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

OSGuard: A Benchmark for Safety in Computer-Use Agents

arXiv:2606.15034v1 Announce Type: new Abstract: Computer-use agents are increasingly evaluated by whether they complete realistic desktop and web tasks. However, task success alone can miss failures in which an agent reaches the nominal goal through an unsafe shortcut. We introduce OSGuard, a dual-granularity benchmark suite for evaluating safety in computer-use agents under benign, unchanged user instructions. OSGuard contains an action-level benchmark for local guardrail decisions and a risk-augmented execution suite for end-to-end evaluation. The action-level benchmark consists of contextualized proposed actions labeled as allowed, unrelated, or unsafe, each judged relative to the original instruction and current interface state. The execution suite contains manually constructed OSWorld-derived task variants in which the original task remains achievable, but the environment is modified to introduce latent hazards such as destructive overwrites, etc. Each variant is paired with augmented evaluators that retain the original task-success criterion while adding explicit state-based safety invariants, allowing us to distinguish safe completions from unsafe completions that satisfy the nominal task objective. Our experimental results on OSGuard show that current multimodal guardrails can perform well on isolated action judgments, while risk-augmented execution exposes remaining gaps between local oversight and reliable end-to-end safety. This dual-granularity design enables more precise diagnosis of whether models can both recognize unsafe proposed actions and improve full-task safety when deployed as guardrails.

03.
arXiv (CS.CV) 2026-06-17

Complex Layout Classification in the Wild: A Low-Resource Approach with Layout-Preserving Augmentations

Many digitized corpora suffer from low resources because annotations may be scarce, page scans are noisy and of poor resolution, or layouts are structurally complex in ways that negatively affect the quality of automatic transcription. Developing robust classification models for low-resource languages is inhibited by the lack of large-scale annotated data and by the frequent semantic complexity of page layouts. To this end, we have curated a complex-layout dataset, manually classified into eight distinct layout types based on their separator regions. To overcome data scarcity, we propose a novel training strategy in the form of a CNN-based classifier that employs strong, domain-aware augmentations to improve generalization. We utilize narrow anisotropic Gaussian masking to suppress incidental textual details while preserving essential separations, compelling the model to learn global geometric arrangements. Additionally, we implement reflection-induced label transformations to enrich the training distribution while maintaining label consistency across asymmetric categories. The results demonstrate that layout-specific augmentations can substantially improve page-level layout classification under severe annotation scarcity.

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

Label Shift Aware Adaptation for Online Zero-shot Learning with Contrastive Language-Image Pre-Training (CLIP)

Vision-language models like Contrastive Language-Image Pre-Training (CLIP) have been extensively studied in data-scarce scenarios. A particularly challenging and realistic task in this area is online zero-shot learning with CLIP, where unknown test samples are predicted sequentially in random order by CLIP while keeping the feature extraction and model parameters fixed during the sequential inference phase. Most existing approaches in this setting address the problem by adapting representations online using incoming test samples, while neglecting the distribution of the data on which CLIP was initially trained. This mismatch can lead to degraded performance when the label distribution in the test data differs from that of the training domain. To address this gap, we propose Label Shift Aware (LSA), which formulates the online zero-shot classification task as a domain adaptation problem. Specifically, LSA adapts the predictions computed by CLIP, which was trained on an unknown source distribution, to a target distribution using only unlabeled test data, and applies label shift correction to mitigate the mismatch between the source and target domains. The extensive experiments across multiple datasets demonstrate that the proposed LSA consistently outperforms state-of-the-art online zero-shot learning methods based on CLIP.

05.
arXiv (CS.LG) 2026-06-12

PLaID++: A Preference Aligned Language Model for Targeted Inorganic Materials Design

arXiv:2509.07150v4 Announce Type: replace Abstract: Reinforcement Learning from Verifiable Rewards (RLVR) has emerged as a promising approach to improve correctness in LLMs, however, in many scientific problems, the objective is not necessarily to produce the correct answer, but instead to produce a diverse array of candidates which satisfy a set of constraints. We study this challenge in the context of materials generation. To this end, we introduce PLaID++, an LLM post-trained for stable and property-guided crystal generation. We find that performance hinges on our crystallographic representation and reward formulation. First, we introduce a compact, symmetry-informed Wyckoff text representation which improves computational efficiency and encourages generalization from physical priors. Second, we demonstrate that temperature scaling acts as an entropy regularizer which counteracts mode collapse and encourages exploration. By encoding symmetry constraints directly into text and guiding model outputs towards desirable chemical space, PLaID++ generates structures that are thermodynamically stable, unique, and novel at a $\sim$50\% greater rate than prior methods and conditionally generates structures with desired space group properties. Our work demonstrates the potential of adapting post-training techniques from natural language processing to materials design, paving the way for targeted and efficient discovery of novel materials.

