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01.
arXiv (CS.CV) 2026-06-16

HSQ-VLM: A Novel Spatially-Constrained Quadrant Segmentation VLM Model for Explainability in Diabetic Retinopathy

Diabetic Retinopathy (DR) is an aggressive retinal disease and a leading cause of global blindness, yet its clinical management is currently hindered by the black-box nature of diagnostic AI. While deep learning models achieve high classification accuracy, there is a critical lack of explainability methods capable of detailing the exact anatomical landmarks and lesion distributions that lead to a clinical decision for DR. Therefore, we propose HSQ-VLM, a novel quadrant segmentation pipeline on fundus images that utilizes a Landmark-Anchored Cartesian Cross-Attention mechanism to unify visual feature extraction with structured clinical reasoning. Unlike traditional methods that rely on arbitrary image partitioning, our pipeline implements 4-quadrant Topological Latent Partitioning (TLP) to dynamically align retinal features with a fovea-centered coordinate system. This allows the Vision-Language Model to generate natural language reports that quantify pathology with anatomical precision. On a dataset of 3,500 high-resolution fundus images, this innovative methodology achieved a lesion detection sensitivity of 99.6% for hemorrhages and 96.4% for microaneurysms, while demonstrating a significant reduction in boundary-ambiguity errors compared to standard segmentation baselines.

02.
arXiv (CS.AI) 2026-06-11

Quality Adaptive Angular Margin Learning for Respiratory Sound Classification

arXiv:2606.11915v1 Announce Type: cross Abstract: We present a quality-adaptive angular-margin learning framework that improves feature generalization by enforcing intra-class compactness and inter-class separability. Our framework, titled QLung, introduces a no-reference audio quality margin derived from spectral entropy and root-mean-square energy, which adaptively scales angular margins based on recording quality. To this end, we propose a log-scaled angular margin that stabilizes training under severe class imbalance. We also use an angular classifier that normalizes features and class weights, ensuring margin penalties are applied consistently on the unit hypersphere. Our approach improves in-distribution performance on the ICBHI dataset by 2.46\% over the cross-entropy baseline, and most significantly, achieves the strongest out-of-distribution performance on the SPRSound dataset compared to prior state-of-the-art methods. Code is available at https://github.com/RSC-Toolkit/QLung.

03.
PLOS Computational Biology 2026-06-01

BeetleAtlas 2: An enhanced <i>Tribolium castaneum</i> web resource for tissue and developmental transcriptomics allowing refinement of gene predictions

by David P. Leader, Muhammad T. Naseem, Janina L. Rinke, Kenneth Veland Halberg BeetleAtlas is an online resource for tissue- and stage-specific transcriptomics in the red flour beetle, Tribolium castaneum. On updating from the original Tcas5.2 genome assembly to the more recent improved icTriCast1.1 genome assembly it became evident that there were major discrepancies between the gene models of the two genome annotations in use: the OGS3 and the NCBI gene sets. As neither was clearly superior we implemented a new design in BeetleAtlas 2 (beetleatlas.org) comprising two parallel ‘modes’ — one incorporating results using the NCBI gene models and a second incorporating those using the OGS3 gene models. This allows direct comparison where equivalent gene models exist: 50–57% of cases. To aid resolution of discrepancies between the two gene model sets and verification of results, gene models are linked to a custom visualization of RNA-seq read coverage of the genome in the UCSC Genome Browser. This displays reads from 22 tissues and life stages superimposed on the icTriCast1.1 genome assembly. Reference tracks show the NCBI gene models, the OGS3 gene models after translation of their coordinates from the Tcas5.2 assembly, and 1050 discontinued NCBI gene models from the previous assembly after a similar transfer of coordinates. We document various situations in which distinct patterns of expression of the tissues can be used to confirm and extend correlations between the two gene sets, resolve discrepancies between them, make corrections and identify putative genes or exons absent from the current gene sets. BeetleAtlas 2 allows those involved in Tribolium research to avoid the pitfalls inherent in incorrect gene models when planning experiments on specific genes and interpreting the results. It also demonstrates how BeetleAtlas 2 might play an important role in establishing a revised gene set for Tribolium castaneum in the future.

