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

A Survey on Agentic Security: Applications, Threats and Defenses

LLM-based agents are now used throughout cybersecurity. While these agents facilitate powerful and autonomous security applications, their autonomy opens up new attack surfaces, and the security community is actively building defenses to secure them. Yet the literature on this subject has grown quickly and unevenly. Existing surveys treat applications, threats, and defenses in isolation, leaving no unified account of how an agent's capabilities, vulnerabilities, and countermeasures interconnect. In this work we present the first holistic survey of the agentic security landscape, structuring the field around the fundamental pillars of Applications, Threats and Defenses. We provide a comprehensive taxonomy of over 260 papers, explaining how agents are used in downstream cybersecurity applications, inherent threats to agentic systems, and countermeasures designed to protect them. In addition, we provide detailed pillar-specific and cross-cutting analyses that show the security-lifecycle coverage of agentic applications, comparison between red-teaming and blue-teaming agents, and the adversarial use of red-teaming applications. On the threat side, we analyze the entry points and agent-loop stages that attacks target, their specificity to the agentic setting, and the threat models they assume. On the defense side, we analyze the prevailing defense strategies, their cost and security trade-offs, and where in the agent lifecycle they are deployed. We further map which defenses cover which attack classes and chart trends in agent architecture, backbone model usage, data modality coverage, and the growth of attack and defense research over time. Taken together, these findings indicate that agentic systems are structurally fragile by default and that securing them will require defenses that span the full agent lifecycle rather than single-layer fixes.

02.
arXiv (CS.CL) 2026-06-19

Connect the Dots: Training LLMs for Long-Lifecycle Agents with Cross-Domain Generalization Via Reinforcement Learning

This work presents a general framework for training large language models (LLMs) to "Connect the Dots" (CoD), a meta-capability required by long-lifecycle agents: as an LLM-based AI agent gets deployed in an environment, it solves a long sequence of tasks while continuously exploring the environment, learning from its own experiences, and iteratively self-updating its context about the environment, thereby achieving progressively better performance on future tasks conditioned on the updated context. Major components of the CoD framework include: (1) algorithm design and infrastructure for end-to-end reinforcement learning (RL) with long rollout sequences interleaving solve-task and update-context episodes; (2) tasks and environments for incentivizing and eliciting the targeted meta-capability in LLMs during training, as well as for faithfully measuring progress during evaluation. We present proof-of-concept implementations of the CoD framework, including a GRPO-style RL algorithm with fine-grained credit assignment, as well as tasks and environments tailored to the targeted meta-capability (rather than domain-specific LLM capabilities or standard task-by-task RL). Empirical results validate the efficacy of end-to-end RL training in the CoD setting, and demonstrate the potential for out-of-distribution generalization – within the training domains, across different domains, and from CoD to Ralph-loop settings – of the elicited meta-capability. Our investigation of CoD connects several lines of prior works, and opens up new opportunities for advancing LLMs and AI agents. To facilitate further research and applications, we release our implementations at \url{https://github.com/agentscope-ai/Trinity-RFT/tree/research/cod/examples/research_cod}.

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

Uncertainty Decomposition for Clarification Seeking in LLM Agents

Recent position papers argue that the classical aleatoric/epistemic uncertainty framework is insufficient for interactive large language model (LLM) agents and call for underspecification-aware, decomposed, and communicable uncertainty representations that can unlock new agent capabilities such as proactive clarification seeking and shared mental-model building. Practical deployment constraints – black-box APIs, interactive latency budgets, and the absence of labeled trajectories – rule out logprob-based, multi-sampling, and training-based methods, leaving prompt-based estimation as the most viable family for surfacing such signals at deployment time. We answer this call with a simple prompt-based decomposition that separates action confidence from request uncertainty (u), enabling the agent to ask for clarification when the task specification is ambiguous. To evaluate it, we introduce two clarification-augmented benchmarks (WebShop-Clarification and ALFWorld-Clarification) in which 50% of tasks are deliberately underspecified, and systematically compare the proposed decomposition against ReAct+UE and Uncertainty-Aware Memory (UAM) across five LLM backbones (GPT-5.1, DeepSeek-v3.2-exp, GLM-4.7, Qwen3.5-35B, GPT-OSS-120B) on these variants together with the standard WebShop, ALFWorld, and REAL benchmarks for fault detection. Averaged across the five backbones, the proposed decomposition improves clarification F1 on ALFWorld-Clarification by 73% over ReAct+UE and by 36% over UAM, and leads clarification F1 on every backbone on WebShop-Clarification and on four of five backbones on ALFWorld-Clarification, indicating that the gains generalize beyond a single LLM.

