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01.
arXiv (CS.LG) 2026-06-19

Fisher-Geometric Sharpness and the Implicit Bias of SGD toward Flat Minima

arXiv:2606.20469v1 Announce Type: new Abstract: A widely held intuition in deep learning is that stochastic gradient descent (SGD) implicitly favors flat minima and that flat minima generalize better, but standard Euclidean measures of flatness such as the trace or maximum eigenvalue of the loss Hessian are not invariant under reparametrizations that preserve the network function, which undermines the theoretical foundations of this narrative. In this study we resolve this issue by grounding flatness in the Riemannian geometry of the statistical manifold induced by the Fisher Information Matrix (FIM). We define Riemannian sharpness mathematically and prove that it is invariant under smooth, function-preserving reparametrizations, which directly addresses the critique of Dinh et al. in the paper ``Sharp minima can generalize for deep nets''.We note that this invariance is a property of the true FIM; the diagonal empirical estimator used in practice (and in all experiments below) inherits invariance only approximately, and exact invariance under arbitrary reparametrizations would require structured estimators such as K-FAC. We formalize the gradient noise of mini-batch SGD as having a covariance structure proportional to the FIM, derive the stationary distribution of the resulting stochastic differential equation, and then show that the probability mass is exponentially concentrated at Riemannian-flat minima. A PAC-Bayes generalization bound controlled explicitly by SR formally links this geometric bias to test performance. Our experiments on MNIST and CIFAR-10 confirm that SR reliably tracks generalization in ways that Euclidean sharpness does not, and that its scaling with $\eta/B$ matches the theoretical predictions. Together these results provide a rigorous, reparametrization-invariant account of why flat minima generalize.

02.
arXiv (CS.CV) 2026-06-12

AudioX-Turbo: A Unified Framework for Efficient Anything-to-Audio Generation

Audio and music generation based on flexible multimodal control signals is a widely applicable topic, with the following key challenges: 1) a unified multimodal modeling framework, 2) large-scale, high-quality training data, and 3) the prohibitive inference cost of multi-step diffusion sampling. As such, we propose AudioX-Turbo, a unified and efficient framework for anything-to-audio generation that integrates varied multimodal conditions (i.e., text, video, and audio signals) in this work. AudioX-Turbo follows a teacher-student paradigm. The teacher AudioX-Base is built on a Multimodal Diffusion Transformer with a Multimodal Adaptive Fusion module that aligns diverse multimodal inputs for high-fidelity synthesis, and is then distilled into the few-step student AudioX-Turbo via Distribution Matching Distillation adapted to flow matching, complemented by a diffusion-based discriminator for high-quality few-step generation. To support the training of AudioX-Turbo, we construct a large-scale, high-quality dataset, IF-caps-Pro, comprising approximately 9.2M samples curated through a two-stage data collection and annotation pipeline. We benchmark AudioX-Turbo across a wide range of tasks, finding that our model achieves superior performance, especially on text-to-audio and text-to-music generation, while operating at only 4 sampling steps and requiring approximately 25x fewer function evaluations (NFE) than multi-step baselines. These results demonstrate that our method is capable of audio generation under flexible multimodal control, showing efficient and powerful instruction-following capabilities. The code and datasets will be available at https://zeyuet.github.io/AudioX-Turbo/.

03.
PLOS Computational Biology 2026-06-10

A mean-field model of neural networks with PV and SOM interneurons reveals connectivity-based mechanisms of gamma oscillations

by Farzin Tahvili, Martin Vinck, Matteo Di Volo Classic theoretical models of cortical oscillations are based on the interactions between two populations of excitatory and inhibitory neurons. Nevertheless, experimental studies and network simulations suggest that interneuron subclasses such as parvalbumin (PV) and somatostatin (SOM) exert distinct control over oscillatory dynamics. Yet, we lack a theoretical understanding of the mechanisms underlying oscillations in E-PV-SOM circuits and of the differences with respect to the classical mechanisms for oscillations in simpler E–I networks. Here, we derive a biologically realistic mean-field model of a canonical three-population E-PV-SOM circuit. This model robustly generates oscillations whose features are consistent with experimental observations, including the relative timing of PV and SOM activity and the effects of optogenetic perturbations. By reducing the model to a linear analytical form, we demonstrate that gamma oscillations emerge directly from the cell-specific connectivity of the three-population circuit. This connectivity motif alone accounts for experimentally observed phase relationships, with PV activity consistently leading that of SOM neurons. Together, this mean field model identifies a distinct structural mechanism giving rise to oscillations in canonical E–PV–SOM circuits and provides theoretical primitives for constructing large-scale, cell-type-specific models of cortical dynamics.

