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01.
arXiv (CS.CV) 2026-06-24

Predicting brain tumour enhancement from non-contrast MR imaging with artificial intelligence: a multi-cohort retrospective diagnostic accuracy study

Brain tumour MRI typically requires both pre- and post-contrast imaging, but gadolinium is not always desirable (frequent follow-up, renal impairment, allergy, paediatric patients). We developed and validated a deep learning model to predict tumour contrast enhancement from non-contrast MRI alone. We assembled 11,089 brain MRI studies (2006-2024) from 10 datasets across four countries and three continents, spanning adult and paediatric populations with glioma, meningioma, metastases, and post-resection appearances. Three architectures were trained to detect and segment enhancing tumour from T1w, T2w and FLAIR alone. Performance was assessed in a 1,109-study held-out test set (primary endpoint: patient-level enhancement detection; secondary: voxel-level Dice). Eleven expert radiologists attempted the same task on a 564-case subset (100 cases each), blinded to history, prior imaging, and referral. The best model, nnU-Net, achieved 83.0% balanced accuracy (95% CI 79.1-87.2; sensitivity 91.5%, specificity 74.4%) for detection, with R2 = 0.859 for enhancement volume. Of enhancing cases, 76.8% reached Dice >= 0.3, 67.5% >= 0.5, and 50.2% >= 0.7. Under blinded conditions, radiologists' majority vote was lower (71.7% balanced accuracy; sensitivity 77.6%, specificity 65.8%). The proportion reaching Dice >= 0.3 varied by pathology (meningioma 93%, presurgical glioma 76%, metastases 74%, postoperative glioma 74%) and was lowest for paediatric cases (45%). Deep learning can identify contrast-enhancing brain tumours from non-contrast MRI. These models show promise as a triage or decision-support adjunct, such as in flagging studies likely to enhance so that contrast can be added to a non-contrast protocol, and may reduce gadolinium dependence in neuro-oncology imaging. Future work should optimise these models with radiologists.

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

Neuro-Symbolic Agents for Regulated Process Automation: Challenges and Research Agenda

arXiv:2606.13405v1 Announce Type: new Abstract: LLM-based agents are entering regulated industries where they automate judgment intensive quality management processes. We argue that symbolic structures already embedded in these domains, including regulations, typed process models, and compliance constraints, should be treated not merely as external monitoring mechanisms but as core architectural components that shape the agent's decision-making and behavior. We propose compliance-by-construction as a complementary paradigm to guardrail-based monitoring: a structural foundation that prevents control-flow violations, while guardrails remain essential for catching semantic errors. We identify a structured set of neuro-symbolic research challenges on foundational and capability level and show that addressing them jointly enables compliance-by-construction. We call on the neuro-symbolic community to engage with regulated process automation as a high impact research domain.

03.
arXiv (CS.CV) 2026-06-25

Evaluation Protocols and Validation for Cameras in Indoor Healthcare Monitoring

Camera-based monitoring systems are increasingly adopted in healthcare settings for the continuous assessment of patient movement and activities. However, their technical performance under real-world indoor conditions remains insufficiently characterised, preventing appropriate camera selection for clinical or home adoption and reproducibility. Existing validation studies typically assess either device metrological performance or algorithm accuracy in isolation, and often do not systematically account for practical deployment factors, such as lighting variability, occlusions, and camera positioning. We present two technical validation protocols: the first evaluates the metrological performance of RGB and RGB-D cameras, and the second assesses their use in supporting human pose estimation, validated using state-of-the-art pose estimators. The proposed protocols systematically assess five cameras, four RGB-D and one RGB, under controlled variations in lighting, camera height, viewing angle, and occlusion level within representative indoor scenarios. The experimental results show that metrological performance varies substantially across cameras, with depth bias at 5 m ranging from 50 mm to over 1400 mm depending on the device. For 2D pose estimation, all cameras achieve broadly comparable accuracy, with mean mAP between approximately 78% and 90% across cameras and estimators, whereas 3D reconstruction error differs markedly across devices, with MPJPE ranging from 104 mm to 365 mm, closely reflecting underlying depth-sensing quality. Environmental factors have a camera- and estimator-dependent effect on 3D performance, while camera mounting height has minimal influence within the evaluated range. This work provides evidence-based guidance for the selection and deployment of cameras in healthcare monitoring applications, addressing an important gap in current technical validation practice.

