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01.
arXiv (CS.LG) 2026-06-12

Robust State-Conditional Feature-Weighted Jump Models for Temporal Clustering

arXiv:2606.13146v1 Announce Type: cross Abstract: We propose a robust feature-weighted jump model for time-dependent clustering. A penalty is used to encourage smoothness of transitions over time, while robustness is achieved through the use of a Tukey's biweight loss function. An additional parameter controls the variability of feature weights across states, allowing the model to assign state-specific relevance to each feature. We illustrate in simulation how the method accurately recovers the true cluster sequence and reliably identifies relevant features, outperforming competing approaches, particularly in the presence of outliers. We conclude with two empirical applications, one on the number of conflict-related homicides in Kosovo in the period 1998-2000, and another on macroeconomic performance of twelve European countries in the period 1949-2024.

02.
arXiv (CS.AI) 2026-06-15

Learning What to Predict: Downstream-Guided Task Design for Continued Pretraining

arXiv:2601.22108v2 Announce Type: replace-cross Abstract: Continued pretraining is optimized with fixed self-supervised tasks but selected by downstream performance, creating a coarse feedback loop in which practitioners evaluate checkpoints, change data mixtures or objectives, and restart runs, while individual updates remain blind to target capabilities. We ask whether a small set of verifiable downstream examples can provide step-level feedback without directly supervising the learner. We introduce V-pretraining, which decouples a learner trained only with a self-supervised loss from a lightweight task designer that constructs targets or views for unlabeled batches. Given the current learner and batch, V-pretraining scores a candidate construction by predicting the first-order reduction in downstream loss after the induced self-supervised update. The designer maximizes this value; the learner then applies the update with targets or views detached, so downstream labels never update learner parameters. We instantiate V-pretraining as adaptive top-K soft targets for language modeling and learned views or masks for self-supervised vision. Across both modalities, V-pretraining improves target capabilities without degrading generalization. Under wall-clock-matched continued pretraining, it improves GSM8K Pass@1 for Qwen models using 1,024 GSM8K examples only as feedback, including a +7.4 point single-run gain for Qwen2.5-0.5B. In vision, it improves DINOv3 transfer to ADE20K semantic segmentation and NYUv2 depth estimation while preserving ImageNet linear accuracy, suggesting that feedback-guided task construction can improve target capabilities without collapsing general-purpose representations.

03.
arXiv (CS.CV) 2026-06-16

Momentum-Guided Semantic Forecasting (MoFore) for Self-Supervised Video Representation Learning

Authors:

Self-supervised video representation learning has recently advanced through contrastive learning, masked reconstruction, and predictive representation learning. Reconstruction-based approaches such as MAE and VideoMAE learn representations by recovering masked visual content [he2022mae,tong2022videomae], while contrastive methods such as CLIP learn semantically meaningful embedding spaces through representation alignment [radford2021clip]. In this work, we introduce a Momentum-Guided Semantic Forecasting framework (MoFore) for self-supervised video representation learning. Instead of optimizing for pixel-level reconstruction or task-specific semantic alignment, the proposed method learns temporally predictive video representations by forecasting future latent embeddings from temporally distant context clips. To improve robustness across temporal scales, we further introduce randomized temporal-gap forecasting during training. The framework combines predictive latent forecasting with contrastive regularization to encourage temporal consistency while preventing representation collapse. Experiments on the UCF101 dataset demonstrate that the proposed framework learns temporally consistent and semantically meaningful video representations without using action labels during training. Quantitative analysis shows strong temporal stability and emergent category-level structure in the learned embedding space, while qualitative retrieval experiments reveal motion-aware organization across related activities. Overall, the results suggest that long-range latent forecasting provides an effective and computationally efficient approach for self-supervised video representation learning without relying on reconstruction-based objectives.

04.
Nature Biotechnology 2026-06-08

Single-cell spatial pharmacobiology for imaging antibody-based therapies in solid tumors

Authors: Unknown Author

We have developed single-cell spatial pharmacobiology (SSP), which combines in situ imaging of a systemically infused fluorescent therapeutic antibody with high-plex spatial proteomics. Applied to head and neck and pancreatic tumors from patients treated in phase 1 trials, SSP revealed marked spatial heterogeneity in antibody delivery and target engagement, which was shaped by conserved stromal barriers.