04.
arXiv (CS.AI) 2026-06-16

Post-Hoc Merging is Not Enough: Many-Shot Model Merging with Loss-Gap Balancing

arXiv:2606.16501v1 Announce Type: new Abstract: Model merging has become a practical post-training strategy for building a single multi-task large language model (LLM) by combining multiple task-specialized models. However, most existing approaches rely on post-hoc merging, in which task-specific models are merged only once after training. This one-shot aggregation often suffers from task interference, leading to information erasure across individual tasks. In this work, we show that replacing post-hoc merging with an iterative many-shot merging protocol is effective in improving multi-task performance. Building on this insight, we propose METIS, Mitigating Erasure from Task Interference for Stable many-shot merging. METIS is a loss-aware many-shot merging method that addresses information erasure in post-hoc merging through task-wise loss-gap weighting and consensus-based masking. Notably, METIS exhibits significant performance improvement on the worst-performing task, effectively mitigating information erasure. (Project page: https://imkyungjin.github.io/METIS/)

05.
arXiv (CS.CV) 2026-06-12

BrainDINO: A Brain MRI Foundation Model for Generalizable Clinical Representation Learning

Brain MRI underpins a wide range of neuroscientific and clinical applications, yet most learning-based methods remain task-specific and require substantial labeled data. Here we show that a single self-supervised representation can generalize across heterogeneous brain MRI endpoints. We trained BrainDINO, a self-distilled foundation model, on approximately 6.6 million unlabeled axial slices from 20 datasets encompassing broad variation in population, disease, and acquisition setting. Using a frozen encoder with lightweight task heads, BrainDINO supported transfer across tumor segmentation, neurodegenerative and neurodevelopmental conditions classification, brain age estimation, post-stroke temporal prediction, molecular status prediction, MRI sequence classification, and survival modeling. Across tasks and supervision regimes, BrainDINO consistently equaled or exceeded natural-image and MRI-specific self-supervised baselines, with particularly strong advantages under label scarcity. Representation analyses further showed anatomically organized and pathology-sensitive feature structure in the absence of task-specific supervision. Our findings indicate that large-scale slice-wise self-supervised learning can yield a unified brain MRI representation that supports diverse neuroimaging tasks without volumetric pretraining or full-network fine-tuning, establishing a scalable foundation for robust and data-efficient brain imaging analysis. Code is available at https://github.com/mclwu22/BrainDINO

06.
arXiv (math.PR) 2026-06-19

Asymptotic properties for fully coupled delayed forward-backward stochastic differential equations

arXiv:2606.19925v1 Announce Type: new Abstract: We investigate the asymptotic behavior of solutions to a class of fully coupled forward-backward stochastic differential equations with time-delayed generators. Such systems arise naturally in stochastic models with memory effects and constitute a significant extension of the classical fully coupled FBSDE framework. The presence of delay introduces additional analytical difficulties due to the dependence of the coefficients on the past trajectories of the solution processes and the resulting non-Markovian structure. Under suitable assumptions on the coefficients, we study the asymptotic properties of a perturbed delayed FBSDE driven by a small noise parameter. We first establish the convergence in distribution of the associated solution processes as the perturbation parameter tends to zero. We then prove almost sure convergence towards the solution of the corresponding deterministic limiting system. As a consequence of these asymptotic results, we derive a large deviation principle for the solution processes. Our results extend the asymptotic analysis of Cruzeiro, Gomes and Zhang (2014) from the classical fully coupled FBSDE setting to the delayed framework, and complement existing works on weakly coupled delayed forward-backward systems. They provide, to the best of our knowledge, the first large deviation principle for fully coupled forward-backward stochastic differential equations with delayed generators.