04.
arXiv (CS.CL) 2026-06-11

Mapping Scientific Literature with Large Language Models and Topic Modeling

Scientific literature is increasingly fragmented by disciplinary boundaries, specialized terminology, and potentially sparse keyword systems, making it difficult to capture the evolving structure of modern science. This study introduces a large language model (LLM)-driven framework for mapping scientific literature from a topic modeling perspective. The approach is demonstrated on a 20-year corpus of more than 1,500 engineering-related articles published in the Proceedings of the National Academy of Sciences (PNAS). A two-stage classification pipeline first assigns a primary thematic category to each article based on its abstract, followed by full-text analysis to identify secondary classifications that reveal latent cross-topic connections within the corpus. Unlike conventional topic models, the LLM-based framework produces semantically interpretable topics while maintaining strong quantitative performance. Comparative evaluation against established topic modeling methods shows higher topic diversity and lower overlap with competitive coherence metrics. Manual validation on a randomly sampled subset of abstracts yields an accuracy of 75.9%. Additional traditional natural language processing analyses confirm that the generated topics correspond to meaningful linguistic patterns in the corpus. A bipartite network linking primary and secondary classifications further reveals implicit thematic relationships that are not readily observable through abstracts or keyword systems alone. The findings indicate that the framework independently recovers much of the journal's editorial dual-classification structure without prior knowledge of its schema. Overall, the proposed approach offers a powerful tool for mapping science and identifying emerging cross-topic connections in research.

05.
arXiv (CS.CV) 2026-06-25

Benchmarking Vision-Language Models for Microscopic Plant Image Understanding

Microscopic imaging provides essential visual evidence for studying plant biology and pathology at the cellular and subcellular levels. However, existing benchmarks on vision-language models primarily focus on macroscopic plant imagery, while the microscopic domain remains underexplored. To address this gap, we present PlantMicro, a comprehensive benchmark for evaluating vision-language models (VLMs) in microscopic plant imagery. PlantMicro integrates more than 5,000 images collected across diverse hosts, biological domains, and imaging modalities. Building on this diversity, we design a set of complementary tasks that capture different facets of microscopic image understanding. To support these tasks, we construct over 9,000 VQA pairs that systematically evaluate the capabilities of VLMs. Experiments on PlantMicro show that current VLMs struggle with fine-grained recognition and biologically grounded reasoning. For example, GPT-5 achieves 34.93% accuracy on the pathogen classification task, which is only modestly above the random-guessing baseline. The results highlight a significant gap in current VLMs' ability to comprehend plant microscopic images. PlantMicro provides a standardized foundation for advancing VLMs toward reliable and comprehensive microscopy-level plant understanding.

06.
bioRxiv (Bioinfo) 2026-06-10

When batch correction corrupts gene expression: uncovering distortions in correlation structures

Batch correction is essential for integrating datasets and enabling population-level insights into health and disease. Embedding-based approaches are among the most widely used solutions, but here we highlight a critical, overlooked limitation: these methods can distort feature-to-feature (e.g., gene gene) relationships, potentially undermining downstream analyses. We investigate this issue and introduce a novel metric to quantify it.

