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

Low-Latency Real-Time Audio Game Commentary System via LLM-Based Parallel Text Generation

We present a low-latency real-time audio game commentary system that generates spoken commentary directly from live gameplay video. In this end-to-end setting, a key bottleneck is accumulated waiting time; conventional pipelines capture frames, generate text, and synthesize speech sequentially for each utterance, and do not request the next generation until speech playback has completed. This strict sequentiality causes long and unnatural silence between utterances. To address this latency bottleneck, our system runs text generation in parallel with speech playback and buffers multiple candidate utterances ahead of time, enabling immediate synthesis at playback boundaries. Experiments on fast-paced game videos show that our parallel design reduces the mean inter-utterance silence from 9.6 seconds to 0.3 seconds compared to sequential baselines. It also improves similarity to professional speaking–silence timing patterns by over 40 %, and a user study with 120 experienced game players confirms significantly improved perceived speaking rhythm. Our demo video is available at: https://youtu.be/pmrRUlvav8M.

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

Tacit Coordination of Large Language Models

arXiv:2601.22184v2 Announce Type: replace-cross Abstract: Large Language Models (LLMs) are increasingly deployed in multi-agent settings that require coordination without communication, from human-AI interaction to safety-critical scenarios. Humans often overcome the absence of communication through focal points: salient solutions that naturally stand out to all participants. We present the first large-scale evaluation of how, when, and why focal points emerge in LLMs, comparing their behaviour with humans across cooperative and competitive games, including realistic search and rescue scenarios, demonstrating when focal points enable effective coordination. Across more than 20 open- and closed-source models, we find that LLMs exhibit a remarkable ability to coordinate without communication, often matching or outperforming humans. However, the same models consistently fail in tasks requiring numerical common sense or culturally nuanced notions of salience. We additionally evaluate simple learning-free strategies that substantially improve coordination both among LLMs and between humans and LLMs. Our results reveal striking coordination capabilities, as well as social limitations in modern LLMs, and offer new insight into the latent notions of salience encoded within them. Our findings caution against assuming that LLMs share humans' cultural and perceptual substrate when deployed in coordination settings.

03.
bioRxiv (Bioinfo) 2026-06-16

Phylogenetic tree inference using generative models

Accurate inference of phylogenetic trees is fundamental to evolutionary biology, yet existing methods rely on complex pipelines involving multiple sequence alignment, explicit evolutionary models, and computationally intensive tree search procedures. Here, we present BetaInfer, a generative framework that reformulates phylogenetic tree inference as a sequence transduction problem. BetaInfer leverages hybrid transformer-based architectures to directly map sets of unaligned sequences to phylogenetic trees represented in Newick format. Trained on large-scale simulated evolutionary data with known ground truth, BetaInfer learns to capture complex evolutionary signals directly from sequence data. Ensemble-based generation of multiple candidate trees further improves robustness, reducing reconstruction error by over 30% relative to single predictions. Across extensive evaluations on both simulated and empirical datasets, BetaInfer achieves competitive performance relative to state-of-the-art phylogenetic pipelines, matching, and in some cases exceeding, the accuracy of established likelihood-based and distance-based methods under a wide range of conditions. Interpretability analyses reveal that BetaInfer leverages internal pairwise-distance computations to synthesize evolutionary relationships into an integrated, global representation that supports direct tree generation. Together, these results demonstrate that generative models can serve as a viable and scalable alternative to standard phylogenetic pipelines.

04.
medRxiv (Medicine) 2026-06-12

Genome-wide association and multi-omics functional screens reveal the genetic architecture of foveal development

Foveal hypoplasia causes visual impairment across congenital eye disorders, yet the genetic programmes governing foveal development remain poorly characterised and no tractable model exists for foveal disease. In the first genome-wide association study of foveal hypoplasia, we identified 42 sentinel variants mapping to 54 effector genes supported by >= 2 criteria from a variant-to-gene framework incorporating developmental multi-omics. Disruption of six effector genes using mutant lines and CRISPR knockouts in the zebrafish high acuity zone recapitulates structural, functional, and ultrastructural hallmarks of foveal hypoplasia, establishing the first vertebrate disease model. Integration with human foetal single-cell and spatial transcriptomics reveals two temporal waves of effector gene expression and identifies Muller glia as critical mediators of foveal patterning. Phenome-wide analyses reveal foveal variants are pleiotropic with refractive, lenticular, and metabolic traits, connecting foveal development to anterior segment and systemic disease biology. These findings should inform mechanistic studies of macular disease.

