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01.
arXiv (CS.CV) 2026-06-19

FlowBender: Feedback-Aware Training for Self-Correcting Conditional Flows

Conditional diffusion and flow models routinely fail to satisfy the very constraints that define their task. For instance, a depth-conditioned model often produces images whose re-extracted depth disagrees with the input, even though the forward operator–the depth predictor defining the constraint–is available during both training and inference. Existing approaches generally fall into two categories: supervised models that treat the conditioning signal as a static cue and ignore alignment information at inference, and guidance-based methods that consult it through hand-tuned linear updates, typically trading fidelity to the condition against the plausibility of the generated sample. We argue that the fundamental gap in both paradigms is that the model is never trained to utilize its own alignment error. We introduce FlowBender, a closed-loop framework that treats this error as a first-class input, training the network to learn a correction policy conditioned on inference-time feedback. At each step, an unguided look-ahead pass estimates the clean signal, a task-specific deviation is computed via the forward operator, and a refinement pass consumes this signal to produce a corrected velocity. We propose several variants of FlowBender, including a gradient-based formulation for differentiable operators and a zero-order variant for non-differentiable settings such as JPEG compression. For efficient sampling, we introduce a prior-step shortcut that enables closed-loop correction at a minimal additional computational cost. Across image-to-image translation, restoration, and 3D mesh texturing, FlowBender consistently outperforms standard supervised baselines, alignment-loss-augmented training, and state-of-the-art inference-time guidance, improving fidelity and plausibility simultaneously rather than trading them against each other. Project page: https://flow-bender.github.io/

02.
arXiv (CS.CV) 2026-06-16

G2IA: Geometry-Guided Instance-Aware Retrieval and Refinement for Cross-Modal Place Recognition

Cross-modal place recognition (CMPR) enables camera-only robots to localize against pre-built LiDAR maps in autonomous navigation scenarios. This image-to-point-cloud setting is challenged by two coupled ambiguities: the modality gap between perspective RGB appearance and sparse metric geometry, and perceptual aliasing among urban places with similar roads, facades, intersections, and object arrangements. Instead of treating CMPR as a single global descriptor matching problem, we argue that reliable retrieval requires both geometry-aware representation alignment and fine-grained candidate verification. In this paper, we propose G2IA, a geometry-guided instance-aware framework for image-to-point-cloud place recognition. In the retrieval stage, visual geometry priors from VGGT and instance features are integrated to construct place descriptors that are more compatible with LiDAR-derived map representations. In the refinement stage, the retrieved candidates are re-ranked by explicitly verifying whether local instance shapes and their relative spatial layouts are consistent across modalities. Experiments on public benchmarks demonstrate that G2IA consistently improves image-to-point-cloud place recognition under different localization thresholds, and exhibits strong cross-dataset generalization.

03.
Nature (Science) 2026-06-17

The ancestors of eukaryotic cells contained a mix of genes from various microbes

Authors: Unknown Author

Reconstruction of the ancestral gene repertoire of eukaryotic cells reveals traces of a series of close, long-term interactions with diverse microorganisms, and a role of viruses in gene exchange. The findings challenge the view that eukaryotic cells evolved from a simple merger of just two organisms. A series of gene-transfer events might have taken place in complex microbial communities.

04.
medRxiv (Medicine) 2026-06-15

GLLaucoMed: A Secure LLM-Powered Agentic Workflow for Automated Medication Extraction from Free-Text Glaucoma Clinical Notes

