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01.
arXiv (CS.AI) 2026-06-25

Offline Multi-agent Continual Cooperation via Skill Partition and Reuse

arXiv:2606.25389v1 Announce Type: new Abstract: Extracting skills from multi-agent offline dataset improves learning efficiency via sharing task-invariant coordination skills among tasks. In settings where tasks occur sequentially and the space of skills grows exponentially, existing approaches that rely on heuristically designed and fixed-sized skill libraries struggle to resolve the problem of distributional shift and interference, facing catastrophic forgetting and plasticity loss. To address this problem and endow agents with the ability to continually discover and reuse coordination skills in open-environment, we propose COMAD, a principled framework for Continual Offline Multi-agent Skill Discovery via Skill Partition and Reuse. We first discover skills from mixed multi-agent behavior data with an auto-encoder to transform coordination knowledge into reusable coordination skills. Then we construct a skill-augmented policy learning objective with multi-head architectures, explicitly guiding the advantage function with reusable skills identified via a density-based reusability estimator. Theoretical analysis shows our method approximates the optimum of a continual skill discovery problem. Empirical results across diverse MARL benchmarks show that COMAD continually expands its skill library to mitigate interference, achieving superior forward and backward transfer for task streams compared to multiple baselines.

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

MOCHI: Motion Enhancement of Collaborative Human-object Interactions

Collaborative human-object interaction shows dynamic and complex movements that require mutual anticipation and continuous adjustment between participants and the shared object. Modeling such collaborative multi-human object interaction (MHOI) scenarios requires high-quality data acquisition as a foundational step; however, this is challenging due to the inherent complexity of MHOI where human-human and human-object interactions occur simultaneously. Such complexity leads to noisy MHOI captures characterized by several artifacts: contact misalignment between hands and objects, motion jitter and temporal inconsistencies in the captured sequences, and missing or incomplete finger-level articulation details. To address these challenges, we present MOCHI (MOtion Enhancement of Collaborative Human-object Interactions), a two-stage framework for enhancing noisy MHOI data. Our approach first generates physically plausible hand grasps through optimization from noisy body input, producing grasps that are both physically plausible and semantically consistent with the body pose, where these optimized grasps are extended into complete hand-object interaction sequences. Consequently, the full-body motion for all participants are refined through a diffusion-based noise optimization framework that uses single-person motion priors. During the optimization process, we introduce optimization objectives to encode human-object and human-human interaction information within these single-person priors. Experimental results demonstrate the effectiveness of our pipeline across diverse MHOI data, either acquired by existing capture methods or synthesized by generative models. We further show robustness of our system across varying numbers of participants and types of interactions, and demonstrate various applications including keyframe-based MHOI creation and data augmentation through varying object geometries.

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

See-and-Reach: Precise Vision-Language Navigation for UAVs within the Field of View

arXiv:2606.20045v1 Announce Type: cross Abstract: UAV Vision-Language Navigation (UAV-VLN) is typically formulated as a holistic search-and-reach problem, where long-range target discovery and final target approach are optimized and evaluated jointly. This formulation makes it difficult to assess a critical capability of aerial embodied agents, namely whether a UAV can accurately ground a visible target and translate vision-language evidence into precise 3D motion once the target enters its field of view. To address this limitation, we introduce UAV-VLN-FOV, a target-visible navigation task that isolates the see-and-reach stage and enables a more diagnostic evaluation of terminal reaching ability. We further propose 3DG-VLN, a vision-language waypoint prediction framework guided by dynamic 3D direction cues to enhance fine-grained visual grounding and spatial direction alignment for precise target reaching. Specifically, 3DG-VLN adaptively processes high-resolution front-view and downward-view observations to preserve fine-grained visual and geometric details for target grounding. It also updates the target-relative direction online during closed-loop navigation, allowing the agent to maintain spatial alignment with the target and reduce accumulated direction drift. To support this task, we construct a dedicated high-resolution benchmark which contains 2,717 trajectories with target-oriented high-level instructions, high-resolution front-view and downward-view egocentric observations, and continuous 3D waypoint annotations. Experiments show that 3DG-VLN outperforms competitive UAV-VLN baselines, achieving a 13.82\% improvement in success rate. Real-world trials further demonstrate the potential of 3DG-VLN for practical see-and-reach navigation. The source code and benchmark are available at https://github.com/xuefanfu/3DG-VLN.

