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01.
arXiv (CS.AI) 2026-06-24

Event-Grounded Question Answering over Long Audio via Structured Retrieval

arXiv:2602.14612v4 Announce Type: replace-cross Abstract: Answering natural-language questions over multi-hour audio requires both event recognition and temporal grounding. Current large audio-language models perform well on short clips, but are limited by context length, query-time cost, and weak temporal localization. We present LA-RAG (Long Audio-Retrieval Augmented Generation), a structured framework that converts continuous audio into timestamped event records using an open-vocabulary Audio Grounding Model (AGM), stores them in a SQL event database, and answers queries through intent-aware retrieval followed by LLM-based generation. LA-RAG supports offline grounding mode, where long recordings are pre-indexed for low-latency QA, and inference-time grounding mode, where query-conditioned grounding is performed for shorter open-ended clips. We create 24-hour Home-IoT and Industrial-IoT audio benchmarks and augment CASTELLA, a real-world audio moment retrieval dataset with QA pairs. In offline grounding mode, LA-RAG achieves 76.88% overall accuracy on Home-IoT and 71.10% on Industrial-IoT, with average query latencies below 0.6 seconds. In inference-time grounding mode, state-of-the-art LALMs achieve competitive event-detection accuracy on CASTELLA-QA but low temporal detection F1. We further show that LALMs augmented with our structured retrieval metadata achieve consistent temporal detection improvements, with F1 gains of 11-17% across baseline models with improved latency. These results show that explicit timestamped grounding and structured retrieval provide a practical complement to generative audio-language models for deployment-oriented long-audio QA.

02.
bioRxiv (Bioinfo) 2026-06-11

EditorForge: An Active-Site-Aware Framework for Inverse-Folding-Based Protein Redesign

Inverse-folding models can rapidly generate protein sequences compatible with a supplied backbone, but unconstrained redesign is poorly suited to enzyme and genome-editor-associated domains, where catalytic, substrate-proximal, and conserved structural regions must remain protected. In this paper, we present EditorForge, a modular constraint-and-audit suite for editor-domain protein redesign that wraps fixed-backbone inverse folding with explicit design masks, fixed-position enforcement, active-site-proximity auditing, active-site-shielded regeneration, and downstream structural quality control. Using full-length Moloney murine leukemia virus reverse transcriptase structure 4MH8 (MMLV RT 4MH8) as a demonstration target, EditorForge first restricted redesign to a bounded 25-position envelope while fixing 428 residues. An initial audit detected active-site-proximal failure modes despite fixed-position integrity. Later, the Active Site Shield module then removed five unsafe design positions, replaced them with lower-contact alternatives, and regenerated candidates under stricter constraints. Post Shield Audit evaluated 24 regenerated candidates, all of which satisfied the hard sequence/mask and active-site-shield constraints. For the eight candidates that were selected or returned for structure-prediction/refolding quality control. Enhanced RefoldQC found that all 8 evaluated predicted structures passed the computational structure-QC screen. That said, the selected 8 candidates passed the computational structure-QC screen, with global C RMSD values of 1.2061–1.5555~[A], active-site C RMSD values of 0.4098–1.8397~[A], mutation-neighborhood C RMSD values of 1.3155-1.6848~[A], and average pLDDT-like confidence values of 94.87-95.11. In short, EditorForge provides a reproducible triage layer that converts general inverse-folding output into constrained and editor-specific candidate sets for downstream structural and biological review on top of existing structural prediction tools.

03.
arXiv (CS.CL) 2026-06-15

Succeeding at Scale: Enterprise Retrieval Benchmark Construction and Index-Preserving Query Adaptation for Multi-Tenant Search

Large-scale multi-tenant retrieval systems generate extensive query logs but lack curated relevance labels for effective domain adaptation, resulting in substantial underutilized "dark data." This challenge is compounded by the high cost of model updates, as jointly fine-tuning query and document encoders requires full corpus re-indexing, which is impractical in multi-tenant settings with thousands of isolated indices. We introduce DevRev-Search, a passage retrieval benchmark for technical customer support built via a fully automated pipeline. Candidate generation uses fusion across diverse sparse and dense retrievers, followed by an LLM-as-a-Judge for consistency filtering and relevance labeling. We further study and systematically evaluate index-preserving query-only adaptation strategies that fine-tune only the query-encoder while keeping the document indices fixed. Experiments on DevRev-Search, SciFact, and FiQA-2018 show that parameter-efficient fine-tuning of the query encoder delivers a remarkable quality-efficiency trade-off, enabling scalable and practical enterprise multi-tenant retrieval.

