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

Graphical conditional generative modeling for digital twin modeling

arXiv:2606.16219v1 Announce Type: cross Abstract: Digital twin modeling, including control and data assimilation under model uncertainty, often faces an open-ended fidelity problem: adding variables, data streams, and time scales can indefinitely increase model complexity, ultimately producing systems that are difficult to maintain, validate, interpret, and use for stress or safety testing. As an alternative, one can seek parsimonious stochastic surrogate models built only on the variables needed to describe the relevant quantities of interest. We introduce a framework for discovering such variables from observational data by identifying which candidate inputs influence the full conditional law of a target quantity, rather than only its conditional mean. This distinction is essential in stochastic, coarse-grained, or partially observed systems, where dependencies may appear through changes in variability, tail behavior, multimodality, or uncertainty rather than through deterministic functional relationships. The framework couples conditional generative modeling, which learns the conditional distribution of the target given candidate inputs, with Gaussian-process-based analysis of variance (through kernel mode decomposition), which enables iterative pruning of non-influential inputs and interpretable structure discovery. In control settings, the resulting surrogate can be interpreted as a learned Markov decision process: the method identifies not only a transition model, but also the state, action, and memory variables needed to make the learned dynamics effectively Markovian. Across examples involving stochastic dynamical systems, missing variables, PDE control, reinforcement learning, and economic data, the discovered structures yield interpretable stochastic surrogates whose downstream performance is comparable to models trained on the full variable set.

02.
bioRxiv (Bioinfo) 2026-06-11

DModE: An end-to-end framework for Differential Modification and Expression Analysis of Nanopore direct RNA sequencing data

Summary: Nanopore direct RNA sequencing (DRS) enables simultaneous quantification of transcript abundance and RNA modifications from native RNA molecules, providing a unique opportunity to study transcriptional and epitranscriptomic regulation within a single experiment. However, comprehensive analysis of DRS data remains challenging, as existing workflows typically focus on individual processing steps and often require manual integration of multiple software packages for expression analysis, modification detection, statistical testing, and visualization. Furthermore, integrated differential expression and differential RNA modification analysis at both gene and isoform resolution remains poorly supported by current workflows. Here, we present DModE (Differential Modification and Expression Analysis), an end-to-end framework for integrated analysis of Nanopore DRS data. DModE combines an Epi2ME-compatible Nextflow preprocessing workflow with a dedicated Python package for downstream statistical analysis, visualization, and reporting. The framework supports differential gene and isoform expression analysis, differential RNA modification analysis at genome and transcript level, metagene profiling, exploratory epitranscriptomic analyses, and integrated assessment of relationships between expression and modification dynamics. Results are automatically summarized in interactive HTML reports, facilitating reproducible and accessible data interpretation. By integrating transcriptomic and epitranscriptomic analyses within a single framework, DModE substantially simplifies comprehensive DRS data analysis and lowers the barrier for studying RNA modification biology using Nanopore sequencing.

03.
arXiv (CS.AI) 2026-06-15

CADET: Physics-Grounded Causal Auditing and Training-Free Deconfounding of End-to-End Driving Planners

Authors:

arXiv:2606.14438v1 Announce Type: cross Abstract: End-to-end (E2E) autonomous-driving planners trained by imitation are prone to statistical shortcuts: they associate scene elements that merely co-occur with expert actions (a roadside object, a building facade) with driving decisions, rather than the variables that causally determine them. Such causal confusion silently compromises reliability in long-tail scenarios, and it is difficult to detect, because prevailing open-loop metrics (L2 displacement and collision rate) are dominated by ego status and do not indicate whether a planner depends on spurious cues. Existing remedies based on causal-intervention training require retraining large models and cannot audit a planner that is already deployed. We present CADET, a training-free framework that audits, benchmarks, and repairs spurious reliance in pretrained E2E planners without any parameter update.

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

Beyond Native Success: Auditing Deployment-Interface Exposure of CLIP Backdoors

Contrastive Language-Image Pre-training models are widely reused across downstream interfaces, including feature extraction, retrieval, reranking, and selection. Existing CLIP backdoor, however, usually validate attacks on a small attack-native task, leaving unclear whether the same poisoned checkpoint remains exposed, weakens, or becomes not applicable when reused through other interfaces. We introduce DIFE, a Deployment-Interface Footprint Evaluation framework that audits backdoored CLIP checkpoints across deployment interfaces. DIFE makes various evaluations comparable by specifying each interface's component readout, trigger channel, target event, reference condition, and metric. DIFE also introduces effective-footprint diagnosis to identify the reusable CLIP component or component combination that carries exposure and explains where risk transfers. Auditing reproduced CLIP backdoors with DIFE reveals a structured landscape: native success is not a checkpoint-level risk certificate, exposure follows component footprints, text-side poisoning does not yield textual-encoder control, and some coupled attacks remain mechanism-bound. This audit reveals a import gapin existing CLIP backdoors: a textual encoder that itself becomes a reusable carrier of adversarial behavior. We therefore introduce BadTextTower to fill this gap. BadTextTower produces strong text-conditioned retrieval, reranking, and selection exposure while leaving visual-only reuse nearly clean.

