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01.
arXiv (CS.AI) 2026-06-18

Large-Scale OD Matrix Estimation with A Deep Learning Method

arXiv:2310.05753v2 Announce Type: replace Abstract: The estimation of origin-destination (OD) matrices is a crucial aspect of Intelligent Transport Systems (ITS). It involves adjusting an initial OD matrix by regressing the current observations like traffic counts of road sections (e.g., using least squares). However, the OD estimation problem lacks sufficient constraints and is mathematically underdetermined. To alleviate this problem, some researchers incorporate a prior OD matrix as a target in the regression to provide more structural constraints. However, this approach is highly dependent on the existing prior matrix, which may be outdated. Others add structural constraints through sensor data, such as vehicle trajectory and speed, which can reflect more current structural constraints in real-time. Our proposed method integrates deep learning and numerical optimization algorithms to infer matrix structure and guide numerical optimization. This approach combines the advantages of both deep learning and numerical optimization algorithms. The neural network(NN) learns to infer structural constraints from probe traffic flows, eliminating dependence on prior information and providing real-time performance. Additionally, due to the generalization capability of NN, this method is economical in engineering. We conducted tests to demonstrate the good generalization performance of our method on a large-scale synthetic dataset. Subsequently, we verified the stability of our method on real traffic data. Our experiments provided confirmation of the benefits of combining NN and numerical optimization.

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

LakeFM: Toward a Foundation Model for Aquatic Ecosystems Using Irregular Multivariate Multi-depth Time Series Data

arXiv:2606.11268v1 Announce Type: new Abstract: Understanding and forecasting lake dynamics is critical for monitoring water quality and ecosystem health across lakes and reservoirs. While machine learning methods have been recently applied to ecological time-series data, existing works assume regular sampling in time and depth, and struggle to generalize across lakes with heterogeneous variables, depths, and observation patterns. To address these limitations, we introduce \textsc{LakeFM}, a foundation model for aquatic systems, pre-trained on large-scale ecological datasets comprising both simulated and observed lakes. Through extensive empirical evaluation, we show that \textsc{LakeFM} learns meaningful representations spanning broader lake-level characteristics, and achieves competitive or often superior-forecasting performance compared to existing time-series foundation and non-foundation models, while producing physically plausible predictions consistent with real-world lake dynamics.

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

Size Doesn't Matter: Cosine-Scored Sparse Autoencoders

arXiv:2606.15054v1 Announce Type: new Abstract: Sparse autoencoders (SAEs) detect features via inner product, so a feature's activation scales with both its directional alignment and the input's norm. Under BatchTopK, high-norm tokens inflate all pre-activations simultaneously, claiming dictionary slots regardless of content alignment. This matters because sublayer normalization has already discarded the magnitude the score measures, so the encoder detects a quantity the model does not read. We replace the score with a learned blend of cosine similarity and input magnitude, letting the optimizer choose how much norm to use; a per-feature extension lets each feature decide independently. In both regimes, training is free to recover inner product but never does, with no feature ever choosing more than half-magnitude dependence. At matched reconstruction, the cosine encoder learns features that align with human-recognizable concepts far more often than standard, filling dictionary slots that inner product wastes on norm detectors. Loss reweighting that equalizes gradients barely closes the gap, confirming forward-pass score geometry as the lever. The advantage is not universal across tasks or depths, but we believe cosine scoring should be the default for dictionary learning on normalized representations.

04.
arXiv (CS.AI) 2026-06-24

CompressKV: Semantic-Retrieval-Guided KV-Cache Compression for Resource-Efficient Long-Context LLM Inference