04.
arXiv (CS.CV) 2026-06-12

AudioX-Turbo: A Unified Framework for Efficient Anything-to-Audio Generation

Audio and music generation based on flexible multimodal control signals is a widely applicable topic, with the following key challenges: 1) a unified multimodal modeling framework, 2) large-scale, high-quality training data, and 3) the prohibitive inference cost of multi-step diffusion sampling. As such, we propose AudioX-Turbo, a unified and efficient framework for anything-to-audio generation that integrates varied multimodal conditions (i.e., text, video, and audio signals) in this work. AudioX-Turbo follows a teacher-student paradigm. The teacher AudioX-Base is built on a Multimodal Diffusion Transformer with a Multimodal Adaptive Fusion module that aligns diverse multimodal inputs for high-fidelity synthesis, and is then distilled into the few-step student AudioX-Turbo via Distribution Matching Distillation adapted to flow matching, complemented by a diffusion-based discriminator for high-quality few-step generation. To support the training of AudioX-Turbo, we construct a large-scale, high-quality dataset, IF-caps-Pro, comprising approximately 9.2M samples curated through a two-stage data collection and annotation pipeline. We benchmark AudioX-Turbo across a wide range of tasks, finding that our model achieves superior performance, especially on text-to-audio and text-to-music generation, while operating at only 4 sampling steps and requiring approximately 25x fewer function evaluations (NFE) than multi-step baselines. These results demonstrate that our method is capable of audio generation under flexible multimodal control, showing efficient and powerful instruction-following capabilities. The code and datasets will be available at https://zeyuet.github.io/AudioX-Turbo/.

05.
arXiv (math.PR) 2026-06-16

Higher-order spectral perturbation expansions II: Kernel matrices and manifold learning

arXiv:2606.16373v1 Announce Type: cross Abstract: We study spectral concentration bounds for kernel matrices as approximation of the corresponding kernel integral operator. Results are established under weak assumptions on the data setting and the reproducing kernel relying only on a Mercer condition and a local Weyl law. This allows us to deal with key features of kernel matrices, such as large multiplicities, large effective dimension, and heavy-tailed distributions. Our results apply to infinite dimensional principal component analysis, manifold learning, and Bayesian nonparametric statistics. We illustrate this via two prototypical examples: The heat kernel on the sphere and a wavelet prior from Bayesian nonparametrics.

06.
medRxiv (Medicine) 2026-06-18

Diabetes is associated with increased nocturnal respiratory rate

Background and Objective: Diabetes mellitus (DM) causes autonomic neuropathy, which may alter nocturnal respiratory rate (NRR). To test the association between DM and NRR, we analyzed elective polysomnograms of four large observational cohorts. Research Design and Methods: We performed cross-sectional analysis of over 25,000 individuals with polysomnograms (PSGs) from the Sleep Heart Health Study (SHHS), Hispanic Community Health Study/Study of Latinos (HCHS/SOL), Osteoporotic Fractures in Men Study (MrOS), and Wisconsin Sleep Cohort (WSC). Patient-level NRRs were derived from inductance plethysmography waveforms. DM status was determined by self-report, physician diagnosis, medication use, or laboratory values, depending on the cohort. We related DM and NRR (continuous and dichotomized) using logistic regression models and adjusted for potential confounders. Cohort-specific results were combined using random-effects meta-analysis. Results: Meta-analysis of unadjusted models showed a pooled odds ratio (OR) of 1.10 (95% CI:1.04-1.17) for each breath-per-minute (brpm) increase in NRR. This association remained significant after multivariable adjustment (OR:1.06, 95% CI:1.02-1.11). Dichotomized analyses similarly showed higher odds of DM across dichotomization thresholds ranging from 15 to 21 brpm. At a threshold of 18 brpm, the unadjusted pooled OR was 1.77 (95% CI:1.23-2.55, P=0.0022), and the adjusted OR was 1.49 (95% CI:1.10-2.02, P=0.0098). Conclusions: Clinically stable outpatients with elevated NRR have an increased prevalence of DM. Additional studies are needed to investigate whether the mechanism is autonomic neuropathy and whether monitoring NRR can detect early complications of DM.