05.
arXiv (math.PR) 2026-06-15

Boltzmann-Like Occupation of Nonequilibrium Steady States on Dense Networks

Authors:

arXiv:2606.14542v1 Announce Type: cross Abstract: A central problem in statistical physics is to extend the Boltzmann distribution to nonequilibrium steady states (NESS). We prove that NESS on large dense networks have Boltzmann-like occupation despite extensive entropy production. We further show that the active-matter heuristic of "low rattling" is asymptotically exact. Intuitively, these NESS spend a greater fraction of their time in states they leave more slowly. This explanation extends to the broader class of "equiaccessible" steady states, which play a role in our analysis akin to that of equilibrium in linear response.

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

URDF Synthesis from RGB-D Sequences via Differentiable Joint Inference and Energy-Consistent Verification

Authors:

Reconstructing simulation-ready digital twins of articulated objects from sensor observations remains constrained by two persistent gaps: (i) part-level geometric reconstruction is decoupled from kinematic-parameter estimation, and (ii) the recovered models often violate basic dynamic invariants such as energy conservation, leading to drift when the URDF is replayed in physics simulators. We present KinemaForge, a constraint-driven pipeline that jointly infers part-level shape, joint topology, and joint parameters from short RGB-D sequences and validates the result against an energy-consistent verifier built on differentiable rigid-body dynamics. The pipeline introduces three components: a kinematic constraint graph that encodes joint-part incidences as soft edges; a differentiable screw-axis solver that backpropagates from rendered observations through Featherstone's articulated-body algorithm to joint parameters; and an energy residual loss that penalises non-physical free responses of the reconstructed model. Across five PartNet-Mobility categories and an internal RGB-D benchmark, KinemaForge reduces the average joint-axis error from 4.52 degrees to 2.83 degrees (-37.4%) over the strongest geometric baseline (PARIS) and from 5.30 degrees to 2.83 degrees (-46.6%) over the interaction-based Ditto baseline, lowers long-horizon simulation drift by 64% (vs. PARIS) over 50 s rollouts, and yields URDFs whose closed-loop manipulation success rate improves by 14.6 percentage points over Ditto in our preliminary evaluation. Code and reconstruction data will be released upon acceptance.

07.
arXiv (math.PR) 2026-06-16

Higher-order spectral perturbation expansions II: Kernel matrices and manifold learning

arXiv:2606.16373v1 Announce Type: cross Abstract: We study spectral concentration bounds for kernel matrices as approximation of the corresponding kernel integral operator. Results are established under weak assumptions on the data setting and the reproducing kernel relying only on a Mercer condition and a local Weyl law. This allows us to deal with key features of kernel matrices, such as large multiplicities, large effective dimension, and heavy-tailed distributions. Our results apply to infinite dimensional principal component analysis, manifold learning, and Bayesian nonparametric statistics. We illustrate this via two prototypical examples: The heat kernel on the sphere and a wavelet prior from Bayesian nonparametrics.

08.
arXiv (CS.LG) 2026-06-19

PU-UNet: Stable Multiplicative Interactions for Medical Image Segmentation

arXiv:2606.20035v1 Announce Type: cross Abstract: Many dense prediction networks rely on additive feature transformations and model higher-order feature interactions only implicitly. Product units provide an explicit mechanism for multiplicative feature modeling, but their logarithmic–exponential formulation can cause numerical instability, which has limited their use in deep dense prediction networks. In this work, we propose Product-Unit U-Net (PU-UNet), a residual U-Net that integrates stable product-unit residual blocks into rich low-resolution stages for medical image segmentation. The proposed formulation combines smooth positivity mapping with log-domain clipping, enabling stable multiplicative feature learning with negligible computational overhead. On ISIC 2018, Kvasir-SEG, and BUSI, PU-UNet achieves Dice scores of 0.942, 0.959, and up to 0.925, respectively. Compared with a matched Residual U-Net baseline, PU-UNet consistently improves Dice and IoU while keeping parameters, FLOPs, and inference latency nearly unchanged, and reduces the image-level false-positive rate on normal BUSI cases from 0.077 to zero. Ablation studies suggest that the gains are associated with product-unit interactions, are strongest under low-resolution placement, and benefit from the proposed stabilization design. These results suggest that stable product-unit residual learning can be an effective way to enhance U-Net-style segmentation networks with explicit multiplicative interactions.

