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01.
Nature Biotechnology 2026-06-19

Efficient site-specific gene addition using R2 retrotransposons in tobacco and rice

作者:

Precise integration of multikilobase DNA fragments remains a major technical barrier in plants. Here we introduce non-long terminal repeat (non-LTR) R2 retrotransposons as a versatile system for targeted gene integration in plants. We reconstituted R2 activity in Nicotiana benthamiana and benchmarked insertion efficiency and fidelity using a TMV-based episomal reporter system. We demonstrate site-specific integration of GFP (2.2 kb) and recombinase-compatible landing pads (0.6 kb) into 28S rDNA arrays, with intact cassette insertion frequencies up to 75% and 53%, respectively. To temporally constrain donor availability and avoid DNA intermediates, we combined in planta effector expression with recombinant RNA virus-mediated donor delivery. We apply R2 retrotransposons for targeted insertion of resistance cassettes within the rDNA of rice callus, achieving integration efficiencies up to 17%. These results position R2 retrotransposons as a double-strand break-free system for RNA-templated insertion of multikilobase gene cassettes at rDNA loci, for safe-harbor trait stacking in plants with potential applications in crop improvement and synthetic biology. Retrotransposons are applied in plants for safe-harbor transgene integration.

02.
arXiv (CS.CV) 2026-06-12

On Pitfalls of $RemOve-And-Retrain$: Data Processing Inequality Perspective

The RemOve-And-Retrain (ROAR) benchmark is widely used to evaluate feature attribution methods, yet its validity remains underexplored from an information-theoretic perspective. We show that model- and data-agnostic post-processing of attribution maps (transformations that, by the data processing inequality, cannot add information about the decision function) can often improve ROAR scores. This means that an improved ROAR ranking is not, by itself, evidence that an attribution map carries more information about the model. We trace this failure mode to a bias toward spatially blurry masks. Experiments on CIFAR-10, SVHN, and CUB-200 show a consistent association between blurriness and ROAR performance, a pattern that also appears in the ROAD variant. We provide guidelines for more cautious removal-based benchmarking, with implications for validating mechanistic understanding of neural network internals.

03.
arXiv (CS.AI) 2026-06-11

GILT: An LLM-Free, Tuning-Free Graph Foundational Model for In-Context Learning

arXiv:2510.04567v3 Announce Type: replace-cross Abstract: Graph Neural Networks (GNNs) are powerful tools for processing relational data but often struggle to generalize to unseen graphs, giving rise to the development of Graph Foundational Models (GFMs). However, current GFMs are challenged by the extreme heterogeneity of graph data, where each graph can possess a unique feature space, label set, and topology. To address this, two main paradigms have emerged. The first leverages Large Language Models (LLMs), but is fundamentally text-dependent, thus struggles to handle the numerical features in vast graphs. The second pre-trains a structure-based model, but the adaptation to new tasks typically requires a costly, per-graph tuning stage, creating a critical efficiency bottleneck. In this work, we move beyond these limitations and introduce Graph In-context Learning Transformer (GILT), a framework built on an LLM-free and tuning-free architecture. GILT introduces a novel token-based framework for in-context learning (ICL) on graphs, reframing classification tasks spanning node, edge and graph levels in a unified framework. This mechanism is the key to handling heterogeneity, as it is designed to operate on generic numerical features. Further, its ability to understand class semantics dynamically from the context enables tuning-free adaptation. Comprehensive experiments show that GILT achieves stronger few-shot performance with significantly less time than LLM-based or tuning-based baselines, validating the effectiveness of our approach. Our code is available at: https://github.com/yiming421/inductnode/.

04.
arXiv (math.PR) 2026-06-17

A note on the $\mathcal{W}_2$-convergence rate of the empirical measure of an ergodic $\mathbb{R}^d$-valued diffusion

arXiv:2502.07704v2 Announce Type: replace Abstract: In this note, we consider a Stochastic Differential Equation under a strong confluence and Lipschitz continuity assumption of the coefficients. For the unique stationary solution, we study the rate of convergence of its empirical measure toward the invariant probability measure. We provide rate for the Wasserstein distance in the mean quadratic and almost sure sense.

