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01.
medRxiv (Medicine) 2026-06-24

Rapid-Response Viral Genome Detection using TWIST Capture and Nanopore Flongle Sequencing

Background: Rapid detection of viral pathogens can be challenging, especially when routine PCR fails. Conventional assays typically detect known viruses which are specifically targeted by the assay, which may result in the failure to identify novel or non-targeted viruses. Broad-range hybrid-capture sequencing enables unbiased detection of viruses, including those that are uncommon or divergent. Methods: We combined the TWIST Comprehensive Viral Research Panel (>3,000 virus species) with Oxford Nanopore Flongle sequencing for easy and quick viral genome detection. The workflow includes random-primed cDNA synthesis, dsDNA conversion, TWIST probe enrichment, and Nanopore sequencing. Performance was evaluated using the QCMD 2024 Viral Metagenomics EQA panel and one clinical sample. Results: All expected targets of the QCMD 2024 Viral Metagenomics EQA panel were detected; eight of thirteen viruses achieved [≥]90% genome coverage. The negative control showed no targeted viral reads. Mixed infections of DNA and RNA viruses were resolved accurately. The workflow from nucleic acid extraction to obtaining sequence data was completed within 3 days.

02.
medRxiv (Medicine) 2026-06-18

Human Intuition vs. Computational Precision: Neurologists, Feature-based Models, and Deep Learning for Stroke Prognosis

Background: Prognostication in large vessel occlusion (LVO) stroke remains challenging. Although several prognostic models exist, their comparison to clinician performance, human-model interaction, and specific sources of human bias remain poorly understood. Methods: Using pre-treatment clinical and CT data from the MR CLEAN trial (n=500), six neurologists predicted three-month modified Rankin Scale (mRS) scores for 40 patients, both unaided and assisted by a validated feature-based model (MR PREDICTS). Human performance was benchmarked against MR PREDICTS and a multimodal, interpretable deep learning (DL) approach using raw imaging data. We explicitly assessed neurologists? ability to estimate model-required imaging features and identified systematic human biases. Models were additionally validated in a larger MR CLEAN trial cohort (n=404). Results: For predicting the full mRS distribution, standalone models achieved good ordinal agreement (MR PREDICTS quadratic weighted kappa (QWK) 0.51 [0.24 to 0.70]; DL model 0.49 [0.25 to 0.67]), significantly outperforming unaided neurologists (QWK 0.27 [0.10, 0.42]). Neurologists showed systematic overoptimism, predicting lower mRS scores than observed. Furthermore, there was poor accuracy in extracting imaging features. Raters? ASPECTS predictions deviated by 3.4 points from the confirmed scores, and collateral score accuracy was 44.6%. However, for predicting binary mRS (0-2 vs. 3-6), accuracy was comparable between unaided neurologists (64.17% [55.42% to 72.92%]) and models (MR PREDICTS 67.50% [52.50% to 82.50%]; DL model 63.16% [47.37% to 78.95%]). Model-assistance modestly improved and harmonized neurologists? predictions (QWK 0.41 [0.22 to 0.55]; binary accuracy 68.75% [58.33% to 78.34%]. Model performance remained robust in the larger cohort. Conclusions: Multimodal prognostic models outperform clinicians in predicting the full range of mRS outcomes, while human error in imaging assessment and systematic optimism bias are primary drivers of prognostic inaccuracy. End-to-end DL models eliminate human-input variability and hold strong potential as an automated second opinion to support prognostication and decision-making in acute LVO stroke.

03.
PLOS Medicine 2026-06-23

Prevalence and epidemiological patterns of <i>Neisseria gonorrhoeae</i> infection in sub-Saharan Africa, 1964–2025: Systematic review, meta-analyses, and meta-regressions

作者:

