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

LandslideAgent with Multimodal LandslideBench: A Domain-Rule-Augmented Agent for Autonomous Landslide Identification and Analysis

Intelligent landslide hazard interpretation is critical for disaster prevention, yet current paradigms struggle to simultaneously extract visual features and high-level geoscientific semantics, while general-purpose vision-language models (VLMs) suffer from perceptual limitations and domain hallucinations in complex geological scenarios. To address these challenges, we propose an instruction-driven agentic framework comprising three components. First, LandslideBench, a multimodal fine-grained dataset with seven subtype labels, high-resolution imagery, pixel-level masks, and high-quality textual descriptions, is constructed via multi-VLM cross-validation and interactive annotation. Then, LandslideVLM, a landslide-oriented VLM, is fine-tuned via LoRA on LandslideBench to enhance geological semantic understanding. Finally, LandslideAgent, a domain rule-enhanced agent taking LandslideVLM as its cognitive backbone, employs a dual-rule controller incorporating structured report metadata constraints and cross-validation identification constraints to regulate automated tool invocation. Experiments demonstrate that LandslideBench provides effective baselines across five mainstream models on fine-grained classification and semantic segmentation. LandslideVLM achieves accuracy improvements of 10.96%, 32.87%, and 15.91% on landslide discrimination, fine-grained classification, and semantic description quality, respectively. LandslideAgent further enables autonomous multi-source spatial data inference, realizing full-process intelligence for landslide identification and analysis.

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

Maximum Entropy Inverse Reinforcement Learning for Mean-Field Games with Average Reward

arXiv:2606.16759v1 Announce Type: new Abstract: We study inverse reinforcement learning for discrete-time, infinite-horizon mean-field games (MFGs) under an average-reward criterion. Expert demonstrations are assumed to arise from a stationary mean-field equilibrium under an unknown reward, and the goal is to recover a policy explaining the observed behaviour via the maximum causal entropy principle. We formulate the inverse problem by enforcing consistency with the expert mean-field term and long-run feature expectations, treating two reward classes within a unified occupation-measure framework. For finite-dimensional linear rewards, we give a convex dual reformulation with an explicit log-partition objective, and prove smoothness and curvature properties justifying constant-step-size gradient descent. For infinite-dimensional RKHS rewards, we develop a Lagrangian relaxation whose inner-maximising policy is characterised by a soft Bellman equation. The main obstacle is the absence of a discount-factor contraction. We resolve this by introducing a minorisation-based sub-stochastic kernel that yields a strict contraction of the soft Bellman operator. We establish Fréchet differentiability and Lipschitz smoothness of the log-likelihood score, leading to a gradient ascent algorithm with convergence guarantees. Two numerical examples, a malware-spread MFG and an RKHS-based consumer-choice model, show that the recovered policies closely match expert behaviour.

03.
arXiv (CS.CV) 2026-06-15

Improving Lunar Topography with Deep Learning Schrödinger Bridges

Increasing the resolution of planetary topography models can enable a better understanding of surface processes and geomorphology; however, existing analytical super-resolution methods are expensive and difficult to apply at large scales. Generative models provide the tools to learn complex relationships within data and can be applied at scale due to hardware accelerators and parallelization. We present a diffusion-based Schrödinger Bridge (SB) generative modeling approach for lunar topography super-resolution, connecting the distribution of low-resolution topography to that of high-resolution topography, incorporating physically-constraining optical imagery. Our approach is inspired by existing Shape-from-Shading methods, which improve a priori low-resolution topography by using optical images at the target resolution. We train SBs on a novel dataset of rendered lunar topography, emulating optical imagery from the Lunar Reconnaissance Orbiter Narrow Angle Camera. The result is a flexible approach for topography super-resolution which can provide pixel-level uncertainties in the reconstruction.

04.
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.

