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01.
arXiv (CS.CV) 2026-06-15

WAM4D: Fast 4D World Action Model via Spatial Register Tokens

World action models (WAMs) have recently shown promise in jointly modeling future observations and executable robot actions. However, most existing WAMs still operate in 2D video or latent spaces, where visually plausible rollouts miss the 3D spatial constraints and occluded contact geometry required for precise manipulation. While geometric foundation models offer strong priors for recovering dense 3D structure and motion from visual observations, forcing WAMs to predict the dense 4D representation introduces costly geometric decoding and slows down causal action generation. To address the trade-off, we present WAM4D, a fast 4D world action model that uses lightweight spatial register tokens as training-time future-depth readouts to transfer pretrained geometric priors into a causal video-action transformer, then removes the register branch for lightweight action inference. To prevent non-causal shortcuts, we further design causal mixture attention for the Mixture-of-Transformers (MoT) WAM backbone, defining modality-specific visibility among video, action, and geometry tokens. Comprehensive experiments on RoboTwin 2.0 and challenging real-world manipulation tasks show that WAM4D improves spatial consistency and achieves competitive action prediction while maintaining efficient inference.

02.
arXiv (quant-ph) 2026-06-17

Coherent Control of an Embedded Bound State Without a Spectral Gap

作者:

arXiv:2606.17685v1 Announce Type: new Abstract: Bound states in the continuum (BICs) can confine photonic excitations in open systems without conventional cavities or band gaps, making them natural candidates for long-lived quantum storage and single-photon control. Their use is limited, however, by two obstacles: they are dark to incident photons, and they lack spectral-gap protection from the surrounding continuum. We overcome both limitations in a giant atom coupled to a one-dimensional waveguide using two temporal control knobs. Atomic-frequency modulation breaks and restores the destructive-interference condition, enabling deterministic capture and release of mode-matched single photons. Coupling modulation instead preserves the BIC condition while tuning the atomic and photonic weights of the stored state. A key result is that this embedded state can nevertheless be controlled adiabatically despite the absence of a spectral gap, with an intrinsic leakage probability linear in the ramp rate. By separating radiative access from BIC-preserving deformation, the protocol turns a dark BIC into a single-photon memory whose fidelity is set by the intrinsic continuum-induced leakage law, providing a route to embedded-state control in open photonic platforms.

03.
arXiv (CS.CL) 2026-06-12

More Context, Larger Models, or Moral Knowledge? A Systematic Study of Schwartz Value Detection in Political Texts

Detecting Schwartz values in political text is difficult because implicit cues often depend on surrounding arguments and fine-grained distinctions between neighboring values. We study when context and explicit moral knowledge help sentence-level value detection. Using the ValuesML/Touché ValueEval format, we compare sentence, window, and full-document inputs; no-RAG and retrieval-augmented settings with a curated moral knowledge base; supervised DeBERTa-v3-base/large encoders; and zero-shot LLMs from 12B to 123B parameters. The results show that more context is not uniformly better: full-document context improves supervised DeBERTa encoders by 3.8-4.8 macro-F1 points over sentence-only input, but does not consistently help zero-shot LLMs. Retrieved moral knowledge is more consistently useful in matched comparisons, improving each tested model family and context condition under early fusion. However, scaling from DeBERTa-v3-base to large and from 12B to larger LLMs does not guarantee gains, and simple early fusion outperforms the tested late-fusion and cross-attention RAG variants for encoders. Per-value analyses show that context and retrieval help most for socially situated or conceptually confusable values. These findings suggest that value-sensitive NLP should evaluate context, knowledge, and model family jointly rather than treating longer inputs or larger models as universal improvements.

04.
arXiv (CS.CV) 2026-06-18

Learning to Distort: Weakly-Supervised Image Quality Transfer for Prostate DWI Correction