arXiv:2606.24467v1 Announce Type: new Abstract: Long-context large language model (LLM) inference is increasingly constrained by the memory footprint and decoding cost of key-value (KV) caches, limiting sustainable deployment on resource-constrained hardware. Existing KV cache eviction methods typically apply heuristic token scoring over all heads in GQA-based LLMs. These methods ignore the different functionalities of attention heads, leading to the eviction of critical tokens and thus degrading the performance of LLMs. To address this issue, we propose CompressKV, a resource-efficient KV-cache compression framework for GQA-based LLMs. Instead of aggregating attention scores from all heads, CompressKV identifies Semantic Retrieval Heads (SRHs) that capture both the initial and final tokens of a prompt and semantically important mid-context evidence, and uses them to select tokens whose KV pairs should be retained. Furthermore, CompressKV allocates cache budgets across layers according to offline estimates of layer-wise eviction error. Experiments on LongBench and Needle-in-a-Haystack show that CompressKV consistently outperforms existing KV-cache eviction methods across memory budgets. Notably, it preserves over 97\% of full-cache performance using only 3\% of the KV cache on LongBench question-answering tasks and achieves 90\% accuracy with just 0.7\% KV storage on Needle-in-a-Haystack. These results demonstrate an improved resource–performance trade-off for long-context LLM inference. Our code is publicly available at: https://github.com/TUDa-HWAI/CompressKV

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

GENERIC-FNO: Embedding Energy Conservation and Entropy Production into Fourier Neural Operators

arXiv:2606.08343v2 Announce Type: replace Abstract: We introduce GENERIC-FNO, the first neural operator to embed the full GENERIC (metriplectic) structure of nonequilibrium thermodynamics – reversible, energy-conserving dynamics and irreversible, entropy-producing dynamics coupled through the degeneracy conditions – directly in function space. Existing structure-preserving neural operators enforce at most a single conservation law or reversible (Hamiltonian) structure, while thermodynamically consistent learning has been confined to finite-dimensional, graph, or particle systems. GENERIC-FNO closes this gap: it learns the energy and entropy functionals as neural operators and parameterizes the Poisson and friction operators as diagonal Fourier multipliers sandwiched between rank-one projections that enforce the degeneracy conditions exactly, by construction, with no penalty term, update projection, or residual. The degeneracy identities hold to machine precision (residuals ~10^-13) for any initialization, dimension, or resolution, so the continuous-time dynamics conserve the learned energy and produce entropy exactly; the explicit time stepping adds only a small O(dt^2) drift (per-step residual ~10^-6). We further note that the (E,S,L,M) decomposition of a given flow is not unique, and introduce a gauge-invariant dissipation diagnostic separating reversible from dissipative dynamics independently of the learned functionals. Across three operator backbones (1D/2D FNOs and DeepONet) and four PDEs spanning reversible, dissipative, and mixed regimes, GENERIC-FNO preserves its exact structural guarantees zero-shot across a 4x super-resolution range (64 to 256), recovers the ground-truth ordering of physical dissipation, and is competitive with strong unconstrained and energy-penalized baselines, outperforming them on several dissipative and mixed problems at comparable or fewer parameters.

06.
arXiv (math.PR) 2026-06-25

On the entropic convergence for piecewise deterministic samplers: speedup and obstruction

arXiv:2606.26086v1 Announce Type: new Abstract: For piecewise deterministic samplers such as Randomized Hamiltonian Monte Carlo (RHMC), Bouncy Particle Sampler (BPS) or Zig-Zag Process (ZZP), long-time exponential convergence rates have been established in previous works using Harris or $L^2$ hypocoercivity approaches. In particular, in the $L^2$ framework, a so-called diffusive-to-ballistic speedup was known for log-concave targets, according to which the convergence rates of these samplers, with suitable parameters, are quadratically improved with respect to the standard overdamped Langevin diffusion process. A recent work by Jianfeng Lu showed that this speedup also holds for the kinetic Langevin diffusion process when the convergence is stated in terms of relative entropy, raising the question whether this also holds for piecewise deterministic samplers. The present work provides a positive and a negative answer to this: first, we show that the speedup holds in entropy for RHMC; second, we show that for BPS or ZZS, even for a standard Gaussian target, a similar result cannot hold, and even that exponential convergence (at any rate) in entropy fails.

07.
arXiv (CS.CL) 2026-06-16

From Awareness to Adherence: Bridging the Context Gap in Spoken Dialogue Systems via Context-Aware Decoding

Despite the success of end-to-end (E2E) spoken dialogue systems, maintaining strict context adherence in multi-round conversations remains a challenge. While prior works attribute these failures to models forgetting dialogue history, we highlight an equally critical but overlooked bottleneck: a gap between latent context awareness and active adherence. Although models internally recognize relevant past utterances, strong parametric priors often overshadow these signals during decoding. To bridge this gap, we propose an audio-adapted Context-Aware Decoding (CAD) approach. By leveraging internal attention mechanisms to isolate key historical rounds, our approach contrasts output distributions with and without this key context during inference, directly amplifying multimodal contextual signals. Evaluations on the Audio MultiChallenge benchmark demonstrate significant improvements in Semantic Memory and Self Coherence subtasks, successfully enforcing strict, context-faithful adherence.