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

DisjunctiveNet: Neural Symbolic Learning via Differentiable Convexified Optimization Layers

arXiv:2605.30456v2 Announce Type: replace Abstract: Many learning tasks in science and engineering are characterized by sparse datasets, which limits the effectiveness of purely data-driven approaches. At the same time, these problems are often accompanied by rich domain knowledge derived from physical laws, operational requirements, and expert heuristics. Such knowledge is frequently expressed as rules involving logical propositions and linear inequalities. Existing neuro-symbolic methods typically enforce these rules approximately through soft penalties, assume input-independent rules when designing specialized architectures, or rely on non-differentiable post-processing at inference time to achieve hard constraint satisfaction. While recent advances in differentiable optimization layers enable end-to-end feasibility enforcement within neural networks, extending these approaches to logical or mixed-integer rules remains challenging due to inherent nonconvexity. In this work, we propose a unified end-to-end framework for enforcing hard, input-dependent mixed integer linear constraints within neural networks. Our approach represents rules as disjunctive constraints and applies hierarchical convex relaxations to obtain convex hull formulations. These relaxations yield tractable linear constraints that can be embedded as differentiable optimization layers while enabling exact rule satisfaction. We demonstrate the effectiveness of the proposed framework on real-world datasets, achieving perfect rule satisfaction and strong predictive performance.

05.
medRxiv (Medicine) 2026-06-18

Empirical Validation and Predictive Utility of the Perinatal Grief Scale in Men after Perinatal Loss

Background. The Perinatal Grief Scale (PGS) is a widely used instrument for assessing grief following pregnancy loss, yet no study has validated it specifically in men despite documented use in several studies. This gap is critical given fathers' persistent underrepresentation in perinatal bereavement research and the absence of empirically supported screening thresholds for this population. Methods. This cross-sectional validation study used data from the OPALE project (Observatory on PerinatAL hEalth) conducted by the CiaoLapo Foundation in Italy. Among 276 fathers who experienced stillbirth or miscarriage, we examined criterion validity by testing the association between PGS scores and trauma-related symptomatology assessed via three validated instruments: the Revised Impact of Event Scale (RIES, n=103), National Stressful Events Survey Short Scale (NSESSS, n=95), and SCL-90 (n=173). We systematically tested multiple threshold combinations to identify optimal discriminative performance. Results. The PGS demonstrated excellent criterion validity. The optimal threshold (PGS >=92) showed sensitivity 81.0%, specificity 81.8%, and Youden's J index 0.628. Fathers scoring >=92 had 19.12 times the odds of high trauma symptoms (95% CI: 9.35 to 39.14, p

06.
PLOS Medicine 2026-05-13

On the evolution of the company we keep: Implications for infectious disease modeling

by Joël Mossong Whom we meet shapes how infections spread. Where earlier focus of mathematical epidemiology was on incorporating age, more recent work has begun to reveal the importance of socioeconomic aspects for understanding and managing future epidemics. In this Perspective, Joël Mossong discusses the importance of understanding social contacts and how they have evolved for infectious disease modeling, and the need to factor in additional considerations such as ethic and socioeconomic backgrounds.

07.
arXiv (CS.AI) 2026-06-24

Neuromorphic Speech Enhancement with Dual-Branch Spiking Neural Networks

arXiv:2606.23761v1 Announce Type: cross Abstract: Spiking neural network (SNN)-based neuromorphic speech enhancement has emerged as a promising paradigm due to its energy efficiency, yet it still underperforms classical artificial neural network (ANN)-based approaches owing to binary activations and the lack of well-designed network architectures. To overcome this limitation, we propose a novel dual-branch spiking neural network architecture equipped with a gated spiking unit (GSU), termed GSU-DBNet. Specifically, GSU-DBNet simultaneously models the speech magnitude spectrum and complex spectrum, predicting the corresponding magnitude and complex spectral masks. Meanwhile, a dual-path GSU module is adopted to exploit temporal and frequency information for enhanced spatiotemporal feature representation. Experiments on a popular benchmark dataset show that GSU-DBNet achieves a PESQ score of 3.04 with only 394K parameters, outperforming existing SNN-based methods while using only 4.5%–10.6% of the parameters of representative ANN-based models.