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

RefGC-SR$^2$: Reference-guided Generated Content Super-Resolution and Refinement

Reference-guided generation (e.g., object compositing, customization) has progressed rapidly, yet current pipelines share a fundamental limitation: the object-centric high-resolution reference image (HRRI) provided by users is downsampled to a fixed low-resolution (LR) before being fed into the model, so the fine-grained details are discarded before the output is even produced. In addition, the generation step then introduces its own artifacts (e.g., identity distortion) on top of this loss. Existing reference-guided generated content refinement (RefGCR) methods can correct some of these artifacts but still operate in the LR domain; reference-guided super-resolution (RefSR) methods recover resolution but assume natural-image degradations and ignore the artifact distribution of generative pipelines. To address both gaps in a single formulation, we introduce a new task: reference-guided generated content super-resolution-refinement (RefGC-SR$^2$), where the original HRRI is reused at the post-processing stage to recover lost details, refine generative artifacts, and upscale the output simultaneously. We construct the first real-world triplet data generation pipeline for this RefGC-SR$^2$ task, training a diptych-conditioned generator to synthesize paired low-quality anchors that public pretrained models cannot provide. We further present a frequency-aware diffusion transformer model for RefGC-SR$^2$ that selectively injects fine details from the HRRI while removing generative artifacts. Extensive experiments demonstrate that our RefGC-SR$^2$ model successfully (i) refines the object identity faithfully with respect to the reference, and (ii) recovers high-resolution details, so that the final result is significantly higher quality and practically more usable compared to existing RefGCR and RefSR baselines.

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

Compiler-First State Space Duality and Portable $O(1)$ Autoregressive Caching for Inference

arXiv:2603.09555v2 Announce Type: replace-cross Abstract: High-throughput Mamba-2 inference is usually tied to fused CUDA and Triton kernels, limiting portability across accelerator backends. We show that the state space duality (SSD) recurrence has a compiler-friendly structure: diagonal per-head dynamics, fixed-size chunking, einsum-dominated compute, and static control flow. Expressing this structure in standard JAX primitives gives a single-source inference path with no custom kernels, a registered JAX PyTree cache, and a compiled on-device autoregressive loop. On a single Google Cloud TPU v6e, batch-1 prefill reaches approximately 140 TFLOPS, or 15% model FLOP utilisation (MFU), the roofline ceiling for this regime, and cached decode reaches up to 64% hardware bandwidth utilisation (HBU). At a 4096-token context, cached decode is 27x–36x faster than full-prefix recomputation across five Mamba-2 checkpoints from 130M to 2.7B parameters. The same source runs unmodified on NVIDIA L40S, where cached decode remains sequence-length independent across all model scales. WikiText-103 validation perplexity matches the Triton reference mamba_ssm v2.2.2 within +/-0.0005 points, and hidden states agree to float32 rounding tolerance. Code is available at https://github.com/CosmoNaught/mamba2-jax.

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

DiRecT: Safe Diffusion-Based Planning via Receding-Horizon Denoising

arXiv:2606.15359v1 Announce Type: new Abstract: Diffusion models have emerged as powerful tools for planning and control by learning multimodal distributions over actions and trajectories. Yet reliable inference-time safety enforcement remains a key barrier to their deployment in safety-critical tasks. Existing approaches typically project each denoising iterate onto the feasible set, even though constraints are defined only on the final clean trajectory. Enforcing feasibility on noisy intermediate samples can therefore overconstrain the sampling dynamics, substantially degrading sample quality. To address this limitation, we introduce DiRecT (Diffusion-based planning via Receding-horizon denoising with Terminal constraints), a training-free algorithm for constrained sampling from diffusion models via stochastic optimal control (SOC). DiRecT enforces constraints only on the final clean sample, avoiding unnecessary restrictions on the intermediate denoising dynamics. Inspired by model predictive control, we derive a principled receding-horizon surrogate for the otherwise intractable constrained SOC formulation, yielding an efficient algorithm that cleanly separates stochastic denoising from constraint satisfaction, progressively steering samples toward feasible final trajectories without distorting the learned diffusion dynamics. Furthermore, DiRecT is highly flexible: it can leverage off-the-shelf or domain-specific optimizers, incorporate priors over environment dynamics, and optimize additional soft rewards. Extensive experiments on safe planning benchmarks demonstrate that DiRecT substantially improves deployment safety and task performance over existing diffusion-based planning baselines.

