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01.
arXiv (CS.AI) 2026-06-16

Orchestrated Reality: From Role-Play to Living, Playable Game Worlds – LLM-Driven World Simulation as a Parameterized-Action POMDP

arXiv:2606.16014v1 Announce Type: cross Abstract: Many games rely on storytelling combined with systems that track levelling, NPC behaviour, and consequence simulation; bridging tightly-authored narrative with deeply-simulated worlds – most acute in sandbox and open-world settings – has been prohibitively expensive. LLM-driven worlds open a new path: a single harness can coordinate numerical state, narrative voice, storytelling pacing, and rule logic together. Realising this requires the LLM system to sustain a persistent world (who is where, what has just happened, what is currently true), which today's deployed systems do not: the narrative voice asserts state in free prose without any validated representation, so a fully autonomous game engine remains infeasible. We treat this as an architectural choice, not a limitation of language models, and report work in progress on a framework – orchestrated reality – that makes the world a canonical object owned by a singleton orchestration agent analogous to the tabletop-RPG Game Master (GM). We formalise an LLM-driven game world for a human player as a Parameterized-Action POMDP: state is a tree of canonical JSON entities, actions decompose as $a=(k, x_k)$ (a discrete intent kind plus structured JSON parameters), the agent observes only a narrative projection $o=O(s)$ of state, and the transition kernel $F$ is an LLM-driven Plan-Diff-Validate-Apply (PDVA) pipeline that commits schema-validated, content-hashed JSON deltas. We give the formal model, a JSON-state example, a worked single-turn example, and a catalogue of 15 illustrative incidents drawn from a real deployment showing the framework in action. Empirical validation through a planned human player study – together with multi-NPC concurrent agency and deployment as an RL environment – is situated as future work.

02.
arXiv (CS.CL) 2026-06-16

A Survey on Agentic Security: Applications, Threats and Defenses

LLM-based agents are now used throughout cybersecurity. While these agents facilitate powerful and autonomous security applications, their autonomy opens up new attack surfaces, and the security community is actively building defenses to secure them. Yet the literature on this subject has grown quickly and unevenly. Existing surveys treat applications, threats, and defenses in isolation, leaving no unified account of how an agent's capabilities, vulnerabilities, and countermeasures interconnect. In this work we present the first holistic survey of the agentic security landscape, structuring the field around the fundamental pillars of Applications, Threats and Defenses. We provide a comprehensive taxonomy of over 260 papers, explaining how agents are used in downstream cybersecurity applications, inherent threats to agentic systems, and countermeasures designed to protect them. In addition, we provide detailed pillar-specific and cross-cutting analyses that show the security-lifecycle coverage of agentic applications, comparison between red-teaming and blue-teaming agents, and the adversarial use of red-teaming applications. On the threat side, we analyze the entry points and agent-loop stages that attacks target, their specificity to the agentic setting, and the threat models they assume. On the defense side, we analyze the prevailing defense strategies, their cost and security trade-offs, and where in the agent lifecycle they are deployed. We further map which defenses cover which attack classes and chart trends in agent architecture, backbone model usage, data modality coverage, and the growth of attack and defense research over time. Taken together, these findings indicate that agentic systems are structurally fragile by default and that securing them will require defenses that span the full agent lifecycle rather than single-layer fixes.

03.
medRxiv (Medicine) 2026-06-12

Crimean-Congo haemorrhagic fever virus transmission: exploring perceptions of human-animal-tick interactions across six districts in Uganda