08.
medRxiv (Medicine) 2026-06-15

Socioeconomic inequalities in smoking prevalence and intensity in Germany: A repeated cross-sectional analysis from 1998 to 2024

Background: Smoking inequalities by socioeconomic status have widened consistently in Germany, but sex-specific trends after 2013 and inequalities in daily cigarette consumption among smokers (intensity) are unknown. We analyzed trends in absolute and relative socioeconomic inequalities in smoking prevalence and intensity among German adults across three decades. Methods: We used 14 waves (1998-2024) of population-representative cross-sectional data from the German Socio-Economic Panel to estimate sex-specific trends in smoking prevalence and intensity in adults aged 25-64. Inequalities were quantified across strata of education, occupation, and equivalized household income using the absolute and relative concentration index with 95% bootstrap confidence intervals. Results: Overall smoking prevalence declined from 35.05% (CI: [33.90%, 36.20%] in 1998 to 22.19% (CI: [21.15%, 23.24%]) in 2024, and mean intensity from 17.49 (CI: [17.09,17.90]) to 13.33 (CI: [12.88, 13.79]) cigarettes/day. Over this period sex-differences in both outcomes narrowed almost completely. Absolute and relative inequalities in smoking prevalence widened across all SES dimensions, particularly for education and occupation. By 2024, inequalities were larger among women than men driven by a stagnating or rising smoking prevalence among low-SES women at least until 2018 alongside continued declines in higher-SES women and for men. Inequalities in smoking intensity, particularly related to income, were generally smaller than those in prevalence. Conclusion: Socioeconomic smoking inequalities in Germany widened from 1998 to 2024 primarily driven by reductions among higher-SES groups and increases in low-SES women. However, recent reductions in low-SES women may indicate a new phase in the smoking epidemic. Health equity considerations should be integrated into a targeted German tobacco control strategy.

09.
arXiv (CS.LG) 2026-06-15

Decompose Sparsely Where You Should, Absorb Densely Where You Should No

arXiv:2606.14040v1 Announce Type: new Abstract: Sparse autoencoders (SAEs) are typically trained to reconstruct the entire residual stream through a sparse dictionary, implicitly assuming that all activation content is amenable to sparse, monosemantic decomposition. We question this assumption and hypothesize that activations contain a low-rank, dense component that is computationally important to the model yet inherently unsuitable for sparse representation, which serves as a major source of the persistent dense latents widely observed in trained SAEs. To test this, we add a small rank-$r$ linear bottleneck in parallel with standard SAEs (BatchTopK and Matryoshka), allowing dense structure to be absorbed before sparse reconstruction. On Gemma-2-2B layer 12, a rank-24 bottleneck reduces dense latent count by up to 84\% while improving sparse probing and targeted probe perturbation on both architectures at matched sparsity. The absorbed component is (i) structurally identifiable as the top principal components and outlier dimensions; (ii) causally necessary, with removing it raising next-token cross-entropy by 7.5$\times$, far exceeding the 2.8$\times$ from removing the geometrically near-identical top-24 PCA directions; and (iii) redundantly encoded by sparse dictionaries, with ablating 787 maximally aligned sparse features raising cross-entropy by only 2.9$\times$ and ablating 2,048 topic-aligned features leaving MMLU topic classification virtually unchanged, whereas removing the scaffold drops it from 98.7\% to chance. Together, our findings identify a compact, semantically informative and causally important component of residual stream activations (which we term a computational scaffold) that standard sparse dictionaries represent inefficiently, suggesting that the scope of sparsity-based interpretability methods warrants careful re-examination.

10.
arXiv (quant-ph) 2026-06-24

Semidefinite programming for understanding the limitations of Lindblad equations

arXiv:2602.01794v2 Announce Type: replace Abstract: Lindbladian quantum master equations (LEs) are the most popular descriptions for quantum systems weakly coupled to baths. But, recent works have established that in many situations such Markovian descriptions are fundamentally limited: they cannot simultaneously capture populations and coherences even to the leading-order in system-bath couplings. This can cause violation of fundamental properties like thermalization and continuity equations associated with local conservation laws, even when such properties are expected in the actual setting. This begs the question: given a physical situation, how do we know if there exists an LE that describes it to a desired accuracy? Here we show that, for both equilibrium and non-equilibrium steady states (NESS), this question can be succinctly formulated as a semidefinite program (SDP), a convex optimization technique. If a solution to the SDP can be found to a desired accuracy, then an LE description is possible for the chosen setting. If not, no LE description is fundamentally attainable, showing that a consistent Markovian treatment is impossible even at weak system-bath coupling for that particular setting. Considering few qubit isotropic XXZ-type models coupled to multiple baths, we find that in most parameter regimes, LE description giving accurate populations and coherences to leading-order is unattainable, leading to rigorous no-go results. However, in some cases, LE description having correct populations but inaccurate coherences, and satisfying local conservation laws, is possible over some of the parameter regimes. Our work highlights the power of semidefinite programming in the analysis of physically consistent LEs, thereby, in understanding the limits of Markovian descriptions at weak system-bath couplings.