07.
arXiv (CS.LG) 2026-06-19

Structure-Oriented Randomized Neural Networks for Poisson-Nernst-Planck and Poisson-Nernst-Planck-Navier-Stokes Systems

arXiv:2606.19912v1 Announce Type: cross Abstract: We develop a structure-oriented randomized neural network framework, termed SO-RaNN, for the Poisson-Nernst-Planck (PNP) system and the Poisson-Nernst-Planck-Navier-Stokes (PNP-NS) system. The decoupled linearized subproblems are solved iteratively by randomized neural networks in a space-time framework. For the concentration variables, a pointwise cut-off is used to enforce positivity at the value level, and discrete mass-scaling factors are computed at selected correction instants and interpolated in time, so as to ensure exact mass matching at those instants and to promote approximate mass preservation between them. To introduce an auxiliary discrete dissipation mechanism, we further employ an SAV-type post-processing correction, which yields monotonicity of the SAV auxiliary variable under the ideal SAV update. For the PNP-NS system, a structure-preserving randomized neural network (SP-RaNN) is used for the velocity field, so that the velocity approximation satisfies the incompressibility constraint pointwise by construction. On the theoretical side, we derive residual-based estimates for the raw, uncorrected RaNN solvers of the linearized subproblems, formulate a conditional local-in-time convergence result for the raw outer Picard iteration of the PNP system, and analyze the value-level positivity correction together with the mass-correction and SAV post-processing steps. For the PNP-NS system, we establish an approximation result for the SP-RaNN space and provide a conditional error statement for the corresponding linearized Oseen-type problem. Numerical experiments demonstrate approximation accuracy in the source-driven manufactured tests and illustrate the intended value-level positivity correction, selected-time mass matching, computed free-energy curves based on the final gauge-fixed potential, and divergence-free approximation in benchmark tests.

08.
arXiv (math.PR) 2026-06-17

Periodicity, type $II_1$ factors and free Poisson laws in interacting Fock spaces

arXiv:2606.18162v1 Announce Type: cross Abstract: We show that the von Neumann algebra generated by position operators in a 2-periodic interacting Fock space is a type $II_1$ factor. On the probabilistic side, we prove that the squared position operators have a Marchenko-Pastur distribution with respect to the vacuum state, yielding a natural realization of free Poisson laws within this framework.

09.
medRxiv (Medicine) 2026-06-17

Treatment of Multi-Drug-Resistant Tuberculosis with Second-Line All-Oral Drugs in Ghana: Incidence of Adverse Events.

Introduction: The treatment of multidrug-resistant tuberculosis (MDR-TB) remains challenging due to the toxicity of second-line medications and suboptimal treatment outcomes. This study aimed to determine the incidence of adverse events and identify factors associated with these events in patients undergoing treatment for MDR-TB with second-line all-oral drugs in Ghana. Methods: This retrospective cohort study reviewed the medical records of 384 MDR-TB patients treated with second-line all-oral drugs at selected health facilities in Ghana, including the Greater Accra Regional Hospital, Eastern Regional Hospital, and Kumasi South Hospital. Data were extracted using the Kobo Collect tool, capturing patient demographics, baseline clinical and laboratory characteristics, treatment regimens, and adverse events. The study period spanned from 2020 to August 2024. Results: The study included a total of 384 MDR-TB patients, with a mean age of 45 years (SD = 15). The majority of patients were male (65.78%), and most were within the 45-64 years age group (33.85%), followed by those aged 25-44 years (31.25%). Regionally, the highest number of cases were reported from the Greater Accra Region (39.06%), followed by the Eastern Region (31.25%) and Kumasi South Hospital (29.69%). Approximately one in four patients (25%) presented with comorbidities, with HIV being the most common (19.5%). The most frequently reported adverse events were diarrhea (14%), dizziness (13.7%), and vomiting (12.3%). Most of these were mild to moderate in severity and tended to decrease as treatment progressed. Severe adverse events, such as leukopenia and acute kidney injury, were rare, occurring in less than 5% of patients. Over the course of treatment, gastrointestinal adverse events such as vomiting and nausea showed a significant decline, indicating possible patient adaptation or improved clinical management. Results from the multivariate Poisson regression analysis revealed that age and comorbidities were significant predictors of adverse events. Patients aged 65 years and above had a 56% lower risk of developing adverse events compared to younger patients (Adjusted Risk Ratio [aRR] = 0.44, 95% CI: 0.25-0.79, p = 0.005). Conversely, patients with comorbid conditions such as diabetes or hypertension were approximately 2.6 times more likely to experience adverse events compared to those without comorbidities (aRR = 2.65, 95% CI: 1.58-4.43, p < 0.001). The effect of sex was not statistically significant after adjustment (aRR = 1.03, 95% CI: 0.70-1.50, p = 0.86). At the end of the treatment period, 74.9% of patients achieved successful outcomes, including both those who were cured and those who completed treatment without being classified as cured. However, 25.1% had unsuccessful outcomes, which included treatment failure, relapse, or death. Conclusion: In conclusion, adverse events are common in the treatment of MDR-TB with second-line All-Oral drugs, with gastrointestinal adverse events being the most prevalent. These findings highlight the importance of monitoring and managing adverse events to optimize treatment outcomes for MDR-TB patients in Ghana.