04.
arXiv (CS.LG) 2026-06-17

Domain-Validity-Gated Metamorphic Testing of Scientific ML Surrogates

arXiv:2606.17529v1 Announce Type: cross Abstract: Scientific machine-learning (SciML) surrogates approximate expensive simulations, but exact expected outputs for arbitrary inputs are unavailable (the oracle problem). Metamorphic testing checks relations across executions, yet a candidate relation is not automatically valid: its preconditions, output mapping, and the numerical floor of the scoring operator determine whether a violation is meaningful. We study how candidate metamorphic relations (MRs) can be screened for domain validity and turned into executable, oracle-free test assets for SciML surrogates. We propose (i) a domain-validity rubric that admits a candidate only when its tolerance dominates the operator's numerical floor and its preconditions hold; (ii) an MR-card executable-asset format recording source cases, transformations, metrics, tolerances, and typed relation-level verdicts; and (iii) a case-study protocol on MeshGraphNets cylinder-flow surrogates, with a claim ledger binding every result to a tracked artifact. On a MeshGraphNets checkpoint, node permutation holds to machine precision, mirror-y is a bounded out-of-distribution stress finding rather than an exact symmetry, and absolute conservation stays deferred while a reference-relative guard passes. The same readings hold across held-out trajectories, a checkpoint roster, three further architectures, and PhysicsNeMo. On a second CFD task (compressible airfoil) the predicate instead rejects incompressible continuity on physical grounds, showing it reasons about domain validity rather than running a fixed checklist. On a second PDE family, FNO Burgers and heat surrogates run full admit/reject/execute verdicts. The evidence spans two CFD tasks and a second PDE family, supporting a validity-aware bridge from candidate MRs to auditable SciML test assets that separates model-level violations from out-of-domain applications.

05.
arXiv (CS.AI) 2026-06-17

Agentic World Modeling: Foundations, Capabilities, Laws, and Beyond

arXiv:2604.22748v3 Announce Type: replace Abstract: As AI systems move from generating text to accomplishing goals through sustained interaction, the ability to model environment dynamics becomes a central bottleneck. Agents that manipulate objects, navigate software, coordinate with others, or design experiments require predictive environment models, yet the term world model carries different meanings across research communities. We introduce a "levels x laws" taxonomy organized along two axes. The first defines three capability levels: L1 Predictor, which learns one-step local transition operators; L2 Simulator, which composes them into multi-step, action-conditioned rollouts that respect domain laws; and L3 Evolver, which autonomously revises its own model when predictions fail against new evidence. The second identifies four governing-law regimes: physical, digital, social, and scientific. These regimes determine what constraints a world model must satisfy and where it is most likely to fail. Using this framework, we synthesize over 400 works and summarize more than 100 representative systems spanning model-based reinforcement learning, video generation, web and GUI agents, multi-agent social simulation, and AI-driven scientific discovery. We analyze methods, failure modes, and evaluation practices across level-regime pairs, propose decision-centric evaluation principles and a minimal reproducible evaluation package, and outline architectural guidance, open problems, and governance challenges. The resulting roadmap connects previously isolated communities and charts a path from passive next-step prediction toward world models that can simulate, and ultimately reshape, the environments in which agents operate. Code and resources are available at: https://github.com/matrix-agent/awesome-agentic-world-modeling.

