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01.
medRxiv (Medicine) 2026-06-19

Extraction of Glaucoma Diagnosis, Type, and Severity from Clinical Notes using Secure Cloud-based Large Language Models

Purpose: To evaluate the performance of secure cloud-based large language models (LLMs) in extracting glaucoma diagnosis, type, and severity from free-text clinical notes in the electronic health record (EHR). Design: Retrospective chart review analysis. Participants: 1,250 subjects from the Bascom Palmer Ophthalmic Repository. Methods: Clinical notes of glaucoma-related encounters between 2014 and 2024 were extracted from the Bascom Palmer Ophthalmic Repository. Two fellowship-trained glaucoma specialists annotated clinical notes for glaucoma presence, type, and severity at the eye level. The dataset was split into development (10%), validation (10%), and test (80%) sets. Development and validation sets were used for prompt engineering and refinement, and the held-out test set was used for evaluation. Five LLMs (Claude Opus 4.6, DeepSeek-V3.2, GPT-5.2, Grok 4.1, and Qwen3.6-35B-A3B) were accessed via Azure AI Foundry within HIPAA-compliant containers. Model performance was assessed using standard metrics. Clinician-entered ICD-10 codes were also compared with adjudicated labels. Main Outcome Measures: Gwet AC1, accuracy, sensitivity, specificity, and F1-score. Results: Inter-grader agreement was high for glaucoma detection (Gwet AC1= 0.930 (95% CI: 0.917-0.945), type classification (Gwet AC1= 0.917 (95% CI: 0.904-0.930), and severity staging (Gwet AC1= 0.901 (95% CI: 0.884-0.916). For glaucoma diagnosis, LLMs demonstrated high overall accuracy, with Claude achieving 97.5%, DeepSeek 96.0%, GPT 96.2%, Grok 94.4%, and Qwen 95.5%. F1 scores for glaucoma detection ranged from 95.4% to 98.9% across models. For glaucoma type classification, accuracies were 97.1%, 94.2%, 94.2%, 94.0%, and 94.4% for Claude, DeepSeek, GPT, Grok, and Qwen, respectively. F1 scores for the most prevalent type (POAG) ranged from 96.3% to 98.9%. For severity staging, accuracies were 95.0%, 94.8%, 94.5%, 94.0%, and 95.2%, respectively, with F1 scores ranging from 89.7% to 96.3% across severity categories and models. ICD-10 codes demonstrated substantially lower performance for type and severity staging, with overall accuracies of 89.2% and 58.5%, respectively. Conclusions: Secure cloud-based LLMs accurately extracted glaucoma diagnosis, type, and severity information from free-text ophthalmology notes, achieving performance approaching expert clinician adjudication while substantially outperforming ICD-based phenotyping approaches, particularly for disease severity classification. These findings demonstrate the potential of LLMs to transform unstructured clinical documentation into scalable, research-ready phenotypic data for large-scale glaucoma cohort development and EHR-based ophthalmic research.

02.
medRxiv (Medicine) 2026-06-12

The Acceptability of Three Co-Created Peer Support Interventions for People Living with Leprosy Reactions in Indonesia: A Mixed-Methods Pilot Study

