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01.
bioRxiv (Bioinfo) 2026-06-20

SAbDab2: The structural antibody database in the age of machine learning

The Structural Antibody Database (SAbDab) is a publicly available repository of experimentally determined antibody structures, first released in 2013. Explicit support for single-domain antibodies was added in 2021, with SAbDab-nano. Recently, increasing interest in antibodies has led to a proliferation of novel antibody formats, while simultaneous advances in machine learning have increased demand for standardised, high-quality structure data. Here, we present SAbDab2, re-engineered for the machine-learning age. It introduces support for a variety of new formats, and makes it easy to retrieve and compare all known structures of a given antibody. In addition, SAbDab2 provides ready access to ML-grade structures of antibody and antibody–antigen-complexes, with standardised, versioned train/test splits. These will be updated every six months going forward, and are available at https://zenodo.org/records/20083995. SAbDab2 itself is updated weekly and is freely available at https://sabdab2.opig.stats.ox.ac.uk.

02.
arXiv (CS.LG) 2026-06-15

Deep Doubly Debiased Longitudinal Effect Estimation with ICE G-Computation

arXiv:2602.12379v2 Announce Type: replace Abstract: Estimating longitudinal treatment effects is essential for sequential decision-making but is challenging due to treatment-confounder feedback. While Iterative Conditional Expectation (ICE) G-computation offers a principled approach, its recursive structure suffers from error propagation, corrupting the learned outcome regression models. We propose D3-Net, a framework that mitigates error propagation in ICE training and then applies a robust final correction. First, to interrupt error propagation during learning, we train the ICE sequence using Sequential Doubly Robust (SDR) pseudo-outcomes, which provide bias-corrected targets for each regression. Second, we employ a multi-task transformer with a covariate simulator head for auxiliary supervision, regularizing representation learning, and a target network to stabilize training dynamics. For the final estimate, we discard the SDR correction and instead use the uncorrected nuisance models to perform Longitudinal Targeted Minimum Loss-Based Estimation (LTMLE) on the original outcomes. This second-stage, targeted debiasing ensures robustness and optimal finite-sample properties. Comprehensive experiments demonstrate that our model, D3-Net, robustly reduces bias and variance across different horizons, counterfactuals, and time-varying confoundings, compared to existing state-of-the-art ICE-based estimators.

03.
arXiv (math.PR) 2026-06-15

Stability of the $k$-Plane Transform on Measures and Hölder-Type Comparisons of Wasserstein Metrics

arXiv:2605.00375v2 Announce Type: replace-cross Abstract: We establish stability estimates for the $k$-plane transform on finite positive Radon measures, with emphasis on Fourier and Wasserstein metrics. We first introduce a metric on $k$-plane transform data and prove a bi-Lipschitz stability estimate showing that this metric is equivalent to a generalized Fourier metric obtained by augmenting the Fourier distance between centered normalized measures with separate barycenter and total mass difference terms. Building on a Hölder-type comparison between Fourier and Wasserstein metrics due to Carrillo and Toscani, we extend this comparison to positive Radon measures under uniform bounds on centered moments of order slightly larger than $2$. This yields Hölder-type stability for the $k$-plane transform in a generalized $2$-Wasserstein metric and, in particular, a $W_2$-stability estimate for centered probability measures. We also compare the $2$-Wasserstein distance with its max-sliced analogue. For centered probability measures with uniformly bounded moments of order slightly larger than $2$, we prove a two-sided Hölder-type comparison between these distances. We then extend the result to positive Radon measures by applying it to centered normalized measures and adding separate barycenter and mass terms. Finally, for absolutely continuous compactly supported probability measures with bounded densities, we prove a strong equivalence between the $2$-Wasserstein distance of the measures and the $(k/2-1)$-order Sobolev norm of the $k$-plane transform data of the difference of their densities.