Single-shot echo-planar prostate diffusion-weighted imaging (DWI) is frequently complicated by geometric distortions, which impact the ability to derive reliable diagnoses from such images. Developing automated correction methods is challenged by the absence of paired distorted and undistorted clinical scans. In this paper, we first propose a novel weakly-supervised image quality transfer (IQT) framework from undistorted to distorted images that utilizes image quality assessment (IQA) signals to supervise the transfer process. Unlike traditional methods that require expensive, voxel-wise paired data or resort to developing unpaired algorithms, our approach utilizes image-level quality labels (here, distorted vs. undistorted) to establish latent quality prototypes within a pre-trained feature space. Recognizing that simulating realistic distortions is more reliable than direct unpaired correction, we describe a weakly-supervised prototype flow matching algorithm to explicitly regularize generative trajectories towards distorted prototypes, producing realistic susceptibility artifacts that mimic clinical degradations. By synthesizing these realistic pairs, we enable a second IQT model to be trained in the forward direction for distortion correction. Experimental results demonstrate that our generated images successfully mimic the diagnostic interference of real-world artifacts, which leads to more capable distortion correction IQT models. In addition to qualitative comparisons, we also conduct exhaustive quantitative evaluations that compare our approach with existing unpaired approaches (e.g., CycleGAN, UNIT-DDPM, and OT-FM) - as either forward or reverse alternatives - by assessing clinical downstream task performance in PI-RADS and Gleason score classification, using both in-distribution and external data sets.

05.
arXiv (CS.CV) 2026-06-16

DifFRACT: Diffusion Feature Reconstruction and Attribution for Circuit Tracing

Mechanistic interpretability seeks to explain neural network behavior by decomposing model computations into interpretable features and circuits. While transcoder-based circuit tracing has recently enabled detailed causal analyses of large language models, multimodal diffusion transformers for image generation remain comparatively opaque. We still lack tools for understanding how semantic information propagates across denoising steps and how text and image representations interact within double-stream MM-DiT architectures. Existing methods provide only partial insight: attention maps expose a limited view of token interactions, while sparse autoencoders can discover interpretable features but do not directly reveal how these features are transformed and composed through nonlinear MLP layers. In this work, we extend transcoder-based circuit tracing to multimodal diffusion transformers. We train timestep-conditioned transcoders that faithfully approximate the input-output behavior of MLP sublayers in FLUX.1[schnell]. By replacing MLPs with transcoders and linearizing the remaining computation, we obtain exact feature-to-feature attribution and recover compact, interpretable circuits. Empirically, our transcoders match or slightly outperform sparse autoencoders on the sparsity-faithfulness tradeoff. The resulting circuits reveal mechanisms underlying attribute binding and cross-stream semantic propagation, and provide causal explanations for systematic generation errors. Moreover, circuit-guided interventions are substantially more precise and effective than standard SAE-based steering. Our results demonstrate that transcoder-based circuit analysis is feasible for state-of-the-art diffusion transformers and provides a powerful framework for understanding and controlling multimodal generative models. The code is available at https://github.com/Artalmaz31/DifFRACT

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

Conformal Bayes under Label Shift: Post-Hoc Calibration vs. In-Training Adaptation

arXiv:2606.11865v1 Announce Type: cross Abstract: Conformal Bayes combines Bayesian posterior predictives with conformal calibration to produce prediction sets that are both statistically valid and geometrically efficient. We study conformal Bayes under label shift from a unified perspective, identifying two complementary approaches that restore nominal target-domain coverage through importance-weighted conformal calibration but operate through independent mechanisms. Post-hoc calibration tilts the posterior predictive toward the target domain and corrects the conformal threshold via an importance-weighted quantile, leaving the parameter posterior unchanged. In-training adaptation tilts the parameter posterior itself to the target domain, producing a corrected predictive whose highest predictive density region serves as the highest predictive density (HPD) based prediction set under the fitted target predictive; efficiency is model-dependent and does not imply finite-sample conditional optimality. Two controlled experiments show that in an unbiased training regime both strategies achieve valid coverage equally, while in a lead-optimization regime in-training adaptation acts as a debiasing operator, reducing interval width at unchanged coverage.

07.
bioRxiv (Bioinfo) 2026-06-20

Seed variation impacts clustering stability in Single-Cell RNA-Seq and can be mitigated by StAbility-BasEd-Reassignment (SABER)

Single-cell RNA-seq clustering is commonly treated as reproducible once a random seed is fixed, yet the choice of seed itself may alter cell assignments and downstream interpretation. We systematically quantified seed-induced clustering variability by running Louvain and Leiden clustering across 100 seeds in Seurat and Scanpy on 28 single-cell RNA-seq datasets from the Human Cell Atlas and IMMUcan. Using Element-Centric Consistency, we found that seed choice affected a substantial fraction of cells, with Scanpy showing more unstable assignments than Seurat on average, 40.46% versus 26.78% unstable cells, respectively. This increased stability came at a marked computational cost: Seurat required approximately 19-fold higher median memory than Scanpy. Seed-dependent clustering variability also propagated to cell-type annotation, particularly among transcriptionally related populations including macrophage/monocyte, endothelial/epithelial and T/NK cell states. To mitigate this instability, we developed StAbility-BasEd Reassignment (SABER), a Scanpy-based framework that identifies seed-sensitive cells across repeated clusterings and reassigns them to stable cluster cores using cosine similarity. SABER improved clustering quality while preserving annotation concordance and reduced median memory usage 3.5-fold compared with Seurat-Louvain. Our results identify seed choice as an underappreciated source of variability in single-cell analysis and provide a scalable strategy to improve clustering robustness.

