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

Spectrum Aware Illumination Estimation Using Multispectral Image

Multispectral (MS) imaging extends beyond conventional RGB imaging by capturing more spectral bands, thereby improving illuminant spectrum estimation (ISE). However, existing methods often fail to fully exploit spectral information, resulting in suboptimal performance under diverse lighting conditions and across different sensor domains. Hence, we propose a deep learning framework with a spatio-spectral feature extraction block, which incorporates spectral attention mechanisms to enhance spectral correlation and preserve illuminant-relevant spatial features. Through the inclusion of an illuminant prior (IP), our approach prioritizes specific channels that provide more meaningful information in an MS image. We also propose a spectral-domain transform across different MS sensor spaces. The results demonstrate that illuminant spectra learned in high-dimensional sensor spaces can be effectively transformed to various lower-dimensional camera sensor spaces without any additional training. To facilitate evaluation, we introduce a real-world MS dataset containing high-dimensional ground-truth illumination spectra captured under diverse lighting conditions. Through extensive experiments, we demonstrate that our method achieves superior accuracy compared to existing models, thus providing a practical solution for real-world ISE. The code and dataset are available at https://github.com/hyejin5/Spectrum-Aware-Illumination-Estimation-Using-Multispectral-Image.

02.
PLOS Medicine 2026-05-06

Pathways of emergency care for severely ill children in Nigerian and Ugandan hospitals: A process mapping study

作者:

by Rami Subhi, Abiodun Sogbesan, Dan Muramuzi, Mikael Burhin, Ayobami A. Bakare, Adegoke G. Falade, Freddy E. Kitutu, Freddie Ssengooba, Carina King, Sumit Kane, Belinda Dawson-McClaren, Hamish R. Graham, the MOXY-Implementation Research Collaboration Background Child mortality remains high in countries with weak emergency care systems. Facility organisation for paediatric emergency care is heterogeneous and under-described. We examined how hospitals in Uganda and Nigeria are organised to deliver emergency care for neonates and children. Methods and findings We conducted a qualitative, multi-method study in 26 purposively selected secondary and tertiary facilities in Uganda and Nigeria from October 2023 to December 2024. Embedded researchers documented patient pathways, resources for care, and care processes for severely ill children (

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

MUFFLe: Efficient Model Update Compression via Generalized Deduplication for Federated Learning

arXiv:2606.14354v1 Announce Type: new Abstract: Federated learning is well suited to edge environments but is often limited by the uplink cost of transmitting model updates. This Work-in-Progress paper presents MUFFLe, a communication-efficient update compression scheme that integrates generalized deduplication (GD) into the FedAvg pipeline. MUFFLe deduplicates repeated patterns across the update vector, yielding a fixed-rate, variable-count compression scheme. Preliminary experiments on IID MNIST with 20 clients show that MUFFLe reaches the target accuracy of $92.93\%$ with 38~MB cumulative uplink communication, compared with 75~MB for 8-bit quantization, 86~MB for Top-$k$ sparsification, and 310~MB for uncompressed FedAvg. These results demonstrate the feasibility of applying GD to communication-efficient federated learning.

04.
arXiv (CS.LG) 2026-06-16

Beyond Artifacts: Towards Generalizable Synthetic Song Detection via Music-Intrinsic Features

arXiv:2606.16612v1 Announce Type: cross Abstract: The rapid advancement of AI music generators highlights the urgent need for reliable Synthetic Song Detection (SSD). Existing SSD methods often rely on low-level artifacts or fixed feature assumptions, struggling to capture generator-agnostic cues. To address this, we propose Sofia (Synthetic-song detection framework via music features), a flexible framework that models music-intrinsic attributes via feature-specific experts and an adaptive Mixture-of-Experts (MoE) module. By configuring Sofia with representative Vocal, Audio-effect, Global structure features, and their combinations, we present their individual and complementary contributions. To comprehensively evaluate our framework, we further construct MUSIC8K, a challenging benchmark featuring lastest emerging generators and realistic audio perturbations. Experiments show that Sofia learns generator-agnostic representations from music-intrinsic features, improving the F1 score by 18.5 points over the strongest baseline on MUSIC8K-O while maintaining strong robustness.