Crimean-Congo haemorrhagic fever virus (CCHFV) causes a viral zoonotic disease transmitted through tick bites and direct contact with infected blood or tissue of infected animals. Socio-ecological and behavioural risk factors for CCHFV exposure in Uganda remain poorly understood, which can lead to the omission of key risk factors in quantitative survey design and limit our wider understanding. In this study, we explored human-animal-tick interaction transmission risks in Uganda. We conducted 24 focus group discussions (FGDs) and 31 key-informant interviews (KIIs) across six environmentally and socio-ecologically diverse districts, between October 2023 and March 2024. Study sites were selected using K-prototype analysis, which combined environmental and socio-ecological variables to identify distinct clusters within Uganda. FGDs were conducted separately with groups of community leaders, men, women and teenagers with stratified purposive sampling. Medical doctors, veterinarians, traditional healers, district surveillance officers, and herdsmen were individually interviewed as key informants and purposively sampled. Data were transcribed and translated into English, and analysed thematically using iterative categorisation in NVivo 14. Most participants reported tick bites, some as frequently as every day. Close contact with animals was common, including sleeping next to them in the same building, largely due to concerns about animal theft. Less frequent but notable practices included slaughtering animals for consumption or sacrifice and interactions with wild animals during hunting. Slaughtering and butchering an animal which was sick or had died was reportedly performed by participants in most districts. Plucking and roasting engorged ticks was a practice described in the Kaabong and Arua districts of Northern Uganda. These practices and behaviours highlight potential key risks of CCHFV transmission and underscore the need for future studies to address specific behaviours, to quantify if, and to what extent, they present an exposure risk. Further work should include underlying reasons for the behaviours, which would help ensure that culturally appropriate interventions are targeted.

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

Sub-Semantic Image Segmentation

Images can be segmented based on visual cues (i.e., texture segmentation) or into objects (i.e., semantic segmentation). We propose a new category of sub-semantic image segmentation that blurs the line between the two. In sub-semantic image segmentation, language is not used to name whole objects. Instead, it is used to partition an image into stable appearance patterns that can be described by language. To do that, we couple a general-purpose vision-language model to SAM 3, a promptable segmentation backbone whose native text pathway can ground rich descriptions into masks. Simple coupling fails for a number of reasons that we identify in the paper, and we overcome them by introducing DETECTURE that resolves three concrete failure modes – language leakage between texture regions, prompt competition inside the segmentation backbone, and semantic distortion at the language-to-mask interface. Since there is no dataset of sub-semantic image segmentation, we introduce one, termed TextureADE. The new dataset is derived from the ADE20K dataset using a system we designed. We compare DETECTURE to a number of baselines and find that it achieves the strongest performance on several datasets using different metrics. Code is available at https://github.com/Scientific-Computing-Lab/TextureDetecture.

05.
arXiv (CS.AI) 2026-06-11

Multimodal Ordinal Modeling of Alzheimer's Disease Severity Using Structural MRI and Clinical Data

arXiv:2606.11794v1 Announce Type: cross Abstract: Neurodegenerative diseases such as Alzheimer's disease (AD) require accurate and scalable tools for assessing disease severity, yet current clinical staging remains time-intensive and prone to variability. We propose an attention-enhanced multimodal machine learning framework with ordinal regression for automated and interpretable AD severity staging. The framework integrates T1-weighted MRI with demographic and genetic variables and compares unimodal and multimodal architectures using ordinal and non-ordinal prediction heads. Models were trained and validated using cohort-stratified splits derived from the ADNI, AIBL, and NIFD datasets. A strictly held-out test set was constructed using subjects excluded from all training, validation, preprocessing, and hyperparameter tuning procedures, with subject-level splitting employed throughout to prevent data leakage. Among unimodal approaches, the T1-weighted MRI model achieved slightly higher adjacent-stage accuracy (0.963) and agreement with clinical staging (QWK 0.444) than the tabular model (QWK 0.433). Integrating imaging, demographic, and genetic information improved overall performance. The multimodal non-ordinal baseline achieved the lowest prediction error (MAE 0.340), whereas the ordinal multimodal model achieved the highest adjacent-stage accuracy (0.970) and strongest agreement with clinical staging (QWK 0.549). These findings indicate that ordinal formulations better capture the ordered structure of the CDR scale and yield predictions more consistent with clinical staging. Explainability analyses using Grad CAM++ and SHAP demonstrated anatomically and clinically plausible model behavior, supporting transparent decision-making. Overall, attention-based multimodal learning with ordinal regression represents a robust, interpretable, and scalable approach for automated AD severity staging and AI-assisted clinical decision support.

