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01.
medRxiv (Medicine) 2026-06-23

Respiratory support with Continuous Positive Airway Pressure in preterm neonates: an analysis of coverage and quality of care in 66 neonatal units in Kenya, Malawi, Nigeria and Tanzania implementing with the NEST360 Alliance

Authors:
Shemwell↗Wainaina↗Lawn↗J. E↗Salim↗Penzias↗R. E↗Malla↗Johari↗Tillya↗Bohne↗C. A↗…

Background: Prematurity is the leading cause of child deaths worldwide, with the highest neonatal mortality in sub Saharan Africa. Respiratory distress syndrome (RDS) is the leading mortality pathway in preterm neonates, but continuous positive airway pressure (CPAP) has high impact. This analysis reports CPAP coverage and quality of care for preterm neonates admitted to 66 neonatal units in Kenya, Malawi, Nigeria and Tanzania. Methods: Analyses used individually linked neonatal inpatient data and cross-sectional health systems data. All admitted neonates were eligible for inclusion (January 2021 through December 2024). Service readiness for CPAP delivery and mean CPAP coverage were described for CPAP eligible newborns (weighing 1500g). Quality of care cascades were constructed to illustrate key indicators. Survival among CPAP eligible neonates was analysed using regression models, stratified by clinical severity scores. Results: 375,255 newborn admissions were analysed in 66 neonatal units. Functional CPAP availability varied with median 16% of days (IQR: 4 to 47%) classified as high demand (>1.5 eligible newborns per CPAP). Of 64,761 CPAP eligible neonates, 22,006 (34%, 95% CI 33 to 34%) received CPAP. All countries showed improvement in CPAP coverage, with Tanzanian hospitals recording 63% increase in mean coverage (p-value=0.001) over time. Quality of care cascades showed treatment was initiated 1 day for 42% (95% CI 41 to 43%) of eligible neonates receiving CPAP. Only 10% of neonates

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03.
arXiv (quant-ph) 2026-06-16

Gaussian superpositions for bosonic encodings

Authors:
Federico Centrone↗Juan Pablo Paz↗Augusto Roncaglia↗

arXiv:2603.15258v2 Announce Type: replace Abstract: Non-Gaussian bosonic states are ubiquitous in interacting light–matter systems, many-body platforms, and relativistic quantum field settings, but their quantitative characterization is hindered by the infinite-dimensional Hilbert space and by the poor scalability of Fock-space truncation methods. We introduce an exact finite-manifold encoding for states supported on a finite span of Gaussian branches, enabling the use of standard finite-dimensional quantum-information tools directly on an effective density matrix whose entries are determined by Gaussian overlaps. As demonstrations, we obtain closed-form and numerically stable evaluations of entropies and relative-entropy non-Gaussianity, and derive an analytic expression for the bipartite entanglement negativity of arbitrary multimode two-branch Gaussian superpositions, including a minimal which-branch dephasing model. Our framework provides a practical bridge between experimentally accessible continuous-variable resources (e.g., cat-like and measurement-conditioned states) and discrete-variable information measures, with immediate applications to benchmarking non-Gaussian resources in several quantum technology platforms.

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

Harnessing cortical geometry, wiring, and function as inductive biases for recurrent neural networks

