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

Recipe-Controlled Decoder Audit for Structural Knowledge-Graph Completion

arXiv:2606.14492v1 Announce Type: new Abstract: We present a recipe-controlled decoder audit (RCDA) for structural transductive knowledge-graph completion (KGC). The audit asks a simple reporting question: before attributing gains to an encoder or training recipe, what changes when the decoder is swapped under the same recipe? Using ComplEx and DistMult as the primary controlled pair, with targeted RotatE/TransE spot-checks, we evaluate seven benchmarks. On five standard KGs, ComplEx-vs-DistMult differences are modest but consistent under our recipe (+0.005 to +0.012 MRR), whereas CompGCN-style encoder effects vary more by dataset. On small KGs, decoder effects become the main diagnostic: Kinship shows a stable ComplEx advantage of +0.143 MRR (6 seeds), while UMLS favours ComplEx by +0.022 MRR in a clean 6-seed server rerun but reverses in an earlier provenance variant. We therefore treat small-KG decoder choice as recipe- and provenance-sensitive rather than as a fixed dataset winner. We further show that decoder choice interacts with encoder depth on WN18RR, and that under our recipe L=0 ComplEx on YAGO3-10 reaches 0.6971 +/- 0.0048 MRR at d=128. The result is a compact audit protocol: report matched decoder rows, log small-KG provenance, and sweep decoder x depth before making encoder-level claims.

02.
medRxiv (Medicine) 2026-06-22

Assessment of adaptive functioning in Angelman syndrome using the Vineland Adaptive Behavior Scales, Third Edition

Purpose: This study examined longitudinal trajectories of adaptive functioning in 331 individuals with Angelman syndrome (AS) using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) and examined differences by molecular subtype. Methods: A total of 331 individuals (156 females, 47%) with genetically confirmed AS (ages 6 months to 52 years) were assessed between 2018 and 2025, including 207 with a deletion subtype, 63 with uniparental disomy or imprinting defect, and 61 with a UBE3A point mutation. Growth scale values were analyzed using linear mixed-effects models with log2-transformed age. Results: Individuals with deletion subtypes demonstrated significantly lower adaptive functioning across domains compared to those with non-deletion subtypes. Adaptive skills across all Vineland-3 subdomains increased nonlinearly with age, showing faster growth early in life that slowed over time, with largely parallel trajectories across subtypes. Conclusion: Individuals with AS demonstrate slow but steady growth in adaptive functioning that continues into adulthood, with progress varying by molecular subtype. These findings provide updated natural history benchmarks and demonstrate the utility of the Vineland-3 for clinical trials.

03.
arXiv (CS.LG) 2026-06-12

PLaID++: A Preference Aligned Language Model for Targeted Inorganic Materials Design

arXiv:2509.07150v4 Announce Type: replace Abstract: Reinforcement Learning from Verifiable Rewards (RLVR) has emerged as a promising approach to improve correctness in LLMs, however, in many scientific problems, the objective is not necessarily to produce the correct answer, but instead to produce a diverse array of candidates which satisfy a set of constraints. We study this challenge in the context of materials generation. To this end, we introduce PLaID++, an LLM post-trained for stable and property-guided crystal generation. We find that performance hinges on our crystallographic representation and reward formulation. First, we introduce a compact, symmetry-informed Wyckoff text representation which improves computational efficiency and encourages generalization from physical priors. Second, we demonstrate that temperature scaling acts as an entropy regularizer which counteracts mode collapse and encourages exploration. By encoding symmetry constraints directly into text and guiding model outputs towards desirable chemical space, PLaID++ generates structures that are thermodynamically stable, unique, and novel at a $\sim$50\% greater rate than prior methods and conditionally generates structures with desired space group properties. Our work demonstrates the potential of adapting post-training techniques from natural language processing to materials design, paving the way for targeted and efficient discovery of novel materials.

