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01.
arXiv (quant-ph) 2026-06-17

Quantum mechanics in configuration space in context

Authors:
Arwa Bukhari↗Margherita Moro↗Max Davies↗Alastair Wilson↗Almut Beige↗

arXiv:2606.17622v1 Announce Type: new Abstract: To enhance the way in which wave-particle duality is implemented in the modelling of quantum mechanical systems, Bukhari et al. [New J. Phys. 27, 084501 (2025)] recently introduced an alternative approach to quantum mechanics, namely quantum mechanics in configuration space. This formalism is based on a physically motivated quantisation of Newtonian mechanics and promotes the classical position-velocity states (x,v) to pairwise distinguishable quantum states. The resulting |x,v> states form the basis of the Hilbert space of individual quantum mechanical particles and evolve along classical trajectories. In this paper, we consider the modelling of a mechanical particle in free space and put quantum mechanics in configuration space into context. It is shown that this formalism increases the continuity between quantum and classical mechanics by avoiding a conceptual inconsistency associated with the definition of momentum in canonical quantisation. In addition, we emphasise that standard quantum mechanics and quantum mechanics in configuration space are based on two distinct formulations of classical mechanics.

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02.
arXiv (CS.CL) 2026-06-17

When Multiple Scripts Matter: Evaluating ASR in Clinical Settings

Authors:
Jean Seo↗Minkyu Kim↗Jeonguk Lee↗Jisoo Jung↗Wooseok Han↗Eunho Yang↗

Automatic speech recognition (ASR) in non-English clinical settings is challenged by multiscript variability, where the same term may appear in multiple valid orthographic forms. Conventional string-matching evaluation metrics often underestimate ASR performance by treating orthographic variants as errors. To address this issue, we introduce MultiClin, a clinical ASR benchmark designed to evaluate robustness to multiscript variability. Experiments across diverse ASR models show that multiscript-aware evaluation provides a fairer assessment of recognition quality than conventional single-reference evaluation. We further investigate the impact of script consistency during training and find that inconsistent script mappings increase orthographic uncertainty and hinder model convergence, with a balanced 50% mapping ratio producing the highest entropy. In contrast, script unification consistently yields the best ASR performance. Our dataset and code are publicly available at: https://github.com/aitrics-ronaldo/Interspeech_MultiClin.

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03.
Nature Medicine 2026-06-17

Why large-scale randomized trials of live-attenuated shingles vaccination for dementia prevention are urgently needed

Authors:
Pascal Geldsetzer↗

In my view, we have never had as robust a body of evidence from observational data on an intervention for dementia as we do for live-attenuated shingles vaccination. Both a recent US National Institutes of Health expert workshop and an international expert consensus on Alzheimer’s disease drug repurposing identified large-scale randomized trials of shingles vaccination for dementia prevention as the crucial next step for the field.

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04.
arXiv (quant-ph) 2026-06-19

Quantum correlations in QBism's reconstruction program

Authors:
Sachin Gupta↗Jacques Pienaar↗

arXiv:2606.07485v2 Announce Type: replace Abstract: QBism recasts quantum theory as a normative framework for an agent's probability assignments, with the Born rule taking the form of a consistency condition known as the Urgleichung. Motivated by this perspective, qplex theories provide a broader class of probabilistic models in which the sets of valid states and measurements are constrained by QBist-inspired geometric conditions. While qplexes have been extensively studied for single systems, their implications for bipartite correlations remain largely unexplored. In this work, we investigate bipartite correlations in qplex theories by expressing joint expectation values as inner products between suitably defined $C$-vectors. This geometric formulation allows Bell-type inequalities to be studied as optimization problems over qplex-compatible probability assignments. We first analyze the CHSH scenario and show that the shared inner-product structure of the $C$-vectors restricts the maximal value to the Tsirelson bound $2\sqrt{2}$. We then turn to the three-outcome CGLMP inequality $I_{2233}$ and find that the same qplex-derived norm and inner-product constraints allow a violation of up to $\leq 2+2\sqrt(3)/3 \approx 3.1547$ versus the quantum maximum of $\approx 2.8729$, thereby exhibiting super-quantum correlations. These results show that qplex geometry captures enough structure to reproduce an important quantum bound in the two-outcome case, but not enough to recover the full set of quantum correlation constraints. The analysis therefore suggests that additional principles are needed to complete the QBist reconstruction of quantum theory.