by Aisha Osman, Hina Akram, Bayan Alemrayat, Sumaya Al-Maraghi, Manale Harfouche, Laith J. Abu-Raddad Background Neisseria gonorrhoeae (NG) infection is a global health concern because of its morbidity and increasing antimicrobial resistance. Sub-Saharan Africa is believed to carry a disproportionately high burden of NG infection, but the epidemiology of NG infection in this region has not been comprehensively synthesized. This study systematically reviewed and analyzed NG prevalence in sub-Saharan Africa to characterize prevalence patterns and identify populations at risk. Methods and findings A systematic review was conducted and reported following PRISMA guidelines. Embase, PubMed, Scopus, and Web of Science were searched from inception to June 4, 2025. Eligible studies reported NG prevalence in sub-Saharan Africa. Random-effects meta-analyses generated pooled prevalence estimates, and random-effects meta-regression analyses identified associations and sources of heterogeneity.Nine hundred fifty publications contributed 1,604 prevalence measures spanning 1964–2025. In the general population, pooled urogenital prevalence was 3.2% (95% confidence interval (CI): 2.9–3.5), with substantial between-study heterogeneity and a wide prediction interval, indicating considerable variation in prevalence across settings. Prevalence was high in key populations: among female sex workers, 11.5% (95% CI: 9.9–13.2) for urogenital and 2.0% (95% CI: 0.4–4.5) for anorectal infection; and among men who have sex with men, 2.8% (95% CI: 2.4–3.3) for urogenital, 8.3% (95% CI: 5.8–11.0) for anorectal, and 5.7% (95% CI: 3.6–8.3) for oropharyngeal infection. Symptomatic men exhibited high urogenital prevalence (51.5%; 95% CI: 47.5–55.5), and symptomatic women showed 9.0% (95% CI: 7.7–10.4). Among women with adverse pregnancy or birth outcomes, urogenital prevalence was 8.6% (95% CI: 5.3–12.6). Meta-regression analyses explained over half of the variability in prevalence, showing a long-term decline of 1% per year, a clear population type gradient, subregional differences, and decreasing prevalence with increasing age, but no variation by sex. These findings may be affected by variability in data availability across countries, anatomical sites, and population groups, as well as heterogeneity across included studies. Conclusions NG prevalence remains markedly high in this region but has declined over time. These findings highlight the need for strengthened surveillance, expanded prevention and diagnostic strategies, and continued monitoring of gonococcal antimicrobial resistance to support effective control efforts in sub-Saharan Africa.

04.
arXiv (CS.CL) 2026-06-19

AtomMem: Building Simple and Effective Memory System for LLM Agents via Atomic Facts

Large language models (LLMs) demonstrate strong reasoning and generation abilities, but their fixed context windows limit long-term information accumulation and reuse across multi-session interactions. Existing memory-augmented systems often construct memory in a coarse and unstable manner, relying on inefficient memory representations or unstable unconstrained updates. To address these challenges, we propose AtomMem, a long-term memory system designed for value-dense storage and stable memory evolution. AtomMem introduces a Fact Executor, which selectively extracts high value atomic facts from long form interactions to serve as highly efficient memory representations. Subsequently, AtomMem organizes these facts into hierarchical event structures and temporal profiles, capturing coherent episodic contexts and tracking dynamically evolving user attributes over time. During retrieval, the system activates an associative memory graph to connect fragmented memories. Experiments on the LoCoMo benchmark confirm that AtomMem achieves state-of-the-art performance across various reasoning tasks, offering a scalable and economically viable solution for deploying intelligent personalized agents.

05.
arXiv (CS.AI) 2026-06-15

STREAM: Multi-Tier LLM Inference Middleware with Dual-Channel HPC Token Streaming

arXiv:2606.13968v1 Announce Type: cross Abstract: Researchers and practitioners working with large language models face a fragmented landscape: local models are free and private but hardware limits the model size and context windows a researcher can use; institutional HPC centers offer powerful GPU resources at no marginal cost and keep data within institutional boundaries, but operate behind firewalls and are designed for batch jobs rather than interactive use; commercial cloud APIs provide frontier-model quality on demand but impose significant cost and data retention policies unsuitable for sensitive research data. No existing system unifies all three. STREAM (Smart Tiered Routing Engine for AI Models) addresses this gap with four contributions: (1) a three-tier routing architecture combining local, HPC, and cloud inference with a local LLM-based complexity judge; (2) a dual-channel HPC streaming architecture that separates the Globus Compute control plane (authentication and job dispatch) from a WebSocket relay data plane (token delivery), enabling sub-second TTFT (0.54 s median, 21.1x over batch mode's 11.40 s) through institutional firewalls without VPN or firewall rule changes, with end-to-end AES-256-GCM encryption ensuring the relay operator cannot read token payloads; (3) tier-aware context summarization that prevents long conversations from forcing simple queries onto expensive tiers; and (4) an HPC-as-API proxy mode that exposes HPC inference as an OpenAI-compatible endpoint callable from any standard client with no HPC expertise, a deployment pattern made practical only by the sub-second TTFT of contribution (2). Llama 3.2 3B achieves 85.1% free-tier retention on a 1,200-query benchmark spanning ten domains. Measured TTFT: 0.26 s local, 0.54 s HPC (relay), 1.68 s cloud.