05.
arXiv (CS.AI) 2026-06-11

READER: Robust Evidence-based Authorship Decoding via Extracted Representations

arXiv:2606.10794v2 Announce Type: replace Abstract: As agentic applications increasingly route user tasks through official and third-party LLM APIs, provenance becomes an operational question: which model generated a given black-box response? We study Dynamic Black-Box LLM Provenance: identifying the source LLM from generations elicited by query-varying, non-predefined prompts rather than a fixed input set or benchmark suite. This setting is difficult because prompt semantics dominate the text, while model-specific authorship traces are weak and inconsistent at the surface level. We introduce READER (Robust Evidence-based Authorship Decoding via Extracted Representations), a lightweight provenance framework that treats a frozen proxy LLM as a reader of hidden authorship evidence. READER maps black-box outputs into proxy activation space, temporally filters token states within each response, and performs Bayesian Evidence Accumulation by summing single-response log-posterior evidence across independently sampled prompts. This avoids fragile mean-pooling of prompt-specific representations while preserving the query-wise evidence needed for calibrated confidence. On Agent500, a 50-target dataset built from agent-style prompts, READER reaches $31.0$-$42.4\%$ top-1 accuracy from a single response and $70.0$-$84.0\%$ from 50 responses, substantially outperforming sentence-encoder fingerprints. Scaling across nine proxy readers further shows that stronger LLMs expose more linearly decodable authorship structure, suggesting that authorship perception is already present in frozen LLM representations and can be converted into reliable multi-query attribution.

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

The Implicit Bias of Steepest Descent with Mini-batch Stochastic Gradient

arXiv:2602.11557v2 Announce Type: replace Abstract: A variety of widely used optimization methods like SignSGD and Muon can be interpreted as instances of steepest descent under different norm-induced geometries. In this work, we study the implicit bias of mini-batch stochastic steepest descent in multi-class classification, characterizing how batch size, momentum, and variance reduction shape the limiting max-margin behavior and convergence rates under general entry-wise and Schatten-$p$ norms. We show that, without momentum, worst-case convergence and successful classification can only be guaranteed with full-batch gradient. In contrast, momentum enables small-batch convergence to an approximate max-margin solution through a batch-momentum trade-off, though it slows convergence. This approach provides fully explicit, dimension-free rates that improve upon prior results. Moreover, we prove that variance reduction can recover the exact full-batch implicit bias for any batch size, albeit at a slower convergence rate. Finally, we further investigate the batch-size-one steepest descent without momentum, and reveal its convergence to a fundamentally different bias via a concrete data example, which reveals a key limitation of purely stochastic updates. Overall, our unified analysis clarifies when stochastic optimization aligns with full-batch behavior, and paves the way for perform deeper explorations of the training behavior of stochastic gradient steepest descent algorithms.

07.
arXiv (CS.AI) 2026-06-19

Hybrid ANN-SNN Pipeline with Local Plasticity

arXiv:2606.20151v1 Announce Type: cross Abstract: This work proposes a hybrid ANN-SNN pipeline that effectively leverages the rich embeddings of pretrained artificial neural networks (ANNs) to enable high-performance spiking neural networks (SNNs). The architecture couples a pretrained EfficientNet encoder with a CoLaNET spiking classifier. We convert the encoder's activations into spike trains via rate-coding and train the subsequent SNN classifier using local, biologically inspired learning rules, bypassing end-to-end gradient propagation. This approach achieves 99.09% accuracy on a 64-class ImageNet benchmark, demonstrating performance on par with conventional deep networks. The work presents a biologically plausible and efficient framework for adapting powerful pretrained encoders to downstream spiking neural network tasks.