Authors:
Mo Shakiba↗Rana Rokni↗Mohammad Mohammadi↗Nima Dehghani↗

arXiv:2606.14975v1 Announce Type: cross Abstract: How the wiring and functional organization of cortex shape recurrent computation remains a central question in both neuroscience and machine learning. Here, we leverage data released through the Machine Intelligence from Cortical Networks (MICrONS) program–a functional connectomics resource spanning multiple areas of mouse visual cortex, in which dense calcium imaging is co-registered with high-resolution electron microscopy reconstruction from the same animal–to build biologically grounded recurrent neural networks. Using neuronal spatial coordinates, anatomical connectivity, and function-derived relationships from nearly 12,000 coregistered excitatory neurons, we initialize recurrent weights and impose communication-aware spatial constraints during learning. Across three cognitive decision-making tasks, networks constrained by cortical structure and function consistently outperform baseline and partially constrained models. Functional weight initialization provides the largest gain, while real spatial embedding yields robust additional improvements across conditions. These biologically grounded networks also develop low-entropy, modular, and small-world organization, and retain strong performance even when recurrence is restricted to positive weights. Together, our results show that the machinery of cortex–its geometry, wiring, and functional structure–can be harnessed as a powerful inductive basis for building recurrent networks that learn more effectively while converging toward key organizational principles of biological computation.

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

High-Order Talagrand and Eldan–Gross Inequalities via Besov-Type Variance Functionals

Authors:
Guangyue Han↗Peijie Li↗

arXiv:2606.14876v1 Announce Type: new Abstract: By introducing high-order Besov-type variance functionals that generalize the canonical variance, we develop a unified framework for proving high-order Talagrand-type inequalities that relate high-order energies to Fourier weights. Applying this machinery, we establish high-order Poincaré-type, $L^p$–$L^q$, isoperimetric-type, Falik–Samorodnitsky and Eldan–Gross inequalities, all with explicit constants, in both the Boolean and Gaussian settings. Fundamentally, our semigroup-based framework relies primarily on hypercontractivity and high-order Bismut-type derivative estimates, and is broadly applicable.

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

Reasoning Text-to-Video Retrieval for Operating Room Clips via Action-Driven Digital Twins

Authors:
Yiqing Shen↗Hao Ding↗Mathias Unberath↗

Text-to-video retrieval in operating rooms (OR) is an enabling technology for OR safety, as it allows stakeholders to retrieve and inspect recordings of specific events. However, because the most safety-critical events may not follow the common structure, to unlock its full potential text-to-video retrieval must be able to handle implicit queries that require reasoning to identify the right video (e.g., the step right before clipping). However, existing methods rely on global embeddings that cannot reason over such queries. We propose OR3, a text-to-video retrieval method that converts clips into action-driven digital twins (ActDTs), grouping concurrent subject-action-object triplets under non-overlapping temporal intervals. Moreover, rather than cross-modal matching through paired encoders, OR3 performs imagination-based retrieval where an LLM generates hypothetical ActDTs from queries. This enables intra-modal matching via a single encoder trained with ActDT-tailored hard negatives. Finally, evidence-grounded refinement revises imagined ActDTs based on discrepancies with top candidates to capture procedure-specific patterns. We construct a benchmark from MM-OR with 276 implicit queries across four reasoning categories over 386 clips from robotic knee procedures. OR3 achieves 57.6 R@1 and 77.3 R@5, outperforming the strongest baseline. These results demonstrate that OR3 enables fine-grained discrimination between visually similar OR video clips through temporal action reasoning.

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07.
arXiv (CS.AI) 2026-06-11

LSTM-Based Detection of Structural Breaks in Property Insurance Loss Reserving: A Climate-Informed Approach

Authors:
Thomas Mbrice↗Shashwat Panigrahi↗

arXiv:2606.11463v1 Announce Type: cross Abstract: Accurate loss reserving is foundational to insurer solvency, yet accelerating climate driven catastrophes systematically violate the stability assumptions on which traditional actuarial methods depend. This white paper presents a research program testing whether Long Short Term Memory (LSTM) neural networks can detect and adapt to these structural breaks faster and more accurately than Chain Ladder, Bornhuetter Ferguson, and Cape Cod methods. Using 15 plus years of regulatory development triangle data from Florida and Louisiana, enriched with NOAA hurricane intensity indices and sea surface temperatures, we hypothesize a targeted improvement of 15, 20% in reserve accuracy for catastrophe exposed years, a threshold grounded both in the prior neural network reserving literature and in the formal convergence results developed here. Beyond empirical validation, we develop a theoretical framework grounding LSTM structural break detection in probabilistic terms, providing formal performance guarantees that compensate for the limited number of catastrophe events in the test period. We document the research design, methodology, expected contributions, and a candid assessment of limitations.

