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01.
arXiv (CS.AI) 2026-06-17

ParkingTransformer: LLM-Enhanced End-to-End Trajectory Planning for Autonomous Parking

arXiv:2606.17082v1 Announce Type: cross Abstract: End-to-end autonomous parking has emerged as a critical task within the realm of autonomous driving. However, existing methods suffer from black-box characteristics, lacking high-level semantic understanding and interpretability, which impedes the realization of seamless long-distance autonomous parking from the road to the target spot. To address these limitations, we propose ParkingTransformer, a novel framework that leverages multi-view perception and the scene understanding capability of Large Language Models (LLMs). By combining trajectory queries with LLMs implicit state features, our method interacts directly with historical information and raw sensor data to output planning trajectories, eliminating the need for dense Bird's-View (BEV) representations. To compensate for the inadequate spatial reasoning ability of LLMs, we introduce 3D positional encoding to explicitly inject spatial geometric awareness. Furthermore, a fixed-window streaming mechanism is designed for historical information processing, significantly improving long-term temporal processing efficiency and inference speed. Additionally, a coarse-to-fine decoding strategy is employed to progressively enhance trajectory precision. Extensive closed-loop experiments are conducted on the CARLA simulator and real-world vehicle platforms. The results demonstrate that our method achieves a driving score of 61.32 in CARLA simulator and an average success rate of 88.70% in real-world experiments, validating the feasibility and effectiveness of the proposed algorithms.

02.
arXiv (CS.CL) 2026-06-11

Beyond Fully Random Masking: Attention-Guided Denoising and Optimization for Diffusion Language Models

Diffusion large language models (dLLMs) offer an efficient alternative to autoregressive models through parallel decoding, yet existing post-training methods largely rely on random masking strategies that overlook intrinsic token dependencies. In this work, we present an empirical analysis of attention in dLLMs and show that tokens attending more strongly to unmasked context exhibit greater generation stability and play a critical role in reasoning. Motivated by these findings, we propose AGDO, an attention-guided denoising and optimization framework that aligns both training and optimization with attention-derived dependencies. AGDO determines the denoising order based on attention structure and emphasizes attention-critical tokens during supervised fine-tuning and reinforcement learning. Experiments on mathematical and coding benchmarks demonstrate that AGDO consistently improves reasoning performance, outperforming state-of-the-art post-training methods for dLLMs.

03.
arXiv (CS.CV) 2026-06-19

SSD: Spatially Speculative Decoding Accelerates Autoregressive Image Generation

Autoregressive models excel in visual generation by treating images as 1D sequences of discrete tokens, mirroring language modeling. However, this flattening discards the intrinsic 2D spatial locality of visual signals, creating severe computational bottlenecks during inference. We introduce Spatially Speculative Decoding (SSD), a framework that aligns the predictive objective with the natural geometry of images. Rather than predicting only the immediate next token in a 1D sequence, our model simultaneously predicts the adjacent horizontal token and the token directly below it. By capitalizing on this 2D spatial correlation, spatially speculative decoding overcomes the memory wall in visual inference. Our approach accelerates autoregressive image generation by up to 13.3x while maintaining high fidelity on DPG-Bench and GenEval. Our results suggest that respecting the underlying geometry of vision unlocks massive computational efficiencies, paving the way for real-time, high-resolution autoregressive generative models.

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

A Comparative Study of Graph Neural Network Layer Selection for Interaction Modelling in Driving Trajectory Prediction

arXiv:2606.14956v1 Announce Type: new Abstract: Autonomous driving systems rely on precise trajectory prediction to plan safe and efficient movement. Graph Neural Networks (GNNs) have become a promising approach for modelling spatiotemporal interactions among road agents. However, designing GNN architectures for trajectory prediction remains non-standardized, with little guidance on which graph layers effectively capture spatial interactions and temporal dynamics. This paper offers a detailed comparative study of 19 graph layer types, focusing on their spatial and temporal processing capabilities to discover the most effective architectures for trajectory prediction. Within the explored hyperparameter setting, we highlight five standout layer combinations, with ARMA, Chebyshev, and topology-aware layers consistently performing better than others. Beyond performance metrics, our findings yield practical design principles: sum-based aggregation is more effective than mean-based methods, multi-head attention mechanisms enable richer interactions, and assigning different weights to different hop distances significantly improves prediction accuracy. These findings offer useful guidance for designing more interpretable and effective trajectory prediction models.

