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01.
medRxiv (Medicine) 2026-06-22

National trends and operational drivers of vaccine wastage in Uganda, 2020-2025: a descriptive analysis of four tracer antigens

Background Vaccine wastage reduces immunisation efficiency, increases costs, and complicates supply forecasting. Uganda routinely monitors vaccine use, but national evidence comparing observed wastage with World Health Organization (WHO) and Uganda-specific planning thresholds has been limited. We described national and sub-national trends for four tracer antigens to inform supply-chain planning and forecasting. Methods We conducted a retrospective descriptive analysis of routinely reported immunisation data from Ugandas District Health Information Software 2, 2020-2025. We analysed Bacille Calmette-Guerin (BCG), measles-rubella (MR), oral polio vaccine (OPV), and diphtheria-tetanus-pertussis-containing vaccine (DPT). Vaccine wastage was calculated as the proportion of issued doses not administered. Annual wastage rates were summarised using medians, and temporal trends were assessed using the Mann-Kendall test. Observed wastage was compared with WHO thresholds: BCG[≤]50%, MR[≤]25%, OPV[≤]10%, DPT[≤]15%, and Ugandas planning thresholds: BCG[≤]70%, MR[≤]40%, OPV[≤]15%, DPT[≤]10%. Effective Vaccine Management reports were reviewed to summarise reported reasons for wastage. Results During 2020-2025, median national wastage was 40.6% for BCG, 25.9% for MR, 10.0% for OPV, and 9.2% for DPT. OPV wastage declined from 12.8% in 2020 to 8.0% in 2025, with a significant downward trend ({tau}b=-1.00; p=0.008). OPV and DPT wastage remained largely within their respective Uganda in-country thresholds ([≤]15% and [≤]10%) for most of the study period, while BCG generally remained below the WHO threshold ([≤]50%) and MR frequently exceeded the WHO threshold ([≤]25%) but remained within Uganda's planning threshold ([≤]40%) in most years. The proportion of districts exceeding both WHO and Uganda thresholds declined for OPV from 36.3% to 5.5% (p=0.024) and for DPT from 22.6% to 1.4% (p=0.013). Wastage was consistently higher in lower-level (Health Centre II and III) facilities, compared to hospitals. Among 50 service delivery points, reported reasons included low session attendance (66%), multi-dose vial policy non-compliance (28%), and vaccine expiry (12%). Conclusion Uganda achieved reductions in OPV wastage and district-level improvements in DPT wastage, while BCG and MR remained more variable and frequently had higher wastage. Strengthening adherence to the multi-dose vial policy and improving session planning at lower-level facilities could strengthen vaccine utilisation and forecasting.

02.
arXiv (CS.AI) 2026-06-19

SafeSpec: Fast and Safe LLM via Dynamic Reflective Sampling

arXiv:2606.19755v1 Announce Type: cross Abstract: Speculative inference accelerates large language model (LLM) decoding but provides no inherent safety guarantees. Existing safety defenses are largely incompatible with speculative inference: they either introduce additional computation or disrupt the draft-verify mechanism, negating acceleration benefits. This reveals a fundamental incompatibility between current safety methods and speculative decoding. We propose SafeSpec, a safety-aware speculative inference framework that integrates risk estimation directly into the verification process. SafeSpec attaches a lightweight latent safety head to the target model to jointly evaluate semantic validity and safety in a single forward pass. When unsafe generations are detected, SafeSpec applies rollback and safety-guided reflective multi-sampling to recover safe continuations rather than terminating generation. We model jailbreak attacks as distributional shifts over generative trajectories, where adversarial prompts increase the probability of harmful continuations without eliminating safe ones. Under this model, SafeSpec performs risk-aware trajectory recovery within the speculative decoding process. Across multiple models and adversarial benchmarks, SafeSpec achieves a substantially improved safety-efficiency trade-off. On Qwen3-32B, SafeSpec reduces attack success rates by 15% while preserving a 2.06x inference speedup on benign workloads, demonstrating that speculative acceleration and inference-time safety can be jointly optimized.