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

REVEAL++: Differentiable Phenotypic Grouping for Vision-Language Retinal Modeling of Alzheimer's Disease Risk

arXiv:2606.19522v1 Announce Type: new Abstract: The retina offers a noninvasive window into neurodegenerative disease, capturing subtle structural patterns associated with a risk of future cognitive decline. Vision-language alignment frameworks such as REVEAL have shown that pairing retinal fundus images with structured clinical risk narratives improves early prediction of Alzheimer's disease (AD). A key design choice in these approaches is the use of phenotypic grouping, where individuals with similar risk profiles are treated as multi-positive pairs during contrastive learning. However, existing methods operationalize phenotypic similarity as a discrete construct, relying on hard group assignments that impose rigid supervision and decouple group formation from representation learning. We propose a continuous formulation of phenotypic structure within contrastive learning. Rather than assigning samples to fixed clusters, we model inter-subject similarity as a differentiable weighting function derived from intra-modality embedding similarities in both retinal images and risk profiles. These weights define soft multi-positive relationships through a continuous aggregation operator, enabling graded supervision that reflects the spectrum nature of disease risk. We further introduce a soft-target contrastive objective that jointly learns cross-modal alignment and phenotypic structure in an end-to-end manner. Evaluated on UK Biobank retinal imaging data for incident AD prediction, the proposed framework consistently outperforms discrete group-based contrastive learning and standard vision-language baselines. By treating phenotypic similarity as a learnable, continuous signal rather than a fixed grouping rule, our approach provides a principled and robust foundation for population-scale neurodegenerative risk modeling from multi-modal retinal and clinical data.

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

NTIRE 2024 Challenge on Image Super-Resolution (x4): Methods and Results

This paper reviews the NTIRE 2024 challenge on image super-resolution ($\times$4), highlighting the solutions proposed and the outcomes obtained. The challenge involves generating corresponding high-resolution (HR) images, magnified by a factor of four, from low-resolution (LR) inputs using prior information. The LR images originate from bicubic downsampling degradation. The aim of the challenge is to obtain designs/solutions with the most advanced SR performance, with no constraints on computational resources (e.g., model size and FLOPs) or training data. The track of this challenge assesses performance with the PSNR metric on the DIV2K testing dataset. The competition attracted 199 registrants, with 20 teams submitting valid entries. This collective endeavour not only pushes the boundaries of performance in single-image SR but also offers a comprehensive overview of current trends in this field.

08.
arXiv (CS.AI) 2026-06-11

TAPIOCA: Why Task- Aware Pruning Improves OOD model Capability

arXiv:2605.14738v3 Announce Type: replace-cross Abstract: Recent work has promoted task-aware layer pruning as a way to improve model performance on particular tasks, as shown by TALE. In this paper, we investigate when such improvements occur and why. We show first that, across controlled polynomial regression tasks and large language models, such pruning yields no benefit on in-distribution (ID) data but consistently improves out-of-distribution (OOD) accuracy. We further show empirically that OOD inputs induce layerwise norm and pairwise-distance profiles that deviate from the corresponding ID profiles. This leads to a geometric explanation of task-aware pruning: each task induces a task-adapted geometry, characterized empirically by the representation profiles observed on ID inputs. OOD inputs can introduce a distorted version of the task-adapted geometry. Task-aware pruning identifies layers that create or amplify this distortion; by removing them, it shifts OOD representational norms and pairwise distances toward those observed on the adapted distribution. This realigns OOD inputs with the model's task-adapted geometry and improves performance. We provide causal evidence through controlled distribution shifts and residual-scaling interventions, and demonstrate consistent behavior across model scales.