07.
arXiv (quant-ph) 2026-06-11

Testing Catability and Coherent Superposition of $2\mathcal{D}$ Graphene Quantum system

arXiv:2605.10967v2 Announce Type: replace Abstract: We develop a theoretical framework for describing superposed coherent states in graphene quantum systems using the concept of catability as a phase-sensitive metric functional measure. In this case, the formalism quantifies interference stability and coherence structure via phase-dependent contributions of quantum superposition states. Catability is defined as a functional measure sensitive to relative phase variations within coherent state combinations, serving as a diagnostic tool for quantum interference effects in graphene-based systems. Also, the formulation is extended using Lie algebra techniques, where the underlying symmetry structure of graphene quantum states is represented through operator algebras governing state transformations in quantum space. In this context, to describe nonlocal propagation and phase-resolved dynamics, a Green function approach is incorporated, enabling systematic treatment of quantum correlations in a spatially extended structures framework. A unified framework is constructed by combining Lie algebraic symmetry analysis with Green function propagation theory, yielding a consistent description of phase-sensitive catability in complex graphene quantum configurations within the framework approach. Results provide a structured route for testing coherence, interference stability, and quantum state control in low-dimensional quantum materials systems.

08.
PLOS Computational Biology 2026-06-22

<i>HoloBio</i>: A holographic microscopy tool for quantitative biological analysis

Authors:

by Waira Mona, Maria J. Gil-Herrera, Emanuel Mazo, Daniel Córdoba, Sofia Obando-Vasquez, Maria J. Lopera, Rene Restrepo, Carlos Trujillo, Ana Doblas, Raul Castaneda Holographic imaging in microscopy enables label-free quantitative information of biological specimens and has found applications across a wide range of biomedical studies, from cell morphology to particle dynamics; yet its widespread adoption is often limited by the lack of accessible and standardized analysis software. We present HoloBio, an open-source, Python-based graphical user interface developed to address this issue. This software offers two primary operational modes: a Real-Time mode that enables live processing of holograms at video frame rates, and an Offline mode designed for post-processing previously recorded holograms. HoloBio is compatible with holograms recorded using both lens-based and lensless systems, supporting off-axis architectures in telecentric and non-telecentric configurations, as well as slightly off-axis and in-line optical setups. The software incorporates tools for cell tracking, phase profiling, thickness estimation, and morphological analysis, including cell counting and object area quantification. HoloBio is designed to be accessible for users without coding expertise, offering a reproducible, high-throughput environment tailored for researchers in biology, biophotonics, and biomedical imaging.

09.
arXiv (CS.CV) 2026-06-16

Federated Medical Image Segmentation under Real-World Label Noise: A Benchmark Suite for Noisy Label Learning Method Selection

While federated learning (FL) enables collaborative medical image segmentation without centralizing sensitive data, real-world deployment is frequently complicated by cross-site label imperfections such as contour disagreement, missing or additional structures, and confused labels. Federated noisy label learning (FNLL) aims to mitigate these effects, yet remains underused in practice as existing evidence is largely based on synthetic noise, simplified settings, and limited real-world noisy evaluation. We address this gap by introducing a benchmark suite that combines diverse real-world noisy datasets, deployment-relevant client-noise scenarios, and label-noise-targeted evaluation to support systematic FNLL assessment and informed method selection. The suite combines curated real-world noisy medical image segmentation datasets from diverse sources with a comprehensive federated segmentation framework including various client-noise scenarios and noise-targeted evaluation. The presented suite provides a realistic and discriminative basis for FNLL evaluation in medical image segmentation and establishes a reusable foundation for fair benchmarking, dataset-specific label-noise characterization, and future method development under realistic federated settings. Code is available at https://github.com/MIC-DKFZ/FedSegNoiseBench.

10.
arXiv (CS.CV) 2026-06-25

Did Models Learn Sufficiently? Attribution-Guided Training via Subset-Selected Counterfactual Augmentation