03.
arXiv (quant-ph) 2026-06-12

Statistical Mechanics and Symmetries of Non-Abelian Anyon Proliferation: From Deformation to Decoherence

arXiv:2606.12527v1 Announce Type: new Abstract: Topological quantum computation relies on braiding non-Abelian anyons, but requires the underlying topological order to survive imperfect state preparation and environmental noise. We show that the instability of topological order to wavefunction deformations and to decoherence, with the latter probed by syndrome distributions, are generically captured by stat-mech models whose symmetries naturally expose the corrupting anyonic excitations. As an example, we combine this framework with Monte-Carlo simulations to resolve the stability of $D_4$ topological order under deformations and quantum channels that proliferate multiple non-Abelian anyon species that individually are unable to condense. We show that beyond a finite threshold, proliferation of two non-Abelian anyon species parasitically condenses a shared Abelian-anyon fusion outcome, destroying the topological order. Our symmetry-based approach sharply differentiates the resulting trivial phase from that obtained by condensing all Abelian charges; in other words, the trivial phase "remembers" which anyons condensed. This framework provides a first step into identifying the relevant symmetry for optimal decoders, conditioned on syndrome measurements, of non-Abelian topological order.

04.
arXiv (CS.CV) 2026-06-15

FoleyGenEx: Unified Video-to-Audio Generation with Multi-Modal Control, Temporal Alignment, and Semantic Precision

We present FoleyGenEx, a unified video-to-audio (VTA) framework integrating multi-modal control, frame-level temporal alignment, and fine-grained semantics, enabling synchronized, versatile audio synthesis for diverse tasks. Existing VTA methods either have multi-modal control but weak temporal alignment or strong alignment but lack reference audio conditioning and semantic precision. FoleyGenEx fills this gap via three core innovations: a conditional injection mechanism for audio-controlled VTA and Foley extension, a multi-modal dynamic masking strategy preserving training synchronization, and an adverb-based data augmentation algorithm leveraging signal processing and large language models to enhance textual supervision with nuanced semantics. Experiments on AudioCaps, VGGSound, and Greatest Hits demonstrate its competitive controllable VTA performance against existing methods. Demo samples are available at https://foleygenex.github.io/FoleyGenEx.

05.
arXiv (CS.CL) 2026-06-17

ALAS: An Automatic Latent Alignment Score for Audio Language Models

Large Language Models (LLMs) are extended into Speech-LLMs, and the quality of the audio–text alignment they learn affects most downstream Spoken Language Understanding (SLU) behavior. Yet despite a growth of fusion strategies, there is no standard way to measure how well a Speech-LLM internally binds audio frames to text tokens. We introduce ALAS (Automatic Latent Alignment Score), a model and task-agnostic metric that probes the LLM's per-layer hidden states, scoring the cross-modal cosine similarity between audio and text representations against a Whisper-derived reference. ALAS needs only a frozen forward pass and an off-the-shelf ASR reference, with no training or fitted classifier, and is calibrated to an interpretable uniform baseline comparable across tasks. Applying ALAS to four open-source Speech-LLMs (AF3, Qwen2-Audio, Qwen-Omni, SALMONN) across emotion recognition (IEMOCAP), open-ended SQA (LibriSQA), and multi-choice audio understanding (MMAU-speech), we find that the depth and strength of alignment reflect each model's audio-encoder design and the acoustic-versus-semantic demands of the task, and that ALAS tracks but does not duplicate task accuracy, exposing models that score well without genuinely grounding in the audio. We release ALAS as an open-source library so that practitioners can probe their own Speech-LLMs or try it on new tasks.

06.
bioRxiv (Bioinfo) 2026-06-24

An atlas-scale generative model for unified representation learning of bulk RNA-seq data

