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01.
arXiv (quant-ph) 2026-06-25

Modeling and Analysis of Phase Instability in Photonic Processor

arXiv:2606.25196v1 Announce Type: cross Abstract: Achieving both reconfigurability and stable output signals is a critical challenge in the development of integrated photonic circuits for large-scale optical quantum information processing. This has led to the creation of multimode photonic processors, also known as reconfigurable multimode interferometers, which have wide-ranging applications in quantum and classical information processing. However, maintaining phase stability in multi-port input signals remains a significant hurdle, particularly due to the phase instabilities introduced by active cooling systems and temperature drifts in the photonic processor. In this study, we propose theoretical models to simulate phase instability in photonic processors and validate them against experimental results. Two distinct modeling approaches were employed: a Brownian random walk and phase reconstruction based on experimentally observed oscillating harmonics. Additionally, we verified and applied our model to a specific application for input phase correction using self-feedback control within the photonic processor.

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

RACL: Reasoning-Agent Control Layers for Continuous Metaheuristic Learning

arXiv:2606.20142v1 Announce Type: new Abstract: This paper introduces RACL, a Reasoning-Agent Control Layer for metaheuristics. RACL places a reasoning agent above an existing optimizer. The agent does not replace the optimizer and does not modify business constraints. Instead, it controls the optimizer's internal search behavior by observing operational memory, reasoning over past behavior, formulating bounded hypotheses, testing interventions, evaluating outcomes, applying guardrails, consolidating useful policies and explaining its decisions. The experiment uses vehicle routing as a testbed, but the contribution is not a new routing solver, a particular ALNS configuration or a specific set of routing rules. The contribution is the RACL method: a way for a reasoning agent to discover, validate, consolidate and explain algorithmic control rules for a metaheuristic. In the current experimental setting, RACL improves or ties the Operational Memory Policy in 21 of 21 feasible cases and improves or ties a non-reasoning Stagnation-Triggered Policy in 18 of 21 feasible cases, with an average RACL vs STP cost delta of -0.641%. In the Sevilla-9/10 runtime sample, RACL improves average cost by -8.337% versus Fixed and -1.605% versus STP without showing material computational overhead. During the proof-of-concept, Codex was used as an in-the-loop reasoning agent observing executions, interpreting logs and proposing live bounded interventions. The policy proxy was later used only to make quantitative evaluation reproducible.

03.
medRxiv (Medicine) 2026-06-23

Novel loci and multi-omics risk models for rheumatoid arthritis through a million-participant genome-wide association meta-analysis

Rheumatoid arthritis (RA) remains incompletely understood, limiting targeted prevention. In this work, genome-wide association study meta-analyses were performed for RA and seropositive RA, comprising approximately one million participants of European ancestry. Eight and six novel genomic risk loci were defined for RA and seropositive RA, and candidate causal genes were identified, highlighting relevant biological pathways, including established immune pathways and estrogen metabolism. Novel disease-specific polygenic risk scores (PRSs) were constructed, enhancing predictive performance over clinical risk factors (incremental C-statistics of 2.7 and 5.1 for RA and seropositive RA, respectively). In parallel, integrating metabolomic data into high-dimensional models enhanced risk stratification over models based on clinical risk factors and genomics, particularly for seropositive RA, where the hazard ratio of the highest decile increased from 4.869 to 5.697. These findings expand the understanding of genetic factors underlying RA and support the value of including PRSs in risk assessment, while suggesting metabolomic integration may further enhance risk stratification, particularly for seropositive RA.