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

Amortized Probabilistic Retrieval of Atmospheric CO2 from OCO-2 Spectra Using Deep Learning with Laplace Approximations and Normalizing Flows

arXiv:2606.17413v1 Announce Type: new Abstract: Space-based monitoring of atmospheric carbon dioxide (CO2) is essential for constraining the global carbon budget. NASA's Orbiting Carbon Observatory-2 (OCO-2) estimates column-averaged dry-air mole fractions of CO2 (XCO2) using high-resolution spectra. However, current operational retrieval algorithms are computationally expensive and do not properly quantify uncertainties. We present a novel deep learning framework that addresses these challenges. Due to the difficulties of ground-truth data for real satellite observations, we develop and validate our approach using a high-fidelity simulation dataset. This dataset, created to support OCO-2 uncertainty quantification (UQ), incorporates realistic forward model errors. Our architecture encodes spectral bands using a multi-branch neural network and estimates posteriors of the full CO2 column or desired summaries thereof using two scalable UQ methods: Laplace approximations and normalizing flows. Our approach has five key advantages relative to operational "full-physics" solvers: (1) Amortization: Inference is orders of magnitude faster, enabling real-time processing of massive data streams; (2) Model error robustness: By training on simulations that explicitly include model discrepancies, our method accounts for systematic errors often neglected by standard inversions; (3) Point estimate accuracy: We achieve superior predictive accuracy compared to baseline methods; (4) Improved UQ: The probabilistic outputs yield better-calibrated uncertainty estimates; and (5) Non-Gaussian posteriors: When utilizing normalizing flows, our framework successfully models complex, asymmetric posterior distributions, overcoming the limitations of the Gaussian assumption. These results suggest that simulation-based deep learning is a viable path toward next-generation operational processing systems.

06.
arXiv (CS.CL) 2026-06-17

OPD-Evolver: Cultivating Holistic Agent Evolver via On-Policy Distillation

Memory has become a standard substrate for self-evolving agents, yet retaining experience is not the same as learning how to evolve through it. Existing memory agents can store trajectories, retrieve reflections, or accumulate skills, but often lack the holistic competence to select useful experience, act on it, write reusable knowledge, and maintain a growing repository. We introduce OPD-Evolver, a slow-fast co-evolution framework that cultivates such an agent evolver through on-policy self-distillation. In the fast loop, OPD-Evolver interacts with a four-level memory hierarchy to read, use, write, and maintain experience for rapid test-time evolution. In the slow loop, outcome-calibrated memory attribution and privileged hindsight distill these four abilities into the deployable policy. Across multi-domain benchmarks, OPD-Evolver surpasses memory systems such as ReasoningBank by up to 11.5%, and training-based methods such as Skill0 by ~5.8%. Further analysis shows that OPD-Evolver internalizes high-value experience and memory management, enabling OPD-Evolver-9B to challenge giant counterparts such as Qwen3.5-397B-A17B and Step-3.5-Flash, pointing beyond memory-augmented agents toward genuinely qualified agent evolvers.

07.
bioRxiv (Bioinfo) 2026-06-16

OmicOS: A Comprehensive Omics Ecosystem Infrastructure and Agent System for the AI Era

