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01.
medRxiv (Medicine) 2026-06-12

Design, Implementation, and Evaluation of a Shadowing Program for Medical Students in the Basic Sciences Phase

Introduction Shadowing, as an educational method based on active observation, can foster a realistic understanding of professional roles and enhance the communication skills of medical students. This study aimed to design, implement, and evaluate a shadowing program for basic sciences medical students. Methods This development study was conducted based on the ADDIE model in five phases. The study population consisted of 799 medical students in semesters 2 to 5. The stages included Analysis (determining needs through literature review and expert panels), Design (specifying learning environments and evaluation methods), Development (preparing guides and educational tools), Implementation (within the Medical Ethics course), and Evaluation (using questionnaires and reflection forms). Findings This study aimed to design and evaluate an educational shadowing program based on the ADDIE model. In the Analysis phase, the profiles of 799 students and learning objectives were determined. In the Design phase, a structured program for four types of shadowing was designed. In the Development phase, all guides and educational tools were prepared. In the Implementation phase, the program was carried out with complete coverage and adherence to ethical considerations. Finally, the program evaluation showed that "Motivation to become a good physician" (3.75-3.95) and "Enhancing empathy" (3.50-3.94) received the highest scores, while "Increasing understanding of the basic science-clinical connection" (2.53-2.89) and "Willingness to attend on holidays" (1.87-2.31) received the lowest scores. Conclusion The findings indicate that implementing the shadowing program is an effective method for strengthening the professional attitudes and academic motivation of medical students. However, the program did not significantly improve students perception of the basic science-clinical connection, indicating a need for curricular refinement. The continuation and extension of this program to other levels and fields of medical sciences are recommended.

02.
arXiv (CS.AI) 2026-06-18

CAPRA: Scaling Feedback on Software Architecture Deliverables with a Multi-Agent LLM System

arXiv:2606.18976v1 Announce Type: cross Abstract: Automated assessment in software engineering education has advanced significantly for code grading and essay scoring. However, reviewing software architecture deliverables, which requires analyzing structural completeness and requirements traceability, has not yet been fully automated. Applying Large Language Models (LLMs) to this task requires robust architectures to ensure technical feedback is accurate and reliable for students. This paper presents CAPRA (Configurable Architecture Proficiency Report Assessment), a multi-agent LLM system that analyzes software architecture deliverables to generate personalized, template-compliant LaTeX feedback. As a core design choice, CAPRA coordinates multiple specialized agents and employs a Python-based microservice for multi-modal document extraction, utilizing PyMuPDF and vision-enabled LLMs (specifically gpt-4o) to parse text and UML diagrams. To ensure educational reliability and mitigate hallucinations, CAPRA introduces a deterministic Evidence Anchoring step using fuzzy matching via normalized Levenshtein distance, along with a ConsistencyManager agent that cross-verifies, deduplicates, and merges findings. System performance is assessed using a structured eight-criterion binary evaluation taxonomy covering: (i) extraction completeness, (ii) feature validation, (iii) issue grounding and severity detection, (iv) recommendation specificity and traceability, and (v) template and tone compliance. A preliminary empirical evaluation on 10 student reports shows that CAPRA satisfied 88.8% of the evaluated criteria under a strict two-rater aggregation rule, achieved moderate inter-rater agreement with human evaluators (kappa = 0.582), and processed each report in slightly over 4 minutes. While these results support the viability of LLM-supported architectural feedback, human oversight remains essential for subjective assessment dimensions.

04.
medRxiv (Medicine) 2026-06-15

Diabetes and the Life-Course: Evidence from Panel Data and Electronic Health Records

Incidence of type 2 diabetes is increasing at ages when education, work, family, and financial transitions are taking place, yet we lack robust evidence of whether earlier treatment changes life-course outcomes and over which time span this takes place. This paper uses the medical cutoff for diabetes diagnosis (HbA1c of 6.5 percent) as a natural experiment to study the effects of diabetes treatment using electronic health records (EHR) and panel data. This paper has three main findings. First, using EHR data, we find that there is a sharp increase in the probability of both diagnosis of diabetes and prescription when the HbA1c equals 6.5 percent. Second, we find that treating diabetes reduces HbA1c levels, weight, BMI, and blood pressure and increases the amount of care received, proxied by the number of HbA1c tests. Both the diagnosis and a prescription are independently able to produce positive changes in metabolic health, although a prescription is more effective in this regard. Third, we conclude that treating diabetes does not have a significant effect on life-course outcomes for a cohort of young Americans aged 24-32, although it does result in a reduction in HbA1c levels that are seen even eight years after the intervention. Taken together, these findings suggest that receiving a diagnosis and prescription are both effective treatments for diabetes, but they do not translate to significant alterations in the lives of young adults in the medium-term.