10.
arXiv (quant-ph) 2026-06-11

Quantum Correlation Hierarchy and Teleportation in Dephased Hydrogen Hyperfine System

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

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

HYDRA-X: Native Unified Multimodal Models with Holistic Visual Tokenizers

Holistic visual tokenizers are fundamental to unified multimodal models (UMMs) as they map diverse visual inputs into a unified representation space. In this paper, we present HYDRA-X, the first UMM that unifies image and video tokenization within a single Vision Transformer (ViT). Our design is driven by two core challenges: efficiently injecting spatiotemporal reconstruction capability into a native ViT, and embedding image- and video-level semantic awareness into the latent space. To address the first, comprehensive ablations reveal two key findings: (1) frame-level causal temporal attention suffices for visual reconstruction, whereas full spatiotemporal attention degrades it; and (2) hierarchical temporal compression substantially outperforms single-step alternatives. To tackle the second, we propose a lightweight decompressor that upsamples temporally compressed features under joint image-video teacher supervision, thereby enforcing complementary semantic structures within the compact latent space. Building on this holistic tokenizer, we further propose a principled improvement of the editing pipeline: source-target interaction should occur at the latent level inside the tokenizer rather than at the semantic level inside the LLM, substantially improving editing consistency and accelerating convergence. Instantiated at the 7B dense model, HYDRA-X achieves strong performance across image and video understanding and generation tasks, paving the way for future unified-tokenizer UMMs.

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

CineDance: Towards Next-Generation Multi-Shot Long-Form Cinematic Audio-Video Generation

The fidelity and structural diversity of training datasets fundamentally determine the capabilities of video generation models. While commercial systems showremarkableabilitytogeneratecinematicnarratives, the progress of open-source models remains limited by the scarcity of high-quality training data. To bridge this gap, we introduce CineDance-1M, a large-scale, open research Text-to-Audio-Video (T2AV) dataset designed specifically for multi-shot, long-form joint audio-video generation. Averaging 92.8 seconds and 24.2 continuous shots per video, it provides configurable, structured annotations for both audio and video modalities. This exceptional quality is achieved through a rigorous three-stage curation pipeline: i) diverse sourcing and comprehensive cleansing, ii) film-theory-inspired narrative parsing, and iii) hierarchical dual-modal captioning. For a comprehensive assessment, we propose CineBench, featuring a diverse prompt suite and a six-dimensional, human-aligned metric system tailored for complex narrative audio-video evaluation. Furthermore, we adapt LTX-2.3 into CineDance, which demonstrates exceptional single-modality quality alongside precise audio-video alignment and robust subject and environment consistency, effectively validating our curation strategy and the high quality of CineDance-1M. We anticipate that this work will serve as a solid foundation for accelerating future research in multi-shot, long-form joint audio-video generation. Our project page is available at https://aliothchen.github.io/projects/CineDance/.