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

Smoothness-Based Derandomization of PAC-Bayes Bounds

Authors:
Alexandre Lemire Paquin↗Brahim Chaib-Draa↗Philippe Gigu\`ere↗

arXiv:2606.19105v1 Announce Type: new Abstract: We study PAC-Bayes derandomization for smooth loss functions. Our goal is to obtain generalization bounds that hold with high probability for deterministic predictors by exploiting smoothness properties of both the loss and the predictor class. We show that passing from the Gibbs predictor to the deterministic predictor at the posterior mean has a precise cost, given by the generalization gap of the Jensen gap class. We control this class through its Rademacher complexity, leading to bounds for deterministic predictors that involve flatness quantities expressed in terms of parameter Jacobians and Hessians of the score map. The framework applies to both bounded and unbounded smooth loss functions, and we specialize the results to linear predictors and smooth neural networks. Finally, the Jacobian and Hessian quantities appearing in the theory motivate a practical regularizer. For BatchNorm networks, we compute this regularizer with respect to effective BatchNorm weights obtained by folding the BatchNorm transformation into the adjacent affine weights. Experiments on CIFAR-10 illustrate the behavior of this regularizer under different batch sizes.

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09.
Nature (Science) 2026-06-08

Daily briefing: Human embryo genomes precisely altered

Authors:
Flora Graham↗

The use of ‘base editing’ to precisely tweak human embryos has divided researchers. Plus, the number of lives saved by less-polluting cars in China and how to tip the world towards a sustainable future. The use of ‘base editing’ to precisely tweak human embryos has divided researchers. Plus, the number of lives saved by less-polluting cars in China and how to tip the world towards a sustainable future.

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10.
arXiv (CS.LG) 2026-06-15

Private Prediction via PAC Privacy

Authors:
Xiaochen Zhu↗Mayuri Sridhar↗Srinivas Devadas↗

arXiv:2601.14033v2 Announce Type: replace Abstract: Machine learning models are increasingly served behind APIs. This renders private prediction, i.e., privatizing a model's outputs rather than its parameters, a natural privacy target: model outputs are lower-dimensional and far more stable to training-data changes than weights. While differential privacy (DP) cannot effectively exploit this as it calibrates noise to worst-case sensitivity that is intractable to bound for non-convex models, we argue that PAC privacy is a natural fit for private prediction. It is instance-based, and calibrates noise to a black-box function's empirical stability to control mutual-information (MI) leakage. The missing ingredient is efficient, adaptive composition. Serving predictions means answering a long stream of adaptively chosen queries from untrusted users; existing composition either fails under adaptivity, grows quadratically, or reverts to input-independent, DP-like noise. We close this gap with a new adversarial composition result via adaptive noise calibration and prove that MI accumulates only linearly under adaptive and adversarial querying. Experiments across modalities show that prediction stability enables high utility even at a tiny per-query budget: on CIFAR-10, we achieve 87.79% accuracy with a per-query MI budget of $2^{-32}$. This enables serving one million queries while provably bounding membership-inference success to 51.08% – the same guarantee as $(0.04, 10^{-5})$-DP. Further, in the presence of auxiliary public data, the large volume of PAC-private predictions enables us to distill a publishable model that can be queried without limit. Concretely, 210,000 private labels on an ImageNet subset distill into a student reaching 91.86% accuracy on CIFAR-10 with membership inference success bounded by 50.49%, comparable to $(0.02, 10^{-5})$-DP.