05.
bioRxiv (Bioinfo) 2026-06-18

fuzzyfold: a high-performance framework for stochastic RNA folding kinetics

作者:

The analysis of nucleic acid secondary structures is overwhelmingly dominated by methods that analyze the thermodynamic equilibrium distribution and which ignore all dynamic aspects of nucleic acid folding. Yet, there are numerous popular examples of nucleic acid folding that rely on kinetic models, such as RNA riboswitches or DNA strand displacement systems. Here, I am presenting fuzzyfold, a Rust-based software package for nucleic acid secondary structure analysis with an explicit focus on stochastic modeling. The framework introduces three-way and four-way shift moves with a biophysically motivated rate-model parameterization, and it is developed with an emphasis on both model flexibility and performance, e.g. allowing for the generation of single co-transcriptional trajectories for thousand-nucleotide long RNA molecules in just a few minutes. The main strength of the fuzzyfold package, however, is its focus on user and developer interfaces for long-term development. It provides easily installable command-line interfaces, e.g. for aggregating data from multiple parallel trajectories efficiently into an ensemble-level dynamic analysis. For developers, the code-base supports straight-forward substitution of thermodynamic and kinetic free-energy models, and a flexible library interface with Python bindings, enabling integration of individual components into custom computational workflows.

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

Efficient, Robust, and Anti-Collusion Fingerprinting of Image Diffusion Models

Model fingerprinting, embedding user-specific identifiers (fingerprints) into generated outputs, has recently emerged as a popular solution to protect the intellectual property rights (IPR) of generative text-to-image (T2I) models and prevent unauthorized redistribution. In this work, we reveal a previously unexplored systematic vulnerability in existing generative model fingerprinting methods: they lack robustness against collusion attacks, where multiple attackers combine their models to remove or obscure the fingerprints. To address this issue, we take the first step towards a robust fingerprinting method for T2I models with anti-collusion capabilities. The proposed method encodes strings of bits, namely fingerprints, into the coefficients of a personalized normalization module (PNM) incorporated into T2I models, so that fingerprints can be reliably recovered from any generated image. To defend against collusion attacks and prevent unauthorized model redistribution, we introduce an anti-collusion mechanism based on lossless function-invariant parameter transformations. This mechanism significantly degrades the image generation quality of colluded models, making them effectively unusable. Moreover, our method allows developers to efficiently create multiple copies of fingerprinted T2I models by reparameterizing the PNM without the need for retraining. We also introduce a worst-case optimization strategy to improve robustness against model-level attacks. Our experiments demonstrate that the proposed method achieves high fidelity and robustness across multiple T2I image generation and editing tasks, with fingerprint extraction accuracy exceeding 99.5%. Compared with existing methods, our method demonstrates, for the first time, a notable proactive robustness to collusion attacks by significantly increasing the FID of colluded models.

07.
arXiv (CS.LG) 2026-06-18

Clustering and Pruning in Causal Data Fusion

arXiv:2505.15215v3 Announce Type: replace-cross Abstract: Data fusion, the process of combining observational and experimental data, can enable the identification of causal effects that would otherwise remain non-identifiable. Although identification algorithms have been developed for specific scenarios, do-calculus remains the only general-purpose tool for causal data fusion, particularly when variables are present in some data sources but not others. However, approaches based on do-calculus may encounter computational challenges as the number of variables increases and the causal graph grows in complexity. Consequently, there exists a need to reduce the size of such models while preserving the essential features. For this purpose, we propose pruning (removing unnecessary variables) and clustering (combining variables) as preprocessing operations for causal data fusion. We generalize earlier results on a single data source and derive conditions for applying pruning and clustering in the case of multiple data sources. We give sufficient conditions for inferring the identifiability or non-identifiability of a causal effect in a larger graph based on a smaller graph and show how to obtain the corresponding identifying functional for identifiable causal effects. Examples from epidemiology and social science demonstrate the use of the results.