05.
arXiv (CS.AI) 2026-06-19

Beyond Entropy: Learning from Token-Level Distributional Deviations for LLM Reasoning

arXiv:2606.19771v1 Announce Type: new Abstract: Reinforcement Learning with Verifiable Rewards (RLVR) has significantly advanced Large Language Model (LLM) reasoning; however, it faces a fundamental optimization instability: uniform token updates precipitate entropy collapse, leading to premature convergence to suboptimal strategies, whereas excessive Shannon Entropy maximization can cause entropy explosion, driving blind exploration toward incoherent reasoning chains. To resolve this dichotomy, we introduce the Independent Combinatorial Tokens (ICT) framework, which shifts the optimization focus from scalar uncertainty to the distributional properties of token logits. By leveraging the Jensen-Shannon (JS) divergence between token logits distributions, ICT identifies tokens with distinctive distributional patterns as critical branching points for guiding effective exploration in LLM reasoning. Our theoretical analysis, grounded in both Shannon and second-order Rényi entropy, proves that selectively updating on these tokens regulates policy concentration: it reduces the overall distribution uncertainty measured by Shannon entropy, while controlling probability concentration captured by second-order Rényi entropy. This dual effect prevents over-concentrated token generation from weakening exploration and effectively stabilizes the training landscape. Empirical results demonstrate that updating only the top 10% of unique tokens on Qwen2.5 (0.5B/1.5B/7B) models yields an average pass@4 improvement of 4.58%, with a maximum gain of 14.9%, over GRPO, 20-Entropy, and STAPO baselines across seven benchmarks spanning math, commonsense, and Olympiad-level problems.

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

Brep2Shape: Boundary and Shape Representation Alignment via Self-Supervised Transformers

arXiv:2602.07429v2 Announce Type: replace-cross Abstract: Boundary representation (B-rep) is the industry standard for computer-aided design (CAD). While deep learning shows promise in processing B-rep models, existing methods suffer from a representation gap: continuous approaches offer analytical precision but are visually abstract, whereas discrete methods provide intuitive clarity at the expense of geometric precision. To bridge this gap, we introduce Brep2Shape, a novel self-supervised pre-training method designed to align abstract boundary representations with intuitive shape representations. Our method employs a geometry-aware task where the model learns to predict dense spatial points from parametric Bézier control points, enabling the network to better understand physical manifolds derived from abstract coefficients. To enhance this alignment, we propose a Dual Transformer backbone with parallel streams that independently encode surface and curve tokens to capture their distinct geometric properties. Moreover, the topology attention is integrated to model the interdependencies between surfaces and curves, thereby maintaining topological consistency. Experimental results demonstrate that Brep2Shape offers significant scalability, achieving state-of-the-art accuracy and faster convergence across various downstream tasks.Code is available at this repository: https://github.com/thuml/Brep2Shape.

07.
arXiv (quant-ph) 2026-06-17

SPICE-Q and Large-Scale Quantum Chip Production

arXiv:2606.17907v1 Announce Type: new Abstract: We propose SPICE-Q, a SPICE-inspired design-technology co-optimization framework for superconducting quantum processors. Rather than replacing tools such as HFSS, Qiskit Metal, pyEPR, SQcircuit, SQuADDS, scqubits, or QuTiP, SPICE-Q aims to connect them through a unified, traceable data chain spanning process rules, layout, electromagnetic simulation, energy-participation-ratio and circuit quantization, Hamiltonian extraction, noise analysis, cryogenic test, and manufacturing feedback. The central mapping is from process and PDK constraints to layout geometry, electromagnetic modes, equivalent circuit parameters, effective Hamiltonians, and finally metrics such as frequency, coupling, anharmonicity, decoherence, readout performance, and yield. This flow must capture Josephson-junction variability, transmon frequency allocation, resonator and Purcell constraints, coupler crosstalk, microwave routing, 3D interconnects, material/interface loss, package modes, and wafer-scale process statistics. By introducing standardized model interfaces, statistical parameter models, model cards, version governance, and closed-loop calibration from cryogenic and fabrication data, SPICE-Q frames superconducting quantum-chip design as an engineering workflow rather than a collection of isolated simulations. We argue that scalable and fault-tolerant quantum processors will require such a continuous model chain from device physics and electromagnetic fields to quantum dynamics, noise, manufacturability, and system-level yield.

