-mind, and strategic reasoning. To compare models against humans, we estimate the $50\%$-task-completion time horizon (TH): the human time required for tasks a model completes with $50\%$ success rate. We complement this with a $50\%$ reasoning token horizon: the minimum number of o3-mini reasoning tokens needed for tasks a model solves with $50\%$ success rate. We find that the no-CoT $50\%$ TH of frontier models has been doubling roughly every year over the past six years, with GPT-5.5's TH reaching over 3 minutes and reasoning token horizon exceeding 1,500 tokens. Our median estimates predict that frontier no-CoT THs could exceed 7 minutes by 2028, and 25 minutes by 2030, though these projections carry substantial uncertainty. We recommend frontier developers track this explicitly.