08.
arXiv (CS.AI) 2026-06-17

Learn to Quantify Social Interaction with Constraints for Pedestrian Walking

作者:

arXiv:2606.17897v1 Announce Type: new Abstract: Long-term human path forecasting in crowds is critical for autonomous moving platforms (like autonomous driving cars and social robots) to avoid collision and make high-quality planning. Although the current research take into account social interactions for prediction, they don't reveal the exact kinds of social interactions happened among people and how the social interactions affect the decision-making process of pedestrians, which further limits its robustness. Social interactions in pedestrian walking are intuitively massive and hard to label and quantify. In this paper, we explore creatively to quantify and interpret how pedestrians interact with others by proposing Learn to Cluster. Our clustering social interactions is probabilistic latent variable generative, learning directly from sequential trajectory observations, scalable to arbitrary number of pedestrians. Learn to cluster is label-free and can be naturally integrated into the training process of the prediction model. The latent variables will then serve as 'labels' to categorize social interactions. Extensive experiments over several trajectory prediction benchmarks demonstrate that our method is able to learn the patterns of social interactions and effectively integrate the patterns to pedestrian trajectory prediction.

09.
arXiv (CS.LG) 2026-06-12

Extracting Governing Equations from Latent Dynamics via Multi-View Contrastive Learning

arXiv:2606.13260v1 Announce Type: new Abstract: Identifying latent dynamical systems from noisy, high-dimensional measurements is a central problem at the intersection of representation learning, system identification, and scientific discovery. We present DYSCO, a multi-view temporal contrastive learning algorithm that jointly recovers latent trajectories and the governing dynamics from such observations, by leveraging multiple independent noisy views of the same underlying process to disentangle signal from noise. By parameterizing the dynamics in a structured functional basis, our framework further enables symbolic recovery of the governing equations within an affine gauge. We offer theoretical guarantees for strong identification up to an affine indeterminacy, extending prior identifiability results to the realistic setting of noisy nonlinear observations. Empirically, we demonstrate accurate recovery of both latent trajectories and flow fields across a diverse set of dynamical regimes (e.g., chaotic, oscillatory, and metastable) under both Gaussian and Poisson observation noise, the latter being particularly relevant for neural recordings.

10.
medRxiv (Medicine) 2026-06-15

Mucosal and Systemic Antibodies Associated with Clinical Protection in a Pertussis Controlled Human Infection Model

Background The engagement of mucosal and systemic immunity in preventing Bordetella pertussis colonization and infection in humans, the impact of prior vaccination on host immunity and protective outcomes, and the dynamics of the host response following exposure remain poorly understood. Methods Healthy adults were challenged with increasing colony-forming units (CFUs) doses, 106-108, of B. pertussis D420 intranasally (NCT05136599). Shedding (PCR and culturing) and symptom development were monitored up to 21 days post-challenge. Serum and nasal wash IgA and IgG were measured before challenge (baseline) and up to 6 months post-challenge. Findings Antibodies increased post-challenge only in infected individuals, primarily nasal IgA. Participants who remained uninfected had higher baseline levels of filamentous hemagglutinin (FHA)- specific mucosal IgA and IgG, and higher serum IgA against fimbriae 2/3 (FIM). FHA was negatively associated with bacterial load and was a key discriminator between shedders and non-shedders, up to one week post-challenge. By day 14 post-challenge, pertussis toxin (PT) IgG and FIM IgA in both serum and mucosal samples were negatively associated with bacterial colonization. The majority (96.7%) of acellular pertussis (aP) vaccine recipients (n=23, median age 2.0 years) became infected, compared to 69.4% of those who received whole-cell pertussis vaccine (n=36; median age 32.0 years), and their antibody responses remained distinct following infection. Interpretation Nasal FHA antibodies emerged as early predictors of protection against pertussis infection, while PT IgG and FIM IgA antibodies may reflect clearance after infection. aP-primed individuals were more susceptible to infection, despite their younger age and more recent vaccination. Funding CDC Contract #75D30122C15467 and CDC IPA Agreement #24IPA2417512 Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, US Department of Health and Human Services.

