Academic Intelligence · Curated Daily

探索全球前沿学术脉络

AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。

01.
arXiv (CS.AI) 2026-06-18

Agentra: A Supervisable Multi-Agent Framework for Enterprise Intrusion Response

arXiv:2606.18325v1 Announce Type: cross Abstract: Enterprise intrusion response still depends on static playbooks and analyst-driven triage, creating delay between alert generation and containment. We present Agentra, a supervisable multi-agent Intrusion Response System (IRS) framework that converts alerts from IDS, EDR, and XDR platforms into structured incident response plans grounded in MITRE ATT&CK, MITRE D3FEND, and NIST CSF 2.0. Agentra decomposes response reasoning across role-scoped agents, validates proposed plans through a bounded Planner–Validator review loop, screens retrieved threat intelligence through a Moderator security gateway, gates actions through an Action Catalog and risk score, and records decisions in an append-only audit log. We evaluate Agentra against a static OASIS CACAO v2.0 cyber-playbook baseline on a 120-event corpus drawn from ThreatHunter-Playbook, Splunk BOTSv3, and DARPA OpTC. The strongest configuration improves FP-aware IRS F1 from 0.61 to 0.84 and restores the projected harmful-action rate to the static baseline level of 0.0% after Planner-only configurations introduce unsafe overreaction. These results indicate that multi-agent response planning can improve ontology-grounded IRS coverage while preserving analyst approval and auditability.

02.
arXiv (CS.CL) 2026-06-16

Let LLMs Judge Each Other: Multi-Agent Peer-Reviewed Reasoning for Medical Question Answering

Objective: To enhance the accuracy, interpretability, and robustness of large language models (LLMs) in medical question answering (MedQA). Method: We designed a multi-agent peer-reviewed reasoning method in which multiple LLM agents independently generate chain-of-thought reasoning with candidate answers, then act as peer reviewers to evaluate each other's reasoning for factual correctness and logical soundness. The highest-rated reasoning chain is selected to produce the final answer. Experiments were conducted with five state-of-the-art LLMs (Llama-3.1-8B, Qwen2.5-7B, Phi-4, DeepSeek-LLM-7B, GPT-oss-20B) on three benchmark datasets: HeadQA, MedQA-USMLE, and PubMedQA. Performance was compared against single-model chain-of-thought reasoning and chain-of-thought-based majority voting. Results: Peer-reviewed reasoning consistently outperformed both baselines. The best model combination achieved an average accuracy of 0.820 across datasets, exceeding the strongest single model (0.777) and majority voting ensembles (up to 0.789). The method also scaled effectively with more participating models, while peer assessments reliably distinguished high- from low-quality reasoning chains. Conclusion: The proposed multi-agent peer-reviewed reasoning method enables LLMs to act as both solvers and evaluators, yielding superior performance in MedQA. By emphasizing reasoning quality rather than answer agreement alone, this approach improves accuracy, interpretability, and robustness, offering a promising direction for trustworthy biomedical AI systems.

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

Mask, Sample, Revise: A Revisable CTMC Inference Stack for Guided Discrete Flow Matching Text-to-Speech

arXiv:2606.13989v1 Announce Type: cross Abstract: Recent alignment-free non-autoregressive (NAR) text-to-speech (TTS) models formulate synthesis as a conditional infilling task, bypassing explicit duration predictors and external aligners. When speech is represented with neural codec tokens, the infilling problem becomes discrete, making Discrete Flow Matching (DFM), a Continuous-Time Markov Chain (CTMC) framework for discrete generation, a natural fit. However, inference-time control for stable low-step conditional infilling remains underexplored. We propose Mask, Sample, Revise, an inference-time CTMC stack for alignment-free DFM-TTS. The stack combines predictor-free guidance to strengthen text conditioning, prompt-matched conditional coupling to align the probability path with the acoustic prompt, and SC-ReMask, a schedule-constrained remasking mechanism that introduces token-to-mask transitions so early de-masking decisions can be revised. These components require no post-hoc fine-tuning and operate in a single tau-leaping sampler. Controlled ablations show that this stack improves intelligibility and robustness in the low-NFE prompted setting, outperforming unguided and guidance-only samplers with substantially more steps.

