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01.
arXiv (CS.AI) 2026-06-11

TreeSeeker: Tree-Structured Trial, Error, and Return in Deep Search

arXiv:2606.11662v1 Announce Type: new Abstract: Deep search requires agents to answer complex questions through multi-step web search, browsing, evidence comparison, and synthesis. A central challenge is deciding how to search when several directions look plausible but only some will later lead to reliable evidence. If an agent greedily follows the current best-looking direction, it may keep extending a weak continuation. If it explores without discipline, it may waste budget on disconnected trials. We propose TreeSeeker, an inference-time framework for controlled trial-and-error in deep search. TreeSeeker organizes search as branch-and-return search over tree-structured states, where each branch is a tentative direction for a sub-goal. At each round, TreeSearch reads all sub-goal trees, identifies active goals, and uses textual UCB signals of value, uncertainty, and risk to select among exploiting a promising branch, exploring an uncertain alternative, or pruning an unproductive continuation and returning to an earlier branch point. TreeMem supports this control loop by keeping evidence, uncertainty, conflicts, progress, and failure cues attached to the branches that produced them, so trial outcomes can guide later decisions. Experiments on XBench-DeepSearch, BrowseComp, and BrowseComp-ZH show that TreeSeeker consistently outperforms strong open-source baselines, suggesting that explicit branch-and-return control complements stronger reasoning and tool execution.

02.
arXiv (math.PR) 2026-06-18

Multi-floor generalization of TASEP

arXiv:2603.13610v2 Announce Type: replace Abstract: We consider an interacting particle system, which generalizes the classical totally asymmetric simple exclusion process (TASEP), in that each site can contain up to a fixed finite number of particles, and the particle movement is governed by a back-pressure (BP) algorithm (also often called MaxWeight). There are $N$ sites (with $N$ finite or infinite), each may contain at most $c$ particles, $1 \le c < \infty$. New particles enter the system at the left-most site $1$ as a Poisson process of rate $\alpha\le 1$, unless site $1$ has $c$ particles. Particles (if any) are removed from the right-most site $N$ as a Poisson process of rate $\beta \le 1$. The left-to-right movement of particles between neighboring sites is governed by the BP rule: one particle moves from site $n$ to $n+1$ at epochs of a rate $1$ Poisson process, as long as the former site has strictly more particles than the latter. When $c=1$, this is the standard TASEP. Our main results address the asymptotics of the stationary distribution of a finite system, and especially the limit of the flux (current) as $N\to\infty$. In particular, we prove that interesting non-trivial phase transitions take place in a system with $c>1$. For example, if $c>1$ and $1/2 \le \beta \le 1$, the maximum limiting flux $1/4$ is achieved as long as $\alpha \ge \alpha_c^*$, where $\alpha_c^* < 1/2$ is some non-trivial threshold. (For the standard TASEP the threshold is $1/2$.) We also put forward a general conjecture about the stationary distribution asymptotics under an arbitrary parameter setting. We illustrate our formal results and the conjecture by simulations, and identify interesting directions for further research.

03.
arXiv (CS.CV) 2026-06-16

Instance-Aware Knowledge Distillation for Semi-Supervised Learning of an On-Board Multi-Task Dense Prediction Model for Collision Avoidance System

Collision avoidance systems have evolved toward camera-based deep learning approaches for driving scene understanding. However, deployment in edge environments such as country clubs is constrained by limited computational resources and unreliable communication infrastructure. Moreover, constructing large-scale datasets for the target domain involves substantial annotation cost. To address these limitations, we propose an instance-aware knowledge distillation framework for semi-supervised learning. Specifically, we generate pseudo labels that mitigate teacher bias by leveraging domain priors from the teacher and instance-centric knowledge from foundation models. The trained lightweight student is deployed in the proposed collision avoidance system and performs multiple dense prediction tasks in real-time. The system detects frontal obstacles and encodes their spatial information into controller area network messages for automated guided vehicle operation. To achieve this, we construct a large-scale country club dataset and perform field validation of the proposed system. Experimental results demonstrate that the student outperforms the large teacher in instance segmentation while mitigating performance degradation in monocular depth estimation. Compared with the teacher, the student reduces FLOPs by 22.68$\times$ and parameters by 14.33$\times$, achieving 6.46 FPS on a low-cost edge device.