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05.
arXiv (quant-ph) 2026-06-19

Maximum entropy principle for quantum processes

Authors:
Siddhartha Das↗Ujjwal Sen↗

arXiv:2506.24079v3 Announce Type: replace Abstract: The maximum entropy principle, as applied to quantum systems, is a fundamental prescript positing that for a quantum system for which we only have partial knowledge, the maximum entropy state consistent with the partial knowledge is a valuable choice as the system's state. An intriguing result is that in case the only prior knowledge is of a fixed energy, the maximum entropy state turns out to be the thermal state, a ubiquitous state in several arenas, especially in statistical mechanics. We extend the consequences of this principle from static quantum states to dynamic quantum processes. We establish that a quantum channel attains maximal output entropy under a fixed energy constraint if and only if it is an absolutely thermalizing channel, where the fixed output is the thermal state corresponding to that energy. Our results have potential implications for understanding the informational and thermodynamic utility of quantum channels under physical constraints. As an application, we examine the consequences for private randomness distillation from fixed energy constrained quantum processes.

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

Convergence to the Brownian CRT for critical branching Markov processe

Authors:
Emma Horton↗Ellen Powell↗

arXiv:2601.05906v2 Announce Type: replace Abstract: We prove an invariance principle for a general class of continuous time critical branching processes with finite variance (non-local) branching mechanism. We show that the genealogical trees, viewed as random compact metric measure spaces, converge under rescaling to the Brownian continuum random tree in the Gromov-Hausdorff-weak topology, establishing a universal scaling limit for critical finite variance branching processes.

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08.
arXiv (CS.LG) 2026-06-16

Distilling latent electrostatics from foundation machine learning interatomic potentials

Authors:
Xiaoyu Wang↗Bingqing Cheng↗

arXiv:2606.15001v1 Announce Type: cross Abstract: Foundation machine learning interatomic potentials (MLIPs) have enabled atomistic simulations across broad regions of chemical and materials space, but many remain computationally expensive and lack explicit electrostatics, limiting their use for systems governed by long-range interactions and electrical response. Previously, we introduced Latent Ewald Summation (LES), which learns latent atomic charges and long-range electrostatics from density functional theory (DFT) energy and force labels alone. Here, we use LES to extract electrostatics that are latent in foundation models: energies and forces predicted by a teacher model are used to train a lightweight LES-augmented student MLIP, with optional fine-tuning on additional DFT data. The resulting models reduce computational cost while providing access to Born effective charge tensors, and infrared spectra. We benchmark student models distilled from a broad set of foundation MLIPs, including UMA, MACE, Orb, eSEN, GemNet-OC, PET, and EquiformerV2-based models, against experimental infrared spectra for liquid water, concentrated hydrochloric acid, and the anatase TiO2(101)-water interface. Across these systems, electrostatic response can be extracted from most foundation MLIPs. The benchmark further shows that the underlying DFT level and dataset used to train the teacher model play a larger role than architecture in determining electrostatic and spectroscopic accuracy. For the TiO2-water interface, fine-tuning with a modest amount of higher-level DFT data improves structural and infrared predictions. LES-based distillation therefore provides a practical route for converting foundation MLIPs into efficient, electrically responsive models, while also testing the physical fidelity encoded in foundation models.

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09.
arXiv (CS.CV) 2026-06-25

ESTANet: Efficient Online Error Detection in Procedural Videos via Prediction Inconsistency

Authors:
Shih-Po Lee↗Reza Ghoddoosian↗Faizan Siddiqui↗Enna Sachdeva↗Behzad Dariush↗