04.
arXiv (CS.AI) 2026-06-18

TLA-Prover: Verifiable TLA+ Specification Synthesis via Preference-Optimized Low-Rank Adaptation

arXiv:2606.06133v2 Announce Type: replace-cross Abstract: TLA+ is a formal specification language for verifying distributed systems and safety-critical protocols. Large language models (LLMs) frequently produce TLA+ specifications that fail the TLC model checker for semantic reasons. Across 25 LLMs, the best public baseline is 26.6% syntactic parse and 8.6% semantic model-check. We present TLA-Prover, a 20-billion-parameter model for TLA+ specification synthesis. Training combines supervised fine-tuning (SFT) on verified examples with repair-based group-relative policy optimization (GRPO). In the GRPO stage, the model learns to fix its own rejected specifications. We also train a direct preference optimization (DPO) variant from the same SFT checkpoint as an ablation. TLC provides the reward signal directly, with no learned reward model. Four tiers grade each output: Bronze (parses), Silver (no warnings), Gold (passes TLC), and Diamond. To reach Diamond, the model's correctness property is automatically altered in a small way; TLC must then detect a violation. If TLC still passes, the property was always-true and contributes nothing; the output fails Diamond. TLA-Prover reaches 9/30 (i.e. pass@1 = 30%) at both Gold and Diamond on a held-out 30-problem benchmark. This is roughly 3.5x the 8.6% untuned baseline. The DPO variant reaches 20% at Diamond. Gold and Diamond coincide at every checkpoint; this prevents the trivial-property failure mode.

05.
arXiv (CS.CV) 2026-06-24

VisCritic: Visual State Comparison as Process Reward for GUI Agents

Authors:

GUI agents powered by vision-language models show strong potential for automating digital tasks, yet frequently fail in long-horizon scenarios due to the absence of step-level verification. Existing process reward models verify actions through textual reasoning alone, missing the visual nature of GUI state changes. We introduce VisCritic, a visual process reward framework that verifies agent actions by directly comparing pre-action and post-action screenshots in visual feature space. VisCritic employs a Siamese vision transformer to extract change-aware representations, coupled with an Action-Aware Critic Head that jointly evaluates action success, task progress, and error type. A critic-training data construction pipeline generates weakly supervised samples from existing trajectories without additional human labels for critic training. Experiments and offline analyses across five benchmarks demonstrate that VisCritic serves as a plug-and-play enhancement for diverse GUI agents, generally improving benchmark metrics while providing visual diagnostic cues.

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

Universal Dynamical Response to Slow Driving in Chaotic Systems

arXiv:2606.23810v1 Announce Type: cross Abstract: We propose a unified perspective on classical and quantum chaos based on the stability of a system's stationary states under slow driving. We probe this sensitivity via the system's susceptibility to the average protocol speed, which we call the ``speed-Fisher information," and relate it to irreversible entropy production in the system. We show that chaotic dynamics manifests as a divergence of the speed-Fisher information with the protocol time, and that this response is controlled by the perturbation's low-frequency spectral weight. This approach to chaos applies to both classical and quantum Hamiltonian systems, and naturally extends to non-Hamiltonian classical flows. We illustrate this framework with simple classical and quantum examples, along with a non-Hamiltonian flow that qualitatively exhibits analogous low-frequency spectral behavior.

07.
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.

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

Stereo Vision-Based Fall Prediction and Detection using Human Pose Estimation on the AMD Kria K26 SOM

Background and Objective: Falls among elderly people can cause serious injury and reduce quality of life. Timely prediction and detection are essential to prevent harm and support well-being. We propose a portable, low-power, battery-operated, vision-based fall prediction and detection system using HPE on an AMD Kria K26 System-on-Module (SOM). The objective is a non-intrusive, privacy-preserving system for real-time fall detection. Methods: The system uses an Intel RealSense D455 range-sensing camera connected to the K26 SOM by USB. It captures synchronized RGB and depth frames, 640 x 480 x 3 and 640 x 480 pixels, at 60 FPS. The SOM runs a three-stage pipeline with quantized YOLOX, Anchor-to-Joint (A2J), and fall-detection models. YOLOX identifies human bounding boxes from RGB frames, then discards the RGB frames to preserve privacy. A2J uses depth frames to estimate 15 joint keypoints per person. A CNN uses selected joint coordinates (x, y, z) to classify fall activity. YOLOX was trained on CrowdHuman; A2J on ITOP, MP-3DHP, UR Fall Detection, and a custom SDSU PSG dataset; and the CNN on UR Fall Detection and SDSU PSG. The design used a single-core DPU with a serial pipeline and a dual-core DPU running YOLOX and A2J with multiple threads. Results: Quantized accuracy was evaluated using IoU >= 50% for YOLOX, mAP with a 10-cm rule for A2J, and classification accuracy, (TP + TN)/(TP + TN + FP + FN), for the CNN. Accuracies were 74%, 84.13%, and 75.85%. Throughput improved from 2.5 FPS for the single-threaded pipeline to 4.5 FPS for the multi-threaded version. Conclusion: Results demonstrate the feasibility of privacy-preserving fall detection on an AMD Kria K26 edge device. On-device HPE and fall classification runs without cloud dependency, supporting elderly monitoring and assistive healthcare. Future work will improve model accuracy and speed.