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

Cryptographic certificates of validity for trustworthy AI

Authors:
Murdoch J. Gabbay↗

arXiv:2606.23768v1 Announce Type: cross Abstract: We propose cryptographic certificates of validity for agentic AI systems. The core idea is to formally specify a correctness or policy condition as a logical predicate, compile this predicate to a witness-checking problem over polynomial constraints, and use a succinct cryptographic proof system (and optionally zero-knowledge) to certify that the condition holds. This offers a middle ground between formal verification of source code, and cryptographic authentication. An agent's action can be accompanied by an independently checkable proof that it satisfies an agreed formal policy, without requiring the verifier to trust the agent or to re-execute computation. We outline the approach at a high level, give the core mathematical translation, relate the proposal to proof-carrying code, zkVMs, formal methods, and agent governance, and note the specification, auditing, and deployment questions that a full implementation must answer.

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12.
Nature (Science) 2026-06-24

Genetic diversity of late Neanderthals in northwestern Europe

Authors:
Alba Bossoms Mesa↗

Archaeological, osteological and genetic evidence suggests that Neanderthals lived in small groups1,2; however, less is known about whether these groups were part of isolated communities or belonged to larger, well-connected populations3. The dense concentration of broadly contemporaneous Neanderthal sites in the Meuse Basin, Belgium4, provides a rare opportunity to study regional populations at high resolution. Here we generated genetic data from 27 Neanderthals who lived less than approximately 52,500 years ago from ten archaeological sites in Belgium and France, including a high-coverage genome from a 45,000-year-old individual from Goyet, Belgium. We show that most of these individuals are more closely related to one another than to other contemporaneous late Neanderthals in Europe. Further, some of these individuals carry DNA from a Neanderthal lineage predating the split of late Neanderthals. Although these Neanderthals overlapped temporally with early modern humans in northwestern Europe from around 47,000 years ago, we find no evidence of recent gene flow from modern humans. They also do not show the genetic signatures of mating among close relatives found in Altai Neanderthals, suggesting that they lived in larger or better-connected groups. Moreover, genetic load did not accumulate over time, arguing against progressive genetic deterioration as a driver of Neanderthal extinction. Genetic sequencing of multiple late Neanderthals living less than 52,500 years ago provides an overview of genetic diversity and demonstrates that even low-coverage nuclear genome data can increase resolution of within-Neanderthal diversity.

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13.
arXiv (CS.LG) 2026-06-12

Learning-Augmented Approximation for Unrelated-Machines Makespan Scheduling

Authors:
Kaito Baba↗Evripidis Bampis↗Giorgos Mitropoulos↗

arXiv:2606.13133v1 Announce Type: cross Abstract: Recently, Antoniadis et al. (ICLR 2025) proposed a framework for incorporating predictions to approximate NP-hard selection problems. Despite its simplicity, this approach tightly matches theoretical lower bounds, making its generalization highly compelling. We address an open question raised in the work of Antoniadis et al., concerning the extension of this approach to other important problems outside the class of selection problems, such as scheduling. We develop a learning-augmented algorithm for the makespan minimization problem on unrelated machines, denoted by $R\|C_{\max}$. By using predictions of heavy job assignments, we achieve a polynomial-time $(1+\varepsilon)$-approximation for accurate predictions that smoothly degrades to a worst-case 2-approximation as the error increases. We conclude our work with an empirical analysis of our method.

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14.
arXiv (CS.AI) 2026-06-12

Learning What to Remember: Observability-Safe Memory Retention via Constrained Optimization for Long-Horizon Language Agents

Authors:
Qingcan Kang↗Liu Mingyang↗Shixiong Kai↗Kaichao Liang↗Tao Zhong↗Mingxuan Yuan↗