04.
arXiv (CS.LG) 2026-06-16

GRASP: Gradient-Aligned Sequential Parameter Transfer for Memory-Efficient Multi-Source Learning

arXiv:2606.14900v1 Announce Type: new Abstract: Multi-source transfer learning faces a fundamental scalability bottleneck: existing approaches require either loading all K source models into memory simultaneously during parameter fusion, requiring O(K) memory, or deploying all models at inference time, making production deployment infeasible. We propose GRASP (Gradient-Aligned Sequential Parameter Transfer), which achieves superior knowledge integration while maintaining O(1) memory consumption through three key innovations: (1) sequential processing that merges one source at a time into an evolving target model, (2) parameter-wise gradient alignment that selectively transfers only parameters whose optimization directions align with the target domain, avoiding negative transfer, and (3) iterative fine-tuning that adapts transferred knowledge before integrating the next source. Extensive experiments across three continual learning benchmarks (Yearbook, CLEAR-10, CLEAR-100) spanning 10 to 108-year temporal distribution shifts and four architectures (1.3M to 25.6M parameters) demonstrate that GRASP achieves 93.5% mean accuracy over all datasets and architectures compared to ensemble method's 71.7% accuracy while requiring only constant memory versus K models for standard multi-source fusion. Critically, GRASP's sequential previously merged models and scales to arbitrarily many sources without memory growth, making it uniquely suitable for resource-constrained deployment and continually evolving source domains.

05.
medRxiv (Medicine) 2026-06-10

Human genetic evidence links serine biosynthesis to diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is a common and disabling condition for which no disease-modifying therapies are available. Glycemic and metabolic drivers do not fully explain why only a subset of individuals with diabetes develop DPN, and genetic contributors remain poorly defined. We aimed to perform a multi-population genome-wide association study (GWAS) of DPN to highlight potential new etiological pathways and therapeutic targets. Methods We performed a multi-population GWAS of neuropathy in people with and without diabetes using the VA Million Veteran Program and UK Biobank, followed by replication in the All of Us Research Program (AoU), and gene-based and gene-set analyses to identify implicated pathways. Causal relationships between circulating serine levels and DPN were further tested using two sample Mendelian randomization. To further evaluate pathogenic potential, we analyzed rare, high impact variants in GWAS implicated genes among individuals with unresolved inherited neuropathies using the GENESIS platform. Findings Among individuals with type 2 diabetes, we identified seven genome wide significant loci (p

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

A Benchmark for Omni-Modal Reasoning in Long Videos

Long-form omni-modal video understanding requires integrating vision, speech, and ambient audio with coherent long-context reasoning. Existing video benchmarks often trade off temporal scale, modality coverage, open-ended interaction, and interpretable scoring. To address this gap, we introduce LongShOTBench, a long video understanding benchmark designed around three coupled goals: holistic omni-modal integration, intent-driven open-ended interaction, and rubric-level diagnosis. It builds single- and multi-turn questions from real viewing scenarios, with systematic tasks probing visual, speech, ambient-audio, temporal, and cross-modal reasoning. Each item includes a reference answer and a weighted criterion-level rubric, letting evaluation identify which perceptual facts, temporal links, modality-grounding requirements, and reasoning steps are satisfied or missed. All samples are manually verified to improve grounding, clarity, and rubric reliability. We also introduce LongShOTAgent, a training-free omni-modal evidence-seeking agent coupling full-video preprocessing with targeted retrieval, query-adaptive segment refinement, and explicit claim verification over visual, speech, and non-speech audio evidence. Its iterative search-refine-verify loop exposes intermediate evidence and lets modality-specific specialists re-analyze relevant moments before answering. We evaluate 105 video-capable models spanning open-source omni-modal models, vision-language systems, audio LLMs, agentic pipelines and closed-source APIs. Current MLLMs remain far from saturating LongShOTBench, while our LongShOTAgent is the strongest training-free system, reaching 66.64% overall. By releasing the benchmark, leaderboard, and method, we provide a shared, interpretable testbed for advancing long-form omni-modal video reasoning. Code, data, and the leaderboard are available at https://longshot.cvmbzuai.com/.

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

AnalogFed: Privacy-Preserving Discovery of Analog Circuits at Scale with Federated Generative AI

arXiv:2507.15104v2 Announce Type: replace-cross Abstract: Recent advances in generative AI (GenAI) have shown transformative potential for modern hardware design. However, existing GenAI-driven approaches fall short of enabling large-scale electronic design automation (EDA) due to the proprietary and siloed nature of hardware datasets, which cannot be centralized for model training. Achieving at-scale GenAI-driven EDA, therefore, requires a novel privacy-preserving framework that can leverage distributed data without compromising confidentiality. This work introduces AnalogFed, the first privacy-preserving framework for large-scale analog circuit topology discovery using federated learning (FedL) and GenAI. AnalogFed establishes the feasibility of collaborative analog topology design while addressing key security challenges: it mitigates membership inference attacks (MIAs) through a novel input perturbation strategy based on dummy token injection, and defends against model inversion attacks with customized, efficient homomorphic encryption. Extensive experiments demonstrate AnalogFed's effectiveness and efficiency, achieving strong privacy protection without degrading model utility. This framework lays the foundation for scalable, multi-party collaboration in next-generation hardware design automation with GenAI.