04.
arXiv (CS.CL) 2026-06-25

The Interplay of Harness Design and Post-Training in LLM Agents

Tool-integrated LLM agents are often wrapped within a harness: the scaffolding that determines which tools are exposed, how they are described, and what auxiliary information accompanies each per-step observation. While agents are routinely post-trained, this scaffolding is typically treated as a fixed engineering detail, with design effort limited to the training-free regime. Moreover, existing post-training algorithms assume a static environment, even though tool environments and tasks often shift upon deployment. To address this gap, we extend $\texttt{ALFWorld}$ (i) to treat the harness as a controllable design dimension and (ii) to support evaluation under task and tool environment shifts. Building on this, we systematically analyze how the harness design influences post-training in both in-distribution and out-of-distribution (OOD) settings. We empirically show that harness-aware post-training not only improves in-distribution performance but also enables agents to robustly adapt to OOD settings. Under a harness with minimal design effort, post-training suffers a drastic performance drop under stronger tool environment shifts, further highlighting the importance of harness-aware post-training under such shifts.

05.
medRxiv (Medicine) 2026-06-24

Structural ethnic inequities in maternal mortality between Indigenous and non-Indigenous women in Paraguay, 2014-2023: a national analysis of territorial, institutional, and preventable factors.

Background: Indigenous women in Paraguay continue to experience disproportionately high maternal mortality despite national efforts to improve maternal health. Evidence on the structural factors underlying these disparities remains limited. Objectives: To analyze structural ethnic inequities in maternal mortality between Indigenous and non-Indigenous women in Paraguay, focusing on territorial patterns, institutional access, and potentially preventable causes of death. Design: National population-based study using maternal mortality records registered in Paraguay between 2014 and 2023. Maternal mortality ratios (MMRs), incidence rate ratios (IRRs), and absolute differences were estimated according to Indigenous status. Logistic regression models were used to assess associations with deaths occurring outside healthcare institutions and specific preventable causes of death. Results: A total of 907 maternal deaths were identified, including 112 among Indigenous women (12.3%). Indigenous women were overrepresented by a factor of 4.8 relative to their population share. Maternal mortality remained consistently higher among Indigenous women throughout the study period, with mortality ratios ranging from 317.7 to 773.6 per 100,000 live births, compared with 58.7 to 145.1 among non-Indigenous women. Absolute inequalities remained persistently high over time. Overall, 24.3% of maternal deaths occurred outside healthcare institutions, with a substantially higher proportion among Indigenous women (44.6% versus 21.5%). After adjustment for age and educational level, Indigenous women had more than three times greater odds of dying outside healthcare institutions (aOR = 3.41; 95% CI: 2.20-5.29). Potentially preventable causes accounted for 42.4% of maternal deaths. Obstetric hemorrhage was strongly associated with Indigenous status (aOR = 3.83; 95% CI: 2.31-6.37). Conclusion: Indigenous women in Paraguay experience a disproportionate burden of maternal mortality characterized by persistent ethnic disparities, higher occurrence of deaths outside healthcare institutions, and a substantial burden of preventable causes of death. These findings suggest the presence of enduring territorial, institutional, and healthcare access barriers that contribute to structural ethnic inequities in maternal health.

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

Surflo: Consistent 3D Surface Flow Model with Global State

Geometry is invariant to viewpoint, which makes any collection of images a redundant encoding of a single 3D state. Existing feed-forward reconstruction models fail to exploit this: per-view methods emit overlapping, unaligned pointmaps that grow linearly with input count, while global-latent methods commit to a fixed, low-resolution output. We introduce Surflo, which compresses a variable number of unposed RGB views into K latent tokens-one global state-and decodes oriented 3D surface points by independently transporting them from noise onto the surface via flow matching. This frees the output from any fixed grid or token budget: the same latent yields from a few thousand to a million points in a single forward pass. To suppress the local inconsistencies inherent to independent per-point decoding, an inference-time guidance term correlates nearby points by injecting a photometric gradient during ODE integration. Surflo matches or surpasses feed-forward baselines on surface metrics, runs an order of magnitude faster than optimization-based methods that require hundreds of views, and is the only feed-forward approach to combine a global latent with arbitrary-resolution decoding.