08.
arXiv (CS.AI) 2026-06-15

DIFF-ERO: A Conformance-Aware Loss for Deep Learning in Process Mining

arXiv:2606.14283v1 Announce Type: cross Abstract: Deep learning has driven many recent advances in process analytics, especially for predictive and prescriptive monitoring. However, standard objectives such as cross-entropy optimize local next-step likelihoods and only implicitly capture control-flow structure. As a result, models can achieve high token-level accuracy while permitting imprecise global behaviour. We introduce DIFF-ERO, a conformance-aware loss function for deep learning models on process data. DIFF-ERO is a differentiable formulation of entropy-based stochastic conformance that incorporates control-flow information during training. Our approach constructs batch-level stochastic transition matrices with soft edge memberships, allowing structural precision and recall signals to directly inform backpropagation. The loss is model-agnostic and can be applied whenever the final representation parametrizes stochastic transitions. We instantiate DIFF-ERO in transformer encoder-decoder pipelines for next-activity prediction and use it jointly with cross-entropy to analyse its theoretical components with respect to convergence. Across benchmarks comparing other loss functions and targets, DIFF-ERO shows improved predictive performance where structure matters most while maintaining parity elsewhere. At the same time, the learned stochastic automaton converges towards the structural ground truth, indicating that the network internalizes process model structure.

09.
PLOS Computational Biology 2026-06-01

A statistical framework for comparing epidemic forests

by Cyril Geismar, Peter J. White, Anne Cori, Thibaut Jombart Inferring who infected whom in an outbreak is essential for characterising transmission dynamics and guiding public health interventions. However, this task is challenging due to limited surveillance data and the complexity of immunological and social interactions. Instead of a single definitive transmission tree, epidemiologists often consider multiple plausible trees forming epidemic forests. Various inference methods and assumptions can yield different epidemic forests, yet no formal test exists to assess whether these differences are statistically significant. We propose such a framework using a chi-square test and permutational multivariate analysis of variance (PERMANOVA). We assessed each method’s ability to distinguish simulated epidemic forests generated under different offspring distributions. While both methods achieved perfect specificity for forests with 100+ trees, PERMANOVA consistently outperformed the chi-square test in sensitivity across all epidemic and forest sizes. Implemented in the R package mixtree, we provide the first statistical framework to robustly compare epidemic forests.

10.
arXiv (CS.LG) 2026-06-16

Test-Time Compute Scaling for ASR with Depth-Conditioned Looped Transformers

arXiv:2606.04678v2 Announce Type: replace Abstract: End-to-end ASR systems typically use fixed-depth acoustic encoders at inference, making it difficult to trade additional test-time computation for improved recognition without training a larger model. A natural approach is to reuse a shared Transformer block recurrently, but we find that naive looping does not fully exploit additional recurrent compute. We introduce LARM, a depth-conditioned looped Transformer that turns recurrent encoder depth into a controllable test-time compute axis. LARM combines sparse CTC checkpoints, supervision-clock embeddings, FiLM depth conditioning, and delayed soft-posterior feedback. These components structure the loop into recognition checkpoints separated by latent refinement phases and allow shared weights to specialize across recurrent steps. On LibriSpeech, LARM improves WER as the number of inference loops increases and achieves performance competitive with deeper unshared-parameter baselines. Our results show that test-time compute scaling can extend beyond autoregressive language-model reasoning to continuous non-autoregressive speech recognition.