08.
bioRxiv (Bioinfo) 2026-06-16

PhenoBIC: operator-free single-cell spatial phenotyping in multiplex imaging data using deep learning of cell staining patterns

Multiplex imaging is a valuable tool for spatially examining tissue microenvironments at the single-cell level to uncover biological and clinical insights. However, most multiplex image analysis workflows currently require manual intervention for cell phenotyping, which slows progress, demands human effort, and yields operator-dependent outputs. Here, we developed PhenoBIC, a pre-trained deep learning model for image classification of the multiplexed biomarker signals in a cell (Biomarker Imprint of a Cell) to classify cell phenotypes. We show that PhenoBIC (F1-score ~0.88) outperforms manual gating (widely used) and other machine learning-based computational approaches for cell marker expression classification. We validated this across multiple biomarkers, tissue sampling strategies (whole biopsies and tissue microarrays), multiplex panels, imaging platforms, and tissue types. We have released our in-house training and validation datasets of ~1.4 million manually curated cell expression ground truth labels. We have also open-sourced PhenoBIC and enabled its community-wide deployment via the QuPath interface.

09.
arXiv (CS.LG) 2026-06-18

Context-Aware Optimization of Follow-Up Intervals for Type 2 Diabetes Care Using Markov Decision Processes

arXiv:2606.19092v1 Announce Type: cross Abstract: Chronic disease management relies on regular patient-provider interactions to follow-up on disease progression and control. For Type 2 Diabetes (T2D), current guidelines prescribe fixed time intervals between subsequent primary care visits for all patients, overlooking heterogeneity in clinical trajectories and patient characteristics. This study introduces a Contextual Markov Decision Process (CMDP) model to optimize subpopulation-specific follow-up interval decisions using Electronic Health Record (EHR) data from 22,154 T2D patients across 10 primary care clinics. Contexts are identified by: i) dimensionality reduction of variables representing the individual health trajectories utilizing Principal Component Analysis, and ii) assigning patients to contexts via principal components and additional patient-level features using clustering. Two distinct contexts emerged, representing a lower- and a higher-risk subpopulation. CMDP-derived policies recommend: (i) follow-up within 1 month if lab value at current visit is unmeasured; (ii) up to 3 months for elevated lab values or recent hospitalizations; and (iii) 6 to 12 months for sustained glycemic control, with shorter follow-up intervals for patients in high-risk context. The optimal policies achieved lower expected cumulative cost than benchmarks (e.g., in the higher-comorbidity context, the CMDP policy reduced cost by about 34.8%, and in the lower-comorbidity context by about 6.4%, relative to an American Diabetes Association-like fixed interval follow-up policy. These findings demonstrate how context-aware approaches can inform adaptive follow-up strategies, and have the potential to advance chronic care management in primary care by synthesizing machine learning and probabilistic decision models.

10.
bioRxiv (Bioinfo) 2026-06-11

DivQuant: Estimation of Species Richness and Entropy from Small Samples

Estimating diversity properties of discrete distributions from a small observed sample is a fundamental problem in algorithmic statistics that has applications in many fields, in particular bioinformatics, but also in ecology or linguistics. The two most common diversity measures are the number of distinct elements in a multiset, also referred to as species richness in ecology or alpha diversity in microbial analysis, and the Shannon entropy, also referred to as evenness. Estimating these properties from a small sample is particularly challenging for distributions with many rare elements. Thus, many estimators have been proposed in the past that, in practice, work well for different types of distributions. We present DivQuant, an optimization-based, extrapolating richness and entropy estimator with three contributions. First, we formulate the upsampling problem as a convex quadratic program with a Neyman {chi}2 objective. Unlike the linear program of its predecessor RichnEst, DivQuant admits confidence intervals via {chi}2 test inversion that are empirically well-calibrated. Second, we replace RichnEst's fixed-threshold fingerprint truncation with the rare/abundant fingerprint split of Valiant and Valiant, which strongly reduces problem size and preserves enough degrees of freedom for the confidence-interval program to remain valid and feasible. Third, we plug the optimal population fingerprint returned by the program into Shannon's entropy formula to obtain an entropy estimate. DivQuant attains close-to-nominal 95% confidence intervals in essentially all tested regimes, including six simulated distribution families, Tara Oceans microbiome data, and 10X Genomics scRNA-seq data, while competing state-of-the-art methods (RichnEst, iNext, PreSeq) miss the true richness in up to 80% of instances, well above the nominal 5%. In addition, DivQuant outperforms classical asymptotic entropy estimators (Miller-Madow, CAE) and the extrapolating iNext estimator. Running times remain competitive, with DivQuant typically completing in seconds. DivQuant is available as a command-line tool at https://gitlab.com/rahmannlab/divquant.