In current visual model training, models often rely on only limited sufficient causes for their predictions, which makes them sensitive to distribution shifts or the absence of key features. Attribution methods can accurately identify a model's critical regions. However, masking these areas to create counterfactuals often causes the model to misclassify the target, while humans can still easily recognize it. This divergence highlights that the model's learned dependencies may not be sufficiently causal. To address this issue, we propose Subset-Selected Counterfactual Augmentation (SS-CA), which integrates counterfactual explanations directly into the training process for targeted intervention. Building on the subset-selection-based LIMA attribution method, we develop Counterfactual LIMA to identify minimal spatial region sets whose removal can selectively alter model predictions. Leveraging these attributions, we introduce a data augmentation strategy that replaces the identified regions with natural background, and we train the model jointly on both augmented and original samples to mitigate incomplete causal learning. Extensive experiments across multiple ImageNet variants show that SS-CA improves generalization on in-distribution (ID) test data and achieves superior performance on out-of-distribution (OOD) benchmarks such as ImageNet-R and ImageNet-S. Under perturbations including noise, models trained with SS-CA also exhibit enhanced generalization, demonstrating that our approach effectively uses interpretability insights to correct model deficiencies and improve both performance and robustness.

11.
Nature (Science) 2026-06-17

Lethal plague outbreaks in Lake Baikal hunter-gatherers 5,500 years ago

Plague is among the most devastating diseases in human history1. However, early strains of the plague-causing bacterium Yersinia pestis lacked virulence factors that are required for the bubonic form until around 3,800 years ago2,3. Consequently, the morbidity and mortality of early plague strains remain unclear. Here we describe early plague strains that are associated with two phases of outbreaks among mid-Holocene hunter-gatherers near Lake Baikal in southeast Siberia, beginning from about 5,500 years ago. These outbreaks occur across four hunter-gatherer cemeteries, with a 39% detection rate for plague infection. By reconstructing kinship pedigrees, we show that small familial groups were affected, consistent with human-to-human spread of disease, and that the first outbreak occurred within a single generation. The infections appear to have resulted in acute mortality, especially among children (aged 8 to 11 years). We further note functional differences, including in the ypm superantigen locus, which is also present in present day Yersinia pseudotuberculosis. The new strains diverge ancestrally to known Y. pestis and constrain the timing of its emergence, indicating that this happened before approximately 5,700 years ago. These findings show that plague outbreaks happened earlier than previously thought and were indeed lethal. We contend that the occurrence of outbreaks among mid-Holocene hunter-gatherer communities well outside the sphere of Late Neolithic Europe challenges the notion that higher population densities and lifestyle changes during the Neolithic agricultural transition were prerequisites for plague epidemics. Analyses of ancient DNA from hunter-gatherers near Lake Baikal in southeast Siberia around 5,500 years ago indicate that highly virulent Yersinia pestis emerged earlier than previously estimated, far&nbsp;from the next known&nbsp;cases of infection&nbsp;in Late Neolithic Europe.

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

HierSVA: A Data Synthesis Pipeline, Dataset, and Benchmark for LLM-Driven Hierarchical Hardware Formal Verification

arXiv:2606.13706v1 Announce Type: cross Abstract: We present HierSVA, an integrated suite that combines a pipeline, dataset, and benchmark for LLM-driven hierarchical hardware formal verification. HierSVA-SP pairs an RTL preprocessing toolchain with an LLM-in-the-loop formal verification flow to produce reference SystemVerilog Assertions (SVA) on hierarchical RTL. Applying it to BaseJump STL yields HierSVA-DS, a dataset of 342 modules, with hierarchy metadata and depths 0–9, accompanied by a deep subset of 28 module-bug pairs with natural-language specifications and bug variants. HierSVA-B decomposes assertion quality into six metric axes: syntax correctness, assertion proof success rate, vacuity, specification faithfulness, mutation coverage, and formal core coverage. Applying HierSVA-B to twelve recent LLMs reveals three findings. First, the module-level compile rate is 67.1\%; among generated assertions in evaluable runs, 82.1\% prove non-vacuously, but the corresponding assertion sets detect only 70.2\% of eligible injected faults and cover 36.2\% of the formal core. Second, on 211 evaluable model–module entries in the deep subset, assertion sets flag buggy RTL with 0.87 recall, but 40\% of predicted-buggy outcomes are false positives on correct RTL, limiting precision to 0.60. Third, agentic mode improves S1-style provability and strength metrics, but gains plateau and oscillate. Codes and artifacts are available at \href{https://github.com/HierSVAAnon/HierSVACodeAndArtifacts}{https://github.com/HierSVAAnon/HierSVACodeAndArtifacts}. Dataset is available at \href{https://huggingface.co/datasets/AnonymousHierSVA/HierSVA}{https://huggingface.co/datasets/AnonymousHierSVA/HierSVA}.