05.
arXiv (CS.LG) 2026-06-17

QueryMarket: Cost-Aware Online Active Learning in Data Markets

arXiv:2606.17805v1 Announce Type: new Abstract: Data acquisition is a major bottleneck for learning in real-time streams: analysts must decide on the fly which labels to purchase while respecting a rolling budget. However, existing online active learning rarely unifies pricing, information gain, and rolling budget constraints under concept drift. We introduce QueryMarket, a market-inspired framework that queries each incoming data point based on its estimated utility to the model and its price. Within this framework, we propose OVBAL (online variance-based active learning), which integrates data pricing with information-driven selection by estimating each sample's marginal utility via a D-optimality criterion with exponential forgetting and executing cost-aware purchases under rolling budget constraints. OVBAL yields a simple, fully online decision rule that adapts to nonstationary streams and heterogeneous label costs. Experiments on synthetic data and a real-world solar power generation forecasting task show that OVBAL is particularly effective under seller-centric pricing and yields a more favorable long-run error-cost trade-off in the real-world task under both pricing schemes.

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

An XAI View on Explainable ASP: Methods, Systems, and Perspectives

arXiv:2601.14764v2 Announce Type: replace Abstract: Answer Set Programming (ASP) is a popular declarative reasoning and problem solving approach in symbolic AI. Its rule-based formalism makes it inherently attractive for explainable and interpretive reasoning, which is gaining importance with the surge of Explainable AI (XAI). A number of explanation approaches and tools for ASP have been developed, which often tackle specific explanatory settings and may not cover all scenarios that ASP users encounter. In this survey, we provide, guided by an XAI perspective, an overview of types of ASP explanations in connection with user questions for explanation, and describe their coverage by current theory and tools. Furthermore, we pinpoint gaps in existing ASP explanations approaches and identify research directions for future work.

07.
arXiv (CS.CL) 2026-06-12

Rigel: Reverse-Engineering the Metal 4.1 Tensor Compute Path on the Apple M4 Max GPU

Apple's Metal 4.1 exposes a tensor compute path: the Metal Performance Primitives (MPP) matmul2d operation over cooperative_tensor fragments, whose interface is documented but whose hardware behavior is deliberately hidden. The specification states which data-type rows are supported, never whether they are hardware-accelerated, where the operation physically executes, what its accumulator width is, or how it partitions matrix fragments across threads. We present Rigel, an empirical characterization of this path on a single Apple M4 Max (a pre-neural-accelerator generation). Using a checksum-gated, provenance-tracked microbenchmark harness, Rigel recovers eleven facts the v4.1 specification hides or contradicts. The headline finding: the Metal 4.1 fp8 (E4M3) matmul2d is emulated, not accelerated: it sustains 0.94x the throughput of fp16 despite reading half the operand bytes, so on M4 it is a memory-footprint feature, not a performance feature. We further show, via a three-signal triangulation (throughput ceiling, comparison against simdgroup_matrix, and per-rail power attribution), that matmul2d executes entirely on the GPU shader cores with no dedicated matrix datapath and no evidence of Apple Neural Engine routing; that it accumulates in >=fp32; and we reconstruct the opaque 8x8 cooperative_tensor fragment layout Apple documents nowhere. Acting on the characterization, a hand-fused GEMM + bias + GELU kernel beats the decomposed path by +6.5-12.9% in the cache-resident regime. All findings are reproducible from committed MIT-licensed code and per-cell CSVs.