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

Detecting Functional Memorization in Code Language Models

Large language models (LLMs) are increasingly used to generate code at scale. Meanwhile, prior work has investigated whether training data may be recoverable from model outputs, by auditing the textual overlap between training examples and model generations. Code, however, can be functionally equivalent while textually dissimilar. In this work, we study functional memorization: extraction of functional logic beyond what verbatim metrics detect. We construct a counterfactual setup for Olmo-3-32B, comparing a midtrained model (exposed to target code) against a pretrained reference (not exposed). We prompt both models with Python function signatures and measure both textual and functional similarity (i.e., LLM-as-a-judge, execution-based). Our results show clear evidence of functional memorization, highlighting the need for auditing metrics that go beyond textual overlap.

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

Distribution-Agnostic Robust Trajectory Optimization via Chance-Constrained Reinforcement Learning

arXiv:2606.13605v1 Announce Type: cross Abstract: This paper presents a distribution-agnostic robust trajectory-optimization framework based on chance-constrained reinforcement learning. The uncertainty is represented here through initial conditions and process noise, with the only requirement being that it can be sampled. A deterministic nominal trajectory is first computed offline, and reinforcement learning is then used only to robustify that baseline through a structured affine closed-loop correction law comprising a feedforward control adjustment and time-varying feedback gains. Probabilistic feasibility is enforced empirically through rollout-based upper-tail quantiles, while terminal dispersion is regulated through covariance-feasibility penalties. The framework is assessed on two materially different trajectory design problems. The flagship case study is a three-dimensional multi-impulse Earth-Mars transfer, where the learned policy is benchmarked against a recent robust trajectory-optimization reference under Gaussian uncertainty and then evaluated under bounded uniform uncertainty and under process disturbances not seen during training. The second case study is a stochastic atmospheric pinpoint rocket landing problem, used to assess portability to a short-horizon continuous-thrust setting with drag, mass depletion, and glide-slope constraints. The results show that the proposed framework can remain competitive in upper-tail fuel cost while preserving probabilistic feasibility, and that the same robustification scaffold can be carried across heterogeneous spacecraft trajectory planning problems without redesign of its core stochastic-control structure.

13.
arXiv (math.PR) 2026-06-18

A simple approach to the L{\o}kka-Zervos dichotomy for absolutely continuous dividend strategies

arXiv:2604.13302v3 Announce Type: replace-cross Abstract: We revisit the optimization problem solved in L{\o}kka & Zervos (2008), i.e., the maximization of dividends, in a Brownian risk model, with the possibility (not the obligation) of making capital injections. Following the approach introduced in Alvarez & Shepp (1998), Renaud & Simard (2021), Renaud et al. (2023), we consider instead absolutely continuous (AC) dividend strategies with an affine bound on the payment rates, while singular capital injections are still allowed. In addition, we incorporate a parameter for the cost of ruin or, said differently, a penalty at ruin in the performance function. We show that the solution is a so-called L{\o}kka-Zervos dichotomy: the surplus is never ruined by making bail-out payments, or no capital is injected and bankruptcy can occur; in either case, dividends are paid at full rate when the surplus is above a threshold. Our framework allows us to provide explicit conditions to express the dichotomy, either using the cost of capital injections or the cost of ruin as a criterion, which also exposes the underlying structure of the solution. In particular, for some values of the parameters, we show that it is optimal to liquidate. Moreover, we perform a numerical analysis highlighting the range of values generated under this AC affine-bound structure.

14.
arXiv (CS.CL) 2026-06-15

Can Post-Training Turn LLMs into Good Medical Coders? An Empirical Study of Generative ICD Coding

Automated International Classification of Diseases (ICD) coding is a core medical-coding task for billing, epidemiology, and clinical decision support. Generative large language models (LLMs) are often reported as weak medical coders, but this finding mainly comes from inference-time settings such as prompting, retrieval, reranking, or tool use, leaving the role of task-specific post-training underexplored. We present a controlled empirical study of post-training for generative ICD coding, comparing discriminative baselines with LLM coders across prompting, supervised fine-tuning, and reinforcement learning under a common protocol and metric set. To our knowledge, this is the first study to evaluate RL-based post-training for generative LLM coders in ICD coding. We further introduce PHI, a diagnostic curriculum that extends GRPO to refine missed-code cases. Our results show that prompting-only evaluation substantially underestimates the potential of LLMs for ICD coding. SFT provides the main capability jump, GRPO further improves code-set prediction beyond SFT, and PHI provides targeted gains on macro-level performance. These findings suggest that the main bottleneck is not the generative formulation alone, but how the model is adapted and optimized for full-taxonomy recall. We release our code, data splits, and checkpoints at https://github.com/AlexandreWANG915/LLM4ICD.