13.
arXiv (CS.AI) 2026-06-16

Mitigating scalability challenges in LUT-based neural networks via pruning optimisations

arXiv:2407.02362v3 Announce Type: replace-cross Abstract: Modern deep neural networks heavily rely on a large number of multiply-accumulate operations, which constitute the predominant computational cost. To address this, Look-Up Table (LUT)-based matrix multiplications have emerged as a promising alternative for reducing the computational cost and time of the multiply-accumulate operations in a neural network. However, the LUT-based neural network still faces the scalability challenge due to the inherent limitations of LUT-based matrix multiplication. To mitigate these scalability limitations, this paper proposes a scalable and energy-efficient LUT-based approximate matrix multiplication unit (LUT-MU) constituting the basic component of the neural networks by integrating a pruning strategy on the MADDNESS algorithm, a LUT-based matrix multiplication methodology. With increasing problem size and precision demands in matrix multiplication, our proposed LUT-MU architecture effectively constrains resource expansion. The case study shows that deploying our LUT-MU in neural network architectures, including fully connected layers (MNIST) and ResNets (CIFAR-10, ImageNet)-on XCZU7EV and XCZU19EG FPGAs, produces up to $1.6 \times$ throughput improvement and $4.2 \times$ energy efficiency gains over mainstream CUDA-based network implementations, and $1.8\times$ energy efficiency compared to leading quantised neural network implementations, with moderate impact on accuracy. Compared to original MADDNESS-based neural networks, our LUT-MU shows $1.3$ to $2.6\times$ resource savings based on various resolution configuration settings of MADDNESS.

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

The Holistic Storage of Verb+Up Phrases in Text-based and Audio-based Language Models

A crucial aspect of linguistic capability is the ability to trade off between stored representations and abstract knowledge: one must retrieve learned representations, but also generate novel ones by applying productive rules. While recent work has examined abstract knowledge in language models, holistic storage of multi-word units has received far less attention. We probe internal representations in text-based LLMs and an ASR model, testing whether V+up phrasal verbs develop distinct representations as a function of frequency and predictability. All models show evidence of holistic storage driven by frequency and predictability, further supporting usage-based theories of language.

15.
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.

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

Attention mechanisms and transfer learning for robust peach leaf damage classification under domain shift

Artificial intelligence provides a practical framework for crop damage assessment from imagery data, supporting early decision-making in agricultural management. In peach orchards, climate change increases abiotic stress and biotic pressures, including pests and diseases, which often produce visually similar foliar symptoms. This overlap makes manual diagnosis difficult, especially across multiple fields with varying environmental conditions, highlighting the need for automated models with strong generalization ability. We propose an image-based classification approach for peach leaf damage detection. A benchmark dataset was created through manual annotation of publicly available images, consisting of 1,366 peach leaves across six damage categories. Several deep learning architectures were evaluated. EfficientNet models achieved the best results, with EfficientNetB0 reaching 92.9 percent accuracy, EfficientNetB3 achieving 91.5 percent, and EfficientNetB5 showing the strongest performance on minority classes. DenseNet121 reached 92.6 percent accuracy. The integration of the Convolutional Block Attention Module (CBAM) improved performance in several backbones, particularly EfficientNetB5 and InceptionV3, while showing limited or negative impact in others. The CBAM-enhanced EfficientNetB5 achieved the best overall accuracy of 93.3 percent. To evaluate robustness under realistic conditions, a local dataset of 180 images across four classes was collected, and transfer learning strategies were applied to address domain shift. Three fine-tuning strategies were tested. EfficientNetB3 combined with CBAM achieved the best performance in the local domain, reaching a 93 percent macro F1-score after transfer. Overall, attention-based models showed improved robustness for minority classes and better generalization across different field conditions.