Background: Leprosy reactions (LR) are immune-mediated complications associated with disability, emotional distress, and social isolation. We identified a gap in affected-individual-informed interventions that aim to improve the management of LR in healthcare settings. To address this gap, we assessed the acceptability of three peer-support interventions co-created with people affected by LR in Indonesia. Methods: Using an interactive learning and action approach, we co-created peer counselling, telesupport groups, and participatory video interventions which were piloted in an urban hospital and 13 rural community clinics. A mixed-methods design was applied with interviews, focus group discussions, and pre-post assessments involving four participant groups. Data were analyzed thematically using an acceptability framework. Results: One hundred participants were enrolled, and 92 completed the pilot intervention between November 2022 and July 2023. Qualitative findings showed that all interventions were acceptable. Peer counselling provided emotional reassurance through shared experiences and was perceived as trustworthy and supportive. Perceived burdens differed by setting, with time constraints in urban facilities and geographical barriers in rural clinics. Knowledge improved significantly among participants of peer counselling and telesupport groups in rural settings. Telesupport groups facilitated connection, information exchange, and continuity of care. Digital access and literacy limited participation for some, particularly in rural areas. The participatory video was perceived as reassuring and informative. Improvements in knowledge, attitude, practices, and mental well-being domain scores were observed among urban participants, but responses in rural settings showed less change. Participants and co-implementers reported increased self-efficacy, participants confidence to perform required behaviors within peer support interventions, with effects shaped by intervention and setting. Conclusions: The three co-created peer-support interventions were acceptable for individuals with LR in diverse healthcare settings. These outcomes highlight the importance and effectiveness of selective, and context-sensitive implementation of one or more peer-support modalities.

03.
arXiv (CS.AI) 2026-06-19

HilDA: Hierarchical Distillation with Diffusion for Advancing Self-Supervised LiDAR Pre-trainin

arXiv:2606.20189v1 Announce Type: cross Abstract: Leveraging Vision Foundation Models (VFMs) for camera-to-LiDAR knowledge distillation offers a promising solution to the scarcity of annotated data needed to represent the immense geometric and kinematic diversity of real-world autonomous driving (AD). However, current approaches typically treat VFMs as black-box teachers, relying exclusively on frame-wise feature similarity. Consequently, they do not fully exploit the teacher's layer-wise semantic structure and global context, as well as the rich spatiotemporal information inherent in LiDAR sequences. We propose HilDA, a self-supervised pretraining framework for LiDAR backbones that better captures the semantic what and geometric where needed for driving tasks. HilDA combines hierarchical distillation comprising multi-layer distillation for progressive semantic alignment and global context distillation for scene-level semantics, with a temporal occupancy diffusion objective promoting spatiotemporal consistency. Models pre-trained with HilDA achieve state-of-the-art results on cross-modal distillation benchmarks and outperform models trained via prior distillation approaches on 3D object detection, scene flow, and semantic occupancy prediction. Code available at: https://maxiuw.github.io/hilda.

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

Predicting Mergeability of Parameter-Efficient Fine-Tuning Updates

arXiv:2606.19549v1 Announce Type: new Abstract: Low-rank adaptation (LoRA) makes it cheap to train many domain- and task-specific language model adapters, but whether two adapters can be merged is usually discovered only after both have been fully trained and evaluated. This late feedback is costly: adapters that are strong in isolation can interfere destructively once their updates are combined. We ask whether this outcome can be anticipated. We formalize adapter mergeability as the degree to which an adapter preserves its single-task utility after merging, and show that it can be forecast from signals measured in the first few percent of training – chiefly how the low-rank updates and their gradients align across tasks and how much they disturb shared representations. We package these signals into MergeProbe, a lightweight predictor that estimates pairwise and set-level retention and turns the estimate into a concrete decision: merge directly, reweight, prune, or route. On MERGE-PEFT, a five-domain benchmark spanning math, code, science, instruction following, and safety, MergeProbe attains the best average and worst-case retention among strong interference-aware merge baselines while adding far less deployment overhead than full task routing. This turns LoRA merging from a post-hoc engineering step into an anticipatory measurement problem.