Biology has accumulated a vast ecosystem of omics methods, but much of this ecosystem remains built for expert humans rather than scientific agents. Methods are scattered across Python packages, R/Bioconductor and CRAN workflows, command-line tools, incompatible data containers and implicit object states, making even routine analyses difficult for an AI system to choose, execute and verify reliably. Here we introduce OmicOS, a comprehensive omics ecosystem infrastructure and agent system that turns OmicVerse V2, an open-source omics community, into an executable foundation for agentic biology. OmicVerse V2 provides the community substrate: scalable AnnDataOOM-compatible rust backends, agent-friendly Python algorithms for single-cell, spatial, bulk and multi-omics analysis, interfaces to single-cell foundation models, and Python-native reconstructions of historically R-centred Bioconductor/CRAN-style workflows. OmicOS makes this substrate actionable by registering analytical functions as state-aware capability contracts, allowing agents to inspect live data objects, select valid methods, execute controlled workflows and record provenance. The result is not a fixed pipeline, but a programmable omics environment in which agents compose real analyses from verified community methods rather than inventing tools. Across external and purpose-built benchmarks, OmicOS ranked first among the evaluated systems, reaching 81.2% on BiomniBench. Adding OmicVerse to a minimal agent improved task completion by up to 34.2 percentage points with qwen-3.6-35b, and controlled ablations showed that the gains came from registry-grounded execution rather than from larger models, documentation retrieval or unrestricted tool exposure. The same infrastructure scaled to atlas-sized data, reproduced R-centred workflows in Python and converted external pathology software into agent-usable skills. In a discovery task starting from a whole-body spatial map and the term Alzheimer disease, OmicOS composed a non-canonical workflow that integrated spatial expression, genetic association, eQTL and colocalization evidence to nominate a colon epithelial risk axis centred on PICALM, CD2AP and CR1. Together, OmicVerse and OmicOS define an open foundation for AI-era omics, showing how a community of biological methods can be transformed into a reliable, extensible and agent-operable system for discovery.

08.
arXiv (CS.LG) 2026-06-15

Operator Calculus for Population-Based Optimization: A Mean-Field Convergence Theory

arXiv:2606.14289v1 Announce Type: cross Abstract: Population-based and distributional optimization methods, from evolution strategies and consensus-based optimization to covariance-matrix adaptation and stochastic gradient methods viewed as distributional dynamics, are widely used for nonconvex or black-box problems, yet their convergence analyses remain fragmented across algorithm-specific techniques. We introduce an operator calculus in which a broad class of such methods, after choosing an appropriate state space and, where necessary, augmenting the state by memory or strategy variables, is described as a composition of three elementary operators (mutation, selection, and recombination) acting on probability measures. Under explicit stability and regularity conditions, the composite operator admits a pre-generator whose continuous-time limit is a transport-reaction-jump (TRJ) PDE that preserves the operator splitting. On this foundation we establish a modular Lyapunov principle. If a state-space Lyapunov function both dissipates under the full generator and controls the relevant search-space gauges, then the state-space Lyapunov functional and the induced search errors decay exponentially. The additive generator structure allows dissipation estimates to be assembled operator by operator, providing a toolkit for certifying convergence of composite mean-field algorithms.

09.
Nature Biotechnology 2026-06-08

Single-cell spatial pharmacobiology for imaging antibody-based therapies in solid tumors

Authors: Unknown Author

We have developed single-cell spatial pharmacobiology (SSP), which combines in situ imaging of a systemically infused fluorescent therapeutic antibody with high-plex spatial proteomics. Applied to head and neck and pancreatic tumors from patients treated in phase 1 trials, SSP revealed marked spatial heterogeneity in antibody delivery and target engagement, which was shaped by conserved stromal barriers.

10.
medRxiv (Medicine) 2026-06-15

Multi-domain AD risk burden and plasma biomarkers in cognitively unimpaired adults

Introduction: Alzheimer's disease (AD) pathology accumulates decades before symptom onset, yet how the cumulative effect of genetic, familial, and modifiable lifestyle risk burden jointly affects plasma biomarker levels and trajectories in cognitively unimpaired older adults remains unknown. Methods: We analyzed data from 261 participants in the PREVENT-AD cohort. A composite risk score integrating APOE e4 status, polygenic score, family history, and modifiable/lifestyle risk was examined against six plasma biomarkers using linear regression and linear mixed-effects models. Results: APOE e4 was the strongest predictor of plasma biomarker levels. Higher composite risk burden was associated with elevated ptau181, ptau217, ptau217/Ab42, and GFAP levels, and lower Ab42/40 levels. A higher risk burden was predictive of accelerated ptau181 accumulation. Discussion: Cumulative AD risk burden is broadly associated with plasma biomarker levels and specifically predicts accelerated ptau181 accumulation in cognitively unimpaired older adults, supporting structured composite risk profiling as a framework for AD risk stratification.