08.
arXiv (CS.CV) 2026-06-12

Augmentation techniques for video surveillance in the visible and thermal spectral range

In intelligent video surveillance, cameras record image sequences during day and night. Commonly, this demands different sensors. To achieve a better performance it is not unusual to combine them. We focus on the case that a long-wave infrared camera records continuously and in addition to this, another camera records in the visible spectral range during daytime and an intelligent algorithm supervises the picked up imagery. More accurate, our task is multispectral CNN-based object detection. At first glance, images originating from the visible spectral range differ between thermal infrared ones in the presence of color and distinct texture information on the one hand and in not containing information about thermal radiation that emits from objects on the other hand. Although color can provide valuable information for classification tasks, effects such as varying illumination and specialties of different sensors still represent significant problems. Anyway, obtaining sufficient and practical thermal infrared datasets for training a deep neural network poses still a challenge. That is the reason why training with the help of data from the visible spectral range could be advantageous, particularly if the data, which has to be evaluated contains both visible and infrared data. However, there is no clear evidence of how strongly variations in thermal radiation, shape, or color information influence classification accuracy. To gain deeper insight into how Convolutional Neural Networks make decisions and what they learn from different sensor input data, we investigate the suitability and robustness of different augmentation techniques...

09.
arXiv (quant-ph) 2026-06-12

Characterizing the functional role of quantum coherence in energy transfer

arXiv:2606.13404v1 Announce Type: new Abstract: Quantum coherence is understood to play a role in excitation energy transfer in open quantum systems, yet a quantitative approach to assessing its influence on the transfer process is still missing. Using Nakajima-Zwanzig projection operators, we derive a general memory kernel identity that enables us to characterize and quantify the impact of coherence in the eigenenergy basis on a generalized rate of energy transfer. Applying our approach to the electronic dynamics of a dimer coupled to a structured phonon bath, we demonstrate how quantum coherence acts to modulate energy transfer.

10.
arXiv (quant-ph) 2026-06-25

A Short Note on the Generators of Controlled Quantum Gates

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.

11.
arXiv (math.PR) 2026-06-24

A parameterized family of balance indices for phylogenetic networks

arXiv:2606.24562v1 Announce Type: cross Abstract: We introduce a new family of balance indices for phylogenetic networks: the $H_\alpha$ indices, where $\alpha$ is a positive real number. This family includes the $B_2$ index as a special case ($\alpha = 1$) and provides a natural extension of the Sackin index to phylogenetic networks. We show that the $H_\alpha$ indices share many structural properties with the $B_2$ index, most notably a "grafting property" that makes it possible to express the $H_\alpha$ index of a network in terms of the $H_\alpha$ indices of its biconnected components. These properties allow us to identify networks that minimize / maximize $H_\alpha$ for various classes of phylogenetic networks, and to study its distribution for several models of random trees and networks (in particular, Galton-Watson trees and binary Markov branching trees, with a focus on the Yule and PDA models). Finally, we show how local limits can be used to analyze the asymptotic behavior of $H_\alpha$ for large trees and networks, and we obtain general results for the moments of $H_\alpha$ for a broad class of random phylogenetic networks known as blowups of Galton-Watson trees.

12.
arXiv (CS.LG) 2026-06-15

Muon$^p$: Muon with Fractional Spectral Powers

arXiv:2606.13867v1 Announce Type: new Abstract: Muon is an increasingly widely used optimizer that replaces a gradient $G=USV^\top$ with its polar factor $UV^\top$, thereby flattening the singular spectrum. However, full flattening discards singular-value information that may matter for adaptation. We introduce Muon$^p$, a Muon-style optimizer that instead uses fractional spectral-power updates $US^pV^\top$ for rational $p\in(0,1)$, interpolating between Muon and gradient descent. To make it practical, we prove that fractional spectral powers cannot be computed by any fixed univariate polynomial iteration, and furthermore derive low-degree odd bivariate recurrences that approximate $US^pV^\top$ using only matrix multiplications, preserving Muon's matrix-multiplication-only structure and compute complexity. We show that Muon$^p$ maximizes the linear improvement in loss under the Schatten $q$-norm for $q=1+\frac{1}{p}$. Empirically, Muon$^p$ is especially effective for finetuning: on billion-scale models, Muon$^p$ improves validation perplexity and downstream task performance. We further analyze when Muon$^p$ is less suitable, through the lens of spectral geometry. Our results reveal important insights on when preserving the singular spectrum can bring significant gains, and introduce a principled way to achieve them.