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

OdysSim: Building Foundation Models for Human Behavior Simulation

Large language models are increasingly deployed as human simulators for interactive evaluation and social simulation. Yet helpfulness-driven post-training pulls them toward a homogeneous, overly agreeable assistant register, creating a behavioral Sim2Real gap. We present OdysSim, the largest open systematic investigation of behavioral foundation models, i.e., models trained to simulate human behavior at scale. We propose SOUL, a taxonomy of five capability axes (CONV, SS, COG, ROLE, EVAL) that unifies 62 datasets and 23 benchmark tasks under one framework. Specifically, we curate the OdysSim corpus (21.4M interactions, 10B tokens, retrofitted with back-generated social contexts), construct the SOUL-Index benchmark, and develop an end-to-end training recipe combining midtraining, task-specific RL, and expert distillation. The resulting open 8B OSim model ranks first or tied-first on 8 of 23 tasks, outperforming any individual frontier model by this count, with the strongest gains on conversational and social tasks. Its outputs are also more human-like in length, formatting, and word choice, and it transfers zero-shot to out-of-distribution user simulation on $\tau$-bench, nearly matching real users on reaction alignment (93.2 vs. 93.5). We further show that LLM-as-judge RL induces reward-hacking patterns, and that our detectors can mitigate them during post-training. Together, our findings suggest that behavioral foundation models require rethinking the LLM training paradigm. We release all artifacts to support future research.

13.
arXiv (CS.CL) 2026-06-11

Cross-modal Consistency Guidance for Robust Emotion Control in Auto-Regressive TTS Models

While Text-to-Speech (TTS) systems enable emotional control via natural-language instructions, expressiveness, naturalness, and speech quality degrade when the target emotion conflicts with the textual semantics. We propose a Cross-modal Consistency Guided Classifier-Free Guidance (CCG-CFG) method with dynamic scales based on the degree of inconsistency between the text emotion and the explicit speech emotion, replacing the dropout condition with the text emotion. We also distill the CCG-CFG guidance signal using a hard-sample mining strategy, improving the TTS model's emotional alignment capability. Evaluations on five emotional corpora and two TTS benchmarks show that our approaches applied to CosyVoice2 achieve up to a 12% absolute improvement in emotion-recognition accuracy and a 10% relative improvement in subjective scores, outperforming baselines including HierSpeech++, Qwen3-TTS, and original CosyVoice2, while preserving intelligibility, naturalness, and high speech quality.

14.
arXiv (CS.AI) 2026-06-16

An Attention Mechanism for Robust Multimodal Integration in a Global Workspace Architecture

arXiv:2602.08597v3 Announce Type: replace Abstract: Robust multimodal systems must remain effective when some modalities are noisy, degraded, or unreliable. Existing multimodal fusion methods often learn modality selection jointly with representation learning, making it difficult to determine whether robustness comes from the selector itself or from full end-to-end co-adaptation. Motivated by Global Workspace Theory (GWT), we study this question using a lightweight top-down modality selector operating on top of a frozen multimodal global workspace. We evaluate our method on two multimodal datasets of increasing complexity: Simple Shapes and MM-IMDb 1.0, under structured modality corruptions. The selector improves robustness while using far fewer trainable parameters than end-to-end attention baselines, and the learned selection strategy transfers better across downstream tasks, corruption regimes, and even to a previously unseen modality. Beyond explicit corruption settings, on the MM-IMDb 1.0 benchmark, we show that the same mechanism improves the global workspace over its no-attention counterpart and yields decent benchmark performance.