11.
arXiv (quant-ph) 2026-06-12

Quantum walk-based optimisation for capacitated vehicle routing with homogeneous and heterogeneous fleets

arXiv:2606.12856v1 Announce Type: new Abstract: The capacitated vehicle routing problem (CVRP) is an appealing candidate for quantum optimisation due to its combinatorial complexity and practical importance. However, the problem's constrained search space poses a challenge for such quantum algorithms. We introduce a quantum walk-based optimisation algorithm (QWOA) for the CVRP with homogeneous or heterogeneous vehicle fleets, addressing this challenge through a continuous-time quantum walk over a product space that coincides with combinatorial structures intrinsic to the CVRP solution space. Relative to the prior QWOA-based formulation, this approach reduces the per-layer gate complexity from $\mathcal{O}(n^{3}\log n)$ to $\mathcal{O}(n^{2}\log n)$ and supports a circuit parameterisation schedule generated by a fixed number of classical parameters. Exact state-vector simulation on instances with up to $n=8$ customers and $K=3$ vehicles demonstrates improved convergence to low-cost solutions using markedly fewer objective function evaluations, with the advantage broadening as problem size increases. These results identify structured product-space walks as a promising tool for optimisation over constrained combinatorial spaces.

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

ViPER: Vision-based Packing-Aware Encoder for Robust Malware Detection

Visualization-based malware detection maps raw binary bytes to grayscale images and applies learned visual classifiers, providing an evasion-resistant and disassembly-free alternative to conventional analysis pipelines. However, executable packing remains a critical failure mode: packed binaries produce high-entropy images that obscure the structural patterns these models rely on. Because packing is also prevalent in benign software (e.g., for compression or copy protection), packing state alone is not a reliable indicator of maliciousness, and existing approaches do not address this challenge within a unified supervised framework. We present ViPER, a Vision-based Packing-Aware Encoder for Robust malware detection. ViPER builds on a LoRA-adapted ViT-B/14 backbone with a dual-head architecture that jointly learns malware classification and packing detection. A packing-aware gating mechanism conditions malware predictions on the inferred packing state, enabling distinct decision boundaries for packed and unpacked inputs. To address packing label skew during training, we employ frequency-weighted losses with stratified sampling over joint class-packing strata. Evaluated on 200,000 Windows PE byteplot images, ViPER achieves a balanced accuracy of 0.8521, ROC-AUC of 0.9260, and AUPR of 0.9279, outperforming representative state-of-the-art baselines across all primary metrics, while attaining a packing detection AUC of 0.9949.

13.
arXiv (CS.AI) 2026-06-11

When Poison Fails After Retrieval: Revisiting Corpus Poisoning under Chunking and Reranking Pipelines

arXiv:2606.11265v1 Announce Type: cross Abstract: Retrieval-Augmented Generation (RAG) systems are vulnerable to corpus poisoning attacks that manipulate downstream model outputs through malicious knowledge injection. Existing studies mainly evaluate poisoning under simplified retrieval settings, overlooking practical RAG pipelines involving document chunking, dense retrieval, reranking, and grounded generation. In this paper, we revisit corpus poisoning under realistic multi-stage retrieval pipelines and show that many existing attacks substantially degrade after reranking despite achieving high retrieval-stage relevance. We identify retrieval granularity mismatch as a key reason for this failure: document-level adversarial signals are often fragmented during chunking, while rerankers favor locally coherent and answer-bearing passages rather than globally optimized semantic similarity. Based on this observation, we propose Chunk-aware and Rerank-Consistent Poisoning (CRCP), a poisoning framework that jointly optimizes retrieval relevance, reranker consistency, and chunk-boundary robustness. CRCP explicitly models chunking transformations during optimization to generate locally self-contained adversarial passages that remain effective under varying chunking configurations. Experiments on standard RAG benchmarks with multiple retrievers and rerankers show that existing poisoning methods are highly sensitive to chunk size and reranking strategies, whereas CRCP achieves substantially higher attack success rates and stronger robustness across realistic retrieval pipelines. Our findings highlight an important realism gap in current RAG security evaluation and suggest that poisoning in modern RAG systems should be studied as a multi-stage retrieval consistency problem rather than a retrieval-only problem.