05.
arXiv (CS.LG) 2026-06-16

Filtered Conformal Ellipsoids for Graph-Native Time Series

arXiv:2606.17014v1 Announce Type: new Abstract: Joint prediction sets for multivariate time series should control a single event while adapting to cross-coordinate dependence. We study filtered conformal ellipsoids: a frozen state-space filter emits a one-step predictive mean and covariance, and split-conformal calibration is applied to the resulting Mahalanobis scores. The filter is used to choose the ellipsoid shape; conformal calibration chooses the scalar radius, so the construction benefits from a learned predictive covariance without relying on Gaussian tail probabilities for coverage. The main difficulty is that filtered scores are dependent and learned recurrent filters need not contract in their raw hidden state; we therefore analyse contraction in an observable predictive-law quotient that identifies hidden states producing the same future sequence of emitted Gaussian laws. Under a stable Bayes Gaussian-projection filter, covariance bounds, and a finite-horizon observability Fisher condition, small excess Gaussian negative log-likelihood implies contraction of the learned emitted laws. Combined with a threshold-autocovariance envelope this yields a Chebyshev-type approximate coverage bound for filtered split-conformal prediction under dependence; a sharper Bernstein-type bound requires an additional geometric-mixing concentration assumption. Under Gaussian oracle realisability we also obtain a near-oracle log-volume comparison within the class of conditionally valid Gaussian ellipsoid rules. We instantiate the framework with a GCN-GRU filter with diagonal-plus-low-rank covariance. On moderate-size graph-native traffic benchmarks (METRLA-$20$ and PEMSBAY-$50$), the learned filter gives sharper at-target ellipsoids than static-covariance and non-filter baselines; at full-graph scale and on non-graph-native datasets, factor and copula baselines can be stronger.

06.
arXiv (CS.CV) 2026-06-24

FiCA: Feed-forward instant Gaussian Codec Avatars from a Single Portrait Image

We introduce FiCA, a Feed-forward, instant Gaussian Codec Avatar generation pipeline that creates lifelike avatars from a single portrait image. Generating a photorealistic and drivable avatar from just a single image is significantly challenging due to the limited visual information available to accurately infer the 3D appearance and geometry of human heads. To address this, we develop a novel system that combines human-centric vision foundation models with a diffusion model. This system is designed to fully exploit partial visual observations to generate lifelike human avatars. Our proposed diffusion model learns a generative mapping from these partial observations to complete and authentic 3D mesh reconstruction. Additionally, we introduce a feed-forward mesh refinement network that enhances the fidelity and identity preservation of the generated avatars, eliminating the need for person-specific test-time optimization. By leveraging a universal prior model that decodes a generated mesh into a set of 3D Gaussians, we generate a photorealistic 3D Gaussian avatar, capable of being driven with novel expressions in real-time. Our experiments demonstrate that the avatars generated by our feed-forward approach faithfully represent diverse identities and surpass the visual quality of avatars produced by recent competing methods.

07.
medRxiv (Medicine) 2026-06-16

Validation of a Smartphone-Image-Based Computer-Vision Model for Lean Mass and Body Fat Estimation Against Dual-Energy X-ray Absorptiometry

Introduction Body composition, rather than body weight alone, is an increasingly important health metric, and preservation of lean mass has become a central concern in obesity treatment, aging, and chronic disease management. Dual-energy X-ray absorptiometry (DXA) provides accurate assessment of fat and lean tissue, but its cost and logistical requirements limit repeated measurement. Computer-vision approaches show promise for estimating adiposity from smartphone images, but lean-mass estimation remains less established. Methods We evaluated a computer-vision body composition model, applied to consumer-grade smartphone photographs, against DXA in a held-out validation sample of 195 adults from an ongoing cross-sectional study. Body fat percentage and total lean mass percentage were co-primary outcomes; for total lean mass percentage, an image-only configuration (no added covariates) was pre-specified as primary. Agreement was quantified using Lin's concordance correlation coefficient (CCC) as the lead statistic, with Pearson correlation, mean absolute error, root mean square error, mean bias, and Bland-Altman limits of agreement. In secondary analyses, appendicular lean mass and total lean mass percentage were each estimated with and without routine anthropometric and demographic inputs (body weight, height, age, and sex). Results Total lean mass percentage agreed with DXA from image features alone (CCC 0.916). Body fat percentage, estimated with routine inputs added, agreed at least as closely (CCC 0.930). Adding routine inputs barely changed agreement for total lean mass percentage but markedly improved it for appendicular lean mass, an absolute quantity that scales with body size. Conclusions A smartphone-image-based model estimated both body fat and lean mass with strong agreement to DXA, with lean mass percentage from image features alone. The approach needs no fixed equipment or ionizing radiation. Whether it can track change over time, including in incretin-based weight loss where lean mass preservation is a concern, was not assessed in this cross-sectional study.