04.
medRxiv (Medicine) 2026-06-22

Substantia Nigra and Subthalamic Nucleus Deep Brain Stimulation Exert Opposing Effects on Novelty Recognition in Parkinson's Disease

Episodic memory plays a critical role in supporting adaptive behavior; however, whether it can be causally regulated in humans via deep subcortical stimulation remains unclear. In the present study, we investigated the differential effects of substantia nigra (SN) and subthalamic nucleus (STN) stimulation on episodic memory, as well as the underlying mechanisms of its associated brain networks, using a recognition memory task combined with concurrent functional magnetic resonance imaging in patients with Parkinson's disease. SN-DBS increased recognition sensitivity and reduced false alarms at both frequencies, whereas 10 Hz STN-DBS reduced sensitivity and increased false alarms. Functional connectivity analyses in the absence of DBS stimulation identified a false recognition-related network linking nigral, pallidal, subthalamic, medial temporal, frontal, and occipital regions. SN-DBS-related false alarm reduction tracked modulation of this circuit and was marked by its baseline vulnerability state. These behavioral effects mapped onto target-dependent parieto-occipital and SN-visual retrieval pathways, supporting a model in which DBS bidirectionally regulates recognition memory through target- and frequency-dependent subcortical-cortical circuits.

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

Multiple Descents in Deep Learning as a Sequence of Order-Chaos Transitions in LSTM Networks

arXiv:2505.20030v2 Announce Type: replace-cross Abstract: We observe a novel `multiple-descent' phenomenon during the learning process of a recurrent neural network called long-short-term memory (LSTM) networks during its training on real-world task, in which the performance goes through long cycles of up and down trends multiple times after the model is overtrained. By carrying out asymptotic stability analysis of the models, we found that the cycles in performance – indicated by loss function in test data – are closely associated with the phase transition process between order and chaos of the model, and the local optimal training step are consistently at the critical transition point between the two phases. More importantly, the most optimal point of the model usually occurs at the first transition from order to chaos, where the `width' of the `edge of chaos' is often the widest, allowing the best exploration of weight configurations for learning.

06.
bioRxiv (Bioinfo) 2026-06-21

Antibody-Antigen Affinity Prediction with Chain-Aware Protein Language Modeling

Motivation: Antibody-antigen affinity determines which antibodies advance in therapeutic discovery, repertoire analysis and affinity maturation, but experimental measurements are sparse relative to the scale of sequence libraries. Structure-based predictors can exploit interface geometry when reliable complexes are available, yet early discovery often requires ranking many heavy-light chain pairs against antigens for which no complex structure exists. Existing sequence-based models are scalable, but frequently compress heavy and light chains into a single antibody representation or concatenate antibody and antigen features obscuring the chain-specific and epitope-specific signals that drive binding. Results: We present AbAffinity, a sequence-only chain-aware three-stream architecture that maintains heavy chain, light chain and antigen as distinct streams. It integrates frozen ESM-2 embeddings with heavy-chain CDR-focused pooling, heavy-light self-attention, adaptive fusion gating and gated cross-attention, training only a compact interaction module. On the SAAINT-DB benchmark, AbAffinity achieves strong predictive performance under ten-fold cross-validation and maintains robust accuracy on novel antigens. It consistently outperforms recent sequence-based models across external benchmarks including SAbDab, AB-Bind and SKEMPI 2.0. Ablation studies highlight the contributions of chain-specific representations, CDR-focused pooling and the gated interaction pathway. Integrated Gradients attributions recover known paratope and epitope residues at structurally validated interfaces. AbAffinity provides a lightweight, explainable sequence-first framework for antibody triage and prioritisation when structural information is limited or unavailable.

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

Variational Test-time Optimization for Diffusion Synchronization

Collaborative generation, which coordinates multiple diffusion trajectories to extend the capabilities of pretrained priors, has emerged as a powerful paradigm for extending the applicability of diffusion models. Among existing approaches, diffusion synchronization provides a scenario-agnostic solution by introducing general guidance mechanisms. However, current synchronization approaches rely heavily on heuristics and still require task-specific tailoring, which limits their generalizability and performance. In this work, we mathematically derive a synchronization framework based on optimal control, providing a principled explanation of diffusion synchronization. During sampling, we optimize control variables to guide multiple trajectories toward coherent solutions while remaining close to the underlying diffusion prior. Our method operates entirely at test-time without additional training, thereby enabling broad applicability across diverse generation scenarios when combined with strong pretrained priors. We demonstrate consistent improvements over baselines on three representative collaborative generation tasks, covering a wide range of modalities and applications. Beyond performance gains, our work establishes a novel foundation for collaborative generation, opening a principled path toward extending pretrained generative models to new collaborative generation settings.