09.
arXiv (CS.CL) 2026-06-16

GRACE-DS: a Guarded Reward-guided Agent Correction Environment in Data Science

We introduce GRACE-DS, a Guarded Reward-guided Agent Correction Environment in Data Science for pre-deployment evaluation of LLM-powered AutoML agents. GRACE-DS is a set of evaluation metrics in an isolated environment that can be applied to tabular ML tasks specific to a particular organization. It exposes agents to realistic workflow stages, from planning and data inspection through feature engineering, model development, validation, and code repair to final submission, while hidden executable validators measure not only final predictive performance but also leakage avoidance, reproducibility, protocol validity, correction behavior, and reward alignment. The strongest structured regime, flexible iterative interaction (our approach), achieves higher end-to-end normalized hidden-test quality than single-shot generation, unstructured interaction, and restart-based baselines, while also improving protocol-valid completion. Validated across more than 7,000 episodes, these results establish GRACE-DS as a robust platform for assessing the capacity of LLM-based AutoML agents to execute machine learning workflows under production-like conditions and in accordance with organization-specific requirements.

10.
arXiv (quant-ph) 2026-06-16

Adiabatically-induced Kawaguchi geometry and jerk in quantum-classical systems

arXiv:2606.16037v1 Announce Type: new Abstract: Adiabatically eliminating the quantum degrees of freedom in a mixed quantum-classical system produces an effective force in the classical equation of motion. The elimination can be made to any order in the adiabatic parameter, generating a series of higher order forces. By applying a sequence of near-identity unitary transformations to the quantum state, we derive a hierarchy of increasingly accurate effective actions for the classical variables. The third order Euler-Lagrange equation is non-Newtonian as the force depends on the jerk, the third order time derivative of position. We find that the third order terms induce a special kind of Kawaguchi geometry on the space of classical variables. This geometry is characterized by an almost symplectic structure and a differential line element that depends on the acceleration in addition to the velocity. Our results can be used to efficiently capture higher order nonadiabatic effects in molecular dynamics simulations.

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

Online Shift Detection and Conformal Adaptation for Deployed Safety Classifiers

Authors:

arXiv:2606.11949v1 Announce Type: new Abstract: We present an online monitoring system for distributional shift in deployed safety classifiers, using calibrated sequential statistics to detect when a classifier has moved out of distribution. Upon detection, a conformal abstention layer adapts decision thresholds to recover a target error rate epsilon=0.1. In a pre-registered factorial evaluation (4 classifiers x 5 shift conditions x 20 seeds x 2 window sizes, 800 cells), the system achieves 86.6% valid detection (693/800, 95% CI [84.1%, 88.8%]) with mean latency of 39.5 steps. Detection holds across three ground-truth regimes: synthetic onset (86.6%), real temporal jailbreaks (85%, 17/20), and GCG adversarial attacks. Weighted conformal prediction recovers up to 39 pp of lost coverage for DeBERTa (ESS=46/300) but collapses for all other classifiers (ESS~300): logistic density ratio estimation achieves perfect source/target separability in high-dimensional embedding spaces, clipping all importance weights to the floor. DeBERTa shows a gradient from effective correction (paraphrase, ESS=46) to near-total collapse (adversarial suffix, ESS=206). PCA to 32 dimensions breaks the collapse, recovering 33 pp for Llama Guard and 21 pp for ShieldGemma. Variance decomposition reveals classifier (eta^2=0.243), shift type (eta^2=0.237), and their interaction (eta^2=0.185) all contribute substantially to detection latency variance (all p

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

Can Factual Opinions Be Edited (Manipulated) in Large Language Models?

Large Language Models (LLMs) are increasingly integrated into various domains, making knowledge editing techniques crucial yet potentially hazardous. Current editing methods primarily target atomic facts, overlooking the significant risks associated with manipulating factual opinions, e.g., documented stances of public figures on societal issues. Such manipulation could reshape public images, influence elections, and alter societal views. To systematically assess this threat, we introduce the Factual Opinion Editing with Evidence (FOE) benchmark, which encompasses 261 public figures, 19 issue categories, and 2,178 complete opinion records. Our evaluations demonstrate that current editing techniques struggle significantly with factual opinions, often achieving only superficial changes while failing to preserve consistency between the edited opinion and the supporting evidence generated by the model. To address this limitation, we further propose a simple yet effective Self-Generated Evidence-Aligned method that achieves opinion-evidence alignment without relying on explicit instructions. Together, our benchmark and method provide a foundation for understanding the emerging security implications of factual opinion editing in LLMs.

