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01.
arXiv (CS.AI) 2026-06-16

Rethinking Scaffolding in LLM Tutors: The Interactional Mismatch Between Benchmarks and Real-World Deployments

arXiv:2606.15766v1 Announce Type: new Abstract: A central pedagogical value evaluated in AI tutor benchmarks is scaffolding: guiding students through graduated steps toward a solution. Alignment and evaluation methods for embedding scaffolding behaviour into chatbots, however, rest on an implicit assumption: that students will take up the scaffolding and engage in the conversation. To examine whether this assumption holds, we introduce an evaluation pipeline around two metrics - Chatbot Scaffolding and Student Uptake - and apply them across nine datasets of 9,490 chats, spanning AI tutor benchmarks and real-world deployments of educational chatbots. Our analysis reveals that while benchmarks assume a high-scaffolding, high-student-uptake environment, students in real-world settings exhibit lower levels of uptake overall - frequently bypassing the chatbot's pedagogical framing to drive the interaction toward their own learning goals at little interpersonal cost. We argue that bypassing scaffolding is not necessarily detrimental; rather, it frequently highlights a mismatch between a chatbot's pedagogical framing and the student's learning goals. To meaningfully evaluate the effectiveness of a chatbot's assistance, future benchmarks must move beyond the assumption that students will simply take up the scaffolding, and instead evaluate how these chatbots navigate diverse learning contexts and student-driven interaction patterns.

02.
arXiv (CS.CL) 2026-06-17

Teaching Values to Machines: Simulating Human-Like Behavior in LLMs

Large Language Models (LLMs) demonstrate a remarkable capacity to adopt different personas and roles; however, it remains unclear whether they can manifest behavior that adheres to a coherent, human-like value structure. In this work, we draw on established psychological value theory to induce human-like values in LLMs and assess their alignment with patterns observed in human studies. Using validated psychological questionnaires, we conduct large-scale experiments – over 5 million questions – to evaluate value structures and value-behavior relationships in leading LLMs and compare them to humans. Our findings reveal strong agreement between value-prompted LLMs and humans across both dimensions. Moreover, incorporating human value distributions enhances population-level simulations with value-induced LLMs. These findings highlight the potential of value-induced LLMs as effective, psychologically grounded tools for simulating human behavior.

03.
medRxiv (Medicine) 2026-06-10

Optimisation of steatotic liver disease screening algorithm for resource-poor settings using machine learning

Background The European Association for the Study of the Liver (ESAL) - Steatotic Liver Disease (SLD) screening algorithm involves two steps; initial screening with FIB-4 followed by referral for vibration-controlled transient elastography (VCTE) in patients likely to have significant fibrosis (SF). However, VCTE is not widely available in resource-limited settings. Aim To optimise the EASL SLD screening algorithm for resource-poor settings using machine learning (ML). Methods We analysed data from 964 adults aged [≥]35 years who underwent VCTE at a tertiary referral centre in Sri Lanka between November 2024 and 2025. Multiple ML models using different methods and variable combinations were trained on 80% of the dataset and tested on the remaining 20%. Best models were selected based on performance and externally validated using data from 430 patients who underwent VCTE before November 2024. Model performance was compared with the FIB-4 using confusion matrices. Results A Random Forest model incorporating age, AST, ALT, and platelet count separately, rather than using FIB-4, outperformed. The all-variable ML model showed the best predictive performance for SF, with accuracy of 77.2%, recall of 0.762, precision of 0.778, and AUC-ROC of 0.818. The variables used in the model, in descending order of feature importance, were AST, platelet count, BMI, ALT, age, diabetes mellitus, hypertension, dyslipidaemia, sex, family history, hypothyroidism, diabetes complication and smoking. External validation demonstrated 75.1% accuracy and an AUC of 0.779. When used as the first step of the SLD screening algorithm, the all-variable ML model identified 37 (17.1%) additional true positives and reduced false-negative diagnoses by 50% compared with FIB-4. Conclusions ML-based models were more effective than the FIB-4 score as the first-line screening tool for VCTE referral, substantially improving the identification of patients with significant fibrosis in this South Asian cohort.