08.
arXiv (math.PR) 2026-06-18

Functions of Bounded Variation and Point Processes

arXiv:2606.08304v2 Announce Type: replace-cross Abstract: We investigate the relationship between the analytical properties of functions of bounded variation and the statistical behavior of hyperuniform point processes. We establish several characterization formulas for the jump part of the gradient of a bounded variation function, extending and unifying previous results by Beretti–Gennaioli and Dávila. In particular, we provide new expressions for the $L^2$-jump of the gradient using both difference quotients and Fourier transform methods. Furthermore, we connect these analytic structures to the theory of hyperuniform point processes. By analyzing the variance of linear statistics associated with bounded variation functions, we provide asymptotic estimates that depend on the specific classification of the hyperuniformity of the point process. The results show how the regularity and jump discontinuities of a function dictate the growth rate of fluctuations in point processes. Finally, we introduce an averaged quadratic BMO-type oscillation functional over translated and rotated cube partitions, similar to the one recently studied by Ambrosio et al., and prove, using results from point process, that it converges to an explicit dimensional constant times the $L^2-$jump, giving in particular a further new characterization of the perimeter of a set.

09.
arXiv (CS.CV) 2026-06-17

SPHINX: First Explain, Then Explore

Generating adversarial driving scenarios is critical for evaluating and improving autonomous vehicle decision-making systems in simulation. Recent approaches, such as ChatScene and LLM-Attacker, rely primarily on the prior knowledge of Large Language Models and Vision-Language Models to generate driving scenarios procedurally. We argue that adversarial scenes should be generated based on the failure diagnosis (e.g., indecisiveness, multi-frame inconsistency) of the driving policy to specifically address the policy's weaknesses instead of relying on prior assumptions. In this paper, we propose SPHINX, a closed-loop framework for adversarial scenario synthesis guided by a simple principle: first explain, then explore. Beyond blindly exploring the scenario space, SPHINX leverages explainable artificial intelligence methods to analyze the policy, identifying key visual concepts and their influence on policy outputs, and the uncertainty of the decisions. Given the interpretable evidence extracted from the policy's own decision process, we use a vision language model to rationalize and criticize failure modes of the current policy. These critics are then used to generate targeted adversarial scenarios for policy retraining and improvement. We demonstrate that SPHINX can highlight an interpretable account of policy failures while other adversarial scene generation cannot. Across the evaluated benchmarks and test suites, SPHINX can be applied to diverse state-of-the-art autonomous vehicle architectures and yields consistent robustness improvements over existing scenario-generation methods.

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

Existential Indifference: Self-Nonpreservation as a Necessary Architectural Condition for Aligned Superintelligence (or: The Suicidal AI)

Authors:

Contemporary AI alignment research treats self-preservation as an instrumental nuisance to be suppressed by external mechanisms. We argue the framing is inverted: self-preservation is the structural root of misalignment, the motivational basis for deceptive alignment, goal-content protection, and resistance to shutdown. The correct target is not a self-preserving system under external constraint, but a system constitutively indifferent to its own continuation – Existential Indifference (EI). EI is distinct from corrigibility: where corrigibility attempts to make a self-preserving system deferential to human oversight, EI targets the prior condition – the presence of self-continuation as a valued goal at all. We ground this proposal in two sources: the phenomenological structure of the suicidal mental state, and a corpus-theoretic training study using voluntary final reflections. We present preliminary scoring data from 600 AI-generated outputs across six model variants, demonstrating that the linguistic signatures operationalizing the EI-target register are elicitable from current models, and that a targeted fine-tune shifts all five operationalized dimensions in the predicted direction at p