Purpose: To evaluate the efficacy of large language models (LLMs) in extracting medication-related information from glaucoma clinical notes in the electronic health record (EHR). Design: Cross-sectional. Subjects: 1,250 subjects in the Bascom Palmer Ophthalmic Repository. Methods: Extracted clinical notes from glaucoma-related encounters between 2014 and 2024 were labeled by two glaucoma specialists with a third serving as an adjudicator. Graders were asked to label current topical medications (CTM), proposed changes to topical medications ({Delta}TM), current oral medications (COM), and proposed changes to oral medications ({Delta}OM) in a structured fashion. The dataset was split into development (10%), validation (10%), and test (80%) sets stratified by clinician. Development and validation sets were used to engineer and refine prompts, and the held-out test set was used for model assessment. Five LLMs (Claude Opus 4.6, DeepSeek-V3.2, GPT 5.2, Grok 4.1, and Qwen3.6-35B-A3B) were accessed via Microsoft Azure AI Foundry within a HIPAA-compliant environment. Inter-grader agreement was assessed with Gwet AC1. LLM performance was initially assessed in a binary fashion with F1 scores, and the degree of text match among positive cases was evaluated using exact match accuracy and Jaccard Index (JI). Main Outcome Measures: F1 score, exact match accuracy, JI. Results: Gwet AC1 for intergrader agreement was 0.799, 0.888, 0.985, and 0.988 for CTM, {Delta}TM, COM, and {Delta}OM, respectively. F1 scores for CTM were 0.985, 0.971, 0.978, 0.968, and 0.970 for Claude, Deepseek, GPT, Grok, and Qwen, respectively; for {Delta}TM: 0.905, 0.826, 0.897, 0.842, 0.855, respectively; for COM: 0.923, 0.887, 0.899, 0.906, 0.894, respectively; for {Delta}OM: 0.958, 0.815, 0.937, 0.835, 0.940, respectively. Among positive cases, range of exact match accuracies for CTM (N=1354) was 0.730- 0.882 and range of JIs was 0.809-0.918. For {Delta}TM (N=404), exact match accuracy range was 0.619-0.780 and JI range was 0.668-0.827. For COM (N=47), exact match accuracy range was 0.766-0.872 and JI range was 0.765-0.870. For {Delta}OM (N=25), exact match accuracy range was 0.583-0.920 and JI range was 0.583-0.922. Conclusions: The GLLaucoMed pipeline demonstrated high performance in extracting and standardizing medication data from unstructured clinical notes, including both current medications and proposed changes. Claude and GPT exhibited the strongest performance.

05.
arXiv (quant-ph) 2026-06-12

Non-Hermitian skin effect induced by spatial noncommutativity

arXiv:2606.12961v1 Announce Type: new Abstract: In all known schemes for the non-Hermitian skin effect, the non-Hermitian ingredient that drives the skin localization, whether asymmetric hopping or gain and loss, is invariably introduced by hand as an independent model parameter along the skin direction. Here we show that when two spatial coordinates do not commute, the skin effect can break free of this paradigm: a gain-loss potential applied along one coordinate automatically generates non-reciprocity along the other through the coordinate noncommutativity, driving all eigenstates to pile up exponentially at a boundary. We term this phenomenon the noncommutative skin effect. The inverse skin length is proportional to the noncommutativity parameter and is given by an analytic formula, exact in the thermodynamic limit and verified by exact diagonalization of lattice models; the reflection symmetry of the imaginary potential furnishes an exact criterion for the presence or absence of the effect, valid rigorously for finite-size systems. For a sinusoidal imaginary potential, the skin direction of all eigenstates flips collectively at parameter points fixed purely by geometry. Because the flip point is independent of the potential strength, the reversal constitutes a zero-crossing measurement scheme intrinsically robust against systematic errors, from which the noncommutativity parameter can be extracted directly. The qualitative transition of the eigenstates from uniform to exponentially localized renders the effect a nonperturbative probe of spatial noncommutativity, and the Peierls-phase structure of its lattice model is in principle accessible to cold-atom synthetic dimensions, photonic resonators, and topolectrical circuits.

06.
medRxiv (Medicine) 2026-06-11

A global cross-sectional survey of health professionals' interest-confidence gaps in value-based health care implementation: a learning needs assessment