06.
bioRxiv (Bioinfo) 2026-06-16

Accelerating String Comparison in RLZ Compressed Sequences via LCE Jumps

Relative Lempel-Ziv (RLZ) is an effective compression method for large, repetitive collections; however, the fundamental primitives required to elevate it from a passive archival format to a tractable representation for compressed construction have yet to be fully established. In this paper, we introduce an algorithmic framework for structurally comparing and lexicographically sorting sequences of RLZ factors. We characterize when direct factor comparisons are necessary and when they can be bypassed using RLZ specific shortcuts. We further introduce a method for extending truncated factors into right-maximal matches, enabling the recovery of matching statistics from the RLZ parse. Experimentally, RLZ sorting achieved speedups of up to 3.93x over character-based sorting. Together, these results advance the use of the RLZ format as a foundation for compressed construction.

07.
arXiv (CS.LG) 2026-06-19

Learning to Emulate Chaos: Adversarial Optimal Transport Regularization

arXiv:2604.21097v2 Announce Type: replace-cross Abstract: Chaos arises in many complex dynamical systems, from weather to power grids, but is difficult to accurately model with data-driven methods such as machine learning emulators. While emulators are promising tools for accelerating simulations and solving inverse problems, they still struggle to learn chaotic dynamics, where sensitivity to initial conditions renders exact long-term forecasts infeasible, especially given noisy data. Recent work instead trains emulators to match the statistical properties of chaotic attractors, but these approaches often rely on handcrafted summary statistics or large, diverse multi-environment datasets. In this work, we propose a family of adversarial optimal transport objectives that can jointly learn high-quality summary statistics and a physically consistent emulator from a single noisy trajectory. We theoretically analyze and experimentally validate a Sinkhorn divergence formulation (2-Wasserstein) and a WGAN-style dual formulation (1-Wasserstein) of our approach. Numerical experiments across a variety of chaotic systems, including ones with high-dimensional spatiotemporal chaos, show that emulators trained using our proposed objectives have significantly improved long-term statistical fidelity.

08.
arXiv (CS.LG) 2026-06-19

Approximate Next Policy Sampling: Replacing Conservative Target Policy Updates in Deep RL

arXiv:2605.05481v2 Announce Type: replace Abstract: We revisit a classic "chicken-and-egg" problem in reinforcement learning: to safely improve a policy, the value function must be accurate on the state-visitation distribution of the updated policy. That distribution over states is unknown and cannot be sampled for the purposes of training the value function. Conservative updates solve this problem, but at the cost of shrinking the policy update. This paper explores an alternative solution, Approximate Next Policy Sampling (ANPS), which addresses the problem by modifying the training distribution rather than constraining the policy update. ANPS is satisfied if the distribution of the training data approximates that of the next policy. To demonstrate the feasibility and efficacy of ANPS, we introduce Stable Value Approximate Policy Iteration (SV-API). SV-API modifies the standard approximate policy iteration loop to hold the target policy fixed while an iteratively updated behavioral policy gathers relevant experience. It only commits to a new policy once a convergence criterion has been met. If certain stability criteria are met, the update is guaranteed to be safe; otherwise, it remains no less safe than standard approximate policy iteration. Applying SV-API to PPO yields Stable Value PPO (SV-PPO), which matches or improves performance on high-dimensional discrete (Atari) and continuous control benchmarks while executing substantially larger target policy updates. These results demonstrate the viability of ANPS as a new solution to this classic challenge in RL.