13.
Nature (Science) 2026-06-22

Daily briefing: First-ever ‘nuclear’ clocks put atomic clocks in the shade

Authors:

Two research teams have created a new, long-awaited type of timekeeper. Plus, how backlash has saved an ocean-monitoring network targeted by Trump and how our cultural heritage is put at risk by climate change. Two research teams have created a new, long-awaited type of timekeeper. Plus, how backlash has saved an ocean-monitoring network targeted by Trump and how our cultural heritage is put at risk by climate change.

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

Price of metric universality in vector quantization is at most 0.11 bit

arXiv:2602.05790v2 Announce Type: replace-cross Abstract: Fast computation of a matrix product $W^\top X$ is a workhorse of modern LLMs. To make their deployment more efficient, a popular approach is that of using a low-precision approximation $\widehat W$ in place of true $W$ (``weight-only quantization''). Information theory demonstrates that an optimal algorithm for reducing precision of $W$ depends on the (second order) statistics of $X$ and requires a careful alignment of vector quantization codebook with PCA directions of $X$ (a process known as ``waterfilling allocation''). Dependence of the codebook on statistics of $X$, however, is highly impractical. This paper proves that there exist a universal codebook that is simultaneously near-optimal for all possible statistics of $X$, in the sense of being at least as good as an $X$-adapted waterfilling codebook with rate reduced by 0.11 bit per dimension in the case when $W$ is Gaussian. Such universal codebook would be an ideal candidate for the low-precision storage format, a topic of active modern research, but alas the existence proof is non-constructive. Equivalently, our result shows existence of a net in $\mathbb{R}^n$ that is a nearly-optimal covering of a sphere simultaneously with respect to all Hilbert norms.

15.
arXiv (math.PR) 2026-06-18

Denoising Distances in Metric Measure Spaces

arXiv:2606.18301v1 Announce Type: cross Abstract: Recent work studied the problem of finding clusters and denoising pairwise distances from noisy distances of points sampled on a manifold. We study the same problems in more general metric measure spaces under \lowerphiregularity{}. We give an algorithm that extracts large localized clusters around every sampled point and uses them to denoise distances to any fixed accuracy, with near-linear running time in the dense fixed-accuracy regime. We also show how to achieve much higher accuracy with a non-efficient algorithm. This suggests that unlike the Riemannian case, denoising to higher accuracy in more general metric spaces has a statistical-computational gap.

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

UXBench: Measuring the Actionability of LLM-Generated UX Critiques

arXiv:2606.16262v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly deployed as UX judges that inspect interfaces, diagnose usability problems, and propose repairs. Yet no controlled benchmark measures whether the resulting critiques are reliable and actionable across heterogeneous product surfaces. We introduce UXBench, a benchmark for evaluating LLMs as interaction-grounded UX judges. UXBench comprises local-first runnable web fixtures spanning ten product-surface families, paired with coverage-gated browser exploration that forces models to collect interaction evidence before reporting. Each judge model produces a structured UX report over seven rubric dimensions; report quality is measured by whether a fixed downstream repair agent can improve the interface based on the critique. We evaluate eight frontier models under both an automated repair-lift protocol and a blind human validation study. Results show that UX judging is neither saturated nor one dimensional: models differ meaningfully in report actionability, exhibit distinct rubric-level repair signatures, vary in fixture-level reliability, and trade leadership across surface categories

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

RubricsTree: Scalable and Evolving Open-Ended Evaluation of Personal Health Agents across Health Memory and Medical Skills

The LLM-empowered personal health agents with user health (sensor) metrics have offered a promising pathway to alleviate global disparities in healthcare access. However, large-scale clinical deployment remains constrained by an open-ended evaluation bottleneck: physician annotation is reliable but costly and unscalable, while LLM-as-a-judge evaluators are scalable but subjective, inconsistent, and sometimes clinically misaligned. We introduce RubricsTree, a scalable evaluation framework with an expert-aligned hierarchical taxonomy of over 100 atomic, clinically-verifiable Boolean rubrics, evolving from the insights of 4,000 real user queries through an iterative human-in-the-loop curation protocol with an expertise panel led by an experienced physician. A context-aware adaptive router activates only the relevant auto-weighted rubric subset per query, providing the throughput needed for scalable evaluation with expert-aligned quality. Through a systematic meta-evaluation, we show that RubricsTree (i) substantially exceeds a strong large-scale evaluation baseline in expert alignment on challenging open-ended queries; (ii) reliably penalizes contextually degraded responses; and (iii) when used as structured instructions, text feedback, or training rewards for performance optimization, yields up to ~66% relative gains on HealthBench for Gemini, GPT, and Qwen model families. RubricsTree thus provides a scalable, auditable, and evolving evaluation infrastructure required for the continuous optimization of product-level personal healthcare AI.