09.
arXiv (math.PR) 2026-06-16

High-Order Talagrand and Eldan–Gross Inequalities via Besov-Type Variance Functionals

arXiv:2606.14876v1 Announce Type: new Abstract: By introducing high-order Besov-type variance functionals that generalize the canonical variance, we develop a unified framework for proving high-order Talagrand-type inequalities that relate high-order energies to Fourier weights. Applying this machinery, we establish high-order Poincaré-type, $L^p$–$L^q$, isoperimetric-type, Falik–Samorodnitsky and Eldan–Gross inequalities, all with explicit constants, in both the Boolean and Gaussian settings. Fundamentally, our semigroup-based framework relies primarily on hypercontractivity and high-order Bismut-type derivative estimates, and is broadly applicable.

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

Follow the Latent Roadmap: Navigating Revocable Decoding for Diffusion LLMs with Anchor Tokens

Diffusion Large Language Models (dLLMs) offer a promising avenue for parallel generation but face a trade-off between decoding speed and quality. While revocable decoding strategies attempt to mitigate errors by verifying and remasking tokens, they typically operate within a mixed-quality context. This leads to two critical failures: Error Propagation, where new tokens absorb toxic information from erroneous context, and Local Error Reinforcement, where errors mutually reinforce each other to evade detection. To alleviate these challenges, we propose ASRD (Anchor Supervised Revocable Decoding), a training-free framework that operates within the embedding space. ASRD explicitly decouples the decoding context into trusted Anchor Tokens, which are identified via temporal consistency, and uncertain candidates. Leveraging a dynamic Anchor Tokens Cache, we introduce two complementary mechanisms: (1) Anchor-Guided Generation, which injects entropy-weighted anchor signals into masked positions to implicitly rectify attention toward the reliable global skeleton; and (2) Anchor-Perturbed Verification, which applies orthogonal perturbations to uncertain candidate tokens, destabilizing and remasking errors driven by fragile local consensus. Extensive experiments on math and coding benchmarks demonstrate that ASRD outperforms recent remasking baselines, achieving accuracy improvements of up to 6.4\% while accelerating inference throughput by up to 7.2$\times$.

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

Evolutionary Two-Stage Hyperparameter Optimization Strategies for Physics-Informed Neural Networks

arXiv:2606.20442v1 Announce Type: new Abstract: Physics-Informed Neural Networks (PINNs) solve Partial Differential Equations (PDEs) by embedding physical laws into neural network training. However, their performance suffers from unstable convergence, training plateaus, and strong sensitivity to architectural and optimization hyperparameters due to the highly non-convex and multi-term structure of the physics-informed loss. In this setting, the outer-loop hyperparameter search is a noisy and black-box optimization problem over heterogeneous parameters, where classical local or gradient-based strategies are easily trapped in suboptimal regions. Evolutionary algorithms, with their population-based exploration and ability to handle mixed, non-differentiable search spaces, provide a more robust mechanism for discovering promising configurations. We propose and investigate a two-stage approach based on evolutionary algorithms that combines exploration and exploitation parts of PINNs training to improve solution accuracy and robustness under fixed computational budgets. In the first stage, we perform low-fidelity training runs with truncated epochs to rapidly screen candidate configurations, treating hyperparameter selection as a black-box outer-loop problem. In the second stage, only the most promising candidates are fully trained with standard gradient-based optimizers to refine the solution. Evaluated on three popular problems, namely Advection, Klein-Gordon and Helmholtz equations, our method consistently outperforms standard training and achieves significantly lower mean error within constrained computational resources.