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

Non-Gaussian Phase Transition and Cascade of Instabilities in the Dissipative Quantum Rabi Model

arXiv:2507.07092v3 Announce Type: replace Abstract: The open quantum Rabi model describes a two-level system coupled to a harmonic oscillator. A Gaussian phase transition for the nonequilibrium steady states has been predicted when the bosonic mode is soft and subject to damping. We show that oscillator dephasing is a relevant perturbation, which leads to a non-Gaussian phase transition and an intriguing cascade of instabilities for $k$-th order bosonic operators, as well as a jump in the steady-state qubit polarization. For the soft-mode limit, the equations of motion form a closed hierarchy and spectral properties can be efficiently studied. To this purpose, we establish a fruitful connection to non-Hermitian Hamiltonians. The results for the phase diagram, stability boundaries, and relevant observables are based on mean-field analysis, exact diagonalization, perturbation theory, and Keldysh field theory.

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

Fourier analysis of quantum neural network with non-linear data embedding

arXiv:2606.14206v1 Announce Type: new Abstract: Fourier analysis has become a crucial tool for understanding the expressivity of Variational Quantum Circuit (VQC) models, as well as an important indicator of barren plateaus (BP). While existing literature has only studied angle-embedded VQCs in a noiseless environment, here we develop the Fourier analysis of VQCs with non-linear data embedding, with particular focus on amplitude embedding, which provides a naturally compact encoding scheme. We first investigate a subtle difference in the domain of input features within amplitude embedding that leads to a distinct expressivity of the zero-frequency Fourier coefficient. By assuming that the ensemble of unitaries generated from the parameter space forms at least a 2-design with respect to the unitary group, we derive, via Weingarten calculus, that the mean of the Fourier coefficients is concentrated at zero, and the variance scales at an exponentially decaying order with respect to the multi-dimensional frequency magnitude. When a noise channel with unitary Kraus operators and probabilities $\{p_k\}$ is taken into account, the variance is further suppressed by a factor $\left(\sum_k p_k^2\right)^{Q}

17.
arXiv (CS.AI) 2026-06-19

Policy-aware Vector Search: A Vision for Fine Grained Access Control in Vector Databases

arXiv:2606.19803v1 Announce Type: cross Abstract: Vector databases are increasingly used in security sensitive contexts with Retrieval Augmented Generation and organizational AI pipelines; however, their security capabilities remain limited. Specifically, Fine-grained Access Control (FGAC) which is required to ensure that data access adheres to user-specific policies is not fully supported in modern vector databases. Unlike relational databases, vector databases combine structured and unstructured attributes to provide semantic, approximate query results, which complicates FGAC implementation. This creates an inherent tension between enforcing FGAC policies correctly, achieving high ANN search recall and maintaining low query latency. In this paper, we present a vision for Policy-aware Vector Search by formalizing the FGAC policy model in vector databases as well as the enforcement problem. We compare various enforcement strategies, present preliminary findings, and identify key open challenges for future research in policy-aware vector search.

18.
arXiv (CS.LG) 2026-06-25

The Urysohn Ladder: Recursive Metric Contraction for Scalable Continual Learning

作者:

arXiv:2512.18471v2 Announce Type: replace Abstract: Continual learning systems face a fundamental geometric obstacle: as experience accumulates on a fixed-capacity manifold, covering numbers grow linearly with time, eventually forcing representational overlap and catastrophic interference. Prevailing approaches attack this problem by expansion - projecting into higher-dimensional spaces via kernels, overparameterization, or replay. We argue the solution is the opposite: contraction. We formalize abstraction as the Urysohn Ladder, a hierarchy of quotient maps that recursively collapse validated metric neighborhoods into compact tokens, converting unbounded ambient-space search into bounded navigation on a low-dimensional intrinsic scaffold. Geometrically, each collapsed token acts as a shortcut - a region of extreme metric contraction that bridges distant experiences, much like a wormhole in the representational manifold. We establish four results that collectively guarantee separability (metric contraction renders nonlinearly entangled structure linearly separable at each quotient level, and this separability propagates faithfully through the entire hierarchy), bounded capacity (covering numbers remain $O(1)$ per quotient level, independent of stream length), stability (parity-partitioned flow/scaffold subspaces enable unbounded plasticity without catastrophic interference), and scalability (inference cost scales with quotient distance, not ambient distance). We validate each claim empirically with pretrained models and real-world datasets. Moreover, we demonstrate the potential of Urysohn Ladder for scalable continual learning via scaffold amortization.