13.
PLOS Computational Biology 2026-06-01

Challenges and progress in RNA velocity: Comparative analysis across multiple biological contexts

by Sarah Ancheta, Leah Dorman, Guillaume Le Treut, Abel Gurung, Greg Huber, Loïc A. Royer, Alejandro Granados, Merlin Lange Single-cell RNA sequencing is revolutionizing our understanding of cell state dynamics, allowing researchers to capture and quantify the transcriptomic profile of a single cell at a specific timepoint. Among the computational techniques used to predict cellular trajectories, RNA velocity has emerged as a predominant tool for modeling transcriptional dynamics. RNA velocity leverages the mRNA maturation process to generate velocity vectors that predict the likely future state of a cell, offering insights into cellular differentiation, aging, and disease progression. Although this technique has shown promise across biological fields, the performance accuracy varies depending on the RNA velocity method and dataset. We established a comparative pipeline and analyzed the performance of five RNA velocity methods on three datasets based on local consistency, method agreement, identification of driver genes, and robustness to sequencing depth. This benchmark provides a resource for scientists to understand the strengths and limitations of different RNA velocity methods.

14.
arXiv (CS.CL) 2026-06-25

Scale or Reason? A Compute-Equivalent Analysis of Reasoning Distillation

Distilling reasoning traces from strong teacher models has become the standard recipe for building capable small language models. Yet reasoning traces are 5-20$\times$ longer than standard instruction fine-tuning (IFT) outputs, meaning every practitioner who chooses reasoning distillation implicitly forgoes training a larger IFT model on the same compute budget. Whether this trade-off is worthwhile remains unaddressed. We study it with a controlled experiment: a single teacher generates paired IFT and reasoning outputs for identical prompts by toggling only its reasoning mode, isolating supervision format as the sole variable. Training students at five scales (0.5B to 14B) and evaluating on 18 benchmarks, we find that at matched FLOPs, IFT lies on or near the Pareto frontier across the majority of configurations. Reasoning reaches the Pareto frontier only on open-ended tasks at 7B and above. Even there, a sequential curriculum mixing just 25-50\% reasoning data with IFT captures most of the accuracy benefit at far lower compute cost.

15.
arXiv (CS.LG) 2026-06-24

FAIRVAR: Fair Federated Learning via Variance Regularization

arXiv:2508.12042v3 Announce Type: replace Abstract: Federated learning (FL) allows collaborative training of machine learning models across multiple parties without sharing raw data. However, heterogeneous data can cause some clients to have disproportionate influence on the global model, leading to disparities in their performance. Fairness, understood as reducing these disparities, is therefore a crucial concern in FL and has been addressed in various ways. We studied performance equitable fairness in FL, where the goal is to minimize performance disparities across clients. We evaluated several existing fairness-aware methods and introduce here a new gradient-variance-regularized method, implemented in two variants: FairGrad (approximate) and FairGrad* (exact). We theoretically characterize the connections between these methods and, empirically, on heterogeneous benchmarks, show that FairGrad and FairGrad* consistently improve fairness by reducing variance in client accuracies, while maintaining competitive or improved mean performance compared to existing fairness-aware baselines.