An efficient and accurate system for detecting errors in procedural tasks is crucial for supporting human needs in daily life, as it can provide instant notifications and guide people to correct mistakes. In this work, we study real-time online error detection in procedural videos from a simple but overlooked perspective: the prediction behavior of action detectors themselves. Instead of designing complex architectures or specialized supervision, we observe that action detectors naturally exhibit different prediction characteristics depending on their sensitivity to input dynamics and temporal context. We therefore propose ESTANet (Error-Sensitive and Temporally-vArying Network), a lightweight framework that detects errors by exploiting inconsistencies among action predictions produced by a small set of action detectors. We construct standard and error-sensitive action detectors that behave similarly on correct executions but respond differently when errors occur. Meanwhile, detectors operating with different temporal contexts further amplify prediction inconsistencies when the procedure deviates from the intended sequence. During inference, we detect errors by aggregating mismatches between standard and error-sensitive predictions through majority voting to flag frames that contain errors. Extensive experiments on EgoPER, Assembly-101-O, and EPIC-Tent-O demonstrate that ESTANet achieves state-of-the-art performance in online error detection while maintaining real-time efficiency with a lightweight architecture. Our results highlight that leveraging the intrinsic properties of action detectors can yield a powerful and practical solution for online error detection without increasing architectural design complexity.

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

We Need to Rethink Benchmarking in Anomaly Detection

Authors:
Philipp R\"ochner↗Simon Kl\"uttermann↗Kevin Kammler↗Franz Rothlauf↗Emmanuel M\"uller↗Daniel Schl\"or↗

arXiv:2507.15584v2 Announce Type: replace Abstract: Despite the continuous proposal of new anomaly detection algorithms and extensive benchmarking efforts, progress seems to stagnate, with only minor performance differences between established baselines and new algorithms. In this position paper, we argue that this stagnation is due to limitations in how we evaluate anomaly detection algorithms. In current benchmarks, a trivial algorithm that only checks for extreme values in individual features performs competitively with state-of-the-art deep learning methods, despite failing on simple cases such as anomalies within an annulus of normal points. Moreover, existing benchmarks do not adequately reflect the diversity of anomaly detection applications, making it difficult for practitioners to reliably select algorithms for their applications. Consequently, we need to rethink benchmarking in anomaly detection. In our opinion, anomaly detection should be studied using scenarios that group applications sharing relevant characteristics, defined through a common taxonomy. Benchmarking within scenarios enables scenario-specific choices for preprocessing, metrics, and model selection, clarifying which advances transfer across similar applications and providing practitioners with reliable guidance for their specific contexts.

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11.
arXiv (CS.LG) 2026-06-17

Meta-classification of one-class classification models using ranking correlation and nearest neighbor

Authors:
Toshitaka Hayashi↗Hamido Fujita↗Dalibor Cimr↗Richard Cimler↗Jitka K\"uhnov\'a↗

arXiv:2606.17858v1 Announce Type: new Abstract: Machine Learning (ML) techniques have been applied to various problems. However, applying ML to ML models is an unexplored direction. For this purpose, this paper considers a meta-classification of one-class classification (OCC) models, because all ML models could be approximated as OCC models. The proposal represents OCC models as normality rankings and classifies them using nearest-neighbor and ranking-correlation metrics. The experiment classifies OCC models, where classes correspond to training datasets, algorithms, and hyperparameters. The proposal achieves high accuracy when class labels are datasets. Moreover, it can classify algorithms when the training datasets contain the same class. In addition, the discussion highlights that the classification of OCC models is essentially the classification of datasets that treats multiple samples as a single input. The experiment demonstrates the classification of datasets using sleeping records. The proposed method can provide a unified solution for classifying OCC models, datasets, and rankings. Source code is uploaded to the public repository https://github.com/ToshiHayashi/ClassOCC.

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

Fast-dLLM++: Fr\'{e}chet Profile Decoding for Faster Diffusion LLM Inference

Authors:
Siva Rajesh Kasa↗Yasong Dai↗Sumit Negi↗Hongdong Li↗

Diffusion large language models promise parallel token generation, yet inference remains bottlenecked by deciding which masked tokens can be safely committed together. Fast-dLLM addressed this with KV caching and confidence-guided parallel decoding, but its decoding theory uses a homogeneous high-confidence assumption that effectively reduces each candidate set to its weakest selected token. We argue that this leaves speed on the table because real decoding steps exhibit heterogeneous confidence profiles. We propose Fast-dLLM++, a training-free extension that introduces Fr\'{echet profile decoding}: selecting parallel commit sets from the full sorted confidence profile rather than a single worst-case confidence. The resulting rule is a heterogeneous-confidence generalization of Fast-dLLM's factor selector and it recovers the previous rule exactly in the equal-confidence case and adds a provable heterogeneity bonus when the selected tokens have uneven confidences. Fast-dLLM++ leaves the model, diffusion process, and cache implementation entirely unchanged, making it a drop-in replacement for existing Fast-dLLM decoding. Experiments on GSM8K, MATH, HumanEval, and MBPP with the LLaDA-8B model show that the theoretical improvement translates directly into empirical gains: profile-aware selection improves the accuracy–throughput frontier by exploiting safe parallelism that weakest-token rules miss, achieving up to 37\% higher throughput at comparable accuracy. Our code release is at https://github.com/Ringo-Star/FastdLLM_plusplus.