11.
medRxiv (Medicine) 2026-06-22

Why drinking episodes escalate differently: Event-level pathways linking hazardous alcohol consumption and sexual risk

Background: Alcohol-involved drinking episodes vary in whether they involve hazardous alcohol consumption alone, near-miss sexual risk, or sexual risk behavior, but the within-event mechanisms underlying this variability remain unclear. Methods: Guided by syndemic theory, we conducted a qualitative event-level analysis using modified grounded theory among adults in the San Francisco Bay Area who reported hazardous alcohol consumption, defined as an Alcohol Use Disorder Identification Test score [≥]16. In-depth interviews elicited narratives of recent heavy drinking episodes and yielded 64 discrete drinking events across 22 participants. We focused on 35 events with evidence of within-event interaction between biopsychosocial and contextual factors. Using constant comparison, we identified escalation pathways, characterized interruption, and examined how events diverge into three outcomes: hazardous alcohol consumption only, hazardous alcohol consumption with near-miss sexual risk (when risk was plausible but not enacted), and hazardous alcohol consumption with sexual risk behavior. Results: Two primary escalation pathways emerged. Dose-driven escalation involved cumulative alcohol or substance exposure that progressively impaired awareness and self-regulation. Meaning-driven escalation involved prioritizing connection, intimacy, or belonging despite awareness of risk. Time-driven continuation extended exposure across contexts and amplified both pathways. Hazardous alcohol consumption-only events more often followed dose-driven pathways, whereas events involving sexual risk behavior more often followed meaning-driven pathways. Near-miss events occurred across both pathways and illustrated how interruption before the escalation constraint point, when the capacity to modify behavior became reduced, could redirect escalation before sexual risk behavior occurred. Across events with similar levels of intoxication narratives, outcomes diverged according to when the interruption occurred and whether it altered escalation. Conclusion: Hazardous drinking episodes diverge into different outcomes based on escalation pathways and the timing and effectiveness of interruption. Early and effective interruption before the escalation constraint point may represent a key target for harm-reduction strategies to prevent progression to sexual risk behavior.

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

SpheriCity: Designing Trustworthy Conversational AI for Sustainability Decision Support

arXiv:2606.13854v1 Announce Type: cross Abstract: We present SpheriCity, an expert-grounded conversational prototype designed to support trustworthy knowledge sensemaking from sustainability reports. City-level circularity assessment reports contain rich information about materials, infrastructure, and policy interventions, yet their length and heterogeneous structure make cross-document synthesis and comparison difficult for practitioners and researchers working on circular economy initiatives. While large language models (LLM) promise faster knowledge access and synthesis, their opaque reasoning, hallucinations, and lack of source transparency introduce risks for trust and interpretability, and require verification in high-stakes sustainability contexts. SpheriCity addresses these challenges through a provenance-first conversational agent that foregrounds evidence traceability, structured synthesis, and interaction scaffolds to support exploratory querying and cross-document synthesis across sustainability reports. We conducted a formative expert review with six sustainability experts using representative queries spanning cross-city comparison, policy summarization, and recommendation-oriented tasks. Experts evaluated responses across dimensions and provided qualitative reflections on the system's usefulness for sustainability knowledge work. Our results reveal that transparent sourcing, contextual explanation, interpretability, and alignment with expert workflow strongly shape expert trust and judgments of system usefulness. This work contributes (1) a conversational prototype for sustainability knowledge sensemaking, (2) an expert-grounded evaluation framework for assessing AI responses in high-stakes knowledge domains, and (3) design insights into how provenance, uncertainty communication, and integration in workflow influence expert users' trust in AI assistance for sustainability decision support.

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

Semantics-Enhanced Retrieval-Augmented Time Series Forecasting

arXiv:2606.14941v1 Announce Type: new Abstract: Time series forecasting models often benefit from historical patterns. Inspired by Retrieval-Augmented Generation (RAG), recent research explored retrieving relevant historical time series segments to enhance forecasting. However, relying solely on time series similarity is often insufficient for retrieval under non-stationarity. To address this, we propose a multimodal approach: a Semantics-Enhanced Retrieval-Augmented Time Series Forecasting framework, SERAF. Unlike mainstream approaches that depend only on time series similarity, SERAF conducts dual retrieval over the time series and their self-generated textual descriptions. It retrieves two complementary sets of historical patterns and corresponding futures, which are selectively and jointly used to guide future predictions. Experiments across seven real-world datasets demonstrate the effectiveness of SERAF in bridging numerical and semantic views of time series compared with state-of-the-art baselines.