13.
arXiv (CS.AI) 2026-06-19

Uncertainty-Aware Reward Modeling for Stable RLHF

arXiv:2606.19818v1 Announce Type: cross Abstract: Reinforcement learning from human feedback (RLHF) aligns large language models by training reward models on preference data and optimizing policies to maximize predicted rewards. However, this pipeline faces two fundamental challenges: (1) reward models cannot signal when their predictions are unreliable, since they usually act as deterministic point estimators; and (2) modern group-based policy optimization can amplify unreliable reward signals, as exemplified by GRPO's uniform treatment of rewards during advantage computation. As policies explore increasingly diverse responses, these two limitations create a critical vulnerability: unreliable reward estimates may be granted disproportionate influence, triggering severe reward hacking. We propose Uncertainty-Aware Reward Modeling (UARM), which equips reward models with calibrated uncertainty via quantile-based conformal prediction and reweights GRPO advantages through heteroscedastic variance decomposition. Experiments across HelpSteer, UltraFeedback, and PKU-SafeRLHF demonstrate that UARM significantly improves reward model calibration, reduces reward hacking, and enhances downstream alignment quality compared to standard GRPO and uncertainty-agnostic baselines.

14.
arXiv (CS.CL) 2026-06-15

Benchmarking Web Agent Safety under E-commerce Deceptive Interfaces

As autonomous web agents are increasingly deployed to perform real-world tasks, ensuring their safety has become a critical concern. In this work, we study web agent behavior under realistic deceptive interfaces in the e-commerce domain. We introduce WebDecept, a lightweight and configurable plugin framework that enables controlled injection of deceptive interface patterns into existing web environments. Using WebDecept, we instantiate seven deceptive patterns commonly observed on the open web, including targeted advertisements, domain redirection, and shopping manipulation. By injecting these patterns into the frontend during task execution, we perform controlled evaluation of multiple multimodal web agents. Our results show that current web agents are highly susceptible to multiple classes of deceptive interfaces, and that prompt-based constraints are often insufficient to mitigate these failures. We further analyze how the design choices of deceptive patterns influence the success of such manipulations. These findings highlight safety challenges that should be addressed as web agents are scaled toward real-world deployment.

15.
arXiv (math.PR) 2026-06-17

Poisson approximation by coupling

arXiv:2605.01894v2 Announce Type: replace Abstract: It is well known that a binomial $(n,p)$ can be approximated by a Poisson distribution with parameter $np$. The typical approach in undergraduate probability texts is to show a convergence result for the distribution of the binomial as $n$ goes to infinity and $np$ converges to some $\lambda$. In this note we use instead the coupling technique to show a much more general result. Moreover, we only use elementary results from probability.

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

Beyond MACs: Hardware Efficient Architecture Design for Vision Backbones

Vision backbone networks play a central role in modern computer vision. Enhancing their efficiency directly benefits a wide range of downstream applications. To measure efficiency, many publications rely on MACs (Multiply Accumulate operations) as a predictor of execution time. In this paper, we experimentally demonstrate the shortcomings of such a metric, especially in the context of edge devices. By contrasting the MAC count and execution time of common architectural design elements, we identify key factors for efficient execution and provide insights to optimize backbone design. Based on these insights, we present LowFormer, a novel vision backbone family. LowFormer features a streamlined macro and micro design that includes Lowtention, a lightweight alternative to Multi-Head Self-Attention. Lowtention not only proves more efficient, but also enables superior results on ImageNet. Additionally, we present an edge GPU version of LowFormer, that can further improve upon its baseline's speed on edge GPU and desktop GPU. We demonstrate LowFormer's wide applicability by evaluating it on smaller image classification datasets, as well as adapting it to several downstream tasks, such as object detection, semantic segmentation, image retrieval, and visual object tracking. LowFormer models consistently achieve remarkable speed-ups across various hardware platforms compared to recent state-of-the-art backbones. Code and models are available at https://github.com/altair199797/LowFormer/blob/main/Beyond_MACs.md.