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

From Isolation to Entanglement: When Do Interpretability Methods Identify and Disentangle Known Concepts?

A goal of interpretability is to recover disentangled representations of latent concepts (features) from the activations of neural networks. The quality of features is typically evaluated in isolation, and under implicit independence assumptions that may not hold in practice. Thus, it is unclear to what extent common featurization methods such as sparse autoencoders (SAEs) and probes disentangle one concept from another. We propose a multi-concept evaluation setting using concepts including sentiment, domain, voice, and tense. We evaluate how well featurizers produce disentangled representations of each concept, observing that features are typically sensitive to only one concept, but also that concepts are distributed across many features. Then, we steer these features, measuring whether each concept is independently manipulable, and whether features interact. Even in idealized settings, steering a feature often affects many concepts, despite a near absence of interaction effects. These results suggest that correlational metrics are insufficient to establish steering selectivity, and that demonstrating that two features operate in separate spaces is insufficient to claim that they will be selective for one concept. These results underscore the importance of multi-concept evaluations in interpretability research.

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

Dual-Domain Equivariant Generative Adversarial Network for Multimodal CT-PET Synthesis

We present a Dual-Domain Equivariant Generative Adversarial Network (DDE-GAN) for multimodal CT-PET image synthesis. Traditional GAN-based approaches often operate solely in the spatial domain and ignore geometric consistency, resulting in limited structural fidelity. DDE-GAN addresses these challenges by jointly learning from both spatial and frequency (Fourier) domains, capturing complementary anatomical and spectral information. Furthermore, rotational equivariance embedded in the physics of the CT and PET measurements are integrated into the loss of both the generator and discriminator to ensure consistent responses under rotations, improving anatomical accuracy. A hierarchical dual-domain training strategy enforces intra- and inter-domain consistency through multi-stage loss functions. Evaluated on the HECKTOR 2022 CT-PET dataset, DDE-GAN achieves superior synthesis quality over baseline models for CT-PET image synthesis. The results demonstrate that combining dual-domain learning with geometric equivariance substantially enhances multimodal image synthesis accuracy and robustness, enabling practical applications in PET completion and data augmentation.

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

Learn Temporal Consistency For Robust Satellite Video Detector

Satellite video object detection (SVOD) for oriented and fine-grained objects plays an important role in satellite applications. Most existing SVOD methods only focus on one or a few coarse-grained categories of moving objects and represent objects with horizontal bounding boxes. They have difficulty extracting complete, accurate, and consistent information about objects in whole satellite videos. In this paper, we propose a satellite video object detection framework based on Temporal Consistency Learning (TCL). TCL adeptly detects oriented and fine-grained objects by leveraging the rich temporal contexts within satellite videos. The framework integrates three key modules: temporal and fine-grained feature aggregation (TFA), structure encoding (SE), and temporal consistency constraint (TCC). TFA and TCC modules facilitate consistent representation learning across frames, while the SE module encodes both appearance and structural information for precise fine-grained recognition. Experimental results on the SAT-MTB benchmark dataset demonstrate TCL's superior performance, achieving a new state-of-the-art oriented and fine-grained detection accuracy of 47.7% mAP–a 4.8% improvement over the baseline. Furthermore, our TCL framework readily accommodates existing image-based detectors, leading to enhanced detection accuracies.

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

On the Optimal Reasoning Length for RL-Trained Language Models

Reinforcement learning substantially improves reasoning in large language models, but it also tends to lengthen chain-of-thought outputs and increase computational cost. Although length-control methods have been proposed, the length-accuracy relationship they induce remains unclear. We train policies with several length-control methods on multiple base models in a controlled setup and find that, across both mathematical reasoning and code generation, accuracy is non-monotonic in output length, peaking at an intermediate value. Mode accuracy, however, continues to improve with length even in settings where sample accuracy plateaus or declines, indicating that the non-monotonic length-accuracy relationship is driven by dispersion around an increasingly correct center.