07.
arXiv (CS.CL) 2026-06-16

Dealing with Annotator Disagreement in Hate Speech Classification

Hate speech detection is a crucial task, especially on social media where harmful content can spread quickly. Collecting social media content (tweets etc.) to train machine learning models is easy, but detecting and categorizing hate speech can be difficult due to the inherently subjective nature. This subjectivity leads to frequent disagreement among annotators, particularly for subtle or borderline content. Traditional approaches either discard non-consensus samples or force a ''gold standard'' through expert adjudication, ignoring valuable information about uncertainty and diverse human perspectives. We examine the largely overlooked problem of annotator disagreement in hate speech classification and evaluate a range of aggregation methods, including majority voting, ordinal strategies (minimum, maximum, and mean), and analyze their impact across binary, 4-class, and 6-class classification tasks. In addition, we leverage annotators' perceived hate speech strength scores to explore regression-based and hybrid modeling approaches. Among others, we show that filtering non-consensus samples results in over-optimistic results and that the perceived strength provides a complementary signal that enhance classification performance. Finally, we establish new state-of-the-art results for hate speech detection in Turkish tweets, and demonstrate that annotator disagreement, when properly modeled, is a valuable resource for building more robust and reliable systems.

08.
arXiv (CS.LG) 2026-06-16

MUNI: Multimodal Unified Latent Diffusion for Coherent Any-to-Any Generation

arXiv:2606.16408v1 Announce Type: new Abstract: We introduce MUNI, an end-to-end multimodal latent diffusion framework for any-to-any generation that unifies subset-conditioned cross-modal generation and unconditional joint sampling through a shared stochastic latent. Existing multimodal generative models are largely LLM-based, which limits leveraging modality-specific generators and requires text-paired data for training. Recent diffusion- and flow-based any-to-any extensions take a different direction but still rely on text-aligned embeddings, fully-paired training, or matched-dimensionality deterministic mappings. MUNI rests on two complementary contributions, one architectural and one in the training objective. First, we extend latent diffusion to multimodal any-to-any generation end-to-end: instead of the standard two-stage recipe that precomputes a frozen latent space and then fits a prior over it, MUNI jointly trains modality-specific encoders, expressive decoders, and a single shared flow-based prior under one objective. Second, we identify that the standard aggregation rules of multimodal variational inference are insufficient once coupled with a learned prior and expressive decoders. A suitable shared latent must simultaneously satisfy coherence across generated modalities, predictive sufficiency of subset latents, and minimality of the latent content. We propose a routed training objective whose structural choices align the latent with these criteria and admit a minimal-sufficiency characterization in the realizable setting. Experiments on PolyMNIST-Quadrant-Labels and a large-scale image-text-audio benchmark show MUNI matching or exceeding the strongest baselines on conditional generation while opening its largest margins on unconditional coherence. Project page: https://muni-proj.github.io/.

09.
Nature (Science) 2026-06-10

Amplified Arctic iceberg traffic reshapes benthic biodiversity

The Arctic is undergoing rapid warming, resulting in retreating sea ice and glaciers1, yet how cryospheric changes propagate into the deep ocean remains poorly understood2. Here we identify a climate-driven mechanism linking accelerating glacier disintegration to an increase in deep-sea hard-bottom habitats far beyond calving fronts. Seafloor observations in Fram Strait show a localized increase in the density and patchiness of dropstones delivered by debris-laden icebergs. At the same time, four decades of shipboard records show that the occurrence of icebergs increased abruptly in the early 2000s. Backtracking links these icebergs to the main outlet glaciers in northeast Greenland and the Russian High Arctic. In northeast Greenland, the timing of glacier destabilization coincides with this rise, whereas sparse satellite coverage in the Russian sector limits temporal attribution despite indications of enhanced glacier activity. A model sensitivity study shows that, apart from intensified calving, a more dynamic sea ice cover enhances downstream transport of glacial ice. Along these pathways, increased iceberg activity could reshape deep-sea habitats through enhanced melt and associated lithogenic input, and elevate navigational hazards as maritime traffic expands in the Arctic. Although modest compared with the iceberg discharges of Pleistocene Heinrich events, this mechanism provides a modern analogue of long-range cryospheric influence on the seafloor in a warming climate. Accelerated Arctic glacier disintegration and a more dynamic sea ice cover are increasing iceberg-delivered dropstones in the deep ocean, reshaping seafloor habitats and extending cryospheric impacts far beyond glaciers.