arXiv:2606.10616v2 Announce Type: replace Abstract: Long-horizon language agents accumulate observations, reasoning traces, and retrieved facts that exceed their finite context windows, making memory retention a fundamental resource-allocation problem. Existing memory systems improve management through heuristic scoring, retrieval optimization, or learned compression, but largely treat retention as a local decision problem and do not explicitly model its long-term consequences under realistic observability constraints. To fill this gap, we formulate memory retention as a constrained stochastic optimization problem with explicit budget feasibility, evidence utility, and delayed costs including miss penalties, reacquisition delays, and stale-information risk. We then propose OSL-MR (Observability-Safe Learning for Memory Retention), a novel framework that enforces a strict separation between online-observable features and offline-available supervision (OAS). OSL-MR combines an evidence learner trained from realized evidence supervision with a Mixed-Score heuristic that serves both as a deployable online-safe baseline and as a structured inductive prior for learning. The resulting policy learns query-conditioned evidence value directly from interaction data while remaining deployable under the same observability constraints. Experiments on LOCOMO and LongMemEval show that OSL-MR consistently outperforms recency-based methods, Generative Agents-style scoring, and other heuristic baselines, particularly under tight memory budgets. The Mixed-Score prior further improves precision while preserving recall, and sensitivity analysis demonstrates robustness across a wide range of cost configurations.

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15.
arXiv (CS.AI) 2026-06-19

RoboSSM: Scalable In-context Imitation Learning via State-Space Models

Authors:
Youngju Yoo↗Jiaheng Hu↗Yifeng Zhu↗Bo Liu↗Qiang Liu↗Roberto Mart\'in-Mart\'in↗Peter Stone↗

arXiv:2509.19658v2 Announce Type: replace-cross Abstract: In-context imitation learning (ICIL) enables robots to learn tasks from prompts consisting of just a handful of demonstrations. By eliminating the need for parameter updates at deployment time, this paradigm supports few-shot adaptation to novel tasks. However, recent ICIL methods rely on Transformers, which have computational limitations and tend to underperform when handling longer prompts than those seen during training. In this work, we introduce RoboSSM, a scalable recipe for in-context imitation learning based on state-space models (SSM). Specifically, RoboSSM replaces Transformers with Longhorn – a state-of-the-art SSM that provides linear-time inference and strong extrapolation capabilities, making it well-suited for long-context prompts. Through diverse experiments on the LIBERO benchmark, we demonstrate the effectiveness of applying SSMs to ICIL, achieving improved generalization to both unseen and long-horizon tasks than Transformer-based ICIL methods by handling longer contexts at test-time. These results show for the first time that SSMs are an efficient and scalable backbone for ICIL. Our code is available at https://github.com/youngjuY/RoboSSM.

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

QueryOcc: Query-based Self-Supervision for 3D Semantic Occupancy

Authors:
Adam Lilja↗Ji Lan↗Junsheng Fu↗Lars Hammarstrand↗

Learning 3D scene geometry and semantics from images is a core challenge in computer vision and a key capability for autonomous driving. Since large-scale 3D annotation is prohibitively expensive, recent work explores self-supervised learning directly from sensor data without manual labels. Existing approaches either rely on 2D rendering consistency, where 3D structure emerges only implicitly, or on discretized voxel grids from accumulated lidar point clouds, limiting spatial precision and scalability. We introduce QueryOcc, a query-based self-supervised framework that learns continuous 3D semantic occupancy directly through independent 4D spatio-temporal queries sampled across adjacent frames. The framework supports supervision from either pseudo-point clouds derived from vision foundation models or raw lidar data. To enable long-range supervision and reasoning under constant memory, we introduce a contractive scene representation that preserves near-field detail while smoothly compressing distant regions. QueryOcc surpasses previous camera-based methods by 26% in semantic RayIoU on the self-supervised Occ3D-nuScenes benchmark while running at 11.6 FPS, demonstrating that direct 4D query supervision enables strong self-supervised occupancy learning. https://research.zenseact.com/publications/queryocc/

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17.
arXiv (math.PR) 2026-06-15

Sectional Curvature for Kantorovich-Wasserstein and Hellinger-Kantorovich Geometries

Authors:
Karl-Theodor Sturm↗

arXiv:2606.14318v1 Announce Type: cross Abstract: We derive an explicit formula for the sectional curvature of the space ${\cal M}(M)$ of finite measures on a Riemannian manifold M. The space ${\cal M}(M)$ is equipped with the Hellinger-Kantorovich metric $HK$. Even in the case M=R^n, the curvature is comprised of two parts: the `lifted part' is negative, and the `twisted part' is positive. It will be analyzed in detail for the multidimensional torus. Our general approach to sectional curvature in geodesic spaces also leads to new insights into the curvature of the space $P_2(M)$ of probability measures on M equipped with the Kantorovich-Wasserstein metric $W_2$.