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

TetherCache: Stabilizing Autoregressive Long-Form Video Generation with Gated Recall and Trusted Alignment

Autoregressive video diffusion models provide a natural formulation for streaming and variable-length video generation by conditioning newly generated frames on previously generated content. However, extending these models to minute-level generation remains challenging: the limited KV-cache budget prevents the model from retaining the full history, while repeatedly conditioning on self-generated frames induces a context distribution shift that accumulates over time, leading to visual artifacts, quality degradation, and temporal drift. In this paper, we propose TetherCache, a training-free and plug-and-play cache management strategy for drift-resistant long video generation. TetherCache organizes the cache into sink, memory, and recent regions, and introduces two complementary mechanisms. First, GRAB (Gated Recall with Attention-Diversity Balancing) selects long-range memory frames using a gated score that combines attention-based relevance with temporal diversity, preserving informative yet diverse historical context under a fixed cache budget. Second, TAME (Trusted Alignment via Memory Editing) lightly edits newly recalled memory tokens by aligning their statistics to a trusted context distribution, reducing the pollution caused by drifted historical features. Built on Self-Forcing, TetherCache consistently improves long-video generation quality on VBench-Long across 30s, 60s, and 240s settings. In particular, for 240s generation, it substantially improves overall and semantic scores while reducing quality drift from 7.84 to 1.33, demonstrating its effectiveness for stable long-horizon autoregressive video diffusion.

07.
arXiv (quant-ph) 2026-06-12

Vacuum photon emission and mean electromagnetic field in pair-creating external backgrounds

arXiv:2606.12547v1 Announce Type: cross Abstract: We develop a perturbative description of vacuum radiative processes in quantum electrodynamics with a prescribed external electromagnetic background capable of producing electron-positron pairs. Since the initial vacuum is then unstable and the in- and out-vacua are inequivalent, radiative observables require a real-time formulation beyond the ordinary in-out approach of vacuum-stable QED. Using the Keldysh-Schwinger-Fradkin nonequilibrium technique, we derive the mean number density of emitted photons through the second nonvanishing order in the fine-structure constant. The leading term, of order $\alpha$, reproduces the known vertex and tadpole mechanisms, while the complete order-$\alpha^2$ correction contains interference, loop, and induced-current contributions. We also give an independent derivation based on the spectral decomposition of the identity operator in the in-Fock space, where the photon number density is represented as a sum of squared transition amplitudes and vacuum-disconnected terms are canceled by the optical theorem generalized to an unstable vacuum. In addition, we compute the mean electromagnetic field through order $e^3$, including the electromagnetic dressing of the induced vacuum current, and verify it using the corresponding Schwinger-Dyson equations. The final formulas are expressed in terms of exact solutions and propagators of the Dirac equation in the external background and apply to general spacetime-dependent field configurations.

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

PaperJury: Due-Process Review for Bounded LaTeX Revision

Pre-submission hardening of human-authored LaTeX computer science papers differs from drafting assistance because it requires adversarial whole-paper review, explicit no-fix outcomes, and bounded artifact-safe revision. Existing writing assistants, critique generators, and judge-centered loops lack durable issue identity across rounds, deterministic routing from critique to adjudication, and manuscript control that can reject invalid concerns or defer author-dependent ones. We present PaperJury, a closed-loop review-verdict-revise-verify system built on a deterministic-versus-semantic split: deterministic orchestration manages decomposition, a frozen claim spine, a durable ledger, routing, stopping, and exact-once patch application, while semantic agents are limited to bounded review, judgment, and repair. PaperJury combines bounded holistic review, contestability-based routing, a due-process trial, and risk-proportional guard chains for anchor-bounded edits, yielding terminal outcomes of invalid-drop, valid-fixable, and author-required. In a two-arm expert-review evaluation on held-out Vision, natural language processing, and machine learning papers against four baselines, we assess issue quality, verdict and routing quality, edit safety, convergence behavior, and cost, supporting the thesis that load-bearing safety and completion logic should reside in deterministic orchestration rather than model discretion. PaperJury is available at https://github.com/u7079256/paperjury.