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

The Hidden Power of Scaling Factor in LoRA Optimization

arXiv:2606.12883v1 Announce Type: new Abstract: In Low-Rank Adaptation (LoRA), the scaling factor $\alpha$ is often treated as a mere complement to the learning rate, yet its role in optimization remains poorly understood. In this paper, we reveal that the scaling factor $\alpha$ and the learning rate function differently, with $\alpha$ emerging as the dominant driver of effective optimization, delivering gains that cannot be replicated by learning rate scaling alone. Through the synergy of extensive empirical analysis and a theoretical Signal-Drift framework, we uncover three findings into LoRA's scaling mechanism: First, LoRA's spectral suppression smooths the optimization landscape, rendering standard hyperparameters overly conservative and creating an optimization gap. Second, when leveraging this smoothness to accelerate convergence, $\alpha$ outperforms the learning rate by amplifying the task signal without increasing the drift ratio. Third, the optimal scaling factor follows a sublinear relationship with the rank, well characterized by a square-root law with an unexpectedly large coefficient, revealing the insufficient scaling of existing rank-tied heuristics. Based on these insights, we propose LoRA-$\alpha$, a minimalist framework that restores $\alpha$ to its principled regime, making LoRA compatible with standard small learning rates. Extensive evaluations across diverse tasks demonstrate that LoRA-$\alpha$ consistently improves performance while streamlining hyperparameter search, unleashing the learning potential of LoRA.

10.
arXiv (CS.CV) 2026-06-16

Mask Proposal Voting Based on Geodesic Framework for Robust Image Segmentation

Despite great advances, finding accurate segmentation remains a challenging task, especially in scenarios with cluttered backgrounds, complex intensity variations and topology appearance. Minimal path models have exhibited their strong ability in addressing image segmentation tasks. However, the performance of minimal paths-based segmentation approaches is heavily influenced by model initialization, hence limiting their application scope in practice. In this work, we propose a novel mask proposal voting framework that overcomes the major drawback of classical approaches, allowing robust segmentation even in complicated scenarios. Firstly, we introduce an efficient method for constructing adaptive domain cuts as a constraint for initializing the region-based min-cut evolution, by which diverse and reliable mask proposal candidates can be generated, substantially increasing the possibility of accurately covering the objective region by these proposals. Secondly, we propose a new mask voting scheme to build a voting score map encoding the final segmentation information. In contrast to classical path voting methods, our model allows incorporating priors to assign different importance to each individual mask. As a consequence, the proposed segmentation model is capable of accurately delineating object boundaries under complex scenarios, and is insensitive to initialization. Experiments demonstrate that our method consistently outperforms state-of-the-art minimal path-based approaches in both accuracy and robustness.

11.
medRxiv (Medicine) 2026-06-15

Two Blood-based Endotypes Reveal Divergent Clinical Outcomes of Fibrotic Hypersensitivity Pneumonitis

Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an antigen-driven, life-threatening interstitial lung disease characterized by heterogeneous radiologic features, clinical outcomes, and treatment responses. Objectives: To identify blood-based fHP endotypes that inform mechanism, prognosis and therapeutic response. Methods: We performed integrative analyses of multi-compartment transcriptomic data derived from whole blood, peripheral blood mononuclear cells, bronchoalveolar lavage, and surgical lung biopsies, alongside circulating plasma proteomics. Multiple clustering algorithms were cross-compared to ensure robustness and reproducibility of endotypes identification. Immune cell composition was inferred using bulk RNA-seq deconvolution and annotated with BAL single-cell RNA-seq. Pathway activities were characterized using Gene Set Enrichment Analysis. Transplant-free survival (TFS) was evaluated for endotype and corticosteroid exposure by Kaplan-Meier methods, with hazard ratios analyzed using multivariable Cox proportional hazards models. Results: Two molecular endotypes, lymphocytic-associated (L-fHP) and non-lymphocytic-associated (N-fHP), were identified and validated. L-fHP showed enrichment of adaptive immune signaling and lymphocyte predominance, whereas N-fHP demonstrated myeloid-cell activation with neutrophil and macrophage predominance. Corticosteroid exposure was associated with worse TFS in L-fHP but not in N-fHP after adjusting for age, sex, and baseline pulmonary function. Compared to L-fHP, N-fHP had poorer baseline pulmonary function, faster 12-month FVC decline, and shorter TFS. N-fHP also exhibited elevated neutrophil-associated markers, including matrix metalloproteinase-9, across paired transcriptomic and proteomic datasets, supporting a neutrophil-driven, cross-compartment disease process. Conclusion: Multi-omic, multi-compartment analysis identifies two reproducible fHP endotypes with distinct clinical outcomes and corticosteroid responses, supporting a precision medicine approach beyond current clinical and radiologic classification.