08.
arXiv (CS.AI) 2026-06-18

DeepInflation: an AI agent for research and model discovery of inflation

arXiv:2601.14288v2 Announce Type: replace-cross Abstract: We present DeepInflation, an AI agent designed for research and model discovery in inflationary cosmology. Built upon a multi-agent architecture, DeepInflation integrates Large Language Models (LLMs) with a symbolic regression (SR) engine and a retrieval-augmented generation (RAG) knowledge base. This framework enables the agent to automatically explore and verify the vast landscape of inflationary potentials while grounding its outputs in established theoretical literature. We demonstrate that DeepInflation can successfully discover simple and viable single-field slow-roll inflationary potentials consistent with the latest observations (with the ACT DR6 results taken as an example) or any given $n_s$ and $r$, and provide accurate theoretical context for obscure inflationary scenarios. DeepInflation serves as a prototype for a new generation of autonomous scientific discovery engines in cosmology, which enables researchers and non-experts alike to explore the inflationary landscape using natural language. This agent is available at https://github.com/pengzy-cosmo/DeepInflation.

09.
arXiv (CS.CV) 2026-06-11

Bridging the Modality Gap in Forensic Image Retrieval

Automated image retrieval plays an increasingly critical role in modern forensic analysis, supporting investigative workflows that rely on efficient comparison of visual evidence. While prior work has focused primarily on developing and optimizing multimodal retrieval systems, limited attention has been paid to evaluating the forensic applicability of these technologies across diverse real-world scenarios. In this study, we present a unified retrieval framework adapted to four key forensic tasks: (1) tattoo image retrieval given a tattoo query image; (2) tattoo retrieval guided by human-expert textual descriptions, modelling the common situation where a witness verbally describes a tattoo; (3) tattoo retrieval from hand-drawn sketches; and (4) face retrieval from forensic face sketches. Our system leverages a multimodal large language model (MLLM) to automatically generate structured textual descriptions for all queries and gallery images, followed by sentence-transformer embedding for text-based comparison. We evaluate retrieval using visual-only embeddings, text-only embeddings and a multimodal fusion strategy that combines text- and image-based similarity scores derived from state-of-the-art visual feature extractors relevant to each task. The fusion of modalities consistently improves retrieval precision and robustness, especially in scenarios where visual information is limited or noisy (e.g., sketches, partial tattoos, or fragmented witness statements). This work highlights the forensic value of a unified multimodal retrieval pipeline and demonstrates how modern MLLMs can operationalize challenging forensic tasks that traditionally rely on manual expert analysis. Our results position multimodal retrieval as a promising tool for supporting investigative workflows involving tattoos, facial composites, and witness descriptions.

10.
arXiv (CS.AI) 2026-06-17

Mental Health AI Safety Claims Must Preserve Temporal Evidence

arXiv:2605.08827v2 Announce Type: replace Abstract: The safety of mental health AI is often judged at the wrong temporal scale. Current evaluations typically score isolated responses, endpoint outcomes, or aggregate dialogue quality, while clinically consequential failures may arise from the order and accumulation of interactions themselves, including delayed escalation, repeated reinforcement, dependency formation, failed repair, and gradual deterioration across turns. This paper argues that this mismatch is not merely a limitation of evaluation coverage but a source of invalid safety conclusions. We introduce Temporal Safety Non-Identifiability, a formal account of why safety properties that depend on sequence, timing, accumulation, or recovery cannot be certified by protocols that discard those features. From this formalization, we develop SCOPE (Safety Claims Over Preserved Evidence) as a general principle for aligning safety claims with the evidence an evaluation actually retains, and instantiate it as SCOPE-MH, a mental-health instantiation of this reporting standard. We operationalize SCOPE-MH through a proof-of-concept on the AnnoMI dataset of expert-annotated motivational interviewing conversations, which reveals mechanisms of failure that per-turn behavior scoring does not represent. We propose SCOPE-MH as a diagnostic complement to existing evaluation infrastructure and argue that evaluation preserving temporal evidence is necessary, not optional, for safety-critical mental health AI deployment.