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13.
bioRxiv (Bioinfo) 2026-06-11

A high-quality chromosome-scale reference genome assembly for Asparagus racemosus var. CIM-Shakti (Shatavari), a medicinal plant of Ayurvedic importance

Authors:
Tyagi↗Sharma↗Shivani↗Gupta↗Paterson↗A. H↗Trivedi↗P. K↗

Asparagus racemosus Wild., commonly known as Shatavari, is an important medicinal plant in Ayurveda and is valued for its steroidal saponins, particularly shatavarin compounds, which contribute to its adaptogenic, galactagogue, immunomodulatory, and therapeutic properties. Despite its medicinal and economic importance, genomic resources for this species have remained limited, restricting molecular breeding, pathway discovery, and comparative evolutionary studies within Asparagaceae. Here, we report a high quality chromosome scale reference genome assembly of A. racemosus var. CIM Shakti generated using PacBio HiFi long read sequencing and Omni C chromatin conformation scaffolding. The pseudo haploid assembly spans 817 Mb across 53 scaffolds, with a scaffold N50 of 98.50 Mb, L50 of 5, and a largest scaffold of 113.80 Mb. Ten major chromosome scale pseudomolecules were resolved, corresponding to the haploid chromosome complement of A. racemosus. The assembly showed high gene space completeness, with BUSCO completeness of 99.8% against the Eukaryota dataset and 98.0% against the Embryophyta dataset. BlobToolKit profiling further supported assembly quality, with GC content of approximately 39 to 40% and no major evidence of contamination. EDTA based repeat annotation identified 580.93 Mb of interspersed repetitive elements, accounting for 71.06% of the 817.57 Mb genome assembly. The repeat landscape was dominated by LTR retrotransposons, particularly Gypsy elements, which accounted for 25.01% of the assembly, followed by unclassified LTR elements at 26.58% and Copia elements at 4.84%. Structural and functional annotation identified 29,199 protein coding genes represented by 29,199 transcript models, 138,433 exons, and 125,201 CDS features. The annotation was structurally robust, with an average gene length of 4,605.1 bp, 4.74 exons per transcript, and 97.80% of transcripts containing multiple exons. The CIM Shakti reference genome provides a foundational genomic resource for investigating steroidal saponin biosynthesis, sex chromosome evolution, repeat driven genome expansion, and comparative genomics in Asparagaceae. This assembly will support future studies on medicinal trait improvement, conservation genomics, and genomics assisted breeding of climate resilient Shatavari cultivars.

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14.
arXiv (math.PR) 2026-06-16

Purely unrectifiable sets, fractal percolation and graphs of functions

Authors:
Zolt\'an Buczolich↗

arXiv:2606.15745v1 Announce Type: cross Abstract: This paper contains a survey of some of the results of the author related to unrectifiablity and is an extended version of the author's talk given at the Second Winter School Geometric Measure Theory Rectifiability vs. Pure Unrectifiability in Hanghzou, China. These results include irregular/purely unrectifiable $1$-sets on the graphs of continuous functions like the Takagi, the Weierstrass-Cellerier and the typical (in the sense of Baire) continuous function. It is also discussed that there exists $ {\alpha}_{0}\alpha_0$. The background of the $1$-unrectifiability is discussed in more detail.