12.
arXiv (quant-ph) 2026-06-16

Generalized Kerr-Cat Qubit Codes

arXiv:2606.14901v1 Announce Type: new Abstract: We present a systematic study of Schrödinger cat codes constructed from Kerr-type coherent states, including displaced Kerr coherent states and Barut–Girardello Kerr coherent states, each admitting two distinct families determined by the sign of the Kerr nonlinearity. By tuning the Kerr parameter and coherent-state amplitude, these states interpolate between $\mathfrak{su}(2)$, $\mathfrak{su}(1,1)$ coherent states, providing a unified and versatile foundation for this type of bosonic quantum error correction. Unlike standard two-component Schrödinger cat codes, where a single photon-loss event induces an uncorrectable bit-flip, the nonlinear phase-space structure of Kerr cat states enables simultaneous detection and correction of both photon-loss and dephasing errors within a unified recovery framework, with optimal recovery operations determined via convex optimization. We demonstrate that Kerr cat encodings significantly outperform conventional cat codes under combined loss and dephasing noise, and that judicious parameter optimization can suppress both error channels to a level that reduces the overhead of additional error correction layers. We further show that Kerr-deformed coherent-state manifolds under engineered two-photon driving emerge as effective steady states of driven-dissipative dynamics, with single-photon decoherence strongly suppressed and leakage outside the protected manifold appearing only as higher-order corrections in the deformation strength. Our extended formalism identifies generalized Kerr Schrödinger cat codes as promising candidates for fault-tolerant bosonic quantum computation in experimental platforms such as nonlinear photonics.

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

Faithful Action-unit Causal Reasoning for Counterfactually Faithful Emotion Explanations

Multimodal models can name the action units (AUs) behind a facial emotion, but their AU->emotion rationales are typically plausible rather than faithful: nothing forces the AUs a model invokes to be the AUs that actually drive its prediction. We cast AU->emotion reasoning as a counterfactual-consistency problem between the rationale, the label, and a structural AU->emotion causal graph G, and propose FACR, which grounds the reasoner in an independently induced, polarity-aware G and trains a counterfactual-faithfulness objective: a do-intervention on an AU that G marks causal for a class must move the prediction, while one it marks irrelevant must leave it unchanged. Faithfulness is thereby both trainable and measurable through a matching interventional metric, which we evaluate against a known causal structure, the PSPI pain-AU composition, as no existing affective-reasoning benchmark allows. We are explicit that this metric tests fidelity to the supplied structure rather than its rediscovery: it asks whether the trained reasoner invokes the AUs the structure marks causal, on held-out subjects and a second dataset. Under subject-independent evaluation on UNBC-PAIN, the objective raises the agreement between the invoked AUs and the PSPI composition from a no-objective baseline of 0.08 to 0.57, at a small detection cost; an unfaithfulness control attributes the gain to the objective. On a cross-dataset emotion transfer, the objective likewise raises fidelity to G on a seven-class task (0.50 to 0.84). Finally, we attach a language verbalizer and extend the audit to the generated text: biasing each action unit's emission by its latent activation makes the rationale faithful by construction, so that ablating an AU removes it from the explanation, a property that transfers to a second language-model backbone, whereas a freely generated rationale is unfaithful.

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

Software Delegation Contracts: Measuring Reviewability in AI Coding-Agent Work

arXiv:2606.17099v1 Announce Type: cross Abstract: AI coding agents increasingly accept assigned software tasks, modify repositories under bounded authority, and return work packages for review. Prior work proposed the software delegation contract, covering the task, authority, returned work package, and acceptance context, as the unit of analysis for delegated coding work, but did not measure its effects. This paper reports a controlled pilot study of explicit delegation contracts for coding agents. We built a dependency-free TypeScript API task environment with seeded defects and documentation gaps, authored ten tasks across five families, and ran 64 agent executions across two model tiers under three conditions: a realistic issue-style prompt, an explicit delegation contract, and a contract with a required evidence bundle. Each run was scored with hidden acceptance tests, mutation checks, and scope analysis, then reviewed by three independent condition-blinded model-based reviewers using a fixed rubric, for 192 reviews. Explicit contracts did not improve objective task outcomes: all 64 runs passed hidden acceptance checks, with zero scope violations. They did improve reviewability. Evidence sufficiency improved in 22 of 30 paired comparisons and worsened in none (+0.83 on a 5-point scale, p < 0.0001, Cliff's delta = 0.66); reviewer ambiguity decreased (p = 0.035); changed-file lists, known-limitations sections, residual-risk sections, and reviewer checklists appeared mostly or only when demanded by the contract. Contracts cost +13% agent tokens and +38% wall-clock time, with larger effects for the weaker model tier. On these small tasks, delegation contracts bought reviewability rather than correctness.