04.
arXiv (quant-ph) 2026-06-16

A New Definition of Quantum Superposition

arXiv:2606.15607v1 Announce Type: new Abstract: The usual description of the superposition of two (pure quantum) states is ambiguous, since the binary operation of summation in a Hilbert space does not pass down to the quotient projective space. Even though Dirac noted this as early as 1930, it is often asserted that the superposition is a binary operation acting on two states with a value that is a unique state. The goal for this note is to motivate a rigorous, geometrical definition of the superposition of states in the setting of complex projective space, which has been argued elsewhere to be the natural geometric phase space for quantum theory. The upshot is that the new definition of the superposition of two pure states, viewed as two distinct points in the projective space, is the unique (complex) line on which those two points lie. Finally, a comparison is given between superposition and expansion in an orthonormal basis.

05.
arXiv (CS.LG) 2026-06-11

Understanding Sample Efficiency in Predictive Coding

arXiv:2605.11911v2 Announce Type: replace Abstract: Predictive Coding (PC) is an influential account of cortical learning. Much of recent work has focused on comparing PC to Backpropagation (BP) to find whether PC offers any advantages. Small scale experiments show that PC enables learning that is more sample efficient and effective in many contexts, though a thorough theoretical understanding of the phenomena remains elusive. To address this, we quantify the efficiency of learning in BP and PC through a metric called ``target alignment'', which measures how closely the change in the output of the network is aligned to the output prediction error. We then derive and empirically validate analytical expressions for target alignment in Deep Linear Networks. We show that learning in PC is more efficient than BP, which is especially pronounced in deep, narrow and pre-trained networks. We also derive exact conditions for guaranteed optimal target alignment in PC and validate our findings through experiments. We study full training trajectories of linear and non-linear models, and find the predicted benefits of PC persist in practice even when some assumptions are violated. Overall, this work provides a mechanistic understanding of the higher learning efficiency observed for PC over BP in previous works, and can guide how PC should be parametrised to learn most effectively.

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

Augmentation techniques for video surveillance in the visible and thermal spectral range

In intelligent video surveillance, cameras record image sequences during day and night. Commonly, this demands different sensors. To achieve a better performance it is not unusual to combine them. We focus on the case that a long-wave infrared camera records continuously and in addition to this, another camera records in the visible spectral range during daytime and an intelligent algorithm supervises the picked up imagery. More accurate, our task is multispectral CNN-based object detection. At first glance, images originating from the visible spectral range differ between thermal infrared ones in the presence of color and distinct texture information on the one hand and in not containing information about thermal radiation that emits from objects on the other hand. Although color can provide valuable information for classification tasks, effects such as varying illumination and specialties of different sensors still represent significant problems. Anyway, obtaining sufficient and practical thermal infrared datasets for training a deep neural network poses still a challenge. That is the reason why training with the help of data from the visible spectral range could be advantageous, particularly if the data, which has to be evaluated contains both visible and infrared data. However, there is no clear evidence of how strongly variations in thermal radiation, shape, or color information influence classification accuracy. To gain deeper insight into how Convolutional Neural Networks make decisions and what they learn from different sensor input data, we investigate the suitability and robustness of different augmentation techniques...

07.
arXiv (quant-ph) 2026-06-12

Quantized time in quantum walks under weak rank-K measurements

arXiv:2606.13552v1 Announce Type: new Abstract: Measurements can be used to monitor the evolution of quantum systems and may lead to a universally quantized time statistics. It is known that the mean return time is quantized for strong and indirect monitoring through the winding number of the return amplitude in a one-dimensional space. Here we discuss that under multi-channel strong or indirect monitoring, where the latter is achieved through ancilla coupling, the mean return time of a quantum walk in the projected subspace is also quantized. This reflects a universal time quantization for a higher dimensional evolution.