11.
arXiv (CS.LG) 2026-06-18

Learning from Your Own Mistakes: Constructing Learnable Micro-Reflective Trajectories for Self-Distillation

arXiv:2606.18844v1 Announce Type: new Abstract: Self-distillation improves reasoning in large language models by using the model's own rollouts as training signal, typically through implicit logit-level alignment that minimizes KL divergence toward a privileged target distribution. However, because this supervision is generated via uncontrolled sampling, it provides no diagnostic insight into the model's specific errors or corrective guidance for its individual failure patterns. Consequently, the model learns to imitate a privileged distribution rather than receiving fine-grained corrections that pinpoint where and why its reasoning fails. In this paper, we propose Trajectory-Augmented Policy Optimization (TAPO), which advances self-distillation from implicit distributional alignment to explicit trajectory construction. During RL training, the model produces both correct and incorrect rollouts to the same query, and TAPO leverages this contrastive structure to construct micro-reflective corrections, new training trajectories that retain the model's erroneous reasoning up to the point of failure, then insert a natural-language diagnosis and corrected reasoning guided by a correct reference from the same sampling group. Since each trajectory is anchored in the learner's own prefix and solutions, the corrective signal preserves the model's on-policy distribution to a greater extent than the position-wise alignment imposed by KL-based methods. To integrate these trajectories, TAPO introduces difficulty-aware candidate selection at the model's capability boundary and decoupled advantage estimation to prevent gradient contamination. Experiments on AIME 2024, AIME 2025, and HMMT 2025 show that TAPO achieves consistent improvements over GRPO under the same number of training steps. Further analysis demonstrates that TAPO strengthens both first-pass reasoning and error-correction effectiveness.

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

AdaSTORM: Scaling LLM Reasoning on Dynamic Graphs via Adaptive Spatio-Temporal Multi-Agent Collaboration

arXiv:2606.16328v1 Announce Type: new Abstract: Large Language Models (LLMs) demonstrate remarkable potential in dynamic graph reasoning, but suffer from a scaling bottleneck: current models can only handle graphs with tens of nodes, constrained by exponential reasoning overhead and finite context windows. While multi-agent systems (MAS) offer collective reasoning and topology-aware orchestration, capabilities naturally suited for graph-structured tasks, their application to dynamic graphs remains unexplored. This paper presents Scaling LLM Reasoning on Dynamic Graphs via Adaptive Spatio-Temporal Multi-Agent Collaboration (AdaSTORM), a framework that reformulates large-scale dynamic graph reasoning into two stages: (i) Adaptive Partitioning, partitioning large-scale dynamic graphs into subregions that match the model's reasoning capacity while minimizing inference cost; and (ii) Collaborative Reasoning, aligning graph partition topologies with a spatio-temporal decoupled multi-agent architecture. AdaSTORM is the first multi-agent framework tailored for dynamic graph reasoning. Extensive experiments show that AdaSTORM successfully breaks through the scaling bottleneck, scaling reasoning to thousand-node graphs with over 90% accuracy across several large-scale dynamic graph settings without external tools, significantly outperforms seven competitive baselines. Furthermore, it achieves state-of-the-art accuracy on existing benchmarks and generalizes robustly to real-world datasets. The source code is available at: https://github.com/irisorchid107/AdaSTORM/.

13.
arXiv (CS.AI) 2026-06-19

DF3DV-1K: A Large-Scale Dataset and Benchmark for Distractor-Free Novel View Synthesis

arXiv:2604.13416v2 Announce Type: replace-cross Abstract: Advances in radiance fields have enabled photorealistic novel view synthesis. In several domains, large-scale real-world datasets have been developed to support comprehensive benchmarking and to facilitate progress beyond scene-specific reconstruction. However, for distractor-free radiance fields, a large-scale dataset with clean and cluttered images per scene remains lacking, limiting the development. To address this gap, we introduce DF3DV-1K, a large-scale real-world dataset comprising 1,048 scenes, each providing clean and cluttered image sets for benchmarking. In total, the dataset contains 89,924 images captured using consumer cameras to mimic casual capture, spanning 128 distractor types and 161 scene themes across indoor and outdoor environments. A curated subset of 41 scenes, DF3DV-41, is systematically designed to evaluate the robustness of distractor-free radiance field methods under challenging scenarios. Using DF3DV-1K, we benchmark nine recent distractor-free radiance field methods and 3D Gaussian Splatting, identifying the most robust methods and the most challenging scenarios. Beyond benchmarking, we demonstrate an application of DF3DV-1K by fine-tuning a diffusion-based 2D enhancer to improve radiance field methods, achieving average improvements of 0.96 dB PSNR and 0.057 LPIPS on the held-out set (e.g., DF3DV-41) and the On-the-go dataset. We hope DF3DV-1K facilitates the development of distractor-free vision and promotes progress beyond scene-specific approaches. The dataset and leaderboard are available at https://johnnylu305.github.io/df3dv1k_web/.

