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01.
arXiv (CS.AI) 2026-06-11

EvalStop: Using World Feedback to Detect and Correct Reward Overoptimization in Multi-Tenant RLHF Platforms

arXiv:2606.04145v2 Announce Type: replace-cross Abstract: Cloud LLM fine-tuning platforms increasingly serve RLHF workloads, where a learned reward model is optimized as a proxy for human quality. As Gao et al. (2023) showed, this proxy diverges from world feedback (downstream eval metrics) under sustained optimization pressure, a phenomenon known as reward overoptimization. Existing platform schedulers ignore this divergence: non-clairvoyant schedulers optimize JCT without any quality signal, SLAQ-style quality-aware schedulers use training loss (a weaker proxy that drops monotonically through hacking), and classical per-job early stopping requires human monitoring and does not free shared GPUs. We propose EvalStop, a composable scheduling primitive that terminates jobs on k consecutive eval-score declines, releases GPUs, preserves the best checkpoint, and delegates to any base scheduler. We frame scheduler-level early stopping as a detection problem and evaluate it in a discrete-event simulator whose RLHF workload mixes reward-hacking and structurally healthy runs, with ground-truth labels hidden from schedulers. On RLHF-heavy workloads (80% RLHF, 64 GPUs), EvalStop achieves precision 98% / recall 99% / FPR 1.5% while improving JCT by 9% and cutting wasted compute by 22% over SRTF-Est (p

02.
arXiv (CS.CL) 2026-06-19

Investigating Human-Model Discrepancies in Speech Quality Assessment via Acoustic and Prosodic Perturbations

Mean opinion score (MOS) prediction models are widely used as proxy metrics in text-to-speech (TTS) research, yet their ability to capture quality differences beyond acoustic fidelity remains unclear. We investigate this via controlled perturbations on speech: acoustic degradation, prosodic errors, and manipulation of speaker-specific characteristics such as pitch and speaking rate. We obtained MOS predictions for these speech samples from both human listeners and the model, and analyzed the differences in their perceptual characteristics. Results show that most models track acoustic degradation well, while all are insensitive to prosodic errors despite large subjective score drops. For speaker characteristics, models exhibit a double dissociation: strong mean fundamental frequency (F0) biases absent in human ratings, yet insensitivity to speaking rate and F0 variability that humans notice. These findings highlight limitations of scalar MOS prediction beyond acoustic fidelity.

03.
bioRxiv (Bioinfo) 2026-06-18

Bioinf-Farma: supervised integration of epitope prediction and recombinant protein developability for automated vaccine candidate prioritization

Vaccine antigen discovery requires prioritizing protein candidates according to both immunogenic potential and recombinant expression feasibility. These properties are typically evaluated using separate computational tools, requiring researchers to integrate heterogeneous outputs through ad hoc workflows. Here, we present BIOINF-farma, a modular platform integrating epitope prediction and developability assessment for rational antigen selection within a unified environment. Candidates can be submitted as amino acid sequences or three-dimensional structures. When experimental structures are unavailable, BIOINF-farma automatically searches for models in AlphaFold DB or performs structure prediction using Boltz-2, ensuring a standardized structural representation for downstream analyses. Antigenicity is quantified by combining structure-based conformational epitope signals (MLCE/REBELOT-BEPPE) and sequence-based linear epitope propensity scores (BepiPred 3.0) into a protein-level Antigenicity Score, with a classification threshold optimized on a manually curated validation dataset. Developability is evaluated through two supervised Random Forest meta-learners that integrate three solubility predictors (DeepSoluE, SoluProt, Protein-Sol) and three thermal stability predictors (TemStaPro, ProLaTherm, BertThermo), whose outputs are combined into an Expression Efficiency Score (EES). By integrating complementary predictive signals, the meta-learning framework achieves greater accuracy and robustness than individual predictors while maintaining performance across a broad range of sequence identities. The Antigenicity Score effectively discriminates antigenic from non-antigenic proteins with a large effect size, whereas EES successfully distinguishes soluble from insoluble outcomes on an independent panel of recombinant proteins expressed in Escherichia coli. BIOINF-farma jointly assesses antigenicity and expression feasibility within a single framework. Its modular architecture facilitates the incorporation of future predictive methods, while its web-based interface makes the full pipeline accessible to users without programming expertise, supporting rapid candidate triage in vaccine research and emerging pathogen responses.