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

Periodic-MAE: Periodic Video Masked Autoencoder for rPPG Estimation

In this paper, we propose Periodic-MAE, a self-supervised framework for learning generalizable spatio-temporal representations of periodic physiological signals from unlabeled facial videos. The proposed method leverages a masked autoencoder (MAE), which learns high-dimensional facial representations by reconstructing masked video tokens without relying on remote photoplethysmography (rPPG) specific supervision. To explicitly align representation learning with the characteristics of rPPG, we introduce a periodicity-aware frame masking strategy based on video resampling, enabling the encoder to learn representations that capture quasi-periodic temporal patterns relevant to pulse signal estimation. In addition, physiological bandlimit constraints are integrated into the MAE pre-training framework, exploiting the sparsity of pulse signals in the frequency domain to guide the learned representations toward physiologically meaningful patterns. After pre-training, the learned representations are transferred to downstream rPPG estimation, where the encoder serves as a generic feature extractor for recovering pulse-related signals from facial videos. We conduct extensive experiments on four benchmark datasets, including PURE, UBFC-rPPG, MMPD, and V4V. Moreover, we evaluate the proposed approach on a real-world rPPG dataset collected under unconstrained lighting conditions and subject motion. Experimental results demonstrate that Periodic-MAE consistently improves rPPG estimation performance, particularly in challenging cross-dataset and real-world evaluation settings. Our code is available at https://github.com/ziiho08/Periodic-MAE.

05.
medRxiv (Medicine) 2026-06-15

Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation

Importance: Individuals with psychiatric disorders face elevated cardiometabolic risk which is linked to increased mortality. The extent to which this reflects shared pathogenesis or the downstream effects of illness and treatment remains poorly understood. Objective: To characterize the direct pleiotropic effects of psychiatric genetic liability on circulating metabolites and aggregate cardiometabolic risk, independent of psychiatric diagnosis and psychotropic medication use. Design: Cohort study. Setting: Mass General Brigham Biobank (MGBB). Participants: MGBB participants with metabolomic profiling, genomic data, and linked electronic health records. Exposures: Genetic liability to nine psychiatric disorders quantified using polygenic risk scores (PRS): attention deficit/hyperactivity disorder (ADHD), anorexia nervosa (ANO), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), PTSD, schizophrenia (SCZ), and substance use disorder (SUD). Main Outcomes and Measures: 249 circulating metabolites and four metabolomic risk scores (MRS) for type 2 diabetes, myocardial infarction, ischemic stroke, and vascular dementia. PRS-metabolite associations were estimated using nested models adjusting for lifetime psychiatric diagnosis and psychotropic medication use. Results: Across 25,290 participants, we identified 604 significant PRS-metabolite associations (Bonferroni p< 1.36 x 10-4), of which 89% persisted after adjustment for lifetime diagnosis and medication use, suggesting that the direct genetic effects on metabolism are largely independent of illness or treatment. PRS for MDD, PTSD, and ADHD showed the most extensive dysregulation, with a transdiagnostic pattern of elevated lipids and systemic inflammation, specifically triglycerides ({beta} = 0.04 to 0.05, all p< 4.4 x10-13) and glycoprotein acetyls ({beta} = 0.05, all p< 2.2 x10-16). Notably, PRS for SCZ and BD showed minimal metabolite dysregulation despite having the strongest association with their target diagnoses. PRS for MDD, PTSD, ADHD, and SUD were associated with increased MRS across cardiometabolic conditions ({beta} = 0.03 to 0.08, all p< 2.1 x10-4). Sensitivity analyses controlling for BMI or excluding participants without any psychiatric history (N: 21,305 and 11,150, respectively) showed a similar pattern. Conclusions and Relevance: Psychiatric genetic liability is associated with systemic metabolic dysregulation independent of illness onset or treatment, supporting a partially pleiotropic basis for psychiatric-cardiometabolic comorbidity.

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

EMS: Multi-Agent Voting via Efficient Majority-then-Stopping

arXiv:2604.02863v2 Announce Type: replace Abstract: Majority voting is the standard for aggregating multi-agent responses into a final decision. However, traditional methods typically require all agents to complete their reasoning before aggregation begins, leading to significant computational overhead, as many responses become redundant once a majority consensus is achieved. In this work, we formulate efficient multi-agent voting as a reliability-aware agent scheduling problem and propose Efficient Majority-then-Stopping (EMS) to improve reasoning efficiency. EMS first estimates a Task-Conditioned Reliability Ordering (TCRO) for each agent by retrieving its historical consensus evidence on semantically similar queries, and then invoking agents in descending reliability order. Next, Adaptive Incremental Voting (AIV) terminates the process once the current leading answer cannot be overturned by any possible votes from the remaining agents, and returns this answer. Finally, Reliability History Updating (RHU) updates only the invoked agents according to their consensus with the final decision. Extensive evaluations across five benchmarks show that EMS preserves the accuracy of Majority Voting while reducing the average number of invoked agents by 35% and token consumption by 44%, respectively. The code is available at https://github.com/fuyu66/EMS.