09.
arXiv (CS.LG) 2026-06-16

Representation Costs in Data Science: Foundations and the Quasi-Banach Spaces of Deep Neural Networks

arXiv:2606.14954v1 Announce Type: cross Abstract: We develop a general framework for analyzing representation costs of parametric data-fitting methods through their parameter-space regularizers. From this abstract perspective, we define representation costs for arbitrary parametric models and reveal their induced (native) function spaces. This unifies recent function-space views of data-fitting methods. We also prove that many natural results hold in this abstract setting, including representer theorems for parametric methods on their native spaces. The framework also rigorously connects parametric methods with their equivalent nonparametric descriptions under sufficient overparameterization. Classical methods and their native spaces, such as kernel methods / reproducing kernel Hilbert spaces, wavelets / Besov spaces, and shallow neural networks / variation spaces emerge as special cases of our abstract framework. A byproduct of "axiomatizing" the study of representation costs is that we also immediately obtain new results for deep neural networks: For depth-$L$ feedforward ReLU networks, their induced native spaces are $p$-normable quasi-Banach spaces with $p = 2/L$. This reveals that the inductive bias of deep neural networks (as given by the representation cost) cannot be captured by norms for depths $L > 2$.

10.
arXiv (CS.CL) 2026-06-12

GENIE: A Fine-Grained Measure for Novelty

Large Language Models have consistently demonstrated a lack of creativity and diversity across tasks. Prior work has focused on addressing whether models are capable of generating creative outputs. Here, we aim to consider novelty and investigate what makes model-generated content novel or not novel in a task-specific manner. We propose a fine-grained evaluation metric GENIE to measure the novelty of responses along task-specific features with respect to a population of responses. We show that unlike GENIE, holistic metrics struggle to capture the high-dimensionality of novelty and do not provide insight on which properties they target. Finally, we use GENIE to measure the effectiveness of mitigation methods that address creativity to better understand where these methods can improve novelty.

11.
arXiv (CS.LG) 2026-06-12

Plan, Don't Pose: Long Composite Motion Generation with Text-Aligned BFM

arXiv:2605.29906v2 Announce Type: replace Abstract: Text-to-motion (T2M) generation has broad applications in character animation, virtual avatars, and human-robot interaction. Existing methods typically generate pose trajectories or motion tokens directly from language, forcing a single model to handle semantic interpretation, long-horizon structure, and low-level physical realization. This coupling makes them costly and often unreliable for long, compositional, or semantically dense prompts. We propose Text2BFM, the first framework that aligns natural language with pretrained Behavioral Foundation Models (BFMs) for T2M generation without relying on heavy end-to-end motion generators. Text2BFM operates in the latent policy space of a frozen BFM, using it as an executable motion prior. A text-aligned variational behavioral bottleneck compresses BFM policy-latent sequences into compact motion representations that are compatible with language and preserve long-horizon behavioral structure. Generation is performed in this compact behavioral manifold with a lightweight conditional generator, and the resulting latent encoded behaviors are decoded into policy latents that drive the pretrained frozen BFM. By decoupling semantic planning from motion execution, Text2BFM achieves efficient, robust T2M generation and strong performance on long, compositional textual descriptions.

12.
arXiv (CS.CV) 2026-06-11

Physics-Driven Spatiotemporal Modeling for AI-Generated Video Detection

AI-generated videos have achieved near-perfect visual realism (e.g., Sora), urgently necessitating reliable detection mechanisms. However, detecting such videos faces significant challenges in modeling high-dimensional spatiotemporal dynamics and identifying subtle anomalies that violate physical laws. In this paper, we propose the first physics-driven AI-generated video detection paradigm based on probability flow conservation principles. Specifically, we propose a statistic called Normalized Spatiotemporal Gradient (NSG), which quantifies the ratio of spatial probability gradients to temporal density changes, explicitly capturing deviations from natural video dynamics. Leveraging pre-trained diffusion models, we develop an NSG estimator through spatial gradients approximation and motion-aware temporal modeling without complex motion decomposition while preserving physical constraints. Building on this, we propose an NSG-based video detection method (NSG-VD) that computes the Maximum Mean Discrepancy (MMD) between NSG features of the test and real videos as a detection metric. Last, we derive an upper bound of NSG feature distances between real and generated videos, proving that generated videos exhibit amplified discrepancies due to distributional shifts. Extensive experiments confirm that NSG-VD outperforms state-of-the-art baselines by 16.00% in Recall and 10.75% in F1-Score, validating the superior performance of NSG-VD. The source code is available at https://github.com/ZSHsh98/NSG-VD.