06.
bioRxiv (Bioinfo) 2026-06-11

Revealing trajectories of multi-modal voxel-level changes in neurodegenerative diseases using latent event mapping

Neurodegenerative diseases are driven by pathological mechanisms that can be indirectly measured in vivo using multi-modal neuroimaging. However, current computational methods that aim to reconstruct trajectories of voxel-level changes in the brain are either not computationally scalable or fully interpretable, limiting their ability to reveal associations between disease progression and underlying mechanisms. Here we introduce Latent Event Mapping (LEMING), a generative unsupervised modelling technique that learns a latent map of disease events along a common pseudo-timeline of events. We apply LEMING to amyloid PET and structural MRI data from the Alzheimer's Disease Neuroimaging Initiative to reveal the first voxel-level trajectories of events in Alzheimer's disease. Notably, we show how LEMING can provide new insights into progression-dependent disease mechanisms. We find that acetylcholine receptor density is significantly positively associated with both late-stage amyloid and atrophy events, suggesting that either these receptors are targeted later in disease progression, or that amyloid does not play an active role. This has strong implications for therapeutics that target acetylcholine receptors, particularly for early-stage intervention strategies.

07.
arXiv (CS.AI) 2026-06-17

Learning Fair Pareto-Optimal Policies in Multi-Objective Reinforcement Learning

arXiv:2606.18111v1 Announce Type: cross Abstract: Fairness is an important aspect of decision-making in multi-objective reinforcement learning (MORL), where policies must ensure both optimality and equity across multiple, potentially conflicting objectives. While single-policy MORL methods can learn fair policies for fixed user preferences using welfare functions such as the generalized Gini welfare function (GGF), they fail to provide the diverse set of policies necessary for dynamic or unknown user preferences. To address this limitation, we formalize the fair optimization problem in multi-policy MORL, where the goal is to learn a set of Pareto-optimal policies that ensure fairness across all possible user preferences. Our key technical contributions are threefold: (1) We show that for concave, piecewise-linear welfare functions (e.g., GGF), fair policies remain in the convex coverage set (CCS), which is an approximated Pareto front for linear scalarization. (2) We demonstrate that non-stationary policies, augmented with accrued reward histories, and stochastic policies improve fairness by dynamically adapting to historical inequities. (3) We propose three novel algorithms, which include integrating GGF with multi-policy multi-objective Q-Learning (MOQL), state-augmented multi-policy MOQL for learning non-statoinary policies, and its novel extension for learning stochastic policies. We evaluate our algorithms across various domains and compare our methods against the state-of-the-art MORL baselines. The empirical results show that our methods learn a set of fair policies that accommodate different user preferences.

08.
arXiv (quant-ph) 2026-06-11

Clifford disentanglers for entanglement reduction in molecular electronic structure simulations

arXiv:2606.12056v1 Announce Type: new Abstract: Entanglement is a key bottleneck limiting the efficiency of tensor-network and quantum simulations of molecular electronic structures. Here, we systematically assess and extend Clifford disentanglers as a structure-preserving approach to entanglement reduction: they can modify the entanglement structure of qubit wavefunctions while retaining the Pauli-string form of qubit Hamiltonians. To enable a practical search over Clifford transformations, we classify Clifford operators by their action on the Schmidt spectrum across a bipartition, reducing the two- and four-qubit search spaces to 20 and 91392 representatives, respectively. Embedded in an iterative Clifford-augmented matrix product state framework, these transformations reduce the energy errors at fixed bond dimension for the molecular test cases studied and mitigate the dependence on orbital orderings and fermion-to-qubit mappings. We further show that Clifford disentanglers can also benefit quantum simulations such as the shallow-circuit variational quantum eigensolver calculations. Together, these results establish Clifford disentanglers as a useful structure-preserving entanglement-engineering tool for tensor-network and quantum simulations of molecular electronic structure, while also clarifying their correlation dependence and motivating future developments.