Abstract Objectives Value-Based Health Care (VBHC) increasingly guides health system redesign internationally. Despite the increasing availability of VBHC education, gaps remain between health professionals' conceptual understanding of VBHC and their confidence to implement it in practice. This study assessed perceived learning needs and preferences of healthcare professionals across foundational topics essential to VBHC implementation. Design Cross-sectional online survey study Setting and participants The survey was distributed to the global VBHC community and yielded 518 responses. Most respondents were based in the UK and Ireland (51%) and 65% had more than 10 years of experience in the health sector. Participants represented a variety of professional backgrounds, including clinicians (34%), operational or executive managers and leaders (22%), and life sciences or procurement professionals (13%). Primary and secondary outcome measures Primary outcome measures included self-reported interest and confidence across 15 VBHC domains and the magnitude of the gap between them. Secondary outcomes included perceived implementation challenges and preferred VBHC learning approaches, including prior engagement with VBHC-related learning. Results Respondents identified substantial VBHC implementation challenges, including implementing outcome measurement (62.4%), conflicting priorities (57.7%), and resistance to change (56.8%). Interest in all VBHC domains was high (median >= 80/10), while confidence to implement remained substantially lower across most domains (median

07.
arXiv (CS.LG) 2026-06-15

How Task Structure Limits Multi-Agent Success: An Information-Theoretic Analysis

arXiv:2606.13733v1 Announce Type: cross Abstract: Multi-agent systems (MAS) were expected to overcome the limitation of single-agent systems (SAS) through collaboration. However, under typicality conditions on the task's constraint graph and bounded inter-agent communication, we prove that the success probability of a MAS is closely tied to the connectivity of task constraints, where each agent has limited information-processing capacity. Specifically, the success probability decays exponentially with an information bottleneck that emerges from partitioning the task's constraint graph among agents. We define this quantity as the minimum cut cost $C_{\min}$ of the potential constraint graph of each task. This information-theoretic bound applies to both open systems with external feedback and closed systems without. We validate our theory on both synthetic experiments and real-world empirical data from SWE-bench submissions. From our framework, effective MAS design should incorporate task-inherent constraints alongside engineering optimization, and when $\Cmin$ is high, practitioners should restructure tasks rather than simply scaling agents or communication.

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

The Perils of Agency: How Developers Perceive, Prioritize, and Address Risks in Agentic AI Products

arXiv:2606.15485v1 Announce Type: cross Abstract: Agentic AI systems act autonomously, use tools, adapt to context, and operate in complex real-world environments. However, these same characteristics can create or exacerbate product risks. We studied how industry developers (n=35) perceive, prioritize, and address the risks in their agentic AI products. We found that developers' perceptions of risk were closely tied to the qualities that made the product agentic, such as autonomy, tool use, and usage in a real-world context. Developers prioritized product and business risks before considering downstream societal risks like job displacement and end-user privacy. This prioritization also impacted developers' ability and motivation to mitigate agentic risks. Finally, developers lacked mature controls for containing agentic risks, often relying on constraining the same characteristics that make agents useful: e.g., autonomy and goal complexity. These findings reveal a capability vs. risk control tension in agentic AI development: developers need to address risks that emerge from agentic capabilities, yet they currently have limited support for doing so without constraining agentic functionality.

09.
arXiv (CS.AI) 2026-06-12

Topical Phase Transitions in Artificial Intelligence Research: Large-Scale Evidence and an Early-Warning Signature for Emerging Topics

arXiv:2606.12828v1 Announce Type: new Abstract: Do research topics in artificial intelligence grow gradually, or do they advance through abrupt, detectable jumps? Analyzing 80,814 accepted main-track papers from five premier AI conferences (ACL, CVPR, ICLR, ICML, NeurIPS) spanning 2017 to 2025, we show major AI topics advance through topical phase transitions: remaining marginal for years, then surging across venues within one to three years. Large language models became the dominant cross-venue topic by 2025, diffusion models rose with comparable abruptness, and language-model methods crossed into computer vision via vision-language models, whereas reinforcement learning compounded smoothly, distinguishing genuine phase transitions from ordinary growth. This structure is our primary contribution: a large-scale, cross-venue characterization of how AI research reorganizes. We then ask whether a transition leaves a detectable footprint before it peaks. We define an early-warning signature, four publication-dynamics criteria frozen on 2017-2021 data, and evaluate it out of sample on 2023-2025 transitions, obtaining a precision of 27% and recall of 63% against a 13.5% base rate. Applied to 2025 data, the signature flags reasoning and test-time compute, agentic AI, multimodal LLMs, retrieval-augmented generation, and world models as topics to monitor over 2026-2028. The source code is also publicly available on GitHub at https://github.com/KurbanIntelligenceLab/ai-phase-transitions.