09.
arXiv (CS.CL) 2026-06-15

LLMs Contain Multitudes: How Deployment Context Reshapes Model-Level Preferences and Values

Large language models (LLMs) are increasingly characterised in recent evaluation work as having stable, model-level preference and value systems. However, accompanying robustness checks are limited to incidental prompt perturbations such as syntax variation and option reordering. This leaves open whether the measured properties survive when the surrounding task context changes, as it does in most real deployments. We test this directly across two established pairwise paradigms: ranking country preferences and eliciting utility judgements. In both, we make the deployment context – the high-level task the model is performing while making concrete value-dependent choices – our controlled variable, varied across framings such as writing a Reddit post or a news article. Across five LLMs and over 1.2M pairwise decisions, deployment context produces variation far larger than prompt paraphrasing and temperature controls. In country preference rankings over 15 countries, context induces widespread, statistically significant rank shifts; the aggregate Global North favouritism reported in prior work is itself context-dependent, with each model's bias shifting systematically across contexts. In utility elicitation over 50 outcomes, broad cross-category ordering is preserved, but fine-grained rankings within domains vary substantially, and cardinal exchange rates between outcomes (e.g. how many lives in one region equal one in another) shift by a factor of 2.47 at the median. Reported model-level preferences and utilities are therefore better understood as context-conditioned measurements than fixed model-level properties: safety guarantees obtained under one framing provide limited assurance in another.

10.
arXiv (math.PR) 2026-06-15

Real-order moments, tail representations, and logarithmic means

arXiv:2606.14019v1 Announce Type: cross Abstract: This paper develops a unified framework for the study of real-order moments of arbitrary random variables. General integral representations are established in terms of cumulative distribution functions and survival functions, covering continuous, discrete, and mixed distributions supported on the whole real line. These formulas extend the classical tail-integral identities for nonnegative random variables and provide a common treatment of positive, fractional, and negative moments. For discrete distributions, explicit series representations are derived in terms of cumulative probabilities, yielding simple criteria for the existence of moments. Applications are presented for the zeta and Skellam distributions, illustrating how tail behavior determines moment finiteness and how moments can be represented geometrically through cumulative distribution functions. In addition, a representation for logarithmic moments is obtained, linking logarithmic means, Laplace transforms, and the classical Frullani identity. The results provide a unified perspective on moment representations and establish useful connections between tail probabilities, distribution functions, Laplace transforms, and moment existence.

11.
arXiv (CS.AI) 2026-06-16

Quantifying the Impact of Lossy Compression on Neural Generative Surrogate Modeling

arXiv:2606.15959v1 Announce Type: cross Abstract: Neural networks are used as generative surrogate models for scientific discovery, which are trainable approximations of scientific simulations. These models enable users to replace time-consuming numerical simulations with learned alternatives, providing quick solutions. However, high-fidelity generative surrogate models require massive training datasets, which can create storage and I/O challenges. Lossy compression is a promising way to reduce this burden, but compression errors may affect the model quality in subtle ways, making it challenging to quantify their impact. In this work, we examine how lossy compression of training data impacts the quality of generative surrogate models. We begin by characterizing the uncertainty inherent in training neural networks, showing that identical training configurations can produce different models. By exploiting this variability, we propose a method to estimate how much compression-induced error a surrogate model can tolerate without affecting its accuracy. Evaluation of two application simulations demonstrates that our approach significantly reduces memory/storage requirements and speeds up training while producing high-quality surrogate models. These results show that lossy compression saves data storage up to 23.7x and 39x with negligible impact on the quality of the surrogate model. Meanwhile, reducing the size of the training data set also enhances the data loading speed and reduces the training time by up to 3x.