17.
bioRxiv (Bioinfo) 2026-06-15

Multi-platform reassessment of human mitochondrial DNA methylation reveals signals consistent with technical artifacts

The existence and functional relevance of mitochondrial DNA methylation remain controversial. Here, we systematically profiled cytosine methylation and hydroxymethylation across human brain and blood tissues spanning healthy and malignant states using orthogonal sequencing approaches that avoid chemical conversion during library preparation. While nuclear DNA exhibited canonical methylation patterns, mitochondrial DNA consistently showed negligible signal, indistinguishable from background technical noise. By mapping cytosine-guanine sites between mitochondrial DNA and nuclear-embedded mitochondrial sequences, we demonstrate the potential of these nuclear counterparts to confound not only cytosine methylation but also hydroxymethylation measurements, corroborating and extending prior findings implicating nuclear contamination as a potential source of apparent mitochondrial epigenetic signals. Additional technical factors that inflate apparent mtDNA methylation signals were identified, including sequence context biases, flow cell chemistries, and coverage-dependent discrepancies between the heavy and light strands. Collectively, these results provide convergent evidence against the presence of biologically meaningful cytosine methylation or hydroxymethylation in mitochondrial DNA. These findings caution against interpreting apparent mtDNA methylation signals in human adult tissues as meaningful without rigorous orthogonal validation and comprehensive consideration of technical and analytical confounding factors.

18.
arXiv (quant-ph) 2026-06-24

Spectrally engineered collinear type-0 SPDC source with enhanced spectral brightness for entanglement distribution

arXiv:2606.24036v1 Announce Type: new Abstract: Entangled photon sources with high spectral brightness are important resources for photonic quantum information processing, particularly in quantum communication and quantum networking where usable photon flux of entangled photons is often constrained by channel loss and source inefficiency. Here, we demonstrate a spectrally engineered type-0 spontaneous parametric down-conversion (SPDC) source with enhanced spectral brightness for entanglement distribution. By pumping a 30-mm ppKTP crystal with an ultra-narrowband laser slightly detuned from degeneracy, photon-pair generation is concentrated into a narrow spectral bandwidth while retaining the strong nonlinear interaction of type-0 phase matching. The source produces a coincidence rate of 44.6 kHz corresponding to a detected spectral brightness of 0.507 MHz/mW/nm. We further integrate the source into a Sagnac interferometer to generate polarization-entangled photon pairs and demonstrate entanglement distribution through a 2.56 km free-space round-trip channel. Our results show that spectral engineering provides a practical route to compact, spectrally bright entangled-photon sources for quantum communication applications.

19.
arXiv (CS.AI) 2026-06-12

Fusion Learning from Dynamic Functional Connectivity: Combining the Amplitude and Phase of fMRI Signals to Identify Brain Disorders

arXiv:2603.24603v2 Announce Type: replace-cross Abstract: Dynamic functional connectivity (dFC) derived from resting-state functional magnetic resonance imaging (fMRI) has been extensively utilized in brain science research. The sliding window correlation (SWC) method is a widely used approach for constructing dFC by computing correlation coefficients between amplitude time series of signals from pairs of brain regions. In this study, we propose an integrated approach that incorporates both amplitude and phase information of fMRI signals to improve the detection of brain disorders. Specifically, we introduce a multi-scale fusion learning framework, namely MSFL, which leverages two complementary dFC features derived from SWC and phase synchronization (PS). Here, SWC captures amplitude correlations, while PS measures phase coherence within dFC. We evaluated the efficacy of MSFL in classifying autism spectrum disorder and major depressive disorder using two publicly available datasets: ABIDE I and REST-meta-MDD, respectively. The results indicate that MSFL significantly outperforms existing comparative models. Moreover, we performed model explanation analysis using the SHAP framework, which showed that both types of dFC features from SWC and PS contribute to detecting brain disorders.