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

Position: Generative Engine Optimization Creates Underexamined Risks, Governance Must Target Concentration, Disclosure, and Academic Blind Spots

arXiv:2606.12439v1 Announce Type: cross Abstract: Large language model (LLM) answer engines are increasingly used for information seeking, shifting visibility from ranked lists to synthesized answers. This enables Generative Engine Optimization (GEO), which targets LLM answer engines' evidence pool and generation. We analyze the search engine optimization (SEO) to GEO transition to identify two risks: (i) concentrated influence from low contestability and system sensitivity, and (ii) undisclosed commercial influence embedded in evidence and reasoning. We then formalize a general GEO pipeline to locate where optimization acts and compare academic and industry practices, revealing a third risk: (iii) academic-industry blind spots driven by visibility and evaluation asymmetries between offline setups and deployed systems. This position argues the need for answer-level governance and measurement: stronger contestability, high-precision disclosure, black-box auditing of material influence, and deployment-aligned metrics for exposure persistence.

16.
arXiv (CS.CL) 2026-06-15

Detecting undisclosed LLM-generated content in parliamentary texts

In this paper, we evaluate the extent of undisclosed LLM-generated content in texts from the parliaments of the United Kingdom and Sweden. In many areas, such as in journalism or in academic writing, there are often requirements to clearly disclose whether AI tools, such as LLMs, have been used. In the case of parliamentary texts, the guidelines on disclosure of AI use are more vague. However, in order to maintain transparency and retain public trust, it is generally recommended that parliamentarians should state whether or not they have used AI when writing texts, such as parliamentary motions. Here, we train an interpretable (glass-box) text classifier using pre-LLM parliamentary texts and LLM-generated versions of such texts. We then apply the classifier to a test set containing recent parliamentary texts, finding a steady increase in undisclosed LLM use, in both parliaments, from 2022 onwards.

17.
arXiv (math.PR) 2026-06-12

Explosion and non-explosion in pure birth Crump–Mode–Jagers branching processes

arXiv:2601.06850v2 Announce Type: replace Abstract: In this short note, we provide an explicit sufficient condition for non-explosion of Crump–Mode–Jagers branching processes with pure birth reproduction. It shows that the standard sufficient condition for explosion, namely the convergence of the series of reciprocals of the birth rates, is – at least for rate sequences without excessive oscillations – remarkably close to being necessary. At the same time, it is not necessary in full generality: we construct a counterexample which also yields a general preferential attachment tree without fitness with an infinite path and no vertices of infinite degree, thereby answering an open question previously raised in the literature.

18.
arXiv (CS.LG) 2026-06-19

Multimodal Concept Bottleneck Models

arXiv:2606.19882v1 Announce Type: cross Abstract: Concept Bottleneck Models (CBMs) enhance the interpretability of deep learning networks by aligning the features extracted from images with natural concepts. However, existing CBMs are constrained in their ability to generalize beyond a fixed set of predefined classes and the risk of non-concept information leakage, where predictive signals outside the intended concepts are inadvertently exploited. In this paper, we propose Multimodal Concept Bottleneck Model (MM-CBM) to address these issues and extend CBMs into CLIP. MM-CBM utilizes dual Concept Bottleneck Layers (CBLs) to align both the image and text embeddings into interpretable features. This allows us to perform new vision tasks like zero-shot classification or image retrieval in an interpretable way. Compared to existing methods, MM-CBM achieves up to 51.26% accuracy improvement on average across four standard benchmarks. Our method maintains high accuracy, staying within ~5% of black-box performance while offering greater interpretability.

19.
Science (Express) 2026-06-18

Dynamic asymmetric strain imprinted into substrates by an oxide thin film | Science

作者: 未知作者

In film-substrate systems, the substrate role is often considered to be limited to providing static mechanical constraints. Dynamic film-substrate interactions when a structural change in the film modifies the substrate are generally disregarded. Using combined X-ray and electron microscopies, we observed that the electrically induced filament in a VO 2 film created strong asymmetric strain in the underlying Al 2 O 3 substate. This asymmetric substrate strain fed back into the film and defined the filament expansion direction, revealing the importance of film-substrate dynamic interactions in determining film functionality. Furthermore, the strain imprint propagated at least tens of microns deep into the substrate, exceeding the film thickness more than 200 times, potentially enabling substrate functionalization as an active mechanical coupling media in 3D-integrated microelectronics architectures.