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

A Mathematical Theory of Value: a synthesis on goal-directed agency under resource constraints

作者:

arXiv:2606.12502v1 Announce Type: cross Abstract: We propose that value – the quantity goal-directed agents create, destroy, and exchange – is a lawful structural quantity in the same category as information. Following Shannon's method, we make one ruthless abstraction: value is the rate at which an agent converts a resource into goal-progress, relative to a frame fixed by its goal. A scale-invariance axiom forces a logarithmic measure, $V=\sum_i k_i \ln e_i$; compounding of a reinvested resource forces the same form via the ergodicity argument of Peters (2019). The two routes are kin rather than independent; their agreement is a consistency check, not an over-determination. We derive a coding theorem of value: $\Delta G \le I(X;Y)$, achieved by Bayes-proportional allocation; realized value decomposes as $G=D(q\|r)-D(q\|p)$, identifying misalignment with measurable waste. For populations, value is frame-relative while price is frame-independent; a fleet that pools its resource and fuses its perception inherits the ceiling $G_{\mathrm{fleet}} \le I(X;Y_{1:m}) \le H(X)$ (a corollary; an earlier sum-form claim was wrong and is corrected in v5). A dynamical layer yields an is/ought asymmetry from which alignment emerges as a control-stability condition with a closed-form residual. We test the single-frame laws on live language models in a pre-registered scale-up: perception mutual information tracks realized capability rather than parameter count (Spearman $\rho = 0.977$ pooled over 30 model$\times$domain points), out-of-sample $\Delta G$ tracks $I(X;Y)$, and over-confidence is measurable dissipation; a further pre-registered test shows the bridge is shape-invariant across four task shapes ($n=42$, slope 0.953). None of the mechanisms is individually new – generalized Kelly, Armstrong & Mindermann (2018), classical control; the contribution is their unification and the governance mapping (incentive design over oversight) that follows.

09.
arXiv (CS.CL) 2026-06-17

TACOMORE: Exploring a replicable prompting protocol for LLM-assisted corpus analysis

As corpus linguistics continues to scale, researchers are facing a growing methodological bottleneck: while computational tools can easily count billions of words, the qualitative interpretation of these data remains a slow and labor-intensive human task. Large Language Models (LLMs) offer a promising way to automate this process, yet their integration into the field is often hindered by concerns over black-box unpredictability and a lack of replicability. This study introduces TACOMORE, a structured prompting framework designed to transform ad-hoc AI interactions into a standardized linguistic protocol. Built upon four foundational principles (Task, Context, Model, and Replicability), the framework guides LLMs to move beyond generic probability prediction to anchoring their reasoning in the specific co-occurrence patterns of a target corpus. We applied this framework to three core corpus tasks, i.e., the analysis of keywords, collocates, and concordances, using an open corpus of COVID-19 research abstracts. After testing three LLMs, we found that while structured prompting improves accuracy and replicability, inherent limitations regarding hallucination persist. This research offers a critical lens into the role of LLMs in corpus linguistics, highlighting their potential as complementary tools while emphasizing the irreplaceable role of human validation.

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

AI Contagion in Social Networks

arXiv:2606.15206v1 Announce Type: cross Abstract: We study how artificial intelligence (AI) interacts with social communication networks to shape the stability of collective knowledge. Agents exchange information through a network while receiving AI-generated content, and AI systems retrain on the aggregate social information they influence. This interaction generates two feedback forces: an AI contagion channel, through which distortions diffuse across the network, and an AI social distortion multiplier, through which retraining amplifies past errors. Despite the high dimensionality of the environment, we show that the long-run behavior of the system admits a two-dimensional representation whose spectral radius determines whether AI-mediated information systems are dynamically stable or unstable. We characterize a sharp regulatory frontier identifying the minimum filtering required for stability and show how network topology shapes systemic informational risk.