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

HawkesNest: A Multi-Axis Synthetic Benchmark for Spatiotemporal Pattern Complexity

arXiv:2606.16863v1 Announce Type: new Abstract: Evaluation of spatiotemporal point process (STPP) models relies heavily on opaque real-world datasets, where latent generative structure is unknown and model failures are difficult to attribute. We introduce HawkesNest, a generator-aligned benchmark for controlled spatiotemporal pattern complexity built on a multivariate Hawkes backbone. HawkesNest defines four complexity axes: space–time entanglement, background heterogeneity, cross-type interaction, and domain topology. Each axis is associated with a deterministic index computed from the latent data-generating mechanism. By varying these axes while holding global rate, stability, and simulation budget fixed, HawkesNest enables diagnostic stress tests of STPP models under known structural difficulty. We verify that the indices are monotone and nearly orthogonal under controlled sweeps. We illustrate its use by showing that Hawkes-family baselines degrade under joint heterogeneity–entanglement complexity, even though they are structurally aligned with the Hawkes data-generating backbone. We further show that HawkesNest exposes neural-model sensitivity: AutoSTPP remains vulnerable under isolated increases in space–time entanglement. Code. Available at https://github.com/YahyaAalaila/HawkesNest

13.
arXiv (math.PR) 2026-06-12

Pathwise integration beyond Young via Faber–Schauder energy spaces

Authors:

arXiv:2606.13331v1 Announce Type: cross Abstract: We develop a pathwise integration theory based on Faber–Schauder energy spaces. The approach replaces the classical Hölder–Young and finite-variation Young conditions by dyadic summability conditions expressed in terms of Faber–Schauder coefficients. On the normalized interval $[0,1]$, these conditions define Banach spaces $\mathcal{E}^p$, which we call Faber–Schauder energy spaces. For $p,q>1$ satisfying $1/p+1/q\ge1$, we prove that every pair $f\in\mathcal{E}^p$ and $g\in\mathcal {E}^q$ admits a continuous pathwise integral $I_{f,g}$, constructed from dyadic left Riemann sums. We call $I_{f,g}$ the Faber–Schauder integral, and show that it depends boundedly and bilinearly on $(f,g)$ in the corresponding energy norms. The integral satisfies additivity, integration by parts, and a dyadic Young–Loève estimate. It is also the uniform limit of classical Riemann–Stieltjes integrals of finite Faber–Schauder approximations. The Faber–Schauder integral agrees with the classical Young integral whenever the latter is available, but also applies to deterministic and Gaussian examples for which neither the Hölder–Young condition nor the finite-variation Young condition can be verified. In this sense, it provides a Faber–Schauder coefficient-based extension of Young's framework.

14.
arXiv (quant-ph) 2026-06-19

Thermodynamic Value of XOR-Game-Induced Side Information in a Szilard Engine

arXiv:2605.12044v3 Announce Type: replace Abstract: We introduce a Szilard-type thermodynamic valuation of side-information channels induced by Bell-type correlations. In each round, a two-level working system is thermalized with a degenerate Hamiltonian, so that its physical microstate is a uniform classical bit. A trusted referee embeds this bit into a finite two-player XOR game, and a correlation resource produces a compressed controller bit. The controller uses only this compressed bit as side information for feedback. The construction is formulated first for arbitrary finite XOR games. The referee encoding makes the game-winning event equivalent to correct prediction of the physical microstate. Consequently, the induced side-information channel is binary symmetric, with success probability equal to the XOR-game winning probability of the supplied behaviour. The reversible Szilard feedback value is therefore fixed by the mutual information between the microstate and the controller record. Optimizing over local, quantum, and nonsignalling behaviour sets turns the corresponding game values into local, quantum, and nonsignalling thermodynamic ceilings. The construction is an effective-channel valuation, not a claim that Bell nonlocality is thermodynamic fuel. The controller receives only the compressed prediction bit, not the auxiliary variables that define the game. The thermodynamic costs of the referee, the correlation resource, and the preprocessing are not included. When controller-memory reset is included in a full cycle, the net work is non-positive, consistently with the second law.