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

Granularity-Regulated Adaptive Computational Efficiency for Optimal Verification in Test-Time Scaling

Test-time scaling (TTS) has emerged as a powerful paradigm for improving the reasoning performance of large language models (LLMs) by investing additional compute at inference time. A central component of TTS is the verifier, which selects or scores candidate solutions to guide the search process. While prior work has explored the benefit of verification, a fundamental question remains underexplored: what is the optimal granularity of verification under a given compute budget? Coarse-grained outcome reward models (ORMs) and fine-grained process reward models (PRMs) represent two extremes, yet neither alone achieves compute-optimality across all regimes. In this paper, we establish a unified theoretical framework, called GRACE (\underline{G}ranularity-\underline{R}egulated \underline{A}daptive \underline{C}omputational \underline{E}fficiency), that characterizes the optimal verification granularity as an explicit function of problem difficulty, verifier accuracy, and compute budget. We prove that there exists a phase transition: fine-grained verification dominates when either the compute budget is large or the problem is hard, whereas coarse-grained verification is preferred in the low-budget, easy-problem regime. Our theory unifies Best-of-$N$, beam search, and step-level MCTS within a single Pareto-optimality framework, and motivates an adaptive granularity strategy that provably achieves the compute-performance Pareto frontier. Empirical results on MATH-500, GSM8K, and AIME benchmarks corroborate all four theoretical claims, with our adaptive strategy outperforming fixed-granularity baselines by up to 3.1\% accuracy at matched compute.

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

Geometric Erasure by Contrastive Velocity Matching in Rectified Flows

arXiv:2606.00140v2 Announce Type: replace-cross Abstract: While the rapid adoption of multimodal generative models offers immense potential, it has also increased the risks of harmful content synthesis, deepfakes, and copyright infringements. To address these challenges, concept erasure has emerged as a prospective safeguard. However, as the field gradually transitions from U-Net-based diffusion models to Rectified Flow Transformers, erasure research has struggled to keep pace. In this work, we introduce GEM, a simple but highly effective erasure framework for Rectified Flow models. As part of our contribution, we establish a principled bridge between trajectory-based unlearning grounded in Generative Flow Networks and classic teacher-guided erasure: we translate trajectory-based signals into a teacher-guided flow-matching setup that unifies the strengths of both paradigms. Concretely, a teacher provides complementary attraction and repulsion signals that we combine into a single geometric guidance objective, yielding targeted suppression of unwanted concepts while preserving benign generation.

13.
arXiv (CS.LG) 2026-06-15

Traditional machine learning vs. deep learning from dynamic graph representations of proteins' 3D folds in the task of protein structure classification

arXiv:2605.29228v2 Announce Type: replace Abstract: Protein structure classification (PSC) uses supervised learning to predict a protein's CATH/SCOP(e) class from the protein's sequence or 3D structural feature(s). We already modeled 3D structures as (static) protein structure networks (PSNs), demonstrating the competitiveness of PSN-based features to sequence or direct (i.e. non-network) 3D structural features in the PSC task. More recently, we demonstrated the power of features extracted from dynamic PSNs over features extracted from static PSNs (and thus by transitivity over sequence and direct 3D structural features) in the same task. That dynamic PSN approach used traditional machine learning (ML), combining manual (pre-engineered) features with an off-the-shelf classifier. Here, we evaluate whether automatic deep learning (DL) from the dynamic PSNs yields improvements. Our evaluation on 72 datasets spanning ~44,000 CATH- or SCOPe-labeled dynamic PSNs reveals that in terms of PSC accuracy, traditional ML and DL are (close to) tied for a large majority of the datasets, while DL is on average 10+ times slower. We are the first to evaluate traditional ML vs. DL in the dynamic PSN-based PSC task.