12.
Nature (Science) 2026-06-22

Why heritage sites are at risk in a warming world — and how to save them

As rising seas and intensifying disasters threaten historic sites worldwide, new ways to understand, preserve and adapt these places are needed urgently. As rising seas and intensifying disasters threaten historic sites worldwide, new ways to understand, preserve and adapt these places are needed urgently.

13.
arXiv (CS.AI) 2026-06-24

An Introduction to Causal Reinforcement Learning

arXiv:2606.24160v1 Announce Type: new Abstract: Causal inference provides a set of principles and tools that allow one to combine data and knowledge about an environment to reason with questions of counterfactual nature, i.e., what would have happened had reality been different, even when no data of this unrealized reality is currently available. Reinforcement learning provides methods to learn a policy that optimizes a specific measure (e.g., reward, regret) when the agent is deployed in an environment and pursues an exploratory, trial-and-error approach. These two disciplines have evolved independently and with virtually no interaction between them. We note that they operate over different aspects of the same building block, counterfactual relations, which makes them umbilically connected. Based on these observations, novel learning opportunities arise when this connection is explicitly acknowledged and mathematized. To realize this potential, we note that any environment where the RL agent is deployed can be decomposed as a collection of autonomous mechanisms with different causal invariances, parsimoniously modeled as a structural causal model; any standard RL setting implicitly encodes such a model. This formalization allows us to put under a unifying treatment different modes of learning, including online, off-policy, and causal calculus learning, which appear unrelated in the literature. However, these modalities are not exhaustive: we introduce several natural and pervasive classes of learning settings that entail novel dimensions of analysis. Specifically, we introduce and discuss through causal lenses generalized policy learning, where to intervene, imitation learning, and counterfactual learning. These tasks lead to a broader view of counterfactual learning and suggest great potential for studying causal inference and reinforcement learning side by side, which we call causal reinforcement learning (CRL).

14.
arXiv (quant-ph) 2026-06-24

Reinforcement Learning to Disentangle Multiqubit Quantum States from Partial Observations

arXiv:2406.07884v3 Announce Type: replace Abstract: Using partial knowledge of a quantum state to control multiqubit entanglement is a largely unexplored paradigm in the emerging field of quantum interactive dynamics with the potential to address outstanding challenges in quantum state preparation and compression, quantum control, and quantum complexity. We present a deep reinforcement learning (RL) approach using an actor-critic algorithm for constructing short disentangling circuits for states with up to 16 qubits. With access to only two-qubit reduced density matrices, our agent decides which pairs of qubits to apply two-qubit gates on; requiring only local information makes it directly applicable on modern NISQ devices, as we demonstrated experimentally on a trapped-ion quantum computer. Utilizing a permutation-equivariant transformer architecture, the agent can autonomously identify qubit permutations within the state, and adjusts the disentangling protocol accordingly. Once trained, it provides circuits from different initial states without further optimization. We demonstrate the agent's ability to identify and exploit the entanglement structure of multi-qubit states. We analyze the disentangling circuits constructed by the agent for 4- and 5-qubit Haar-random states, and observe strong correlations between consecutive gates and among the qubits involved. Through extensive benchmarking, we show the efficacy of the RL approach to find disentangling protocols with minimal gate resources. We explore the resilience of our trained agents to noise, highlighting their potential for real-world quantum computing applications. Analyzing optimal disentangling protocols, we report a general circuit to prepare an arbitrary 4-qubit state using at most 5 two-qubit (10 CNOT) gates.