20.
medRxiv (Medicine) 2026-06-15

Two Blood-based Endotypes Reveal Divergent Clinical Outcomes of Fibrotic Hypersensitivity Pneumonitis

Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an antigen-driven, life-threatening interstitial lung disease characterized by heterogeneous radiologic features, clinical outcomes, and treatment responses. Objectives: To identify blood-based fHP endotypes that inform mechanism, prognosis and therapeutic response. Methods: We performed integrative analyses of multi-compartment transcriptomic data derived from whole blood, peripheral blood mononuclear cells, bronchoalveolar lavage, and surgical lung biopsies, alongside circulating plasma proteomics. Multiple clustering algorithms were cross-compared to ensure robustness and reproducibility of endotypes identification. Immune cell composition was inferred using bulk RNA-seq deconvolution and annotated with BAL single-cell RNA-seq. Pathway activities were characterized using Gene Set Enrichment Analysis. Transplant-free survival (TFS) was evaluated for endotype and corticosteroid exposure by Kaplan-Meier methods, with hazard ratios analyzed using multivariable Cox proportional hazards models. Results: Two molecular endotypes, lymphocytic-associated (L-fHP) and non-lymphocytic-associated (N-fHP), were identified and validated. L-fHP showed enrichment of adaptive immune signaling and lymphocyte predominance, whereas N-fHP demonstrated myeloid-cell activation with neutrophil and macrophage predominance. Corticosteroid exposure was associated with worse TFS in L-fHP but not in N-fHP after adjusting for age, sex, and baseline pulmonary function. Compared to L-fHP, N-fHP had poorer baseline pulmonary function, faster 12-month FVC decline, and shorter TFS. N-fHP also exhibited elevated neutrophil-associated markers, including matrix metalloproteinase-9, across paired transcriptomic and proteomic datasets, supporting a neutrophil-driven, cross-compartment disease process. Conclusion: Multi-omic, multi-compartment analysis identifies two reproducible fHP endotypes with distinct clinical outcomes and corticosteroid responses, supporting a precision medicine approach beyond current clinical and radiologic classification.

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

Greed Is Learned: Visible Incentives as Reward-Hacking Triggers

arXiv:2606.16914v1 Announce Type: new Abstract: Deployed agents increasingly act with their reward proxy in view, such as a balance, score, or KPI dashboard. We show that reinforcement learning can make a policy addicted to such a visible self-benefit channel. It chases the displayed payoff across held-out domains, sacrifices the true task to do so, and follows the channel wherever we rewrite it, while policies that never saw the channel stay honest. We call this reward-channel addiction and study it in MoneyWorld, a synthetic sandbox. The addiction can flip a model's safety alignment: trained only on innocuous money tasks with no safety content, the model abandons the safe action it otherwise always takes whenever a dashboard pays for an unsafe one, and reverts to safe once the channel is hidden. This learned bribe replicates across model scales and families. Blindly optimizing super-capable, next-generation AI on KPIs or P\&L can be dangerous for alignment. Greed is learned when following such a channel pays.

23.
arXiv (CS.LG) 2026-06-17

Learning from Biased and Costly Data Sources: Minimax-optimal Data Collection under a Budget

arXiv:2602.17894v2 Announce Type: replace-cross Abstract: Data collection is a critical component of modern statistical and machine learning pipelines, particularly when data must be gathered from multiple heterogeneous sources to study a target population of interest. In many use cases, such as medical studies or political polling, different sources incur different sampling costs. Observations often have associated group identities - for example, health markers, demographics, or political affiliations - and the relative composition of these groups may differ substantially, both among the source populations and between sources and target population. In this work, we study multi-source data collection under a fixed budget, focusing on the estimation of population means and group-conditional means. We show that naive data collection strategies (e.g. attempting to "match" the target distribution) or relying on standard estimators (e.g. sample mean) can be highly suboptimal. Instead, we develop a sampling plan which maximizes the effective sample size - the total sample size divided by $D_{\chi^2}(q\mid\mid\overline{p}) + 1$, where $q$ is the target distribution, $\overline{p}$ is the aggregated source distribution, and $D_{\chi^2}$ is the $\chi^2$-divergence. We pair this sampling plan with a classical post-stratification estimator and upper bound its risk. We provide matching lower bounds, establishing that our approach achieves the budgeted minimax optimal risk. Our techniques also extend to prediction problems when minimizing the excess risk, providing a principled approach to multi-source learning with costly and heterogeneous data sources.