12.
arXiv (quant-ph) 2026-06-19

Emergency hub placement with a neutral-atom quantum computer

arXiv:2606.19589v1 Announce Type: new Abstract: We study the problem of emergency operation center placement in disaster response, where a minimal number of hubs must be selected to ensure timely coverage of all affected locations. This task can be formulated as a minimum dominating set problem on a graph encoding reachability within a target response time. We propose a hybrid quantum-classical approximation framework that leverages neutral-atom quantum computers as independent set samplers. Candidate dominating sets are constructed from both small maximal independent sets and complements of large independent sets, and are subsequently refined via a lightweight classical procedure. We benchmark the approach on synthetic instances and realistic case studies, and implement it on the Fresnel quantum processor by Pasqal, solving instances of up to 100 nodes. Our results show that quantum-generated samples, despite hardware noise, enable near-optimal solutions of the placement problem. Overall, our results demonstrate that neutral-atom devices operating in analog mode can already be used to tackle graph optimization problems for real-world applications.

13.
arXiv (CS.CV) 2026-06-12

RepWAM: World Action Modeling with Representation Visual-Action Tokenizers

This work presents RepWAM, a representation-centric world action model (WAM) built on representation visual-action tokenizers. Existing WAMs typically inherit reconstruction-oriented video tokenizers from pretrained video generation models. Although these tokenizers preserve visual fidelity, pixel reconstruction alone provides limited guidance for learning instruction-following dynamics that connect future prediction with robot control. To address this, we explore a semantic visual-action latent space for representation-centric world action modeling. Specifically, we train a representation visual-action tokenizer that maps visual inputs into aligned visual and latent action tokens. We then pretrain our WAM to jointly model future visual states and the latent actions that connect them under language instructions, followed by adaptation to real robot trajectories for closed-loop manipulation. Experiments on real-world manipulation tasks and simulation benchmarks show that RepWAM delivers strong performance across diverse manipulation settings, while ablations highlight the value of semantic visual-action tokenization over reconstruction-oriented alternatives. These results establish representation visual-action tokenization as a promising foundation for world action models and a step toward generalist robot policies. Code and weights will be available at https://github.com/wdrink/RepWAM.

14.
arXiv (CS.LG) 2026-06-17

Toward Controllable Catalyst Inverse Design via Large-Scale Autoregressive Pretraining

arXiv:2606.17445v1 Announce Type: new Abstract: Inverse design of heterogeneous catalysts remains challenging because catalyst surfaces exhibit substantial structural complexity with coupled surface-adsorbate interactions across a vast chemical space that is difficult to explore efficiently through conventional screening alone. Although machine learning-based high-throughput screening has accelerated catalyst discovery, its efficiency inevitably declines as the search space grows, motivating the development of generative models that can directly construct catalysts with target properties. Here, we present a conditional catalyst generative model based on the Generative Pretrained Transformer architecture with a numerical embedding layer that enables the generation of catalyst structures conditioned on both categorical and continuous properties within a single autoregressive framework. The model was pretrained on 133 million catalyst structures and subsequently fine-tuned on approximately 460,000 optimized structures with associated categorical properties and binding energies for conditional generation. The resulting model achieved 98% structural validity, 95% optimization validity, and high categorical condition fidelity, with a 93 % joint match rate for adsorbate type and composition. For binding energy conditioning, the match rate of approximately 20% represents a four-fold improvement over the baseline training distribution, and the generated distributions shift systematically toward the target values, enabling a 1.5 to 4-fold improvement in screening efficiency for reaction-targeted catalyst discovery without additional fine-tuning. These results show that large-scale autoregressive pre-training, combined with explicit property conditioning, provides a practical route toward controllable catalyst generation and accelerated catalysts discovery.