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

Dynamical low-rank methods for the Wigner equation I: separable difference potential

arXiv:2606.24190v1 Announce Type: cross Abstract: Recent advances in dynamical low-rank approximation (DLRA) have demonstrated its effectiveness in high-dimensional simulations. However, existing DLRA algorithms still face significant challenges when handling systems that involve complex collision terms, including the pseudo-differential operator ($\Psi$) in the Wigner equation, a representative operator characterized by nonlocality. It is deserving to carry out a series of works to develop the DLRA algorithms for solving the Wigner equation. As the first step in this series of works, we propose an efficient DLRA algorithm for the Wigner equation, using a separable decomposition of the difference potential. We combine this separable assumption with two often-used truncations of $\Psi$, namely $\mathcal{K}$-truncation and $\mathcal{Y}$-truncation, to obtain a kind of separated representation of $\Psi$. Complexity analysis and several challenging experiments, including harmonic oscillators, Gaussian barrier scattering, electron-electron scattering, and a Helium-like system, all of which satisfy the separable assumption, confirm that the proposed DLRA algorithm has significant advantages, achieving a reduction in computational effort by one to two orders of magnitude in both runtime and memory requirements compared to the full-grid approach. It is worth noting that, even in the absence of a predetermined low-rank structure for the solution, DLRA can still serve as a numerical scheme that balances efficiency and accuracy.

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

Entropy-Gradient Inversion: Moving Toward Internal Mechanism of Large Reasoning Models

The advancement of Large Reasoning Models (LRMs) has catalyzed a paradigm shift from reactive ``fast thinking'' text generation to systematic, step-by-step ``slow thinking'' reasoning, unlocking state-of-the-art performance in complex mathematical and logical tasks. However, the field faces the fundamental gap between token-level behavioral analysis and internal reasoning mechanisms, and the instability of reinforcement learning (RL) for reasoning optimization relying on costly external verifiers. We identify and formally define Entropy-Gradient Inversion, a robust negative correlation between token entropy and logit gradients that acts as a definitive geometric fingerprint for LRM reasoning capability. Building on this, we propose Correlation-Regularized Group Policy Optimization (CorR-PO), which embeds this inversion signature into RL reward regularization. Extensive experiments on various reasoning benchmarks across multiple model scales show CorR-PO consistently outperforms state-of-the-art baselines, confirming that stronger inversion directly correlates with superior reasoning performance.

08.
arXiv (quant-ph) 2026-06-15

No classical particle limit for massless quanta

arXiv:2606.14632v1 Announce Type: new Abstract: We investigate whether relativistic massless classical particles may emerge as the classical limit of massless quanta. To address this question independently of any specific dynamics, environment, or pointer basis, we develop an axiomatic and purely kinematical framework for the coarse-graining approach. In this formulation, a candidate classical phase space is taken as the outcome space of a POVM subject only to minimal classicality and covariance under the relevant spacetime symmetry group. Applying this framework to the Poincaré group, we prove a no-go theorem for massless particles: the covariance requirement is incompatible with the operational conditions for classicality. The theorem leaves open field-like limits of massless quanta, for example the emergence of electromagnetic or gravitational fields, while ruling out classical massless particles, such as classical photons or gravitons.