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18.
arXiv (CS.AI) 2026-06-12

PI-Hunter: Automated Red-Teaming for Exposing and Localizing Prompt Injections

Authors:
Pengfei He↗Lesly Miculicich↗Vishesh Sharma↗Ash Fox↗George Lee↗Jiliang Tang↗Tomas Pfister↗Long T. Le↗

arXiv:2606.12737v1 Announce Type: cross Abstract: Large Language Models (LLMs) are rapidly evolving into agentic systems that interact with external tools and environments, introducing new security risks such as indirect prompt injection attacks through untrusted external sources. Existing defenses mainly focus on blocking malicious content at inference time, and current red-teaming methods primarily optimize attack success. As a result, developers have limited visibility into how latent prompt injections emerge and propagate through agents. We propose PI-Hunter, an automated agentic auditing framework for proactive vulnerability exposure in LLM agents. PI-Hunter constructs realistic source-aware test cases and iteratively evolves them through feedback-driven exploration to induce agents to retrieve and reveal latent malicious instructions embedded within external environments. Extensive experiments across multiple benchmarks, agent architectures, attacks, and defenses demonstrate that PI-Hunter substantially improves vulnerability exposure and attack-surface coverage over strong automated red-teaming baselines, while remaining effective under existing prompt injection defenses.

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19.
arXiv (quant-ph) 2026-06-12

Electric Field Distortions in Surface Ion Traps with Integrated Nanophotonics

Authors:
Guochun Du↗Elena Jordan↗Tanja E. Mehlst\"aubler↗

arXiv:2503.20387v3 Announce Type: replace Abstract: The integration of photonic components into surface ion traps provides a scalable approach for trapped-ion quantum computing, sensing, and metrology, enabling compact systems with enhanced stability and precision. However, the introduction of optical apertures in the trap electrodes can distort the trapping electric field. This can lead to excess micromotion (EMM) and ion displacement which degrade the performance of quantum logic operations and optical clocks. In this work, we systematically investigate the electric field distortion in a surface ion trap with integrated waveguides and grating couplers using Finite Element Method (FEM) simulations. We analyze methods to reduce these distortions by exploiting symmetries and transparent conductive oxide materials.

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20.
arXiv (CS.AI) 2026-06-16

No One-Size-Fits-All Neurons: Task-based Neurons for Artificial Neural Networks

Authors:
Feng-Lei Fan↗Meng Wang↗Hang-Cheng Dong↗Jianwei Ma↗Tieyong Zeng↗

arXiv:2405.02369v2 Announce Type: replace-cross Abstract: In the past decade, many successful networks are on novel architectures, which almost exclusively use the same type of neurons. Recently, more and more deep learning studies have been inspired by the idea of NeuroAI and the neuronal diversity observed in human brains, leading to the proposal of novel artificial neuron designs. Designing well-performing neurons represents a new dimension relative to designing well-performing neural architectures. Biologically, the brain does not rely on a single type of neuron that universally functions in all aspects. Instead, in our brain, neurons are often task-based. In this study, we address the following question: since the human brain is a task-based neuron user, can the artificial network design go from the task-based architecture design to the task-based neuron design? Since methodologically there are no one-size-fits-all neurons, given the same structure, task-based neurons can enhance the feature representation ability relative to the existing universal neurons due to the intrinsic inductive bias for the task. Specifically, we propose a two-step framework for prototyping task-based neurons. As the initial step, we evaluate the proposed framework using polynomials as base functions. Empirically, systematic experimental results on synthetic data, classic benchmarks, and real-world applications show that the proposed task-based neuron design is not only feasible but also delivers competitive performance over other state-of-the-art models.