11.
arXiv (CS.CV) 2026-06-24

Systematic Exploration of 4-Expert Heterogeneous Mixture-of-Experts via Automated Pipeline Search

We present an automated large-scale search pipeline for heterogeneous 4-Expert Mixture-of-Experts (MoE4) architectures within the LEMUR neural network dataset ecosystem. Building on a hand-crafted heterogeneous MoE reference model, we replace manual design with a deterministic code-assembly generator that systematically combines base architecture families drawn from the LEMUR database into MoE4 ensembles, each governed by a convolutional gating network with temperature scaling, mixup augmentation, and cosine-annealed learning rate scheduling. Over a 28-day campaign on an NVIDIA RTX 4090, the pipeline generated 4,463 candidate models across 197 batches, of which 1,021 were evaluated successfully. A critical finding emerged from the campaign: due to alphabetical enumeration via itertools.combinations, the entire explored search space (4.8% of the theoretical 23,751 possible 4-family combinations) is anchored to a single family, AirNet. We characterise this coverage bias precisely, identify the root cause in the generator, and propose a stratified random sampling fix. Within the AirNet anchored scope, ShuffleNet and MobileNetV3 consistently co-produce the highest-accuracy ensembles (mean accuracy up to 0.632), while FractalNet and MNASNet are identified as low-yield families warranting exclusion in future campaigns. The pipeline, analysis artefacts, and corrected generator are released as part of the open-source NNGPT project at https://github.com/ABrain-One/nn-gpt

12.
arXiv (CS.CV) 2026-06-16

Cascaded Sparse Autoencoders Learn Multi-Level Visual Concepts in Multimodal LLMs

Multimodal Large Language Models (MLLMs) have demonstrated strong performance on vision-language tasks, yet their internal visual representations remain difficult to interpret. Sparse Autoencoders (SAEs) provide a scalable way to decompose dense model activations into sparse, interpretable features. However, existing SAE architectures primarily recover flat feature dictionaries and are less suited for explicit multi-level concept organization. In this paper, we introduce cascaded sparse autoencoders (CSAEs) for learning hierarchical visual concepts in MLLMs. Rather than nesting or stacking SAE sparse activation codes, CSAEs train a second-level SAE directly on the decoder weights of the first-level SAE, treating learned low-level feature directions as inputs for higher-level abstraction. This design enables CSAEs to learn "concepts of concepts" while avoiding drawbacks from the shared-prefix coupling of nesting, Matryoshka-style hierarchies and the bottlenecks of naively stacked SAEs. Experiments across Qwen3-VL, Gemma-3, and LLaVA on multiple visual datasets show that CSAEs improve interpretability in terms of hierarchical concept coherence over state-of-the-art SAE baselines. Results on concept steering further demonstrate that the learned concept groups support effective group-level interventions in MLLM outputs.

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

Reroute, Don't Remove: Recoverable Visual Token Routing for Vision-Language Models

Vision-language models (VLMs) project images into hundreds to thousands of visual tokens, making decoder inference expensive in both attention computation and KV-cache memory. Existing visual-token reduction methods largely follow a rank-and-remove paradigm: they score visual tokens, keep a compact subset, and permanently discard the rest. We show that this irreversible action is fragile because visual-token importance changes across decoder depth; tokens ranked low at one stage may become relevant in later layers, especially for grounding-sensitive queries. We propose Reroute, a training-free plug-in that replaces removal with recoverable routing. At each routing stage, selected vision tokens pass through decoder blocks, while deferred tokens bypass the stage and re-enter the candidate pool at the next routing decision. Reroute reuses existing attention-score ranking rules and stage-wise schedules, preserving the theoretical TFLOPs and KV-cache budget class of the pruning method it augments. Across FastV, PDrop, and Nüwa variants on LLaVA-1.5 and Qwen backbones, reroute improves grounding under aggressive token reduction while maintaining general VQA performance. These results suggest that VLM token reduction should not be viewed only as irreversible pruning, but also as recoverable routing. The code can be found here: https://github.com/elmma/mllm-reroute/