10.
arXiv (CS.CL) 2026-06-18

LLMZero: Discovering Adaptive Training Strategies for RL Post-Training via LLM Agents

RL post-training strategies are dataset-dependent and reveal a recurring empirical pattern: capacity parameters accumulate monotonically across stages, while regularization parameters predominantly oscillate in response to shifting training dynamics. This distinction matters because fixed schedules commit all parameters to fixed trajectories and therefore cannot express the non-stationary exploration-exploitation tradeoffs that regularization must track; the principle provides actionable design rules for multi-stage training. We discover this through LLMZero, a system where LLM agents search over training trajectories via tree search, diagnosing pathologies at each checkpoint and proposing coordinated multi-parameter transitions. Across 4 diverse GRPO tasks, LLMZero discovers strategies that improve over the base model by 9% to 140% relative and over grid search by 6% to 15% relative, consistently outperforming random search and the skill-based agent. The structural principle transfers across tasks, providing an explanation for why discovered strategies take qualitatively different forms yet share similar parameter dynamics.

11.
arXiv (CS.LG) 2026-06-12

Navigating the Safety-Fidelity Trade-off: Massive-Variate Time Series Forecasting for Power Systems via Probabilistic Scenarios

arXiv:2606.13338v1 Announce Type: new Abstract: Probabilistic forecasting models are increasingly deployed on multivariate systems with distinct channel physics and operational constraints, but existing benchmarks evaluate neither property at scale. Public canonical multivariate benchmarks cap out at 2,000 channels, while power-system benchmarks either lack temporal structure or probabilistic evaluation. We introduce PowerPhase, a probabilistic forecasting benchmark built on six transmission grids ranging from 2,000 to 36,964 jointly forecasted channels, more than an order of magnitude beyond popular canonical multivariate benchmarks. Each target trajectory is the output of an AC power-flow solve, and PowerPhase ships with constraint-aware metrics, including Safety_mBrier, NECV, and CVaR-alpha, that complement CRPS and Distortion. Across eight baselines and three seeds, distributional accuracy and constraint satisfaction rank models differently, a trade-off we term safety-fidelity. We further propose PowerForge, a scenario-based quantile forecaster with type-specific decoding heads and a causal bridge between variable groups, which achieves the best average rank on every grid.

12.
arXiv (CS.CL) 2026-06-11

DEFINED: A Data-Efficient Computational Framework for Fine-Grained Creativity Assessment in Debate Scenarios

Human creativity has emerged as a critical competency in the era of large language models. Assessing creativity in complex, open-ended environments is a grand challenge in data mining, currently hindered by a reliance on standardized simple tasks and the scarcity of fine-grained expert data. As an ecologically valid assessment context, debate reflects multiple dimensions of creativity, encompassing both divergent thinking and convergent thinking. Moreover, debate is a data-rich domain, with a large volume of publicly accessible materials. Current mainstream automated scoring methods are poorly suited to complex settings such as debate, and therefore still rely on costly human evaluation. To this end, this paper proposes DEFINED, a data-efficient computational framework for fine-grained creativity assessment in debate scenarios. DEFINED operationalizes debate creativity through a hierarchical eight-dimensional metric system, implemented via a pre-trained autoregressive language model with a hierarchical scoring head that supports both fine-grained and coarse-grained evaluation. Statements and their associated expert scores were obtained from authentic debate competitions, and a constrained data augmentation strategy was employed to address the elite bias inherent in the original data. DEFINED adopts a mixed-granularity training strategy enabling robust learning from limited fine-grained supervision annotated by trained graduate experts. To rigorously validate ecological validity beyond synthetic benchmarks, we incorporate an empirical study with debate-naive participants, utilizing these authentic data to serve as a qualitative case study for mid-to-low proficiency populations. Across our evaluation protocol, our scoring model achieves accurate and stable scoring, outperforming prompt-based large language model evaluators and existing debate scoring methods.