09.
arXiv (CS.AI) 2026-06-11

KAN-MLP-Mixer: A comprehensive investigation of the usage of Kolmogorov-Arnold Networks (KANs) for improving IMU-based Human Activity Recognition

arXiv:2605.19031v2 Announce Type: replace Abstract: Kolmogorov-Arnold Networks (KANs) have demonstrated an exceptional ability to learn complex functions on clean, low-dimensional data but struggle to maintain performance on noisy and imperfect real-world datasets. In contrast, conventional multi-layer perceptrons (MLPs) are far more tolerant to noise and computationally efficient. Replacing all MLP components with KANs in HAR models often degrades accuracy and computation efficiency, highlighting an open challenge: how to combine KANs' precision with MLPs' noise robustness and efficiency. To address this, we systematically explore various placements of KAN modules within deep HAR networks and propose a hybrid architecture that strategically synergizes the strengths of both paradigms, which uses a KAN-based input embedding layer, retains MLP layers for intermediate feature mixing, and introduces a specialized LarctanKAN module for final activity classification. Across eight public HAR datasets, the hybrid KAN-MLP model achieves an average macro F1 score relative improvement of 5.33\% compared pure-MLP model, significantly outperforming standalone KAN and MLP baselines. Furthermore, integrating this hybrid strategy into other state-of-the-art HAR architectures consistently boosts their performance. Our findings demonstrate that a carefully orchestrated combination of KAN, MLP, or other conventional neural components yields more robust and accurate HAR models for real-world wearable sensing environments.

10.
medRxiv (Medicine) 2026-06-23

Associations Between Social Responsiveness and Sleep Disruption are Modulated by Chronotype in Early Adolescence: Cross-Sectional and Prospective Findings from 10,108 Participants of the Adolescent Brain and Cognitive Development (ABCD) Study

Background: Sleep disruption is prevalent in people with neurodevelopmental disorders such as autism but is not clear whether it occurs as an endophenotype or secondary to other behaviours. The ABCD Study is a population-based longitudinal study that monitors the health, demography and lifestyle of over 11,000 children in the US. In this study we leverage these data to investigate whether traits consistent with autism (social responsiveness) are associated with sleep disruption independent of lifestyle and other behavioural measures. Methods: Autistic traits were assessed using the Social Responsiveness Scale at age 11, and sleep disruption and behavioural outcomes were assessed at ages 11 and 13 years using the Sleep Disturbance Scale, and the Child Behaviour Check List, respectively. Demographic, health and lifestyle-related variables were assessed by caregiver questionnaires. Regression models were applied to investigate associations between autistic traits and sleep outcomes. Results: There was a significant cross-sectional association between sleep disturbance and SRS at age 11 years old that was independent of sex, ethnicity, socioeconomic position, physical activity, sedentary behaviour and anxiety/depression ({beta} = 0.12, 95% CI (0.07, 0.17); p < 0.001), that persisted at age 13, and that was modulated by chronotype, with evening types showing a stronger association. Discussion: Social responsiveness assessed in early adolescence (age 11) were associated with sleep disruption independent of multiple confounding factors and were prospectively associated with sleep disruption at age 13 years. These findings contribute to the evidence that disruption of sleep and circadian timing may have a primary role in the neurobiological mechanisms that mediate autistic traits.

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

Unintended Effects of Geographic Conditioning in Large Language Models

Modern conversational AI systems frequently rely on user metadata to localize responses, yet the unintended regional biases introduced by this hidden context remain poorly understood. In this work, we evaluate location leakage: the phenomenon where a model generates geographic references despite receiving a geographically neutral user prompt. Across both creative writing and open-ended Q&A prompts, even state-of-the-art LLMs systematically favor region-specific outputs when exposed to location metadata, with leakage spiking by up to 793 times above baseline (e.g., from 0.04% to 31.7% for Llama 3.1-8B, and 21.3% and 8.8% for Qwen3-8B and Claude Sonnet 4.6, respectively). Our analysis further shows a novel structural conditioning effect: replacing the injected location with the placeholder "Unknown" still elevates leakage by up to 72 times above baseline, demonstrating that the user profile frame itself, independent of any geographic content, acts as a generative conditioning signal.