12.
arXiv (quant-ph) 2026-06-11

Coupled integrated photonic quantum memristors using a single photon source made of a colour center

arXiv:2602.14736v2 Announce Type: replace Abstract: Photonic quantum memristors provide a measurement-induced route to nonlinear and history-dependent quantum dynamics. Experimental demonstrations have so far focused on isolated devices or simple cascaded devices configurations. Here, we experimentally realize and characterize a network of two coupled photonic quantum memristors with crossed feedback, implemented on a silicon nitride photonic integrated circuit and fed by a room-temperature single-photon source based on a silicon-vacancy color center SiV$^-$ in a nanodiamond. Each memristor consists of an integrated Mach-Zehnder interferometer whose transfer function is adaptively updated by photon detection events on another memristor, thus generating novel non-Markovian input-output dynamics with an enhanced memristive behaviour compared to single devices. In particular, we report inter-memristor input-output hysteresis curves exhibiting larger form factors and displaying self-intersecting loops, respectively revealing marked bistability and self-intersecting hysteresis geometry. Furthermore, numerical simulations show how these features emerge from the interplay between memory depth and relative input phase, for both intra- and inter-memristor input-output relations. We experimentally test the performance of our system in the NARMA task. Our results establish coupled integrated photonic quantum memristors as scalable nonlinear building blocks and highlight their potential for implementing compact quantum neuromorphic and reservoir computing architectures.

13.
medRxiv (Medicine) 2026-06-22

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

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

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

EmbodiTTA: Resource-Efficient Test-Time Adaptation for Embodied Visual Systems

Continual Test-time adaptation (CTTA) continuously adapts the deployed model on every incoming batch of data. While achieving optimal accuracy, existing CTTA approaches present poor real-world applicability on resource-constrained edge devices, due to the substantial memory overhead and energy consumption. In this work, we first introduce a novel paradigm – on-demand TTA – which triggers adaptation only when a significant domain shift is detected. Then, we present OD-TTA, an on-demand TTA framework for accurate and efficient adaptation on edge devices. OD-TTA comprises three innovative techniques: 1) a lightweight domain shift detection mechanism to activate TTA only when it is needed, drastically reducing the overall computation overhead, 2) a source domain selection module that chooses an appropriate source model for adaptation, ensuring high and robust accuracy, 3) a decoupled Batch Normalization (BN) update scheme to enable memory-efficient adaptation with small batch sizes. Extensive experiments show that OD-TTA achieves comparable and even better performance while reducing the energy and computation overhead remarkably, making TTA a practical reality.

15.
arXiv (CS.CL) 2026-06-17

Moderating Illicit Online Image Promotion for Unsafe User-Generated Content Games Using Large Vision-Language Models

Online user generated content games (UGCGs) are increasingly popular among children and adolescents for social interaction and more creative online entertainment. However, they pose a heightened risk of exposure to explicit content, raising growing concerns for the online safety of children and adolescents. Despite these concerns, few studies have addressed the issue of illicit image-based promotions of unsafe UGCGs on social media, which can inadvertently attract young users. This challenge arises from the difficulty of obtaining comprehensive training data for UGCG images and the unique nature of these images, which differ from traditional unsafe content. In this work, we take the first step towards studying the threat of illicit promotions of unsafe UGCGs. We collect a real-world dataset comprising 2,924 images that display diverse sexually explicit and violent content used to promote UGCGs by their game creators. Our in-depth studies reveal a new understanding of this problem and the urgent need for automatically flagging illicit UGCG promotions. We additionally create a cutting-edge system, UGCG-Guard, designed to aid social media platforms in effectively identifying images used for illicit UGCG promotions. This system leverages recently introduced large vision-language models (VLMs) and employs a novel conditional prompting strategy for zero-shot domain adaptation, along with chain-of-thought (CoT) reasoning for contextual identification. UGCG-Guard achieves outstanding results, with an accuracy rate of 94% in detecting these images used for the illicit promotion of such games in real-world scenarios.