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15.
medRxiv (Medicine) 2026-06-24

Predicting 24-Month MCI-to-Alzheimer's Conversion Using Routine Clinical Assessments Without Neuroimaging or Genetic Testing

Authors:
Choe↗

ABSTRACT INTRODUCTION: Early identification of individuals with mild cognitive impairment (MCI) at high risk of conversion to Alzheimer's disease (AD) is essential for timely intervention. We evaluated whether routinely obtainable clinical assessments can accurately predict 24-month MC to AD conversion. METHODS: Data from 2,430 participants with MCI in the Alzheimer's Disease Neuroimaging Initiative were analyzed. XGBoost, Random Forest, and Logistic Regression models were evaluated. SHAP-based feature selection and feature ablation analyses assessed the incremental value of APOE4 genotype. RESULTS: A six-feature model incorporating age, sex, education, RAVLT Immediate Recall, MMSE, and EcogSPTotal achieved an AUC of 0.922 (95% CI, 0.911~0.933). APOE4 provided negligible additional predictive value once cognitive measures were included. The XGBoost model outperformed Clinical Dementia Rating Sum of Boxes classification. DISCUSSION: Routine cognitive assessments accurately predict 24-month MCI-to-AD progression without biomarkers, neuroimaging, or genetic testing, offering a practical, low-cost tool for clinical risk stratification.

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16.
arXiv (quant-ph) 2026-06-19

Locally Gentle State Certification for High Dimensional Quantum Systems

Authors:
Cristina Butucea↗Jan Johannes↗Henning Stein↗

arXiv:2602.04550v3 Announce Type: replace Abstract: Standard approaches to quantum statistical inference rely on measurements that induce a collapse of the wave function, effectively consuming the quantum state to extract information. In this work, we investigate the fundamental limits of locally-gentle quantum state certification, where the learning algorithm is constrained to perturb the state by at most $\alpha$ in trace norm, thereby allowing for the reuse of samples. We analyze the hypothesis testing problem of distinguishing whether an unknown state $\rho$ is equal to a reference $\rho_0$ or $\epsilon$-far from it. We derive the minimax sample complexity for this problem, quantifying the information-theoretic price of non-destructive measurements. Specifically, by constructing explicit measurement operators, we show that the constraint of $\alpha$-gentleness imposes a sample size penalty of $\frac{d}{\alpha^2}$, yielding a total sample complexity of $n = \Theta(\frac{d^3}{\epsilon^2 \alpha^2})$. Our results clarify the trade-off between information extraction and state disturbance, and highlight deep connections between physical measurement constraints and privacy mechanisms in quantum learning. Crucially, we find that the sample size penalty incurred by enforcing $\alpha$-gentleness scales linearly with the Hilbert-space dimension $d$ rather than the number of parameters $d^2-1$ typical for high-dimensional private estimation.

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

Adjusted Cup-Product Neural Layer

Authors:
Snigdha Chandan Khilar↗

arXiv:2606.13568v1 Announce Type: new Abstract: Many important observables in physics and geometry are cup products of cochains. The adjusted cup product neural layer has been introduced in this paper. It is a neural primitive that hard wires the cup product with an adjustment term from higher gauge theory. This creates a readout that is gauge invariant by design. Their main theoretical result shows that on a closed cycle the output relies entirely on the adjustment coefficient. Setting this coefficient to zero removes the output completely regardless of other parameters. Thus the adjustment is the only source of gauge invariant signal. They prove this observable is a nonzero quadratic form and is exactly invariant under one and two gauge transformations.

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18.
arXiv (math.PR) 2026-06-17

Convergence Analysis of the Random Bisection Method

Authors:
Ludovick Bouthat↗Philippe-Andr\'e Luneau↗Philippe Petitclerc↗

arXiv:2603.20483v2 Announce Type: replace-cross Abstract: We propose a generalized version of the bisection method where the cutting point between the two subintervals is chosen at random following an arbitrary distribution. We compute expected convergence rates with respect to any arbitrary a priori distribution for the position of the root in the initial interval and proved that it depends only on the the expectation $\mathbb{E}[c(1-c)]$ of the cut $c$. We also provide a generalization of the method for $K$ random cuts and study its convergence properties. Most probabilistic derivations are kept fairly simple for the ease of understanding of a larger audience. Our theoretical results are then validated numerically using statistical simulation.

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19.
arXiv (quant-ph) 2026-06-25

A Short Note on the Generators of Controlled Quantum Gates

Authors:
Richard M. Milbradt↗Christian B. Mendl↗

arXiv:2606.25789v1 Announce Type: new Abstract: We present the analytical generators for arbitrary multi-qubit controlled gates. Closed forms for the generating Hamiltonians are given for gates with both multiple control and target qubits, as well as for arbitrary control conditions. This allows us to go beyond gate-based simulations of quantum circuits and incorporate decoherence and other noise in simulations of quantum computers. We exemplify this by simulating the impact of a harmonic oscillator interacting with two qubits during the application of a controlled NOT gate.