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

Semantic-Anchored Evidential Fusion for Domain-Robust Whole-Slide Survival Analysis

arXiv:2606.19966v1 Announce Type: cross Abstract: Whole-slide images (WSIs) are widely used for computational cancer prognosis. However, most existing methods primarily focus on in-domain performance and fail to generalize across clinical centers. This limitation stems from their reliance on pixel-derived representations that are highly susceptible to domain-specific artifacts caused by staining protocols and scanner hardware. We hypothesize that high-level pathology semantics, such as tumor grade and micro-environmental architecture, provide a domain-invariant semantic representation that mirrors the robust diagnostic logic of human pathologists. Therefore, we propose a Semantic-Anchored Evidential Fusion Survival (SAEFS) framework, where SAEFS derives semantic anchors from WSIs via Visual Question Answering (VQA), employs a dual-stream WSI evidence extraction architecture, uses Dirichlet-based Subjective Logic to model uncertainty, and fuses semantic and visual evidence through a cautious conjunction rule to avoid overconfident fusion from correlated sources. Trained exclusively on one source domain and evaluated zero-shot across four unseen domains, SAEFS consistently outperforms state-of-the-art models both in prediction accuracy and reliability, improving the average C-index by 10.2%. Quantitative analyses further show that VQA-derived semantic features exhibit significantly lower cross-center divergence than pixel-derived features, highlighting their robustness for cross-center clinical applications.

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

Zero-Shot Cross-City Generalization in End-to-End Autonomous Driving: Self-Supervised versus Supervised Representations

End-to-end autonomous driving models are typically trained on multi-city datasets using supervised ImageNet-pretrained backbones, yet their ability to generalize to unseen cities remains largely unexamined. When training and evaluation data are geographically mixed, models may implicitly rely on city-specific cues, masking failure modes that would occur under real-world domain shifts when generalizing to new locations. In this work, we formulate zero-shot cross-city transfer as a controlled representation-level stress test for end-to-end autonomous driving and ask how visual pretraining affects transfer behavior under geographic domain shift. We conduct a comprehensive study by integrating self-supervised backbones I-JEPA, DINOv2, and MAE into planning frameworks. We evaluate performance under strict geographic splits on nuScenes in the open-loop setting and on NAVSIM in the closed-loop evaluation protocol. Our experiments reveal a substantial generalization gap when transferring models across cities with different road topologies, traffic conventions, and visual environments. In open-loop evaluation, a supervised backbone exhibits severe degradation when transferring between cities, yet some domain-specific self-supervised methods can substantially reduce both displacement and collision degradation. In closed-loop evaluation, self-supervised pretraining improves average out-of-distribution PDMS in several single-city training settings. Our results provide empirical evidence that representation learning influences the robustness of cross-city planning and motivate zero-shot geographic transfer as an important stress test for evaluating end-to-end autonomous driving systems.

19.
bioRxiv (Bioinfo) 2026-06-22

PanRes: A database of latent and acquired antimicrobial resistance allowing 3D-based protein homology search

Antimicrobial resistance databases are central to genomic surveillance, but resistance determinants remain distributed across resources with different scopes, structures, and annotations. We developed PanRes, a curated resistance database of 11,717 genes integrating acquired and latent determinants of antibiotic, biocide, and metal resistance within a unified ontology. We predicted representative protein structures and clustered them by structural similarity, grouping proteins into 598 structurally conserved clusters coherent despite sequence divergence. Their structure-guided alignments were used to build Hidden Markov Models (HMMs) for remote homology search. In wastewater metagenomes from seven European cities, PanRes 3D-based HMMs expanded detection beyond high-confidence BLAST, with 35.2% of retained hits identified only by the HMMs and generally showing greater divergence from known proteins. For beta-lactamases, several proteins retained beta-lactamase-like folds and catalytic geometry despite weak sequence similarity. PanRes is available through an interactive web platform (https://panres.rambio.dk/), a structure-informed resource for exploring the whole resistome.