14.
arXiv (CS.CL) 2026-06-11

Pass@K Policy Optimization: Solving Harder Reinforcement Learning Problems

Reinforcement Learning (RL) algorithms sample multiple n>1 solution attempts for each problem and reward them independently. This optimizes for pass@1 performance and prioritizes the strength of isolated samples at the expense of the diversity and collective utility of sets of samples. This under-utilizes the sampling capacity, limiting exploration and eventual improvement on harder examples. As a fix, we propose Pass-at-k Policy Optimization (PKPO), a transformation on the final rewards which leads to direct optimization of pass@k performance, thus optimizing for sets of samples that maximize reward when considered jointly. Our contribution is to derive novel low variance unbiased estimators for pass@k and its gradient, in both the binary and continuous reward settings. We show optimization with our estimators reduces to standard RL with rewards that have been jointly transformed by a stable and efficient transformation function. While previous efforts are restricted to k=n, ours is the first to enable robust optimization of pass@k for any arbitrary k

15.
arXiv (CS.CV) 2026-06-18

Reference-Driven Multi-Speaker Audio Scene Generation from In-the-Wild Priors

Existing multi-speaker dialogue systems bind speakers to utterances through structured supervision: per-turn tags, multi-stream transcriptions, or learnable speaker embeddings. These systems operate within speech-only pipelines that produce clean vocal sequences without the ambient texture of real conversations. We take a different approach. Our method, ScenA, conditions a text-to-audio flow-matching foundation model, pretrained on large-scale in-the-wild data, directly on multiple reference voices and a free-form natural language prompt that describes an entire multi-speaker audio scene. Leveraging such a foundational model allows us to inherit its capacity for natural, non-studio audio: background noise, room acoustics, overlapping dialogue, and spontaneous paralinguistic events, while adding multi-speaker control without any per-turn structure. Concretely, reference latents are concatenated into the model's token sequence and distinguished by lightweight identity-aware positional encodings. However, we identify a critical obstacle to this approach: the Reference Shortcut. During training under standard noise schedules, the model can identify the matching reference by acoustic similarity to the noisy target, bypassing the text prompt entirely. We address this with a high-noise-biased timestep distribution that forces the model to rely on the text prompt for speaker assignment. We evaluate ScenA on the CoVoMix2-Dialogue benchmark, showing that it outperforms existing multi-speaker systems on speaker-binding metrics while generating rich conversational audio with overlapping speech, emotional vocalizations, and ambient sound. Our results demonstrate the advantage of using a general-purpose audio model conditioned on a free-form scene description, rather than passing structured dialog scripts through a speech-only pipeline.

16.
arXiv (CS.CL) 2026-06-18

STARE: Surprisal-Guided Token-Level Advantage Reweighting for Policy Entropy Stability

Reinforcement Learning with Verifiable Rewards algorithms like GRPO have emerged as the dominant post-training paradigm for complex reasoning in LLMs, yet commonly suffer from policy entropy collapse during training. We conduct a first-order gradient analysis of token-level entropy dynamics under GRPO and identify a token-level credit assignment mismatch: the per-token entropy variation decomposes into the product of the trajectory-level advantage and an entropy sensitivity function over the next-token distribution, yielding an advantage-surprisal four-quadrant structure and a near-criticality property. Motivated by it, we propose STARE (Surprisal-guided Token-level Advantage Reweighting for policy Entropy stability), which identifies entropy-critical token subsets via batch-internal surprisal quantiles, selectively reweights their effective advantages, and incorporates a target-entropy closed-loop gate for stable entropy regulation. Across model scales from 1.5B to 32B and three task families (Short CoT, Long CoT, and Multi-Turn Tool Use), STARE sustains stable RL training over thousands of steps while maintaining policy entropy within the target band. On AIME24 and AIME25, STARE outperforms DAPO and other competitive baselines by 4%-8% in average accuracy, with reflection tokens and response length growing in tandem, indicating sustained exploration-exploitation balance that further unlocks RL training potential.Code is available at https://github.com/hp-luo/STARE.