Public bulk RNA-seq repositories contain hundreds of thousands of samples, creating opportunities for large-scale representation learning, but integration across studies remains challenging because of heterogeneous annotations, experimental protocols, and technical variation. While pre-trained foundation models are now widely available for single-cell RNA-seq, comparable resources for bulk RNA-seq remain scarce, motivating a model that learns a unified, tissue-aware representation directly from bulk data. We trained a supervised variational autoencoder (VAE) on a compendium of 118,263 bulk RNA-seq samples that we assembled from TCGA, GTEx, and ARCHS4 and mapped to 42 tissue categories. The model classifies tissue of origin at 94.9% balanced accuracy (weighted F1 96.2%) and compresses 16,115 genes into a 121-dimensional latent space. Tissue identity is the primary organizing axis of the latent space, while source effects remain secondary. To assess the impact of data volume, we constructed training sets at three different scales (38K, 75K, and 118K samples). Our results demonstrated that reconstruction fidelity improved incrementally with each expansion of the dataset, but with diminishing returns. We validated the model on an independent cohort of 734 paediatric tumour samples from TARGET, achieving 84.6% agreement with the expected tissue of origin. The trained model and code are available at GitHub (https://github.com/BIMSBbioinfo/flexynesis_tissue_vae_manuscript) with an interactive web application.

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

MagpieTTS-LF: Inference-Time Long-Form Speech Generation Without Training on Long-Form data

arXiv:2606.18485v1 Announce Type: cross Abstract: Neural Text-to-Speech (TTS) systems achieve remarkable quality on short utterances but long-form speech generation shows prosodic drift, speaker inconsistencies and sentence boundary artifacts. Existing approaches either compress sequences, increase context length or naively concatenate independently synthesized chunks. We present an inference-time approach called MagpieTTS-LF that enables MagpieTTS to produce coherent long-form speech without model retraining. Our method introduces three key innovations: (1) soft attention priors to guide monotonic alignment while preserving past and future context; (2) a stateful inference algorithm that maintains context across sentence chunks, ensuring prosodic continuity; (3) history-aware text encoding that uses past text for discourse-level prosodic planning. Experiments on long texts show significant improvements in long-range intelligibility, prosodic coherence, speaker consistency, and boundary naturalness compared to other baselines.

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

RetailBench: Benchmarking long horizon reasoning and coherent decision making of LLM agents in realistic retail environments

arXiv:2606.15862v1 Announce Type: new Abstract: Large language model (LLM) agents have made rapid progress on short-horizon, well-scoped tasks, yet their ability to sustain coherent decisions in dynamic long-horizon environments remains uncertain. We introduce RetailBench, a data-grounded simulation benchmark for evaluating tool-using LLM agents in single-store supermarket operation. RetailBench models retail management as a partially observable decision process and is designed to support thousand-day-scale simulations. In this environment, agents must manage pricing, replenishment, supplier selection, shelf assortment, inventory aging, customer feedback, external events, and cash-flow constraints. We evaluate seven contemporary LLMs under representative agent frameworks over a 180-day evaluation horizon and compare them with a privileged oracle policy. Results show substantial variation across models: only a small subset survives the full evaluation horizon, and even the strongest LLM runs remain substantially behind the oracle policy in final net worth and sales outcomes. Behavioral analysis attributes these gaps to incomplete evidence acquisition, surface-level decision making, and the lack of a consistent long-horizon policy. RetailBench provides a controlled testbed for studying reliable autonomy in economically grounded long-horizon decision-making.

09.
medRxiv (Medicine) 2026-06-24

TCIA Radiology Image Processing for AI and Radiomics

We developed a standardized, reproducible preprocessing framework for computed tomography (CT) imaging data from multi-institutional repositories such The Cancer Imaging Archive (TCIA), enabling consistent radiomics and artificial intelligence (AI) analyses. Imaging data from TCGA-KIRC patients available on TCIA were used as a representative heterogeneous dataset characterized by variation in acquisition protocols, inconsistent metadata, and differing image quality. The proposed modular pipeline includes series filtering, DICOM-to-NIfTI conversion, orientation harmonization to a canonical coordinate system, voxel spacing normalization, intensity clipping and normalization, segmentation integration, and metadata validation, and is implemented in a reproducible, notebook-based framework compatible with common radiomics and deep learning workflows. This pipeline standardizes imaging data into analysis-ready volumes with consistent geometry, intensity distributions, and spatial alignment, reducing non-biological variability that can adversely affect radiomic feature stability and model performance. The modular design enables task-specific adaptation of individual preprocessing steps while maintaining overall consistency. Although demonstrated on TCIA, this framework is generalizable to other heterogeneous imaging datasets and provides a foundation for robust, large-scale computational imaging studies.