13.
arXiv (CS.CL) 2026-06-17

Scaling Enterprise Agent Routing: Degradation, Diagnosis, and Recovery

Production LLM assistants route user requests to growing libraries of specialized tools, but how does routing accuracy degrade as the catalog scales? We study single-step routing on a 110-agent, 584-tool catalog from a deployed enterprise productivity assistant, evaluating three frontier models from 10 to 110 agents. Routing F1 on under-specified requests drops 16–23 percentage points across models. An oracle analysis decomposes the degradation into a retrieval gap (the model cannot surface the right tool) and a confusion gap (even with perfect retrieval, the oracle ceiling drops 10pp). Embedding-based shortlisting recovers +10–11pp F1 at full scale across all three models and two providers. A production annotation study (1,435 human-labeled utterances, three annotators) confirms the recovery on real traffic at +10–17pp despite 10–15pp lower absolute performance.

14.
arXiv (quant-ph) 2026-06-11

Fermions are fundamentally more nonlocal than Bosons

arXiv:2606.12363v1 Announce Type: new Abstract: Bell's theorem shows that entangled quantum particles can exhibit correlations that classical particles cannot reproduce without an additional nonlocal resource, such as communication. In this sense, quantum particles are fundamentally more nonlocal than classical ones, and entanglement becomes unavoidable in physics. Here we prove the analogous result within quantum theory itself: indistinguishable fermions transmitted through a quantum network can generate correlations that distinguishable particles or indistinguishable bosons cannot reproduce without additional communication. In the same sense, fermions are fundamentally more nonlocal than bosons or distinguishable particles, motivating fermionic anticommutation and indistinguishability as unavoidable operational resources. Our result further implies that fermions can strictly surpass all qubit-based protocols for certain distributed computing tasks, demonstrating that a complete understanding of information processing requires going beyond qubits to fermionic information carriers - febits.

15.
arXiv (CS.CL) 2026-06-11

Context-Aware Multimodal Claim Verification in Spoken Dialogues

Every day, millions absorb claims from podcasts and streams that no fact-checker ever sees. Spoken misinformation is built through conversation, where credibility comes not from facts alone but from how claims are framed, reinforced, or left unchallenged across turns. Yet fact-checking has focused on isolated text, leaving dialogue audio under-studied. We introduce MAD2, a new Multi-turn Audio Dialogues benchmark for spoken claim verification, containing 1,000 two-speaker dialogues with 3,368 check-worthy claims and approximately 10 hours of audio, and propose calibrated multimodal fusion of a context-aware audio encoder and a dialogue-aware text model. Across settings, adding dialogue context improves verification, but the gains depend on scenario type. Using only preceding context often matches offline performance, supporting live-moderation settings, and audio contributes most when transcript-based models are destabilized by additional context. Overall, conversational structure matters more for verification than misinformation framing.

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

Wasserstein Convergence of ODE-Based Samplers in Decentralized Diffusion Model via Velocity Field Decomposition

arXiv:2606.15835v1 Announce Type: cross Abstract: Diffusion models have achieved impressive empirical success in generative tasks, and their convergence theory is now relatively well understood. Motivated by privacy and scalability, recent decentralized diffusion architectures replace a single global velocity field with multiple local experts and a routing mechanism, yielding a sampling dynamics with stochastic expert switching that falls outside standard diffusion convergence analyses. In this work, We study a decentralized diffusion framework with stochastic velocity fields and ODE-based sampling. We establish a convergence guarantee in Wasserstein-2 distance, showing that the distribution of the $N$-step discretization converges to the analytical solution at rate $\mathcal{O}(N^{-1/2}+\varepsilon)$ in $W_2$, where $\varepsilon$ captures the neural approximation errors. To our knowledge, this is the first $W_2$ convergence result for decentralized diffusion models with an ODE-based sampling scheme.

17.
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.

18.
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.