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

Self-Evolving Multi-Agent Systems via Textual Backpropagation

arXiv:2506.09046v3 Announce Type: replace-cross Abstract: Leveraging multiple Large Language Models (LLMs) has proven effective for addressing complex, high-dimensional tasks, but current approaches often rely on static, manually engineered multi-agent configurations. To overcome these constraints, we present the Agentic Neural Network (ANN), a framework that conceptualizes multi-agent collaboration as a layered neural network architecture. In this design, each agent operates as a node, and each layer forms a cooperative team focused on a specific subtask. Our framework follows a two-phase optimization strategy: (1) Forward Phase - Drawing inspiration from neural network forward passes, tasks are dynamically decomposed into subtasks, and cooperative agent teams with suitable aggregation methods are constructed layer by layer. (2) Backward Phase - Mirroring backpropagation, we refine both global and local collaboration through iterative feedback, allowing agents to self-evolve their roles, prompts, and coordination. This neuro-symbolic approach enables our framework to create new or specialized agent teams post-training, delivering notable gains in accuracy and adaptability. Across seven benchmark datasets, our work surpasses leading multi-agent baselines under the same configurations, showing consistent performance improvements.

08.
arXiv (CS.CV) 2026-06-25

Tensorion: A Tensor-Aware Generalization of the Muon Optimizer

Common first-order optimizers, such as Adam, implicitly treat each parameter block as an unstructured vector, which disregards the multilinear weight structure present in many modern machine learning models. Recent work has shown that exploiting matrix structure can improve optimization dynamics. A notable example is Muon, which performs steepest descent under the spectral norm constraint. We take the next step and introduce Tensorion, a tensor-aware optimizer that extends Muon's constrained optimization perspective from matrices to higher-order tensors. Tensorion is built around a linear minimization oracle (LMO) over a tensor norm ball. The norm is carefully chosen to balance two objectives: tightly bounding the tensor spectral norm, while still keeping the LMO tractable. This LMO becomes computable because it reduces to operations on adaptively selected unfolding matrices. Notably, when restricted to order-2 tensors (i.e., matrices), Tensorion recovers Muon exactly. Experiments on tensor-based computer vision problems suggest that Tensorion can offer improved convergence behavior and more stable gradient updates compared with Adam-based and existing tensor-aware baselines in the evaluated settings.

09.
arXiv (CS.LG) 2026-06-15

Mitigating Heterogeneity-Induced Drift in Hierarchical Sign-Based Federated Learning

arXiv:2602.02355v2 Announce Type: replace-cross Abstract: Hierarchical federated learning (HFL) is well suited for large-scale wireless and Internet of Things systems, where devices communicate with nearby edge servers before reaching the cloud. In these environments, uplink bandwidth and latency impose strict communication constraints, making aggressive gradient compression essential. One-bit sign-based stochastic gradient descent methods provide an attractive solution in flat federated settings, but their behavior in hierarchical edge–cloud architectures remains insufficiently understood, especially under inter-cluster data heterogeneity. To address this gap, we develop a sign-based HFL framework in which devices transmit binary stochastic-gradient signs to edge servers, edge servers apply majority voting, and the cloud periodically aggregates edge models. Our analysis reveals that inter-cluster heterogeneity induces a persistent bias term in the convergence bound, reflecting the drift of edge models toward local objectives. This term cannot be removed by increasing the number of training rounds or by tuning standard hyperparameters alone. We therefore propose \(\mathtt{DC-HierSignSGD}\), a drift-corrected sign-based HFL algorithm in which devices apply a cloud-assisted gradient correction before taking the sign. We show that this pre-sign correction mitigates the non-vanishing heterogeneity-induced bias while preserving binary device–edge communication during the repeated local sign-update steps. Experiments under severe inter-cluster heterogeneity demonstrate that \(\mathtt{DC-HierSignSGD}\) improves the stability and accuracy of sign-based HFL and achieves performance comparable to full-precision hierarchical SGD with substantially lower device–edge communication.