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

HorusEye: Language as Dynamic Attention for Emergency Visual Analysis

作者:

We introduce HorusEye, Language as Dynamic Attention for Emergency Visual Analysis. Our investigation followed five stages. The first one is benchmarking RefCOCO-Degraded, a dataset of 15,244 images (3,811 base images x 4 conditions: Clean, Fog, Smoke and Thermal) with systematic visual degradation. Through four research questions, we evaluate multiple VLMs (Gemini, Qwen2-VL, BLIP-2, LLaVA, Kosmos-2) across visual grounding the second stage, language feedback recovery the third one, health VQA tasks the fourth, and hallucination analysis the final stage. Our key finding is that language feedback effectiveness is model-dependent: Gemini achieves +47.3% improvement in thermal conditions through iterative language feedback, while Qwen2-VL shows -5.1% degradation under the same protocol. We also identify the 'Thermal Paradox' where cropping strategies that improve RGB performance catastrophically fail in thermal imagery. Furthermore, BLIP-2 uniquely hallucinates more under degradation, making it unsuitable for emergency deployment

20.
arXiv (CS.AI) 2026-06-12

Humor Style Drives Laughter, Topic Shapes Acceptability: Evaluating Bilingual Personal and Political Robot-Delivered AI Jokes

arXiv:2606.13256v1 Announce Type: cross Abstract: Humor plays a central role in human social relationships, and recent advances in computational humor create new opportunities for integrating humor into human-robot interaction (HRI). While large language models (LLMs) can generate diverse forms of humor, it remains unclear how humor style, joke content, and language preference shape perceptions of robot-delivered humor in group settings. In this exploratory study, we employed a mixed factorial design in which participants evaluated AI-generated jokes delivered by a robot in a university classroom. We examined the effects of humor type (Affiliative, Self-Enhancing, Aggressive, Self-Defeating) and joke content (person-related vs. political) on perceived funniness and appropriateness, as well as preferred language. Results show that humor type significantly influences funniness, with Aggressive and Affiliative humor rated higher, while joke content primarily affects appropriateness, with person-related jokes preferred over political ones. Language preference was shaped by both joke content and participants' self-reported fluency and humor practices.

21.
medRxiv (Medicine) 2026-06-10

Human genetic evidence links serine biosynthesis to diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is a common and disabling condition for which no disease-modifying therapies are available. Glycemic and metabolic drivers do not fully explain why only a subset of individuals with diabetes develop DPN, and genetic contributors remain poorly defined. We aimed to perform a multi-population genome-wide association study (GWAS) of DPN to highlight potential new etiological pathways and therapeutic targets. Methods We performed a multi-population GWAS of neuropathy in people with and without diabetes using the VA Million Veteran Program and UK Biobank, followed by replication in the All of Us Research Program (AoU), and gene-based and gene-set analyses to identify implicated pathways. Causal relationships between circulating serine levels and DPN were further tested using two sample Mendelian randomization. To further evaluate pathogenic potential, we analyzed rare, high impact variants in GWAS implicated genes among individuals with unresolved inherited neuropathies using the GENESIS platform. Findings Among individuals with type 2 diabetes, we identified seven genome wide significant loci (p

22.
arXiv (CS.LG) 2026-06-12

Crossing the Validation Crisis: Cross-Validation Reduces Benchmarking Variance Surprisingly Well

arXiv:2606.12552v1 Announce Type: new Abstract: Modern machine learning progresses through empirical work, benchmarking new methods to evaluate relative performance. However, the statistical variability inherent to evaluation - exacerbated by the stochastic nature of many algorithms - often makes performance estimation unreliable due to the limited test samples available, leading to a validation crisis in which genuine advances are difficult to discern. In this work, we show that cross-validation improves markedly confidence when evaluating and comparing learning algorithm performances. We introduce the concept of sample gain, which quantifies the virtual data augmentation achieved by using multiple cross-validation splits to reduce benchmarking variance. Experiments on both synthetic and real-world datasets (histopathologic scans and NLP fine-tuning) demonstrate that multiple splits can substantially improve the reliability and stability of performance estimates, with diminishing returns often setting in later than expected. We also introduce a procedure to dynamically early-stop cross-validation by estimating from the first few folds if subsequent folds will bring large sample gains. Our findings highlight the value of pushing cross-validation on available samples to achieve robust and reliable benchmarking.