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

When Does Delegation Beat Majority? A Delegation-Based Aggregator for Multi-Sample LLM Inference

arXiv:2606.08098v2 Announce Type: replace Abstract: Majority voting over sampled answers is the dominant unsupervised aggregator for multi-sample LLM inference. In this paper, we show a delegation-based aggregator (Propagational Proxy Voting, PPV; Sakai et al., 2025) yields an unsupervised consensus rule that beats majority on MMLU-Pro by +1.5 pp overall and +2.24 pp on the non-trivial subset (paired McNemar p ~ 1.0e-14, n = 8,099). Majority discards two signals that every sample carries: within-group letter entropy and between-group reasoning geometry. PPV exposes per-voter levers that consume exactly these two signals: When (how much weight a voter keeps on its own pick) and Whom (how it splits the remainder across peers). We drive When with letter entropy and Whom with per-question-centered embedding cosine. Our method needs no gold labels and no auxiliary training: per-question, we partition 128 sampled generations into 16 groups, compute each group's letter-level semantic entropy and reasoning embedding centroid, and feed both into a stochastic delegation matrix whose stationary distribution selects the consensus answer. We walk through an example in which PPV overturns a clear 10-6 majority for the wrong letter: the 10-voter majority cluster is geometrically incoherent (mean within-cluster cosine -0.02) while the 6-voter minority is tight (+0.26), so propagated delegation mass concentrates on the minority's answer even though entropy alone would keep the majority ahead. We further report delegation strategies with negative results that constrain the design space for unsupervised LLM aggregation. No within-question ensemble of confidence modes closes the oracle gap.

21.
arXiv (math.PR) 2026-06-15

Hierarchical symmetry selects log-Poisson cascades: classification, uniqueness, and stability

arXiv:2604.01632v2 Announce Type: replace Abstract: Within i.i.d. multiplicative cascades, a single axiom – the hierarchical symmetry, a linear contraction on incremental scaling exponents – is shown to be necessary and sufficient for the cascade multiplier to be log-Poisson. We prove: (1) a characterization theorem determining the log-Poisson law with explicit parameters, within the class of all multipliers with finite lattice moments; (2) a classification theorem locating the log-Poisson class inside the log-infinitely-divisible family and identifying the mechanism by which every rival sub-family fails the symmetry; (3) a stability theorem with sharp constants – $(1+\beta)^{1/2}$ when the limiting increment is known, $\sqrt{2}$ when it is fitted – and (4) an unconditional propagation theorem transferring the bound to the multiplier distribution at the sharp rate $\Theta(\sqrt{\varepsilon})$, with a matching lower bound. Beyond independence, the classification extends exactly at the level of asymptotic statistics (limiting cumulant generating function, large deviations, multifractal spectrum) and provably not at the level of laws: an explicit stationary ergodic Markov multiplier satisfies the symmetry exactly with a non-log-Poisson marginal, while exchangeable multipliers collapse to the i.i.d. log-Poisson cascade and finite-state Markov multipliers cannot satisfy the symmetry at all. In the continuous category of exactly scale-invariant log-infinitely-divisible multifractal random measures, no finite moment window of structure-function exponents identifies the cascade class, whereas at the level of the scale-invariance generator the symmetry selects exactly the Barral-Mandelbrot compound Poisson cascade, with scale-ratio-free stability constants. The proofs reduce to second-moment identities on [0,1] via the change of variables $u = e^{kx}$, boundedness of the multiplier, and multiplicative couplings.

22.
medRxiv (Medicine) 2026-06-17

Hormonal Contraceptives Drive Genital Lipid Metabolism Reprogramming and Susceptibility to HIV Infection

Heterosexual genital HIV transmission is a major driver of new infections, particularly in women, making them disproportionately vulnerable to HIV acquisition. Previous studies have associated injectable hormonal contraceptives (HC) with increasing susceptibility to HIV. Yet, the underlying molecular mechanism remains incompletely understood. Given the structural and signaling role of lipids in the female genital tract, cervicovaginal lipidomic profiling has the potential to reveal the mechanistic interplay among HC, lipidome, and HIV susceptibility in the female genital tract. We conducted untargeted cervicovaginal lipidomics study in a cohort of high-risk, HIV-negative, Kenyan sex workers who were using injectable depot medroxyprogesterone acetate (DMPA), oral contraceptive pill (OCP), or no hormonal contraception (NH). Genital lipids were quantitatively analyzed using liquid chromatography-mass spectrometry (LC-MS) and bioinformatics platforms. A total of 1045 lipid species were identified in the cervicovaginal lavage samples. Injectable DMPA significantly downregulated major structural and signaling membrane lipids, including phospholipids, ceramides, sphingomyelins, and glycosphingolipids (p