08.
arXiv (CS.AI) 2026-06-11

Geometric Erasure by Contrastive Velocity Matching in Rectified Flows

arXiv:2606.00140v2 Announce Type: replace-cross Abstract: While the rapid adoption of multimodal generative models offers immense potential, it has also increased the risks of harmful content synthesis, deepfakes, and copyright infringements. To address these challenges, concept erasure has emerged as a prospective safeguard. However, as the field gradually transitions from U-Net-based diffusion models to Rectified Flow Transformers, erasure research has struggled to keep pace. In this work, we introduce GEM, a simple but highly effective erasure framework for Rectified Flow models. As part of our contribution, we establish a principled bridge between trajectory-based unlearning grounded in Generative Flow Networks and classic teacher-guided erasure: we translate trajectory-based signals into a teacher-guided flow-matching setup that unifies the strengths of both paradigms. Concretely, a teacher provides complementary attraction and repulsion signals that we combine into a single geometric guidance objective, yielding targeted suppression of unwanted concepts while preserving benign generation.

09.
arXiv (CS.CL) 2026-06-17

Toward Accessible Psychotherapy Training Using AI-Driven Interactive Patient Avatars

Training psychotherapists in evidence-based interventions such as Acceptance and Commitment Therapy (ACT) requires repeated practice with meaningful feedback, yet opportunities for safe, standardized training are limited by ethical, logistical, and resource constraints. We introduce a system designed to support ACT-oriented psychotherapy training through spoken dialogue with an embodied virtual patient. The system uses large language models to simulate patient behavior conditioned on profiles derived from real therapy sessions and configurable clinical scenarios, while a separate automated evaluator provides turn-by-turn feedback on therapist responses based on established ACT fidelity criteria. Rather than aiming to replace supervision, the system is intended to support deliberate practice by enabling experimentation, reflection, and immediate feedback in low-risk settings. Expert evaluation with practicing psychologists confirmed high realism in patient behavior and demonstrated that immediate turn-by-turn ACT feedback increased therapists' awareness of intervention choices and enabled effective experimentation with alternative responses. Quantitative evaluation across 49 therapy transcripts identified GPT-4o-mini as the optimal feedback model, achieving the lowest mean absolute error (MAE = 6.12) in replicating human supervisor ACT fidelity ratings with statistically significant agreement. This work demonstrates the potential of fidelity-aware simulated patients as a scalable complement to psychotherapy training.

10.
arXiv (quant-ph) 2026-06-16

What does measuring one qubit reveal about another? $K$-networks as a directed diagnostic for quantum circuits

arXiv:2606.16549v1 Announce Type: new Abstract: Many-qubit circuit states are hard to inspect directly, so they are often summarized by pairwise graph weights. Common pairwise weights report symmetric correlations, while many circuit questions are directed and basis-specific: if qubit $i$ is measured in a given basis, how strongly does the outcome reshape the conditional state of qubit $j$? We define $K_{i\to j}$, a directed, basis-conditioned edge weight for this question. It is large when the two measurement outcomes occur with comparable probability and leave qubit $j$ in clearly different conditional states; it is zero when the source outcome is deterministic or the target states are indistinguishable. The scalar uses standard binary-ensemble distinguishability; the paper's contribution is to turn this conditional comparison into a directed network layer for circuit states. The resulting networks are computable from two-qubit reduced density matrices. They are diagnostic (not entanglement measures): for pure two-qubit states $K$ reduces to the tangle $C^2$ (squared concurrence)[WoottersConcurrence,CKWTangle], while separable mixed states can reach $K=1$. Examples on teleportation, Grover, QAOA, and random circuit families show the intended use: $K$-networks map feed-forward, phase, and interaction-graph structure that symmetric or computational-basis summaries can leave weak or absent.