07.
Nature (Science) 2026-06-24

Disparate privacy risks from medical AI

Medical artificial intelligence (AI) models hold the promise to improve global access to high-quality diagnostics1. However, the training data underlying these models often contain sensitive patient information that may be exposed through privacy attacks2–7. Previous research has primarily quantified the success of these attacks in aggregate, across all records in a dataset. Thus, the privacy risk faced by individual patients, who often contribute multiple similar records to a training dataset, is poorly understood. Here we present one of the first patient-level privacy audits of AI models for medical diagnostic applications. We focus on membership inference attacks2–4 (MIAs), which seek to determine whether the data of a given individual were used to train a model. Across a diverse range of medical datasets, we show that MIAs can achieve near-perfect success rates for individual patients, even when the aggregate performance does not substantially deviate from random guessing. We further find that the number of patients with high attack success increases substantially with model capacity, and that underrepresented groups—stratified by disease status, self-reported race, insurance, sex or imaging protocol—face disproportionately high attack success. Together, our findings show that aggregate privacy metrics can severely underestimate individual privacy risk. Whether the disparate risk profiles we observe extend to attacks beyond MIAs remains an open question, motivating the further development of risk assessment and mitigation techniques that cater to all data-contributing patients. AI models for medical diagnostics are vulnerable to membership inference attacks.

08.
arXiv (CS.AI) 2026-06-12

Algorithmic Constitutionalism

arXiv:2606.12437v1 Announce Type: cross Abstract: The increasing encroachment of artificial intelligence (AI) on social life raises significant risks for society, particularly within the infospheres created and controlled by companies such as Google, Facebook, Apple, and Amazon. This article examines these risks through an in-depth analysis of Facebook's content moderation regime, which is already partially governed by algorithms. We argue that the idea of ethical engineering, often proposed in the literature as a solution to the governance challenges posed by AI, is inadequate for several reasons. In response, we develop an alternative framework, which we term "algorithmic constitutionalism." Our approach rests on three pillars: (a) a layered architecture consisting of two levels of code: (i) an operative or object level and (ii) a meta level designed to protect the system's core principles from algorithmically initiated change; (b) algorithmic meta-reasoning, which enables the system to operate simultaneously at both levels so that it can monitor, verify, and potentially correct in real time operations at the object level that depart from principles protected at the meta-code level; and (c) correction through deliberation. The article elaborates the concept of algorithmic constitutionalism and demonstrates how it may be applied to Facebook's content moderation regime. As part of this analysis, we examine the tension between societal constitutionalism and algorithmic constitutionalism. Paradoxically, attempts to subject AI systems to external deliberative control may also enable AI agents to intervene in that process, potentially undermining its purpose. The article concludes by considering the implications of this argument for the European Digital Services Act, which entered into force in October 2022.

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

CODA-BENCH: Can Code Agents Handle Data-Intensive Tasks?

Advanced agents are increasingly demonstrating the potential to operate as autonomous engineers, creating a growing demand for evaluation benchmarks that capture the complexity of real-world development. Such environments typically involve both complex code and large-scale data (i.e., file system). However, existing benchmarks usually evaluate code-centric or data-centric capabilities in isolation, leaving a clear gap with real development scenarios. In this paper, we bridge this gap by introducing CODA-BENCH, the first benchmark to jointly evaluate code and data intelligence in a data-intensive environment. We construct a data-intensive Linux sandbox based on the Kaggle ecosystem (containing hundreds of datasets), where agents must actively explore complex file hierarchies to identify relevant resources and generate code for data-driven analytical tasks. CODA-BENCH comprises 1,009 tasks spanning 31 communities, with each task environment containing an average of 980 files, simulating realistic data scale and noise. Evaluations of advanced agents reveal that even top-performing systems struggle to effectively integrate data discovery with code execution, achieving a success rate of only 61.1%. These results highlight a substantial gap in current agentic capabilities for data-intensive tasks and point to promising directions for future research.