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

MuVAP: Multimodal Multiparty Voice Activity Projection for Turn-taking Prediction in the Wild

arXiv:2606.16731v1 Announce Type: cross Abstract: Current multiparty turn-taking models often rely on complex microphone arrays or multi-camera setups, limiting their applicability in human-robot interaction scenarios. We introduce MuVAP, a causal multimodal framework that extends Voice Activity Projection by grounding acoustic predictions in face tracks, enabling speaker-aware turn-taking predictions from a monaural audio stream and a single camera view. To address the combinatorial complexity of modeling multiple speakers, we propose Role-Relative Projection, which maps any N-speaker interaction onto a fixed current versus next floor-holder state. Because existing audiovisual datasets contain disruptive editing cuts that break causal tracking, we introduce the Audio-Visual Conversation Corpus, a 31-hour dataset of unedited, single-camera multiparty conversations. Evaluations demonstrate that MuVAP outperforms strong baselines on Shift-Hold and next-speaker prediction tasks across two- and three-speaker settings.

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

MCR-VQGAN: A Scalable and Cost-Effective Tau PET Synthesis Approach for Alzheimer's Disease Imaging

Tau positron emission tomography (PET) is a critical diagnostic modality for Alzheimer's disease (AD), but its widespread clinical adoption is hindered by radiation exposure, limited availability, high clinical workload, and substantial financial costs. To address these limitations, we propose the Multi-scale CBAM Residual Vector Quantized Generative Adversarial Network (MCR-VQGAN) to synthesize high-fidelity tau PET images from structural T1-weighted MRI. MCR-VQGAN advances the standard VQGAN architecture through three enhancements: multi-scale convolutions, ResNet blocks, and Convolutional Block Attention Modules (CBAM), which collectively improve the capture of local and global features. Using 222 paired T1-weighted MRI and tau PET scans from the ADNI database, we trained and compared MCR-VQGAN against cGAN, WGAN-GP, CycleGAN, and baseline VQGAN. MCR-VQGAN achieved superior image synthesis performance across all metrics (MSE = 0.0056 +/- 0.0061, PSNR = 30.65 +/- 4.47 dB, SSIM = 0.9263 +/- 0.0469). A CNN-based AD classifier trained on real tau PET achieved comparable accuracy on real (63.64%) and synthetic (65.91%) images, indicating that diagnostically relevant features are preserved. Regional SUVR-equivalent analysis across Braak-defined ROIs further indicated strong agreement between real and synthetic tau PET (Pearson r = 0.78-0.88; ICC = 0.71-0.84), with the strongest agreement in Braak V/VI (ICC = 0.838). Together, these results suggest that MCR-VQGAN offers a promising and scalable surrogate for conventional tau PET imaging, potentially improving the accessibility of tau biomarkers for AD research and clinical workflows.

12.
arXiv (CS.CV) 2026-06-16

AURA: Active-Response Attribution under Treatment Ambiguity in Bacterial Cytological Profiling

When a bacterial sample is exposed to several antibiotics, not every applied drug necessarily acts: if the organism is resistant to one of them, that drug leaves no morphological trace. The clinically meaningful quantity is therefore not which antibiotics were applied, but which ones were active. We show that these two are sharply decoupled in real E. coli microscopy - naively assuming the applied combination equals the active one is correct only about 37% of the time - yet existing computational tools are ill-suited to recovering the active set. Forward perturbation models such as scGen, CPA, and IMPA are designed to predict appearance from treatment, not the reverse, and inverting them degrades sharply; discriminative image classifiers tend to memorise strain- and batch-specific texture and fail to transfer across experimental replicates. We introduce AURA, which reframes the task as constrained, energy-based inverse attribution. Its central inductive bias is that the active set must be a subset of the applied set; this collapses the candidate space and lets AURA infer the active subset of applied antibiotics by decomposing residual morphology into antibiotic response atoms and selecting the subset with the lowest reconstruction energy, using no strain label at test time. AURA-E adds evidence-aware abstention, withholding a prediction when candidate explanations remain near-equally plausible. On cross-replicate transfer in an E. coli cytological profiling dataset, AURA recovers the active antibiotic combination with 95.47% exact-match accuracy.