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

LatentGym: A Testbed For Cross-Task Experiential Learning With Controllable Latent Structure

arXiv:2606.15306v1 Announce Type: cross Abstract: We envision continually learning agentic systems that become more useful over time: as they encounter sequences of related tasks, they should infer the hidden structure shared across those tasks and use it to improve future decisions. This cross-task experiential learning capability is pivotal in domains such as personalization and interactive assistance, but existing training/evaluation frameworks do not provide shared, controllable latent structures and cannot measure whether or why agents improve. We introduce LatentGym: a controllable suite in which each environment is organized around a ground-truth latent variable governing the structure across tasks. Our construction yields metrics that separate exploration (whether the agent's actions gather information about the latent) from exploitation (whether the agent uses what it has gathered). We demonstrate our suite on empirical studies addressing three questions: how and why frontier models fail to adapt across related tasks; whether post-training on related task sequences improves general cross-task adaptation, and where those gains come from; and how design choices such as inter-task feedback shape training dynamics and generalization. Together, these results establish a controlled foundation for studying how LLM agents learn from experience across tasks, and for designing agents that adapt more reliably in sequential, personalized, and interactive settings.

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

Self-Recognition Finetuning can Prevent and Reverse Emergent Misalignment

Emergent misalignment (EM) has been linked to the activation of misaligned persona vectors and evil character traits, suggesting that EM operates through disruption of the model's aligned character rather than direct learning of harmful content. Motivated by this connection, we study self-generated text recognition (SGTR) finetuning as a character-targeted intervention that is distinct from existing in-training defenses. We conduct two-stage finetuning experiments across three models (GPT-4.1, Qwen2.5-32B-Instruct, Seed-OSS-36B-Instruct) and multiple EM datasets to compare SGTR finetuning against benign finetuning baselines (correct domain-specific data, general knowledge, and word counting) to find it an effective defense in both reversal and prevention settings. We find that all interventions produce comparable EM reversal, but only when restoring capabilities that EM had degraded. For prevention, only SGTR finetuning consistently reduces misalignment without exacerbating any individual metric, suggesting that character fortification specifically drives prevention. We provide further evidence for EM's relation to the LLM's default character by showing that EM finetuning induces diversity into the LLM's identity self-reports, artificially corrupting self-recognition exacerbates misalignment caused by EM finetuning, and that removing the model's identity-bearing system prompt substantially reduces the effect of EM finetuning. Together, these findings reframe EM not as the adoption of a coherent misaligned persona but as the destabilization of aligned character.

17.
arXiv (CS.LG) 2026-06-16

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

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

18.
arXiv (quant-ph) 2026-06-19

Inhibited radiative decay enhances single-photon emitters

arXiv:2511.23301v2 Announce Type: replace Abstract: Quantum networks and modular quantum computers require efficient spin-photon interfaces, often realized using optical resonators that enhance radiative decay on a desired transition. However, this requires small mode volumes and high quality factors, which limits multiplexing capacity and demands precise frequency tuning. Here, we demonstrate an alternative approach that circumvents these bottlenecks for upscaling. Using a W1 silicon photonic crystal waveguide with a tailored photonic bandgap, we selectively inhibit unwanted decay pathways, thereby redirecting emission to the desired transition. This enables efficient photon collection over a large frequency range, allowing the resolution and individual addressing of tens of erbium dopants. Their lifetimes are preserved, or even increased, compared to bulk material. The extended mode volume of the devices enables the use of lower dopant concentrations, thereby improving emitter coherence. Our approach can be combined with Purcell enhancement and applied to other spin-qubit platforms, opening intriguing perspectives for photonic quantum technologies.