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

VHDLSuite: Unified Pipeline for LLM VHDL Generation with Data Synthesis and Evaluation

arXiv:2606.13735v1 Announce Type: cross Abstract: Large Language Models (LLM) have shown impressive capabilities in Register Transfer Level (RTL) code generation, particularly for Verilog. However, evaluating their performance with other Hardware Description Languages (HDL), especially VHDL, remains limited although its distinct language characteristics, such as stricter semantic rules, introduce evaluation considerations that differ from Verilog. This lack of coverage restricts fully understanding of how well current models generalize across hardware design languages with differing structures and semantics. To address this gap, we introduce VHDLSuite, a benchmark-centered infrastructure for scalable VHDL generation evaluation, integrating automated benchmark synthesis, executable validation, and multi-model diagnostic analysis. First, we propose a data pipeline that automatically converts Verilog designs and their accompanying testbenches into executable VHDL benchmark instances, followed by VUnit/GHDL-based validation to ensure each released task is compilable, runnable, and consistently checkable in the VHDL environment. Second, we introduce VHDLBench, a benchmark with over 200 VHDL problems with complete and validated testbenches across a wide range of complexity levels. Third, we extensively evaluate cutting-edge LLMs and uncover key challenges specific on LLM-aided VHDL generation. Our findings provide important insights and support future work in multi-language hardware design automation.Our data pipeline, benchmark, and evaluation framework will be open-sourced.

16.
arXiv (CS.CV) 2026-06-11

From Nominal Intensity to Equivalent Rainfall: A Path-Based Credibility Evaluation Framework for Simulated Rainfall in Autonomous-Driving Perception Tests

Credible simulated-rainfall conditions are essential for identifying perception-system boundaries and supporting SOTIF-oriented risk assessment in automated driving. However, closed-field tests are often described only by nominal rainfall intensity or single-point measurements, making it difficult to align simulated rain fields with real rainfall and map test results to real-world scenarios. This paper proposes a path-based credibility evaluation method for simulated rainfall in autonomous-driving perception tests. Using the drop size and velocity joint distribution of real rainfall as the reference, each candidate path is represented by path-equivalent rainfall intensity, an uncertainty band, and a path-averaged Realism of Raindrop Distribution (RRD) score. Lidar target point-cloud count and mean reflectivity are further used for perception-consistency correction, quantifying the proxy capability of each simulated-rainfall path for real-rainfall perception effects. Experiments are conducted using about 10,000 real-rainfall raindrop-spectrum samples, 728 RainSense perception samples, and 45 spatial sampling points in a 2.4 m x 7.2 m simulated-rainfall area. Results show that spatial non-uniformity remains under the same nominal condition, confirming the need for path-based evaluation. The method identifies Path IV and Path VI as preferable candidates, with results of 11.54 +/- 0.31 mm/h, RRD = 0.43, and 8.28 +/- 0.34 mm/h, RRD = 0.46, respectively. These paths show more balanced performance in rainfall-intensity stability, raindrop-spectrum realism, and perception consistency. The proposed method supports path selection, condition description, and credible interpretation of autonomous-driving perception tests under rainfall.

17.
arXiv (math.PR) 2026-06-18

Rigidity of infinite exchangeable sequences with Gaussian marginals

arXiv:2606.18654v1 Announce Type: new Abstract: We study infinite exchangeable sequences with Gaussian one-dimensional marginals. We formulate the conjecture that joint Gaussianity of a single pair of coordinates forces the entire sequence to be a Gaussian process. Although this conjecture remains open, we prove that joint Gaussianity of the first four coordinates is sufficient. We also establish the corresponding two-point criterion under the additional assumption that the directing measure is almost surely infinitely divisible.