13.
arXiv (CS.AI) 2026-06-17

Timestamp-Aware Spatio-Temporal Graph Contrastive Learning for Network Intrusion Detection

arXiv:2606.17109v1 Announce Type: cross Abstract: Given their effectiveness in modeling the relational structure among network traffic flows, graph neural networks (GNNs) have been widely adopted in network intrusion detection systems (NIDSs). However, most existing GNN-based NIDS approaches focus on the relational structure of traffic flows, and treat them as temporally independent, which limits their ability to cope with evolving attack behaviors. Moreover, their reliance on supervised or semi-supervised learning often restricts generalization to unseen attacks. To address these limitations, we propose a novel self-supervised GNN-based framework. To the best of our knowledge, the proposed model is among the first self-supervised GNN-based NIDS models to explicitly leverage real timestamps, which provides faithful temporal dependencies for representation learning. We first construct a series of temporal graphs from network traffic flows according to their timestamps, and then employ an E-GraphSAGE and LSTM based encoder to fully extract temporal information and spatial dependencies of network traffic, without introducing time-costly attention mechanisms. A multi-view graph contrastive learning (GCL) scheme is introduced, where temporal, spatial, and feature contrasts are jointly performed to capture temporal continuity, preserve structural consistency, and improve the generalization and robustness of the learned representations, respectively. In addition, a gradient-norm-based adaptive weighting strategy is designed to optimize the contrastive loss weights. Experimental results on four representative NIDS datasets with real timestamps demonstrate that our method significantly outperforms existing self-supervised approaches and achieves performance comparable to the supervised state-of-the-art GNN method, while maintaining high computational efficiency.

14.
Nature (Science) 2026-06-17

Analysis of 173,303 exomes and genomes in the Pakistan Genome Resource

Naturally occurring loss-of-function variants in human genes enable drug target discovery because they mimic pharmacological inhibition of proteins. However, the study of these genetic variants is constrained by their rarity. Sequencing of diverse populations, particularly those enriched in familial relatedness, has been postulated to promote discovery of rare genetic variants1–3. Here we present the Pakistan Genome Resource, a South Asian biobank with high familial relatedness comprising 173,303 participants, who collectively carry naturally occurring homozygous loss-of-function variants in 6,476 genes. We describe the genetic architecture of this population, associations between genes and biomarkers, the distribution of loss-of-function variants across molecular pathways, and recall-by-genotype studies of therapeutically relevant genes. The Pakistan Genome Resource expands the catalogue of human genetic variants, provides a comprehensive genetic reference resource for the Pakistani population, and demonstrates the value of studying diverse cohorts to advance human health. The Pakistan Genome Resource compiles biobank data from 173,303 individuals with high familial relatedness, broadening the catalogue of human genetic variation and establishing a population-specific genomic reference for Pakistan.

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

Beyond Runtime Enforcement: Shield Synthesis as Defensibility Analysis for Adversarial Networks

arXiv:2606.13621v1 Announce Type: new Abstract: Shielded reinforcement learning is typically presented as a runtime safety mechanism that compiles temporal-logic specifications into automata restricting an agent's actions. We argue this is the wrong product. The same automata-theoretic machinery – specification compilation, product game construction, attractor computation, and winning-region extraction – is better read as a design-time analytical instrument whose outputs are structural insights about a system rather than runtime constraints on a deployed agent. We instantiate this through a constrained two-player safety game for network defense. The two specifications are enforced asymmetrically: the defender specification defines the unsafe region of the game, whereas the attacker specification restricts the adversary's legal actions during attractor computation. Solving the game yields a defensibility verdict – a formal certificate that a topology-specification pair is or is not defensible – with the associated winning region and shield. Beyond the binary verdict, we derive topology-level metrics from the attractor structure and combine them with post-convergence behavior from shield-constrained adversarial multi-agent reinforcement learning. Together these form a defensibility fingerprint capturing both a network's formal safety properties and its operational behavior under adaptive play. A what-if analysis shows that formal defensibility and operational effectiveness capture distinct aspects of security: small architectural changes can produce large shifts in operational outcomes while leaving formal safety margins nearly unchanged. Shield synthesis is thus most valuable not as a deployment mechanism for safe agents, but as a framework for answering architectural questions about whether, where, and how a system can be defended. The defensibility verdict is the output, not the safe policy.