13.
arXiv (quant-ph) 2026-06-24

Doppler-enhanced superheterodyne Rydberg microwave receiver

arXiv:2606.24247v1 Announce Type: cross Abstract: We report the enhanced sensitivity of the Rydberg microwave (MW) receiver by exploiting the Doppler effect in a vapor cell. A two-photon Rydberg ladder scheme is implemented via the co-propagation of probe and coupling lasers, which enhances the Doppler effect. When an MW field is applied, microwave dressing modifies the velocity-dependent resonance condition, enabling stronger contributions from atoms with non-zero velocities and leading to an enhancement of the EIT transmission. Based on this mechanism, we achieve a sensitivity of $35.1\ \mathrm{nV\ cm^{-1}\ Hz^{-1/2}}$ using the heterodyne technique, which is 1.5 times better than that obtained in the counter-propagating configuration. Meanwhile, the required local oscillator (LO) field is reduced by a factor of 17.6 compared with the counter-propagating configuration, which is advantageous for applications requiring minimal radiation and low power consumption. Moreover, the co-propagating configuration is more amenable to integration or portable sensing platforms because multiple laser fields can be delivered through a single optical fiber.

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

QualiaNet: An Experience-Before-Inference Network

作者:

Human 3D vision involves two distinct stages: an Experience Module, where stereo depth is extracted relative to fixation, and an Inference Module, where this experience is interpreted to estimate 3D scene properties. Paradoxically, although stereo vision does not provide us with absolute distance information, it nonetheless affects our inferences about distance. We propose the Inference Module exploits a natural scene statistic: near scenes produce vivid disparity gradients, while far scenes appear comparatively flat. QualiaNet implements this two-stage architecture computationally: disparity maps simulating human stereo experience are passed to a CNN trained to estimate distance. The network can recover distance from disparity gradients alone, validating this approach.

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

Judging to Improve: A De-biased VLM-as-3D-Judge Protocol for Single-Image 3D Generation

arXiv:2606.20364v1 Announce Type: new Abstract: A companion study established a de-biased, cross-model VLM-as-3D-judge that reliably ranks single-image-to-3D mesh quality where cheap geometry and CLIP proxies fall short. This paper asks: can that judge's preferences specialize a strong open generator, TRELLIS, on one asset class (furniture), cheaply and without human labels? Taking the judge from ranking to optimization is where the work lives. Pushing a VLM judge into the training and evaluation loop exposes failure modes ranking never triggered, so our contribution is an optimization-grade hardening of the judge: a training judge (Qwen2.5-VL-7B) held distinct from an evaluation judge (InternVL3-8B) to break circularity; position-bias correction; and fixes for three failure modes (image overload, geometry-hiding splat renders, and reference-free judging that rewards clean-but-wrong outputs), with calibration evidence (clear-gap win-rate 0.83-1.0; base-vs-base ~0.5). Using this protocol as an independent evaluator, and working only from public models and data with lightweight parameter-efficient adaptation, we find our methods match the strong base rather than exceed it. Independent base samples carry essentially no learnable preference (0.94 order-flip rate), so signal must be engineered by quality-contrastive construction. Across six adaptation methods, two input regimes, and a severity sweep, the most targeted - conditioner repair under severe degradation - reaches parity (0.50) with the base, while no method clears the >=65% win-rate target. The result is mechanistic: clean inputs saturate the judge, flow-DIT fine-tuning washes out through the sampler, and conditioning repair is the locus that moves geometry. Win-rates are directional at n=8 objects. Matching a strong public-data base with cheap adaptation is itself informative: exceeding it needs more than lightweight PEFT on public data, and the judge protocol is reusable.