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20.
arXiv (quant-ph) 2026-06-15

Quantum geometrical description of hole spin qubits far away from the $\Gamma$-point

Authors:
Zolt\'an Gy\"orgy↗Dmitry Miserev↗Jelena Klinovaja↗Daniel Loss↗

arXiv:2606.14683v1 Announce Type: cross Abstract: Hole spin qubits provide one of the leading platforms for spin-based quantum computing due to their large intrinsic spin-orbit interaction (SOI), which enables fast electrical manipulation. The SOI of planar quantum dots has mostly been investigated in theoretical studies by examining the SOI already present in the two-dimensional hole gas (2DHG). Here, we study the SOI created by the in-plane confinement by deriving non-perturbative effective Hamiltonians numerically for hole spin qubits. We find that the quantum geometry of the 2DHG naturally emerges, leading to a meaningful non-perturbative definition of pseudospin valid far away from the $\Gamma$-point. The SOI of the 2DHG and of the in-plane confinement have different forms; therefore, they cannot be turned off simultaneously, ruining the perfect spin-orbit switch functionality of spin qubits. We construct effective Hamiltonians using the symmetry approach for various low-dimensional hole systems: (i) a heavy-hole confined in a SiGe/Ge/SiGe heterostructure, (ii) a light-hole confined in SnGe/Ge, (iii) a gate-defined nanowire in SiGe/Ge/SiGe, and (iv) a hole confined in a Ge/Si core/shell nanowire. The non-perturbative effective Hamiltonians provide results with excellent agreement with the full Hamiltonians.

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22.
arXiv (CS.AI) 2026-06-24

AI Tokenomics: The Economics of Tokens, Computation, and Pricing in Foundation Models

Authors:
Quanyan Zhu↗

arXiv:2606.24616v1 Announce Type: new Abstract: Tokens have become the practical accounting unit for modern foundation model services, linking information processing, computation, memory use, energy expenditure, pricing, and economic value. This paper develops a framework for AI tokenomics: the study of how tokens are generated, consumed, priced, allocated, and optimized across AI systems. We connect token-level technical costs to workflow-level production functions, enterprise resource allocation, measurement and instrumentation methods, and emerging market-design questions. The framework shows that token expenditure and economic value are distinct: value depends on marginal productivity, workflow position, hidden reasoning activity, risk, and downstream propagation effects. The paper concludes by identifying open research directions in hidden-token measurement, empirical calibration, token productivity, dynamic allocation, and token-based markets.

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23.
arXiv (CS.CV) 2026-06-17

AlignDrive: Aligned Lateral-Longitudinal Planning for End-to-End Autonomous Driving

Authors:
Yanhao Wu↗Haoyang Zhang↗Fei He↗Rui Wu↗Yanhu Shan↗Congpei Qiu↗Liang Gao↗Wei Ke↗Tong Zhang↗

Practical autonomous driving requires models that generalize by reasoning through spatial-temporal possibilities to exclude unsafe outcomes. While state-of-the-art (SOTA) methods use parallel planning architectures, they fail to explicitly couple speed decisions with agent behavior along the driving path, leading to suboptimal coordination. To address this, we propose a cascaded framework that transforms longitudinal planning from an independent prediction task into a path-conditioned reasoning process. On the model side, we introduce an anchor-based regression design that conditions longitudinal prediction on the lateral drive path, and reformulate longitudinal planning as 1D displacement prediction along the path. This reduces geometric uncertainty and sharpens the model's focus on interaction-driven dynamics. On the data side, we introduce a planning-oriented data augmentation strategy that simulates rare safety-critical events by programmatically inserting agents and relabeling longitudinal targets to enforce collision avoidance. Evaluated on the challenging Bench2Drive benchmark, our method achieves SOTA performance with a driving score of 89.07 and a success rate of 73.18%, demonstrating significantly improved coordination and safety. Further evaluation on Fail2Drive confirms strong generalization to rare edge cases where parallel formulations typically fail. Project page:https://yanhaowu.github.io/AlignDrive/.