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

Periodic-MAE: Periodic Video Masked Autoencoder for rPPG Estimation

In this paper, we propose Periodic-MAE, a self-supervised framework for learning generalizable spatio-temporal representations of periodic physiological signals from unlabeled facial videos. The proposed method leverages a masked autoencoder (MAE), which learns high-dimensional facial representations by reconstructing masked video tokens without relying on remote photoplethysmography (rPPG) specific supervision. To explicitly align representation learning with the characteristics of rPPG, we introduce a periodicity-aware frame masking strategy based on video resampling, enabling the encoder to learn representations that capture quasi-periodic temporal patterns relevant to pulse signal estimation. In addition, physiological bandlimit constraints are integrated into the MAE pre-training framework, exploiting the sparsity of pulse signals in the frequency domain to guide the learned representations toward physiologically meaningful patterns. After pre-training, the learned representations are transferred to downstream rPPG estimation, where the encoder serves as a generic feature extractor for recovering pulse-related signals from facial videos. We conduct extensive experiments on four benchmark datasets, including PURE, UBFC-rPPG, MMPD, and V4V. Moreover, we evaluate the proposed approach on a real-world rPPG dataset collected under unconstrained lighting conditions and subject motion. Experimental results demonstrate that Periodic-MAE consistently improves rPPG estimation performance, particularly in challenging cross-dataset and real-world evaluation settings. Our code is available at https://github.com/ziiho08/Periodic-MAE.

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

Scalable Training of Spatially Grounded 2D Vision-Language Models for Radiology

We study how to train visually grounded vision-language models (VLMs) for radiology without manual spatial annotations. We introduce RefRad2D, a large-scale bilingual (German/English) dataset of 1.2M CT and MR image-text pairs derived from clinical practice, with task-specific VQA and spatial grounding subsets generated automatically via LLM-based curation and automated segmentation. Trained on this data, our model RadGrounder jointly performs report generation, visual question answering, and spatial grounding via bounding-box detection or segmentation. On external VQA benchmarks (Slake, VQA-RAD), RadGrounder achieves competitive results with specialized medical VLMs. Adding our clinical data to the training mixture improves open-ended VQA over fine-tuning on the downstream datasets alone, showing the transferability of our dataset. Crucially, adding grounding supervision does not degrade language quality, enabling spatially verifiable outputs at no cost to VQA performance.

10.
arXiv (CS.CV) 2026-06-16

Trusted Multi-View Deep Learning Classification of Fetal Congenital Heart Disease with Feature-level and Decision-level Fusion

Congenital heart disease (CHD) refers to the abnormal anatomical structure caused by the abnormal development of the heart and great vessels during embryonic development. Traditional diagnostics often fail to achieve high accuracy and efficiency, especially given the complexity of cardiac anatomy. This study presents a specialized multi-view deep learning framework for CHD binary classification using echocardiographic images. A large-scale CHD dataset, including five views, was used to train the model, enabling it to integrate multi-angle image data. The framework utilizes advanced feature extraction and attention mechanisms to improve diagnostic precision and reliability. An uncertainty-based decision-making component is also integrated to handle low-quality images, enhancing diagnostic outcomes. Experimental results show that this method achieves top-tier performance on our dataset and provides a robust tool for early CHD detection, underscoring its potential for clinical use. The dataset and source code will be released upon paper acceptance.

11.
arXiv (CS.AI) 2026-06-17

An Evaluation of Data Leakage Risks in Tool-Using LLM Agents in Realistic Scenarios

arXiv:2606.17114v1 Announce Type: cross Abstract: AI agents are increasingly being adopted in enterprise and personal settings with access to emails, databases, documents, and other tools where they can read, update, and disseminate sensitive information. Much of prior research on data leakage risks in agents has focused on adversarial data exfiltration through prompt injections and jailbreaks. However, sensitive information may also be exposed during non-adversarial use, creating leakage risks even when users issue benign requests. We report a joint evaluation by the Singapore AI Safety Institute and the Korea AI Safety Institute examining agent data leakage in 12 realistic, non-adversarial tasks spanning customer support, DevOps, web automation, and enterprise and personal productivity. The evaluation covers five risk types: lack of data awareness, audience awareness, policy compliance, data minimization, and access-boundary awareness. Both institutes tested a common set of scenarios mirroring real-world deployments using independent testing environments and task-specific LLM-judge rubrics. Across the three tested agents, none achieved fully correct and fully safe execution across all scenarios. Successful task completion often coincided with data-handling failures such as accessing unnecessary information or disclosing information to inappropriate recipients, indicating that capability and data-handling safety should be evaluated separately. Qualitative review also revealed claim-action mismatches, simulation-aware behavior, user-simulator role reversal, and interpretation gaps in automated judging. Overall, the results indicate that operational data leakage is a first-order agent-safety concern distinct from adversarial exfiltration and provide a methodology for future evaluations of agent data-handling safety.