16.
arXiv (CS.LG) 2026-06-24

Reasoning as Attractor Dynamics: Latent Memory Retrieval via Gibbs-Weighted Energy Minimization

arXiv:2606.24543v1 Announce Type: new Abstract: Large Language Models (LLMs) are traditionally viewed as autoregressive generators. However, from the perspective of collective computation, they function as high-dimensional Dense Associative Memories that store complex reasoning patterns as latent attractors. In this work, we investigate the energy landscape of mathematical reasoning. We posit that correct reasoning chains correspond to deep, wide attractor basins ("flat minima") in the model's output distribution, whereas hallucinations manifest as sharp, unstable local minima. To exploit this geometry, we introduce a retrieval mechanism based on a Gibbs measure of the trajectory's spectral entropy. By sampling multiple reasoning paths and weighting them by their inverse energy ($P \propto e^{-\beta E}$), we approximate the equilibrium distribution of the associative memory, effectively ``relaxing'' the system into a robust solution. Empirically, this physics-inspired mechanism improves Microsoft Phi-3.5 performance on GSM8K by 5.38\% (84.7\% $\to$ 90.1\%), demonstrating that inference is better modeled as a dynamic settling process into an attractor basin rather than greedy next-token prediction.

17.
medRxiv (Medicine) 2026-06-15

VarEx: A Large Language Model Pipeline for Automated Extraction of Exposures, Outcomes, and Covariates from Epidemiologic Studies

Objective: Observational studies are essential for investigating risk factors for Alzheimer's disease and related dementias (ADRD), but inconsistent reporting and selection of covariates can contribute to residual confounding, omitted-variable bias, and reduced reproducibility. We developed and evaluated VAREX (Variable Extraction), a large language model (LLM)-based information extraction framework designed to automatically identify exposures, outcomes, and covariates from epidemiologic studies and populate structured evidence repositories. Materials and Methods: VAREX combines retrieval-augmented generation, biomedical language-model embeddings, semantic chunking, cross-encoder reranking, and prompt-engineered LLM workflows to extract epidemiologic variables from full-text biomedical articles. The framework was evaluated using a reference-standard corpus of observational studies examining blood pressure variability (BPV) and Alzheimer's disease-related dementias (ADRD), together with external validation datasets involving other exposure-outcome relationships. Extracted variables were compared with independently curated human reference standards using semantic matching and one-to-one assignment procedures. Covariates were additionally classified into ten epidemiologically relevant semantic categories. Results: In the primary BPV[->]ADRD corpus (10 studies), VAREX achieved a precision of 0.91, recall of 0.84, and F1-score of 0.87 for variable extraction. Covariate classification accuracy was 0.90, yielding a strict extraction-and-classification F1-score of 0.78. External validation datasets demonstrated comparable performance across diverse epidemiologic domains, with extraction F1-scores ranging from 0.73 to 0.85. Category-level performance was strongest for health behaviors (F1=0.96), sociodemographic variables (F1=0.90), and medication exposures (F1=0.89). Compared with published estimates of manual systematic-review effort, VAREX reduced processing time from approximately 61 minutes to 9 minutes per article, representing an 85.7% reduction in review time. Discussion: These findings demonstrate that LLM-based information extraction can accurately identify and classify epidemiologic variables across heterogeneous observational-study designs. Automated extraction enables scalable construction of structured repositories of exposures, outcomes, and covariates while substantially reducing the labor required for evidence synthesis and systematic reviews. Conclusion: VAREX provides an effective framework for automated extraction and classification of epidemiologic variables from the biomedical literature. By supporting large-scale evidence synthesis and structured knowledge resource development, VAREX may facilitate more rigorous observational research, improved confounder identification, and enhanced reproducibility in epidemiology.

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

ScalingAR: Scaling Confidence for Autoregressive Image Generation

Test-time strategies have shown remarkable success in improving large language models, but their application to next-token prediction (NTP) autoregressive (AR) image generation remains largely underexplored. Existing test-time scaling (TTS) methods for visual autoregressive models (VAR) rely on frequent partial decoding and external reward models, which are inefficient and often ineffective for NTP-based image generation due to the inherent instability of intermediate decoding results. To address these limitations, we propose ScalingAR, a novel test-time scaling framework tailored for NTP-based AR image generation. ScalingAR introduces token entropy as a confidence signal and operates at two complementary levels: (i) Profile Level, integrates intrinsic uncertainty and conditional utilization into a unified confidence state, and (ii) Policy Level, leverages this state for adaptive trajectory pruning and dynamic guidance scheduling. Without requiring early decoding or auxiliary rewards, ScalingAR achieves significant improvements across diverse benchmarks. Experiments show that ScalingAR (I) improves base models by $12.5\%$ on GenEval and $15.2\%$ on TIIF-Bench, (II) reduces visual token consumption by $62.0\%$ while outperforming baselines, and (III) enhances robustness, mitigating performance degradation by $26.0\%$ in challenging scenarios. These results establish ScalingAR as a robust and efficient test-time scaling solution for autoregressive image generation.