04.
arXiv (CS.LG) 2026-06-19

Bioacoustic Geolocation: Species Sounds as Geographic Signals

arXiv:2505.18726v3 Announce Type: replace-cross Abstract: Can we determine someone's geographic location solely from the sounds they hear? Are acoustic signals enough to localize within a country, state, or even city? In this work, we tackle the challenge of global-scale audio geolocation, with a particular focus on wildlife and natural sounds. We posit that bioacoustic signals contain informative geolocation cues because of well-defined geographic ranges of species. To test this hypothesis, we benchmark image geolocation and soundscape mapping methods, design oracles and species-centric baselines, and propose a hybrid approach that combines species range prediction with retrieval-based geolocation. We further ask whether geolocation improves with species-diverse recordings and spatiotemporal aggregation across neighboring samples. Finally, we extend our study to multimodal geolocation with case studies from movies that combine both audio and visual content. Our results highlight the potential of incorporating bioacoustic signals into geospatial tasks, motivating future work on species recognition and audio geolocation.

05.
arXiv (CS.AI) 2026-06-15

A Benchmark and Framework for Evaluating Next Action Predictions in Spreadsheets

arXiv:2606.13802v1 Announce Type: cross Abstract: Predictive code completion greatly accelerates how quickly developers work. In spreadsheets, despite being much more common, such auto-completion features are virtually non-existent. To address this gap, we introduce a benchmark for systems that observe a sequence of user actions in a spreadsheet and predict future actions. Two challenges are (1) the absence of edit histories in public spreadsheet corpora and (2) the complex space of spreadsheet actions (spatial, temporal, composite). To address (1), we manually curate 52 sequences of 12K actions that recreate spreadsheets from public corpora, seeded by parametrized heuristics and LLM refinement. To address (2), we propose an online evaluation that expects a prediction after each user action, accepts or rejects that prediction, updates the future actions upon acceptance, and repeats this until the target spreadsheet is obtained. We use multiple baseline predictors (including zero-shot LLMs, fine-tuned SLMs, and classical models) and analyze different properties that our benchmark teaches us, including but not limited to: properties of saved actions and false positives, efficiency, effect of user profiles, effect of triggers, and effect of context.

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

Transfer-matrix functions for algebraically decaying interactions in variational infinite matrix product states

Authors:

arXiv:2606.20522v1 Announce Type: cross Abstract: Variational infinite matrix product state (iMPS) calculations usually make Hamiltonians with algebraically decaying interactions compatible with standard MPO algorithms by first replacing the target Hamiltonian with a finite-pole sum-of-exponentials surrogate, thereby introducing a Hamiltonian-representation residual. We formulate the fixed-$D$ variational energy without introducing such a surrogate. For a fixed finite-$D$ MPS, the algebraic tail can be summed directly through the connected transfer matrix: the tail $e^{\mathrm{i} Qr}/r^\alpha$ is represented by the matrix function $F_{\alpha,Q}(\widetilde{T}_A)$, with $F_{\alpha,Q}(z)=\operatorname{Li}_\alpha(e^{\mathrm{i} Q}\,z)/z$. We evaluate the resulting matrix-function action using a Krylov method and obtain stable gradients by combining a Fréchet adjoint with implicit fixed-point differentiation. Benchmarks on long-range free fermions and the inverse-square Heisenberg family, including the Haldane–Shastry point, validate the transfer-matrix-function formulation. A long-range Ising-chain calculation illustrates a practical consequence of avoiding a finite-pole Hamiltonian representation. At a fixed, independently known critical field, finite-pole surrogate Hamiltonians can bias a critical diagnostic away from criticality, whereas the matrix-function calculation retains the expected critical signatures of the target algebraic Hamiltonian.