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

A polarity-aware multi-relational model for the signed interaction prediction in biological networks

arXiv:2407.07357v3 Announce Type: replace Abstract: Predicting signed interactions in biological networks is crucial for understanding drug mechanisms and facilitating drug repurposing. While deep graph models have demonstrated success in modeling complex biological systems, existing approaches often fail to distinguish between positive and negative interactions, limiting their utility for precise pharmacological predictions. In this study, we propose a novel deep graph model, PAMR (polarity-aware multi-relational model), designed to predict both polar (e.g., activation, inhibition) and non-polar (e.g., binding, affect) chemical-gene interactions. Our model integrates graph convolutional networks with tensor decomposition to enhance feature representation and incorporates a conflict-aware sampling strategy to resolve polarity ambiguities. We introduce new evaluation metrics, polarity discrimination score (PDS) and CP@100, to assess the model's ability to differentiate interaction types. Experimental results demonstrate that PAMR outperforms baseline models, achieving superior classification accuracy and improved discrimination of polar edges. Specifically, PAMR-CL attains a Macro AUROC of 0.9072 and CP@100 of 0.974, surpassing RGCN, GraphSAGE, TransE, and BioNet baselines. A case study on nicotine further identifies two novel chemical-gene suppression links, S100A6 and SPP1, that are corroborated by independent experimental literature. Furthermore, we analyze the impact of subgraph components on predictive performance, revealing that additional network structures do not always enhance accuracy. These findings highlight the importance of polarity-aware modeling in drug discovery and network pharmacology, providing a scalable computational framework for polarity-aware chemical-gene interaction prediction and network pharmacology analysis.

24.
PLOS Computational Biology 2026-06-01

Histology-informed spatial domain identification through multi-view graph convolutional networks

作者:

by Huihui Zhang, Jiaxing Chang, Zirong Li, Yue Sun, Pinli Hu, Haoxiu Wang, Hang Yang, Yonglin Ren, Xingtan Zhang, Zehua Chen, Kok Wai Wong, Haojing Shao Identifying spatial domains is crucial in spatial transcriptomics, yet effectively integrating gene expression, spatial location, and histology remains challenging. We present STESH, a Spatial Transcriptomics clustering method that combines Expression, Spatial information and Histology. STESH extracts histological features using a convolutional neural network and generates expression, histology, spatial, and collaborative convolution modules for a multi-view graph convolutional network with a decoder and attention mechanism. We evaluated STESH on multiple tissue types and technology platforms. STESH consistently outperformed ten state-of-the-art methods, achieving superior clustering accuracy with the highest scores in adjusted Rand index, normalized mutual information, and Fowlkes-Mallows index.

25.
arXiv (CS.LG) 2026-06-19

A deep learning framework for jointly solving transient Fokker-Planck equations with arbitrary parameters and initial distributions

arXiv:2604.06001v2 Announce Type: replace-cross Abstract: Efficiently solving the Fokker-Planck equation (FPE) is central to analyzing complex parameterized stochastic systems. However, current numerical methods lack parallel computation capabilities across varying conditions, severely limiting comprehensive parameter exploration and transient analysis. This paper introduces a deep learning-based pseudo-analytical probability solution (PAPS) that, via a single training process, simultaneously resolves transient FPE solutions for arbitrary multi-modal initial distributions, system parameters, and time points. The core idea is to unify initial, transient, and stationary distributions via Gaussian mixture distributions (GMDs) and develop a constraint-preserving autoencoder that bijectively maps constrained GMD parameters to unconstrained, low-dimensional latent representations. In this representation space, the panoramic transient dynamics across varying initial conditions and system parameters can be modeled by a single evolution network. Extensive experiments on paradigmatic systems demonstrate that the proposed PAPS maintains high accuracy while achieving inference speeds four orders of magnitude faster than GPU-accelerated Monte Carlo simulations. This efficiency leap enables previously intractable real-time parameter sweeps and systematic investigations of stochastic bifurcations. By decoupling representation learning from physics-informed transient dynamics, our work establishes a scalable paradigm for probabilistic modeling of multi-dimensional, parameterized stochastic systems.