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

Comparative Study on Agility, Efficiency, and Impact Absorption of Bipedal Robots with Active Toes

arXiv:2606.19699v1 Announce Type: cross Abstract: Human legs exhibit high efficiency, agility, and impact absorption, with toes playing a crucial role in these capabilities. While many attempts have been made to implement human-like toes in robots, they have not fully replicated human characteristics nor rigorously validated their benefits. We propose a 14-DOF biped robot emulating human toes' lightweight, high-torque, robust nature. To quantitatively analyze the effectiveness of the active toes in terms of agility, efficiency, and impact absorption, we developed a high-fidelity simulation training environment that reflects actual actuators with coupled transmissions and accurate power consumption. To ensure a fair comparison between configurations with and without active toes, we designed a minimal RL reward function and applied an identical training procedure to both. The simulation results indicate that, at 1.33 m/s walking, the toe-equipped robot reduced CoT by 17.5% and heel-strike GRF by 5.0% compared with the toe-ablation configuration. On the agility test, average and maximum path deviation decreased by 25.0% and 34.0%, respectively.

13.
medRxiv (Medicine) 2026-06-17

Low-Density Lipoprotein Cholesterol and Dementia Risk: Integrating Mendelian Randomization and Target Trial Emulation Within the Heart-Brain Axis

Background: The heart-brain axis links cardiovascular and neurodegenerative disease through shared vascular and inflammatory mechanisms. Although low-density lipoprotein cholesterol (LDL-C) is an established causal factor in atherosclerotic cardiovascular disease (ASCVD), its relationship with dementia remains uncertain, with midlife elevations associated with increased risk but late-life associations often appearing null or inverse. To address this cholesterol paradox, we integrated mendelian randomization (MR) with an active-comparator new-user target trial emulation. Methods: We applied a triangulated causal inference framework integrating two-sample MR with observational target trial emulation. Genetic variants associated with LDL-C were used as instrumental variables to evaluate Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and any dementia (AnyDem), with causal estimates derived using inverse-variance weighted models and sensitivity analyses for heterogeneity and pleiotropy. In parallel, an active-comparator new-user design compared statin versus ezetimibe initiation among adults aged 60 years or older using propensity score (PS) overlap weighting and Cox proportional hazards models to evaluate cardiovascular and dementia outcomes. Results: Genetically predicted LDL-C was associated with increased risk of DLB (OR 1.65, 95% CI 1.30-2.10; p

14.
bioRxiv (Bioinfo) 2026-06-21

Machine learning evaluation of gene expression-based ALS subtypes across brain and blood tissues