15.
arXiv (CS.CV) 2026-06-16

Focus When Necessary: Adaptive Routing and Collaborative Grounding for Training-Free Visual Grounding

While Multimodal Large Language Models (MLLMs) excel in cross-modal reasoning, they often struggle to perceive fine-grained details in complex high-resolution images. Recent training-free methods address this through image scaling and localized cropping. However, applying these manipulations indiscriminately introduces computational redundancy for simple queries and can degrade accuracy by truncating essential global context or introducing irrelevant background noise. To this end, we propose LazyMCoT, a dynamic and training-free framework that adaptively allocates visual grounding efforts based on sample difficulty. The framework features an Adaptive Routing mechanism that evaluates predictive uncertainty using first-token statistics from a single forward pass. This efficiently bypasses confident cases while ensuring the recall of difficult samples via conformal calibration. For these challenging cases, a Collaborative Grounding module integrates the inherent cross-modal attention of the model with an external visual expert through a two-stage refinement process. This refinement process generates a precise localized display to recover small or occluded targets. Extensive experiments across diverse benchmarks demonstrate that LazyMCoT rivals training-based approaches by simultaneously improving reasoning accuracy and reducing average inference latency. Our code is availble at https://github.com/TencentBAC/LazyMCoT.

16.
arXiv (CS.LG) 2026-06-12

Single vs. Multiple Branches in DeepONet and S-DeepONet: Network Architecture Follows Coupling in Multiphysics Systems

arXiv:2507.03660v2 Announce Type: replace Abstract: `Real-time prediction of complex physical systems requires surrogate models that learn from data while representing strong multiphysics coupling. Deep Operator Networks have shown success in single-physics problems, yet their effectiveness in capturing nonlinear interactions in coupled systems (such as thermo-mechanical or electro-thermal coupling) remains underexplored. Here we pose a practical question: should the architecture of a neural operator reflect the strength of physical coupling it aims to model? We compare single-branch and multi-branch designs, in both feedforward and sequential recurrent forms, across three representative systems: a reaction–diffusion problem with heterogeneous sources, a nonlinear thermo-electrical problem with temperature-dependent conductivity and Joule heating, and a viscoplastic thermo-mechanical model of steel solidification. Single-branch networks consistently outperform multi-branch variants in tightly coupled regimes by encouraging shared latent representations, whereas multi-branch designs remain favorable for decoupled or single-physics tasks. Once trained, these surrogates deliver full-field predictions up to $1.8 \times 10^4$ times faster than physics-based solvers.

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

An energy-based uncertainty principle and low-energy state preparation

作者:

arXiv:2603.15495v2 Announce Type: replace Abstract: Preparing low-energy states of many-body Hamiltonians is a central challenge in quantum computing, quantum complexity, and condensed matter physics. Existing approaches often get trapped in suboptimal states such as high-energy eigenstates or, more generally, low-variance states that resist further energy reduction. In this work, we explore a different perspective: instead of optimizing with respect to a single Hamiltonian, we leverage the fact that many systems admit families of Hamiltonians that share similar low-energy subspaces but differ at higher energies. We show that this redundancy can be turned into an algorithmic resource by establishing an energy-based uncertainty principle, which implies that these Hamiltonians cannot simultaneously admit low-variance states at higher energies. This suggests a simple strategy of alternating energy-lowering steps across such Hamiltonians, which we investigate numerically on several models. We also introduce a sparse variant where the uncertainty principle yields quadratically larger variance at higher energies, leading to more pronounced energy change. Overall, this work suggests a range of open questions at the interface of random matrix theory, local Hamiltonians and low-energy state preparation, aimed at understanding when such approaches are practical and how they can be analyzed rigorously.