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21.
arXiv (CS.AI) 2026-06-11

Risk Under Pressure: Compute-Aware Evaluation of Adversarial Robustness in Language Models

Authors:
Malikeh Ehghaghi↗Bogl\'arka Ecsedi↗Marsha Chechik↗Colin Raffel↗

arXiv:2606.11409v1 Announce Type: cross Abstract: Adversarial robustness evaluations of large language models (LLMs) typically report attack success rate (ASR) under fixed query budgets, implicitly treating all attacks as equally costly. In practice, the computational expense of different attack strategies can vary by orders of magnitude. Consequently, ASR at a fixed budget can obscure the true effort required to jailbreak a model, thereby making it hard to determine whether an attack's cost justifies its payoff to the attacker. We propose a compute-aware evaluation framework based on computational pressure, measured in cumulative floating-point operations (FLOPs), as a proxy for adversarial effort. We introduce risk-compute curves, which map compute budgets to attack risk, and derive two metrics that summarize the average pressure required for a given attack to succeed. Across ten models spanning three families and four different stages in language model training and alignment, evaluated with three attack strategies (gradient-based, iterative refinement, and template-based) on two jailbreak robustness benchmarks, we find: (1) alignment training has non-monotonic effects on compute-space robustness; (2) scaling model size reduces gradient-based attack effectiveness but has limited impact on cheaper template-based attacks; (3) gradient-based attacks optimized on a surrogate model can transfer to a separate target model, providing a way to reduce attacker costs; (4) compute cost varies by up to ${\approx}5{\times}$ across harm categories within a single model; and (5) safety-aligned RL increases aggregate cost while leaving some categories disproportionately accessible. We release our framework to enable compute-aware risk assessment and evaluation.

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22.
bioRxiv (Bioinfo) 2026-06-19

FeatureMSEA: Metabolic Feature-based Metabolite Set Enrichment Analysis

Authors:
Liu↗Wang↗Huan↗Shen↗

Liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics detects thousands of metabolic features, but converting these chemical signals into metabolite set-level biological knowledge remains challenging. This is because most features lack unambiguous metabolite identities. Conventional metabolite set enrichment analysis (MSEA) generally requires identified metabolites and metabolite-level ranked inputs, leaving much of the untargeted feature space unused. Here, we present FeatureMSEA, a feature rank-based framework for metabolite set enrichment directly from metabolic features with ambiguous annotations. FeatureMSEA integrates multi-evidence feature-to-metabolite annotation, feature rank-based enrichment scoring, permutation-based inference, and iterative leading-edge-guided annotation refinement, with an optional LLM-assisted module for post-enrichment interpretation. In null comparisons of randomly split healthy samples, FeatureMSEA detected no significant metabolite sets, whereas metabolite-set spike-in simulations showed recovery of implanted signals. In a cerebrospinal fluid metabolomics study of Huntington's disease, FeatureMSEA identified dysregulated metabolite sets related to amino acid metabolism, mitochondrial energy metabolism, and neuroactive signaling. MS/MS-based annotation analysis further showed that FeatureMSEA refinement reduced annotation ambiguity and prioritized chemically consistent candidate metabolites. In summary, FeatureMSEA provides a general framework for extracting metabolite set-level biological insights from LC-MS untargeted metabolomics in which confident metabolite identification remains incomplete.