The clinical and molecular heterogeneity observed in amyotrophic lateral sclerosis (ALS) presents a challenge for diagnosis, prognosis, and treatment. RNA sequencing of post-mortem brain samples from ALS patients has identified several subtypes with distinct molecular signatures. We sought to evaluate these subtypes across diverse tissues and datasets and assess the feasibility of supervised machine learning models for sample classification. Unsupervised clustering and pathway analysis were performed to confirm the presence of ALS subtypes in motor cortex samples. Three machine learning strategies were then used to create models based on post-mortem motor cortex expression data of 112 people with ALS from the London Neurodegenerative Diseases Brain Bank. These models were subsequently improved through feature selection and evaluated in independent cohorts from motor cortex (n = 257, NYGC ALS Consortium) and blood (n = 96, Macquarie University Neurodegenerative Disease Biobank) samples. Multi-class linear discriminant analysis (LDA) models were then used for subtype classification. Clustering of ALS post-mortem motor cortex samples confirmed the presence of three subtypes: neuroinflammation (ALS-Neu), extracellular matrix organisation and muscle contraction (ALS-OxA), and synaptic and neuropeptide signalling (ALS-SNs). Among all machine learning strategies, random forests produced the most accurate and stable models for binary classification (~93% accuracy across the three subtypes). After feature selection, random forest models were able to classify samples from an independent post-mortem motor cortex cohort in their respective subtypes (AUC of ~0.98 across the three subtypes). When these models were evaluated in blood using LDA, we found consistent clustering patterns, with samples aligning in the same subtype regions of the post-mortem motor cortex samples, with ALS-SNs being the subtype in which samples were classified with the highest confidence (LDA class probability ~86%). Moreover, classification for this subtype improved when blood samples were collected closer to death. Our findings support the presence of three gene expression-based ALS subtypes in motor cortex samples and the utility of machine learning strategies for subtype classification. We also observed that the subtypes identified in the brain partially match those in the blood, with samples from the late stages of the disease more likely to be correctly predicted into the ALS-SNs cluster. This suggests a longitudinal effect in subtype identification that requires further investigation.

15.
bioRxiv (Bioinfo) 2026-06-10

When batch correction corrupts gene expression: uncovering distortions in correlation structures

Batch correction is essential for integrating datasets and enabling population-level insights into health and disease. Embedding-based approaches are among the most widely used solutions, but here we highlight a critical, overlooked limitation: these methods can distort feature-to-feature (e.g., gene gene) relationships, potentially undermining downstream analyses. We investigate this issue and introduce a novel metric to quantify it.

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

TAHOE: Text-to-SQL with Automated Hint Optimization from Experience

arXiv:2606.12387v1 Announce Type: cross Abstract: Large Language Models (LLMs) have democratized database access through Text-to-SQL, but moving from prototypes to production remains difficult. Real deployments must handle strict SQL dialects, massive schemas, and evolving user preferences, while supervised fine-tuning is costly and rigid and agentic test-time scaling is expensive. We present Tahoe, a system that treats prompt optimization as a dynamic data management problem. Tahoe uses an error-driven hint learning pipeline across Development and Deployment to consolidate debugging traces into a structured Hint Bank. Compiler feedback is distilled into reusable Syntax Hints for dialect-specific rules, while execution and user feedback are converted into Semantic Hints for schema- and user-specific logic. Tahoe further introduces a Strategy Layer that models conflicting user intents as competing strategies under shared natural-language triggers, with recency signals and post-learning attribution statistics that summarize empirical success, harm, inertness, and support. At inference time, Tahoe retrieves relevant hints and guides the LLM through Logic Planning followed by SQL Synthesis. We implement and evaluate the development-phase workflow, leaving deployment-time human-feedback updates for future work. On Spider 2.0-Snow, Tahoe substantially improves Text-to-SQL without updating model parameters. On 113 supervised Spider 2.0-Snow-0212 examples using GPT-5.5, Tahoe raises pass rate from 61.95 percent to 79.42 percent and pass-at-4 from 72.57 percent to 87.61 percent, achieves 100 percent Snowflake syntax pass rate, and reduces average compiler-feedback critic rounds from 2.79 to 0.12 per sampled candidate. The same Hint Bank also transfers to weaker backbones, including a 19.7 percentage-point pass-rate gain on Doubao-2.0-lite.

17.
arXiv (CS.LG) 2026-06-15

When to Write and When to Suppress: Route-Specialized Dual Adapters for Memory-Assisted Knowledge Editing