08.
arXiv (CS.LG) 2026-06-11

A prior-free blind detection of information leakage from model predictions

arXiv:2606.11267v1 Announce Type: new Abstract: Data leakage – contamination of a model with information unavailable at baseline – is the dominant reproducibility failure in machine-learning-based science, yet detection tools require training code, external data, or domain expertise. None operates on the artifact an auditor most often holds: the model's output. We ask what can be decided about leakage from predictions and outcomes alone. We give a decision-theoretic framework in which leakage diagnostics are functionals of the predicted-risk/outcome law, parameterized by a threshold-weighting linked to proper scoring rules and decision-curve analysis. We prove a sharp impossibility: a recalibrated leak matching an honest model's calibration and discrimination is indistinguishable from honest performance by any function of the predictions, so the broad class is detectable only against an externally supplied ceiling on achievable discrimination. We then prove what leakage cannot hide: a near-deterministic subgroup – the signature of a near-label leak – produces a sustained unit-purity head that no legitimate predictor of a non-deterministic outcome can manufacture, yielding a prior-free test. These results organize leakage into a trichotomy – miscalibrated, broad-calibrated, and deterministic – each with a matched detector and failure mode. We validate on UK Biobank using time-windowed comorbidity leakage with known, graded severity, measuring a detection floor of $\Delta\cstar \approx 0.007$ on this endpoint, below which residual leakage is undetectable from output and too small to alter conclusions. The numerical floor is cohort- and endpoint-specific; the structural lesson is general: output-only detection fails where residual leakage is indistinguishable from an honestly stronger predictor. The test returns a verdict on a prediction vector in under a second on commodity hardware.

09.
arXiv (math.PR) 2026-06-16

Large Deviations for the Nonlinear Schrödinger Equation with Randomized Quasi-Periodic Initial Data in Higher Dimensions: Subcritical Case

arXiv:2604.17253v2 Announce Type: replace Abstract: We study the cubic weakly nonlinear Schrödinger equation with randomized spatially quasi-periodic initial data in higher dimensions. Under a polynomial decay assumption in Fourier space, we establish a Large Deviations Principle for rogue waves in the so-called subcritical time regime. The proof proceeds in two main steps. We first characterize the distribution of the linear solution and establish the corresponding linear large deviations principle. The lower bound is obtained via pointwise estimates, while the upper bound follows from a combination of truncation and probabilistic arguments. {The method used in this step appears to be new; compare with [GGKS23].} We then perform a detailed combinatorial analysis of the Picard iteration, deriving an effective bound for the Duhamel term and thereby establishing the nonlinear large deviations principle.

10.
arXiv (CS.CV) 2026-06-17

MLLMs Get It Right, Then Get It Wrong: Tracing and Correcting Late-Layer Textual Bias

When vision contradicts text, multimodal large language models (MLLMs) consistently favor text, even when images provide clear evidence otherwise. This bias poses risks for applications requiring visual grounding, yet its cause remains unclear. In this paper, we uncover a surprising finding: models often get it right initially, forming correct vision-based predictions in their intermediate layers, before changing their minds and favoring text in the final output. We call this "late-layer textual override". The visual information is encoded, it simply does not survive to the output. More intriguingly, we find that how predictions change reveals whether they're correct: 85% of failures shift toward text, while 89% of successes shift toward vision. This directional signature enables a simple but powerful intervention: when we detect a confident visual prediction being suppressed, we restore it. We propose CALRD (Conflict-Aware Layer Reference Decoding), a training-free method that recovers overridden predictions at inference time. Experiments across five MLLMs of varying architectures demonstrate up to 9.4% absolute improvements on conflict benchmarks while largely preserving standard performance, without training or external knowledge. It recovers what the model already knew but failed to preserve.