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

CoCoGEC: Counterfactual Generation for Robust Grammatical Error Correction

Grammatical error correction (GEC) systems are usually trained and evaluated on GEC benchmarks, but their performance often drops sharply once the surrounding context is slightly perturbed or extended. This indicates that the existing GEC models usually fail to understand the error patterns in the varying contexts. In this paper, we thoroughly investigate the counterfactuals for GEC tasks, where the subtle changes to the contexts could lead to the label flipping issue. We propose CoCoGEC, a counterfactual generation framework that creates copies of training instances with error-irrelevant contexts altered. Our framework systematically generates counterfactuals by (1) generating intra- and inter-sentence counterfactuals that maintain the error patterns as well as syntax of the original instances by altering the word-level and sentence-level contexts; (2) revising the generated counterfactuals by selecting the instances with flipped labels and high GEC Mutual Information (MI) coefficient. Extensive experiments show that our method substantially improves the stability of GEC models, outperforming a set of data augmentation baselines. Particularly, it could achieve absolute F0.5 gains of +9.9, +11.3, and +20.8 points on the perturbed BEA-19*,CoNLL-14*, and TEM-8* data set.Our code is released at https://github.com/Quinnok/CoCoGEC

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

KVEraser: Learning to Steer KV Cache for Efficient Localized Context Erasing

Post-hoc context erasing over the KV cache is challenging because a local edit has a global consequence: once a span has been processed, its influence propagates into the cached states of all subsequent tokens. This issue arises naturally in long-context LLM applications, where stale retrieved facts, incorrect tool observations, retracted user preferences, or harmful prompt injections may be identified only after prefill. Exact erasing must then recompute all tokens after the deleted span, making its computational cost depend on suffix length rather than erased-span length. We introduce KVEraser, a learned KV-cache editing method for efficient localized context erasing. Given a processed context and a span to remove, KVEraser replaces only the KV states of the erased interval with learned steering states while reusing the remaining cache unchanged. To learn a transferable erasing mechanism, we build a two-stage training pipeline: generic span-neighbor pre-training teaches the eraser to suppress the influence of the erased span, while task-specific fine-tuning adapts this capability to downstream scenarios. Experiments show that KVEraser nearly matches full recomputation in post-erasure performance on in-domain tasks across 1K–32K context lengths, while its latency increases by only 24% compared with a 17.6x increase for full recomputation. KVEraser also generalizes to unseen long-document QA tasks with harmful factual distractors, achieving the best performance among approximate baselines with a 3–4x speedup over full recomputation.

13.
arXiv (CS.LG) 2026-06-11

Mahalanobis-Guided Latent OOD Detection for Hybrid ES-DRL Control in Time-Varying Systems

arXiv:2606.11474v1 Announce Type: new Abstract: In this paper, we study Mahalanobis-guided latent out-of-distribution (OOD) detection for test-time RL controller switching in nonlinear time-varying systems. RL controllers can quickly control high-dimensional systems within the training distribution, but their performance can degrade when time-varying dynamics produce unseen observations. We consider a combined ES–DRL controller, where RL provides fast in-distribution actions and bounded extremum seeking (ES) provides robust model-independent control under OOD operation. The key challenge is deciding when to switch. We train a variational autoencoder (VAE) on in-distribution beam-profile observations and use Mahalanobis distance in the VAE latent space to detect OOD beam profiles at test time. This OOD decision sets a binary switch that selects either the RL controller or the ES controller. We evaluate the approach in safety-critical particle accelerator control. In this setting, spatial magnet motion creates OOD beam profiles that were not seen during RL training. Visualization of the VAE latent space shows that the proposed method identifies this OOD scenario and provides an interpretable signal for switching between RL and ES in the combined controller.