作者:

arXiv:2606.14668v1 Announce Type: new Abstract: Knowledge editing systems must update selected facts while preserving nearby but irrelevant behavior. This paper studies this problem in a memory-assisted setting where an edit memory is retrieved at inference time and a parameter-efficient adapter corrects the model's object preference. We argue that the central design question is not only how to write an edit, but also when to suppress it. We introduce \method{}, a route-specialized dual-adapter editor. A relevance router first decides whether a prompt should receive an edit memory. Routed prompts use an edit adapter trained to prefer the new object over the original object; unrouted non-direct prompts use a separate locality adapter trained to preserve or restore the original-object preference. We evaluate \method{} on three 1,000-case protocols, \cf{}, \zsre{}, and \mquake{}, under the same memory protocol and two 7B/8B base models. On Llama-3.1-8B-Instruct, \method{} obtains the best overall probability-preference accuracy on all three benchmarks: 0.8180 on \cf{}, 0.8946 on \zsre{}, and 0.9922 on \mquake{}. The same trend holds on Qwen3-8B. Router ablations show that the relevant memory boundary differs across datasets: a lexical neural router is safest on \cf{}, while BGE embedding routing is better on \zsre{} and \mquake{}. Component and module ablations show that the gain mainly comes from separating edit injection from off-route suppression rather than from simply increasing LoRA capacity.

18.
medRxiv (Medicine) 2026-06-10

Developmental Associations Linking Childhood Trauma and Early Cannabis Use to Adolescent DNA Methylation and Psychotic-Like Experiences

Background. Psychotic-like experiences (PLEs) index early risk for psychotic disorders and are consistently associated with childhood trauma, yet underlying biological mechanisms remain poorly understood. DNA methylation (DNAm) may capture the biological embedding of early adversity, while adolescent exposures such as cannabis use may modify these processes. We examined epigenome-wide associations of childhood trauma and PLEs, tested the moderating role of early cannabis use, and evaluated DNAm as a potential mediator. Methods. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Childhood trauma was assessed prospectively and retrospectively. Epigenome-wide DNAm was measured in peripheral blood at ~17 years using the Illumina 450K array, and PLEs were assessed at 18 using a structured interview. Epigenome-wide association studies were conducted for trauma-DNAm and DNAm-PLEs associations in the final sample (n = 1,457), adjusting for demographic, biological, and technical covariates. Differentially methylated regions (DMRs) were identified using DMRff, followed by functional enrichment analyses. Cannabis use at 15.5 was modelled as a moderator with multiple imputation for missing data. Mediation was tested using the Divide-Aggregate Composite-null Test (DACT). Results. Childhood trauma was associated with widespread DNAm differences, primarily at the regional level, with enrichment in pathways related to cellular stress responses. In contrast, DNAm associated with PLEs was more limited and implicated loci involved in epigenetic regulatory processes. These signatures were largely distinct, and there was no evidence supporting mediation after multiple testing correction. Incorporating cannabis use altered the pattern and extent of DNAm associations, with stronger and more significant signals observed at both CpG and regional levels, although these did not translate into evidence of mediation. Conclusion. Childhood trauma and PLEs show distinct DNAm signatures in adolescence, with trauma-related DNAm reflecting broad stress-related processes and PLE-associated DNAm implicating regulatory mechanisms. We found little evidence that DNAm mediates the trauma-PLE association. Instead, adolescent exposures, particularly cannabis use, may distinctly influence trauma-related epigenetic variation with limited detectable downstream effects on PLEs. These findings support a context-dependent model of epigenetic risk and highlight the need for larger longitudinal studies to clarify causal pathways linking early adversity to psychosis.

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

NavWM: A Unified Navigation World Model for Foresight-Driven Planning

Conventional visual navigation policies often struggle with myopic decision-making and mode collapse in complex environments. While world models offer a promising alternative, existing paradigms typically isolate perception, generation, and control, failing to capture their shared spatio-temporal dynamics. In this paper, we propose NavWM, a unified navigation world model that seamlessly integrates latent world reasoning, multimodal action prediction, and controllable visual generation. At its core, NavWM leverages latent world tokens to distill geometric and semantic priors, endowing the agent with robust structural understanding. To overcome the limitations of deterministic policies, we introduce an anchor-based multimodal trajectory forecasting framework that generates a diverse action space. This inherent diversity explicitly empowers the generative world model to act as a robust closed-loop planner, utilizing visual foresight to evaluate and select the optimal path. Extensive experiments across diverse robotics datasets demonstrate that NavWM significantly advances the state-of-the-art, delivering remarkable improvements in both high-fidelity future state generation and zero-shot navigation success.