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

Polyp-D2ATL: Deep Domain-Adaptive Transfer Learning for Colorectal Polyp Classification under Label Distribution Shift

Early and highly accurate prediction of colorectal polyps, as an important sign of one of the most dangerous types of cancer, will result in saving more lives. Despite the advancements in colorectal polyp classification, many challenges remain in obtaining an automated polyp prediction system that is able to diagnose the difficult-to-predict polyps accompanied by different features in real scenarios, where the model can handle imbalanced data, label distribution shift, and cross-modality generalization successfully. In this study, we propose Polyp-D2ATL, a novel framework accompanied by a specific training strategy, which mitigates these limitations and effectively predicts the different classes of polyps belonging to the NICE classification. Our extensive experiments on the PICCOLO validation and test sets demonstrate that the proposed Polyp-D2ATL significantly outperforms existing state-of-the-art models across various reliable metrics, achieving an accuracy of 82.38%, a Macro-F1 of 77.49%, and a specificity of 87.47% on the validation set, alongside consistent improvements on the held-out test set which demonstrates the generalization capacity and clinical applicability of the proposed approach.

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

AME: A Multi-Type Contributor Attribution Framework in Generative AI Markets

Generative AI enables value creation through multi-stage collaboration among heterogeneous contributors, including training data, base models, fine-tuning behaviors, and prompts. However, how to fairly allocate the data value remains largely unexplored. This paper formulates multi-stage generative AI value allocation as a new research problem and identifies three core challenges: heterogeneous data contribution valuation, data rights mapping, and trustworthy execution. We propose AME (Attribution-Mapping-Execution) framework, a unified framework that integrates data contribution valuation, data rights mapping, and trustworthy execution into a single workflow. Experimental results demonstrate that AME framework achieves data value allocation outcomes more consistent with human reference judgments while maintaining low-cost trustworthy execution. Our work provides an initial foundation for value assessment and revenue allocation in generative AI data markets.

13.
arXiv (math.PR) 2026-06-19

On creating convexity in high dimensions

arXiv:2502.10382v3 Announce Type: replace-cross Abstract: Given a subset $A$ of $\mathbb{R}^n$, we define \begin{align*} \mathrm{conv}_k(A) := \left\{ \lambda_1 s_1 + \cdots + \lambda_k s_k : \lambda_i \in [0,1], \sum_{i=1}^k \lambda_i = 1 , s_i \in A \right\} \end{align*} to be the set of vectors in $\mathbb{R}^n$ that can be written as a $k$-fold convex combination of vectors in $A$. Let $\gamma_n$ denote the standard Gaussian measure on $\mathbb{R}^n$. We show that for every $\varepsilon > 0$, there exists a subset $A$ of $\mathbb{R}^n$ with Gaussian measure $\gamma_n(A) \geq 1- \varepsilon$ such that for all $k = O_\varepsilon(\sqrt{\log \log(n)})$, $\mathrm{conv}_k(A)$ contains no convex set $K$ of Gaussian measure $\gamma_n(K) \geq \varepsilon$. This result acts as a complement to the recent affirmative resolution of Talagrand's convexity conjecture by Hua, Song, and Tudose, which states that a universal dilation of the threefold Minkowski sum $A+A+A$ of a large set $A$ guarantees a large convex subset. Our approach utilises concentration properties of random copulas and the application of optimal transport techniques to the empirical coordinate measures of vectors in high dimensions.