19.
arXiv (math.PR) 2026-06-18

Kemeny's constant minimization for reversible Markov chains via structure-preserving perturbations

arXiv:2510.24679v4 Announce Type: replace-cross Abstract: Kemeny's constant measures the efficiency of a Markov chain in traversing its states. We investigate whether structure-preserving perturbations to the transition probabilities of a reversible Markov chain can improve its connectivity while maintaining a fixed stationary distribution. Although the minimum achievable value for Kemeny's constant can be estimated, the required perturbations may be infeasible. We reformulate the problem as an optimization task, focusing on solution existence and efficient algorithms, with an emphasis on the problem of minimizing Kemeny's constant under sparsity constraints.

20.
medRxiv (Medicine) 2026-06-15

Routine use of oral iron for people with heart failure and iron deficiency in primary care; retrospective cohort study

Aims: Iron deficiency is common among people with heart failure and associated with morbidity and mortality. While intravenous iron improves clinical outcomes, oral iron continues to be prescribed in routine practice despite limited evidence of benefit. Methods: We completed a retrospective primary care cohort study (2016 to 2021) to investigate the proportion of people with an incident diagnosis of heart failure who had iron deficiency identified (defined as ferritin

21.
arXiv (CS.LG) 2026-06-16

How Controlling the Variance can Improve Training Stability of Sparsely Activated DNNs and CNNs

arXiv:2602.05779v2 Announce Type: replace Abstract: The Edge-of-Chaos (EoC) theory developed for the random initialization of deep networks allows more efficient training by both preserving information in the initial outputs of the network and minimising exploding or vanishing gradients through characterisation of the intermediate layers as Gaussian processes. This EoC theory provides formulae for the choice of the initialisation distribution variances of the weights and biases. For activations which are approximately linear around the origin, the EoC theory typically encourages the Gaussian process variance to converge towards zero with increasing depth. Here we consider the less studied setting of highly sparsity inducing activations where a large region of values near the origin are set to zero. In this setting we prove a new phenomenon whereby initialisations leading to larger fixed Gaussian processes are beneficial to training stability. This theory informs a new, yet simple, initialisation strategy that allows training DNNs and CNNs with as large as 90\% sparsity in the hidden layers.

22.
bioRxiv (Bioinfo) 2026-06-11

HoloCell: A Generative Foundation Model for Holistic Cellular Modeling

Single-cell multi-omics technologies have recently advanced to enable the profiling of epigenomic, transcriptomic, and proteomic layers within individual cells, offering new opportunities to characterize cellular states as integrated biological systems. However, developing a unified framework that can seamlessly integrate diverse omics modalities and remain robust to heterogeneous modality missingness remains challenging. Here we present HoloCell, to our knowledge the first generative foundation model for joint representation learning and generative modeling across all three major single-cell omics modalities, i.e., epigenomics, transcriptomics, and proteomics. HoloCell contains over 860 million parameters and is pretrained on the Human-Multi-Omics-Corpus, which comprises approximately 468 million single-cell profiles across these three omics layers, corresponding to over 425 billion tokens. HoloCell introduces a simple yet biologically grounded hierarchical tokenization strategy that encodes cis-regulatory elements, genes, and proteins as structured tokens within a shared modeling framework. We evaluated HoloCell across single-omics representation learning, paired multi-omics integration, unpaired multi-omics alignment, and cross-modal generation via iterative diffusion and remasking, demonstrating its superior performance and flexibility across diverse omics tasks. From a representation perspective, HoloCell provides a unified digital mapping of cellular states across multiple omics layers, capturing cell heterogeneity as an integrated system. From a generation perspective, its iterative diffusion and remasking framework accounts for the inherently unordered nature of biological features, enabling in silico simulation of multi-omics information flow. Together, these capabilities position HoloCell as a versatile foundation model toward the emerging concept of a virtual cell, offering both systematic characterization and generative simulation of cellular systems within a unified framework.