10.
arXiv (quant-ph) 2026-06-24

Erasure cost of a quantum process: A thermodynamic meaning of the dynamical min-entropy

arXiv:2506.05307v5 Announce Type: replace Abstract: The erasure of information is fundamentally an irreversible logical operation, carrying profound consequences for the energetics of computation and information processing. We investigate the thermodynamic costs associated with erasing (and preparing) quantum processes. Specifically, we analyze an arbitrary bipartite unitary gate acting on logical and ancillary input-output systems, where the ancillary input is always initialized in the ground state. We focus on the adversarial erasure cost of the reduced dynamics - that is, the minimal thermodynamic work cost to erase the logical output of the gate for any logical input, assuming full access to the ancilla but no access to any purifying reference of the logical input state. We determine that this adversarial erasure cost is directly proportional to the negative min-entropy of the reduced dynamics, thereby giving the dynamical min-entropy a clear operational meaning. The dynamical min-entropy can take positive and negative values, depending on the underlying quantum dynamics. The negative value of the erasure cost implies that the extraction of thermodynamic work is possible instead of its consumption during the process. A key foundation of this result is the quantum process decoupling theorem, which quantitatively relates the decoupling ability of a process with its min-entropy. This insight bridges thermodynamics, information theory, and the fundamental limits of quantum computation.

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

K-Prism: A Knowledge-Guided and Prompt Integrated Universal Medical Image Segmentation Model

Medical image segmentation is fundamental to clinical decision-making, yet existing models remain fragmented. They are usually trained on single knowledge sources and specific to individual tasks, modalities, or organs. This fragmentation contrasts sharply with clinical practice, where experts seamlessly integrate diverse knowledge: anatomical priors from training, exemplar-based reasoning from reference cases, and iterative refinement through real-time interaction. We present $K-Prism$, a unified segmentation framework that mirrors this clinical flexibility by systematically integrating three knowledge paradigms: (i) $semantic priors$ learned from annotated datasets, (ii) $in-context knowledge$ from few-shot reference examples, and (iii) $interactive feedback$ from user inputs like clicks or scribbles. Our key insight is that these heterogeneous knowledge sources can be encoded into a dual-prompt representation: 1-D sparse prompts defining $what$ to segment and 2-D dense prompts indicating $where$ to attend, which are then dynamically routed through a Mixture-of-Experts (MoE) decoder. This design enables flexible switching between paradigms and joint training across diverse tasks without architectural modifications. Comprehensive experiments on 18 public datasets spanning diverse modalities (CT, MRI, X-ray, pathology, ultrasound, etc.) demonstrate that K-Prism achieves state-of-the-art performance across semantic, in-context, and interactive segmentation settings.

12.
Nature Biotechnology 2026-06-19

Optimized R2 retroelement complexes for DNA insertion into plant genomes

Traditional approaches for DNA insertion into plant genomes using Agrobacterium tumefaciens result in random integration. Newer genetic engineering methods based on nucleases, prime editors, transposases and recombinases extend capabilities but remain constrained with low efficiencies, off-target integration or limited payload size. Here we adapt the avian Taeniopygia guttata R2 protein (R2Tg) for targeted DNA insertion into plant genomes by engineering R2Tg expression cassettes and RNA payloads carrying intron-disrupted reporters, with optimized ribosomal DNA homology arms and untranslated regions. In Arabidopsis thaliana protoplasts, Nicotiana benthamiana leaves and Solanum lycopersicum seedlings, our R2Tg editor system achieves targeted insertion of full-length payloads ranging from 2.2 kb to 5 kb. In Nicotiana benthamiana leaves, integration occurs, on average, at 1 copy per genome, which is 30 times more efficient than that achieved by Cas9 homology-directed repair. This work establishes an R2Tg ribonucleoprotein platform for targeted DNA insertion into plant genomes, using a multicopy genomic safe-harbor site to enable efficient addition of multikilobase genes. R2 retrotransposons are used to integrate DNA into plant and crop 25S ribosomal DNA sites.