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

When to Align, When to Predict: A Phase Diagram for Multimodal Learning

arXiv:2606.11190v2 Announce Type: replace Abstract: Cross-modal alignment (CA) and cross-modal prediction (CP) are the dominant paradigms for multimodal representation learning, yet there is no systematic understanding of when each succeeds, when each fails, and when cross-modal training helps at all – a gap that leaves practitioners, especially in scientific domains like biomedicine or astrophysics, with heterogeneous instruments and multiple levels of organization and measurement, unable to diagnose why standard methods underperform the best single modality. We develop a unified linear framework that addresses both questions. Under a spiked signal-plus-noise model with structured cross-modal nuisance correlation, we derive separation ratios for both objectives that expose complementary failure modes: alignment whitens each modality and fails when nuisance is strongly correlated across views; prediction encodes whatever is cross-predictable through a one-sided whitening, with recovery governed by source-modality quality. The resulting phase diagram partitions multimodal problems into four regimes: Both, CA only, CP only, and Neither. We present a data-driven procedure to locate real-world datasets in this diagram using a small labeled subsample, identifying the preferred objective and prediction direction before any cross-modal training. Experiments on synthetic data, stereo-vision benchmarks, image-caption pairs, and real astrophysical data validate the predictions in the nonlinear regime, including the Neither regime where cross-modal training is actively harmful. Our framework lets practitioners diagnose their multimodal problem and choose the right objective before committing to training. Code to reproduce the results is available at https://github.com/IlayMalinyak/mm_align_vs_pred.

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

Scaling Laws of Global Weather Models

arXiv:2602.22962v2 Announce Type: replace Abstract: Data-driven models are revolutionizing weather forecasting. To optimize training efficiency and model performance, this paper analyzes empirical scaling laws within this domain. We investigate the relationship between model performance (validation loss) and three key factors: model size ($N$), dataset size ($D$), and compute budget ($C$). Across a range of models, we find that Aurora exhibits the strongest data-scaling behavior: increasing the training dataset by 10x reduces validation loss by up to 3.2x. GraphCast demonstrates the highest parameter efficiency, yet suffers from limited hardware utilization. Our compute-optimal analysis indicates that, under fixed compute budgets, allocating resources to more total training data yields greater performance gains than increasing model size. Furthermore, we analyze model shape and uncover scaling behaviors that differ fundamentally from those observed in language models: weather forecasting models consistently favor increased width over depth. These findings suggest that future weather models should prioritize wider architectures and larger effective training datasets to maximize predictive performance.

13.
arXiv (CS.AI) 2026-06-19

Measuring Curriculum Alignment across Topical Coverage, Competency, and Cognitive Depth: A Longitudinal Framework Applied to CS2013 and CS2023

arXiv:2606.19469v1 Announce Type: new Abstract: Undergraduate computer science is governed by international curricular guidelines revised about once a decade, yet programs lack a reliable, reproducible way to measure how completely they cover the current guidelines and how that coverage shifts when the guidelines are restructured. We address this with a human-in-the-loop pipeline that measures a program's coverage of an external body of knowledge, applied longitudinally to one accredited BSc in Computer Science against Computer Science Curricula 2013 (CS2013) and 2023 (CS2023). The pipeline represents the program and each guideline as structured corpora, generates candidate course-to-knowledge-unit matches by semantic retrieval, and confirms them through human judgment under an explicit coverage definition. Of seven benchmarked retrievers, a reciprocal-rank-fusion ensemble was strongest, and a reputed long-context model underperformed a small sentence model, so retriever choice must be measured. Both maps were validated by an independent second rater (Cohen's kappa 0.64 for CS2023, 0.69 for CS2013). The program covers 49.7% of CS2023 and 50.9% of CS2013 knowledge units, near-constant across a decade. Extending the same retrieve-then-confirm design to competency articulation and cognitive depth shows that the program articulates the competency for ~88% of covered units under each guideline, yet delivers it at the recommended depth for 76% of present units under CS2023 against 95% under CS2013, a gap reflecting the newer guideline's raised expectations, not the program. The longitudinal comparison separates persistent structural gaps (parallel and distributed computing, foundations of programming languages, systems fundamentals), uncovered against both guidelines and ABET, from differences that reflect the standard's evolution. The instrument is reusable and available from the authors on request.