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

Quantifying and detecting quantum-state texture

arXiv:2604.07257v2 Announce Type: replace Abstract: Quantum-state texture is a recently proposed quantum resource that characterizes the inhomogeneity of a quantum state's matrix element distribution in the computational basis, enriching our understanding of quantum state structure. To expand its quantification toolkit and establish detection methods, in this article, we investigate the resource theory of texture from both quantitative and detection perspectives. First, we construct a texture measure $\mathcal{T}^{GR}_{\alpha,z}(\rho)$ based on the $\alpha$-$z$ Rényi relative entropy and present some of its inherent properties. Second, we analyze the mathematical relationships between several existing texture measures, revealing connections among different quantifiers. Finally, drawing on the witness concept from other resource theories, we systematically introduce texture witnesses into the texture theory and provide examples of texture witnesses with special properties.

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

SAERec: Constructing Fine-grained Interpretable Intents Priors via Sparse Autoencoders for Recommendation

arXiv:2606.18897v1 Announce Type: cross Abstract: Intent-based recommender systems have gained significant attention for improving accuracy and interpretability by modeling the underlying motivations behind user behaviors. Most existing models derive intents directly from user sequences via clustering or prototype learning. However, they are sensitive to sequence quality, require presetting the number of intents, and lack explicit semantic grounding. These issues lead to an incomplete and coarse intent set and limit the effectiveness of recommendation. In this paper, we propose the Sparse Autoencoder for intent-based recommendation (SAERec), a novel recommender that automatically constructs a fine-grained and interpretable intent space from a textual corpus to guide recommendation. Rather than treating texts as side signals, SAERec leverages them as high information density evidence for intent construction. Specifically, we first extract a comprehensive set of fine-grained interpretable intents from the latent space of large language models (LLMs) by using a sparse autoencoder (SAE) to disentangle and interpret text embeddings, which isolates intent-related semantics from textual noise. Then, for each user, we retrieve relevant intents from this set as priors to guide recommendation. It contains personal intents matching a user's current interests and public intents capturing general item patterns shared across users (e.g., quality, price). Finally, to integrate retrieved intents into sequence modeling, we propose a multi-branch attention mechanism that captures temporal dependencies and injects both personal and public intent signals, followed by an adaptive fusion layer to construct the final user representation for recommendation. Extensive experiments on public datasets demonstrate the superiority of SAERec, consistently outperforming state-of-the-art baselines while providing human-understandable explanations.

18.
arXiv (quant-ph) 2026-06-11

On the Addressability Problem on CSS Codes

arXiv:2502.13889v4 Announce Type: replace Abstract: Recent discoveries in asymptotically good quantum codes have intensified research on their application in quantum computation and fault-tolerant operations. This study focuses on the addressability problem within CSS codes: we ask what circuits might implement logical gates on strict subsets of logical qubits. With some notion of fault-tolerance, we prove several impossibility results: for CSS codes with non-zero rate, one cannot address a logical $H$, $HS$, $SH$, or $\mathsf{CNOT}$ to any non-empty strict subset of logical qubits using a circuit made only from 1-local Clifford gates. Furthermore, we show that one cannot permute the logical qubits in a code purely by permuting the physical qubits, if the rate of the code is (asymptotically) greater than 1/3 and the distance is at least 3. We can show a similar no-go result for $\mathsf{CNOT}$s and $\mathsf{CZ}$s between two such high-rate codes, albeit under a more restrictive assumption on the circuit, which we call "global" (though recent addressable CCZ gates use global circuits). This work pioneers the study of distance-preserving addressability in quantum codes, mainly by considering automorphisms of the code. This perspective offers new insights and potential directions for future research. We argue that studying this trade off between addressability and efficiency of the codes is essential to understand better how to do efficient quantum computation.

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

Cross-Modal Benchmarking for Robotic Perception in Natural Environments

Natural environments present a complex challenge to robotics perception systems. Current models, particularly vision foundation models, are largely trained on structured, urban environments leading to weaknesses in their perception for field robotics tasks. We showcase the limitations of current models using our recently released WildCross benchmark, a new cross-modal benchmark for place recognition and metric depth estimation in large-scale natural environments. WildCross comprises over 476K sequential RGB frames with semi-dense depth and surface normal annotations, each aligned with accurate 6DoF pose and synchronized dense lidar submaps. In this work, we provide an expanded analysis of the benchmark results from the recent WildCross benchmark, with particular emphasis on expanded metric depth estimation experiments. Access to the code repository and dataset for this work can be found at https://csiro-robotics.github.io/WildCross.