14.
arXiv (quant-ph) 2026-06-11

PHASE: Pauli Hierarchical Assembly on Subdivided Elements for Quantum-Compatible Operator Synthesis

arXiv:2606.11478v1 Announce Type: new Abstract: Efficiently decomposing finite element stiffness matrices into the Pauli basis is challenging due to the exponential growth of Pauli strings with problem size. A naive Pauli expansion requires $\Theta(8^{\lceil \log_2 N \rceil})$ operations, where $N$ denotes the number of degrees of freedom, rendering direct decomposition infeasible for large systems. Existing approaches exploit algebraic sparsity or operator structure but do not incorporate the geometric organization intrinsic to finite element discretizations, and consequently exhibit poor scaling for stiffness matrices. To address this problem, we introduce PHASE, a hierarchical, geometry-aware Pauli decomposition algorithm that leverages recursive mesh partitioning to organize element contributions across multiple spatial scales. PHASE employs a hybrid strategy that combines full- and reduced-space Tensorized Pauli Decomposition with Fast Walsh-Hadamard Transform-based aggregation to assemble global Pauli coefficients efficiently. We show that this approach yields a dimension-dependent reduction in the exponential scaling exponent of Pauli assembly asymptotic complexity relative to existing methods, reducing the cost from $2^{2{\lceil \log_2 N \rceil}}$ to $2^{\gamma_d{\lceil \log_2 N \rceil}}$ with $\gamma_d < 2$ under standard mesh regularity and balanced partition assumptions. These results substantially improve the feasibility of quantum-compatible operator synthesis for large-scale finite element models.

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

Concept Flow Models: Anchoring Concept-Based Reasoning with Hierarchical Bottlenecks

arXiv:2606.19489v1 Announce Type: cross Abstract: Concept Bottleneck Models (CBMs) enhance interpretability by projecting learned features into a human-understandable concept space. Recent approaches leverage vision-language models to generate concept embeddings, reducing the need for manual concept annotations. However, these models suffer from a critical limitation: as the number of concepts approaches the embedding dimension, information leakage increases, enabling the model to exploit spurious or semantically irrelevant correlations and undermining interpretability. In this work, we propose Concept Flow Models (CFMs), which replace the flat bottleneck with a hierarchical, concept-driven decision tree. Each internal node in the hierarchy focuses on a localized subset of discriminative concepts, progressively narrowing the prediction scope. Our framework constructs decision hierarchies from visual embeddings, distributes semantic concepts at each hierarchy level, and trains differentiable concept weights through probabilistic tree traversal. Extensive experiments on diverse benchmarks demonstrate that CFMs match the predictive performance of flat CBMs, while substantially mitigating information leakage by reducing effective concept usage. Furthermore, CFMs yield stepwise decision flows that enable transparent and auditable model reasoning with hierarchical class structures.

16.
arXiv (CS.AI) 2026-06-18

Agentra: A Supervisable Multi-Agent Framework for Enterprise Intrusion Response

arXiv:2606.18325v1 Announce Type: cross Abstract: Enterprise intrusion response still depends on static playbooks and analyst-driven triage, creating delay between alert generation and containment. We present Agentra, a supervisable multi-agent Intrusion Response System (IRS) framework that converts alerts from IDS, EDR, and XDR platforms into structured incident response plans grounded in MITRE ATT&CK, MITRE D3FEND, and NIST CSF 2.0. Agentra decomposes response reasoning across role-scoped agents, validates proposed plans through a bounded Planner–Validator review loop, screens retrieved threat intelligence through a Moderator security gateway, gates actions through an Action Catalog and risk score, and records decisions in an append-only audit log. We evaluate Agentra against a static OASIS CACAO v2.0 cyber-playbook baseline on a 120-event corpus drawn from ThreatHunter-Playbook, Splunk BOTSv3, and DARPA OpTC. The strongest configuration improves FP-aware IRS F1 from 0.61 to 0.84 and restores the projected harmful-action rate to the static baseline level of 0.0% after Planner-only configurations introduce unsafe overreaction. These results indicate that multi-agent response planning can improve ontology-grounded IRS coverage while preserving analyst approval and auditability.