15.
arXiv (quant-ph) 2026-06-16

Quantum Illumination with Symmetry-Constrained Random Unitaries

arXiv:2606.15586v1 Announce Type: new Abstract: Quantum illumination provides a quantum advantage in detecting weakly reflecting objects embedded in a noisy environment, even when environmental noise destroys most of the initial entanglement. We investigate this advantage using Haar-random probe states constrained to symmetry-resolved subspaces. Employing tools from quantum channel discrimination and asymptotic hypothesis testing, we derive the discrimination exponents associated with Haar-random probe ensembles and identify the role of symmetry in determining their performance. We show that typical states drawn from fixed-charge sectors achieve the same asymptotic quantum-illumination advantage as maximally entangled probes. In particular, we show that the effective thermal-noise suppression and the corresponding Chernoff exponent are governed by the dimension of the accessible symmetry sector. Our results reveal that the operational resource underlying quantum illumination can be generalized from fine-tuned structure of a specific probe state to the existence of a large symmetry-protected correlation subspace. These findings establish a direct connection between quantum illumination, symmetry-resolved typicality, and quantum channel discrimination, and demonstrate that near-optimal quantum hypothesis testing resources can emerge naturally from generic many-body quantum states constrained by conservation laws.

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

Models That Know How Evaluations Are Designed Score Safer

The validity of AI safety evaluations depends on models behaving consistently across controlled and deployment settings. Prior work has identified test-time contextual cues, such as hypothetical scenarios, as a source of verbalized evaluation awareness and subsequent behavioral shift. In this paper, we investigate a potential explanation of this phenomenon: evaluation meta-knowledge, defined as parametric knowledge about the structural traits that characterize evaluations. Similar to dataset contamination, where benchmark exposure leads to higher performance through memorization, we hypothesize that models trained on texts describing evaluation practices may implicitly learn to recognize and respond to evaluation-like contexts, for instance, through exposure to scientific articles or social media posts about AI benchmarking. To test this, we fine-tune models on synthetic documents describing evaluation traits such as verifiable structures or moral dilemmas. Evaluating this fine-tuned model on six safety benchmarks, we find that it is significantly safer than the base model and control model. This behavioral shift persists even when restricting the analysis to responses lacking explicit verbalization of evaluation awareness. Our results demonstrate that evaluation meta-knowledge may inflate safety benchmark performance, introducing a novel confounder that is independent of explicit memorization or verbalized evaluation awareness, thus, challenging to detect. These findings have important implications for the design and interpretation of AI safety evaluations. Our code and models are available at https://github.com/compass-group-tue/arxiv2026_evaluation_meta_knowledge.

17.
medRxiv (Medicine) 2026-06-16

Enteral docosahexaenoic and arachidonic acid supplementation and retinopathy of prematurity: a re-analysis of randomized controlled trials in preterm infants

Background. A recent meta-analysis by Dang et al. [1] concluded that enteral supplementation with docosahexaenoic acid (DHA), with or without arachidonic acid (ARA) did not significantly affect retinopathy of prematurity (ROP) outcomes in preterm infants. Of four eligible trials that supplemented both DHA and ARA, only two contributed to each ROP outcome analyzed, and severe ROP was not assessed. Methods. We replicated the eligibility criteria and search strategy of Dang et al., restricted to trials that supplemented both DHA and ARA, and reanalyzed three ROP endpoints (any ROP, ROP requiring treatment, and severe ROP [stage 3 and/or treated]) using complete outcome records from all eligible trials. Crude risk ratios (RR) were pooled by Mantel-Haenszel fixed-effect meta-analysis. Gestational age-adjusted odds ratios (adjOR) were pooled on the log scale by inverse-variance random-effects meta-analysis with restricted maximum likelihood (REML) estimation of between-study variance and Hartung-Knapp confidence intervals. Results. Five trials were included; one trial was identified in our replicated search but was excluded by Dang et al. without a stated rationale. The pooled estimate for any ROP was consistent with Dang et al. (RR 0.87 [95% CI 0.71-1.08]; adjOR 0.70 [0.46-1.08]). For ROP requiring treatment, the crude RR suggested a lower risk but did not reach statistical significance (RR 0.60 [0.35-1.04]), whereas the gestational age-adjusted estimate indicated lower odds (adjOR 0.47 [0.23-0.94]). For severe ROP, DHA+ARA supplementation produced a significant protective effect in both unadjusted and adjusted models (RR 0.56 [0.36-0.86]; adjOR 0.42 [0.19-0.96]). Conclusions. When all eligible trials contribute to each endpoint and severe ROP is included as an outcome, enteral DHA+ARA supplementation reduces severe ROP and is associated with lower odds of ROP requiring treatment after adjustment for gestational age. These findings differ from the conclusions of Dang et al. and support reconsideration of DHA+ARA supplementation as a strategy to reduce sight-threatening ROP in preterm infants.