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

Prior-Informed Flow Matching for Graph Reconstruction

arXiv:2601.22107v2 Announce Type: replace Abstract: We introduce Prior-Informed Flow Matching (PIFM), a conditional flow model for graph reconstruction. Reconstructing graphs from partial observations remains a key challenge; classical embedding methods often lack global consistency, while modern generative models struggle to incorporate structural priors. PIFM bridges this gap by integrating embedding-based priors with continuous-time flow matching. Grounded in a permutation equivariant version of the distortion-perception theory, our method first uses a prior, such as GraphSAGE or node2vec, to form an informed initial estimate of the adjacency matrix based on local information. It then applies rectified flow matching to refine this estimate, transporting it toward the true distribution of clean graphs and learning a global coupling. Experiments on different datasets demonstrate that PIFM consistently enhances classical embeddings, outperforming them and state-of-the-art generative baselines in reconstruction accuracy.

17.
arXiv (CS.CV) 2026-06-18

A Multi-Domain Benchmark for Detecting AI-Generated Text-Rich Images from GPT-Image-2

Text-rich images often contain privacy-sensitive, transactional, or decision-relevant information. As recent multimodal image generation models become increasingly capable of synthesizing realistic textual content and structured visual designs, detecting AI-generated text-rich images has become an important challenge for digital trust and content authenticity. Existing benchmarks, however, largely focus on object-centric images and provide limited coverage of scenarios where textual semantics and layout organization are central. In this paper, we introduce a multi-domain benchmark for detecting text-rich images generated by OpenAI's GPT Image 2. The benchmark contains 8,602 images across six representative categories: commercial posters, infographics, academic posters, receipts, tables, and UI screenshots. Using this benchmark, we evaluate five representative AI-generated image detectors in a zero-shot setting and analyze their overall, category-wise, and post-processing robustness. Our results show that detector performance is highly domain-dependent: methods that perform well in some categories often fail on others, and even the strongest conventional detector exhibits severe sensitivity to JPEG compression. We further conduct an exploratory evaluation with a multimodal vision-language model, revealing both its promise and its limitations on structured formats. These findings highlight the need for text- and layout-aware detection methods for modern AI-generated images. Our dataset is released at XXX.

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

ORCA: A Platform for Open-Source Dexterity Research

arXiv:2606.14561v1 Announce Type: cross Abstract: Robotics manipulation research increasingly focuses on two-finger parallel grippers for their effectiveness, affordability, and ease of teleoperation. Grippers are nonetheless limited by their form factor, often requiring bimanual setups even for simple reorientation tasks. Anthropomorphic hands are a more natural platform for dexterous robot learning – closer to the human hand, and capable of learning from human video – yet they remain hard to use in learning research: even where open and accessible hand hardware exists, the software for control, simulation, teleoperation, and retargeting is scattered in one-off code bases, and largely disconnected from the robot-learning ecosystem. In this work, we introduce the \orca~learning stack, an open-source research stack for dexterity as a first-class robot learning domain. Our \orca~stack unifies low-level control, simulation, teleoperation from a range of consumer platforms, and hand retargeting, behind a single interface, and integrates natively with popular robot-learning frameworks such as \lerobot, so dexterous hand researchers can leverage the same data, training, and evaluation pipelines used for non-dexterous robot learning. We demonstrate a complete end-to-end workflow, collecting expert demonstrations of an in-hand reorientation task by teleoperation with a consumer-grade VR headset, training an autonomous policy with \lerobot, and evaluating the learned policy in a fully reproducible and observable setup. We open-source the entire stack as a shared, reproducible foundation for dexterous-manipulation research.

19.
arXiv (quant-ph) 2026-06-15

Simultaneous Estimation of Partial-Transpose Moments with Active Memory Independent of the Moment Order

arXiv:2606.14204v1 Announce Type: new Abstract: We study the simultaneous estimation of partial-transpose moments $p_j(\rho_{AB})=\mathrm{Tr}[(\rho_{AB}^{T_B})^j]$, $j=2,\ldots,K$, of an unknown bipartite $n$-qubit state from independent copies under an explicit active-memory constraint. We give a sequential qubit-reuse realization of the partial-transpose permutation that uses at most $2n+1$ active qubits, independent of $K$, and estimates all moments $p_2,\ldots,p_K$ to uniform additive error $\epsilon$ with total copy complexity $O(K\log K/\epsilon^2)$. We also prove two converse bounds. First, any uniformly accurate simultaneous estimator requires $\Omega(K/\epsilon^2)$ copies in the worst case. Second, the same scaling holds on an explicit isospectral two-qubit negative-partial-transpose (NPT) family whose ordinary moments are constant while the partial-transpose moments vary. These results characterize the copy complexity of the partial-transpose moment hierarchy up to a logarithmic factor and extend simultaneous nonlinear-functional estimation from ordinary state powers to partial-transpose spectral data under active quantum memory independent of the target moment order.