14.
arXiv (quant-ph) 2026-06-15

No classical particle limit for massless quanta

arXiv:2606.14632v1 Announce Type: new Abstract: We investigate whether relativistic massless classical particles may emerge as the classical limit of massless quanta. To address this question independently of any specific dynamics, environment, or pointer basis, we develop an axiomatic and purely kinematical framework for the coarse-graining approach. In this formulation, a candidate classical phase space is taken as the outcome space of a POVM subject only to minimal classicality and covariance under the relevant spacetime symmetry group. Applying this framework to the Poincaré group, we prove a no-go theorem for massless particles: the covariance requirement is incompatible with the operational conditions for classicality. The theorem leaves open field-like limits of massless quanta, for example the emergence of electromagnetic or gravitational fields, while ruling out classical massless particles, such as classical photons or gravitons.

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

Nightjar: Dynamic Adaptive Speculative Decoding for Large Language Models Serving

arXiv:2512.22420v5 Announce Type: replace-cross Abstract: Speculative decoding (SD) accelerates LLM inference by verifying draft tokens in parallel. However, this method presents a critical trade-off: it improves throughput in low-load, memory-bound systems but degrades performance in high-load, compute-bound environments due to verification overhead. Existing speculative decoding methods use fixed lengths and cannot adapt to workload changes or decide when to stop speculation. The cost of restarting speculative inference also remains unquantified. Under high load, the benefit of speculation diminishes, while retaining the draft model reduces KV cache capacity, limiting batch size and degrading throughput. To overcome this, we propose Nightjar, a resource-aware adaptive speculative framework. It first adjusts to the request load by dynamically selecting the optimal speculative length for different batch sizes. Crucially, Nightjar proactively disables speculative decoding when the MAB planner determines that speculation is no longer beneficial, and during the disabled phase, offloads the draft model to the CPU only under GPU memory pressure. This reclaims memory for the KV cache, thereby facilitating larger batch sizes and maximizing overall system throughput. Experiments show that Nightjar achieves up to 14.76% higher throughput than standard speculative decoding and up to 20.18% lower latency in the main benchmark suite under dynamic request arrival rates for real-time LLM serving scenarios.

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

Stream3D: Sequential Multi-View 3D Generation via Evidential Memory

View-conditioned 3D generators such as SAM 3D, TRELLIS, and Hunyuan3D produce high-quality object reconstructions from a single view, but real-world visual observation often arrives as long monocular streams. Naively applying these generators to each streaming frame independently leads to severe temporal inconsistency in the generated results. To address this problem, we propose Stream3D, the first training-free streaming mechanism that turns a frozen view-conditioned 3D generator into a streaming generator with constant cross-chunk memory. Stream3D achieves this by maintaining a compact evidential memory, which selectively caches the most informative historical frames based on a proposed evidence score mechanism. As the stream progresses, the memory dynamically updates to retain a fixed number of informative frames, preventing the memory footprint from growing linearly with sequence length. This also prevents degradation over long sequences and keeps the underlying generator completely unchanged without retraining, architectural modifications, or auxiliary losses. Evaluated on both realistic and synthetic streaming benchmarks, Stream3D outperforms latent-transport baselines, including KV-cache reuse and flow-based feature editing, across both photometric and geometric metrics. More details can be found at: https://stream-3d.github.io/stream3d.github.io/.

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

MedicalAgentsBench for Complex Medical Reasoning: Comparing Internalized Reasoning Models versus Externalized Agent-based Frameworks

Complex medical reasoning requires integrating heterogeneous clinical evidence across multiple inference steps. Large language models (LLMs) now approach this through two routes: internalized reasoning and externalized agent scaffolding (frameworks that decompose problems collaboratively amongst multiple LLMs). To determine whether these routes are exclusive or complementary, we introduce MedicalAgentsBench, a filtered benchmark of 862 complex clinical questions drawn from the union of eight medical datasets via difficulty-aware curation and contamination screening. Evaluating three internalized reasoning models (DeepSeek-R1, o1-mini, and o3-mini), seven base models, and nine externalized agent-based methods, we find that internalized and externalized approaches each independently improve performance, and that their benefits compound: the highest accuracy is achieved by layering agent workflows onto an internalized reasoning model (i.e., o3-mini + MDAgents with 35.1%). Pareto analysis shows this combination dominates the cost-performance frontier; moreover, lightweight optimization on inexpensive models offers an entry point for resource-constrained settings. Our benchmark is at https://github.com/gersteinlab/MedicalAgentsBench.