14.
arXiv (quant-ph) 2026-06-19

Near-Optimal Learning of Local Lindbladians

arXiv:2606.20535v1 Announce Type: new Abstract: We study the problem of learning local Lindbladians from black-box access to the physical evolution, and the goal is to estimate all Hamiltonian and dissipative coefficients. We give an algorithm built directly from finite-time channel probes, which runs the unknown evolution for short times, estimates the corresponding Pauli transfer matrices from classical shadows, and converts these estimates into Lindbladian coefficients by stable local Fourier inversions. For fixed locality and bounded dissipative site degree, the uses of the dynamical evolution and total evolution time scale as $\widetilde{O}(\Lambda^2/\varepsilon^2)$ and $\widetilde{O}(\Lambda/\varepsilon^2)$ respectively, in the local dynamical strength bound $\Lambda$ and target accuracy $\varepsilon$, with only logarithmic dependence on the number of qubits. The algorithm is non-adaptive, uses no ancillas, and uses only random product states as inputs followed by random Pauli measurements. The method does not require knowing the support of the Lindbladian in advance. We complement the algorithm with matching lower bounds, showing that the learning algorithm is near-optimal both in physical dynamics accesses and in total evolution time. We construct a single-qubit dephasing Lindbladian family that already requires $\Omega(\Lambda^2/\varepsilon^2)$ channel uses and $\Omega(\Lambda/\varepsilon^2)$ total evolution time, even for adaptive algorithms with arbitrary ancillas and measurements. In particular, the lower bounds imply that the Heisenberg-limited scaling achievable for Hamiltonian learning is information-theoretically impossible once dissipative coefficients must be estimated.

15.
arXiv (quant-ph) 2026-06-11

Linear Combination of Hamiltonian Simulation with Commutator Scaling

arXiv:2606.11475v1 Announce Type: new Abstract: The Linear Combination of Hamiltonian Simulation (LCHS) framework simulates dissipative linear dynamics by representing time evolution as an integral over unitary operators, which is discretized by quadrature and implemented via Hamiltonian simulation. While existing analyses achieve near-optimal scaling in time and precision using norm-based quantities of the dissipative generator, we show that implementing the Hamiltonian simulation steps with Multi-Product Formulas (MPFs) yields commutator-sensitive error and complexity bounds. We demonstrate that the quadrature rule affects not only discretization error but also commutator structure and query complexity. This dependence is quantified through post-quadrature analysis for abstract MPF error profiles and for general time-independent and local Hamiltonians using known commutator-sensitive MPF error estimates. We compare uniform trapezoidal and free-scale sinh–sinh quadrature, showing improved quadrature-cardinality scaling for the latter, and illustrate the framework with applications to fractional diffusion, advection–diffusion, and open quantum systems.

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

Seeing Before Colliding: Anticipatory Safe RL with Frozen Vision-Language Models

arXiv:2606.11266v1 Announce Type: new Abstract: The cost signal that constrained-RL algorithms optimize against is almost always reactive: the simulator emits a non-zero cost only after a collision has begun, and the Lagrange multiplier of PPO-Lagrangian grows only after the episode budget has been exceeded. At race speeds, where collisions are instantaneous and irreversible, any safety mechanism that waits for cost to accumulate is structurally too late. We present VLM-Safe-RL, a framework that integrates a frozen vision-language model into the CMDP Lagrangian update as an anticipatory cost term. The framework comprises four contributions: (i) Decoupled Dual-Path CLIP, independent reward/cost paths that respect the CMDP's factorization; (ii) VLM-Lagrange, an augmented multiplier update that incorporates a per-step VLM cost as an anticipatory term; (iii) Confidence Gating, a Bayes-optimal weight derived from a logistic noise model on the CLIP margin; and (iv) VLMPPOLag, the composed algorithm. On Safety-Gymnasium FormulaOne L2, our principal evaluation ($n{=}5$ seeds, $10^{6}$ steps, budget $d_{lim}{=}25$) VLMPPOLag$+$Conf is the only configuration in our default budget comparison that simultaneously retains substantive return ($J_r{\approx}40$) and holds cost within budget on a majority of seeds; the five constraint-aware baselines (PPOLag, CPO, CPPOPID, CPO-CLG, PPOLag-RND) each fail at least one requirement. The mechanism generalizes to held-out MetaDrive Medium (catastrophe rate $41\%{\to}26\%$, 95\% bootstrap CI $[-26,-5]$\,pp) and shows directionally consistent transfer to Bullet Safety-Gym; we report honestly where it does not (MetaDrive Easy/Hard, Qwen2-VL backbone) and trace the Hard failure to a Lagrangian-regulation pathology rather than the VLM signal itself. To our knowledge, this is the first work to use frozen VLM signals as an anticipatory cost term inside the CMDP Lagrangian update.