18.
arXiv (quant-ph) 2026-06-11

Scaling-optimal purification of noisy qubit unitary channels

arXiv:2606.12394v1 Announce Type: new Abstract: We consider the problem of purifying noisy qubit unitary channels. Given the ability to apply an unknown qubit unitary channel followed by depolarizing noise, we aim to construct a superchannel that purifies the noisy unitary back to the original unknown unitary. We first provide numerical evidence that sequential strategies can strictly outperform parallel strategies when the number of channel uses is finite, highlighting the fundamental distinction from state purification. We then provide a concrete $\mathrm{U}(2)$-covariant parallel protocol based on a novel entanglement-assisted quantum error-correcting code that suppresses the first-order noise strength as $O(1/n)$ with $n$ channel uses and show this scaling is asymptotically optimal in the low-noise regime, even when sequential strategies are allowed.

19.
medRxiv (Medicine) 2026-06-16

Care Delivery Gap framework: a proof-of-concept patient-reported measure of guideline-referenced care-process omissions in sickle cell disease

Abstract Background:Sickle cell disease (SCD) is concentrated in sub-Saharan Africa, where delivery of guideline-referenced care remains challenging. Current evaluation approaches rely largely on access indicators and clinical outcomes, which do not directly measure care delivery. We developed the Care Delivery Gap (CDG) framework, a patient-reported approach for identifying care-process omissions, and conducted a proof-of-concept study to assess feasibility and explore variation across income strata. Methods: We conducted a cross-sectional framework-development study involving a proof-of-concept sample of 52 individuals with SCD or caregivers recruited through clinics and moderated SCD communities across Africa, North America, and Europe between June 2025 and March 2026. The CDG framework assessed patient-reported omissions in specialist involvement, follow-up continuity, cardiovascular screening, and biochemical surveillance. Analyses were descriptive. Results: Substantial multi-domain care-process omissions were identified despite high reported healthcare engagement. Across geographic income strata, cardiovascular screening was reported by 4/35 (11%) LMIC versus 16/17 (94%) HIC participants, and regular follow-up within the preceding 12 months by 14/35 (40%) versus 16/17 (94%), respectively. High CDG scores, representing 1 omissions across three or four domains, occurred in 20/35 (57%) LMIC compared with 1/17 (6%) HIC participants. Similar disparities were observed across specialist review and vitamin B12 surveillance domains. Conclusion: A structured patient-reported framework identified multi-domain omissions in guideline-referenced SCD care, including among individuals reporting healthcare access. The divergence between access indicators and reported care delivery suggests that service contact alone may not reflect care quality. The framework provides a feasible foundation for future process-level quality measurement in high-burden settings.

20.
arXiv (CS.LG) 2026-06-12

Learning-Augmented Approximation for Unrelated-Machines Makespan Scheduling

arXiv:2606.13133v1 Announce Type: cross Abstract: Recently, Antoniadis et al. (ICLR 2025) proposed a framework for incorporating predictions to approximate NP-hard selection problems. Despite its simplicity, this approach tightly matches theoretical lower bounds, making its generalization highly compelling. We address an open question raised in the work of Antoniadis et al., concerning the extension of this approach to other important problems outside the class of selection problems, such as scheduling. We develop a learning-augmented algorithm for the makespan minimization problem on unrelated machines, denoted by $R\|C_{\max}$. By using predictions of heavy job assignments, we achieve a polynomial-time $(1+\varepsilon)$-approximation for accurate predictions that smoothly degrades to a worst-case 2-approximation as the error increases. We conclude our work with an empirical analysis of our method.

21.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Authors:

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.

22.
medRxiv (Medicine) 2026-06-22

A Drug-Specific, Half-Life-Adjusted Framework for Classifying CNS-Active Systemic Therapy Exposure During and After Radiotherapy

Clinical oncology datasets often store systemic therapy as a regimen label with a start date and an end date. Those records are clinically recognizable but can be analytically incomplete when the research question concerns whether a patient was exposed to a concurrent CNS-active drug (cCNS-aD) or an adjuvant CNS-active drug (aCNS-aD) around radiotherapy. Contemporary CNS-oncology studies usually define CNS activity by empiric drug lists and define concurrency by fixed calendar windows, although the literature shows substantial heterogeneity across both concepts. This paper proposes a generalizable framework for converting raw systemic therapy records into reproducible cCNS-aD and aCNS-aD variables, useful in subgrouping for clinical studies. The framework uses a transparent CNS scoring model based on three clinical evidence components: intracranial objective response rate, consensus CNS endorsement, and intrathecal route of administration. It then defines a pharmacokinetic exposure proxy as the recorded end date plus five half-lives. Concurrent exposure is classified by overlap with the radiotherapy interval, while post-radiotherapy exposure is classified by overlap with a prespecified post-RT attribution window. The framework separately identifies post-RT pharmacokinetic persistence and post-RT treatment initiation, allowing investigators to distinguish continued exposure from true adjuvant initiation. This is a methodological framework and reference implementation. Implementation audits and endpoint-specific sensitivity analyses remain necessary before use as a definitive exposure classifier