14.
arXiv (CS.CL) 2026-06-16

Less is More: Improving LLM Reasoning with Minimal Test-Time Intervention

Recent progress in large language models (LLMs) has focused on test-time scaling to improve reasoning via increased inference computation, but often at the cost of efficiency. We revisit test-time behavior and uncover a simple yet underexplored phenomenon: reasoning uncertainty is highly localized-only a small subset of high-entropy tokens dominantly affects output correctness. Motivated by this, we propose Minimal Test-Time Intervention (MTI), a training-free framework that enhances reasoning accuracy and stability with minimal overhead. MTI includes: (i) Selective CFG intervention, applying classifier-free guidance only at uncertain positions; and (ii) Lightweight negative-prompt guidance, reusing the main model's KV cache to approximate unconditional decoding efficiently. MTI yields consistent gains across general, coding, and STEM tasks-e.g., +9.28% average improvement on six benchmarks for DeepSeek-R1-7B and +11.25% on AIME2024 using Ling-mini-2.0-while remaining highly efficient.

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

On the Reliability of Cue Conflict and Beyond

Understanding how neural networks rely on visual cues offers a human-interpretable view of their internal decision processes. The cue-conflict benchmark has been influential in probing shape-texture preference and in motivating the insight that stronger, human-like shape bias is often associated with improved in-domain performance. However, we find that the current stylization-based instantiation can yield unstable and ambiguous bias estimates. Specifically, stylization may not reliably instantiate perceptually valid and separable cues nor control their relative informativeness, ratio-based bias can obscure absolute cue sensitivity, and restricting evaluation to preselected classes can distort model predictions by ignoring the full decision space. Together, these factors can confound preference with cue validity, cue balance, and recognizability artifacts. We introduce REFINED-BIAS, an integrated dataset and evaluation framework for reliable and interpretable shape-texture bias diagnosis. REFINED-BIAS constructs balanced, human- and model- recognizable cue pairs using explicit definitions of shape and texture, and measures cue-specific sensitivity over the full label space via a ranking-based metric, enabling fairer cross-model comparisons. Across diverse training regimes and architectures, REFINED-BIAS enables fairer cross-model comparison, more faithful diagnosis of shape and texture biases, and clearer empirical conclusions, resolving inconsistencies that prior cue-conflict evaluations could not reliably disambiguate.

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

Navigating Distribution Shifts in Medical Image Analysis: A Survey

Medical Image Analysis (MedIA) has become indispensable in modern healthcare, enhancing clinical diagnostics and personalized treatment. Despite the remarkable advancements supported by deep learning (DL) technologies, their practical deployment faces challenges posed by distribution shifts, where models trained on specific datasets underperform on others from varying hospitals, or patient populations. To address this issue, researchers have been actively developing strategies to increase the adaptability of DL models, enabling their effective use in unfamiliar environments. This paper systematically reviews approaches that apply DL techniques to MedIA systems affected by distribution shifts. Rather than organizing existing methods by technical characteristics, we explicitly bridge real-world clinical constraints – such as limited data accessibility, strict privacy requirements, and heterogeneous collaboration protocols – with the technical paradigms able to address them. By establishing this connection between operational constraints and methodological evolution, we categorize existing works into Joint Training, Federated Learning, Fine-tuning, and Domain Generalization, each aligned with specific healthcare scenarios. Beyond this taxonomy, our empirical analysis suggests that, as domain information becomes progressively less accessible across these paradigms, performance improvements become increasingly constrained, and further uncovers a gradual shift in methodological focus from explicit distribution alignment toward uncertainty-aware modeling, ultimately pointing to the need for more deployability-aware design in real-world MedIA.

17.
PLOS Computational Biology 2026-06-11

A zero-parameter first-principles gate framework for full-length TP53 missense variant interpretation

by Masamichi Iizumi Missense variant interpretation often achieves useful predictive performance but remains mechanistically opaque, particularly in proteins that combine structured domains with intrinsically disordered regions (IDRs). We developed Gate & Channel, a zero-parameter, first-principles framework for full-length TP53 missense variant analysis in which each prediction is generated by explicit IF-THEN gates derived from physicochemistry, geometry, structural constraints, and polymer physics rather than fitted weights. Variants are evaluated across independent channels representing distinct physical failure modes; a variant is predicted disruptive if any gate closes. A second hierarchical layer (“Geta”) encodes physically grounded post-closure exceptions, allowing sensitivity and specificity to be improved on disjoint variant populations. The v18 framework consists of 12 channels and 2 Getas spanning structured domains and IDRs, capturing DNA-contact disruption, Zn coordination, burial-dependent packing, secondary-structure compatibility, post-translational modification chemistry, short linear motif disruption (including a multi-partner coupled-folding face), proline-directed kinase recognition, and IDR-specific proline and glycine backbone constraints. Across 1,369 TP53 missense variants, the framework achieved 84.5% sensitivity and 89.1% positive predictive value, with 90.9% sensitivity preserved in the DNA-binding core and all 9/9 hotspot mutations captured. A post hoc audit of discordant IDR calls indicated that many apparent false positives had plausible molecular rationales, consistent with a distinction between molecular mechanism disruption and clinical penetrance. Applied to KRAS, TDP-43, and BRCA1, the same channels capture the dominant pathogenic mechanisms in each protein as a proof of principle, while residual missed variants name specific gates yet to be written. The framework is distributed as the open-source Python package pathogenicity-gates (v0.5.1, MIT). These results show that a substantial fraction of full-length TP53 missense variation can be resolved through explicit, auditable physical gates that carry meaning beyond TP53, with each remaining failure naming the next rule to be written.