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

Findings of the MAGMaR 2026 Shared Task

This overview paper presents the results of the shared task for the second workshop on Multimodal Augmented Generation via Multimodal Retrieval (MAGMaR). In this shared task participants submitted systems focused on either (i) video retrieval or (ii) grounded generation of articles given retrieved videos. Teams could submit to either task. For the retrieval task, we had 2 participating teams that submitted a total of 17 systems – all of which beat a baseline derived from the winner of last year's shared task. On the generation side, we had 4 teams submit 16 systems. All teams had at least one generated report that was labeled the best by a human annotator.

21.
PLOS Computational Biology 2026-06-18

Mechanisms underlying spontaneous and evoked calcium responses in oligodendrocyte precursor cells: A modeling investigation

Authors:

by Martin Lardy, Leqi Wang, Claire Guerrier, Veronica T. Cheli, Pablo M. Paez, Anmar Khadra Calcium (Ca2+) signaling has emerged as a central regulator of activity-dependent myelination in oligodendrocytes. These Ca2+ signals encompass both the stimulus-independent spontaneous Ca2+ local transients (SCaLTs) generated intrinsically in a voltage-independent manner or facilitated by the membrane voltage, as well as evoked responses triggered by ATP and glutamate release. To investigate the regulatory mechanisms underlying this combined spiking activity, we developed a stochastic spatiotemporal flux-balance model of Ca2+ transients in oligodendrocyte precursor cells (OPCs). The model incorporates all the relevant fluxes in these cells and integrates membrane voltage dynamics with a Ca2+-induced Ca2+-release (CICR) mechanism using parameters fitted to Ca2+ fluorescence recordings. The model reproduced the intrinsic and voltage-facilitated SCaLTs in OPCs in the absence of purinergic and glutamatergic receptors, and captured the three distinct patterns of evoked Ca2+ responses induced by prolonged ATP and glutamate stimulations identified using machine classifier. The model highlighted the role of ATP and glutamate in generating these clusters, and showed that the fast dynamics of CICR is key to producing these evoked responses. Further analysis of the model also revealed that voltage-gated L- and T-type Ca2+ channels slightly increase the frequency of SCaLTs, while stimulation with ATP and glutamate, using randomly distributed pulses mimicking in vivo conditions, leads to an increase in both the amplitudes of Ca2+ spikes (i.e., the combination of SCaLTs and evoked responses) and the prevalence of wide spikes, especially upon glutamate stimulation. Bifurcation analysis of the deterministic version of the model, in the absence of diffusion, demonstrated that ATP and glutamate stimulation can shift the system into an oscillatory regime, thereby increasing the deterministic component of SCaLT dynamics. This study thus offers a comprehensive representation of OPC Ca2+ transients linking recorded in vitro behaviors to in vivo dynamics.

22.
medRxiv (Medicine) 2026-06-12

Design, Implementation, and Evaluation of a Shadowing Program for Medical Students in the Basic Sciences Phase

Introduction Shadowing, as an educational method based on active observation, can foster a realistic understanding of professional roles and enhance the communication skills of medical students. This study aimed to design, implement, and evaluate a shadowing program for basic sciences medical students. Methods This development study was conducted based on the ADDIE model in five phases. The study population consisted of 799 medical students in semesters 2 to 5. The stages included Analysis (determining needs through literature review and expert panels), Design (specifying learning environments and evaluation methods), Development (preparing guides and educational tools), Implementation (within the Medical Ethics course), and Evaluation (using questionnaires and reflection forms). Findings This study aimed to design and evaluate an educational shadowing program based on the ADDIE model. In the Analysis phase, the profiles of 799 students and learning objectives were determined. In the Design phase, a structured program for four types of shadowing was designed. In the Development phase, all guides and educational tools were prepared. In the Implementation phase, the program was carried out with complete coverage and adherence to ethical considerations. Finally, the program evaluation showed that "Motivation to become a good physician" (3.75-3.95) and "Enhancing empathy" (3.50-3.94) received the highest scores, while "Increasing understanding of the basic science-clinical connection" (2.53-2.89) and "Willingness to attend on holidays" (1.87-2.31) received the lowest scores. Conclusion The findings indicate that implementing the shadowing program is an effective method for strengthening the professional attitudes and academic motivation of medical students. However, the program did not significantly improve students perception of the basic science-clinical connection, indicating a need for curricular refinement. The continuation and extension of this program to other levels and fields of medical sciences are recommended.