20.
medRxiv (Medicine) 2026-06-18

Cardiac rhythm development: A wearable device index of risk for physical and mental illness in adolescence

Objective. The autonomic nervous system, which regulates cardiac rhythm, undergoes pronounced maturation across adolescence. How cardiac rhythm develops over this period, however, and whether individual differences in its development forecast mental and physical illness, remain open questions. We used three waves of Fitbit data from the Adolescent Brain Cognitive Development (ABCD) Study to characterize the developmental trajectory of the cardiac rhythm and to test whether variation in that trajectory predicts onset of psychopathology and cardiometabolic disease. Methods. 8,301 adolescents contributed 242,811 valid Fitbit wear days across Waves 2 (Mage=12), 4 (Mage=14), and 6 (Mage=16). Cosinor mixed-effects models yielded three rhythm parameters per session: mesor (24-hour mean), amplitude (diurnal swing), and acrophase (peak timing). We first characterized age- and sex-specific trajectories, cross-wave stability, and factors shaping the rhythm. We then used parallel-process latent growth models to test whether within-person changes in rhythm tracked symptom trajectories, and hierarchical logistic models to test whether rhythm parameters predicted the first clinical onset of psychopathology and of obesity and hypertension. Results. The cardiac rhythm changed substantially across adolescence: mesor decreased, amplitude flattened, and acrophase shifted later. Within-person change in the rhythm tracked change in blood pressure, BMI, and trajectories of depression and ADHD symptoms. Higher mesor predicted incident onset of all five outcomes controlling for demographics, baseline symptoms, and behavior (ORs 1.36-1.54); amplitude, acrophase, and rhythm instability conferred additional risk. Conclusions. The 24-hour cardiac rhythm is a passively measurable substrate of adolescent autonomic development that indexes transdiagnostic risk for psychiatric and cardiometabolic illness.

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

Beyond Uniform Forgetting: A Study of Sequential Direct Preference Optimization Across Preference Settings

Aligning language models with human preferences often requires optimising multiple behavioural objectives. A practical approach is to apply these objectives sequentially using preference optimisation methods such as Direct Preference Optimisation (DPO), but it remains unclear whether later training uniformly degrades preferences learned earlier or whether the effect depends on the relationship between objectives. We study sequential DPO across four preference settings covering distributional conflict, multi-attribute interaction, strong safety signal, and compatible response-quality objectives. Using Llama-3.1-8B-Instruct with LoRA adapters, we evaluate all objectives after every stage with a fixed base-model reference. We find that sequential DPO does not produce a single forgetting pattern; preference change ranges from partial degradation to stability, pair-level redistribution, or positive transfer depending on objective relationship, signal strength, and training order. Pair-level analysis using length-normalised policy margins shows that aggregate metrics can mask heterogeneous changes across preference pairs, whereas quartile decomposition reveals that high-confidence pairs can either degrade or improve depending on the setting. Mechanistic diagnostics show that Stage~2 gradients and adapter updates are near-orthogonal to the previous objective across all settings, providing little evidence that direct gradient opposition is the primary driver. These findings suggest that future sequential alignment pipelines should account for objective compatibility and signal strength, rather than assuming that later objectives affect earlier preferences uniformly.

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

Human-Guided Agentic AI for Multimodal Clinical Prediction: Lessons from the AgentDS Healthcare Benchmark

arXiv:2602.19502v2 Announce Type: replace Abstract: Agentic AI systems are increasingly capable of autonomous data science workflows, yet clinical prediction tasks demand domain expertise that purely automated approaches struggle to provide. We investigate how human guidance of agentic AI can improve multimodal clinical prediction, presenting our approach to all three AgentDS Healthcare benchmark challenges: 30-day hospital readmission prediction (Macro-F1 = 0.8986), emergency department cost forecasting (MAE = $465.13), and discharge readiness assessment (Macro-F1 = 0.7939). Across these tasks, human analysts directed the agentic workflow at key decision points, multimodal feature engineering from clinical notes, scanned PDF billing receipts, and time-series vital signs; task-appropriate model selection; and clinically informed validation strategies. Our approach ranked 5th overall in the healthcare domain, with a 3rd-place finish on the discharge readiness task. Ablation studies reveal that human-guided decisions compounded to a cumulative gain of +0.065 F1 over automated baselines, with multimodal feature extraction contributing the largest single improvement (+0.041 F1). We distill three generalizable lessons: (1) domain-informed feature engineering at each pipeline stage yields compounding gains that outperform extensive automated search; (2) multimodal data integration requires task-specific human judgment that no single extraction strategy generalizes across clinical text, PDFs, and time-series; and (3) deliberate ensemble diversity with clinically motivated model configurations outperforms random hyperparameter search. These findings offer practical guidance for teams deploying agentic AI in healthcare settings where interpretability, reproducibility, and clinical validity are essential.