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

Robust and Fast Training via Per-Sample Clipping

arXiv:2605.02701v2 Announce Type: replace-cross Abstract: We propose a robust gradient estimator based on per-sample gradient clipping and analyze its properties both theoretically and empirically. We show that the resulting method, per-sample clipped SGD (PS-Clip-SGD), achieves optimal in-expectation convergence rates for non-convex optimization problems under heavy-tailed gradient noise. Moreover, we establish high-probability convergence guarantees that match the in-expectation rates up to polylogarithmic factors in the failure probability. We complement our theoretical results with multiple numerical experiments. In particular, we demonstrate that PS-Clip-SGD outperforms both vanilla SGD with momentum and standard gradient clipping when training AlexNet on the CIFAR-100 dataset, even after accounting for the additional computational time caused by per-sample clipping. We also empirically show that, in the presence of gradient accumulation, applying clipping at the mini-batch level can improve training performance while incurring virtually no additional computational cost. This finding is particularly interesting, as it contradicts the common practice of applying clipping only after all accumulation steps have been completed.

20.
arXiv (CS.AI) 2026-06-24

A Unified Framework for Runtime Verification and Model-Based Diagnosis in LOLA

arXiv:2606.23720v1 Announce Type: cross Abstract: We present an integrated framework that unifies runtime verification and model-based diagnosis within the stream specification language LOLA. By encoding system descriptions, component health states, and observations into a single stream-based formalism, the approach enables continuous, online fault localization directly alongside fault detection, without requiring separate toolchains. The framework supports both time-invariant and transient faults, and naturally accommodates nondeterministic observations.

22.
Nature (Science) 2026-06-10

Mitochondria directly interact with the nuclear pore complex

Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example has been contact with the endoplasmic reticulum at mitochondrial-associated endoplasmic reticulum membranes1, which control pathways including redox and calcium homeostasis2,3. Recent studies have also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signalling4,5. Here we identify direct interactions between mitochondria and nuclear pores. Using two unbiased proteomic screens, GST pulldown and BioID, we found that VDAC1 was the top mitochondrial candidate that interacts with the filamentous nuclear pore protein RANBP2. In vitro RANBP2 CRISPR knockout, RANBP2 truncation or site-directed mutagenesis of RANBP2–VDAC1 interacting amino acids resulted in reduced mitochondria–nucleus proximity and decreased nuclear ATP and phosphocreatine levels. This was accompanied by a decline in the levels of the nuclear phosphoproteome and downregulation of pathways involved in histone modification, cellular differentiation and transcriptional regulation in vitro. Moreover, deletion of the RANBP2 C-terminal domain in vivo in mice resulted in embryonic lethality due to cardiac and neural crest differentiation defects. Collectively, these results describe a mechanism by which mitochondria directly interact with the nuclear pore complex, a phenomenon critical for regulation of nuclear energetics and cellular differentiation. Undoubtedly, additional roles of this interaction remain to be revealed. Mitochondria interact directly with the nuclear pore complex via VDAC1–RANBP2 binding to sustain nuclear ATP levels.

23.
medRxiv (Medicine) 2026-06-12

Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive molecular complexity, profound stromal remodeling, and limited responsiveness to systemic therapies. Although gemcitabine-based regimens remain widely utilized, the molecular pathways that influence treatment-associated biological variation are incompletely understood. The TGF{beta} and JAK/STAT signaling networks are recognized regulators of tumor progression, immune modulation, and therapeutic resistance; however, their genomic architecture in clinically stratified PDAC populations remains poorly defined. Methods: We employed a conversational artificial intelligence-driven analytical framework to investigate TGF{beta} and JAK/STAT pathway alterations in a cohort of 184 PDAC patients. Clinical and molecular data were integrated to generate age- and treatment-stratified cohorts, enabling pathway-level and gene-level analyses according to gemcitabine exposure. Findings generated through AI-assisted interrogation were subsequently evaluated using conventional statistical approaches. Results: TGF{beta} pathway alterations were identified in approximately one-quarter to one-third of tumors across clinical subgroups and demonstrated relatively stable frequencies regardless of age at diagnosis or gemcitabine treatment status. Gene-level analyses revealed that pathway disruption was predominantly driven by recurrent alterations in SMAD4, with additional low-frequency events involving TGFBR1 and TGFBR2. Notably, TGFBR2 mutations were significantly more frequent among late-onset PDAC patients receiving gemcitabine compared with untreated late-onset patients (8.8% vs. 1.4%; p = 0.04), suggesting a potential treatment-associated enrichment. In contrast, JAK/STAT pathway alterations were rare throughout the cohort, with only isolated mutations observed in pathway components including JAK1, JAK2, JAK3, STAT1, STAT3, and related regulatory genes. No significant differences in JAK/STAT alteration frequencies were identified according to age or treatment exposure. Conclusions: TGF{beta} and JAK/STAT pathways exhibit distinct genomic architectures in PDAC. TGF{beta} pathway disruption represents a recurrent feature of disease biology, largely driven by SMAD4 alterations, while TGFBR2 enrichment in gemcitabine-treated late-onset tumors suggests a potential context-specific association worthy of further investigation. Conversely, genomic alterations within the JAK/STAT pathway are uncommon, indicating that pathway activity may be regulated predominantly through non-genomic mechanisms. These findings demonstrate the utility of conversational artificial intelligence agents for rapid, scalable, and clinically contextualized pathway interrogation and support future studies integrating multi-omic data to refine precision medicine strategies in PDAC.