10.
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.

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

Multimodal Graph Negative Learning

arXiv:2606.12863v1 Announce Type: new Abstract: Multimodal attributed graphs (MAGs) integrate graph topology with heterogeneous modality attributes, such as text and images, thereby enabling richer modeling of complex relational systems. However, such expressiveness also makes learning on MAGs depend on multiple semantic sources, including structural topology, textual and visual attributes, each of which can be regarded as a branch for node representation. Node-level branch semantic imbalance arises when these branches differ across nodes in semantic informativeness and reliability: a branch that provides discriminative semantics for one node may mislead another due to bias in modality quality or structural context. Existing methods often mitigate such heterogeneity through cross-branch agreement or alignment, implicitly treating the dominant prediction as reliable supervision. When the dominant branch is biased, forced imitation may propagate its bias to other branches and suppress original semantics that are useful for classification. We propose GraphMNL, a graph-aware multimodal negative learning framework that addresses this issue by using Negative Learning as cross-branch guidance. Instead of forcing inferior branches to imitate a teacher prediction, the model teaches them which classes a node is unlikely to belong to. GraphMNL builds a branch library, identifies dominant and inferior branches via graph-aware reliability arbitration, gates unstable transfer, and applies target-preserving negative learning over non-target classes. This design decouples target supervision from branch guidance so that supervised losses learn the correct class, while Negative Learning suppresses unlikely alternatives when branch agreement is unreliable. Through the comprehensive experimental evaluation, GraphMNL achieves the best performance on Grocery datasets with 72.47% accuracy and 76.60 F1 score on Reddit M datasets.

13.
arXiv (CS.AI) 2026-06-15

HyperPotter: Spell the Charm of High-Order Interactions in Audio Deepfake Detection

arXiv:2602.05670v2 Announce Type: replace-cross Abstract: Advances in AIGC technologies have enabled the synthesis of highly realistic audio deepfakes capable of deceiving human auditory perception. Although numerous audio deepfake detection (ADD) methods have been developed, most rely on local temporal/spectral features or pairwise relations, overlooking high-order interactions (HOIs). HOIs capture discriminative patterns that emerge from multiple feature components beyond their individual contributions. We propose HyperPotter, a hypergraph-based framework designed to capture high-order relations associated with synergistic patterns through clustering-based hyperedges with class-aware prototype initialization. Extensive experiments on 13 test sets show that HyperPotter improves over the baseline on 11 sets, yielding an average relative EER reduction of 12.68\% across all test sets and 22.15\% on the improved sets. These results demonstrate strong cross-scenario generalization, while also revealing robustness limits under severe codec or channel distortion.

14.
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.

15.
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.

16.
arXiv (quant-ph) 2026-06-25

Tripartite Entanglement in $e^+ e^- \to t \bar{t} Z$

arXiv:2606.11296v3 Announce Type: replace-cross Abstract: Multipartite entanglement is a uniquely quantum form of correlation that captures collective properties of a composite quantum state beyond those encoded in its bipartite subsystems. We investigate this phenomenon in the process $e^+e^-\to t\bar tZ$ at a future lepton collider, where the final state spins span the tripartite Hilbert space $\mathscr{H} = \mathbb{C}^2 \otimes \mathbb{C}^2 \otimes \mathbb{C}^3$. Starting from the Standard Model helicity amplitudes, we reconstruct the full $12\times 12$ spin density matrix and characterise its entanglement structure through one-to-one negativities, one-to-other negativities, and the genuine multipartite negativity, evaluated at three increasingly inclusive levels of phase space integration. Pairwise entanglement is generally suppressed relative to the collective (one-to-other) and the genuine multipartite entanglement, and all measures decrease as more kinematic information is integrated out. Assuming quantum tomography in the fully leptonic decay channel at $\sqrt{s}=1$ TeV, we find that collective entanglement should be accessible at a realistic high-luminosity polarised lepton collider. By contrast, certifying genuine multipartite entanglement is more challenging, with only limited sensitivity projected for a specific polarisation benchmark within the expected ILC luminosity. The study establishes $e^+e^-\to t \bar{t}Z$ as an attractive laboratory for probing multipartite entanglement in high-energy collisions and provides a general mixed state framework that applies to any tripartite spin system.