12.
arXiv (quant-ph) 2026-06-16

Watching a Superconducting Coplanar Waveguide Heat Up with a Single Color Center

arXiv:2606.15398v1 Announce Type: new Abstract: Single color centers in diamond offer a local probe of their cryogenic environment, providing a direct way to quantify heating in spin-control hardware. Here, we establish a single spectrally stable tin-vacancy (SnV) center as an on-chip thermometer for a diamond membrane and use it to characterize microwave- and radio-frequency-induced heating in a superconducting coplanar waveguide patterned on the same chip. We first calibrate the temperature dependence of the optical C-transition frequency and linewidth from $20\,\mathrm{K}$ down to the few-kelvin regime. At lower temperatures, where the optical response becomes weakly temperature dependent, we use the spin-lattice relaxation time $T_1$ as a complementary thermometer and tune its sensitivity with the transverse magnetic-field component. Applying this local thermometer to a niobium coplanar waveguide, we observe magnetic-field-dependent superconducting breakdown under GHz drive, accompanied by abrupt heating of the diamond. In contrast, at $20\,\mathrm{MHz}$ and $400\,\mathrm{mT}$, relevant for nuclear-spin control, we detect no measurable heating up to the breakdown threshold of $9.4\,\mathrm{dBm}$, corresponding to $B_\mathrm{ac}\sim1.2\,\mathrm{mT}$. These results define a safe operating window for superconducting microwave and RF control structures in diamond-based quantum nodes.

13.
arXiv (CS.LG) 2026-06-15

Federated Learning for Feature Generalization with Convex Constraints

arXiv:2606.14416v1 Announce Type: new Abstract: Federated learning (FL) often struggles with generalization due to heterogeneous client data. Local models are prone to overfitting their local data distributions, and even transferable features can be distorted during aggregation. To address these challenges, we propose FedCONST, an approach that adaptively modulates update magnitudes based on the parameter strength of the global model. This prevents over-emphasizing well-learned parameters while reinforcing underdeveloped ones. Specifically, FedCONST employs linear convex constraints to ensure training stability and preserve locally learned generalization capabilities during aggregation. A Gradient Signal to Noise Ratio (GSNR) analysis further validates the effectiveness of FedCONST in enhancing feature transferability and robustness. As a result, FedCONST effectively aligns local and global objectives, mitigating overfitting and promoting stronger generalization across diverse FL environments, achieving state-of-the-art performance.

14.
arXiv (CS.CL) 2026-06-12

Attention Expansion: Enhancing Keyphrase Extraction from Long Documents with Attention-Augmented Contextualized Embeddings

Pre-trained language models (PLMs) have achieved strong performance in keyphrase extraction (KPE), largely due to their ability to generate rich contextualized representations. However, long-document KPE remains challenging because salient keyphrase evidence may be scattered across distant document sections that cannot be jointly captured within the limited context window of most PLMs. Although long-context large language models (LLMs) can process broader textual contexts, their computational cost limits their practicality for efficient and high-throughput KPE. To overcome this limitation, we propose an attention expansion mechanism that augments PLM token representations with information from surrounding out-of-context chunks using pre-trained word embeddings. The proposed mechanism expands the effective contextual scope of PLM-based KPE models without requiring full-document attention or expensive LLM-based inference. We evaluate our approach across five PLM backbones, including general-purpose, scientific, task-specific, and long-context encoders, using two training regimes and five benchmark corpora from scientific and news domains. Experimental results demonstrate that attention expansion consistently enhances KPE performance across all evaluation settings, outperforming state-of-the-art models and yielding notable improvements in F1 score. The improvements extend to domain-specific, task-specialized, and native long-context models, showing that the proposed mechanism provides complementary information rather than merely compensating for limited input length. These results establish attention expansion as an efficient and effective strategy for long-document KPE.