14.
arXiv (CS.AI) 2026-06-19

Frequency-Aware Flow Matching for Continuous and Consistent Robotic Action Generation

arXiv:2606.20135v1 Announce Type: cross Abstract: Flow matching has emerged as a standard paradigm for robotic manipulation owing to its strong expressive power for modelling complex, multimodal action distributions, alongside similar approaches like diffusion policy. However, existing methods rely on discretized action chunks, making them brittle to demonstrations collected at heterogeneous control frequencies and prone to temporally inconsistent actions that degrade control stability. In this paper, we propose Frequency-Aware Flow Matching (FAFM), which outputs continuous, temporally consistent actions. To handle heterogeneous frequency input, we transform discrete action sequences into the frequency domain with the discrete cosine transform (DCT), perform flow matching over the resulting coefficients, and reconstruct continuous actions via cosine basis expansion. To generate temporally consistent actions, we regularize the first-order temporal derivative to promote smooth actions. This corresponds to a Sobolev-type constraint that suppresses high-frequency errors and discourages abrupt action changes. Our FAFM is simple, introduces no additional network parameters and applies to standalone flow-matching policies and vision-language action models. Across synthetic toy benchmark, obstacle avoidance, LapGym, and LIBERO, FAFM improves success rates, multimodal expressivity, motion smoothness, convergence speed, robustness to mechanical bias and mixed-frequency input. These gains are consistent when deployed on a real-world Franka robot. Code available at https://anonymous.4open.science/r/FAFM.

15.
arXiv (CS.AI) 2026-06-19

ITNet: A Learnable Integral Transform That Subsumes Convolution, Attention, and Recurrence

arXiv:2606.19538v1 Announce Type: new Abstract: Convolutional networks, recurrent networks, and transformers each encode different inductive biases – locality, sequential memory, and content-dependent pairwise interaction – and have remained mathematically distinct since their inception. We show that this fragmentation reflects not a fundamental diversity in how signals should be processed, but rather incomplete views of a single underlying mathematical object: a learnable integral transform. We introduce the Integral Transform Network (ITNet), a unified architecture built around a learnable kernel that depends jointly on positions and features. This kernel is implemented as a small neural network, specifically an MLP, that models pairwise interactions, enabling the model to adapt its behavior from data. We show that convolution, self-attention (including multi-head), and autoregressive recurrence (including LSTM, GRU, S4, and Mamba) arise as special cases under appropriate parameterizations, and that ITNet is a universal approximator of continuous operators. To make this practical, we develop tiled kernel fusion, importance-weighted Monte Carlo integration, and learned low-rank factorization, enabling efficient and scalable computation. A single ITNet architecture with a shared operator and lightweight modality-specific encoders matches or exceeds specialized baselines on ImageNet-1K , GLUE, ModelNet40, VQA\,v2 and NLVR2. The results demonstrate that a single learned interaction mechanism can recover the behavior of all three architectural families from data.

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

Flow Matching for Efficient and Scalable Data Assimilation

arXiv:2508.13313v4 Announce Type: replace-cross Abstract: Data assimilation (DA) estimates a dynamical system's state from noisy observations. Recent generative models like the ensemble score filter (EnSF) improve DA in high-dimensional nonlinear settings but are computationally expensive. We introduce the ensemble flow filter (EnFF), a training-free, flow matching (FM)-based framework that accelerates sampling and offers flexibility in flow design. EnFF uses Monte Carlo estimators for the marginal flow field, localized guidance for observation assimilation, and utilizes a novel flow path that exploits the Bayesian DA formulation. It generalizes classical filters such as the bootstrap particle filter and ensemble Kalman filter. Experiments on high-dimensional benchmarks demonstrate EnFF's improved cost-accuracy tradeoffs and scalability, highlighting FM's potential for efficient, scalable DA. Code is available at https://github.com/Utah-Math-Data-Science/Data-Assimilation-Flow-Matching.

17.
arXiv (CS.AI) 2026-06-16

AdaSTORM: Scaling LLM Reasoning on Dynamic Graphs via Adaptive Spatio-Temporal Multi-Agent Collaboration

arXiv:2606.16328v1 Announce Type: new Abstract: Large Language Models (LLMs) demonstrate remarkable potential in dynamic graph reasoning, but suffer from a scaling bottleneck: current models can only handle graphs with tens of nodes, constrained by exponential reasoning overhead and finite context windows. While multi-agent systems (MAS) offer collective reasoning and topology-aware orchestration, capabilities naturally suited for graph-structured tasks, their application to dynamic graphs remains unexplored. This paper presents Scaling LLM Reasoning on Dynamic Graphs via Adaptive Spatio-Temporal Multi-Agent Collaboration (AdaSTORM), a framework that reformulates large-scale dynamic graph reasoning into two stages: (i) Adaptive Partitioning, partitioning large-scale dynamic graphs into subregions that match the model's reasoning capacity while minimizing inference cost; and (ii) Collaborative Reasoning, aligning graph partition topologies with a spatio-temporal decoupled multi-agent architecture. AdaSTORM is the first multi-agent framework tailored for dynamic graph reasoning. Extensive experiments show that AdaSTORM successfully breaks through the scaling bottleneck, scaling reasoning to thousand-node graphs with over 90% accuracy across several large-scale dynamic graph settings without external tools, significantly outperforms seven competitive baselines. Furthermore, it achieves state-of-the-art accuracy on existing benchmarks and generalizes robustly to real-world datasets. The source code is available at: https://github.com/irisorchid107/AdaSTORM/.