14.
medRxiv (Medicine) 2026-06-10

Towards the Virtual Amyotrophic Lateral Sclerosis Patient: Inferring Cortical Excitability through Whole-Brain Dynamical Modeling

Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem neurodegenerative disorder in which motor-neuron degeneration is accompanied by widespread alterations in cortical dynamics. Among its most reproducible neurophysiological signatures is cortical hyperexcitability, yet how this local excitability imbalance shapes distributed whole-brain activity remains poorly understood. Here, we combined source-reconstructed resting-state MEG data, tractography-informed whole-brain modeling, and simulation-based inference to investigate whether ALS-related alterations in large-scale brain dynamics can be mechanistically explained by changes in cortical excitability. First, we characterized empirical brain dynamics using complementary features spanning regional activity amplitude and variability, functional connectivity, and avalanche-based metrics. These analyses revealed significant alterations in ALS patients relative to healthy controls, as well as associations with clinical impairment and disease staging. To mechanistically interpret these changes, we employed a reduced Wong-Wang whole-brain model in which local recurrent excitation modulates emergent large-scale neural dynamics. Simulations showed that increasing excitability systematically reproduced the empirical dynamical signatures observed in ALS. We then applied a simulation-based inference framework to estimate latent excitability parameters directly from empirical observations. Whole-brain model inversion revealed increased excitability in ALS patients compared with controls. The recovered excitability parameter was associated with disease staging, supporting its clinical relevance as a model-derived descriptor of ALS progression. Finally, by extending the model to estimate frontal and non-frontal excitability separately, we found that ALS-related alterations were predominantly associated with increased frontal excitability, whereas non-frontal regions appeared comparatively less affected. The recovered parameters related to disease staging. Together, these findings provide a mechanistic framework linking altered large-scale brain dynamics in ALS to selective cortical hyperexcitability, explaining how local excitability changes can give rise to global network reorganization. More broadly, they show how computational model inversion can recover latent multiscale pathophysiological processes from empirical neural recordings, offering a non-perturbative alternative to complex experimental paradigms typically required to causally probe local-to-global mechanisms.

15.
arXiv (CS.LG) 2026-06-17

Maximin Relative Improvement: Fair Learning as a Bargaining Problem

arXiv:2602.04155v2 Announce Type: replace-cross Abstract: When deploying a single predictor across multiple subpopulations, we propose a fundamentally different approach: interpreting group fairness as a bargaining problem among subpopulations. This game-theoretic perspective reveals that existing robust optimization methods such as minimizing worst-group loss or regret correspond to classical bargaining solutions and embody different fairness principles. We propose relative improvement, the ratio of actual risk reduction to potential reduction from a baseline predictor, which recovers the Kalai-Smorodinsky solution. Unlike absolute-scale methods that may not be comparable when groups have different potential predictability, relative improvement provides axiomatic justification including scale invariance and individual monotonicity. We establish finite-sample convergence guarantees under mild conditions.

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

Pushing the Boundaries of Natural Reasoning: Interleaved Bonus from Formal-Logic Verification

arXiv:2601.22642v2 Announce Type: replace Abstract: Large Language Models (LLMs) show remarkable capabilities, yet their stochastic next-token prediction creates logical inconsistencies and reward hacking that formal symbolic systems avoid. To bridge this gap, we introduce a formal logic verification-guided framework that dynamically interleaves formal symbolic verification with the natural language generation process, providing real-time feedback to detect and rectify errors as they occur. Distinguished from previous neuro-symbolic methods limited by passive post-hoc validation, our approach actively penalizes intermediate fallacies during the reasoning chain. We operationalize this framework via a novel two-stage training pipeline that synergizes formal logic verification-guided supervised fine-tuning and policy optimization. Extensive evaluation on six benchmarks spanning mathematical, logical, and general reasoning demonstrates that our 7B and 14B models outperform state-of-the-art baselines by average margins of 10.4% and 14.2%, respectively. These results validate that formal verification can serve as a scalable mechanism to significantly push the performance boundaries of advanced LLM reasoning.