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

QCI Connect: A Modular Full-Stack Quantum Computing Platform

arXiv:2606.14456v1 Announce Type: new Abstract: In a world of various competing quantum computing architectures, hardware-agnostic, full-stack platforms are necessary to bring the full power of quantum computing hardware to domain experts via the cloud. QCI Connect and its Software Development Kit provide a reference architecture for a full-stack platform with a modular design and open-source interface definitions, built to facilitate a community-driven application ecosystem. Here, we present its overall design and features, central interfaces, and lessons learned, both for users of the platform and as a reference guide for future developments.

16.
medRxiv (Medicine) 2026-06-12

Deconvolution-based cell-type specific DNA methylation-wide and transcriptome-wide association studies identify risk CpG sites and genes associated with colorectal cancer risk

Bulk tissue-based DNA methylation-wide (MWAS) and transcriptome-wide association studies (TWAS) have identified CpG sites and genes associated with colorectal cancer (CRC) risk, but do not account for cellular heterogeneity. To address this, we developed a deconvolution-informed framework to infer cell-type specific DNA methylation and gene expression profiles from bulk normal colon tissues using reference single-cell epigenomic and transcriptomic datasets. We performed cell-type specific MWAS (ctMWAS) using deconvoluted DNA methylation data from 293 normal colon samples and conducted cell-type specific TWAS (ctTWAS) using deconvoluted gene expression data from 707 normal colon samples. Genetically predicted methylation and expression models were integrated with CRC GWAS summary statistics (78,473 cases and 107,143 controls) to identify risk-associated CpG sites and genes. Through ctMWAS, ctTWAS, and colocalization analyses, we identified 178 significant cell-type-specific CpG sites in 106 loci and 68 risk genes in 40 loci, including 26 previously unreported loci. Through additional integrative methylation-gene analysis, we prioritized 132 candidate risk genes, the majority of which were supported by multi-omics evidence and stage-specific dysregulation across the adenoma-carcinoma and serrated-carcinoma progression pathways. Pathway enrichment analyses implicated pathways involved in DNA double-strand break repair, TP53 regulation, TGF-{beta} signaling, and innate immune responses. Among prioritized genes, 14 were identified as putative druggable targets linked to 90 FDA-approved or clinical-stage drugs. Experimental validation supports an oncogenic role for SF3A3. These findings demonstrate that deconvolution-informed integrative analyses enable cell-type-resolved identification of epigenetic and transcriptional mechanisms underlying CRC susceptibility and provide insights into disease biology, prevention, and therapeutic target discovery.

17.
arXiv (quant-ph) 2026-06-25

Optimizing Pump Conditions of Parametric Amplifiers for Fast Multiplexed Readout of Superconducting Qubits

arXiv:2606.22080v2 Announce Type: replace Abstract: Low-noise parametric amplifiers are widely used as the first-stage amplifier in qubit readout chains. The performance of parametric amplifiers depends sensitively on the choice of the pump condition. We propose a strategy for determining the pump condition that is tailored for fast multiplexed readout. Choosing the amplifier pump to maximize the signal-to-noise ratio (SNR) improvement at the readout frequency of the limiting qubit–the qubit that requires the longest readout time to reach a target SNR–minimizes the total multiplexed readout time. We demonstrate our pump calibration strategy experimentally on a five-qubit multiplexed readout chain with a traveling-wave parametric amplifier. Using our strategy, we reduce the multiplexed readout time by 320 ns compared to optimizing the average SNR improvement on all qubits, without degrading the target SNR for any qubit.