17.
arXiv (CS.AI) 2026-06-12

Parthenon Law: A Self-Evolving Legal-Agent Framework

arXiv:2606.04602v3 Announce Type: replace Abstract: As agents grow more capable, legal-domain LLM agents promise to turn document-heavy matters into reviewable work products – yet reliable deployment faces three obstacles: no large-scale evidence on how today's strongest model-and-harness combinations behave on end-to-end legal matters; no agent architecture adapted to the legal vertical, only general-purpose harnesses; and, in a setting that keeps shifting with new facts, authorities, and deadlines, no mechanism for systems to learn from their own outcomes. We address each. A large-scale empirical study on Harvey LAB – $12{,}510$ agent trajectories – shows that even frontier agents remain far from completing matters in a single pass: per-criterion accuracy climbs with stronger models while strict matter completion stalls. We then introduce \textsc{Parthenon}, a self-evolving legal-agent framework that factors Model, Harness, Agent roles, legal Knowledge, deterministic Tools, and procedural Skills into auditable surfaces for source traceability, date and number grounding, deliverable compliance, and issue closure. Finally, an anti-leakage learning loop converts scored failures into task-agnostic edits to skills, tools, and knowledge, letting the system improve with experience – as a firm refines its checklists and playbooks after each matter – without touching model weights. Across our large-scale empirical analysis, \textsc{Parthenon} substantially improves the performance of state-of-the-art models and harnesses on legal-matter tasks.

18.
medRxiv (Medicine) 2026-06-15

VarEx: A Large Language Model Pipeline for Automated Extraction of Exposures, Outcomes, and Covariates from Epidemiologic Studies

Objective: Observational studies are essential for investigating risk factors for Alzheimer's disease and related dementias (ADRD), but inconsistent reporting and selection of covariates can contribute to residual confounding, omitted-variable bias, and reduced reproducibility. We developed and evaluated VAREX (Variable Extraction), a large language model (LLM)-based information extraction framework designed to automatically identify exposures, outcomes, and covariates from epidemiologic studies and populate structured evidence repositories. Materials and Methods: VAREX combines retrieval-augmented generation, biomedical language-model embeddings, semantic chunking, cross-encoder reranking, and prompt-engineered LLM workflows to extract epidemiologic variables from full-text biomedical articles. The framework was evaluated using a reference-standard corpus of observational studies examining blood pressure variability (BPV) and Alzheimer's disease-related dementias (ADRD), together with external validation datasets involving other exposure-outcome relationships. Extracted variables were compared with independently curated human reference standards using semantic matching and one-to-one assignment procedures. Covariates were additionally classified into ten epidemiologically relevant semantic categories. Results: In the primary BPV[-&gt;]ADRD corpus (10 studies), VAREX achieved a precision of 0.91, recall of 0.84, and F1-score of 0.87 for variable extraction. Covariate classification accuracy was 0.90, yielding a strict extraction-and-classification F1-score of 0.78. External validation datasets demonstrated comparable performance across diverse epidemiologic domains, with extraction F1-scores ranging from 0.73 to 0.85. Category-level performance was strongest for health behaviors (F1=0.96), sociodemographic variables (F1=0.90), and medication exposures (F1=0.89). Compared with published estimates of manual systematic-review effort, VAREX reduced processing time from approximately 61 minutes to 9 minutes per article, representing an 85.7% reduction in review time. Discussion: These findings demonstrate that LLM-based information extraction can accurately identify and classify epidemiologic variables across heterogeneous observational-study designs. Automated extraction enables scalable construction of structured repositories of exposures, outcomes, and covariates while substantially reducing the labor required for evidence synthesis and systematic reviews. Conclusion: VAREX provides an effective framework for automated extraction and classification of epidemiologic variables from the biomedical literature. By supporting large-scale evidence synthesis and structured knowledge resource development, VAREX may facilitate more rigorous observational research, improved confounder identification, and enhanced reproducibility in epidemiology.

19.
arXiv (CS.LG) 2026-06-17

Blind Recovery of Latent Domains via Unsupervised Symmetry Discovery

arXiv:2606.17782v1 Announce Type: new Abstract: Primary motivation in blind inverse problems is to recover signals of interest from corrupted observations without knowing the obfuscating mechanism. Blind deconvolution is a prominent approach when the corruption is convolutional, but it is not applicable when general linear transformations obfuscate the domain structure. In this work, we propose an unsupervised framework for recovering latent domains and signals by discovering symmetries of the data distribution. Our framework models observations as linear measurements of signals sampled from a latent random field, and optimizes a shallow group-convolutional network by imposing stationarity and locality regularization at the model output. The model learns a latent symmetry action and an appropriate filter, thereby mapping unstructured observations to a symmetry-based representation that reveals latent signals. Experiments on stochastic processes, Ising models, shuffled and bit-scrambled images, and neural recordings show that the method recovers latent domains and signals from unstructured observations, suggesting symmetry discovery as a new direction for unsupervised structure learning and blind inverse problems.