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

Towards Fast GNN Surrogates for CO2 Migration in Complex Geological Formations

arXiv:2606.17180v1 Announce Type: new Abstract: This chapter discusses how a data-driven machine learning approach can reproduce key aspects of the physical behavior of multiphase flows in complex geological formations. We propose an end-to-end graph neural surrogate tailored to CO$_2$ plume migration forecasting in geological storage. The method is evaluated on the SPE11A benchmark, a well-known industry test case designed to assess CO$_2$ storage scenarios and characterized by sharp gas-water interfaces, strong advective transport, and rapid convective mixing with fingering development. The benchmark is reformulated as a graph in which nodes represent computational cells and edges encode transmissibility-based interactions enriched with geometric attributes. Directional transport arising from grid geometry, permeability contrasts, and geological heterogeneity is captured through an anisotropic message-passing mechanism, where interaction weights are computed via geometry-conditioned edge embeddings, biasing message aggregation toward physically relevant transport directions. Temporal evolution is modeled in latent space using an autoregressive residual formulation trained with multi-step supervision. The proposed model produces competitive forecasts of gas saturation and liquid-phase density, which are key indicators for CO$_2$ storage monitoring, with cumulative errors that remain moderate over extended forecasting horizons.

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

DragMesh-2: Physically Plausible Dexterous Hand-Object Interaction with Articulated Objects

Dexterous interaction with articulated objects is important for household, assistive, and humanoid manipulation, where multi-finger hands can provide compliant contact patterns beyond parallel-jaw grasping. However, articulated-object manipulation differs from static-object manipulation: the target part cannot be directly actuated, and its motion must emerge through sustained physical hand–handle contact. This makes the transition from object-centric articulated generation to hand-driven dexterous hand–object interaction non-trivial, since geometric trajectory replay or open-loop execution does not model the contact dynamics required to move the articulated part. Moreover, policies trained only for task completion under fixed dynamics can overfit nominal contact loads, especially without tactile or force feedback, and may degrade when the contact load changes. To address these challenges, we present DragMesh-2, a contact-driven framework for dexterous interaction with articulated objects that extends articulated interaction from object-centric generation to hand-driven dexterous hand–object interaction, where articulated motion must arise through physical contact. We further propose PICA, a physically informed contact-aware training mechanism that injects physical signals into policy learning without tactile or force feedback, improving robustness and task success under changing contact loads. Finally, we conduct systematic evaluation across multiple damping conditions and articulated-object categories to study robustness under contact-load variation, and provide a pure-geometry dexterous interaction resource to support future loco-manipulation and humanoid hand–object interaction research. Across seven GAPartNet objects, DragMesh-2 achieves stronger robustness under contact-load variation than the compared methods while maintaining high task success across damping conditions.

19.
arXiv (CS.AI) 2026-06-12

From Verdict to Process: Agentic Reinforcement Learning for Multi-Stage Fact Verification

arXiv:2606.13262v1 Announce Type: new Abstract: Recent approaches combining Large Language Models (LLMs) with retrieval-augmented reasoning have shown promise for automated fact verification. To process complex claims, these verification pipelines typically execute multi-stage workflows that coordinate tightly coupled modules, including claim decomposition, evidence gathering, and verdict prediction. However, existing methods optimize individual stages in isolation or rely on fixed heuristics, which limits adaptive coordination among stages and can lead to suboptimal outcomes. In this work, we propose ProFact, an agentic reinforcement learning framework for end-to-end optimization of multi-stage fact verification trajectories. ProFact trains a unified policy to coordinate claim decomposition, evidence seeking, answer generation, and verdict prediction. To address the sparse and delayed supervision provided by final veracity labels, ProFact introduces process-aware rewards that provide stage-level learning signals throughout the verification process. Empirical evaluation shows that ProFact consistently outperforms strong baselines in both verification performance and inference efficiency. These results highlight the effectiveness of process-aware trajectory optimization for multi-stage fact verification.