18.
medRxiv (Medicine) 2026-06-22

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

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

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

Neural Bayesian Anomaly Mitigation: A Robust Loss that Doubles as an Unsupervised Contamination Classifier

arXiv:2606.16524v1 Announce Type: new Abstract: Engineered robust losses such as Huber, Student-$t$, and generalised cross-entropy make supervised models tolerant of contamination but cannot answer which observations are corrupted. We introduce Neural Bayesian Anomaly Mitigation (NBAM), a general-purpose drop-in loss derived from a Bayesian latent-switch mixture model: the marginal likelihood defines a robust supervised loss, and the associated posterior defines an unsupervised contamination classifier. Like Huber or Student-$t$, NBAM can replace the standard training loss in any supervised pipeline; unlike them, it additionally learns a structured contamination model and returns a calibrated per-sample contamination posterior. A learned input-dependent prior $\pi_\phi(x)$ captures the spatial locality of contamination, so that samples near known corruptions are more likely to be flagged, while an Occam penalty emerges automatically and regularises against over-flagging. On CIFAR-10 with asymmetric label contamination, NBAM recovers the structure of the corruption process without supervision: the contamination posterior separates clean from corrupted samples, and the learned anomaly head identifies the direction of every label-flip pair. Alongside these capabilities, NBAM outperforms the four robust-loss baselines considered here at contamination rates 0.2-0.6.

20.
arXiv (CS.CV) 2026-06-11

MedVeriSeg: Teaching LISA-Like Medical Segmentation Models to Verify Query Validity Without Extra Training

Despite recent progress in text-prompt-based medical image segmentation, existing LISA-like MLLM-based methods typically generate masks regardless of whether the target specified in the query is present, leading to hallucinated segmentation. In this work, we propose MedVeriSeg, a training-free query verification framework that enables LISA-like medical segmentation models to reject false segmentation queries. MedVeriSeg first quantifies the response quality between the [SEG] token and image features through a Similarity Response Quality Scoring Module. To further improve robustness, it employs a Lightweight Routed Multi-Agent Verification Module, which fuses quantitative score evidence with qualitative agent evidence to comprehensively verify the validity of the query. To support systematic evaluation, we construct MedVeriSeg-Bench, a benchmark designed for query verification in medical image segmentation. Experimental results demonstrate that MedVeriSeg effectively identifies false segmentation queries and reduces hallucinated segmentation, while maintaining a high acceptance rate for valid queries, thereby largely preserving the segmentation utility of LISA-like medical segmentation models.

21.
arXiv (CS.CL) 2026-06-25

Continual Knowledge Updating in LLM Systems: Learning Through Multi-Timescale Memory Dynamics

LLMs are trained once, then deployed into a world that never stops changing. External memory compensates for this, but most systems manage it explicitly rather than letting it adapt on its own. Biological memory works differently: coupled multi-timescale dynamics make new associations immediately usable, strengthen what repetition confirms, and let the rest fade. We argue that external memory should follow a similar principle. In Memini, this view takes the form of an associative memory that organizes knowledge as a directed graph. Each edge carries two coupled internal variables, one fast and one slow, following the Benna-Fusi model of synaptic consolidation. From this coupling, episodic sensitivity, gradual consolidation, and selective forgetting are expected to emerge as facets of a single mechanism, reframing external memory as a learning substrate that reorganizes through its own dynamics. This workshop article describes an early-stage conceptual design without experimental evaluation.

22.
PLOS Computational Biology 2026-06-22

Integrative modelling of innate immune response dynamics during virus infection

by Ramya Boddepalli, Harsh Chhajera, Rahul Roya Positive-sense RNA viruses that constitute a large class of human pathogens employ various strategies to suppress and evade host immune defenses. Understanding the dynamic interaction between the viral life cycle and immune signaling is crucial to designing effective antiviral strategies. Although significant progress has been made, quantitative models that can accurately capture the intricate interactions and the intertwined dynamics during viral infection of cells remain missing. In this study, we develop a comprehensive mathematical model that integrates the intracellular viral life cycle with key cellular innate immune pathways, including RIG-I-mediated detection and JAK-STAT signaling. The model provides mechanistic insights into long-standing observations, capturing both virus-specific dynamics and innate immune response, and the key components driving their coupled dynamics. For example, a comparison of viruses shows how the Japanese Encephalitis virus undergoes a dramatic reduction in viral load in cells, due to its rapid replication that robustly activates the RIG-I pathway, in contrast to the poor immune control of Hepatitis C virus. More importantly, our model demonstrates how virus-host interactions exhibit a sharp transition boundary behavior, where minor differences in immune strength or viral suppression capacity can determine whether infections resolve or persist. We propose that ISG mRNA translation and viral replication predominantly dictate these bimodal infection outcomes. Additionally, the model not only recapitulates IFN desensitization but also identifies the molecular players involved. We demonstrate how our model’s ability to capture IFN dynamics allows us to predict optimal timing and dosing strategies for interferon-based prophylactic therapies. Together, our approach reveals fundamental features that govern the delicate balance between the establishment of infection and immune control in RNA virus infections.