20.
arXiv (CS.LG) 2026-06-16

Federated Foundation Language Model Post-Training Should Focus on Open-Source Models

arXiv:2505.23593v4 Announce Type: replace Abstract: Post-training of foundation language models has emerged as a promising research domain in federated learning (FL) with the goal to enable privacy-preserving model improvements and adaptations to user's downstream tasks. Recent advances in this area adopt centralized post-training approaches that build upon black-box foundation language models where there is no access to model weights and architecture details. Although the use of black-box models has been successful in centralized post-training, their blind replication in FL raises several concerns. Our opinion is that using black-box models in FL contradicts the core principles of federation such as data privacy and autonomy. In this paper, we critically analyze the usage of black-box models in federated post-training, and provide a detailed account of various aspects of openness and their implications for FL.

21.
arXiv (CS.AI) 2026-06-16

S-SPPO: Semantic-Calibrated Self-Play Preference Optimization

arXiv:2606.01561v2 Announce Type: replace Abstract: Aligning Large Language Models (LLMs) with human preferences is often formulated via Direct Preference Optimization (DPO). However, the standard Bradley-Terry instantiation of DPO is limited in modeling common departures from transitivity in human preferences. To address this, recent work has introduced Self-Play Preference Optimization (SPPO), which iteratively refines the policy by training on self-generated win-lose pairs. Our investigation, however, reveals a critical instability in SPPO: the optimization is prone to policy degeneration when the preference oracle assigns overly confident wins to semantically indistinguishable responses. To mitigate this, we propose S-SPPO, a dual-space semantic calibration framework comprising: i) Supervision Calibration via semantic gating, which anneals win rate targets toward the maximum-entropy baseline as semantic overlap increases; and ii) Representation Calibration via latent repulsion to enforce geometric diversity to prevent manifold collapse and maintain latent diversity between chosen and rejected samples. Theoretically, we show that the calibration preserves the constant-sum game structure, facilitating convergence to a Nash Equilibrium. Empirically, S-SPPO avoids the performance degradation seen in prior methods, achieving 52.19% win rate and 47.46% length-controlled win rate on AlpacaEval 2.0 with Llama-3-8B, without using additional human-annotated preferences during training. The code will be available at https://github.com/xiwenc1/s-sppo.

22.
arXiv (CS.LG) 2026-06-16

Structured Nonparametric Variational Inference for Dependent Latent Modeling

arXiv:2606.15458v1 Announce Type: cross Abstract: Variational inference (VI) is a core engine of modern AI, enabling scalable approximate Bayesian learning and uncertainty-aware training of large probabilistic and generative models. In this paper, we propose Structured Nonparametric Variational Inference (SN-VI), a novel framework for modeling complex dependencies among latent variables in posterior approximation, leveraging multivariate spline techniques. Unlike traditional methods that rely on the mean-field assumption, SN-VI preserves intricate latent variable dependencies, providing a flexible and accurate approximation of posteriors with arbitrary shapes. We establish rigorous theoretical guarantees, including the derivation of the lower bound for the variational objective and proof of asymptotic consistency in posterior estimation. To facilitate practical implementation, we develop an algorithm that automatically identifies dependent latent variables and their underlying dependence structure, without requiring manual specification. Simulation studies validate the effectiveness of SN-VI in approximating posterior distributions with bounded support and complex dependencies. The proposed method has been successfully applied to high-dimensional structured data, including computer vision datasets and spatial transcriptomics. In these applications, SN-VI demonstrates improved generative model performance and effectively uncovers coupled biological signals through the learned dependency structure.