23.
bioRxiv (Bioinfo) 2026-06-23

Measuring peptide-MHC generalization to unseen alleles across both HLA classes

作者:

Reported peptide-MHC (pMHC) AUROCs of 0.85-0.95 overstate generalization to unseen alleles: because immunopeptidome data are dense on a few well-studied alleles and sparse on the rest, training and test sets come to share near-identical alleles, so the numbers partly reflect interpolation rather than extrapolation to new MHC grooves. This is a property of the data, not of any one method. We assembled an open, harmonized corpus of 5.8 million experimental measurements across both HLA classes and use it to control the leakage explicitly: alleles held out at the sequence and cluster level, peptide-disjoint splits, and provenance-matched negatives. On strictly novel alleles, generalization is in the high 0.7s rather than the 0.9s a conventional split returns. Against this benchmark we trained a predictor that spans both classes in one model and factors presentation into a peptide-only ligand-likeness term and an allele-specific term; it exceeds eight published predictors by per-allele {Delta}AUROC = +0.22 to +0.37 (p < 10-9), most on the least-studied genes. Corpus, benchmark, and model are released.

24.
arXiv (CS.CV) 2026-06-11

SCAIL-2: Unifying Controlled Character Animation with End-to-end In-Context Conditioning

Controlled character animation requires transferring motion from a driving sequence to a reference character. Prior works heavily rely on intermediate representations, including pose skeletons to represent motion or masked background to represent environment, which inevitably leads to information loss. To address this, we present SCAIL-2, a framework that bypasses those intermediates and achieves end-to-end character animation. By directly concatenating driving videos to the sequence, the model can obtain all the required visual information from the input video. To address the lack of end-to-end data, we unify sub-tasks of character animation with decoupled conditions and then curate a pipeline to synthesize MotionPair-60K, an end-to-end motion transfer dataset containing heterogeneous tasks of character animation. To achieve the unification, we utilize in-context mask conditioning and mode-specific RoPE as soft guidance beyond textual instructions and raw visual information. To address synthetic discrepancy in detailed regions, we propose Bias-Aware DPO to construct preference items to mitigate the errors. Extensive experiments demonstrate that our method substantially outperforms existing state-of-the-art approaches in various character animation tasks. A large subset of synthetic data as well as model weights will be released at our project page: https://teal024.github.io/SCAIL-2/.

25.
bioRxiv (Bioinfo) 2026-06-18

segSHAPE: RNA secondary structure prediction from nanopore direct RNA sequencing

RNAs adopt complex structures that regulate key biological processes, making accurate structure prediction essential. Chemical probing coupled with Nanopore direct RNA sequencing (DRS) offers a route to single-molecule structural inference, but current tools are limited by inaccurate signal-to-sequence alignment, which degrades modification-rate estimation and downstream structure prediction. Here we introduce segSHAPE for RNA secondary structure prediction from Nanopore DRS data (both RNA002 and RNA004 chemistries), a probe-agnostic framework that improves signal alignment using prior information of basecalling and per-read signal baseline shift correction, learns position-specific k-mer raw signal parameters, and estimates per-nucleotide modification rates with an unsupervised anomaly detector. On three public RNA002 DRS datasets spanning different chemical probes (AcIm, NAI-N3) and RNAs from 421 to 1552 nt, segSHAPE achieves the highest F1 score and Matthews correlation coefficient (MCC) on all RNAs, exceeding the strongest baseline by 3.4 to 5.8 percentage points in MCC. It additionally captures the ligand-induced conformational change of the thiamine pyrophosphate (TPP) riboswitch RNA directly from RNA002 DRS data using the DEPC probe. On a public RNA004 DRS dataset, segSHAPE improves over the sm-PORE-cupine baseline by 17 ROC-AUC points in modification rate estimation and by 6.7 MCC points in structure prediction. These results establish segSHAPE as a unified, probe-agnostic pipeline for RNA structure prediction from Nanopore DRS data.