19.
arXiv (math.PR) 2026-06-11

The $K$-th nearest neighbor random walk on a Poisson point process gets trapped

arXiv:2606.11271v1 Announce Type: new Abstract: The $K$-th nearest neighbor random walk $(X_n)_{n \geq 0}$ on a homogeneous Poisson point process $\chi$ on $\R^d$ ($d\geq 1$), starts at the origin and at each step picks its next Poisson point among its closest neighbors according to i.i.d. labels having the same distribution as $K$. Our main result (Theorem 1) states that the number of Poisson points visited by $(X_n)_{n \geq 0}$ admits an exponential decay whenever the random variable $K$ has a bounded support (BS). In particular, the $K$-th nearest neighbor random walk visits finitely many Poisson points if and only if $K$ satisfies Assumption (BS). To prove it, we introduce the key notion of pioneer point which allows us to deal with the region of $\R^d$ already explored by $(X_n)_{n \geq 0}$. Still under Assumption (BS), we also prove an exponential decay for the Euclidean length of the trajectory performed by $(X_n)_{n \geq 0}$ (Theorem 2). Finally, and quite surprisingly, we exhibit an example of label distribution with bounded support for which the $K$-th nearest neighbor random walk discovers new Poisson points after a number of steps whose tail distribution is at least polynomial (Theorem 3).

20.
arXiv (CS.AI) 2026-06-15

Evidence-Gated LLM Priors for Multi-Objective Bayesian Optimization

arXiv:2606.01730v2 Announce Type: replace Abstract: Large language models (LLMs) are increasingly used as heuristic advisors for black-box optimization, yet their suggestions and self-reported confidence are not necessarily calibrated to downstream objective values. This issue becomes more pronounced in multi-objective Bayesian optimization, where different objectives may require different expert knowledge and where an LLM expert can be useful for one objective but misleading for another. We study how to use LLM-generated expert priors in discrete multi-objective Bayesian optimization without blindly trusting them. We propose an objective-wise reputation-market mechanism that treats each expert-objective pair as a falsifiable prior source. Expert weights are updated online from observed objective feedback, discounted over time, and gated by market-level trust. We then introduce a decoupled counterfactual gate that can use the LLM prior without confidence, use it with confidence, or abstain from the LLM prior entirely. Across controlled synthetic stress tests and three molecule optimization benchmarks with \qwenflash{}-generated expert priors, we find that dynamic objective-wise calibration improves robustness over fixed LLM priors. However, raw LLM confidence is not reliably beneficial: on ESOL, confidence is positively correlated with prediction error; on FreeSolv, confidence can help; and on Lipophilicity, ignoring confidence remains strongest. Our fixed three-arm counterfactual gate improves over the first counterfactual variant on ESOL and FreeSolv, while an attempted margin portfolio exposes a useful negative result: margin selection should be acquisition-aware rather than based only on one-step prior error.

21.
medRxiv (Medicine) 2026-06-23

Food Colorings in Child-Targeted Ultra-Processed Foods in Brazil: Market Prevalence and Parental Perceptions

Child-targeted marketing on packaged foods can shape children's food preferences and parents' purchasing decisions, yet many products with child-targeted marketing are ultra-processed foods (UPFs) and contain cosmetic additives such as food colorings, which have raised concerns about adverse effects on children's health and behavior. This mixed-methods study examined the prevalence of food colorings in child-directed UPFs and explored parents' perceptions and knowledge of these additives in beverages commonly consumed by children. Quantitative data were obtained from the Mintel Global New Products Database to identify child-directed products launched in Brazil between 2018 and 2021, measured as having at least one child-targeted marketing strategy in the food package, and whether they contained food colorings. Qualitative data came from seven focus groups with parents of children aged 2-5 and 6-11 years in Brazil, alongside a brief survey assessing participants' ability to identify food colorings on product labels. Among 5,078 UPFs launched during the study period, 23.0% contained child-targeted marketing, and 40.3% of these had food colorings. The highest prevalence was observed in carbonated beverages, candies, and ice creams, in which more than half of products contained food colorings. Parents generally understood that food colorings are used to make products more attractive to children and associated them with potential health risks, but reported difficulties avoiding them. These findings highlight the widespread presence of food colorings in child-targeted UPFs in Brazil and underscore the need for stronger regulatory measures to restrict the use of food colorings and improve labelling on food packages.