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

The MAMA-MIA Challenge: Advancing Generalizability and Fairness in Breast MRI Tumor Segmentation and Treatment Response Prediction

arXiv:2603.01250v2 Announce Type: replace-cross Abstract: Breast cancer is the most frequently diagnosed malignancy among women worldwide and a leading cause of cancer-related mortality. Dynamic contrast-enhanced magnetic resonance imaging plays a central role in tumor characterization and treatment monitoring, particularly in patients receiving neoadjuvant chemotherapy. However, existing artificial intelligence models for breast magnetic resonance imaging are typically developed and evaluated using heterogeneous datasets, study populations, and assessment protocols, making direct comparison difficult and limiting understanding of model robustness across institutions and clinically relevant patient subgroups. The MAMA-MIA Challenge was designed to address these challenges by providing a standardized benchmark for the joint evaluation of primary tumor segmentation and prediction of pathologic complete response using pre-treatment magnetic resonance imaging only. The training cohort comprised 1,506 patients from multiple institutions in the United States, while evaluation was conducted on an external test set of 574 patients from three independent European centers to assess cross-continental and cross-institutional generalization. A unified scoring framework combined predictive performance with subgroup consistency across age, menopausal status, and breast density. Twenty-six international teams participated in the final evaluation phase. Results demonstrate substantial performance variability under a common external evaluation framework and reveal trade-offs between overall accuracy and subgroup fairness. The challenge provides standardized datasets, evaluation protocols, and public resources to promote the development of robust and equitable artificial intelligence systems for breast cancer imaging.

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

Revisiting LLM Adaptation for 3D CT Report Generation: A Study of Scaling and Diagnostic Priors

Recent advances in multimodal learning, including large language models (LLMs) and vision-language models (VLMs), have demonstrated strong adaptability to natural images. However, extending their use to the medical domain, particularly for volumetric (3D) images, is challenging due to high computational complexity, volumetric dependencies and the semantic gap between visual features and clinical terminology. Naively fine-tuning LLMs on limited medical data often leads to overfitting and clinical hallucination, where linguistic fluency is prioritized over clinical factuality. In this study, we investigate parameter-efficient adaptation strategies for volumetric CT report generation and introduce RAD3D-Prefix, a lightweight diagnostic-prior conditioning framework that minimizes the need for extensive parameter training. This module integrates image embeddings with multi-label diagnostic classification logits, preserving critical clinical details while bridging the semantic gap. By keeping the LLM frozen, our method requires minimal trainable parameters and mitigates the risk of overfitting on small, domain-specific datasets. Through a systematic study spanning LLMs from 96.1M to 1.6B parameters, we find that fine-tuning is most beneficial for smaller LLMs, whereas freezing larger (~1B+ LLMs and training only lightweight projection layers provides a superior trade-off between performance, generalization, and computational efficiency. Across multiple automatic metrics and a clinical reader study, RAD3D-Prefix outperforms comparable parameter-efficient baselines and demonstrates strong out-of-domain generalization while using substantially fewer trainable parameters than fully fine-tuned alternatives.