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

FireRed-Image-Edit-1.0 Technical Report

We present FireRed-Image-Edit, a diffusion transformer for instruction-based image editing that achieves state-of-the-art performance through systematic optimization of data curation, training methodology, and evaluation design. We construct a 1.6B-sample training corpus, comprising 900M text-to-image and 700M image editing pairs from diverse sources. After rigorous cleaning, stratification, auto-labeling, and two-stage filtering, we retain over 100M high-quality samples balanced between generation and editing, ensuring strong semantic coverage and instruction alignment. Our multi-stage training pipeline progressively builds editing capability via pre-training, supervised fine-tuning, and reinforcement learning. To improve data efficiency, we introduce a Multi-Condition Aware Bucket Sampler for variable-resolution batching and Stochastic Instruction Alignment with dynamic prompt re-indexing. To stabilize optimization and enhance controllability, we propose Asymmetric Gradient Optimization for DPO, DiffusionNFT with layout-aware OCR rewards for text editing, and a differentiable Consistency Loss for identity preservation. We further establish REDEdit-Bench, a comprehensive benchmark spanning 15 editing categories, including newly introduced beautification and low-level enhancement tasks. Extensive experiments on REDEdit-Bench and public benchmarks (ImgEdit and GEdit) demonstrate competitive or superior performance against both open-source and proprietary systems. To support future research, our code, models, and benchmark suite are publicly available at https://github.com/FireRedTeam/FireRed-Image-Edit/ .

10.
Nature (Science) 2026-06-17

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

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

11.
arXiv (CS.CL) 2026-06-18

LegalWorld: A Life-Cycle Interactive Environment for Legal Agents

Civil litigation is inherently a life-cycle process: what a lawyer drafts on day one constrains what unfolds at trial months later. Yet existing legal benchmarks evaluate isolated subtasks, and prior legal-agent simulators reinitialize each scenario from shared ground truth, leaving cross-stage causal dependencies unmodeled. We present LegalWorld, a life-cycle interactive environment that models Chinese civil litigation as a causally connected state chain of five stages (seven sub-scenarios), grounded in 75,309 paired Chinese civil judgments. We pair it with reusable infrastructure (local memory, global case memory, a Skill/Tool library) that keeps each dispute consistent across its full life cycle. Building on this environment, we construct LongJud-Bench to evaluate agent capability across all five connected stages. 18,992 ratings from 217 legal-background evaluators confirm that LegalWorld trajectories are procedurally faithful and role-consistent; and a capability-level cross-model evaluation reveals sharp divergences that aggregate scores cannot expose, with no single backbone leading across consultation, drafting, and courtroom advocacy. Detailed resources will be released publicly.

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

VeriGeo: Controllable Geometry Question Generation with Numerical and Analytical Verification

arXiv:2606.14176v1 Announce Type: new Abstract: Geometry problem generation is useful for AI-assisted education and multimodal mathematical reasoning, but reliable synthesis remains difficult because the problem statement, diagram, constraints, and solution should be mutually consistent. Existing methods often trade off controllability and reliability: seed-based rewriting is flexible but weakly verifiable, whereas diagram-first construction improves validity but is less suited to arbitrary user-specified constraints. We introduce VeriGeo, a controllable geometry generation framework grounded in executable reasoning traces. Given user constraints such as target concepts and difficulty, an Author agent generates a problem and diagram, and a Solver agent produces a proof-aligned solution. Both agents use a shared action sequence that connects natural language, diagrams, geometric constraints, and proof steps into a verifiable representation. A three-stage pipeline checks numerical consistency, analytical realizability, and global consistency, using verification-guided reflection to repair recoverable failures and reject unrecoverable ones. Across five LLM backbones, raw generations frequently fail these checks, while VeriGeo repairs a substantial fraction of the invalid attempts. Supervised fine-tuning on 8.7k examples generated by VeriGeo achieves the best reported GeoQA performance among end-to-end multimodal LLM-based solvers, and obtains strong results on PGPS9K and MathVista-GPS, demonstrating the effectiveness of verified synthetic data for improving multimodal geometry reasoning.