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

Beyond Weights and Gradients: A Taxonomy of Federated Learning Messages

arXiv:2606.16891v1 Announce Type: cross Abstract: Federated Learning is rapidly evolving beyond the exchange of traditional model weights and gradients, yet existing definitions fail to capture the full scope of modern payloads like synthetic data and federated analytics. This paper addresses the gap by proposing a formal mathematical definition of a federated message that accounts for both utility and privacy. We introduce a taxonomy that organizes these exchanges into three categories: model structures, statistical summaries, and data-conditioned representations. By evaluating these groups based on computational demands, communication costs, and privacy risks, we provide a clearer understanding of the trade-offs involved in decentralized training. Our review of 202 recent publications highlights a significant shift since 2021 toward diverse messaging paradigms, signaling a move away from standard deep learning updates toward more specialized information sharing. This framework provides a structured path for future research to optimize federated systems for varying hardware and security requirements.

18.
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.

19.
arXiv (quant-ph) 2026-06-11

A saturation-absorption rubidium magnetometer with multilevel optical Bloch-equation modeling for intermediate-to-high fields

arXiv:2601.09115v2 Announce Type: replace Abstract: We present SASHMAG (Saturated Absorption Spectroscopy High-field MAGnetometer), an atomic sensor designed for precision magnetic-field measurements in the intermediate-to-high field regime ($>0.2\,T$) using Rubidium-87 ($^{87}Rb$). The sensor operates in the hyperfine Paschen-Back regime, where the hyperfine and Zeeman interactions decouple, and utilizes counter-propagating pump-probe configuration in Faraday geometry to resolve isolated, Doppler-free Zeeman transitions. To interpret the resulting spectra in this strongly field-dependent regime, we developed a comprehensive multilevel optical Bloch-equation model solved explicitly in the uncoupled $\ket{m_I, m_J}$ basis, capturing state mixing and nonlinear saturation dynamics. This model reproduces measured spectra at sub-Doppler resolution and is consistent with analytical expectations for power broadening and thermal Doppler scaling. Magnetic field estimation is performed using a physics-constrained optimization routine that infers the magnetic field by minimizing the residual between experimentally extracted line centers and calculated transition frequencies from the field-dependent Hamiltonian. We demonstrate magnetic field retrieval from $0.2\,T$ to $0.4\,T$ with a precision of $\pm 0.0017 \,T$). Furthermore, the validated simulation establishes a foundation for generating synthetic training datasets, paving the way for autonomous, Machine Learning-enhanced magnetometry in applications ranging from MRI to fusion reactors.

20.
bioRxiv (Bioinfo) 2026-06-11

SPARK: A Systems-level Computational Framework for Reconstructing Transcriptomic State Organisation in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) exhibits substantial molecular heterogeneity, which complicates tumour stratification and limits the ability of mutation-centric models to capture tumour behaviour and predict patient outcomes. This study investigates whether coordinated transcriptomic programs can provide a systems-level representation of tumour states. Bulk RNA-sequencing data from the TCGA-LUAD cohort were analysed to reconstruct pathway-level transcriptomic organisation using a stability-optimised network framework (SPARK). This analysis identified eight transcriptomic modules representing coordinated biological processes active across tumours. Module activity scores were subsequently used to derive a composite Transcriptomic Risk Score through elastic-net Cox proportional hazards modelling. The resulting risk score showed a significant association with overall survival in the discovery cohort and improved prognostic discrimination beyond clinical variables. An independent evaluation in the CPTAC-LUAD cohort confirmed the prognostic signal and preserved risk stratification across patient groups. Unsupervised clustering of module activity further revealed three transcriptomic patient groups characterised by distinct biological programs, genomic alteration patterns, and survival outcomes. Single-cell analysis also demonstrated that the identified transcriptomic modules reflect coordinated organisation of the tumour-immune-stromal ecosystem across cellular compartments. Together, these findings suggest that LUAD heterogeneity can be organised into coordinated transcriptomic programs with measurable clinical relevance, providing a systems-level framework for representing tumour molecular states.