18.
medRxiv (Medicine) 2026-06-15

Beyond the Apnea-Hypopnea Index: Physiological and Demographic Predictors of Excessive Daytime Sleepiness in Obstructive Sleep Apnea

Excessive daytime sleepiness (EDS) is a common but inconsistently predicted symptom of obstructive sleep apnea (OSA). OSA is typically diagnosed with polysomnography (PSG), and the current standard for severity assessment is the apnea-hypopnea index (AHI). AHI has many limitations, including its inability to explain physiological mechanisms or reflect variability in patient symptoms, such as EDS. This retrospective study aims to find physiological and demographic parameters that better predict EDS in patients with OSA and to evaluate whether these parameters outperform AHI using PSG data from the Mount Sinai Integrative Sleep Center. Clinical variables used to predict EDS included arousal index (AI), average oxygen desaturation during sleep, average heart rate during sleep, and AHI, along with demographic variables including age, sex, and BMI. Hypothesis tests, logistic regression models, and decision tree classifier models were performed on the data to discriminate sleepy from nonsleepy patients as determined by an Epworth Sleepiness Scale (ESS) score [≥] 10. AI and oxygen desaturation were found to be the most predictive physiological variables, and sex and BMI were found to be the most predictive demographic variables. The final decision tree model with these four variables outperformed the AHI in predicting EDS. These findings suggest that daytime sleepiness in OSA can be better explained by measures of apnea burden, oxygenation impairment, and patient demographics than by AHI alone, although these remain only modestly predictive. Future studies should focus on investigating more comprehensive physiological markers, multi-night sleep data, and more objective assessments of sleepiness.

19.
medRxiv (Medicine) 2026-06-18

Device assessed 24-hour movement behaviour and cardiovascular disease mortality amongst cancer survivors.

Background: Cancer survivors face elevated risks of mortality from cardiovascular disease (CVD). The potential importance of physical activity (PA) and other behaviours across the 24-hour day (e.g. sedentary behaviour (SB) and sleep) for CVD-mortality risk is not well understood in this at-risk population. Objectives: To assess the importance of 24-hour movement behaviour, using a compositional approach, for mitigating CVD-mortality amongst cancer survivors. Methods: Participants with a prior cancer diagnosis were drawn from the UK Biobank accelerometry sub-study (n=6,158). Accelerometer-derived movement (moderate-to-vigorous PA (MVPA), vigorous PA (VPA), moderate PA (MPA), light PA (LPA), SB, sleep) was examined in relation to CVD-mortality, identified from health record linkage data (using Fine-Gray Cox proportional-hazards models adjusted for demographic, health, lifestyle covariates). Results: Median follow-up was 8.0 years (Q1-Q3: 7.4-8.5), with n=500 (8.2%) deaths (CVD-deaths: n=118). Greater MVPA, in place of any other behaviour, was inversely associated with CVD-mortality with e.g. 10% lower hazard if MVPA theoretically replaced 7 minutes (mins)/day SB (Hazard ratio (HR): 0.91, (95% Confidence Interval: 0.86-0.95)), 9 mins/day LPA (HR: 0.90, 0.83-0.97), or 11 mins/day sleep (HR: 0.90, 0.83-0.97). The VPA component of MVPA proved critical, requiring only ~1-2 additional mins/day for equivalent hazard reduction. Sleep duration, was also inversely associated with CVD-mortality. A 10% lower hazard required replacing 29 mins/day of SB with sleep (HR: 0.90, 0.84-0.96); no other behavioural replacement amongst SB, sleep or LPA could provide an equivalent risk reduction. Conclusions: Among cancer survivors, the most potent reduction in CVD-mortality followed theoretically reallocating time to higher intensity movement.