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

Adaptive Identification and Modeling of Clinical Pathways with Process Mining

arXiv:2512.03787v2 Announce Type: replace Abstract: Clinical pathways are specialized healthcare plans that model patient treatment procedures. They are developed to provide criteria-based progression and standardize patient treatment, thereby improving care, reducing resource use, and accelerating patient recovery. However, manual modeling of these pathways based on clinical guidelines and domain expertise is difficult and may not reflect the actual best practices for different variations or combinations of diseases. We propose a two-phase modeling method using process mining, which extends the knowledge base of clinical pathways by leveraging conformance checking diagnostics. In the first phase, historical data of a given disease is collected to capture treatment in the form of a process model. In the second phase, new data is compared against the reference model to verify conformance. Based on the conformance checking results, the knowledge base can be expanded with more specific models tailored to new variants or disease combinations. We demonstrate our approach using Synthea, a benchmark dataset simulating patient treatments for SARS-CoV-2 infections with varying COVID-19 complications. The results show that our method enables expanding the knowledge base of clinical pathways with sufficient precision, peaking to 95.62% AUC while maintaining an arc-degree simplicity of 67.11%.

24.
medRxiv (Medicine) 2026-06-24

Cognitive-emotional responses to ultrasonic neuromodulation of anterior cingulate cortex

The anterior cingulate cortex (ACC) is a key brain center involved in cognitive and emotional processing that is implicated in a variety of neuropsychiatric disorders including chronic pain and depression. Circuit-targeted diagnosis and treatment of these disorders will require the capacity to precisely modulate ACC subregions. Toward that end, we recently developed and validated a novel low-intensity transcranial focused ultrasound device that can noninvasively and directly modulate ACC subdivisions in humans with millimeter precision. Here we describe the subjective reports of 36 individuals diagnosed with either chronic pain or major depression who received repeated brief stimulation trials (807 active, 797 sham; duration 30s-3min) spanning the dorsoventral extent of the ACC. Sonication immediately altered cognitive-emotional states (odds ratio 5.6, active versus sham), eliciting a positive-valence experience more often than negative (29% versus 8%) in both diagnostic groups. Sham-adjusted response rate varied across ACC targets, with the largest effects (Cohen's d ~ 0.8) observed in pregenual and subgenual ACC in subjects with chronic pain and depression, respectively. These rapid trial-by-trial responses to ACC stimulation predicted subsequent improvements in pain and depression severity at 24 hours. Collectively, these findings reveal that transcranial ultrasound can robustly evoke immediate, target-specific, clinically meaningful changes in cognitive-emotional state, demonstrating the potential of ultrasonic neuromodulation as a tool for individualized probing of circuit function and dysfunction.

25.
bioRxiv (Bioinfo) 2026-06-24

An atlas-scale generative model for unified representation learning of bulk RNA-seq data

Public bulk RNA-seq repositories contain hundreds of thousands of samples, creating opportunities for large-scale representation learning, but integration across studies remains challenging because of heterogeneous annotations, experimental protocols, and technical variation. While pre-trained foundation models are now widely available for single-cell RNA-seq, comparable resources for bulk RNA-seq remain scarce, motivating a model that learns a unified, tissue-aware representation directly from bulk data. We trained a supervised variational autoencoder (VAE) on a compendium of 118,263 bulk RNA-seq samples that we assembled from TCGA, GTEx, and ARCHS4 and mapped to 42 tissue categories. The model classifies tissue of origin at 94.9% balanced accuracy (weighted F1 96.2%) and compresses 16,115 genes into a 121-dimensional latent space. Tissue identity is the primary organizing axis of the latent space, while source effects remain secondary. To assess the impact of data volume, we constructed training sets at three different scales (38K, 75K, and 118K samples). Our results demonstrated that reconstruction fidelity improved incrementally with each expansion of the dataset, but with diminishing returns. We validated the model on an independent cohort of 734 paediatric tumour samples from TARGET, achieving 84.6% agreement with the expected tissue of origin. The trained model and code are available at GitHub (https://github.com/BIMSBbioinfo/flexynesis_tissue_vae_manuscript) with an interactive web application.