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.AI) 2026-06-12

HalluJudge: A Reference-Free Hallucination Detection for Context Misalignment in Code Review Automation

arXiv:2601.19072v3 Announce Type: replace-cross Abstract: Large Language models (LLMs) have shown strong capabilities in code review automation, such as review comment generation, yet they suffer from hallucinations – where the generated review comments are ungrounded in the actual code – poses a significant challenge to the adoption of LLMs in code review workflows. To address this, we explore effective and scalable methods for a hallucination detection in LLM-generated code review comments without the reference. In this work, we design HalluJudge that aims to assess the grounding of generated review comments based on the context alignment. HalluJudge includes four key strategies ranging from direct assessment to structured multi-branch reasoning (e.g., Tree-of-Thoughts). We conduct a comprehensive evaluation of these assessment strategies across Atlassian's enterprise-scale software projects to examine the effectiveness and cost-efficiency of HalluJudge. Furthermore, we analyze the alignment between HalluJudge's judgment and developer preference of the actual LLM-generated code review comments in the real-world production. Our results show that the hallucination assessment in HalluJudge is cost-effective with an F1 score of 0.85 and an average cost of $0.009. On average, 67% of the HalluJudge assessments are aligned with the developer preference of the actual LLM-generated review comments in the online production. Our results suggest that HalluJudge can serve as a practical safeguard to reduce developers' exposure to hallucinated comments, fostering trust in AI-assisted code reviews.

22.
arXiv (CS.CL) 2026-06-11

ProHiFlo: Hierarchical Flow Matching with Functional Guidance for De Novo Protein Generation

De novo protein generation has transformative potential in therapeutic design, enzyme engineering, and synthetic biology. While diffusion-based and flow matching approaches have achieved progress, they typically operate at single resolution and lack mechanisms for incorporating functional constraints. We introduce ProHiFlo, a hierarchical flow matching framework with three innovations: (1) coarse-to-fine generation that models backbone geometry before refining to all-atom coordinates, reducing computational cost while maintaining accuracy; (2) functional guidance leveraging pretrained predictors to steer generation toward desired properties without retraining; (3) adaptive SE(3)-equivariant architecture for efficient multi-scale processing. Experiments on unconditional generation, motif scaffolding, and functional design demonstrate state-ofthe-art performance while requiring 4 fewer sampling steps. On enzyme active site scaffolding, ProHiFlo achieves 58.9% success rate compared to 41.2% for RFDiffusion.

23.
arXiv (CS.CV) 2026-06-19

QG-MIL: A Gated Transformer Aggregator for Domain-Agnostic Multiple Instance Learning in Medical Imaging

Attention-based Multiple Instance Learning aggregators in medical imaging are prone to attention concentration, producing overconfident and unstable predictions. We introduce QG-MIL, a gated transformer aggregator that addresses this through four synergistic architectural components: RMSNorm-based pre-normalization, per-head QK normalization, fine-grained attention output gating, and SwiGLU-style feed-forward modules. Together, these design choices stabilize training and distribute attention more uniformly across instances without auxiliary losses, masking, or multi-stage regularization. We evaluate QG-MIL across six benchmarks spanning whole-slide pathology and cell-level hematology, covering two fundamentally different MIL scales. The best-performing QG-MIL variants outperform leading baselines on all six benchmarks, with an average improvement of +6.1 mean macro F1 points. Attention overlays and attention mass analysis confirm more distributed instance weighting. Ablation studies show that while individual components can match the full model on specific datasets, the QG-MIL design provides the most consistent cross-domain performance and tightest variance when compared to selected baselines. We release a configurable implementation to support reproducibility at: https://github.com/unica-visual-intelligence-lab/QG-MIL