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

Modeling Doppler Shifts in Radial-Velocity Data with Deep Learning toward Earth-mass Exoplanet Detection

arXiv:2606.18464v1 Announce Type: cross Abstract: Detecting the tiny Doppler shifts induced by Earth-mass planets in stellar radial-velocity measurements remains extremely challenging due to stellar activity. Many deep-learning methods performing well on simulated data remain difficult to apply reliably on real stellar spectra. The aim of this work is to develop a deep-learning framework that generalizes to real, unseen spectra and improves the detectability of Earth-mass planets in radial-velocity data. We train artificial neural networks on HARPS-N solar spectra with injected planetary signals, using physics-motivated spectral representations based on flux and line-formation temperature, together with their velocity gradients. Two training strategies are explored: hold-out testing and cross-validation. Model robustness is enhanced through genetic-algorithm-based hyperparameter optimization, and predictive uncertainty is quantified using Monte Carlo dropout. Our most precise neural network model reliably retrieves, under the cross-validation strategy, the amplitudes, phases, and orbital periods of planetary signals with amplitudes greater than or equal to 25 cm/s and periods between 10 and 550 days. In addition, in all cases tested here, the successfully recovered signals correspond to the most significant peaks in the periodograms of the Doppler-shift predictions. Temperature-based spectral-shell representations consistently outperform flux-based shells. We also release doppleriann, a Python package implementing the proposed framework. Our results demonstrate that combining physically motivated spectral representations with deep learning provides a promising pathway toward the detection of Earth-mass planets in radial-velocity data from real observations, supported by a modeling framework that is both physically grounded and statistically rigorous, incorporating uncertainty quantification and optimized training strategies.

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

StepGuard: Guarding Web Navigation via Single-Step Calibration

arXiv:2606.17871v1 Announce Type: new Abstract: Web navigation requires agents to follow natural language goals, interact with web pages, and produce accurate answers. While recent advances leverage vision-language models and reinforcement learning, existing methods still suffer from single-step fragility due to reward misalignment and error propagation. To tackle the reward entanglement, we design Dynamic Dual-Policy Optimization (DDPO), which dynamically switches between a navigation-first mode for exploration and an answer-first mode for question-answering to mitigate reward conflict. To calibrate the single-step error, we propose Confidence-Guided Adaptive Navigation Reflection (CANR), a mechanism that estimates per-step confidence, triggers reflection only when necessary, and uses contrastive rewards to encourage self-correction to calibrate the single-step inaccuracy. With the above as the main components, we finally develop our StepGuard, a new framework of Guarding Web Navigation via Single-Step Calibration. Experiments demonstrate that our approach significantly improves navigation and answer accuracy, setting new state-of-the-art performance on standard web navigation benchmarks.

09.
arXiv (CS.LG) 2026-06-16

Dynestyx: A Probabilistic Programming Library for Dynamical Systems

arXiv:2606.16985v1 Announce Type: cross Abstract: State-space models (SSMs) are the standard formalism for Bayesian treatment of dynamical systems, with natural applications in statistics, signal processing, and machine learning. Despite their importance in both theory and application, dynamical systems have proven difficult to incorporate in modern probabilistic programming languages (PPLs), making state-of-the-art methods less accessible to practitioners and introducing friction in following the "Bayesian workflow." We introduce dynestyx, a probabilistic programming library with first-class support for SSMs, including state-of-the-art methods in the estimation of both states and parameters. Through a single, unified interface, users may specify arbitrary priors for discrete-time or continuous-time dynamical systems, perform inference over mixed-effect data, and make state and parameter estimates with principled uncertainty quantification.