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

Open-World Video Segmentation

While video segmentation has advanced rapidly on short clips and closed-set benchmarks, open-world video segmentation remains largely unexplored. The challenge is twofold: (1) existing methods are not designed to support object discovery and identity maintenance in long videos of dynamic ego-motion, and (2) existing evaluation protocols rely on a rigid 1:1 matching that unfairly penalizes semantically valid predictions with mismatched granularity. To address both gaps, we introduce Savvy, a practical and strong system for zero-shot open-world long-horizon video segmentation. Savvy combines hierarchical mask discovery, deferred admission, and track consolidation to support persistent object discovery, safe track promotion, and stable long-range identity maintenance. We further propose OGA, a granularity-aware evaluation suite for open-world video segmentation. Built on a Granularity-Agnostic (GA) matching protocol, OGA relaxes conventional 1:1 matching to an n:1 mapping, but still enforces temporal rigor by detecting support discontinuities through sever points and scoring each reference object through its dominant coherent fragment. This prevents fragmented or flickering support from being over-rewarded while enabling GA-adapted metrics and structural diagnostics: identity persistence (IP), and identity concentration (IC). On VIPSeg, we show that standard 1:1 evaluation substantially underestimates open-world methods, whereas GA evaluation recovers much of their suppressed performance. On the more realistic long-horizon benchmarks: ScanNet and HM3D, Savvy consistently outperforms strong baselines across both classical and proposed metrics, including STQ, VPQ$_\infty$, IP and IC. Together, these results establish a practical benchmark and a strong baseline for open-world long-horizon video segmentation.

14.
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.

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

Quantile Transfer for Reliable Operating Point Selection in Visual Place Recognition

Visual Place Recognition (VPR) is a key component for localisation in Global Navigation Satellite System (GNSS)-denied environments, but its performance critically depends on selecting an image matching threshold (operating point) that balances precision and recall. Thresholds are typically hand-tuned offline for a specific environment and fixed during deployment, leading to degraded performance under environmental change. We propose a method that automatically selects the operating point of a VPR system to maximise recall at 100% precision. The method uses a small calibration traversal with known correspondences and transfers thresholds to deployment via quantile normalisation of similarity score distributions. This quantile transfer ensures that thresholds remain stable across calibration sizes and query subsets. Experiments with seven state-of-the-art VPR techniques across five benchmark datasets demonstrate that our proposed approach consistently outperforms existing baselines, enabling the underlying VPR technique to operate at 100% precision in approximately twice as many deployment scenarios (median improvement), while retrieving up to 29% more correct matches at that precision. The method eliminates manual tuning by adapting to new environments and generalising across operating conditions. Our code is available at https://github.com/DhyeyR-007/Quantile-Transfer-for-Reliable-VPR.

16.
bioRxiv (Bioinfo) 2026-06-18

Bioinf-Farma: supervised integration of epitope prediction and recombinant protein developability for automated vaccine candidate prioritization

Vaccine antigen discovery requires prioritizing protein candidates according to both immunogenic potential and recombinant expression feasibility. These properties are typically evaluated using separate computational tools, requiring researchers to integrate heterogeneous outputs through ad hoc workflows. Here, we present BIOINF-farma, a modular platform integrating epitope prediction and developability assessment for rational antigen selection within a unified environment. Candidates can be submitted as amino acid sequences or three-dimensional structures. When experimental structures are unavailable, BIOINF-farma automatically searches for models in AlphaFold DB or performs structure prediction using Boltz-2, ensuring a standardized structural representation for downstream analyses. Antigenicity is quantified by combining structure-based conformational epitope signals (MLCE/REBELOT-BEPPE) and sequence-based linear epitope propensity scores (BepiPred 3.0) into a protein-level Antigenicity Score, with a classification threshold optimized on a manually curated validation dataset. Developability is evaluated through two supervised Random Forest meta-learners that integrate three solubility predictors (DeepSoluE, SoluProt, Protein-Sol) and three thermal stability predictors (TemStaPro, ProLaTherm, BertThermo), whose outputs are combined into an Expression Efficiency Score (EES). By integrating complementary predictive signals, the meta-learning framework achieves greater accuracy and robustness than individual predictors while maintaining performance across a broad range of sequence identities. The Antigenicity Score effectively discriminates antigenic from non-antigenic proteins with a large effect size, whereas EES successfully distinguishes soluble from insoluble outcomes on an independent panel of recombinant proteins expressed in Escherichia coli. BIOINF-farma jointly assesses antigenicity and expression feasibility within a single framework. Its modular architecture facilitates the incorporation of future predictive methods, while its web-based interface makes the full pipeline accessible to users without programming expertise, supporting rapid candidate triage in vaccine research and emerging pathogen responses.