21.
medRxiv (Medicine) 2026-06-15

Longitudinal monitoring exposes correlated temporal protein variations in the female plasma proteome

The plasma proteome is a valuable resource for assessment of the physiological state of the donor. Containing hundreds of different proteins of variable concentrations, it displays substantial inter-donor differences in individual protein levels, making each plasma proteome highly donor-specific. Less is known about intra-donor variability in the plasma proteome over time, although such variations may even be more indicative of a changing physiological state. Here we assessed data obtained from the TIMES cohort, comprising 51 apparently healthy participants monitored monthly over 12 months, focusing especially on temporal variations in blood protein levels. Most strikingly, we observed that several women in this cohort revealed strongly correlated temporal variations in their plasma proteome, including most notably PZP, SHBG, FETUB, AGT, SERPINA6, SERPINA7, CP, APOL1 and KNG1, with levels sometimes fluctuating by more than 20-fold. In contrast, such variations were absent in men. Some of the fluctuating proteins have been known to be hormone-regulated (e.g., PZP, SHBG), but for others this was not yet fully clear. Through the tight co-variation observed for these proteins in the plasma proteome of women, we can conclude that all these proteins are similarly hormone regulated. The findings reported here not only corroborate previous studies showing estrogen-dependent regulation of several plasma proteins, but also extend this category to include also CP, APOL1, and KNG1. As these latter have been often proposed as candidate biomarkers, they should be validated in sex-balanced cohorts and interpreted with caution, especially in large-scale plasma proteomics studies wherein often only one or a few sampling time points are measured per donor.

22.
arXiv (CS.CL) 2026-06-19

Efficiently Representing Algorithms With Chain-of-Thought Transformers

The increasing popularity of reasoning models – language models that output a series of reasoning or thought tokens before producing an answer – is justified, in part, by theoretical results showing that chain-of-thought (CoT) transformers can simulate Turing machines, and thus perform arbitrary computation. However, the Turing machine, while suitable for complexity-theoretic analysis, is not convenient, intuitive, or efficient for discussing algorithms. Algorithms are typically designed and analyzed at a higher level of abstraction, captured by the Word RAM model with random-access memory and unit-cost operations on $\bigO(\log n)$-bit words. As a result, Word RAM algorithms can be substantially more efficient than their Turing machine counterparts, raising the question: Can CoT transformers efficiently simulate Word RAM algorithms? For instance, can they sort $n$ items in $\bigO(n \log n)$ steps or run Dijkstra's algorithm in $\bigO(E + V \log V)$ steps? We answer affirmatively, up to poly-logarithmic overhead. We first establish this for finite-precision transformers with poly-logarithmic width and rightmost unique hard attention, then strengthen the result to two more practical settings with finite width and log-precision: continuous CoT, where reasoning takes the form of vectors rather than tokens, and a hybrid architecture in which transformer layers sit atop a recurrent (linear RNN) layer. In all three cases, we find that CoT can efficiently simulate any Word RAM algorithm with only a poly-logarithmic overhead in $n$. This overhead reduces to log-square when the Word RAM has a ``flat'' instruction set, and only logarithmic for multiplication-free flat instructions – in stark contrast to known CoT simulations of Turing machines, which require quadratic overhead over Word RAM.