14.
medRxiv (Medicine) 2026-06-23

Blood-brain barrier dysfunction in cerebral amyloid angiopathy is associated with disseminated cortical superficial siderosis

Background: Blood-brain barrier (BBB) dysfunction is increasingly recognized as a feature of cerebral amyloid angiopathy (CAA) and has been linked to hemorrhagic imaging manifestations such as cortical superficial siderosis. However, it remains unclear whether neurovascular barrier dysfunction can be captured by routinely available fluid biomarkers and whether such markers identify clinically relevant hemorrhage-prone CAA phenotypes. The CSF/serum albumin quotient (QAlb) is an established marker of neurovascular barrier dysfunction. We investigated QAlb levels in CAA and their association with imaging markers of disease severity. Methods: We included 225 participants (115 with CAA, 72 with Alzheimers disease [AD], 38 healthy controls) with CSF biomarkers and standardized MRI evaluation. Pathologic QAlb levels were identified via the age-corrected Reiber-formula. Group differences and determinants of pathological QAlb were assessed using uni- and multivariable regression analyses. The diagnostic relevance was assessed by receiver operating characteristic analysis. Results: QAlb levels were higher in CAA than in controls (ratio of means [RoM] 1.43, 95% CI 1.28-1.58) and patients with AD (RoM 1.22, 95% CI 1.10-1.35; both p

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

Whole-Brain Connectomic Graph Model Enables Whole-Body Locomotion Control in Fruit Fly

arXiv:2602.17997v3 Announce Type: replace Abstract: Animals perform coordinated whole-body movements under the control of neural systems shaped by brain-wide connectivity. The mapping of the whole-brain neural connections, or the connectomes, provides a natural graph for modeling sensorimotor information flow, yet its potential as a neural controller for embodied agents remains largely unexplored. Here, we introduce the Fly-connectomic Graph Model, which directly instantiates the whole-brain connectome of an adult Drosophila as a graph-structured neural controller for movements of a simulated biomechanical fruit fly via deep reinforcement learning. We achieve stable performance across diverse locomotion tasks, as well as better sample efficiency compared to both graph and non-graph baselines. Our results demonstrate a biologically informed way towards effective control policy design by translating whole-brain wiring principles into actionable architectural priors, while also improving the interpretability through dynamic information flow. This work also highlights the potential to bridge neuromechanics with embodied intelligence by providing a computational platform for investigating the sensorimotor transformation underlying animal behavior and a paradigm to advance the development of more nature-aligned intelligent systems.

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

Blended Chart Surfaces: A Seamless Explicit Representation for Smooth Surface Fitting

A surface representation suitable for geometry processing should be compact and explicit, provide global smoothness guarantees, support a wide range of surface topologies, and offer reliable access to differential quantities such as normals and surface energies, while remaining compatible with modern differentiable optimization. Existing neural representations typically sacrifice one or more of these properties: implicit fields typically require iso-surfacing for downstream use, while explicit neural maps are constrained by canonical-domain parametrizations or exhibit seam artifacts between local charts. We introduce Blended Chart Surfaces, a compact, network-free, explicit representation that is smooth by construction and anchored to user-provided topology. Given a coarse proxy mesh encoding the intended surface topology and approximate geometry, Blended Chart Surfaces jointly optimize for a polynomial map at each proxy vertex using an off-the-shelf optimizer to fit to an implicit target shape, avoiding the need for an input parametrization. Neighboring maps are fused using a smooth 'one-ring coordinate' blending scheme, decoupling topology and coarse geometry (carried by the proxy) from geometric details (carried by the local patches). The surface is globally smooth, fully differentiable, and enables stable evaluation of derivatives, making differential quantities and surface energies directly accessible. Additionally, our construction is equivariant to rigid motions and scaling of the proxy mesh. We evaluate Blended Chart Surfaces on various topologies and geometric complexity, and compare against explicit alternatives including interpolating-function baselines and mesh-displacement MLPs. Across these, Blended Chart Surfaces achieve a favorable trade-off among compactness, simplicity, access to differential quantities, and expressivity while remaining smooth across patch boundaries.