20.
medRxiv (Medicine) 2026-06-17

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

Despite recent advances in next-generation sequencing, genetic diagnostic rates for dilated cardiomyopathy (DCM) remain low. Among paediatric DCM, causes are often heritable, with a greater frequency of de novo, recessive and syndromic causes of disease. Novel diagnostic methods are therefore required to solve monogenic cases. To assess the value of proteomics as a diagnostic tool for paediatric DCM, we obtained left ventricle myocardial samples from paediatric patients undergoing heart transplantation at the Royal Children's Hospital, Melbourne. We performed genome sequencing and proteomics and leveraged this multi-omics dataset to uncover the molecular cause of disease in a gene elusive proband. The proband carried a heterozygous JPH2 frameshift variant identified on clinical exome sequencing. However, proteomic analysis showed a pronounced downregulation of JPH2, suggestive of biallelic loss-of-function. Closer inspection of the genomic data revealed a large inversion (~8.34 Mb) with a breakpoint falling within intron 5 of JPH2 that displaces the 3'UTR from the coding transcript. The two variants were confirmed to be in trans using long read DNA sequencing, consistent with a diagnosis of JPH2 autosomal recessive DCM. Finally, we applied RNA sequencing with total RNA library preparation to show that transcripts containing a 3'UTR were reduced to ~10% relative to controls. As a proof-of-principle, we present the first reported use of proteomics from explanted cardiac tissue to provide a genetic diagnosis. Our methodology has broad relevance to patients with genetically unsolved Mendelian diseases, who might undergo organ transplantation as part of clinical management.

21.
arXiv (CS.CL) 2026-06-16

A Self Consistency Based Reranking for Narrative Question Answering

Narrative question answering (NQA) is a challenging task in natural language processing that requires models to understand long textual contexts, capture relationships across events, and generate coherent responses. Despite recent advances in pretrained language models, most existing approaches rely on a single decoding output during inference, making them sensitive to generation variability and often resulting in incomplete or inconsistent answers .To address this limitation, we propose a self-ensemble Self-Consistency-Based reranking framework for narrative question answering. The proposed method generates multiple candidate answers for each story-question pair and selects the final answer based on semantic agreement among the generated responses. This allows the model to explore diverse answer formulations while improving robustness through consensus-based selection without requiring modifications to the underlying architecture .The framework combines pretrained and fine-tuned language generation with multi-answer inference and similarity-based reranking. We evaluate the proposed approach on the NarrativeQA dataset using multiple models, including FLAN-T5 (Base and Small) and Pegasus-Large, under both baseline and fine-tuned settings .Experimental results demonstrate that the proposed method consistently improves performance across all models. In particular, FLAN-T5-Base achieves the best overall performance, improving from 82.32% to 86.66% (+4.34%) when combined with self-ensemble inference. Additionally, the largest improvement is observed with Pegasus-Large, which increases from 72.50% to 87.07% (+14.57%), highlighting the effectiveness of the proposed strategy.

22.
bioRxiv (Bioinfo) 2026-06-15

RepGene: Toward a Unified Gene Representation Space Robust to Missing Biological Views

Genes can be described through multiple heterogeneous biological views, including genomic sequence, transcript sequence, protein sequence, textual knowledge, and single-cell expression context, yet existing gene embeddings remain largely modality-specific and difficult to compare or reuse when many views are unavailable. We study a narrower but practically important question: whether pretrained embeddings from these distinct sources can be organized into a shared gene representation interface that remains usable under severe missing-modality conditions. To investigate this question, we introduce RepGene, a lightweight single-branch framework that combines modality adapters, a shared encoder, presence-aware fusion, and self-supervised cross-view objectives to map five biological views into one latent space. Our goal is not to claim a new multimodal learning principle or to establish superiority over all simpler fusion strategies, but to provide an initial technical instantiation for testing whether such a shared interface is feasible in a fixed-feature setting. Under a two-stage protocol in which RepGene is trained self-supervised on frozen upstream embeddings and evaluated by downstream linear probing, we find preliminary evidence that the learned representation is broadly competitive in the full-modality setting and remains informative when only partial modality subsets are observed at inference time. The strongest signal in our study is robustness under missing views: average performance changes are often limited when one modality is removed, and even single-view inference remains non-trivial in the evaluated benchmark regime.These results do not resolve unified biological representation learning, and they should be interpreted in light of incomplete simple-fusion baselines, limited architectural ablation, benchmark dependence, and possible upstream feature exposure. We therefore position RepGene as a feasibility study and a starting point for stronger comparisons, broader benchmarks, and leakage-aware validation.