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

Compositional Reasoning Depth Predicts Clinical AI Failure: Empirical Evidence Consistent with Transformer Compositionality Limits in Electronic Health Record Question Answering

作者:

Aggregate accuracy benchmarks conceal a systematic structure in how large language models fail at electronic health record (EHR) question answering: questions requiring more inferential steps produce disproportionately more errors. Motivated by theoretical results on transformer compositionality limits, we introduce a pre-specified hop-count taxonomy – the number of distinct reasoning steps required to answer a clinical question from an EHR – as a principled predictor of model failure. We annotate 313 clinician-generated MedAlign EHR question-answer pairs across four hop levels and evaluate 301 questions in a within-model ablation (claude-sonnet-4-6, zero-shot vs. extended thinking) and cross-architecture replications (gpt-4o and gpt-5.4-2026-03-05, zero-shot). All three models, spanning two providers and two OpenAI generations (GPT-4 and GPT-5), show monotone accuracy decline with hop count: Claude Sonnet zero-shot falls from 30.6% (hop=1) to 17.6% (hop=4) (Cochran-Armitage z=-2.30, p=0.011; OR per hop 0.72, 95% CI [0.56,0.92], p=0.008); GPT-4o replicates this (37.8% to 14.7%; OR 0.58 [0.45,0.75], p

21.
medRxiv (Medicine) 2026-06-19

A soluble bi-specific fusion protein for the improved expansion of human CD8+ CAR-T cells

The success of Chimeric Antigen Receptor (CAR) T cell therapy is heavily dependent on the quality of the final cellular product. Current expansion protocols often rely on reagents that require removal from cell culture media, posing logistical challenges in manufacturing, and can also lead to terminal differentiation. Here, we evaluate the use of a soluble, bead-free T cell activator, T cell expansion protein (T-CEP), as a streamlined alternative for generating potent CAR-T cells. Human T cells were activated with T-CEP or known T cell activators (Dynabeads and TransAct) and transduced with either CD19 or interleukin-13 (IL-13) mutein (tetravariant-13; TV-13)-based CAR lentiviral vectors. Our results demonstrate that T-CEP supports robust CAR-T cell expansion and achieves transduction efficiencies comparable to commercial reagents for both types of CAR-T cells. Notably, T-CEP significantly favored the expansion of CD8+ T cells, yielding an enhanced CD27+ phenotype and a lower CD4:CD8 ratio compared to TransAct. Cytotoxicity assays confirmed that T-CEP-expanded CAR-T cells possess cytolytic function equivalent to commercial reagents for both CARs, while exhibiting lower levels of inflammatory cytokine secretion. In summary, T-CEP represents a competitive alternative to existing expansion agents, as it does not require its removal during CAR-T manufacturing and generates a CD8+ dominant, less-differentiated phenotype without compromising efficacy.

22.
arXiv (CS.LG) 2026-06-19

Comparative Study of Neural Surrogate Architectures for Autoregressive Prediction of Internal Battery States

arXiv:2606.20053v1 Announce Type: new Abstract: The Doyle-Fuller-Newman (DFN) model resolves internal electrochemical states in lithium-ion batteries with high fidelity. However, the numerical solution of its governing equations is computationally prohibitive for real-time deployment, limiting scalability from individual cells to pack and fleet-scale applications. While machine learning surrogates can substantially reduce inference latency through GPU acceleration, most existing approaches learn solution approximations tied to specific operating conditions rather than learning generalizable state-evolution dynamics. This work presents a systematic comparison of four neural network architectures (MLP, ResNet, U-Net, FNO) formulated as autoregressive state-transition operators that predict full DFN internal states across a wide range of operating conditions. To ensure a controlled architectural comparison, all models are trained under a unified framework using multi-step unrolling and current-conditioning, isolating the impact of spatial inductive bias. Results demonstrate that the U-Net's multi-scale feature hierarchy achieves a mean final-step nRMSE of 3% averaged across all internal state variables after 300-step autoregressive rollouts, while providing a 5.38x speed-up over the numerical solver. These findings highlight spatial inductive bias as a critical determinant of surrogate performance, advancing the development of surrogates for internal state observability for next-generation battery management systems and digital twins.