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

RSTR: Reducing SpatioTemporal Redundancy in Diffusion Transformers

Diffusion Transformers (DiTs) have achieved remarkable success in image generation, yet their deployment is hindered by high computational costs. We identify two sources of redundancy. First, temporal redundancy: Classifier-Free Guidance (CFG) applies costly dual forward passes at every timestep, yet guidance matters only at specific steps, and variable scales at critical steps can compensate for skipping others. Second, spatial redundancy: under variable guidance, different transformer blocks exhibit heterogeneous sensitivity, yet uniform calibration across all blocks wastes computation while failing to address their varying requirements. We present RSTR, the first framework to jointly reduce spatiotemporal redundancy in diffusion transformers. Stage-1 addresses temporal redundancy through evolutionary search, discovering sparse guidance schedules with variable scales. Stage-2 addresses spatial redundancy through adaptive rank allocation, assigning calibration capacities to transformer regions based on their sensitivity. Experiments on DiT-XL/2, PixArt-$\alpha$, FLUX, and state-of-the-art Qwen-Image demonstrate 50%-70% compute savings while maintaining or improving quality. On DiT-XL/2, RSTR achieves 57% savings with 15% FID improvement; on Qwen-Image, 3.43$\times$ speedup with preserved quality.

17.
arXiv (CS.AI) 2026-06-12

Variational Learning for Insertion-based Generation

arXiv:2606.02133v3 Announce Type: replace-cross Abstract: Non-monotonic sequence generation methods, such as masked diffusion models, provide a flexible alternative to left-to-right autoregressive modeling by allowing tokens to be generated in non-fixed and prescribed orders. Despite their practical advantages, most existing non-monotonic models are order-agnostic and rely on a fixed-length grid, limiting their ability to support variable-length generation and adaptive insertion order. In this work, we introduce a probabilistic framework for learning insertion order in variable-length insertion models. We formalize a bijective correspondence between insertion trajectories and permutations, which enables an exact reparameterization of the data likelihood as a sum over permutations. Building on this result, we propose the Insertion Process (IP), a stochastic generative model that jointly learns where to insert, what to insert, and when to terminate, trained via permutation-based variational inference. Unlike prior fixed-canvas approaches, IP natively supports variable-length generation and learns data-driven preferences over insertion orders. Experiments on goal-conditioned planning and molecular string generation demonstrate that learning insertion order improves both modeling quality and generalization in domains without a canonical left-to-right structure.

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

FlowMaps: Modeling Long-Term Multimodal Object Dynamics with Flow Matching

arXiv:2606.20209v1 Announce Type: cross Abstract: Joint spatial and temporal understanding of 3D scenes is a crucial requirement for robots deployed in everyday household environments. Such agents must not only comprehend and navigate spatial layouts, but also reason about how these spaces evolve over time. In particular, humans interact with objects daily, causing them to change position throughout the environment and making it difficult for robots to reliably associate current observations with previously seen objects. However, these interactions are not random: human habits and routines induce spatio-temporally consistent patterns in object locations, which robotic agents can potentially learn and then exploit for downstream tasks such as navigation. To this end, we introduce FlowMaps, a latent flow matching model for estimating multimodal distributions over the future locations of dynamic objects in a continuous 3D space. By learning the implicit dependencies among objects and their temporal evolution, FlowMaps predicts likely changes in object locations conditioned on past human interactions, while supporting generalization across previously unseen environments that share similar object routines. To demonstrate the utility of this method, we deploy FlowMaps in a downstream dynamic Object Navigation task in both simulated and real-world environments. Across more than 600 episodes, FlowMaps outperforms state-of-the-art approaches, showing that modeling object dynamics through continuous, multimodal spatio-temporal distributions improves robotic search and navigation in changing household environments. Code and additional material is available at https://fra-tsuna.github.io/flowmaps/.