17.
arXiv (CS.LG) 2026-06-18

Identifying Structural Biases from Causal Mechanism Shifts

arXiv:2606.18834v1 Announce Type: new Abstract: Causal discovery methods commonly assume that all data is independently and identically distributed (i.i.d.) and that there are no unmeasured variables affecting the system. In practice, these assumptions are often violated, leading to inaccurate inference. In this paper, we study how to identify hidden confounding and selection biases from causal mechanism shifts. In particular, we show that structural biases lead to dependent mechanism shifts. That is, by considering for which variables the mechanisms change given data from different environments, we can tell which variables are unbiased, which are subject to hidden confounding, and which are undergoing selection bias. We formalize this into an empirically testable criterion based on mutual information, and show under which conditions it identifies structural biases. To tell which nodes are subject to what kind of bias, we introduce the StruBI algorithm. Experiments on synthetic and real-world data show that StruBI works well in practice, accurately recovering affected variable sets and types of biases, outperforming the state-of-the-art by a wide margin.

18.
bioRxiv (Bioinfo) 2026-06-17

Posterior-calibrated multimodal motor states reveal longitudinal and imaging-associated heterogeneity in Parkinson's disease

Parkinson's disease (PD) motor heterogeneity is commonly summarized by hard subtype labels, although clinical states vary longitudinally, severity can dominate unsupervised structure, and model uncertainty is rarely calibrated. We developed a posterior and refit-stability calibrated multimodal motor state framework that assigns probabilistic MDS-UPDRS-III motor states, aggregates them at the patient level, separates global burden from residual tremor-axial profile, and tests whether imaging can recover the resulting posterior distribution. In 29,366 aligned PPMI motor-posterior visits spanning 4,773 participant identifiers, patient-level state families were stable on average (modal-family fraction 0.925; 95% CI 0.921 - 0.930), but 25.5% of patients transitioned state over follow-up (95% CI 24.1 - 26.7%). PD-only cohort definitions produced smaller denominators and are reported as sensitivity cohorts with rerun calibration and imaging-posterior checks. Severity and covariates explained substantial motor-domain variance, especially bradykinesia (rsecond=0.850), but residual profile modeling retained five active components across total-severity, principal-component, leave-one-domain, non-target-burden, and clinical-only severity axes. Refit-stability calibration with 250 patient-blocked bootstrap refits showed high nominal posterior confidence (0.989) but lower empirical label consistency (0.849), quantifying overconfidence rather than hiding it. Patient-held-out temporal modeling predicted future axial burden (best XGBoost rsecond=0.605) and future state transition (XGBoost AUC=0.830; 95% CI 0.822 - 0.837). DaTSCAN plus FreeSurfer ROI features predicted patient-level soft motor posterior vectors (RF jsd=0.209; 95% CI 0.199 - 0.220; macro-AUROC=0.692), while severity/demographic-adjusted imaging features further improved soft posterior recovery (jsd=0.188). BioFIND transfer reproduced clinically meaningful endpoint gradients after state assignment in 225 external patients, supporting external face validity rather than definitive transportability. These results support PD motor phenotypic states as calibrated, dynamic, clinically interpretable profiles with convergent imaging associations, not as definitive biological subtypes.

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

Uncertainty-Aware Longitudinal Forecasting of Alzheimer's Disease Progression Using Deep Learning

arXiv:2606.24604v1 Announce Type: new Abstract: Longitudinal modelling of Alzheimer's disease progression is clinically useful only if it can describe not just the most likely next diagnosis, but how a patient may evolve over time and how reliable that forecast is. Most deep learning approaches reduce this problem to single-step classification, treating cognitively normal, mild cognitive impairment, and dementia as flat categories while providing limited insight into how uncertainty accumulates across future visits. We propose a probabilistic framework that combines ordinal diagnosis prediction, multi-horizon trajectory generation, and decomposed uncertainty estimation. A Temporal Fusion Transformer encoder is adapted with a CORAL ordinal output layer, asymmetric loss weighting, and converter oversampling to respect disease-stage ordering and improve sensitivity to MCI-to-dementia transitions. Conditioned on the learned patient-context representation, an autoregressive Mixture Density Network generates five-year probabilistic trajectories for diagnosis state, CDR Sum of Boxes, MMSE orientation, and hippocampal volume. On ADNI, the model outperforms linear, recurrent, and transformer baselines for next-visit diagnosis prediction, with the strongest gains on MCI-versus-dementia discrimination. Generated trajectories achieve near-nominal 90% credible interval coverage, widening uncertainty across the forecast horizon, and biomarker dynamics consistent with expected Alzheimer's disease progression. We further separate aleatoric from epistemic uncertainty using analytic mixture variance and a five-member bootstrap ensemble, which provides the strongest encoder diversity and output-level epistemic signal. Epistemic uncertainty is higher for rare progression archetypes, MCI and dementia patients, and under external evaluation on OASIS-3, where it increases alongside prediction error.