23.
medRxiv (Medicine) 2026-06-12

Reduced nighttime smartphone use among cohabiting partners: a longitudinal study under the lens of social control of health behaviors theory

Objective: We examined the link between cohabitation with a partner and nighttime smartphone use through the social control of health behavior theory. Background: Nighttime smartphone use is a behavioral risk factor for sleep problems. While previous research has predominantly focused on individual-level risks of sleep disturbances, the role of social context remains underexplored. Theoretical frameworks, specifically the Social Control of Health Behavior, suggest that social relationships regulate health-related behaviors; however, it is unclear how far this regulation extends to modern digital behaviors among couples. Method: We analyzed survey data from three waves of the SmartSleep Study (2018, 2020, and 2023; total N = 25,028), including a longitudinal follow-up subset (N = 1,003). We tested multivariate associations between living with a partner, changes in cohabitation status and frequent nighttime smartphone use by fitting generalized linear mixed-effects models. Additionally, we mapped the complex interplay between indicators of social integration, social support, smartphone use, and sleep quality using hierarchical clustering of non-linear correlations. Results: Cohabiting participants had lower odds of frequent nighttime smartphone use compared to those living alone (OR = 0.66; 95% CI: 0.61, 0.72). This lower risk was driven primarily by cohabitation with a partner (OR = 0.49; 95% CI: 0.36, 0.66). Longitudinal analysis supported these findings, showing that sustained cohabitation was associated with less frequent nighttime use (OR = 0.56; 95% CI: 0.38, 0.82). Clustering analysis revealed that indicators of social integration and support clustered with favorable sleep quality. Conclusion: Our findings suggest that the health-protective effects of cohabitation with a partner extend to digital behaviors. Consistent with social control of health behavior theory, the presence of a partner appears to reduce frequent nighttime smartphone use, highlighting the critical importance of considering social context when addressing digital health hygiene and promoting sleep.

24.
Nature (Science) 2026-06-10

Building user-driven climate adaptation products

Climate adaptation products have traditionally been developed using a supply-driven model reliant on available climate information, leading to usability gaps1–4. To better meet user needs, the climate services field has recognized a need to shift towards a demand-driven model emphasizing co-production, that is, user-driven, scientifically informed products created through shared knowledge practices1–5. However, co-production can be challenging, especially for researchers unfamiliar with the approach or for digital and software-based products with complex user needs2,5–8. User-centred design, from the human–computer interaction field, offers a process that could complement co-production approaches to product development, yet its potential remains underexplored2. Here we show how user-centred design can be integrated into, and strengthen, co-production approaches for building user-driven climate adaptation products. Through a systematic review of the co-production and user-centred design literature, we identify key processes, mechanisms and best practices for both approaches. Our findings offer practical guidance for researchers and propose an integrated approach for developing climate adaptation products that are useful, usable and used. A systematic review and analysis shows how user-centred design can be integrated into, and strengthen, co-production approaches for building user-driven climate adaptation products.

25.
medRxiv (Medicine) 2026-06-11

Global population frequencies of NAT2 star alleles observed in three large biobanks

NAT2 is an important pharmacogene which encodes the N-acetyltransferase 2 enzyme that is involved in the metabolism of multiple medications, and variants in this gene can affect patient response to these medications. CPIC has published a clinical guideline for prescribing hydralazine using NAT2 genotypes. Just prior to the guideline, updated NAT2 star allele numbering and definitions were released, differing somewhat from the historical nomenclature. Clinical pharmacogenomic testing panels often test for the most common star alleles, so knowledge of the most common updated NAT2 star alleles is critical for the implementation of the CPIC NAT2/hydralazine guideline. We first determine NAT2 diplotype frequencies from UK Biobank (UKBB) 200k phased genomes, then analyzed allele, diplotype, and phenotype population frequencies from the All of Us Research program, PennMedicine BioBank (PMBB) and UKBB 500k datasets. We found that analyzing NAT2 diplotypes from phased data provides critical information for algorithms designed to predict diplotypes from unphased data. We observed that NAT2*5, *6, and *4 were the most common star alleles in that order, and the top 11 most frequent NAT2 star alleles were the same across all biobanks. However, differences in star allele frequencies across biogeographical populations were observed. The largest difference led to a higher frequency of NAT2 poor metabolizer phenotypes as compared to rapid and intermediate metabolizer phenotypes in all global populations except in the EAS population, where NAT2 poor metabolizers were in the minority.