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

Spatially Selective Self-Training for Unsupervised Building Change Detection

Unsupervised building change detection aims to learn building-change masks from unlabeled bi-temporal remote sensing images. Existing label-free methods often follow a discrepancy-to-mask paradigm, directly using temporal differences, frozen foundation-model responses, prompt-based outputs, or post-processing results as final change maps. Although these strategies provide annotation-free cues, they do not learn a task-specific building-change detector and remain vulnerable to the gap between generic temporal discrepancies and building-defined structural changes. In practice, such discrepancies are often noisy and task-irrelevant, as appearance shifts, registration errors, and non-building modifications can produce strong but misleading responses. To address this problem, we propose SST-CD, a spatially selective self-training framework that reformulates fully label-free building change detection as end-to-end detector learning under noisy pseudo supervision. SST-CD uses temporal discrepancies as candidate pseudo labels and trains the detector only on spatially reliable pixels, whose reliability is estimated by a local consistency criterion that filters inconsistent regions from supervision. To further stabilize noisy self-training, a lightweight feature adapter recalibrates bi-temporal features, while a prototype-based decoder produces compact change and no-change representations. Experiments on LEVIR-CD, WHU-CD, and DSIFN-CD show that SST-CD achieves F1 scores of 83.08%, 91.69%, and 86.60%, respectively, outperforming existing unsupervised and label-free baselines.

20.
arXiv (quant-ph) 2026-06-16

Quantum coherence and Leggett-Garg inequality

arXiv:2606.15717v1 Announce Type: new Abstract: In this paper, we attempt to establish the relationship between quantum coherence and the violation of the Leggett-Garg inequality. In particular, employing the Lindblad equation, we obtain the pseudo-density matrix for a damping system to study the effect of environment interaction on the violation of this inequality in a two-state quantum system. It is shown that the violation of the Leggett-Garg inequality can be observed as long as temporal evolution does not induce decoherence. This statement is independent of the initial state of the system. Furthermore, similar to the Horodecki criterion for the CHSH inequality (R. Horodecki et al. Phys. Lett. {\bf A200}, 340), we study necessary and sufficient conditions for violating the Leggett-Garg inequality. Hereby, under the circumstance that the inequality violation occurs, an upper bound for the time interval between consecutive measurements with respect to the time scale of interaction with the environment (the relaxation time) is obtained.

21.
medRxiv (Medicine) 2026-06-24

Who funds stroke trials in Europe? A survey of funding sources for randomised controlled stroke trials by the European Stroke Organisation Trials Alliance (ESOTA) network

Abstract Aims and scope Evidence from randomised controlled trials (RCTs) has transformed stroke care. There are no systematically collected data on the amount of public funding, critical to delivering trials, going into stroke RCTs. To understand the extent of stroke RCT funding by national and EU funding bodies across Europe, the European Stroke Organisation Trials Alliance (ESOTA) conducted a survey of its member nations. Methods This is an observational study of research funding in Europe. The ESOTA steering group sent an electronic survey to the leads of the 16 participating national networks from 14 countries. Structured survey questions included who the funding bodies were in each country, the number of RCT applications put forward for public national or EU funding, the number of successful and failed applications, and the amount of funding granted between 01/01/2022 and 31/12/2023. Results Responses were received from 13 of 14 participating countries. There was significant variation in the number of grant applications submitted by individual countries, ranging from 0-17 during the 24-month survey period. The median number of funded studies per country was 1 (IQR 3, range 0-9) representing a median success rate of 47.1 % (IQR 21.1-59.4%), with no RCTs granted joint European funding. Conclusions Our survey highlights significant inequities in stroke trial funding across Europe. Given the encouraging rate of successful applications overall, it is important for all member networks to submit proposals. This is particularly pertinent for multicentre trials, given the evolution of evidence base in stroke towards large trials, across diverse populations.

22.
medRxiv (Medicine) 2026-06-10

Impact of Early Treatment on Symptom Improvement and Procedural Events among Men with BPH and Bothersome Lower Urinary Tract Symptoms: A Contemporary Analysis of the American Urological Association Quality (AQUA) Registry