23.
medRxiv (Medicine) 2026-06-15

Pulmonary extracellular vesicles drive alveolar macrophage dysfunction via microRNA transfer in Acute Respiratory Distress Syndrome

Background: Alveolar macrophage (AM) dysfunction contributes to Acute Respiratory Distress Syndrome (ARDS) pathogenesis. We investigated the role of extracellular vesicles (EVs) in mediating this dysfunction. Methods: Pulmonary EVs were isolated from broncho-alveolar lavage and non-directed bronchial lavage samples of ventilated sepsis patients with and without ARDS, and post-operative control patients via ultracentrifugation. AMs were isolated from lung tissue resections of lobectomy patients. AMs were treated with pooled EVs for 24 hours prior to functional, metabolic and autophagy profiling. EV cargo was profiled via small RNA transcriptomics and proteomics. Mechanistic role of EV microRNAs was assessed via mimic / antagomir transfection. Results: Pulmonary EVs from sepsis patients with ARDS impaired AM efferocytosis, and control EVs had no effect. ARDS EV treatment enhanced AM mitochondrial-linked respiration, but not glycolysis. ARDS EV treatment impaired LC3B-II and LAMP1 expression, indicating dysregulated AM autophagy-lysosomal machinery. Proteomics revealed downregulation of innate immune pathways in ARDS EVs. Transcriptomics revealed enrichment of 24 microRNAs in ARDS EVs; miR-652-3p was the most enriched, validated by RT-qPCR. EV miR-652-3p was associated with 90-day mortality (9.20 vs 0.59 RQ, p=0.0295) and inversely correlated with oxygenation (PaO2/FiO2). AM transfection with miR-652-3p mimic induced similar dysregulation of function and autophagy as ARDS EVs. Transfection of ARDS EVs with antagomirs to miR-652-3p prior to AM treatment partially rescued efferocytosis and autophagy. Conclusions: Targeting EV miR-652-3p may restore alveolar macrophage function and reduce excessive inflammation, thus offering a novel therapeutic strategy for patients with ARDS.

24.
arXiv (CS.AI) 2026-06-19

Optimal Scheduling in a Question-Answering Forum of Knowledge Workers

arXiv:2606.19759v1 Announce Type: new Abstract: As individuals turn to the Internet to find answers to questions they may have, several Question Answering (QA) forums have evolved, where users knowledgeable in certain topics can contribute their expertise to answering these requests for information. While these are currently volunteer based, we consider a future version employing knowledge workers who are experts in certain topics. In such a system, the request-answer processes forming the queuing system may utilize schedulers that assign requests in different topics to the experts in the forum, who may be able to answer them according to their expertise levels in different topics. With this model, we calculate the capacity of the system for handling the requests while keeping the system stable, and design schedulers that achieve capacity. We also investigate how collaboration between experts in answering requests can potentially increase capacity.

25.
Nature (Science) 2026-06-25

Base editing reveals an essential role for NANOG in human embryogenesis

Understanding how the first cell lineages in human development are specified and maintained has fundamental importance and clinical implications for regenerative medicine, infertility and pregnancy loss. While mouse models have provided valuable insights into transcription factors regulating early development, translating these findings to human embryos has been limited by ethical, technical and biological constraints. Functional studies of transcription factors in human embryos have been hindered by nuclease-based genome-editing approaches that induce genotoxicity1-3. To overcome this, we applied adenine base editing (ABE8e)4,5 to precisely target an exon splice donor site, resulting in a splicing defect and functional knockout of NANOG, representing the first application of base editing to study a developmental regulator in human embryos. This approach did not trigger genotoxicity and showed limited off-target editing. Loss of NANOG disrupts pluripotent epiblast specification and instead cells differentiate toward a primitive endoderm (yolk sac) or trophectoderm (placental) transcriptional programme. Retention of primitive endoderm differentiation in NANOG-edited human embryos reveals a functional compensation distinct from mouse, underscoring the importance of directly investigating human development. Our findings demonstrate an essential role for NANOG in human pluripotency and epiblast specification, and highlight the utility of base editing for functional interrogation of human development.