10.
arXiv (CS.CV) 2026-06-19

Relighting as a Probe of Visual Priors via Augmented Latent Intrinsics

Image-to-image relighting requires representations that separate illumination from scene properties while preserving dense geometry, material, and photometric cues. We use this task as a probe of visual priors: unlike recognition tasks that reward invariance, relighting tests whether visual features retain the information needed for light transfer. Through a controlled generative relighting framework, we find that strong semantic encoders can degrade relighting quality, exposing a semantic–photometric trade-off between abstraction and physical fidelity. We introduce Augmented Latent Intrinsics (ALI), which balances this trade-off by fusing dense, pixel-aligned visual features into a latent-intrinsic relighting model and refining it with self-supervision on unlabeled real image pairs. ALI improves relighting quality, especially on glossy, metallic, and transparent materials, and demonstrates that generative relighting is an effective tool for quantifying what visual encoders encode about the physical world.

11.
medRxiv (Medicine) 2026-06-20

EpiLink: a simulation-based compatibility model for genomic transmission clustering in infectious disease surveillance

Identifying recently linked infections from pathogen genome sequences is central to infectious disease surveillance, yet many clustering approaches rely on fixed genetic distance thresholds whose relationship to transmission is often unclear. This limitation is especially important in rapidly growing outbreaks and superspreading events, where many cases may be sampled close together in time and share little genetic variation, making true transmission links difficult to distinguish from other closely related infections. Supervised models can improve discrimination, but they require labelled transmission data that are rarely available during outbreak response. We developed EpiLink, a threshold-free method that estimates whether two cases are compatible with recent transmission. Here, compatibility means how well the observed genetic distance and sampling-time difference between two cases fit what would be expected if they were linked by defined recent transmission scenarios. EpiLink simulates plausible recent transmission histories while accounting for uncertainty in infection timing, testing delay, and mutation accumulation, then assigns higher scores to pairs whose observed differences are typical of those simulations. EpiLink was evaluated using both synthetic and empirical SARS-CoV-2 outbreak data from the 2020 Boston epidemic. Two EpiLink variants were compared to a logistic regression model trained on labelled transmission data. One EpiLink variant assumed deterministic mutation accumulation, with genetic differences proportional to elapsed evolutionary time; the other accounted for stochasticity by sampling mutation counts from a Poisson distribution. The logistic regression model performed better at distinguishing linked from unlinked pairs, but EpiLink achieved comparable clustering accuracy. In the Boston data, EpiLink recovered clusters enriched for documented conference and skilled nursing facility outbreaks. EpiLink thus provides an interpretable, simulation-based approach for identifying recent transmission clusters when fixed thresholds are difficult to justify and labelled transmission data are unavailable.

12.
bioRxiv (Bioinfo) 2026-06-15

SMS: Symmetric Mediation Statistics for Powerful High-Dimensional Mediation Analysis

Background: Mediation analysis of high-dimensional features, particularly molecular-level omics features, provides important opportunities to uncover biological mechanisms underlying human health and disease. However, two central statistical challenges remain: testing the composite-null hypothesis and maintaining power when the exposure-mediator and mediator-outcome associations differ substantially in statistical significance. Existing methods typically rely on accurate estimation of the proportions of the three null types or on the maximum of the two association p-values, and may not always control the FDR well and may have limited power under imbalanced significance. Methods: We propose SMS, a new statistical framework based on symmetric mediation statistics. By exploiting symmetry, SMS calibrates the composite null distribution as a whole for FDR control. It also allows flexible combinations of the two association p-values, including the maximum, and then enables construction of an omnibus test. Moreover, it permits direct use of effect-size estimates, bypassing the need to compute p-values. Results: SMS controlled the FDR across a wide range of simulation scenarios while achieving a substantial sensitivity gain, often around 20 percentage points, over existing methods including HDMT, DACT, and DEI-B. Applications to a metabolomics dataset and a DNA methylation dataset further corroborated these findings. Notably, SMS discovered five plausible mediators in the metabolomics dataset that were missed by all existing methods considered.