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

Towards Pareto-Optimal Tool-Integrated Agents with Pareto Ranking Policy Optimization

Recent advances in tool-integrated language agents have significantly improved their ability to solve complex reasoning tasks. However, existing alignment methods predominantly focus on maximizing task accuracy, while overlooking auxiliary objectives such as tool-use efficiency, which are essential for practical deployment. To address this gap, we introduce ParetoPO, a two-stage multi-objective optimization framework for aligning tool-using large language models (LLMs) under competing objectives. In the first stage, ParetoPO leverages hypervolume-guided dynamic scalarization to adapt reward weights based on global Pareto frontier progress. In the second stage, it replaces scalarized learning signals with Pareto-ranking-based advantage computation, promoting nondominated trajectories through dominance-aware credit assignment. This design enables fine-grained, action-level optimization across multiple conflicting objectives. Experimental results on mathematic reasoning and multi-hop QA tasks show that ParetoPO consistently discovers policies with superior accuracy-efficiency trade-offs compared to static and heuristic baselines.

19.
arXiv (CS.LG) 2026-06-16

Deep Learning-Based Lunar Crater Terrain Relative Navigation

arXiv:2606.14776v1 Announce Type: cross Abstract: Accurate position estimation is crucial for the successful implementation of future lunar landings using autonomous vehicles, especially in dangerous environments with sparse terrain features. In this paper, we propose a terrain relative navigation (TRN) algorithm combining our deep-learning crater detector, which was designed specifically for the NASA Crater Detection Challenge problem, and an Extended Kalman Filter (EKF). Our detector analyzes crater features from the monocular images acquired from orbit, and their matches with craters from a global database are identified via a Hungarian assignment approach followed by the consensus-based outliers removal method. The estimated measurements are then used to refine an EKF, where spacecraft pose estimation in the Lunar-Centered Lunar-Fixed (LCLF) frame of reference, augmented with altitude aiding information, constrains radial drift. The simulation results indicate that even if the spacecraft is off from its actual location up to 5 km, TRN could recover from this situation, achieving navigation error reduction to a few hundred meters. It should be noted that in order to maintain crater feature correspondences, it is important to match the image resolution and the scales within the scene to the detector training set distribution.

20.
arXiv (CS.CL) 2026-06-11

TokenRatio: Principled Token-Level Preference Optimization via Ratio Matching

Direct Preference Optimization (DPO) is a widely used RL-free method for aligning language models from pairwise preferences, but it models preferences over full sequences even though generation is driven by per-token decisions. Existing token-level extensions typically decompose a sequence-level Bradley-Terry objective across timesteps, leaving per-prefix (state-wise) optimality implicit. We study how to recover token-level preference optimality using only standard sequence-level pairwise comparisons. We introduce Token-level Bregman Preference Optimization (TBPO), which posits a token-level Bradley-Terry preference model over next-token actions conditioned on the prefix, and derive a Bregman-divergence density-ratio matching objective that generalizes the logistic/DPO loss while preserving the optimal policy induced by the token-level model and maintaining DPO-like simplicity. We introduce two instantiations: TBPO-Q, which explicitly learns a lightweight state baseline, and TBPO-A, which removes the baseline through advantage normalization. Across instruction following, helpfulness/harmlessness, and summarization benchmarks, TBPO improves alignment quality and training stability and increases output diversity relative to strong sequence-level and token-level baselines.