13.
arXiv (quant-ph) 2026-06-12

Testing the problem of time with cold atoms

arXiv:2509.07745v3 Announce Type: replace-cross Abstract: We realize a cold-atom system to quantitatively test relational constructions of time. A well-isolated atomic Bose-Einstein condensate evolves in a conservative trap that is partitioned by a thin optical barrier into an observed and unobserved sector, with negligible dissipation on the experimental timescale. Motivated by relational-time approaches discussed in the Wheeler-DeWitt framework, we ask whether the dynamics of the observed sector can be ordered using only internal degrees of freedom. To this end, we construct an entropic time from an experimentally defined coarse-grained entropy, and demonstrate that it can robustly order the events in the observed sector across repeated cycles of expansion and recollapse. We finally derive an effective Schroedinger equation parameterized by this internal time and show that it is able to reproduce the measured evolution. These results establish a controlled experimental setting in which relational-time constructions can be quantitatively tested.

14.
arXiv (quant-ph) 2026-06-25

How to improve the accuracy of semiclassical and quasiclassical dynamics with and without generalized quantum master equations

arXiv:2603.04563v2 Announce Type: replace-cross Abstract: Semi- and quasi-classical (SC) theories can handle arbitrary interatomic interactions and are thus well-suited to predict quantum dynamics in condensed phases that encode energy and charge transport, spectroscopic responses, and chemical reactivity. However, SC theories can be computationally expensive and inaccurate. When combined with generalized quantum master equations (GQMEs), the resulting SC-GQMEs have been observed to enhance the efficiency and accuracy of SC dynamics. Yet, while the mechanism responsible for improved efficiency is clear, the underlying improved accuracy remains elusive. What is worse, SC-GQMEs can yield unphysical dynamics in challenging parameter regimes – a shortcoming that might be avoided if the mechanism of accuracy improvement were understood. Here, we uncover this mechanism. We leverage short-time analyses to prove that exact, "left-handed" time-derivatives delay the onset of SC inaccuracy, and show that their numerical integration yields dynamics with improved accuracy, even without the GQME. We find, however, that these derivatives are a double-edged sword: while offering greater short-time accuracy, they become unphysical in challenging parameter regimes. Because short-lived memory kernels can leverage short-time accuracy while circumventing long-time instability, we develop a protocol to unambiguously determine the memory kernel cutoff, even in challenging regimes where previous treatments had failed. Our insights into accuracy improvement and kernel cutoff protocol can be expected to apply to complex systems that go beyond simple models.

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

Contact-Based Fringe Projection Profilometry for High-Resolution 3-D Surface Measurement of Reflective and Transparent Objects

This paper presents a contact-based 3-D surface measurement method based on a Digital Fringe Projection (DFP) system, belonging to the vision-based tactile sensing family pioneered by the commercially successful GelSight sensor. Such sensors have proven effective for robotic fingertip manipulation and contact sensing. However, because GelSight employs photometric stereo with RGB LEDs, it does not measure absolute depth directly but instead infers it by integrating estimated surface gradients, which can accumulate reconstruction errors; in addition, it becomes increasingly difficult to calibrate as the sensing area grows, and its depth accuracy is challenged on highly reflective or transparent objects. To overcome these drawbacks, we propose a fringe-projection-based contact measurement technique that performs triangulation-based 3-D reconstruction on a coated silicone contact surface, providing dense per-pixel surface geometry and full-field 3-D shape measurement over the contact region. By integrating high-accuracy digital fringe projection into the sensor, our approach simplifies calibration over larger areas and enhances depth precision for complex surfaces. Experimental results, including a direct comparison with a GelSight Mini sensor, a sphere-fitting accuracy evaluation, and an uncertainty analysis, confirm that the proposed method significantly improves the accuracy and stability of structured-light-based 3-D measurements, allowing reliable reconstruction of objects with diverse optical properties.