18.
arXiv (CS.CV) 2026-06-12

GRIP: Feedback-Guided Prompt Retrieval for Large Multimodal Models

In-Context Learning (ICL) has become a powerful mechanism for adapting Large Language Models (LLMs) to new tasks without fine-tuning. Extending this concept to Large Multimodal Models (LMMs), Multimodal In-Context Learning (M-ICL) relies on retrieving relevant examples, such as images, captions, or question-answer pairs, to guide predictions across tasks like classification, captioning, and visual question answering (VQA). Most existing approaches select in-context examples based on feature-space similarity, assuming that semantically similar samples provide the most useful context. However, our systematic analysis reveals that this assumption does not always hold: visually similar examples are not necessarily those that most effectively enhance in-context learning performance. To address this, we propose the Guided Retrieval of In-context Prompts (GRIP), a learnable vision-only retrieval framework that leverages feedback from LMMs to identify examples that truly improve model predictions. GRIP learns to distinguish beneficial from detrimental in-context examples through contrastive training, refining retrieval beyond pure similarity. Across three multimodal tasks, namely classification, captioning, and VQA, GRIP improves consistently over similarity-based retrieval on Qwen2.5-VL-7B, with its strongest gains in classification on Idefics2-8B. Moreover, we demonstrate that retrievers trained with feedback from one open LMM can be transferred to other models without retraining, including closed-source GPT-4o and Gemini, enabling scalable and cost-efficient deployment of M-ICL. Code will be published upon acceptance.

19.
arXiv (CS.CL) 2026-06-16

Multi-Turn Reflective Masking Elicits Reasoning in Mask Diffusion Models

While reasoning on autoregressive (AR) models is often performed by chain-of-thought reasoning and reflection, their refinement of previous outputs still relies on fully sequential generation, even when only local edits are needed. In contrast, the masking mechanism in Mask Diffusion Models (MDMs) naturally supports explicit local edits on previous outputs, allowing selective refinement without discarding previous answers and generating another from scratch. While this property more closely aligns with how humans correct mistakes by iterative local refinement, existing MDMs do not support multi-turn masking and denoising. We propose Reflective Masking (RM), which elicits such an intrinsic reasoning capability in MDMs via lightweight post-training. RM provides a native test-time scaling, where an MDM iteratively revisits and revises its prior outputs based on evolving context. To exploit insights from previous turns like AR reasoning, we further introduce History Reference, a parameter-free mechanism that leverages intermediate denoising states during revision. Our approach requires no architectural changes and is easily applicable to existing MDMs. Across diverse tasks and modalities, including text generation, Sudoku, and image editing, Reflective Masking consistently outperforms standard masking-based baselines and demonstrates strong generality, positioning RM as a fundamental primitive for reasoning on MDMs.

20.
Nature (Science) 2026-06-17

Towards autonomous medical artificial intelligence agents

Authors:

Large language models (LLMs) show great potential for clinical decision-making, yet most applications remain narrow, task-specific chat tools rather than systems integrated into clinical workflows1,2. However, building physician copilots will require models that operate within the electronic health record (EHR), with governed access to patient data and the ability to initiate permitted EHR actions within defined safety constraints. Yet it remains unproven whether such a system can manage patient cases with physician-level performance. Here we show that MIRA (Medical Intelligence for Reasoning and Action), an autonomous artificial intelligence agent operating in a sandboxed EHR environment, can navigate a large clinical action space to obtain patient histories; order and interpret laboratory, imaging and microbiology tests; generate differential diagnoses; and formulate treatment plans such as prescribing medications, scheduling surgical procedures and planning admissions. In simulations on real patient cases spanning multiple diagnoses, MIRA outperformed physicians in diagnostic accuracy and made guideline-concordant, medication-safe and appropriate admission decisions. Compared with previous LLM applications that addressed isolated subtasks or provided free-text advice, these results suggest that an EHR-integrated artificial intelligence agent can turn clinical intent into structured, actionable EHR operations, possibly making it a more effective decision-support partner for physicians. Further work is needed to establish generalization, safety and governance through prospective, real-world studies. A large language model artificial intelligence agent operating in a sandboxed electronic health record system can autonomously take patient histories, order tests, interpret findings, diagnose conditions and propose treatments, outperforming experienced clinicians while adhering to safety standards and clinical guidelines.