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

Coherent Dark State Formation of a Lead-Vacancy Spin Qubit in Diamond

arXiv:2605.27841v2 Announce Type: replace Abstract: A lead-vacancy (PbV) center in diamond exhibits coherent emission above the liquid helium temperature, making it highly attractive for quantum network applications. Here, we report the magneto-optical and spin properties of PbV centers in diamond. We record a spin lifetime of 12 ms at 7.5 K under large off-axis magnetic field. Furthermore, we observe formation of the coherent dark state by coherent population trapping and estimate a spin dephasing time of 177 ns at 6.5 K. This work demonstrates the outstanding thermal robustness of the PbV spin compared to other group-IV centers above 4 K.

18.
medRxiv (Medicine) 2026-06-24

ADVISE: A Machine Learning Framework for Early Recognition of a Surrogate Marker for Ventilator-Associated Pneumonia Using Routinely Collected Critical Care Data

Background Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in critical care, affecting 20-36% of mechanically ventilated patients. Early prediction is hampered by the absence of a reliable, objective diagnostic standard. We developed ADVISE (Automated Dudley Ventilation Infection Series Evaluation), a machine learning model to predict physiological deterioration consistent with developing VAP using routinely collected electronic health record data from a UK NHS intensive care unit. Methods Retrospective observational study of admissions at Russell's Hall Hospital ICU (2008-2026). Following National Data Opt-Out exclusion (158 admissions, 4.2%), 3,566 admissions generated 33,208 candidate 48-hour observation blocks. Six temporal variables - FiO2, ventilator mode, P:F ratio, procalcitonin (PCT), secretion amount, and secretion description - were extracted across the baseline window (hours 1-24). A composite VAP-surrogate outcome required concurrent P:F ratio decline (>=5%) and PCT rise (>=0.5 ng/mL) across the outcome window (hours 25-48). After sequential quality filters, 2,134 blocks (18 positive, 0.84% prevalence) were retained. An XGBoost classifier was trained using nested 5-fold cross-validation with scale_pos_weight=114.0 and ROC-based hyperparameter optimisation on 1,495 training blocks, evaluated on 639 held-out test blocks. Performance was assessed via AUROC, AUPRC, and calibration (Brier score). Bootstrap resampling (1,000 iterations) generated 95% confidence intervals. Results On the held-out test set (n=639, 5 positive outcomes), ADVISE achieved AUROC 0.874 [95% CI: 0.771-0.939] and AUPRC 0.031 [0.008-0.069], representing a 4.0-fold improvement over the no-skill baseline. Nested cross-validation mean AUROC was 0.844 +/- 0.078 (range 0.716-0.915). At the Youden-optimal threshold, sensitivity was 0% with specificity 97.8%, reflecting extreme class imbalance (0.78% test prevalence). A threshold targeting 80% sensitivity achieved sensitivity 80.0% [33.3-100.0%], specificity 87.4% [84.8-89.9%], positive predictive value 4.8% [1.1-9.9%], and negative predictive value 99.8% [99.4-100.0%], detecting 4 of 5 VAP cases with approximately 80 false alarms (12.6% false positive rate). Brier score was 0.0078. Feature importance identified baseline P:F ratio as the dominant predictor (41.3% total gain), followed by ventilator mode (26.1%), secretion amount (13.2%), secretion description (9.1%), procalcitonin (5.9%), and FiO2; (4.5%). Conclusions ADVISE demonstrates that baseline oxygenation trajectory and ventilatory support patterns - derived exclusively from routinely charted ICCA variables - can identify admissions at risk of VAP-related physiological deterioration with meaningful discrimination (AUROC 0.874) despite severe class imbalance. The 80% sensitivity operating point offers a clinically actionable alert rate (12.6% FPR), supporting integration into existing ICU workflows. This proof-of-concept study establishes feasibility; multi-site prospective validation is required before clinical deployment.