16.
arXiv (quant-ph) 2026-06-25

Quantum Primitive for Output-Hiding Function Sharing

arXiv:2606.25080v1 Announce Type: new Abstract: A quantum information-theoretic primitive is introduced for determining a discrete-valued function that depends on multiple parties' local private inputs. The primitive permits the parties to mutually learn each others' local inputs, and thereby determine function values, while their individual systems remain independent of these inputs. The resulting function values are shared among the parties, but may remain information-theoretically hidden from any external observer, as well as from adversarial state-preparation or measurement processes within the quantum system, in every iteration. In particular, while classically producing a shared function with these information-theoretic properties requires the use of private keys or hidden randomness, in the proposed setting it is achieved using quantum resources alone. I outline the primitive's general properties while applications across a broad range of secure quantum communication and computation settings including: quantum key distribution, multi-party coordination and decision schemes, function evaluation, and in some settings, protocols for fairly generated private coins, are relegated to further publications.

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

NTIRE 2024 Challenge on Image Super-Resolution (x4): Methods and Results

This paper reviews the NTIRE 2024 challenge on image super-resolution ($\times$4), highlighting the solutions proposed and the outcomes obtained. The challenge involves generating corresponding high-resolution (HR) images, magnified by a factor of four, from low-resolution (LR) inputs using prior information. The LR images originate from bicubic downsampling degradation. The aim of the challenge is to obtain designs/solutions with the most advanced SR performance, with no constraints on computational resources (e.g., model size and FLOPs) or training data. The track of this challenge assesses performance with the PSNR metric on the DIV2K testing dataset. The competition attracted 199 registrants, with 20 teams submitting valid entries. This collective endeavour not only pushes the boundaries of performance in single-image SR but also offers a comprehensive overview of current trends in this field.

18.
arXiv (math.PR) 2026-06-25

Exponential Rank Bounds for Random Matrices

arXiv:2606.25204v1 Announce Type: new Abstract: Fix $b\in(0,1)$, let $1\leq k\leq n$, and let $A=(A_{ij})$ be an $n\times n$ random matrix with independent real entries satisfying $$ \sup_{x\in\mathbb{R}}\mathbb{P}\{A_{ij}=x\}\leq b0$ such that $$ \mathbb{P}\{\operatorname{rank} A\leq n-k\}\leq \exp(-cnk), \qquad 1\leq k\leq n. $$

19.
arXiv (quant-ph) 2026-06-17

Robust Spin Splitting and Strain-Controlled Optical Response in Monolayer CrC2N4 for Valleytronic and Optoelectronic Applications

arXiv:2606.17329v1 Announce Type: cross Abstract: Monolayer CrC2N4 recently emerged as a promising two-dimensional semiconductor, yet its spin-orbit-coupled (SOC) physics and strain-tunable optical response remained largely unexplored. Here, we investigated the electronic, valley, charge-transfer, and optical properties of pristine and biaxially strained monolayer CrC2N4 using first-principles calculations. The monolayer exhibited a direct band gap at the K/K' valleys. SOC produced valley contrasting out-of-plane spin polarization, yielding a moderate valence band spin splitting of 51.9 meV and a small conduction band spin splitting of 1.7 meV. Orbital-resolved analysis showed that the edge states were mainly governed by Cr-d and N-p hybridization, while Bader analysis indicated polar-covalent bonding through charge transfer toward N atoms. Biaxial strain in the range of -4% to +4% tuned the band gap from 1.987 to 1.421 eV and drove an indirect-to-direct gap transition near -1% strain. Tensile strain enhanced the Berry curvature and red-shifted the optical response toward the visible-near-infrared region. These results suggested monolayer CrC2N4 as a promising platform for strain-engineered valleytronic and optoelectronic device applications.

21.
arXiv (CS.AI) 2026-06-17

FoundCause: Causal Discovery with Latent Confounders from Observational Data

arXiv:2606.17516v1 Announce Type: cross Abstract: Causal discovery from observational data remains challenging due to the need to recover directed structure and latent confounding without interventions. We propose FoundCause, an amortized causal discovery model trained entirely on synthetic data that maps datasets directly to causal graphs in a single forward pass. By learning from large collections of simulated structural causal models, FoundCause captures transferable statistical patterns that generalize beyond individual datasets. The architecture incorporates several key inductive biases for causal discovery. It uses a permutation-invariant transformer encoder with alternating attention over samples and variables to jointly model cross-variable dependence and per-variable distributions. Pairwise statistical features derived from classical asymmetry measures are injected through statistics-conditioned attention, guiding the model toward known causal signals. A factorized decoder separates edge existence from direction, while a triangular refinement module enables reasoning over higher-order causal motifs such as chains and colliders. In addition, a dedicated confounder module based on learnable latent tokens explicitly models hidden common causes, and the model explicitly handles missing data via its masked input representation. To our knowledge, FoundCause is the first amortized causal discovery approach to explicitly model latent confounding. FoundCause outperforms 11 classical non-amortized methods (e.g., PC, GES, NOTEARS-style optimization) and 4 amortized causal discovery methods on 15 real-world datasets, achieving +9.6% improvement in $F_1$, +1.2% in AUROC, and an 18.9% reduction in structural Hamming distance relative to the strongest non-amortized methods, while performing inference in a single forward pass.