17.
Nature Medicine 2026-06-08

Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0–IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60–1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.

18.
arXiv (math.PR) 2026-06-19

Theory of uncertain probability: can we derive the probability density function of uncertain random experiments with continuously changing conditions?

作者:

arXiv:2606.20169v1 Announce Type: new Abstract: This paper aims to explore the formation mechanism of probability distribution in situations where the differences among random experiments are distinguishable, and these differences continue to evolve along with the dynamic changes in conditions and their mechanisms of action. To this end, we are motivated to devise a new theoretical system – theory of uncertain probability (TUP) with Kolmogorov's system and nonlinear theories as special cases. TUP develops a novel model that integrates probability and uncertainty as well as the known and unknown to more accurately depict numerous typical random phenomena under more realistic assumptions, and thus provides appropriate tools for greater variety of real needs. It also allows for pioneering interpretation of the causal mechanisms underlying many important distributional characteristics and incorporation of pathwise property to distribution model.

19.
arXiv (CS.LG) 2026-06-18

Be Your Own Teacher: Steering Protein Language Models via Unsupervised Reward Optimization

arXiv:2606.18961v1 Announce Type: new Abstract: Protein language models (PLMs) have emerged as powerful tools for controllable biomolecular design, yet their post-training adaptation typically relies on costly wet-lab validation or curated preference datasets. To overcome this supervision bottleneck, we introduce unsupervised reward optimization of PLMs, a comprehensive framework for steerable protein generation without ground-truth labels. Our key insight is that task-agnostic rewards, which combine intrinsic model uncertainty with extrinsic semantic consistency informed by protein representation models, exhibit strong correlation with controllability measures across base models and temperature regimes. Building upon this discovery, we propose two offline algorithms: Soft Reward Optimization (SRO) and Binarized Reward Optimization (BRO), which effectively maximize the classical RLHF objective induced by these proxy rewards. Extensive experiments on compositional out-of-distribution prompts demonstrate that both methods significantly outperform competitive baselines (DPO, KTO), while approaching oracle performance across multiple sampling temperatures, model scales and protein families. Moreover, PLMs fine-tuned with unsupervised rewards can achieve consistently higher coverage compared to their base model in pass@k evaluations. By enabling self-improvement of PLMs through their own generated experience, our framework provides a scalable pathway toward controllable biomolecular design in settings where labeled preferences or experimental feedback are scarce or unavailable.

20.
bioRxiv (Bioinfo) 2026-06-13

Virus-human protein-protein interactions predict viral phenotypes

Viral phenotypes such as host and tissue tropism are critical determinants of viral infection and transmission. Inferring viral phenotypes presents unique challenges compared to cellular organisms, as viruses rely entirely on host machinery for replication and survival. Current methods for predicting viral phenotypes mainly rely on viral genomic data, often overlooking host-related information. Here, we evaluated the utility of predicted virus-human protein-protein interactions (PPIs) in inferring diverse viral phenotypes using machine-learning algorithms. For predicting human infectivity, a PPI-based machine learning model outperformed both virus genomic and protein sequence-based models that used large language model embeddings. It also surpassed previous methods that incorporated both viral and host genomic data. The human proteins identified by the model were significantly enriched in functions related to viral infection and immune response. In predicting various phenotypes of human RNA viruses, PPI-based models performed better than virus sequence-based models in forecasting virulence, human transmissibility and transmission routes, while showing comparable performance to genomic sequence-based models in predicting tissue tropism. Finally, we demonstrated that a PPI-based model could distinguish high-risk HPV genotypes from low-risk ones. Proteins associated with high-risk HPV were involved in apoptosis and immune regulation, whereas those linked to low-risk HPV were enriched in telomere maintenance and DNA repair. Collectively, this study is the first to demonstrate the value of predicted virus-human PPIs in inferring viral phenotypes, thereby enhancing our understanding of the molecular mechanisms underlying these phenotypes. It also provides effective tools for risk assessment of emerging viruses, contributing to improved pandemic preparedness.