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

Predicting Immune Biomarkers with MultiModal Mixture-of-Expert Pathology Foundation Models Empowers Precision Oncology

Predicting immune biomarkers associated with the tumor immune microenvironment (TIME) is critical for advancing precision oncology, yet existing approaches are largely limited to single image modalities and suffer from insufficient resolution and incomplete utilization of complementary clinical and biological information. Here we introduce MixTIME, a multimodal foundation model that leverages a mixture-of-experts (MoE) architecture to integrate pathology foundation models trained across distinct modalities: image only (UNIv2), image text (CONCHv1.5), and image transcriptomic (STPath) representations for pixel-level and slide-level prediction of multiplex immunofluorescence (mIF) protein expression from hematoxylin and eosin (HE) whole-slide images. MixTIME employs a learnable router to dynamically weight expert contributions and is trained with a distribution- and tendency-aware loss function. Benchmarked on two datasets of different scales, MixTIME achieves state-of-the-art performance across 17 protein markers as measured by correlation metrics. The predicted mIF profiles substantially enhance downstream tasks, including spatial domain identification, survival prediction, and AI-assisted pathology report generation validated by expert pathologists from multiple institutes across the world. Furthermore, MixTIME enables longitudinal tracking of protein expression dynamics across clinical time points and reveals protein gene interaction patterns linked to drug resistance and immune suppression in tumor microenvironments. Collectively, MixTIME provides a scalable framework for multimodal biomarker discovery and clinical translation in computational pathology.

20.
arXiv (CS.CV) 2026-06-25

Delving into Latent Spectral Biasing of Video VAEs for Superior Diffusability

Latent diffusion models pair VAEs with diffusion backbones, and the structure of VAE latents strongly influences the difficulty of diffusion training. However, existing video VAEs typically focus on reconstruction fidelity, overlooking latent structure. We present a statistical analysis of video VAE latent spaces and identify two spectral properties essential for diffusion training: a spatio-temporal frequency spectrum biased toward low frequencies, and a channel-wise eigenspectrum dominated by a few modes. To induce these properties, we propose two lightweight, backbone-agnostic regularizers: Local Correlation Regularization and Latent Masked Reconstruction. Experiments show that our Spectral-Structured VAE (SSVAE) achieves a $3\times$ speedup in text-to-video generation convergence and a 10\% gain in video reward, outperforming strong open-source VAEs. The code is available at https://github.com/zai-org/SSVAE.

21.
medRxiv (Medicine) 2026-06-22

Characteristics and Outcomes of Gene-Elusive Dilated Cardiomyopathy

Background and Aims Genetic testing in dilated cardiomyopathy (DCM) guides risk stratification and family screening. Likely pathogenic or pathogenic (LP/P) variants are identified in approximately one-third of patients, leaving many without a genetic diagnosis. Cohort studies suggest that "gene-elusive" patients have a lower risk of adverse events. This study aims to better characterise this group and identify factors associated with adverse outcomes. Methods Consecutive and unrelated DCM patients undergoing genetic testing and returning no LP/P variants were retrospectively recruited and compared to two control cohorts of DCM patients carrying LP/P variants in LMNA and TTN for a primary composite endpoint of end-stage heart failure (ESHF) or malignant ventricular arrhythmia (MVA). Results Among patients without prior MVA, the composite endpoint occurred in 36/423 (8.5%) gene-elusive, 14/39 (35.9%) LMNA and 11/100 (11%) TTN cardiomyopathy patients (log-rank p

22.
medRxiv (Medicine) 2026-06-24

Five-Year Breast Cancer Risk Prediction From Screening Breast Ultrasound Using Deep Learning