13.
arXiv (CS.CV) 2026-06-11

Feature extraction for plant growth estimation

Precision agriculture requires the estimation of plant growth stages in real-time. When the plant growth stage is known, the wastage of resources in cultivation, such as nutrients and water, is reduced as only the required resources need to be supplied. Plants at different growth stages, however, have similar morphological features, which can make autonomous growth stage estimation difficult. This paper presents two feature extraction methods for growth stage estimation: one that uses a bank of Gabor filters and morphological operations, and the other that uses pre-trained convolutional neural networks (CNNs) and transfer learning. We test these methods on a publicly available plant growth stage dataset (``bccr-segset``) for two species, canola and radish, grown and captured under indoor conditions. The two proposed feature extraction methods are compared, using support vector machines and boosted trees as classifiers. We find that both methods are suitable for real-time applications, and that CNN features outperform the hand-crafted features, both with regard to speed and accuracy. The best system (VGG-19 features, classified with a radial basis function support vector machine) obtained an accuracy of 98.4% for both species, processing an image in 0.08 seconds.

14.
PLOS Computational Biology 2026-06-12

A new method for augmenting short time series, with application to pain events in sickle cell disease

Authors:

by Kumar Utkarsh, Nirmish R. Shah, Tanvi Banerjee, Daniel M. Abrams Researchers across different fields, including but not limited to ecology, biology, and healthcare, often face the challenge of sparse data. Such sparsity can lead to uncertainties, estimation difficulties, and potential biases in modeling. Here we introduce a novel data augmentation method that combines multiple sparse time series datasets when they share similar statistical properties, thereby improving parameter estimation and model selection reliability. We demonstrate the effectiveness of this approach through validation studies comparing Hawkes and Poisson processes, followed by application to subjective pain dynamics in patients with sickle cell disease (SCD), a condition affecting millions worldwide, particularly those of African, Mediterranean, Middle Eastern, and Indian descent.

15.
arXiv (CS.CL) 2026-06-16

Multi-Turn Reflective Masking Elicits Reasoning in Mask Diffusion Models

While reasoning on autoregressive (AR) models is often performed by chain-of-thought reasoning and reflection, their refinement of previous outputs still relies on fully sequential generation, even when only local edits are needed. In contrast, the masking mechanism in Mask Diffusion Models (MDMs) naturally supports explicit local edits on previous outputs, allowing selective refinement without discarding previous answers and generating another from scratch. While this property more closely aligns with how humans correct mistakes by iterative local refinement, existing MDMs do not support multi-turn masking and denoising. We propose Reflective Masking (RM), which elicits such an intrinsic reasoning capability in MDMs via lightweight post-training. RM provides a native test-time scaling, where an MDM iteratively revisits and revises its prior outputs based on evolving context. To exploit insights from previous turns like AR reasoning, we further introduce History Reference, a parameter-free mechanism that leverages intermediate denoising states during revision. Our approach requires no architectural changes and is easily applicable to existing MDMs. Across diverse tasks and modalities, including text generation, Sudoku, and image editing, Reflective Masking consistently outperforms standard masking-based baselines and demonstrates strong generality, positioning RM as a fundamental primitive for reasoning on MDMs.

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

ACCORD: Action-Conditioned Contextual Grounding for Language Agents

User instructions are often underspecified because humans rely on implicit assumptions about the surrounding environment. For large language model (LLM) agents operating in information-rich digital and physical environments, these assumptions cannot be inferred from the instruction alone; they must be recovered from the current state of tools, data, interfaces, and observations. Effective execution therefore requires agents to identify missing context, ground it in observed evidence, and carry it forward into subsequent actions. We show that current agents often fail to do so. They act from assumed rather than observed specifics, overlook information they could have gathered, and fail to incorporate evidence that has already been returned. Building on this insight, we propose ACCORD (Action-Conditioned Contextual Grounding), a simple and effective agent framework for adaptive grounding. Before each action, ACCORD actively probes the environment for missing information and integrates relevant context from the agent's trajectory that would otherwise be overlooked. Requiring no additional training or task-success signals, ACCORD improves task-goal completion on AppWorld by up to +20.6 points with GPT-5-mini, from 42.0% to 62.6%, compared to strong baselines. These gains persist with a substantially stronger base model (+10.8 with Claude-4.5-sonnet), an open-weight model (+10.1 with Qwen3.5-27B-FP8), and on the embodied AlfWorld benchmark (+7.4 success rate with GPT-5-mini).