17.
arXiv (CS.LG) 2026-06-19

Humanoid Everyday: A Comprehensive Robotic Dataset for Open-World Humanoid Manipulation

arXiv:2510.08807v2 Announce Type: replace-cross Abstract: From loco-motion to dextrous manipulation, humanoid robots have made remarkable strides in demonstrating complex full-body capabilities. However, the majority of current robot learning datasets and benchmarks mainly focus on stationary robot arms, and the few existing humanoid datasets are either confined to fixed environments or limited in task diversity, often lacking human-humanoid interaction and lower-body locomotion. Moreover, there are a few standardized evaluation platforms for benchmarking learning-based policies on humanoid data. In this work, we present Humanoid Everyday, a large-scale and diverse humanoid manipulation dataset characterized by extensive task variety involving dextrous object manipulation, human-humanoid interaction, locomotion-integrated actions, and more. Leveraging a highly efficient human-supervised teleoperation pipeline, Humanoid Everyday aggregates high-quality multimodal sensory data, including RGB, depth, LiDAR, and tactile inputs, together with natural language annotations, comprising 10.3k trajectories and over 3 million frames of data across 260 tasks across 7 broad categories. In addition, we conduct an analysis of representative policy learning methods on our dataset, providing insights into their strengths and limitations across different task categories. For standardized evaluation, we introduce a cloud-based evaluation platform that allows researchers to seamlessly deploy their policies in our controlled setting and receive performance feedback. By releasing Humanoid Everyday along with our policy learning analysis and a standardized cloud-based evaluation platform, we intend to advance research in general-purpose humanoid manipulation and lay the groundwork for more capable and embodied robotic agents in real-world scenarios. Our dataset, data collection code, and cloud evaluation website are made publicly available on our project website.

18.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

Migratory cells tend to have soft nuclei that deform and penetrate narrow spaces1,2. Extensive nuclear deformation during migration can cause nuclear-envelope rupture and DNA damage in cancer cells, which may contribute to malignant transformation during tumour progression3–6. However, the importance of DNA damage in physiological migration is less well understood. Here we demonstrate that the migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-stranded breaks (DSBs) due to mechanostress during passage through narrow interstitial spaces. In contrast to many other migratory cells, these DSBs occur without detectable nuclear envelope rupture. Confined migration increases topoisomerase-IIβ covalently bound DSBs, and these lesions are repaired through non-homologous end-joining during brain development without causing cell death. Genome sequencing revealed that DSBs tend to occur at transcriptionally inactive regions. The deletion of ligase IV at the onset of neuronal migration leads to persistent DSB accumulation in cerebellar neurons with moderate transcriptional changes in genes related to synaptic function, neuronal development and stress and immune responses. The mutant mouse develops mild motor deficits in later life, suggesting that the DNA damage generated during normal brain development poses a potential disease risk if left unrepaired. The migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-strand breaks due to mechanostress during passage through narrow interstitial spaces.

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

A Solver-Free Training Method for Predict-then-Optimize

arXiv:2606.19587v1 Announce Type: cross Abstract: We propose a scalable method for training prediction (machine learning) models in the predict-then-optimize paradigm, where model outputs serve as coefficients for a subsequent linear optimization task. Directly minimizing the empirical decision regret is intractable for linear programming and combinatorial optimization since the decision mapping is piecewise constant, and the gradients are zero almost everywhere. While existing methods address this by smoothing the differentiation process, they suffer from scalability issues, since a computationally expensive solver call is required for every gradient evaluation. To address this, we propose a decision-focused learning pipeline based on a measure transformation principle, which yields a new surrogate loss that is completely optimization-solver-free during training. We establish theoretical guarantees, including Fisher consistency and excess risk bounds. Empirically, our method achieves decision quality competitive with state-of-the-art methods while reducing training time by orders of magnitude.