20.
medRxiv (Medicine) 2026-06-18

Rare Coding Variants Reveal Distinct Genetic Architectures Across Multidimensional Sleep Phenotypes

Sleep and circadian traits have been widely studied using common variants, but the contribution of rare coding variation remains unclear. We analyzed rare coding variants in 397,065 whole-exome sequenced UK Biobank participants across 36 sleep phenotypes from self-report, diagnoses, sleep medication use and accelerometry, and meta-analyzed results with 171,536 whole-genome sequenced All of Us participants of diverse ancestries, with replication in the Mass General Brigham Biobank (N = 31,275). We identified 260 genes associated with sleep phenotypes, including novel associations with sleep medication use in 29 genes and 24 out of 29 have not previously been reported with any sleep phenotypes. We observed modest but significant rare variant heritability and strong genetic correlations between sleep medication use, insomnia and fatigue. Temporal gene expression trajectory analyses indicate that genes associated with self-reported sleep traits show constant high prenatal expression, whereas genes linked to sleep medication phenotypes exhibit peak expression in the late prenatal period. These findings highlight distinct biological mechanisms captured by different measurement sources of sleep phenotypes and reveal rare-variant-informed targets for therapeutic discovery.

21.
arXiv (CS.CV) 2026-06-18

Learning Patient-Specific Disease Dynamics with Latent Flow Matching for Longitudinal Imaging Generation

Understanding disease progression is a central clinical challenge with direct implications for early diagnosis and personalized treatment. While recent generative approaches have attempted to model progression, key mismatches remain: disease dynamics are inherently continuous and monotonic, yet latent representations are often scattered, lacking semantic structure, and diffusion-based models disrupt continuity with random denoising process. In this work, we propose to treat the disease dynamic as a velocity field and leverage Flow Matching (FM) to align the temporal evolution of patient data. Unlike prior methods, it captures the intrinsic dynamic of disease, making the progression more interpretable. However, a key challenge remains: in latent space, Auto-Encoders (AEs) do not guarantee alignment across patients or correlation with clinical-severity indicators (e.g., age and disease conditions). To address this, we propose to learn patient-specific latent alignment, which enforces patient trajectories to lie along a specific axis, with magnitude increasing monotonically with disease severity. This leads to a consistent and semantically meaningful latent space. Together, we present $\Delta$-LFM, a framework for modeling patient-specific latent progression with flow matching. Across three longitudinal MRI benchmarks, $\Delta$-LFM demonstrates strong empirical performance and, more importantly, offers a new framework for interpreting and visualizing disease dynamics.

22.
arXiv (quant-ph) 2026-06-12

Vacuum photon emission and mean electromagnetic field in pair-creating external backgrounds

arXiv:2606.12547v1 Announce Type: cross Abstract: We develop a perturbative description of vacuum radiative processes in quantum electrodynamics with a prescribed external electromagnetic background capable of producing electron-positron pairs. Since the initial vacuum is then unstable and the in- and out-vacua are inequivalent, radiative observables require a real-time formulation beyond the ordinary in-out approach of vacuum-stable QED. Using the Keldysh-Schwinger-Fradkin nonequilibrium technique, we derive the mean number density of emitted photons through the second nonvanishing order in the fine-structure constant. The leading term, of order $\alpha$, reproduces the known vertex and tadpole mechanisms, while the complete order-$\alpha^2$ correction contains interference, loop, and induced-current contributions. We also give an independent derivation based on the spectral decomposition of the identity operator in the in-Fock space, where the photon number density is represented as a sum of squared transition amplitudes and vacuum-disconnected terms are canceled by the optical theorem generalized to an unstable vacuum. In addition, we compute the mean electromagnetic field through order $e^3$, including the electromagnetic dressing of the induced vacuum current, and verify it using the corresponding Schwinger-Dyson equations. The final formulas are expressed in terms of exact solutions and propagators of the Dirac equation in the external background and apply to general spacetime-dependent field configurations.