21.
bioRxiv (Bioinfo) 2026-06-11

A Deep Hypergraph Learning Model for Predicting Antimicrobial Combination Effects Across Bacterial Targets

Antimicrobial resistance (AMR) creates an urgent need for efficient strategies to identify effective antibacterial combinations. Combination therapy, including antimicrobial peptides (AMPs) paired with conventional antibiotics, is a promising approach, but exhaustive experimental screening across drug pairs and bacterial targets is impractical. This study introduces a hybrid GCN-based hypergraph neural network (HGNN) for predicting antimicrobial-agent combination outcomes against bacterial targets. Each antimicrobial-agent-antimicrobial-agent-bacterium triplet is represented as a ternary hyperedge, enabling the model to learn context-dependent interaction patterns. The framework integrates SMILES-derived molecular graph embeddings for antimicrobial agents, including conventional antibiotics and AMPs, with taxonomy-derived bacterial representations. The prediction task was formulated as a three-class classification problem: synergy, antagonism, and non-interaction. The non-interaction class included experimentally verified indifferent records and synthetic presumed non-interaction triplets generated by negative sampling. Model development used drug-pair-grouped splitting, five-fold grouped cross-validation within the training/validation partition, and final evaluation on a held-out test set. On the held-out three-class test set, the selected GCN-based HGNN achieved an accuracy of 0.83, weighted F1-score of 0.84, macro F1-score of 0.80, and ROC-AUC of 0.95. Per-class evaluation showed accuracies of 0.80 for synergy, 0.92 for antagonism, and 0.85 for non-interaction. Pair-type analysis showed strong performance across AMP-AMP, AMP-conventional antibiotic, and conventional antibiotic-conventional antibiotic combinations. These findings suggest that hypergraph-based representation learning can support computational prioritization of antimicrobial combinations for experimental follow-up. Further studies will be needed to improve model interpretability and to perform prospective validation of predicted synergistic combinations.

22.
arXiv (CS.CV) 2026-06-16

Classifying by Proxy: Explainable and Reproducible Ensemble of Proxy Tasks for Child Sexual Abuse Imagery Classification

Child Sexual Abuse Imagery (CSAI) classification systems are needed solutions for lessening the psychological impacts often felt by law enforcement agents responsible for evaluating these materials and for efficient removal of these materials from the web. However, due to the nature of the task, researching and developing such systems is not a trivial endeavor. The images are highly sensitive, and the related datasets are under restrictive access regimes, which means most studies in the area are not reproducible or distributable and are therefore hard to compare and validate. More concerning still, most models for this task today lack an aspect often desired by law enforcement agents: explainability. In this paper, we apply an ensemble of Proxy Tasks – tasks that correlate to CSAI classification – yielding improvements in reproducibility, explainability, and security for distribution. This concept is applied for the first time to real CSAI, with a novel selection of relevant Proxy Tasks (selected from the CSAI literature) and training adaptations to the original framework. Our final model achieves competitive results, yielding 91.9% balanced accuracy on the RCPD dataset with the best Proxy Task combination. We furthermore contrast these results with the best-in-class representation learning model, DINO, and show that our ensemble improves accuracy and provides explanations for its classification results, a feature that a single deep learning model can seldom provide.