21.
medRxiv (Medicine) 2026-06-22

Genetic modifiers of psychiatric, motor, and cognitive symptoms in Huntington's disease

The Enroll HD natural history platform provides rich longitudinal phenotypes enabling genome wide analyses across diverse clinical domains. Psychiatric symptoms are a major source of morbidity in Huntington's disease (HD), yet the genetic architecture underlying their onset is poorly understood. We analyzed ~18,000 people with HD (PwHD) to define genetic determinants of ages at psychiatric, motor, and cognitive symptom onset, and HD diagnosis. GWAS meta analysis recapitulated 11 established modifiers of motor onset and identified a novel locus spanning RAB3B/ZFYVE9 associated with age at violent/aggressive behavior onset. Exome wide analyses in Enroll HD participants implicated rare variants in FAN1, PMS1, POLD1, and HTT. Several HD modifiers of motor and cognitive symptom onset (MSH3, FAN1, HTT) also influenced psychiatric symptom onset, whereas PMS1 and POLD1 showed significant association with motor symptom onset. Psychiatric polygenic scores predicted psychiatric symptom onset, revealing a hybrid architecture combining psychiatric liability in general population with HD- or repeat expansion disease (RED) specific pathways.

22.
arXiv (quant-ph) 2026-06-11

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

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

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

Optimal Hidden-Target Learning for Online Inventory Optimization on General Convex Sets

arXiv:2606.14679v1 Announce Type: new Abstract: Online inventory optimization (OIO) is online convex optimization with physical memory: inventory carryover makes the feasible action set depend on the past. A natural principle, used in stochastic inventory learning and recently in OIO under a single linear capacity constraint, is to maintain a hidden target chosen by an online learner and implement its projection onto the currently feasible order-up-to set. We prove that this simple principle is optimal for OIO on arbitrary bounded convex capacity sets. With online gradient descent as the base learner, the method improves the best known regret guarantee for OIO on general convex sets from inverse to inverse-square-root dependence on the common-demand probability, and we prove a matching lower bound. The same principle gives the first polylogarithmic regret guarantee for strongly convex losses and the first dynamic regret guarantee adapting to Euclidean path variation on general convex capacity sets. The analysis introduces a norm alignment principle: the right state variable is the distance from the hidden target to the feasible set, measured in the same norm as the projection. Under norm alignment, this distance evolves pathwise as a scalar queue, with target movement as arrival and common demand as service. This reduction to one-dimensional queue control resolves the state dependence and extends the guarantees to general convex capacity sets, beyond the reach of prior productwise approaches. Experiments on synthetic and real-world inventory data corroborate the theory.

24.
medRxiv (Medicine) 2026-06-22

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes

OBJECTIVE To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

25.
medRxiv (Medicine) 2026-06-16

High-Risk Anti-Seizure Medication Use in Childbearing-Age People with Epilepsy in a Taenia solium Endemic Region

Background: People of childbearing potential with epilepsy in regions endemic for Taenia solium, where neurocysticercosis (NCC) is highly prevalent, represent a vulnerable population due to the elevated burden of epilepsy and resource limitations. Clinical practice in these settings remains poorly characterized. This study characterized anti-seizure medication (ASM) prescribing patterns by medication risk profiles among people of childbearing potential with epilepsy in Northern Peru, a region highly endemic for T. solium. Methods: Participants were drawn from a prospective, population-based epilepsy cohort in Tumbes, Peru (2006 to 2020). The analytic population included females with epilepsy aged 15 to 49 years. The primary outcome was pregnancy-associated ASM risk of congenital malformations and adverse neurodevelopmental outcomes. ASMs were classified as ''Established Low Risk'' (lamotrigine, levetiracetam), ''Possible Risk/Inadequate Data'' (carbamazepine, phenobarbital, phenytoin), and ''Established High Risk'' (valproic acid). Prescription patterns were examined in relation to demographic and clinical characteristics. Results: Among 1,975 individuals with epilepsy, 685 were people of childbearing potential. Approximately 34.9% met criteria for probable or definite NCC. Most ASM prescriptions were in the ''Possible Risk/Inadequate Data'' category (87.0%), and 12.8% received ''Established High Risk'' medications. In multivariable analysis, high-risk prescribing was associated with prior ASM use and polytherapy. Discussion: People of childbearing potential with epilepsy were predominantly treated with carbamazepine, phenytoin, phenobarbital, and valproate, reflecting local ASM availability. Despite evidence supporting lamotrigine and levetiracetam in pregnancy, prescribing patterns reflect local formulary constraints. These findings highlight a gap between guideline recommendations and real-world prescribing in resource-limited settings, underscoring the need for context-specific treatment strategies.