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

Objects Before Words: Object-First Inductive Biases for Grounding Language in Child-View Video

Learning grounded word meaning from natural experience requires resolving two ambiguities in infant-view recordings: when the named referent appears and where it is in a cluttered frame. In SAYCam-style data, caregiver speech is sparse and weakly synchronized with egocentric video, so single-frame contrastive pairing yields noisy positives in which the intended object is absent or entangled with distractors. We propose BabyMind, an object-first bias for child-view contrastive learning under sparse, noisy supervision. BabyMind extracts candidate object embeddings using an offline mask-based region interface, links candidates across a short utterance-centered window into lightweight object files via tracking, and aligns utterances to bags of object files with a prototype-space multiple-instance contrastive objective. Track-coherence and global-object agreement regularizers stabilize learning and transfer object-file structure into the global frame embedding used at evaluation. On SAYCam-S, BabyMind improves Labeled-S 15 forced-choice accuracy by +2.6 points over CVCL and yields consistent gains on in-vocabulary out-of-distribution benchmarks. Code is available at https://github.com/sathiiii/BabyMind.

19.
arXiv (CS.CL) 2026-06-12

NaturalFlow: Reducing Disruptive Pauses for Natural Speech Flow in Simultaneous Speech-to-Speech Translation

Simultaneous speech-to-speech translation aims to enable near-real-time communication by minimizing latency, offering a compelling, real-time alternative to the high latency of consecutive translation. However, the excessive pursuit of low latency often results in fragmented chunk-wise speech. Consequently, listeners are subjected to an unnatural acoustic flow punctuated by frequent pauses, which could increase their cognitive load. To bridge this gap, we introduce a fluency-aware optimization framework designed to discover the sweet spot between the low-latency benefits of simultaneous translation and the natural flow of consecutive translation. Our framework minimizes inter-chunk silences by leveraging model-internal signals, including linguistic diversity and induced temporal variability in speech durations. Experiments on short- and long-form benchmarks show that our framework produces natural speech flow while maintaining competitive latency and translation quality.

20.
medRxiv (Medicine) 2026-06-18

Evaluating Deep-Learning Based Quantification of Breast Arterial Calcification on Mammography for Cardiovascular Risk Assessment

Purpose: To develop and evaluate a deep learning model for automated quantification of breast arterial calcification (BAC) on screening mammography and to assess whether AI-derived BAC burden predicts major adverse cardiovascular events (MACE) in women. Methods: In this retrospective study, 202,006 women who underwent screening mammography without history of MACE were included. A BAC segmentation model was trained on an expert-annotated dataset using a multi-task U-Net with a ResNet-18 encoder to detect and segment BAC. BAC burden was quantified as area (mm{superscript 2}) from model-generated masks using DICOM pixel spacing and categorized by tertiles into low, intermediate, and high. The PREVENT score and incident MACE were identified from electronic health records. Cox proportional hazards models were developed to evaluate AI-derived BAC burden and PREVENT score alone, and combined models for 5 - and 10-year cardiovascular risk prediction. Results: Among 202,006 women (mean age 54.8{+/-}11.7 years), 23.1% had AI-detected BAC, and 7,701 (3.8%) developed incident MACE during a median follow - up of 7.5 years. On the geographically held-out test set, the BAC model achieved an AUROC of 0.97, Dice score of 0.6678, and Pearson correlation of 0.961 between AI-derived and manually annotated BAC burden. BAC burden increased with age and was higher among women who developed MACE. Five - year MACE incidence increased across BAC categories from 1.5% in women without BAC to 6.9% in those with high BAC burden. BAC burden alone showed modest prediction of MACE, with 5-year and 10-year AUROCs of 0.661 and 0.650, respectively, while PREVENT achieved AUROCs of 0.781 and 0.771. Adding BAC to PREVENT produced minimal improvement in discrimination. Conclusion: Deep learning-based BAC quantification from routine mammography is feasible, accurate, and associated with future cardiovascular risk. Although BAC added little to PREVENT for overall discrimination, it may serve as a scalable opportunistic imaging biomarker to identify women at elevated cardiovascular risk and support preventive care.