17.
arXiv (CS.AI) 2026-06-16

Heteroskedastic Signals in Budgeted LLM Verification: Structural Heterogeneity Limits Optimization Gains

Authors:

arXiv:2606.15841v1 Announce Type: new Abstract: Large language model (LLM) systems increasingly use uncertainty signals to allocate limited computation across verification, test-time scaling, tool execution, and other selective-compute decisions. Such policies rely on a global signal comparability assumption: equal scores should carry comparable decision value across inputs. Using budgeted verification as a controlled diagnostic setting, we identify a failure mode of this assumption: uncertainty quality is heteroskedastic across cost strata, with some regions exhibiting near-random discriminability despite concentrating many errors. Under an explicit local model, we characterize the resulting distortion of global allocation and show that its upper bound scales with cross-stratum signal-quality dispersion. We separate weak signals, optimization instability, and structural heterogeneity through a controlled intervention hierarchy: Threshold, MP-Adapt, MP-Strat, and a deliberately simple cost-stratified thresholding intervention (CST). Across MBPP and MATH using Qwen3-8B, LLaMA3-8B, and GPT-4o-mini, global online adaptation yields inconsistent gains over static thresholding; MP-Strat partially recovers performance, while CST improves hit rate by up to 17 percentage points in strongly heterogeneous settings without gradient updates. These results identify structural heterogeneity, rather than optimizer weakness alone, as the primary bottleneck in the observed settings. More broadly, misaligned feedback structure cannot always be repaired by stronger optimization.

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

A Study of Belief Revision Postulates in Multi-Agent Systems (Extended Version)

arXiv:2605.02249v2 Announce Type: replace Abstract: We investigate the belief revision problem in epistemic planning, i.e., what will be the beliefs of all agents in a multi-agent system after an agent gains the belief in some state property. Based on the standard representation in epistemic planning of agents' beliefs via a single multi-agent Kripke model, we generalize the classical AGM belief revision postulates to the multi-agent setting, with the aim to provide a formal framework for evaluating dynamic epistemic reasoning frameworks in which the beliefs of all agents as the result of actions are computed. As an example of a simple operator that satisfies all of the generalized AGM postulates, we present generalized full-meet multi-agent belief revision. We moreover define a generalization of the standard postulates for iterated revision, present a more sophisticated, event model based revision operator, and discuss the potential issues in defining an epistemic operator on Kripke models that can satisfy all of the generalized postulates for iterated multi-agent belief revision.

20.
arXiv (CS.AI) 2026-06-15

Refusal Beyond a Single Direction: A Preliminary Comparison of Diff-in-Means and INLP

arXiv:2606.13720v1 Announce Type: new Abstract: Arditi et al. (2024) has shown that refusal in safety fine-tuned chat models is mediated by a single linear direction in the residual stream, recoverable by a difference-in-means (DiM) of harmful and harmless activations. We compare DiM-based interventions (activation addition and directional ablation) with two interventions derived from Iterative Nullspace Projection (INLP) – nullspace projection and counterfactual flipping – on five open-weight chat models, asking whether INLP can match DiM at steering refusal and whether its richer parameterisation yields more tweakable interventions. INLP counterfactual flipping is competitive with DiM directional ablation on refusal suppression, while nullspace projection is consistently weaker. Restricting INLP to the leading directions of the extracted subspace preserves most of the suppression effect at near-baseline perplexity, giving a tunable capability. Geometrically, the two INLP interventions land in qualitatively different regions of activation space: nullspace projection collapses transformed activations between the harmful and harmless clusters, while counterfactual flipping moves them into the opposite cluster, suggesting that the model encodes the absence of a concept differently from its opposite – an intriguing distinction that warrants further investigation in future work.