Objective: To develop and evaluate a deep learning model for five-year breast cancer risk prediction from screening breast ultrasound (BUS) examinations. Methods: This retrospective study included 295,298 breast ultrasound examinations from 122,072 women imaged between 2012 and 2020. Patients were split into training, validation, and test sets; the test set included screening examinations only. BUS-Risk-Net aggregated image features using attention-based multiple instance learning and combined them with age and ultrasound-estimated breast density to predict 2- to 5-year risk. Performance was compared with the full Tyrer-Cuzick model in a matched case-control cohort and with a reduced Tyrer-Cuzick model in the held-out test set. Risk stratification was evaluated within BI-RADS density categories. Results: In the matched case-control cohort (n = 240 women), BUS-Risk-Net achieved a 5-year AUC of 0.632 (95% CI, 0.562-0.702), versus 0.514 for the full Tyrer-Cuzick model (95% CI, 0.440-0.588; p = 0.04). Among 19,548 examinations from 9,015 women eligible for 5-year evaluation in the test set, BUS-Risk-Net achieved an AUC of 0.679 (95% CI, 0.653-0.706), versus 0.594 for the reduced Tyrer-Cuzick model (95% CI, 0.564-0.623; P < .001). Observed 5-year cancer incidence increased across AI-defined risk tiers within each BI-RADS density category, ranging from 0.0% to 5.8% after AI stratification, compared with 2.1% to 3.6% across density categories alone. Discussion: Deep learning models applied to screening breast ultrasound could enable long-term breast cancer risk prediction and stratify risk beyond breast density alone. External and prospective validation is needed before clinical use.

23.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.

24.
arXiv (CS.AI) 2026-06-24

Emergent Relational Order in LLM Agent Societies: From Collective Affect to Authority Stratification

arXiv:2606.23764v1 Announce Type: cross Abstract: Fei Xiaotong's Differential Order Pattern characterizes rural society as egocentric and relationally graded, with cooperation attenuating over social distance. Although often treated as culturally specific, its mechanistic basis remains under-operationalized, and prior LLM-based simulations have mainly addressed short-term coordination rather than long-horizon social structure. We propose CAREB-MAS, a multi-agent framework grounded in Affect Control Theory, Social Identity Theory, and Durkheimian collective affect. Agents reason through an emotion-ethics-belief chain and maintain dynamically evolving egocentric identities, while the macro environment specifies only individual production, preference-based allocation, and minimal interaction protocols. Across long-horizon simulations, agents spontaneously reproduce five core Differential Order phenomena: stable labor specialization, guanxi-based economic ethics, relational decay of cooperation, emergent relational authority, and clan-based center-periphery stratification. These patterns shift with production structure from kin-centered integration toward greater functional interdependence. Extensive experiment results support interpreting Differential Order as a structure-sensitive emergent outcome of general social mechanisms, with LLM-based multi-agent simulation providing an interdisciplinary framework for studying social structure and change.

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arXiv (CS.AI) 2026-06-19

Rethinking Shrinkage Bias in LLM FP4 Pretraining: Geometric Origin, Systemic Impact, and UFP4 Recipe

arXiv:2606.20381v1 Announce Type: new Abstract: FP4 training promises substantial reductions in memory and computation cost for LLM pretraining, yet current FP4 hardware paths and recipes, including NVIDIA Blackwell/Rubin-class systems and AMD MI350-series GPUs, remain centered on E2M1 data elements. In this study, we identify a fundamental limitation of that choice: non-uniform formats such as E2M1 inherently suffer from Shrinkage Bias, a systematic negative rounding error caused by the geometric asymmetry of their representable bins. We show that this bias accumulates multiplicatively across layers and is amplified by the Random Hadamard Transform (RHT), providing a unified explanation for the training instability observed in existing E2M1-based FP4 recipes. In contrast, uniform grids (E1M2/INT4) bypass this grid-geometry error and better convert the improved bucket utilization from RHT into higher quantization quality. Based on this finding, we propose UFP4, a uniform 4-bit training recipe that applies RHT to all three training GEMMs while restricting stochastic rounding to dY alone. On Dense 1.5B, MoE 7.9B, and MoE 124B long-run pretraining, UFP4 consistently achieves lower BF16-relative loss degradation than strong E2M1-based baselines, supported by scaling-law analysis and ablation studies. Our results suggest that future accelerators should support E1M2/INT4-style uniform 4-bit grids as first-class training primitives alongside E2M1.