22.
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.

23.
medRxiv (Medicine) 2026-06-12

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

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

24.
medRxiv (Medicine) 2026-06-19

Within-host pathogen population diversity predicts treatment response in tuberculosis

Background: Tuberculosis (TB) treatment outcomes remain suboptimal, and standard clinical diagnostics cannot reliably identify patients at high risk of treatment failure or relapse at the time of diagnosis. While within-host Mycobacterium tuberculosis genetic diversity is hypothesized to reflect the viable bacterial burden and adaptive capacity of the infection, its clinical prognostic value remains unknown. Methods: We conducted a prospective cohort study of 364 patients with newly diagnosed, rifampicin-susceptible pulmonary TB in South Africa. Patients received standard 6-month therapy and were monitored for up to two years to ascertain composite unfavorable outcomes (treatment failure, death, or relapse). To accurately detect low-frequency (unfixed) genetic variants and eliminate reference bias artifacts, we mapped medium to high depth short-read sequences against matched, patient-specific long-read assemblies. The association between baseline pathogen genetic diversity and clinical outcomes was evaluated using multivariable Cox proportional-hazards models. Results: After bioinformatic filtering, true unfixed variants were relatively rare but significantly enriched in genes mediating pathogen adaptation and drug tolerance, including transporter proteins and two-component regulatory systems. Within-host bacterial genetic diversity (i.e., the total number of unfixed variants) ranged from 0-20, with a median of 1 per patient. In survival analysis adjusting for known clinical risk factors–including HIV status, prior TB, baseline smear positivity, and radiographic lung involvement–baseline within-host genetic diversity emerged as a strong, independent predictor of unfavorable treatment outcomes. For patients with greater than 3 unfixed variants at diagnosis, each increase of 5 unfixed variants was associated with more than double the risk of a composite unfavorable outcome (adjusted Hazard Ratio, 2.36; 95% CI, 1.27 to 4.39; p=0.007). Conclusions: Baseline within-host pathogen genetic diversity is an independent predictor of unfavorable TB treatment outcomes. As sequencing becomes increasingly integrated into routine diagnostics, quantifying unfixed variants is an accessible approach that promises to risk-stratify patients and guide the duration of individualized regimens.

25.
arXiv (CS.CV) 2026-06-12

OccAny: Generalized Unconstrained Urban 3D Occupancy

Relying on in-domain annotations and precise sensor-rig priors, existing 3D occupancy prediction methods are limited in both scalability and out-of-domain generalization. While recent visual geometry foundation models exhibit strong generalization capabilities, they were mainly designed for general purposes and lack one or more key ingredients required for urban occupancy prediction, namely metric prediction, geometry completion in cluttered scenes and adaptation to urban scenarios. We address this gap and present OccAny, the first unconstrained urban 3D occupancy model capable of operating on out-of-domain uncalibrated scenes to predict and complete metric occupancy coupled with segmentation features. OccAny is versatile and can predict occupancy from sequential, monocular, or surround-view images. Our contributions are three-fold: (i) we propose the first generalized 3D occupancy framework with (ii) Segmentation Forcing that improves occupancy quality while enabling mask-level prediction, and (iii) a Novel View Rendering pipeline that infers novel-view geometry to enable test-time view augmentation for geometry completion. Extensive experiments demonstrate that OccAny outperforms all visual geometry baselines on 3D occupancy prediction task, while remaining competitive with in-domain self-supervised methods across three input settings on two established urban occupancy prediction datasets. Our code is available at https://github.com/valeoai/OccAny .