23.
Nature (Science) 2026-06-17

Structure of the pre-initiation complex explains CMGE biogenesis

When cells enter S phase, bidirectional DNA replication is initiated through the kinase-regulated recruitment of three activators (Cdc45, GINS and Pol ε) to a duplex-DNA-loaded double hexamer of minichromosome maintenance (MCM) ATPases. Together, these proteins form two CMGE helicases that establish divergent replication forks as they become separated1. Here, to gain an understanding of CMGE biogenesis, we reconstituted the pre-initiation complex with purified yeast proteins. The cryo-electron-microscopy structure shows a set of firing factors caught in the act of assembling two symmetrical CMGEs. We show how stepwise complex formation reshapes MCM in preparation for DNA opening, and we explain how ATP promotes firing-factor ejection and CMGE maturation. We find that although Sld2 facilitates the recruitment of GINS to MCM, as expected, it also aids the efficient separation of the CMGE dimer, and is essential for the ejection of the lagging strand from MCM. These findings have direct implications for our understanding of the metazoan Sld2 orthologue, RECQL4, and point to a replication-fork establishment mechanism that is conserved across eukaryotes. Cryo-electron microscopy and biochemical reconstitution experiments in yeast provide insight into the assembly of the CMGE complex, a helicase that establishes bidirectional DNA replication in eukaryotic cells, and elucidate the role of the firing factor Sld2.

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

OnDeFog: Online Decision Transformer under Frame Dropping

arXiv:2606.19721v1 Announce Type: cross Abstract: In challenging real-world reinforcement learning applications, communication delays or sensor failures often cause frame dropping, in which the agent cannot receive the dropped states and associated rewards. To address the performance degradation caused by frame dropping, the Decision Transformer under Random Frame Dropping (DeFog) was developed by incorporating additional mechanisms into the decision transformer to tackle frame dropping. Although DeFog can mitigate performance degradation in frame-dropping environments, since DeFog is an offline learning method, it struggles to effectively generalize to novel states not adequately represented in the training dataset. In this study, we propose OnDeFog, which integrates the mechanisms in DeFog with the online decision transformer (ODT), an online reinforcement learning method that learns policies through direct environmental interaction. Comprehensive experimental evaluation demonstrates that our proposed OnDeFog achieves superior performance compared to ODT in environments characterized by high dropping frame rate and outperforms DeFog on datasets containing a large amount of low-reward data.

25.
arXiv (CS.CL) 2026-06-17

EngTrace: A Symbolic Benchmark for Verifiable Process Supervision of Engineering Reasoning

Large Language Models (LLMs) are increasingly entering specialized, safety-critical engineering workflows governed by strict quantitative standards and immutable physical laws, making rigorous evaluation of their reasoning capabilities imperative. However, existing benchmarks such as MMLU, MATH, and HumanEval assess isolated cognitive skills, failing to capture the physically grounded reasoning central to engineering, where scientific principles, quantitative modeling, and practical constraints must converge. To enable verifiable process supervision in engineering, we introduce EngTrace, a symbolic benchmark built on 90 parameterized templates, each generating unique, contamination-resistant problem instances, spanning three major engineering branches, nine core domains, and 20 distinct areas, yielding 1,350 test cases that stress-test generalization across diverse physical scenarios. Moving beyond outcome matching, we introduce a verifiable two-stage evaluation framework that uses a tiered protocol to validate intermediate reasoning traces alongside final answers through automated procedural checks and a heterogeneous AI Tribunal. Our evaluation of 27 leading LLMs reveals a distinct trade-off between numeric precision and trace fidelity, identifying a complexity cliff where abstract mathematical pre-training fails to translate into the integrative reasoning required for advanced engineering tasks.