23.
arXiv (math.PR) 2026-06-18

A simple approach to the L{\o}kka-Zervos dichotomy for absolutely continuous dividend strategies

arXiv:2604.13302v3 Announce Type: replace-cross Abstract: We revisit the optimization problem solved in L{\o}kka & Zervos (2008), i.e., the maximization of dividends, in a Brownian risk model, with the possibility (not the obligation) of making capital injections. Following the approach introduced in Alvarez & Shepp (1998), Renaud & Simard (2021), Renaud et al. (2023), we consider instead absolutely continuous (AC) dividend strategies with an affine bound on the payment rates, while singular capital injections are still allowed. In addition, we incorporate a parameter for the cost of ruin or, said differently, a penalty at ruin in the performance function. We show that the solution is a so-called L{\o}kka-Zervos dichotomy: the surplus is never ruined by making bail-out payments, or no capital is injected and bankruptcy can occur; in either case, dividends are paid at full rate when the surplus is above a threshold. Our framework allows us to provide explicit conditions to express the dichotomy, either using the cost of capital injections or the cost of ruin as a criterion, which also exposes the underlying structure of the solution. In particular, for some values of the parameters, we show that it is optimal to liquidate. Moreover, we perform a numerical analysis highlighting the range of values generated under this AC affine-bound structure.

24.
arXiv (CS.AI) 2026-06-15

Capability Minimization as a Safety Primitive: Risk-Aware Causal Gating for Least-Privilege LLM Agents

arXiv:2606.13884v1 Announce Type: new Abstract: Modern decision systems increasingly rely on learned components whose outputs may be confident yet wrong, exposing downstream actions to costly errors. We introduce Risk-Aware Causal Gating (RACG), a framework that decides whether to act on, defer, or abstain from a model's prediction by combining causal effect estimation with calibrated risk control. RACG models the causal pathway from candidate actions to outcomes and gates each decision according to an estimated counterfactual risk rather than raw predictive confidence. To make gating reliable, we derive distribution-free bounds on the probability of acting under high-risk conditions and show how these bounds translate into operating thresholds that satisfy user-specified safety constraints. We further propose an adaptive gating policy that adjusts to distribution shift by monitoring discrepancies between predicted and realized outcomes, tightening the gate when causal assumptions appear violated. Across simulated interventions and real-world decision benchmarks, RACG reduces high-cost errors substantially while preserving most of the utility of an ungated policy, and it outperforms confidence-based and selective-prediction baselines at matched abstention rates. Our results indicate that explicitly separating causal risk from predictive uncertainty yields decision systems that are both safer and more transparent, offering a principled mechanism for trustworthy automation in high-stakes settings.

25.
Nature Medicine 2026-06-12

General-purpose large language models outperform specialized clinical AI tools on medical benchmarks

Specialized clinical artificial intelligence (AI) tools are entering medical practice despite scarce independent evaluation. We quantitatively evaluate two clinical AI tools, OpenEvidence and UpToDate Expert AI, built on large language models (LLMs) against three frontier LLMs: GPT-5.2, Gemini 3.1 Pro and Claude Opus 4.6. Our evaluation has three stages: (1) 500 MedQA questions testing medical knowledge, (2) 500 HealthBench items measuring alignment with clinicians and (3) the real clinical queries (RCQ) benchmark, built from 100 de-identified queries from physicians to a general-purpose language model in a live clinical environment. For the RCQ benchmark, 12 US clinicians performed randomized, blinded review of model outputs, producing 1,800 model–question annotations. Frontier LLMs outperformed clinical AI tools in all three evaluations. Clinical AI tools performed comparably to auto-enabled Google Search AI Overview on the RCQ. These findings highlight the need for independent, real-world evaluation of AI tools before they enter clinical settings. In an independent evaluation, frontier large language models outperformed specialized clinical artificial intelligence tools on medical knowledge, clinician alignment and real-world clinical queries.