23.
arXiv (CS.AI) 2026-06-24

A Fair Evaluation of Graph Foundation Models for Node Property Prediction

arXiv:2606.24509v1 Announce Type: cross Abstract: Due to the wide use of graph-structured data in different fields of industry and science, the development of Graph Foundation Models (GFMs) has recently attracted a lot of attention. While many different types of models are called GFMs, particular interest has been paid to GFMs designed for node property prediction tasks, which is one of the most popular settings in Graph ML with lots of real-world applications from fraud detection in financial and social networks to recommendation systems for e-commerce and user-generated content platforms. While a number of GFMs for this task have been recently proposed, the field has not converged to a unified evaluation setting, and different works evaluate their models in widely different ways, preventing reliable comparison of GFMs with each other and with other types of models. In this work, we conduct a fair and rigorous reevaluation of 9 recent GFMs for node property prediction, comparing them to strong Graph Neural Network (GNN) baselines. We find that, among these GFMs, only the most recent ones based on the Prior-data Fitted Networks paradigm outperform well-tuned GNNs in predictive performance, although at a higher inference cost.

24.
PLOS Computational Biology 2026-06-05

A multiscale, Bayesian inference approach to augment mechanistic models of cell signaling with machine-learning predictions of binding affinity

by Holly A. Huber, Stacey D. Finley Computational models in systems biology are often underdetermined—that is, there is little data relative to the complexity and size of the model. This lack of data is primarily due to limits in our ability to observe specific biological systems and restricts the utility of computational models. To reduce this uncertainty, recent methods have explored augmenting parameter inference of systems biology models with predictions from machine learning models. Such approaches expand the pool of data that is applicable for the inference problem. Here, we explore augmenting the parameter inference of intracellular signaling models. We choose to investigate signaling because experimental measurements of the variables of interest, protein dynamics, are still quite limited. To investigate, we propose a novel, multiscale, Bayesian inference approach that augments traditional signaling data with predictions of binding affinity. These predictions are generated using a machine learning pipeline with measurements of amino acid sequence, from the Universal Protein Resource, or protein structure, from the Protein Data Bank, as inputs. We find that we can successfully integrate these measurements into the inference problem using our novel framework. Excitingly, this integration significantly improves the parameter estimates of signaling models. We demonstrate that how much this improvement impacts predictions of signaling depends on the sensitivity of the prediction to perturbations in the parameter values. Overall, the framework we establish here improves the parameter inference of intracellular signaling models by successfully bridging data on protein sequence and structure with systems-level signaling.

25.
arXiv (quant-ph) 2026-06-24

Wigner's Phase Space Current for Variable Beam Splitters – Phase Space Rotations and Newtonian Trajectories

arXiv:2606.24334v1 Announce Type: new Abstract: Beam splitters allow us to superpose two continuous single mode quantum systems. To study the behaviour of beam splitters' strongly mode mixing dynamics we consider variable beam splitters acting on Wigner's phase space distribution, W , the evolution of which is governed by the continuity-equation {\partial \tau} W = - {\nabla} J. We derive the form of the corresponding Wigner current, J. J's form allows us to use a classical trajectories-approach to analyze the influence of the two modes on each other. We show that the dynamics for variable beam splitters amounts to a rotation confined within the plane of the two positions together with the same simultaneous rotation confined within the plane of the two momenta. In this way explicit and very transparent expressions for the rotated Wigner distributions and Wigner currents can be given in terms of classical trajectories. This helps us to gain deeper insights and perform geometrical analyses of the mixing of modes at beam splitters.