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

Temporal Difference Learning for Diffusion Models

Diffusion models are typically trained with objectives that focus on local denoising targets at individual time steps (or adjacent pairs), which do not enforce consistency between predictions along the denoising trajectory. This lack of cross-time consistency can degrade performance, especially for few-step samplers. We introduce a temporal difference (TD) objective that penalizes inconsistency of the model's multi-step progress along the denoising path. By reformulating the diffusion process as a Markov reward process and casting denoising as a policy evaluation problem in reinforcement learning, we derive a unified TD approach that applies to both discrete- and continuous-time diffusion formulations. We further propose a principled sample-based reweighting method that stabilizes training. Empirically, we show that using our TD training can significantly improve sample quality measured by FID, with stronger advantages when the number of sampling steps is small, highlighting its practical utility under low-computation-budget scenarios. We provide ablation studies to justify our design choices, including pairwise loss reweighting, regularization weight, and one-step stride. Overall, our TD approach can be a general drop-in that enforces cross-time consistency and improves generation quality across different diffusion generative models.

23.
medRxiv (Medicine) 2026-06-15

Quantitative insights into the role of phages and plasmids in the persistence of nontuberculous mycobacteria in chloraminated drinking water

Nontuberculous mycobacteria (NTM) are opportunistic pathogens that persist in chloraminated drinking water systems, yet the roles of phages and plasmids in their persistence remain largely unexplored. Using genome-resolved and quantitative metagenomics, we characterized NTM, phages, prophages, and plasmids in a chloraminated building plumbing system. Bacterial metagenome-assembled genomes (MAGs) and viral operational taxonomic units (vOTUs) were quantified at mean concentrations of 8.41 * 10^7 and 8.00 * 10^8 copies/L, respectively, including seven NTM MAGs at a mean total concentration of 4.01 * 10^5 copies/L. NTM concentrations were highest at the site with the lowest bacterial and viral diversity. Predicted NTM-infecting virus concentrations were inversely related to NTM concentrations across sites, suggesting complex phage-host dynamics that warrant direct experimental investigation. NTM, putative phages, prophages, and plasmids encoded functions related to disinfectant tolerance, stress response, metal resistance, and secretion. These findings identify phage interactions, prophages, and plasmids as overlooked genomic and ecological dimensions of NTM persistence in engineered water systems.

24.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

作者:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

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

Beyond AHI: An Interpretable Causal-Discovery-Guided Framework for Sleep Recovery in Connected Health

arXiv:2606.18506v1 Announce Type: new Abstract: Objective sleep assessment relies on polysomnography (PSG), yet clinical impact is often better reflected in patient-reported outcomes (PROs) such as sleepiness and fatigue. Existing summary indices, including the Apnea-Hypopnea Index (AHI), provide limited insight into the multidomain physiology underlying functional recovery. We propose an interpretable, causal-discovery–guided framework for deriving a hierarchical Sleep Recovery Score (SRS) from multimodal PSG. Using two large population cohorts (MESA: n=1540; MrOS: n=825), we apply directed acyclic graph (DAG) learning to identify candidate physiological drivers spanning respiratory burden, hypoxic burden, sleep fragmentation, sleep architecture, and autonomic regulation. Although derived from clinical PSG, these domains map naturally to sensing streams increasingly available in connected health technologies, including wearable ECG, oximetry, and sleep-stage estimation devices. To preserve mechanistic plausibility, we introduce a two-stage screening process that combines physiology-based constraints with constrained LLM-assisted auditing to identify and remove structural confounders and construct-overlapping variables. Across cohorts, these five domains emerge as recurrent physiological domains associated with recovery, and the resulting SRS shows up to 2.5$\times$ stronger alignment with perceived recovery than AHI. By linking multimodal sleep physiology to patient-centered outcomes through an interpretable, bias-aware, and domain structured framework, this work provides a practical foundation for recovery modeling across both clinical sleep studies and emerging smart and connected health settings.