20.
bioRxiv (Bioinfo) 2026-06-10

Folding the unfoldable 2: using AlphaFold and ESMFold to explore spurious proteins

Motivation: Spurious protein sequences, resulting from gene prediction errors, theoretically should not yield folded structures. AlphaFold2 was previously shown to predict short spurious sequences with high pLDDT scores and was therefore unlikely to distinguish between real proteins and spurious proteins which are usually short. We evaluate whether newer structure prediction methods (ESMFold and AlphaFold3) similarly predict short sequences with high pLDDT or if they better discriminate between spurious and real proteins. Results: All three structure prediction methods (ESMFold, AlphaFold2, and AlphaFold3) predict short spurious sequences from AntiFam with unexpectedly high pLDDT scores, however the discrimination between spurious and real proteins improves beyond 100 amino acids. By analysing sequences with disparate pTM and pLDDT scores, we identified two likely spurious shadow ORFs in Swiss-Prot and one potentially non-spurious AntiFam entry. Using the structure prediction scores, we developed a Gaussian Process Model and evaluated its performance on AlphaFold DB, identifying potential spurious proteins at scale. While limited on its own, this model can increase confidence in spurious protein identification when combined with other methods.

21.
medRxiv (Medicine) 2026-06-10

Frozen elephant trunk repair in heritable thoracic aortic disease: Impact of genetic aortopathy on long-term outcomes - A multicenter analysis

Aims This multicenter study aims to compare outcomes of total aortic arch replacement (TAR) using the frozen elephant trunk (FET) technique in patients with and without heritable thoracic aortic disease (HTAD) and to assess whether HTAD influences postprocedural adverse aortic events (AAEs). Methods From 06/2007 to 05/2024, aortic databases from 13 European centers were screened for HTAD patients undergoing TAR with FET. All consecutive dissection and aneurysm non-HTAD patients from the four core centers served as comparator. The primary outcome was AAE, a composite of diameter progression, distal stent graft induced new entry (dSINE), malperfusion, rupture and pseudoaneurysm at 5 years after FET implantation. Results Of 2739 FET patients, 196 (7.2%) were diagnosed with HTAD. The control group consisted of 867 non-HTAD FET patients. Marfan syndrome was the most common condition (72%), followed by Loeys-Dietz syndrome (11%), vascular Ehlers-Danlos syndrome (5.6%) and Turner syndrome (2.0%). Seventeen (8.8%) patients were diagnosed with ns-HTAD. At 5 years 46 (24%) AAEs occurred in the HTAD group, 169 (20%) in the non-HTAD group (p=0.2). Diameter progression was the most common event (10% vs. 12%; p=0.6), followed by dSINE (5.8% vs. 4.5%; p=0.5), malperfusion (4.2% vs. 3.3%; p=0.5), rupture (2.1% vs. 0.7%; p=0.09) and pseudoaneurysm (0.5% vs. 0.2%; p=0.5). Conclusions The FET technique appears safe and effective for acute and chronic aortic disease in HTAD patients, with outcomes comparable to non-HTAD cases and no increase in graft-related complications, challenging traditional concerns about stent graft use in genetically mediated aortic disease.

22.
medRxiv (Medicine) 2026-06-15

Wellbeing After Stroke-2 (WAterS-2): a feasibility study with process evaluation exploring inclusive, accessible, online psychological support after stroke

Objectives: Explore feasibility and acceptability of upskilling a workforce to deliver a co-developed intervention, based on Acceptance and Commitment Therapy (ACT), to support psychological adjustment post-stroke targeting underserved groups. Design: Multi-site, single-arm feasibility study with embedded mixed-methods process evaluation (ISRCTN17628580). Setting: Four NHS community stroke services across England. Participants: 1. Stroke survivors [≥]18 years of age, [≥]4 months post-stroke, reporting psychological difficulties adjusting to stroke, able to consent and access remote group sessions in English; 2. Group facilitators from NHS stroke services, not ACT specialists. Intervention: WAterS-2: an eight-session, remotely-delivered ACT-informed group intervention. Outcome measures: Recruitment, fidelity, safety, acceptability and perceived value were assessed using fidelity checklists, post-intervention surveys and semi-structured interviews with stroke survivors and facilitators. Clinical outcomes including mood (HADS), wellbeing (ONS4), psychological flexibility (AAQ-ABI), measured post-group and three-months later. Results: Nineteen stroke survivors recruited (mean 9.6 months post-stroke; n=5 (26%) minoritised ethnicities; n=10 (52%) with aphasia). Thirteen facilitators - including two peer support workers - delivered the intervention with fidelity following structured training across four services. Drop-out was low (2/19; 11%); with 15 (79%) attending [≥]5/8 sessions. Remote data collection was feasible (79% follow-up completion), with no adverse events recorded. Acceptability was high: survivors valued peer connection, grounding and mindfulness practices. ACT metaphors were helpful for some but challenging for others, including some with aphasia. Online delivery was suitable but limited informal connection. Facilitators reported increased capability, incorporating ACT skills into routine care. NHS workforce pressures and geographically-constrained referral pathways limited recruitment reach. Conclusions: WAterS-2 is feasible, safe, acceptable and inclusive. A mixed workforce, including NHS peer support workers, can be upskilled to deliver with fidelity. Inclusion of underserved groups is achievable but requires active strategies beyond standard NHS referral routes. Findings inform a provisional logic model and a future pragmatic trial.