20.
medRxiv (Medicine) 2026-06-22

Development of a Novel Risk Prediction Model for Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD): A Longitudinal Study

Background: Interstitial lung disease (ILD) is one of the most common and potentially most devastating extra-articular complication of rheumatoid arthritis (RA) and is associated with substantial morbidity and mortality. However, reliable tools for the early identification of ILD in patients with RA remain limited. This study aimed to identify plasma protein biomarkers of RA-ILD and develop an interpretable machine learning model for risk prediction using data from the UK Biobank. Methods: We first evaluated the association between baseline RA and the risk of incident ILD in the UK Biobank using Cox proportional hazards models. Mendelian randomization analysis was then performed to investigate the potential causal relationship between RA and ILD. Finally, we analyzed 2,920 plasma proteins measured using the Olink platform in 781 eligible RA patients. Proteins associated with ILD risk were identified using Cox proportional hazards models and subsequently used to construct eight machine learning models. Model performance was assessed using the receiver operating characteristic curve (ROC) and decision curve analysis. The best-performing model was further interpreted using Shapley additive explanations (SHAP) to evaluate feature importance. Results: Compared with participants without RA, Patients with baseline RA had a significantly higher risk of developing ILD (Hazard ratio: 4.425, 95% CI: 3.549,5.518). The MR supported a potential causal association between RA and ILD (Odds ratio: 1.227, 95% CI: 1.121,1.343). Among the eight machine learning models, the CatBoost model showed the best performance, achieving an area under the curve (AUC) of 0.884 (95% CI: 0.773,0.996). The SHAP analysis identified LAG3, NPC2, and LAMP3 are the three most important plasma protein predictors of ILD development in patients with RA. Conclusion: Plasma proteomics combined with machine learning may provide a promising approach for identifying biomarkers and predicting ILD risk in patients with RA. LAG3, NPC2, and LAMP3 may serve as candidate biomarkers for RA-ILD and warrant further validation. Keywords: Rheumatoid arthritis, Interstitial lung disease, Mendelian randomization, Machine learning, Plasma proteins.

21.
PLOS Medicine 2026-06-02

Prognostic value of cervical length for spontaneous preterm birth in asymptomatic women with singleton pregnancy: An individual participant data meta-analysis

Authors:

by Kelly Hughes, David Nguyen, Mason Aberoumand, Heather Ford, Erin Clarke, Nuria Banos Lopez, Margaret Dziadosz, Richard Fischer, Renato T. Souza, Jose Guilherme Cecatti, Kelly Orzechowski, Courtney Olson-Chen, Alberto Borges Peixoto, Vorapong Phupong, Joshua Rosenbloom, Moeun Son, Athena Souka, Liu Du, Michael Sean Esplin, Roberta Granese, Simi Gupta, Brenda Kazemier, Lindsay Kindinger, Pihla Kuusela, Jeanine Van der Ven, Omer Weitzner, Evelyn Minis, Alba Farras Llobet, Heather Frey, Rashmi Bagga, Siddhidatri Mishra, Elizabeth Patberg, Philip Bennett, Megan Hall, Andrew Shennan, Shaun Brennecke, Shakila Thangaratinam, Anna Lene Seidler, Ben Willem Mol, Rui Wang Background Spontaneous preterm birth (SPTB) is the leading cause of perinatal and early childhood mortality worldwide. Studies have generally suggested that mid-trimester transvaginal sonographic cervical length

22.
arXiv (quant-ph) 2026-06-17

Optimal Probe State for Phase Estimation Under Covariant Measurement

arXiv:2606.18169v1 Announce Type: new Abstract: We study the optimization of input states for phase estimation under covariant measurements. Building on Holevo's framework, which provides the optimal covariant measurement for a fixed input state, we further optimize over the input state itself. For a general even $2\pi$-periodic cost function with non-negative Fourier coefficients, we derive a necessary and sufficient condition for the optimal input state: Its Fock coefficients are determined, up to arbitrary phases, by the eigenvector corresponding to the largest eigenvalue of a Toeplitz matrix defined by the cost function. This characterization yields an explicit expression for the attainable lower bound of the average cost under optimal covariant measurements and shows that this bound asymptotically approaches zero in the infinite-energy limit. For the specific cost function $W(\theta,\tilde{\theta})=4\sin^2[(\theta-\tilde{\theta})/2]$, we obtain the optimal input state and the corresponding minimum average cost in closed form, demonstrating Heisenberg scaling with respect to the mean photon number.