20.
Nature Medicine 2026-06-15

Adaptive deep brain stimulation for dynamic gait control in Parkinson’s disease: a randomized feasibility trial

A randomized crossover study of five patients with Parkinson’s disease (PD) demonstrates that gait-synchronized adaptive deep brain stimulation is feasible and safe, and reduces falls compared with continuous stimulation. Gait dysfunction in PD is a major source of disability and is often insufficiently treated by continuous deep brain stimulation (cDBS). Although adaptive DBS (aDBS) has shown efficacy for other motor symptoms using β-based, state-driven neural signals, gait is a dynamic, cyclical behavior that may require temporally precise modulation. Here we evaluated a behavior-contingent aDBS approach that synchronizes stimulation to gait phase. We reported a single-center, blinded, randomized, crossover study evaluating the feasibility of identifying patient-specific biomarkers to drive aDBS. The primary outcome was feasibility of successful identification of gait-phase biomarkers to implement aDBS. Five participants with PD undergoing pallidal DBS and subdural electrode paddle implantation were enrolled. We successfully identified personalized gait-phase biomarkers from cortical or pallidal field potentials in all five patients and embedded them into a bidirectional neurostimulator. During acute in-clinic testing, aDBS improved step variability and step symmetry versus cDBS. Three participants subsequently completed a double-blinded, multi-day crossover phase. In this setting, aDBS maintained general motor symptom control, reduced falls and yielded patient-specific gait improvements. No adverse events occurred and aDBS was well tolerated. These findings establish the feasibility of biomarker-driven, movement-synchronized neuromodulation and support the development of a larger randomized trial to determine clinical efficacy. ClinicalTrial.gov registration: NCT04675398 . A randomized crossover study shows that gait-phase-synchronized adaptive deep brain stimulation is feasible and safe, and reduces falls compared to continuous stimulation in Parkinson’s disease.

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

Domain Generalizable Adaptation of 3D Vision-Language Models via Regularized Fine-Tuning

Domain adaptation remains a central challenge in 3D vision, especially for multimodal foundation models that align 3D point clouds with visual and textual data. While these models demonstrate strong general capabilities, adapting them to downstream domains with limited data often leads to overfitting and catastrophic forgetting. To address this, we introduce ReFine3D, a regularized fine-tuning framework designed for domain-generalizable tuning of 3D large multimodal models (LMMs). ReFine3D combines selective layer tuning with two targeted regularization strategies: multi-view consistency across augmented point clouds and text diversity through synonym-based prompts generated by large language models. Additionally, we incorporate point-rendered vision supervision and a test-time augmentation mechanism with confidence-based aggregation to further enhance robustness. Extensive experiments across different 3D domain generalization benchmarks show that ReFine3D improves base-to-novel class generalization by 1.36%, cross-dataset transfer by 2.43%, robustness to corruption by 1.80%, and few-shot accuracy by up to 3.11%, outperforming prior state-of-the-art methods with minimal added computational overhead.

22.
arXiv (CS.AI) 2026-06-15

Unsupervised Learning of Efficient Exploration: Pre-training Adaptive Policies via Self-Imposed Goals

arXiv:2601.19810v2 Announce Type: replace-cross Abstract: Unsupervised pre-training can equip reinforcement learning agents with prior knowledge and accelerate learning in downstream tasks. A promising direction, grounded in human development, investigates agents that learn by setting and pursuing their own goals. The core challenge lies in how to effectively generate, select, and learn from such goals. Our focus is on broad distributions of downstream tasks where solving every task zero-shot is infeasible. Such settings naturally arise when the target tasks lie outside of the pre-training distribution or when their identities are unknown to the agent. In this work, we (i) optimize for efficient multi-episode exploration and adaptation within a meta-learning framework, and (ii) guide the training curriculum with evolving estimates of the agent's post-adaptation performance. We present ULEE, an unsupervised meta-learning method that combines an in-context learner with an adversarial goal-generation strategy that maintains training at the frontier of the agent's capabilities. On XLand-MiniGrid benchmarks, ULEE pre-training yields improved exploration and adaptation abilities that generalize to novel objectives, environment dynamics, and map structures. The resulting policy attains improved zero-shot and few-shot performance, and provides a strong initialization for longer fine-tuning processes. It outperforms learning from scratch, DIAYN pre-training, and alternative curricula. Code is available at: https://github.com/Octavio-Pappalardo/ulee-jax