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24.
PLOS Medicine 2026-05-15

Spatial transcriptomic-metabolic features of tumor foci and tumor capsule in microvascular invasion with hepatocellular carcinoma: A spatial multi-omics study

Authors:
Zhi-Hui Luo↗

by Zhi-Hui Luo, Na Wang, Jingwei Zhao, Fei Long, Si Wu, Wei Zhong, Wei-Ming Chen, Bicheng Wang, Kun Wang, Yufeng Yuan, Jingjiao Zhou, Chunhui Yuan, Fubing Wang Background Microvascular invasion (MVI) is closely related to the recurrence and metastasis of hepatocellular carcinoma (HCC), but the underlying cellular mechanism remains largely elusive. This study aims to elucidate the regional cellular discrepancy between MVI-positive (MVI+) and MVI-negative (MVI−) HCC by integrating Spatial transcriptomics (ST) and spatial metabolomics (SM). Methods and findings ST and SM were performed on six tissue samples from four patients (including 2 MVI+, 2 MVI−, and 2 paratumor tissues), with the integration of 79 public single-cell RNA sequencing datasets of HCC. Patient identity was used as a covariate in the linear equation for regional differentially expressed gene analysis with the ST data. Clinical validation was conducted through multiplex immunofluorescence staining in 79 patients, together with external validation in the cancer genome atlas (TCGA)-liver hepatocellular carcinoma (LIHC) cohort (n = 299) and an independent microarray dataset (n = 62). For cell-type-specific metabolic profiling, spatial transcriptomic-metabolic registration was performed. The functional roles of key metabolites were further validated in vitro using inflammatory cancer-associated fibroblasts (iCAFs) derived from hepatic stellate cells (HSCs) and primary CAFs through co-culture models and various functional assays assessing cell proliferation, migration, and invasion. In the tumor lesion, a malignant STMN1+HMGN2+GPC3+ cell subtype enriched in MVI+ HCC was identified, which exhibited enhanced proliferative activity and was associated with poor prognosis. This finding was further confirmed in a local cohort of 79 patients, where multiplex immunofluorescence staining for the three genes (STMN1, HMGN2, and GPC3) showed significantly higher expression in the MVI+ group than in the MVI− group (p = 0.046). Integrated SM analysis further revealed that this cell population underwent metabolic reprogramming characterized by suppressed glycerolipid metabolism. In the tumor capsule, iCAFs-related genes were downregulated in MVI+ cases, and iCAFs were located distally from the tumor boundary. Spatial metabolite mapping showed a strong correlation between taurine and iCAFs, and functional assays demonstrated that taurine promotes HCC proliferation and migration by suppressing iCAF activity. One limitation of this study is the small sample size of spatial omics data, which hinders a more complete molecular functional analysis of the STMN1+HMGN2+GPC3+ cell subtype and iCAFs in MVI+ HCC. Larger-scale ST cohorts are required to further validate and expand the findings of this study. Conclusions This integrative spatial atlas proposes a hypothesis that there exists a highly proliferative and metabolically reprogrammed malignant cell subtype in the tumor lesion of MVI+ HCC, and that taurine in the tumor capsule modulates iCAF activity to influence tumor progression. The exploratory results provide mechanistic insights into MVI-related HCC progression and offer potential avenues for targeted therapeutic intervention of MVI+ HCC.

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25.
arXiv (CS.AI) 2026-06-15

The Perceived Fragility of Explanations in Audio Models: Manipulation of Attribution with Unchanged Predictions

Authors:
Piotr Kit{\l}owski↗Dominik Wi\k{a}cek↗Mateusz Modrzejewski↗

arXiv:2606.14466v1 Announce Type: cross Abstract: This paper investigates the fragility of post-hoc explanation methods in audio deepfake detection. While previous work on explanation manipulation focused on images using standard $L_p$ metrics, we introduce a psychoacoustic framework that optimizes inaudible perturbations to decouple model attributions from final classifications. We evaluate this vulnerability across state-of-the-art architectures under strict prediction-preserving constraints. By evaluating the manipulation cost through domain-specific perceptual audio quality metrics alongside explanation alignment criteria, our framework demonstrates that an adversary can systematically distort automated explanation heatmaps while preserving the predicted deepfake label. Full code available at: https://github.com/cncPomper/Audio-XAI

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