20.
medRxiv (Medicine) 2026-06-17

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

Despite recent advances in next-generation sequencing, genetic diagnostic rates for dilated cardiomyopathy (DCM) remain low. Among paediatric DCM, causes are often heritable, with a greater frequency of de novo, recessive and syndromic causes of disease. Novel diagnostic methods are therefore required to solve monogenic cases. To assess the value of proteomics as a diagnostic tool for paediatric DCM, we obtained left ventricle myocardial samples from paediatric patients undergoing heart transplantation at the Royal Children's Hospital, Melbourne. We performed genome sequencing and proteomics and leveraged this multi-omics dataset to uncover the molecular cause of disease in a gene elusive proband. The proband carried a heterozygous JPH2 frameshift variant identified on clinical exome sequencing. However, proteomic analysis showed a pronounced downregulation of JPH2, suggestive of biallelic loss-of-function. Closer inspection of the genomic data revealed a large inversion (~8.34 Mb) with a breakpoint falling within intron 5 of JPH2 that displaces the 3'UTR from the coding transcript. The two variants were confirmed to be in trans using long read DNA sequencing, consistent with a diagnosis of JPH2 autosomal recessive DCM. Finally, we applied RNA sequencing with total RNA library preparation to show that transcripts containing a 3'UTR were reduced to ~10% relative to controls. As a proof-of-principle, we present the first reported use of proteomics from explanted cardiac tissue to provide a genetic diagnosis. Our methodology has broad relevance to patients with genetically unsolved Mendelian diseases, who might undergo organ transplantation as part of clinical management.

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

Geometry-Preserving Encoder/Decoder in Latent Generative Models

arXiv:2501.09876v4 Announce Type: replace-cross Abstract: Generative modeling aims to generate new data samples that resemble a given dataset. When using diffusion models for this task, one of the main challenges is solving the problem in the input space, which tends to be very high-dimensional. To address this, recent approaches solve diffusion models in the latent space through an encoder that maps from the data space to a lower-dimensional latent space, improving training efficiency and achieving state-of-the-art results. The variational autoencoder (VAE) is the most commonly used encoder/decoder framework in this domain, known for its ability to learn latent representations and generate data samples. In this paper, we introduce a novel encoder/decoder framework with theoretical properties distinct from those of the VAE, specifically designed to preserve the geometric structure of the data distribution. We demonstrate the significant advantages of this geometry-preserving encoder in the training process of both the encoder and decoder. Additionally, we provide theoretical results proving convergence of the training process, including convergence guarantees for encoder training, and results showing faster convergence of decoder training when using the geometry-preserving encoder.

22.
medRxiv (Medicine) 2026-06-15

CDH13 is associated with cellular viability after exposure to ionizing radiation using genome-wide screening

Background: It is well known that genetic variants contribute to cellular sensitivity to chemotherapeutic agents and ionizing radiation (IR). The aim of this study was to identify single nucleotide polymorphisms (SNPs) and genes associated with the spectrum of normal cellular sensitivity of lymphoblastoid cell lines (LCLs) towards ionizing radiation and mitomycin C (MMC). Methods: In a first step, we determined the viability of LCLs established from male participants of the Berlin Aging Study II (BASE-II) aged >=62 years following treatments with increasing doses of IR (n=137 cell lines) or MMC (n=140 cell lines) using the alamarBlue assay. Results from intra-experimental triplicates and three independent experiments for each cell line and treatment were used to calculate the area under the curves (AUCs) representing the specific sensitivity to IR and MMC of each LCL. The data from these experiments were subsequently used as outcomes in genome-wide association studies (GWASs). In addition, we calculated polygenic risk scores (PGS) from UK Biobank GWAS results for four cancer-related phenotypes and assessed the extent to which the variance in the IR and MMC sensitivity is explained by these PGS. Results: The GWAS analyses revealed one variant, rs74728080, located in CDH13 on chromosome 16, to show genome-wide significant (p < 5 x 10-8, beta = 2.81) association with cellular viability after treatment with IR. In the GWAS on MMC sensitivity the most interesting signal was elicited by SNP rs113978558 in an intron of the PLD5 gene on chromosome 1 (p = 9.232 x 10-8; beta = 1.44). Several other SNPs with statistically suggestive (i.e., p < 1 x 10-5) evidence of association with IR or MMC sensitivity were identified. PGSs calculations from GWAS of four cancer-related traits in UKB explained ~5% and ~3% of phenotypic variance in IR- and MMC-induced cell viability, respectively. Conclusion: The genome-wide significant association of rs74728080 with IR sensitivity and the location of this variant in CDH13 is interesting and functionally highly plausible given its known involvement in oxidative-stress response and function as tumor suppressor. Taken together, our novel data suggest that CDH13 may be genuinely involved in regulating cellular IR sensitivity.