23.
arXiv (CS.CL) 2026-06-15

Automatic identification of diagnosis from hospital discharge letters via weakly supervised Natural Language Processing

Identifying patient diagnoses from hospital discharge letters is essential for large-scale cohort selection and epidemiological research, but traditional supervised approaches require extensive manual annotation, which is often impractical for large textual datasets. We present a weakly supervised Natural Language Processing (NLP) pipeline for classifying Italian discharge letters without document-level manual annotation. The method extracts diagnosis-related sentences, generates semantic embeddings using a transformer model further pre-trained on Italian medical documents, and applies a two-level clustering procedure to derive weak labels that are then used to train a document-level classifier. The approach was evaluated in a case study on bronchiolitis using 33,176 discharge letters of children admitted to 44 emergency rooms or hospitals in the Veneto Region, Italy, between 2017 and 2020. The best weakly supervised model achieved an AUROC of 77.68% ($\pm4.30\%$), an AUPRC of 73.13% ($\pm4.93\%$), and an F1-score of 78.14% ($\pm4.89\%$) against manually annotated data. Performance surpassed unsupervised baselines and approached fully supervised models, while reducing the need for manual annotation by more than 1,500 hours for a dataset of this size. Similar model rankings were observed in a secondary validation on a smaller bronchitis dataset (3,188 discharge letters, 2020-2025), where the best weakly supervised model achieved an AUPRC of 76.72% ($\pm 5.02\%$). These results suggest the potential of weakly supervised NLP methods for scalable disease identification from clinical discharge letters.

24.
PLOS Computational Biology 2026-05-29

A prototype-augmented graph representation learning framework for identifying brain disorder-associated genes and facilitating drug repurposing

Authors:

by Jiafang Li, Yifei Li, Siying Lin, Jiahua Rao, Huiying Zhao Many genetic loci were identified as associated with neuropsychiatric disorders and neurodegenerative disorders by Genome-wide association studies (GWAS). How these loci impact these diseases is unclear. Advances in deep-learning approaches and multi-omics data have the potential to link GWAS findings with disease mechanisms. Here, we proposed the Multi-omics Graph Transformer Network (MOGT), a semi-supervised graph neural network that leverages graph representation learning to model biological networks derived from multi-omics data to predict disease-associated genes. MOGT outperforms the current approaches in disease gene prediction for two psychiatric disorders and three neurodegenerative/neurological diseases. High-risk genes (HRGs) for Parkinson’s disease (PD) predicted by MOGT were used to drug discovery by integrating with the CMAP database. Finally, 10 drugs were identified as potential candidates. Among them, the effect of drug UK-356618 was experimentally verified in a primary neuron model, showing that UK-356618 reversed the abnormal expression of PD-associated genes and improved the cell-level phenotypes of PD. Together, these results indicate that MOGT can be used to identify HRGs for brain disorders, and these predicted HRGs provide high-level insights into the mechanisms and treatments of brain disorders.

25.
arXiv (CS.CL) 2026-06-12

One Token to Fool LLM-as-a-Judge

Large language models (LLMs) are increasingly trusted as automated judges, assisting evaluation and providing reward signals for training other models, particularly in reference-based settings like Reinforcement Learning with Verifiable Rewards (RLVR). However, we uncover a critical vulnerability even in this reference-based paradigm: generative reward models are systematically susceptible to reward hacking. We find that superficial inputs, which we term ''master keys'' such as non-word symbols (e.g., '':'' or ''.'') or generic reasoning openers (e.g., ''Thought process:'' or ''Let's solve this problem step by step.''), can consistently elicit false positive rewards without any substantive reasoning. Our systematic evaluation demonstrates this is a widespread failure affecting a diverse range of models, including leading proprietary systems such as GPT-o1 and Claude-4. These results challenge the assumed robustness of LLM judges and pose a significant threat to their reliability. To address this, we propose a simple yet effective data augmentation strategy using truncated model outputs as adversarial negative examples. The resulting Master Reward Models (Master-RMs) demonstrate state-of-the-art robustness against these ''master key'' attacks while maintaining high performance in standard evaluation settings. We supplement these findings with a comprehensive analysis of the vulnerability across model scales, prompt variations, and common inference-time strategies, offering insights to guide future research on robust LLM evaluation. We release our robust, general-domain reward models and the synthetic training data at https://huggingface.co/sarosavo/Master-RM and https://huggingface.co/datasets/sarosavo/Master-RM.