PURPOSE: As the armamentarium of BPH therapies continues to expand, it remains imperative to maximize patient satisfaction and minimize decisional regret. We sought to determine the impact of time from BPH diagnosis to index treatment on symptom improvement and subsequent procedural events. MATERIALS AND METHODS: We queried the American Urological Association Quality Registry for men [&ge;] 40 years old with BPH, available IPSS data, and no receipt of prior BPH treatment. Index treatment included medication, surgery, or minimally invasive surgical therapy (MIST). Outcomes included IPSS over 3 years of follow-up, change in percentage of mild lower urinary tract symptoms (LUTS) by 3 months, and time to procedural event. Patients were stratified by time from index diagnosis to treatment by 3 years. Outcomes were compared across time-to-treatment cohorts with appropriate statistical tests with p < 0.05 as significant. RESULTS: 43,919 patients met criteria with 19,642 pursuing treatments. Patients pursued treatment at comparably lower baseline IPSS compared to prior prospective series. Patients undergoing surgery and MIST had significantly higher baseline IPSS, while medical comorbidities were significantly more common among men initiating pharmacotherapy. Early surgery and MIST were associated with significant improvement in IPSS within 6-12 months and an increase in mild LUTS by 3 months. All forms of early treatment were associated with delayed time to procedural events, including catheterization and fulguration. CONCLUSIONS: Early procedural intervention for BPH is associated with early symptom improvement and delayed time to procedural events among real-world, contemporary practice.

23.
arXiv (CS.CL) 2026-06-16

AdaPLD: Adaptive Retrieval and Reuse for Efficient Model-Free Speculative Decoding

Speculative decoding accelerates generation by verifying multiple drafted tokens in a single target-model forward pass, reducing sequential decoding iterations. Model-free variants avoid auxiliary draft models by reusing text and model states already available during generation, but their speedup depends on the reliability of the constructed drafts. We identify two limitations of existing reuse-based methods: lexically anchored retrieval has limited recall under surface-form variation, and deterministic span copying can be brittle when the retrieved context does not uniquely determine the continuation. We propose AdaPLD, a training-free method that adaptively improves both retrieval and draft construction. AdaPLD preserves high-precision lexical reuse while using semantic similarity to recover additional reuse opportunities when lexical matching fails. It further constructs branched reuse hypotheses to account for continuation uncertainty, rather than relying on a single copied span. Across diverse benchmarks, AdaPLD reduces target-model forward passes and achieves up to $3.10\times$ decoding speedup.

24.
arXiv (CS.CL) 2026-06-18

UMA-Split: unimodal aggregation for both English and Mandarin non-autoregressive speech recognition

This paper proposes a unimodal aggregation (UMA) based nonautoregressive model for both English and Mandarin speech recognition. The original UMA explicitly segments and aggregates acoustic frames (with unimodal weights that first monotonically increase and then decrease) of the same text token to learn better representations than regular connectionist temporal classification (CTC). However, it only works well in Mandarin. It struggles with other languages, such as English, for which a single syllable may be tokenized into multiple fine-grained tokens, or a token spans fewer than 3 acoustic frames and fails to form unimodal weights. To address this problem, we propose allowing each UMA-aggregated frame map to multiple tokens, via a simple split module that generates two tokens from each aggregated frame before computing the CTC loss.

25.
Nature Biotechnology 2026-06-23

Efficient generation of epitope-targeted antibodies with Germinal

Obtaining antibodies to specific protein targets is a widely important yet experimentally laborious process. Meanwhile, computational methods for antibody design have been limited by low success rates that require resource-intensive screening. Here we introduce Germinal, a broadly enabling generative pipeline that designs antibodies against specific epitopes with nanomolar binding affinities while requiring only low-n experimental testing. Our method co-optimizes antibody structure and sequence by integrating a structure predictor with an antibody-specific protein language model to perform de novo design of functional complementarity-determining regions onto a user-specified structural framework. When tested against four diverse protein targets, Germinal designed functional antibodies across all targets and binder formats, testing only 43–101 designs for each antigen. Validated designs also exhibited robust expression in mammalian cells and high sequence and structural novelty. We provide open-source code and full computational and experimental protocols to facilitate wide adoption. Germinal achieves epitope-targeted, de novo complementarity-determining region design with high experimental success rates.