23.
arXiv (CS.AI) 2026-06-17

When Life Gives You BC, Make Q-functions: Extracting Q-values from Behavior Cloning for On-Robot Reinforcement Learning

arXiv:2605.05172v2 Announce Type: replace-cross Abstract: Behavior Cloning (BC) has emerged as a highly effective paradigm for robot learning. However, BC lacks a self-guided mechanism for online improvement after demonstrations have been collected. Existing offline-to-online learning methods often cause policies to replace previously learned good actions due to a distribution mismatch between offline data and online learning. In this work, we propose Q2RL, Q-Estimation and Q-Gating from BC for Reinforcement Learning, an algorithm for efficient offline-to-online learning. Our method consists of two parts: (1) Q-Estimation extracts a Q-function from a BC policy using a few interaction steps with the environment, followed by online RL with (2) Q-Gating, which switches between BC and RL policy actions based on their respective Q-values to collect samples for RL policy training. Across manipulation tasks from D4RL and robomimic benchmarks, Q2RL outperforms SOTA offline-to-online learning baselines on success rate and time to convergence. Q2RL is efficient enough to be applied in an on-robot RL setting, learning robust policies for contact-rich and high precision manipulation tasks such as pipe assembly and kitting, in 1-2 hours of online interaction, achieving success rates of up to 100% and up to 3.75x improvement against the original BC policy. Code and video are available at https://pages.rai-inst.com/q2rl_website/

24.
arXiv (CS.LG) 2026-06-25

TRACER: Training-Free Closed-Loop Structured Inference for Traffic Accident Reconstruction

arXiv:2606.25002v1 Announce Type: new Abstract: Traffic accident reconstruction is a forensic inverse problem that requires recovering physically consistent motion from sparse and heterogeneous evidence. Existing learning-based approaches predominantly optimize for semantic plausibility or visual realism, rather than quantitative agreement with measurable geometry and dynamics. Here, we present TRACER, a training-free framework that formulates reconstruction as a closed-loop structured inference process. Instead of directly generating dense trajectories, our framework constructs and iteratively refines event-anchored motion hypotheses under geometric, kinematic, and interaction constraints, guided by structured case memory and consistency-driven diagnosis. This design enables incremental, interpretable corrections when evidence is insufficient, making the accident reconstruction process more aligned with the workflow of human experts. Experiments on real-world accident data show that TRACER achieves improved geometric fidelity, velocity consistency, and collision accuracy over both data-driven and physics-based baselines.

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medRxiv (Medicine) 2026-06-15

Population-scale genomics reveals divergent pathogenicity of variant classes across paralogous collagen IV genes

Monoallelic pathogenic or likely pathogenic variants in COL4A3 and COL4A4 occur in approximately 1 in 106 individuals, yet whether these paralogous genes confer equivalent pathogenicity for the same variant classes has not been tested at population scale. Using whole-genome sequencing data from the UK Biobank (UKB; n = 500,000), with replication in the All of Us Research Program (n = 414,000), we performed per-variant association testing, gene-based collapsing analyses and phenome-wide association studies (PheWAS) across haematuria, proteinuria and chronic kidney disease. We identified 64 COL4A3 and 92 COL4A4 rare variants significantly associated with haematuria or proteinuria, generating a quantitative allelic series for clinical variant interpretation. Glycine substitutions within collagenous domains conferred similar risks in both genes. In contrast, truncating and non-collagenous domain (NC1) missense variants were strongly associated with haematuria and proteinuria in COL4A4 carriers but showed substantially attenuated or absent associations in COL4A3 carriers despite comparable carrier frequencies and predicted pathogenicity scores. These findings were independently replicated in All of Us. Genome-wide association analysis identified the COL4A3/COL4A4 locus as the dominant genetic determinant of haematuria, with the signal attributable to the aggregate effects of rare coding variants and no evidence of independent common variant or trans-acting modifier effects. These findings demonstrate substantial gene-specific differences in tolerance to truncating and NC1 variants between COL4A3 and COL4A4, challenging assumptions of equivalent pathogenicity across paralogous collagen IV genes. Gene identity and not variant class alone, should inform risk stratification, variant interpretation and genetic counselling in individuals carrying collagen IV risk genotypes.