21.
arXiv (CS.LG) 2026-06-18

Gaussian Mixture Attention: Linear-Time Sequence Mixing via Probabilistic Latent Routing

arXiv:2606.18283v1 Announce Type: new Abstract: The dense token-to-token interaction pattern of standard dot-product attention remains a central bottleneck in scaling Transformer architectures to long contexts. We introduce Gaussian Mixture Attention (GMA), a probabilistic attention-style sequence mixer that replaces explicit pairwise query–key comparison with routing through $K$ learned Gaussian mixture components. Queries and keys are mapped to posterior responsibility vectors over a shared latent routing space; their overlap defines an implicit responsibility-space affinity, while values are written into and read from a $K$-slot latent memory. By exploiting the associativity of matrix multiplication, GMA avoids materializing the induced $N\times N$ affinity matrix and instead uses two responsibility matrices whose dominant activation storage scales as $\mathcal{O}(NK)$ rather than $\mathcal{O}(N^2)$ for fixed $K$. We formulate bidirectional and causal variants of GMA, provide an end-to-end differentiable parameterization of the Gaussian mixture components, and analyze its responsibility-modulated gradient structure, constrained non-negative low-rank affinity interpretation, and local routing stability. Empirically, GMA exhibits the intended fixed-$K$ linear memory scaling and is competitive with attention-style baselines on long-context classification, while causal GMA improves over tested linear/random-feature attention variants on WikiText-103 but remains behind optimized causal SDPA and Mamba in the current implementation. Analysis of learned responsibilities further shows broad component usage and moderate alignment with surface-form token categories, supporting GMA as a probabilistic, interpretable, fixed-$K$ linear-time attention-style alternative rather than a universal replacement for optimized softmax attention or state-space models.

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

Advanced Machine Learning and Deep Learning Techniques for Enhanced Cattle Identification and Detection: A Comprehensive Review

arXiv:2606.15655v1 Announce Type: new Abstract: The need for effective cattle identification technology is now more acutely felt than ever in maintaining biosecurity, food safety, and supply chain efficacy in livestock management. This paper presents a systematic review of recent research in cattle identification using machine learning and deep learning techniques. The present systematic review measures the effectiveness of traditional and modern cattle identification techniques using studies from major academic databases, where articles were subjected to full-text review. Among these techniques, classical Machine Learning Techniques such as K-Nearest Neighbors and Support Vector Machines have demonstrated good results in cattle identification; however, Deep Learning Techniques, such as Convolutional Neural Networks, Residual Networks, and You Only Look Once, are better in cognition, detection, and identification tasks. Feature extraction relies on common techniques like Local Binary Pattern (LBP), Speeded-Up Robust Features (SURF), and Scale-Invariant Feature Transform (SIFT), while key features commonly used in these studies include muzzle prints and coat patterns. The review highlights key hurdles involving cattle identification, such as the limited number of publicly accessible datasets, issues with data quality susceptible to environmental changes and animal mobility, and high demand for real-time processing ability. The paper aims to inform researchers, policymakers, and stakeholders about implementing scalable, humane, and effective cattle identification systems to achieve sustainable livestock management.

23.
medRxiv (Medicine) 2026-06-10

Assessment of the accuracy of lung lesions diagnosis in adolescents with osteosarcoma using artificial intelligence

Background. Lung metastases in osteosarcoma (OS) are the main cause of the death. The accuracy of the diagnosis of nodules by computed tomography (CT) of the lungs is critically important for determining the disseminated stage of the disease and planning surgical treatment. The use of artificial intelligence (AI) in the search for lung nodules increases the accuracy of diagnosis and reduces the chance of missing metastases. Objective: to evaluate the accuracy of lung nodules diagnosis in adolescents with OS using AI. Methods. A retrospective assessment of CT scans of adolescents with OS was performed. A pathological nodule with an average size of [≥]4 mm was considered a target finding. The diagnostic accuracy of an AI algorithm previously trained on an adult dataset was evaluated, and the number of false positives (FP) and false negatives (FN) was determined. Sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value, negative predictive value, and F1-measure were calculated. Based on the obtained results, the effectiveness of the algorithm was assessed. Results. 248 CT scans of adolescents with OS were evaluated. The following results were obtained: in 5 cases, the AI algorithm showed a FP result (2.02%), in 34 cases, it showed a FN result (13.71%), and in 209 cases, a correct result (both true positive and true negative) (84.27%). The diagnostic accuracy of the algorithm was 0.843 (95% CI 0.794-0.887). The application of the AI algorithm in the practice of an X-ray doctor in a specific clinical task would allow to increase the sensitivity from 0.805 to 0.891, while ensuring an absolute decrease in the number of FN results by 8.59% and a relative decrease by 44%. Conclusion. The obtained results confirm the practical value of the application of the AI algorithm and justify the implementation of AI-assisted systems in the diagnostic protocols for lung metastases in adolescents with OS.