24.
arXiv (CS.AI) 2026-06-11

SpikeDecoder: Realizing the GPT Architecture with Spiking Neural Networks

arXiv:2606.12287v1 Announce Type: cross Abstract: The Transformer architecture is widely regarded as the most powerful tool for natural language processing, but due to a high number of complex operations, it inherently faces the issue of high energy consumption. To address this issue, we consider Spiking Neural Networks (SNNs), which are an energy-efficient alternative to conventional Artificial Neural Networks (ANNs) due to their naturally event-driven approach to processing information. However, this inherently makes them difficult to train. Often, many SNN-based models circumvent this issue by converting pre-trained ANNs. More recently, attempts have been made to design directly trainable SNN-based adaptations of the Transformer model structure. Although the results showed great promise, the application field was computer vision. Moreover, the proposed model incorporates only encoder blocks. In this paper, we propose SpikeDecoder, a fully SNN-based implementation of the Transformer decoder block, for applications in natural language processing. In a series of experiments, we analyze the impact of exchanging different blocks of the ANN model with spike-based alternatives to identify trade-offs and significant sources of performance loss. We further investigate the role of residual connections and the selection of SNN-compatible normalization techniques. Besides the work on the model architecture, we formulate and compare different embedding methods to project text data into spikes. Finally, we demonstrate that our proposed SNN-based decoder block reduces the theoretical energy consumption by 87% to 93% compared to the ANN baseline.

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

RoSE: Round-robin Synthetic Data Evaluation for Selecting LLM Generators without Human Test Sets

LLMs are powerful generators of synthetic data, which are used for training smaller, specific models. This is especially valuable for low-resource languages, where human-labelled data is scarce but LLMs can still produce high-quality text. However, LLMs differ in how useful their outputs are for training. Selecting the best LLM as a generator is challenging because extrinsic evaluation requires costly human annotations (which are often unavailable for low-resource languages), while intrinsic metrics correlate poorly with downstream performance. We introduce Round robin Synthetic data Evaluation (RoSE), a proxy metric for selecting the best LLM generator without human test sets. RoSE trains a small model on the outputs of a candidate generator (LLM) and then evaluates it on generated synthetic examples from all other candidate LLMs. The final RoSE score is the mean performance of this small model. Across six LLMs, eleven languages, and three tasks (sentiment, topic, intent), RoSE identifies the optimal generator more often than any other intrinsic heuristics. RoSE outperforms intrinsic heuristics and comes within 0.76 percentage points of the optimal generator baseline. This result is measured in terms of downstream performance, obtained by training a small model on the chosen generator's outputs (optimal vs. proxy metric selected) and evaluating it on human-labelled test data. Additionally, RoSE is the only metric to achieve a positive correlation with performance on human test data.