23.
medRxiv (Medicine) 2026-06-15

Anti-Platelet Factor 4 Antibody Clonal Heterogeneity and MGUS Status in HIT

Background Monoclonal gammopathy of thrombotic significance (MGTS) is a recently described chronic prothrombotic condition characterized by monoclonal anti-PF4 antibodies that are detected above the polyclonal antibody background in patient sera (i.e. present as monoclonal gammopathy of undetermined significance, MGUS). Due to conflicting data in the published literature on antibody clonality in heparin-induced thrombocytopenia (HIT), we evaluated clonality and abundance of anti-PF4 antibodies in HIT, including investigating whether an MGUS, if present in HIT, represents the causative anti-PF4 antibody. Methods Blood samples from 15 patients with HIT were subject to Platelet Factor 4-dependent antigen-based and functional tests. The unmanipulated serum antibody repertoire and isolated anti-PF4 antibodies were subjected to mass spectrometric evaluation. Results Two of the 15 HIT patients had an IgG MGUS. Notably, anti-PF4 antibodies were not synonymous with the MGUS antibody in either of the two patients. Eight of the 15 patients demonstrated monoclonal anti-PF4 antibodies, however, none of the anti-PF4 antibodies were detectable as an MGUS upon evaluation of the entire serum antibody repertoire, reflecting their low abundance. In the seven patients with multiple anti-PF4 antibodies, non-monoclonality was confirmed by analysis of deglycosylated antibody heavy chains. Conclusions Anti-PF4 HIT antibodies are monoclonal in approximately 50% of HIT patients, however, antibody abundance is low such that they are not detectable over the polyclonal IgG background (i.e. are MGUS-negative), differentiating HIT from MGTS. This observation helps explain the transient nature of HIT relative to the persistent prothrombotic state seen in MGTS.

24.
medRxiv (Medicine) 2026-06-15

Recruitment, Retention Approaches and Community Engagement in the THRIVE pilot Trial: Lessons Learned from a Food is Medicine Trial

Background: Recruitment of underrepresented populations, including Black and Hispanic populations, for Food is Medicine (FIM) and cardiovascular trials, may pose significant challenges. Methods: We implemented a multi-component recruitment approach for the THRIVE (AdapTive personalized dietitian coacHing and messaging with pRoduce prescrIptions to improVE healthy dietary behaviors) pilot trial to engage primarily Black and Hispanic adults in a Food is Medicine for hypertension intervention. The recruitment approaches included community engagement at approximately 40 community events (cultural festivals and neighborhood gatherings); partnerships with 8 community and faith-based service hubs and food distribution sites; recruitment through safety net primary care clinics, digital outreach via the study website, and social media campaigns; and direct recruitment at places of worship. We report lessons learned from the community engagement process, recruitment efficiency, representativeness, and retention outcomes. Results: Within 6 months, the enrollment target was exceeded by 40%, with an accrual index of 1.04. Over 1,000 individuals were reached through the direct-to-community engagement process, while faith-based partnerships engaged about 900 adults. There were 2,673 visits to the study webpage, and social media achieved 12,259 impressions with 399 clicks. About 95% of participants resided within 10 miles of the faith-based recruitment sites. Face-to-face engagement at the food distribution sites within faith-based organizations or community service hubs outperformed digital methods. Faith leader endorsements and follow-up in-person meetings (following unsuccessful email outreach) dramatically increased recruitment. Regarding retention, pre-randomization attrition was 6%, and 82% of participants completed the study. Conclusion: Culturally tailored, community-engaged recruitment grounded in faith-based and local community partnerships, was highly effective in engaging Black and Hispanic populations in this FIM cardiovascular trial. This provides a replicable model for implementing equitable and sustainable cardiovascular health interventions.

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

Second-Order Approximation of Limit Order Books in a Single-Scale Regime

arXiv:2308.00805v3 Announce Type: replace-cross Abstract: We establish a first- and second-order approximation for an infinite dimensional limit order book model in a single (critical) scaling regime where market and limit orders arrive at a common time scale. With our choice of scaling we obtain non-degenerate first- and second-order approximations for the price and volume dynamics. While the first-order approximation is given by a coupled ODE-PDE system, the second-order approximation is described in terms of an infinite-dimensional stochastic evolution equation driven by a cylindrical Brownian motion. The driving noise processes exhibit a non-trivial correlation in terms of the model parameters. We prove that the evolution equation has a unique solution and that the sequence of standardized limit order book models converges weakly to the solution of the evolution equation. The proof uses a non-standard martingale problem. We calibrate a linearized model to market data and explain how our model can be used for deriving confidence intervals of portfolio liquidation values.