23.
bioRxiv (Bioinfo) 2026-06-23

biomeStat: Using Agentic AI for Scalable Genomic Epidemiology Demonstrated Through End-to-End Analysis of 1,000 Asian Dengue Virus Genomes

Genomic epidemiology workflows typically require expert curation of multiple specialized tools, extensive manual parameter tuning, and access to heterogeneous compute infrastructure. While standard generative AI models often hallucinate in complex biological domains, we introduce biomeStat: an autonomous AI agent that functions as a strict deterministic orchestrator. By automatically writing code to execute established bioinformatics tools in sandboxed environments, biomeStat dynamically provisions compute resources (CPU and GPU) and guarantees reproducibility, making it immediately useful for scientists without requiring command-line expertise. To demonstrate the platform, we performed a fully autonomous genomic epidemiology and structural analysis of 1,000 Dengue virus (DENV) genomes sampled from 16 Asian countries between 2000 and 2025. The agent seamlessly orchestrated phylogenetic reconstruction (IQ-TREE, TreeTime), Bayesian phylodynamics (BEAST2 via NVIDIA H200 GPU), selection pressure analysis (HyPhy), and structural mapping (PyMOL). The analysis was completed in under 24 hours of wall-clock time, revealing endemic stability (R_e ~1.0) and identifying 1,869 candidate immune escape sites structurally colocalized with B-cell and T-cell epitopes. Furthermore, the agent validated 176 highly conserved drug target residues across the viral replication complex, confirming that resistance-associated positions for emerging antivirals JNJ-1802 and NITD-688 remain absolutely conserved across all four serotypes. By bridging the gap between natural language intent and deterministic computational execution, biomeStat reduces weeks of expert effort into a single-session analysis with full methodological transparency.

24.
arXiv (CS.AI) 2026-06-11

RoVE: Rotary Value Embeddings Attention for Relative Position-dependent Value Pathways

arXiv:2606.11275v1 Announce Type: cross Abstract: Rotary Position Embeddings (RoPE) make attention scores position-relative but leave the value pathway position-blind: the message sent by a value token is the same regardless of its distance from the query. We propose RoVE, a parameter-free modification that makes values position-sensitive by rotating them simultaneously with keys, and show that it turns RoPE attention into attentive convolution. This new perspective unifies several independent formulations of the same operation across computer vision, robotics, and modern LLM architectures. Trained 124M and 354M GPT-2 models show consistent empirical gains over RoPE on few-shot in-context learning, out-of-distribution perplexity, and long-context retrieval, with the clearest improvements on tasks that require long-range aggregation.

25.
arXiv (math.PR) 2026-06-17

Cutoff for asymmetric shelf shuffle

arXiv:2606.18039v1 Announce Type: new Abstract: A mechanical shuffler consists of $m$ shelves. A deck of $n$ cards, arranged in increasing order, is dealt from the bottom sequentially. Each card is assigned a shelf uniformly at random and placed on the top (bottom) of the existing pile with probability $p$ ($1-p$) independently. We refer to this as asymmetric shelf-shuffle. We find the law $\nu_{n, m}^{(p)}$ of the permutation induced by the asymmetric shelf-shuffle and show that the pair consisting of the number of descents and the number of valleys is a sufficient statistic. This generalizes a result of Diaconis, Fulman, and Holmes (Ann. Appl. Prob., 2013) corresponding to the case $p=1/2$. For $p=1/2$, Chen and Ottolini (ECP, 2025) established the cutoff in the total variation distance near $\lfloor n^{5/4}\rfloor$. We establish the cutoff for the asymmetric shelf shuffle. Let $\nu_n$ be the uniform measure on the set of all permutations $S_n$ of $\{1, \ldots, n\}$. For a fixed $p\neq 1/2$ and $c>0$, we show that \[\operatorname{TV}\left(\nu_{n, \lfloor cn^{3/2}\rfloor }^{(p)}, \nu_n\right)=1-2\Phi\left(-\frac{|2p-1|}{4\sqrt{3}c}\right)+O_{c, p}(n^{-1/2})\;.\] We also establish the cutoff in the separation distance near $m\approx n^{2}$ and in the relative entropy near $m=n^{3/2}$. In both cases, we also obtain the cutoff profile explicitly.