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23.
bioRxiv (Bioinfo) 2026-06-17

An Integrated Framework for Transcriptomic Characterization and Lorentzian Hyperbolic Visualization of a High-Risk Topological Branch in Alzheimer's Disease

Authors:
Zeng↗Pu↗Tao↗Wei↗Zhao↗Cai↗Ge↗

Alzheimer's disease (AD) is a highly heterogeneous brain disorder in which molecular alterations vary across brain regions, disease stages, and patient subgroups. This study introduces an integrated analytical framework for characterizing transcriptomic variation associated with a high-risk topological branch, which was identified based on Lorentz distance in postmortem Brodmann area 36 samples from the Mount Sinai Brain Bank cohort, where over 70% of samples were in Braak stages V-VI. The framework integrates weighted gene co-expression network analysis, repeated stability-based differential expression analysis, network-level gene filtering, Gene Ontology enrichment, and nested stratified cross-validation to evaluate whether topological branch-associated genes capture biologically meaningful signals and carry predictive information for high-Braak group status. The identified gene sets were functionally enriched for neuronal development, neuron projection organization, synaptic signaling, vesicle fusion, and regulated synaptic release, suggesting that the high-risk topological branch reflects biologically relevant transcriptomic programs linked to neurodegenerative progression. Nested cross-validation further showed that the selected genes achieved measurable internal predictive performance for distinguishing high-Braak samples. As a second methodological contribution, we introduced a Lorentzian hyperbolic variant of t-distributed stochastic neighbor embedding (Lorentz t-SNE) to explore latent non-Euclidean structure in transcriptomic data. This method embeds samples in hyperbolic space, providing an alternative to Euclidean embeddings for representing hierarchical or nonlinear structures. Compared with conventional Euclidean embeddings, the proposed Lorentz t-SNE revealed a more localized organization of high-Braak samples. Together, these results demonstrate the utility of the proposed analytical framework and Lorentz t-SNE for investigating heterogeneous, potentially non-Euclidean organization in AD transcriptomes.

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24.
arXiv (CS.CL) 2026-06-12

AI SciBrief as a Gateway to Research: A Framework for Onboarding Students into New Research Areas

Authors:
Andrei Lazarev↗Dmitrii Sedov↗

Students at all levels of higher education face a significant barrier in the form of information overload, which often paralyzes the initial stages of the research process and suppresses motivation. In response, this article introduces a pedagogical framework that leverages AI SciBrief, a platform powered by a Large Language Model (LLM) designed to automatically generate digests of scientific trends. We describe how this multidisciplinary tool - with initial coverage in finance, medicine, and education - can be integrated into the curriculum to overcome this "entry barrier." The framework provides concrete methodologies for utilizing these digests to facilitate topic selection for term papers, accelerate literature reviews for dissertations, and enable postgraduate students to continuously monitor emerging trends. We conclude that AI SciBrief functions as a "gateway to research" effectively reducing students' cognitive load and empowering them to transition more rapidly from information searching to knowledge creation.

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25.
PLOS Computational Biology 2026-06-03

IsoPepTracker: An interactive web application for peptide-driven isoform analysis

Authors:
Araf Mahmud↗

by Araf Mahmud, Chen Huang Alternative splicing affects 95% of multi-exon genes, generating protein isoforms with distinct functions. While current alternative splicing analyses effectively identify splice events at the RNA level, they provide limited protein-level insight. To address this gap, we developed IsoPepTracker (https://www.isopeptracker.org), a user-friendly web application for analyzing and visualizing differential peptides across canonical and novel isoforms that are theoretically detectable by shotgun mass spectrometry-based proteomics. IsoPepTracker features four modules: Canonical Isoform Analysis, Novel Isoform Discovery, Peptide Sequence Search, and Alternative Splicing Analysis. Each module is tailored for distinct and complementary proteogenomics analyses. Users can input genes, novel cDNA sequences, peptides, or alternative splicing results to pinpoint peptides of interest and identify their associations with target genes or isoforms. We demonstrate the straightforward application of IsoPepTracker in proteogenomics through case studies. IsoPepTracker not only provides informative peptide signatures to understand the protein-level consequences of alternative splicing but also supplies peptide candidates for validation in shotgun proteomics.

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