23.
medRxiv (Medicine) 2026-06-18

Predicting Motor Recovery After Stroke: Utility and Limits of Corticospinal Tract Biomarkers

Background: Corticospinal tract (CST) damage is a major cause of post-stroke motor deficits. However, it remains unclear which estimates of CST damage best predict motor recovery, especially regarding different aspects of motor control. While conventional CST-lesion metrics offer superior feasibility, data-driven machine learning (ML) approaches may better capture patients propensity for task-specific recovery with important implication for their use as future clinical biomarkers. Methods: Providing the first direct longitudinal comparison of these approaches based exclusively on CST-lesion patterns, we evaluated six conventional CST-lesion metrics and a voxel-wise ML approach using clinical MRI data from 127 acute ischemic stroke patients. Acute impairment and outcome (>3 months post-stroke) were assessed for basal and complex motor functions. Conventional CST-lesion metrics and ML were used to predict task-specific motor impairment and outcome. Results: All conventional CST-lesion metrics correlated significantly with both acute impairment and motor outcome across motor domains, with metrics weighted for CST narrowing and tract probability performing best. However, predictive performance for unseen patients was low. ML outperformed conventional markers in predicting acute impairment across motor domains and basal motor outcome, but failed to predict complex motor outcome. Topographically, predictive voxels clustered within and above the posterior limb of the internal capsule, with distinct CST subregions associated with basal versus complex motor impairment, consistent with a task-specific somatotopic organization. Conclusions: The predictive utility of CST biomarkers was task- and timepoint-dependent. While ML may improve predictive performance, complex motor outcome remained difficult to predict, likely reflecting greater reliance on distributed cortical reorganization beyond the CST. By revealing task-specific CST subregions, voxel-wise ML provides an anatomically informed foundation for future predictive models. Such future models should combine CST biomarkers with measures of broader motor network integrity to enable individualized prognosis tailored to specific motor domains and recovery stages.

24.
arXiv (CS.AI) 2026-06-19

Creativity Reconsidered: Generative AI and the Problem of Intentional Agency

arXiv:2601.15797v2 Announce Type: replace Abstract: Many theorists maintain that conscious intentional agency is a necessary condition of creativity. We argue that this requirement, which we call the Intentional Agency Condition (IAC), should be abandoned. We motivate this by highlighting the problems this criterion encounters in the face of recent advances in generative AI, which is ostensibly creative despite being incapable of intentional agency. We present two corpus analyses to illustrate the rapidly increasing tendency of people to predicate creativity to generative AI. In response to this predicament, theorists of creativity have proposed a range of conflicting solutions, which we critically evaluate. We find that none of these satisfyingly resolves the initial predicament, and we therefore propose a novel approach. Our claim is that ascriptions of creativity are dependent on what we call creative ability. This solution explains why intentional agency is important for judgements of creativity, without being a necessary condition. Our approach thereby accommodates AI creativity without dismissing the intuition that perceived intentions are of key importance for ascriptions of creativity.

25.
arXiv (CS.CL) 2026-06-11

ClawEnvKit: Automatic Environment Generation for Claw-Like Agents

Constructing environments for training and evaluating claw-like agents remains a manual, human-intensive process that does not scale. We argue that what is needed is not just a dataset, but an automated pipeline capable of generating diverse, verified environments on demand. To this end, we introduce ClawEnvKit, an autonomous generation pipeline that instantiates this formalism from natural language descriptions. The pipeline comprises three modules: (1) a parser that extracts structured generation parameters from natural language input; (2) a generator that produces the task specification, tool interface, and scoring configuration; and (3) a validator that enforces feasibility, diversity, structural validity, and internal consistency across the generated environments. Using ClawEnvKit, we construct Auto-ClawEval, the first large-scale benchmark for claw-like agents, comprising 1,040 environments across 24 categories. Empirically, Auto-ClawEval matches or exceeds human-curated environments on coherence and clarity at 13,800x lower cost. Evaluated across 4 model families and 8 agent harness frameworks, we find that harness engineering boosts performance by up to 15.7 percentage points over a bare ReAct baseline, completion remains the primary axis of variation with no model saturating the benchmark, and automated generation enables evaluation at a scale previously infeasible. Beyond static benchmarking, ClawEnvKit enables live evaluation: users describe a desired capability in natural language and obtain a verified environment on demand, turning evaluation into a continuous, user-driven process. The same mechanism serves as an on-demand training environment generator, producing task distributions that adapt to an agent's current weaknesses rather than being bounded by existing user logs.