23.
medRxiv (Medicine) 2026-06-19

Grey- and white-matter resilience to tau, cognition and sex in Alzheimer's disease

INTRODUCTION: Brain resilience to tau has been mainly studied in relation to grey matter, while its role in white matter remains unclear in Alzheimer's disease (AD). Sex may moderate associations between brain resilience and cognition. METHODS: We analyzed medial temporal lobe tau PET SUVR, entorhinal cortical thickness, cingulum-hippocampal mean diffusivity, and cognition in 205 amyloid-positive individuals from ADNI. Associations between grey- and white-matter resilience to tau and cognitive performance or decline were examined using linear and mixed-effects models, including sex interactions and stratified analyses. RESULTS: Higher grey-matter resilience to tau related to better cross-sectional memory and language performance (p

24.
medRxiv (Medicine) 2026-06-22

Between Patterns and Predictions: Interpretable Latent EEG Representations for Clinical Insights

Electroencephalography (EEG) captures rich brain dynamics, yet in clinical practice this complexity is often reduced to simplified summaries or categorical labels, limiting its interpretability for decision-making. We tested the hypothesis that a pretrained latent embedding framework, the Universal Map of EEG (UM-EEG), can preserve clinically meaningful structure across heterogeneous datasets and provide a generalizable representation of brain states. We applied UM-EEG, without retraining, to three independent cohorts spanning distinct clinical contexts: long-term EEG recordings from cardiac arrest patients (n = 576), subarachnoid hemorrhage (n = 100), and routine clinical EEG recordings containing physiological and pathological patterns (n = 141). EEG segments were projected into a shared 128-dimensional space anchored by expert-derived reference states, including wakefulness, sleep stages, ictal-interictal continuum activity, and burst suppression. Across datasets, favorable outcome or physiological recordings were consistently located closer to healthy reference states, whereas poor outcome and pathological recordings shifted toward pathological regions of the embedding space. Trajectory-derived geometric and temporal features discriminated outcome in cardiac arrest (ROC-AUC 0.83) and subarachnoid hemorrhage (ROC-AUC 0.76), and distinguished physiological from pathological routine EEGs (ROC-AUC 0.93). In routine EEG, similarity relationships derived from embedding trajectories correlated with those derived from structured clinical reports, indicating that the latent space recapitulates clinically relevant organization. These findings show that a fixed, semantically structured EEG embedding generalizes across etiologies and recording settings, enabling prognostic stratification and contextual interpretation while preserving the relational structure of brain states.

25.
arXiv (CS.CV) 2026-06-11

Traits Run Deeper: Trait-Specific Asymmetric Fusion for Personality Assessment

Personality assessment aims to infer stable personality traits from dynamic behaviors across language, voice, and facial cues. Since different personality dimensions are revealed through distinct behavioral perspectives, modeling trait-specific evidence is challenging. However, most existing approaches adopt a uniform multimodal fusion strategy across all dimensions, assuming identical modality contributions. This overlooks trait-specific modality preferences and introduces cross-modal interference. To address this issue, we propose a novel personality assessment framework called Traits Run Deeper, which consists of three components. Specifically, the Multimodal Foundation Representation (MFR) module constructs personality-oriented multimodal inputs and leverages psychology-informed semantic templates as anchors, enabling foundation models to capture trait-relevant information. Building upon MFR, the Trait-Specific Modality Fusion (TSMF) module acts as an asymmetric fusion mechanism, allowing each dimension to selectively exploit different modality pathways from modality-specific modeling to complementary fusion. Thus, TSMF captures heterogeneous modality preferences while reducing cross-modal contamination. Furthermore, the Distribution-Calibrated Personality Regression (DCPR) module mitigates label imbalance and central tendency bias through target distribution calibration, improving robustness and stability. Experimental results on the AVI Challenge 2026 validation set demonstrate the effectiveness of the proposed framework, reducing mean squared error (MSE) by approximately 25% compared with the baseline. Consistent improvements are observed on the official test set, where our method achieves the best performance and ranks first in the Personality Assessment Track. The source code will be made available at https://github.com/MSA-LMC/AVI2026.