21.
arXiv (CS.LG) 2026-06-19

Interactive Pareto navigation for deep multi-task learning

arXiv:2606.19521v1 Announce Type: new Abstract: In multi-task learning, handling an increasing number of objectives can quickly become challenging, both in terms of the computational resources and the decision maker's capacity to choose appropriate trade-offs. A widely used approach is thus to aggregate the individual losses in a single loss function by a weighted sum. This often fails to capture either the decision maker's preferences as a result of the shape of the Pareto front, or requires multiple adjustments and computations which becomes prohibitively expensive in deep learning applications. To address these issues, we introduce a novel framework, Preference Pareto Exploration (PPE), which enforces the decision maker's preferences while accounting for the geometry of the Pareto set in an interactive exploration process. PPE is based on a predictor-corrector method that performs predictor steps tangential to the manifold of Pareto-optimal solutions, following the decision maker's preference. The subsequent corrector step results in a new trade-off reflecting this preference. To avoid explicit Hessian computations when characterizing the tangent space of the manifold, we employ a Krylov subspace method that relies solely on matrix-vector products. These products can be efficiently obtained via automatic differentiation, ensuring both efficiency and robustness throughout the optimization process. The method's functionality and performance are demonstrated using both toy problems and examples from deep learning.

22.
medRxiv (Medicine) 2026-06-15

Evaluation of AI-Generated Synthetic Data for Clinical Research in Secondary Cardiovascular Prevention among Dyslipidemia Patients

Background: Access to high-quality clinical data is essential for advancing medical research and developing effective medical statistical and Artificial Intelligence models. However, privacy regulations and logistical barriers often hinder timely access to real-world data. Synthetic data offer a promising solution, preserving the statistical characteristics of original datasets while protecting patient privacy. Objectives: This study investigates the use of synthetic data for secondary cardiovascular prevention in patients with dyslipidemia, using two real-world datasets from Centro Cardiologico Monzino. Methods: Given the high dimensionality and limited sample size of the datasets, we employed a custom generative framework based on Large Language Models (LLMs). Pre-trained LLMs were fine-tuned on original clinical records to synthesize tabular data replicating source-data distributions. Fine-tuning was performed within the Centro Cardiologico Monzino's secure infrastructure to ensure data sovereignty. We evaluate clinical utility and privacy using fidelity and privacy metrics, identifying the optimal generative model and benchmarking against traditional anonymization methods. Results: Synthetic data achieved a superior trade-off than classically anonymized datasets. Real and synthetic datasets showed strong agreement, with significant distributional differences limited to few variables. Models trained on synthetic data replicated key associations from the original dataset, including therapy modification and creatine phosphokinase as predictors of SAMS, and pharmacological intensity as the main driver of LDL-C reduction. Conclusions: Results support the feasibility of using synthetic data as a proxy for real-world datasets in exploratory analyses and model development. Despite slight attenuation of some effect sizes, preserved clinical relationships reinforce the validity of synthetic data in medical research.

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

AAPA: Adversarially Anchored Preference Alignment for Post-Training of Large Language Models

arXiv:2509.25148v2 Announce Type: replace Abstract: Post-training alignment of large language models often combines supervised fine-tuning (SFT) on expert demonstrations with reinforcement learning (RL) from preference or verifiable feedback. SFT provides a useful behavioral anchor but can overfit to static demonstrations, whereas RL encourages exploration but may drift from expert behavior or exploit imperfect rewards. We propose AAPA (Adversarially Anchored Preference Alignment), a plug-in framework that augments existing post-training objectives with a sentence-level adversarial anchoring signal. AAPA compares policy rollouts with offline, pre-collected expert responses using a fixed lightweight discriminator, and therefore requires neither online teacher inference nor discriminator co-training during policy optimization. The same anchoring term can be added to SFT, GRPO, and CHORD while preserving their original training pipelines. Experiments on instruction-following benchmarks show that AAPA consistently improves the corresponding base objectives across model scales. In particular, the staged AAPA configuration improves over a strong GRPO baseline by 5.77\% on \texttt{Qwen3-0.6B} and 3.75\% on \texttt{Qwen3-4B}. Further analyses on response length, log-probability distributions, and discriminator variants suggest that adversarial anchoring provides a stable semantic grounding signal for preference optimization. Code is available at \url{https://github.com/IsFaqq/AAPA}.

25.
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