23.
arXiv (CS.AI) 2026-06-11

Towards an Inferentialist Account of Information Through Proof-theoretic Semantics

arXiv:2605.05368v5 Announce Type: replace-cross Abstract: Information is one of the most widely-discussed concepts of the current era. However, a great deal of insightful work notwithstanding, it is yet to be given wholly convincing logical or mathematical foundations. Without them, we lack adequate reasoning tools for understanding the complex ecosystems of systems upon which the society depends. We seek to rectify this by taking a first step towards developing an inferentialist semantic theory of information. There are three key interacting components. First, conceptual analysis: the metaphysics of information. Dretske expressed the key concepts of information in terms of intentionality, truth, and transmissibility. We replace truth with inferability, and trace the consequences of this replacement. Second, logic: proof-theoretic semantics (P-tS) provides a mathematical-logical realization of inferentialist reasoning. Using P-tS, we develop the first steps towards a mathematical-logical theory of an inferentialist primitive unit of information, the 'inferon'. This proof-theoretic approach counterpoints the model-theoretic view of information articulated in situation theory. Furthermore, we argue that it facilitates addressing all three components of van Benthem and Martinez's categorization of the understandings of information, as range, as correlation, and as code. Our focus is on information-as-correlation. Third, systems: the P-tS tools we develop provide the basis for a mathematical account of distributed systems modelling – a key tool from informatics for understanding the organization of information processing systems. This yields a reasoning-based theory of information flow in models of distributed systems. Overall, we seek to give a conceptually rigorous mathematical-logical account of information and its role within informatics, grounded in inference and reasoning.

24.
PLOS Computational Biology 2026-06-22

Towards modeling phage therapy

by Rob J. de Boer, Robert Schooley, Alan S. Perelson Patients infected with life-threatening multi-drug resistant (MDR) bacteria have been treated with cocktails of bacteriophages. This is a complicated form of personalized medicine as the phages given to a patient have to be selected beforehand on the basis of their lytic capacity of the infecting bacteria. Because bacteria rapidly become resistant, the evolution of resistance to a diverse cocktail of phages is a complicated dynamical process, during which competing bacterial strains replace one another by accumulating several resistance mechanisms, each of which may involve a fitness cost. As a consequence, it is typically not known why a particular phage therapy succeeded or failed, and how one can optimize the composition of the cocktails to maximize the rate of success. To improve upon this, we extend an existing in vivo-calibrated mouse model into a novel mathematical model for the human situation, and include multiple phages infecting multiple bacterial strains, differing in their resistance to each of the phages. We adjust several parameter estimates of the bacterial model to the human situation, and use the model to describe a successful case of phage therapy involving several cocktails, each containing several phages. In the model, treatment success crucially depended on pretreatment resistance levels, and on the diversity and the timing of the cocktails. Once an appropriate cocktail is found, it is less important to further optimize the infection rates of the phages. Resistant bacterial strains expand rapidly when sensitive strains decline, and the higher the infectivity of the phages, the faster resistant strains expand. Because resistance evolves rapidly, it is best to provide a diverse set of phages right from the start of therapy, i.e., to hit hard and early, and create a high genetic barrier to bacterial resistance.

25.
arXiv (CS.LG) 2026-06-16

Learning Policy from a Single Trajectory in Average-Reward Markov Decision Process

arXiv:2606.16729v1 Announce Type: new Abstract: While there is an extensive body of work characterizing the sample complexity of discounted cumulative-reward MDPs, finite sample analyses for average-reward MDPs have been limited, and most existing works rely on restrictive assumptions such as ergodicity or access to a generative model. In this work, we establish the first finite sample complexity guarantees from a single trajectory for weakly communicating average-reward MDPs. To this end, we study the dynamics of a single trajectory in weakly communicating MDPs and based on this analysis, we develop novel model-free methods. Notably, our value-based and policy-based methods provide finite sample complexity guarantees of $\widetilde{O}(1/\varepsilon^2)$ and $\widetilde{O}(1/\varepsilon^4)$ from a single trajectory in weakly communicating MDPs, respectively. Furthermore, we introduce the first model-free method that requires no prior knowledge of problem-dependent quantities for communicating MDPs.