23.
arXiv (CS.AI) 2026-06-11

HiGR: Industrial-Scale Hierarchical Generative Slate Recommendation Framework in Tencent

arXiv:2512.24787v4 Announce Type: replace-cross Abstract: Slate recommendation, which presents users with a ranked item list in a single display, is ubiquitous across mainstream online platforms. While recent generative recommendation methods have shown strong potential in modeling item sequences with semantic IDs, directly applying them to industrial-scale slate recommendation faces a fundamental disconnect: entangled SID spaces confound high-level list planning, fine-grained autoregressive decoding over long sequences limits semantic planning efficiency, and token-level objectives misalign with holistic slate quality. In this paper, we propose HiGR, an industrial-scale hierarchical generative framework for slate recommendation that bridges this disconnect through a co-designed pipeline. First, HiGR learns structured SIDs via a Prefix-Contrastive Residual Quantized VAE (PCRQ-VAE). By enforcing high-level prefixes to capture shared semantics, PCRQ-VAE creates a controllable discrete space that acts as a prerequisite for efficient planning. Leveraging this structured space, our Hierarchical Slate Decoder (HSD) shifts autoregressive modeling from entangled token-level decoding to coarse-grained preference embeddings. This design significantly reduces inference latency while allowing explicit global slate structure planning. Finally, this stable planning space enables an ORPO-based listwise alignment mechanism to optimize triple-objective implicit feedback-ranking fidelity, genuine user interest, and diversity. Extensive offline experiments show that HiGR outperforms state-of-the-art baselines by over 10% in offline recommendation quality while achieving a $5\times$ inference speedup. Online A/B tests on Tencent platforms further improve watch time by 1.22% and video plays by 1.73%. HiGR has been deployed on multiple Tencent platform surfaces, serving hundreds of millions of users and proving its industrial-scale applicability.

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

Holo-World: Unified Camera, Object and Weather Control for Video World Model

Video world models are moving toward preserving an observed world under controllable camera and object motion while allowing its environmental state to change. Yet these controls remain isolated, and weather generation typically relies on a source video or reconstructed scene that already specifies future structure. We study a first-frame-anchored source-to-state setting, where the model starts from a single image and follows explicit camera and object controls and an optional weather instruction, then generates a video that either preserves the source world or transfers it to a target weather state. To address these challenges, we first build HoloStateData, a state video dataset that turns diverse videos into unified control samples for camera, object, and weather supervision. Second, we introduce Holo-World, a unified controllable video world model that jointly controls scene from a single image. Its Unified Scene Adapter factorizes world preservation and weather transfer into distinct parameter subspaces, using rendered background, geometry buffers, and object controls to maintain controlled scene structure while modeling weather-dependent appearance and particle effects. Additionally, Scene-Weather Decomposed CFG guides scene and weather residuals separately, strengthening target weather effects without over-amplifying the full condition. Quantitative and qualitative experiments demonstrate that Holo-World maintains precise camera and object control with consistent scene structure while transferring scenes into diverse target weather state, outperforming video-to-video weather editing baselines on weather-state generation. Our project page is available at \url{https://xiangchenyin.github.io/Holo-World/}.

25.
arXiv (CS.LG) 2026-06-16

Decoupling Inference from State Updates in Low-Latency Feature Engines via Probabilistic Thinning

arXiv:2606.16981v1 Announce Type: cross Abstract: Streaming data systems increasingly underpin Machine Learning workflows that maintain large numbers of continuously updated aggregations. In production settings, each incoming event typically triggers read-modify-write operations to persistent storage, making high-frequency state updates a dominant source of latency, contention, and operational cost. In this work, we decouple inference from state persistence in streaming Machine Learning pipelines via probabilistic thinning: every event is scored, but durable state updates are selectively triggered by informative events. Unlike approaches that shed input or state, we show that persistence-path control is achievable without a high-frequency in-memory control plane or cross-worker coordination, relying exclusively on approximate statistics retrieved from disk-backed key-value stores. We model the resulting stochastic processes, derive bounds on filtering rates, and prove that common time-based aggregations remain unbiased under variance-aware formulations, preventing systemic error accumulation. We evaluate the approach in a controlled setting that isolates per-event costs, demonstrating substantial reductions in storage Input/Output and serialization overhead. Across experiments, up to 90% of events are excluded from the persistence path while preserving and in some cases improving downstream utility.