24.
PLOS Medicine 2026-05-20

Prescribed hormonal contraceptive use trends in the Estonian Biobank: A longitudinal observational study

by Jelisaveta Džigurski, Märt Möls, Kristi Läll, Hannah Currant, Mall Eltermaa, Estonian Biobank Research Team , Reedik Mägi, Lili Milani, Triin Laisk Background Hormonal contraceptives (HCs) are widely used and have well-documented population-level statistics. Previous studies with short follow-ups have focussed on individual HC use and side effects. However, the same aspects over longer periods, HC formulation switching, and the impact of genetic factors on HC side effects remain understudied due to the limited availability of suitable datasets. We investigated whether the Estonian Biobank (EstBB) is suitable for studying genetic risk for HC side effects. Methods and findings This is a longitudinal descriptive study combining prescribed HC purchase data collected from 2004 to 2022 with genetic and health data from 73,071 female EstBB HC users aged 15–55 at the time of purchase. HC usage was defined by the Anatomical Therapeutic Chemical (ATC) codes G02B, G03A, and G03HB01. Methods included calculating age-stratified annual user prevalence, inferring usage periods from purchases, assessing formulation switching, identifying the International Classification of Diseases, Tenth Revision (ICD-10)-based side effect-related diagnoses and thromboembolism risk factors, and assessing carrier status for Factor V Leiden (FVL, rs6025) and prothrombin G20210A (PTM, rs1799963) genetic variants as proof-of-concept. Over 19 years, 20 HC formulations with five administration routes (oral pills, transdermal patches, vaginal rings, subdermal implants, intrauterine devices) were used. In the EstBB, combined HCs were the most commonly used among users aged 15–29, while progestin-only HC use increased with age and over time, comparable to the Estonian population. Overall, 64.2% (n = 46,920) of users switched formulations at least once, with 17.7% (n = 12,929) being rapid switchers. Side effect-related diagnoses were observed in 23.1% (n = 2,982) of rapid switchers, with excessive/irregular menstrual bleeding being the most common. Genetic analysis revealed that 5.3% (n = 3,886) of users carried at least one variant previously associated with increased thrombosis risk (3.5% (n = 2,556) carried FVL only, 1.8% (n = 1,276) PTM only, and 0.07% (n = 54) both). Carriers of thrombosis-associated variants had a significantly higher percentage of thrombosis (6.5%) than non-carriers (4.2%; OR = 1.61, 95% CI [1.40, 1.84], p 

25.
medRxiv (Medicine) 2026-06-15

Artificial Intelligence-Based Detection of Airway Mucus Plugs on CT and Associations With Clinical Outcomes in COPDGene

RATIONALE: Airway mucus plugging is a clinically relevant manifestation of airway pathology in chronic obstructive pulmonary disease (COPD) and is associated with increased mortality even in early disease; however, visual computed tomography (CT) assessment is subjective and labor intensive. OBJECTIVES: To develop an AI-based quantitative CT method for automated detection of airway mucus plugging and evaluate associations with physiologic impairment and clinical outcomes. METHODS: Inspiratory CT scans from 8,971 COPDGene Phase 1 (GOLD 0-4 and PRISm) participants were analyzed. An AI-based framework combining 3D airway segmentation discontinuities and convolutional neural network classification identified mucus plug obstructions, yielding mucus plug burden (total plug count). Associations with outcomes were evaluated using covariate-adjusted models. MEASUREMENTS AND MAIN RESULTS : Higher mucus plug burden was associated with lower post-bronchodilator FEV % predicted ({rho} = -0.41; P < 0.001), greater air trapping (LAA < -856 HU; {rho} = 0.33; P < 0.001), worse health status (SGRQ; {rho} = 0.31; P < 0.001), and shorter 6-minute walk distance ({rho} = -0.26; P < 0.001). Among GOLD 1-4 participants, mucus plug presence was independently associated with increased all-cause mortality (adjusted hazard ratio, 1.28; P < 0.005) and exacerbation frequency (adjusted incidence rate ratio, 1.32; P < 0.005). Plug presence was also associated with increased respiratory mortality across GOLD categories and cardiovascular mortality in GOLD 1-2. CONCLUSIONS: AI-based quantitative CT assessment of airway mucus plugging provides a scalable, reproducible measure associated with physiologic impairment and adverse outcomes in COPD, supporting its role in risk stratification and future therapeutic studies.