23.
arXiv (CS.LG) 2026-06-12

FedBiCross: Personalized One-Shot Federated Learning on Medical Images

arXiv:2601.01901v4 Announce Type: replace Abstract: Data-free knowledge distillation-based one-shot federated learning (OSFL) trains a model in a single communication round without sharing raw data, making OSFL attractive for privacy-sensitive medical applications. However, existing methods aggregate predictions from all clients to form a global teacher. Under non-IID data, conflicting predictions dilute each other during averaging, yielding less informative soft labels that weaken distillation. We propose FedBiCross, a personalized OSFL framework with three stages: (1) clustering clients by model output similarity to form coherent sub-ensembles, (2) bi-level cross-cluster optimization that learns adaptive weights to selectively leverage beneficial cross-cluster knowledge while suppressing negative transfer, and (3) personalized distillation for client-specific adaptation. Experiments on four medical image datasets demonstrate that FedBiCross consistently outperforms state-of-the-art baselines across different non-IID degrees.

24.
arXiv (CS.AI) 2026-06-18

Robust Regularized Policy Iteration under Transition Uncertainty

arXiv:2603.09344v3 Announce Type: replace Abstract: Offline reinforcement learning (RL) enables data-efficient and safe policy learning without online exploration, but its performance often degrades under distribution shift. The learned policy may visit out-of-distribution state-action pairs where value estimates and learned dynamics are unreliable. To address policy-induced extrapolation and transition uncertainty in a unified framework, we formulate offline RL as robust policy optimization, treating the transition kernel as a decision variable within an uncertainty set and optimizing the policy against the worst-case dynamics. We propose Robust Regularized Policy Iteration (RRPI), which replaces the intractable max-min bilevel objective with a tractable KL-regularized surrogate and derives an efficient policy iteration procedure based on a robust regularized Bellman operator. We provide theoretical guarantees by showing that the proposed operator is a $\gamma$-contraction and that iteratively updating the surrogate yields monotonic improvement of the original robust objective with convergence. Experiments on D4RL benchmarks demonstrate that RRPI achieves strong average performance, outperforming recent baselines including percentile-based methods on the majority of environments while remaining competitive on the rest. Moreover, RRPI exhibits robust performance by aligning lower $Q$-values with high epistemic uncertainty, which prevents the policy from executing unreliable out-of-distribution actions.

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

Greedy Coordinate Diffusion: Effective and Semantically Coherent Adversarial Attacks via Diffusion Guidance

arXiv:2606.15531v1 Announce Type: new Abstract: Fine-tuning aligned language models on benign tasks (e.g. math tutoring) systematically breaks safety guardrails, even when training data contains no harmful content. While mechanistic approaches have shed light on where alignment resides in model weights, they do not by provide a general formal framework for deriving guarantees about when fine-tuning degrades it – leaving the field without principled tools for predicting or preventing alignment collapse. We develop a local geometric framework through geometric analysis of parameter-space trajectories and apply it to understand the fragility of alignment in fine-tuning. While first-order analysis suggests orthogonal updates are safe, we prove this is illusory: the curvature of the fine-tuning loss induces second-order acceleration that can induce second-order drift into alignment-sensitive regions. We formalize a construct of our framework as the Alignment Instability Condition (AIC), three geometric properties that, when present, are sufficient to guarantee degradation. Our main result proves quartic onset of alignment degradation along gradient-flow trajectories, determined by how sharply alignment depends on specific parameters and how strongly tasks couple to these parameters. These findings yield formal sufficient conditions under which static first-order protection can fail under gradient descent. We further empirically validate the framework's foundations, showing that the Fisher Information Matrix provides a proxy for the degree of safety degradation across diverse fine-tuning.