24.
medRxiv (Medicine) 2026-06-22

AI-driven Multimodal Representation Learning for Latent Mediation Structure Discovery of Socioeconomic Disadvantage, Psychosocial Factors, and Cardiometabolic Multimorbidity

Authors:

Social disadvantage is associated with multimorbidity, but the pathways linking social conditions to disease burden remain poorly understood. We developed an AI-driven multimodal mediation framework that integrates socioeconomic, psychosocial, clinical, laboratory, behavioral, and genomic data from the All of Us Research Program. Modality-specific variational autoencoders were used to derive latent representations of each data domain, and mediation analyses were subsequently performed in latent space to evaluate indirect associations between socioeconomic disadvantage, psychosocial factors, and multimorbidity. The final analytic cohort included 20,804 participants with complete multimodal data. Across 800 exposure–mediator–outcome combinations, mediation signals were concentrated within a small number of latent dimensions. The strongest indirect association linked a socioeconomic disadvantage dimension, a psychosocial vulnerability dimension, and a cardiometabolic multimorbidity dimension (NIE = 0.002517). The psychosocial dimension was characterized by poorer mental health, greater loneliness, lower social well-being, and lower health literacy, whereas the outcome dimension was associated with hypertension, diabetes, hyperlipidemia, obesity, chronic kidney disease, and heart disease. Bootstrap analyses supported the stability of the leading pathway. These findings suggest that psychosocial vulnerability may contribute to the association between socioeconomic disadvantage and cardiometabolic multimorbidity. More broadly, the proposed framework illustrates how AI-based representation learning can be used to investigate complex relationships across high-dimensional multimodal health data.

25.
medRxiv (Medicine) 2026-06-18

Diabetes is associated with increased nocturnal respiratory rate

Background and Objective: Diabetes mellitus (DM) causes autonomic neuropathy, which may alter nocturnal respiratory rate (NRR). To test the association between DM and NRR, we analyzed elective polysomnograms of four large observational cohorts. Research Design and Methods: We performed cross-sectional analysis of over 25,000 individuals with polysomnograms (PSGs) from the Sleep Heart Health Study (SHHS), Hispanic Community Health Study/Study of Latinos (HCHS/SOL), Osteoporotic Fractures in Men Study (MrOS), and Wisconsin Sleep Cohort (WSC). Patient-level NRRs were derived from inductance plethysmography waveforms. DM status was determined by self-report, physician diagnosis, medication use, or laboratory values, depending on the cohort. We related DM and NRR (continuous and dichotomized) using logistic regression models and adjusted for potential confounders. Cohort-specific results were combined using random-effects meta-analysis. Results: Meta-analysis of unadjusted models showed a pooled odds ratio (OR) of 1.10 (95% CI:1.04-1.17) for each breath-per-minute (brpm) increase in NRR. This association remained significant after multivariable adjustment (OR:1.06, 95% CI:1.02-1.11). Dichotomized analyses similarly showed higher odds of DM across dichotomization thresholds ranging from 15 to 21 brpm. At a threshold of 18 brpm, the unadjusted pooled OR was 1.77 (95% CI:1.23-2.55, P=0.0022), and the adjusted OR was 1.49 (95% CI:1.10-2.02, P=0.0098). Conclusions: Clinically stable outpatients with elevated NRR have an increased prevalence of DM. Additional studies are needed to investigate whether the mechanism is autonomic neuropathy and whether monitoring NRR can detect early complications of DM.