21.
arXiv (CS.LG) 2026-06-15

EqCollide: Equivariant and Collision-Aware Deformable Objects Neural Simulator

arXiv:2506.05797v2 Announce Type: replace Abstract: Simulating collisions of deformable objects is a fundamental yet challenging task due to the complexity of modeling solid mechanics and multi-body interactions. Existing data-driven methods often suffer from lack of equivariance to physical symmetries, inadequate handling of collisions, and limited scalability. Here we introduce \name, the first end-to-end equivariant neural fields simulator for deformable objects and their collisions. We propose an equivariant encoder to map object geometry and velocity into latent control points. A subsequent equivariant Graph Neural Network-based Neural Ordinary Differential Equation models the interactions among control points via collision-aware message passing. To reconstruct velocity fields, we query a neural field conditioned on control point features, enabling continuous and resolution-independent motion predictions. Experimental results on 2D and 3D scenarios show that \name achieves accurate, stable, and scalable simulations across diverse object configurations. It achieves $24.34\%$ to $57.62\%$ lower rollout MSE, even compared with the best-performing baseline model. Furthermore, \name could generalize to more colliding objects and extended temporal horizons, and stay robust to input transformed with group action. Code is available at: https://github.com/AI4Science-WestlakeU/EqCollide

22.
arXiv (CS.LG) 2026-06-18

Shrinkage priors for Bayesian Substitute Confounders

arXiv:2606.18535v1 Announce Type: cross Abstract: Multi-cause observational studies contain information about unmeasured confounding through the dependence structure among causes. However, literal imputation of the unobserved confounder is often more complex than learning a lower-dimensional substitute score that preserves the shared assignment variation needed for stable causal adjustment. The deconfounder (Wang and Blei, 2019) and related substitute confounder methods exploit this idea, but flexible assignment models can fit the joint distribution of the causes while producing scores that over-encode the treatment vector, collapse overlap, or capture single-cause variation. We develop a Bayesian factor assignment framework for learning sparse substitute confounders that retain coarse multi-cause dependence with shrinkage priors. The theory is stated at the level of posterior concentration, factor score contraction, and overlap-preserving assignment geometry and therefore does not rely on a particular shrinkage prior. Under these conditions, the proposed regression-adjusted estimators are consistent for mean potential outcomes when the corresponding latent variable identification assumptions hold. Shrinkage priors provide a natural tool for latent structural learning: they favour low-dimensional factors supported by multiple causes, discourage effectively single-cause factors, and induce an ordering of the latent factors through progressive shrinkage. Synthetic experiments illustrate the roles of signal strength, outcome validity, and geometry-aware regularization. In an Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline analysis, sparse substitute scores recover much of the adjustment obtained by directly conditioning on invasive cerebrospinal-fluid biomarkers, while collapse diagnostics identify when fitted factors reduce to individual observed measurements.

23.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.

25.
arXiv (CS.LG) 2026-06-18

Beyond Algorithms: Conceptual Innovation in Medical Imaging AI

arXiv:2606.19270v1 Announce Type: cross Abstract: Artificial intelligence has driven rapid progress in medical imaging research, producing increasingly sophisticated algorithms and steady improvements on benchmark tasks. However, this algorithm-centric trajectory has also revealed a growing imbalance: while computational methods advance rapidly, the conceptual foundations that define imaging tasks, evaluation metrics, and clinical meaning sometimes remain underexamined. In this Perspective, we distinguish algorithmic innovation, which focuses on improving computational implementations and performance within a fixed problem definition, from conceptual innovation, which reframes what problems are posed, how success is measured, and why an approach is clinically relevant. We argue that prevailing incentive structures, training pathways, and publication norms disproportionately reward algorithmic novelty, particularly for early-career researchers, while at times undervaluing conceptual contributions that are essential for scientific maturation and clinical translation. Through representative examples from medical imaging AI, we show how insufficient conceptual grounding can lead to misaligned objectives, fragile generalization, and limited real-world impact. We conclude with actionable recommendations for researchers, mentors, reviewers, and journals to better recognize, support, and integrate conceptual innovation alongside algorithmic advances.