24.
arXiv (CS.AI) 2026-06-16

Beyond Rebalancing: Benchmarking Binary Classifiers Under Class Imbalance Without Rebalancing Techniques

arXiv:2509.07605v2 Announce Type: replace-cross Abstract: Class imbalance poses a significant challenge to supervised classification, particularly in critical domains like medical diagnostics and anomaly detection where minority class instances are rare. While numerous studies have explored rebalancing techniques to address this issue, less attention has been given to evaluating the performance of binary classifiers under imbalance when no such techniques are applied. Therefore, the goal of this study is to assess the performance of binary classifiers "as-is", without performing any explicit rebalancing. Specifically, we systematically evaluate the robustness of a diverse set of binary classifiers across both real-world and synthetic datasets, under progressively reduced minority class sizes, using one-shot and few-shot scenarios as baselines. Our approach also explores varying data complexities through synthetic decision boundary generation to simulate real-world conditions. In addition to standard classifiers, we include experiments using undersampling, oversampling strategies, and one-class classification (OCC) methods to examine their behavior under severe imbalance. The results confirm that classification becomes more difficult as data complexity increases and the minority class size decreases. While traditional classifiers deteriorate under extreme imbalance, advanced models like TabPFN and boosting-based ensembles retain relatively higher performance and better generalization compared to traditional classifiers. Visual interpretability and evaluation metrics further validate these findings. Our work offers valuable guidance on model selection for imbalanced learning, providing insights into classifier robustness without dependence on explicit rebalancing techniques.

25.
medRxiv (Medicine) 2026-06-18

Biomedical Capacity, Governance, and Health Security: A Dominican Republic Research Analysis of Stakeholder Perspectives

The COVID-19 pandemic exposed critical vulnerabilities in globally concentrated biomedical supply chains and accelerated interest in nearshoring and hemispheric health-security strategies. The Dominican Republic, already the third-largest medical device exporter in Latin America, occupies a strategically significant but institutionally constrained position within this realignment. This study evaluates stakeholder perceptions of the principal opportunities and barriers affecting biomedical ecosystem development in the Dominican Republic, with particular attention to governance, workforce capacity, and value-chain upgrading pathways. Methods. A concurrent mixed-methods design was employed, integrating a cross-sectional electronic survey of 142 purposively sampled domain experts (administered September-December 2025) with a qualitative executive consultation with senior government and industry leaders. Survey analyses combined descriptive statistics, one-sample t-tests against the scale neutral midpoint, chi-square goodness-of-fit tests, Friedman non-parametric ranking, Spearman rank correlations, and exploratory linear and logistic multivariable regression. Qualitative responses were analyzed using a framework approach grounded in the Triple Helix model of innovation systems. Results. Perceived government support was significantly below neutral (mean = 2.67, SD = 1.12; p = 0.034). Workforce shortages (83.3%) and weak academia-industry collaboration (71.4%) were the most frequently endorsed barriers ({chi}2(5) = 18.7, p = 0.002). Regulatory modernization (88.1%) and workforce development (85.7%) ranked as the highest-priority policy levers (Friedman p = 0.005). Clinical trials and contract research organization services were the dominant sub-sector priority (76.2%, binomial p < 0.001). In multivariable analysis, perceived government support, talent availability, and confidence in IP protection jointly explained 46% of the variance in sector competitiveness (R2 = 0.46, p < 0.001). Strong majority support existed for a formal public-private biomedical coordination authority (73.8%, p < 0.001).Conclusion. Institutional credibility and advanced human capital–rather than geography or market access–are the perceived binding constraints on the Dominican Republics biomedical trajectory. Regulatory modernization, targeted workforce investment, and the establishment of a national biomedical coordination authority represent the highest-leverage interventions for positioning the country as a hemispheric hub for biomedical manufacturing, clinical research, and health security.