04.
medRxiv (Medicine) 2026-06-12

Integrative Mechanisms of Early Clinical and Research Training (ECART) in Orthopaedic Medical Education: A Qualitative Single-Case Study

Background: Early clinical exposure and student participation in research are important components of medical training. They may support learning motivation, evidence literacy, and self-directed learning. In many programmes, however, clinical training and research training remain separated. Few studies have explained, within a real teaching team, how learners turn clinical phenomena into researchable questions and how research participation can reshape their clinical understanding. Early Clinical and Research Training (ECART) is a clinical-research integration approach developed by an orthopaedic team at the Second Hospital of Shandong University. Methods: We conducted a theory-informed, interpretivist qualitative single-case study. The case was an orthopaedic clinical-research team at the Second Hospital of Shandong University. Participants included medical undergraduates, academic degree graduate students, professional degree graduate students, clinical teachers, and research platform leads. We used purposive sampling with maximum variation. Data were collected through semi-structured interviews and de-identified teaching documents. Data were analysed using the framework method and were interpreted with a Context-Activity-Mechanism-Outcome (CAMO) logic. Results: The analysis showed that ECART was not simply early entry into the clinic or early entry into the laboratory. It was a team-based learning process centred on real medical problems. Four themes were identified. First, early clinical exposure helped learners make real problems visible and nameable, rather than merely increasing exposure. Second, clinical-research connection followed different pathways. Professional degree graduate students often started from clinical uncertainties in residency training and case management, and moved toward evidence-informed small projects. Academic degree graduate students often started from literature gaps, experimental findings, and mechanistic hypotheses, and then used clinical feedback to calibrate meaning. Third, research training, through literature reading, group meetings, experimental design, data review, and mentor questioning, helped learners move from completing tasks to explaining problems. Fourth, sustained ECART depended on a tiered team ecology formed by clinical teachers, research mentors, research platforms, and senior peers. Based on these findings, we refined the ECART programme theory: real medical problems are translated through explanation, searching, experimentalisation, and feedback-based reinterpretation into research questions that learners can understand, discuss, and test. This process supports problem formation, evidence awareness, mechanistic reasoning, translational judgement, and career clarification. Conclusion: ECART is best understood as a clinical-research integrated learning ecology that emerges from real team practice, rather than as a fixed standardised course. Its educational value lies in a recurring cycle of real problems, research translation, multi-source feedback, and clinical reinterpretation. This framework may inform the design, evaluation, and contextual adaptation of clinical-research integration pathways in medical education.

05.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

06.
bioRxiv (Bioinfo) 2026-06-15

Multiple Fault Analysis and Drug Therapy on Signaling Pathways Using Dynamic Bayesian Network-based Model

Cell growth is an intricate biological phenomenon that is closely regulated by the interplay between various growth factors and transcription factors. Signaling pathways are the main mediators in this event, which provide the driving force for mitosis or sometimes meiosis. However, when malfunctions occur within the biological network, they can cause uncontrolled cell division, regardless of external stimuli. By employing Dynamic Bayesian Networks (DBNs), these malfunctions can be explicitly simulated, offering insights into their effects on cellular behavior and growth regulation. To a significant extent, the resultant outcomes can be mitigated through the use of reduced drug combinations. This study delves into the intricacies of signaling pathway behavior under the influence of concurrent malfunctions. Initially, we replicate the effects of these dysfunctions within DBNs. Subsequently, drug therapy is applied to alleviate their impact. Our methodology introduces a parameter known as efficiency_score, enabling the identification of optimized drug combinations without prior knowledge of specific dysfunctions. Particularly relevant in the context of realistic cancer conditions, these tailored drug inhibition points demonstrate enhanced efficacy compared to conventional treatments. Leveraging GPU acceleration throughout the modeling process accelerates the analysis of multiple faults within the biological networks, rendering our approach notably faster and more efficient.

07.
arXiv (CS.AI) 2026-06-12

Constructing Evaluation Datasets for Procedural Reasoning: Balancing Naturalness, Grounding, and Multi-Hop Coverage

arXiv:2606.12767v1 Announce Type: new Abstract: Evaluating procedural reasoning in AI-supported learning systems requires question-answer datasets that are both learner-like and grounded in the instructional knowledge the system is expected to use. We study how TMK-based question generation strategies affect dataset quality for procedural and multi-hop reasoning. We compare three strategies: strict generation from Task-Method-Knowledge (TMK) models, transcript-first generation with post-hoc TMK filtering, and TMK-aware generation that combines transcripts with structured guidance. To evaluate generated items, we introduce a grounding validation framework based on closed-set evidence units extracted from TMK models. The framework measures whether answers are supported by the underlying representation, whether questions are self-contained, and whether they target multi-hop procedural reasoning. Across 23 instructional topics and 690 generated question-answer pairs, strict TMK generation achieves the strongest overall quality, with 96.5% grounded questions and 92.6% usable questions. Transcript-first generation produces more learner-like questions but more context-dependent or weakly grounded items, while TMK-aware generation yields high raw multi-hop coverage but lower grounding. These results show that procedural richness and natural phrasing do not guarantee representational grounding, motivating explicit representation-aware validation for evaluation datasets in AI-supported learning.

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

Sensor-Conditioned Representation Learning via Scene-Relevant Observation Quotients

arXiv:2606.16210v1 Announce Type: new Abstract: Learned representations in intelligent sensing systems are often evaluated by reconstruction fidelity or downstream prediction accuracy, but these criteria do not specify which latent distinctions are justified by the sensing process. In sensor-conditioned environments, nuisance factors can change measurements without changing the scene, while distinct scenes may be indistinguishable under limited sensing capability. This paper formulates sensor-conditioned representation correctness as preserving sensing-supported scene distinctions while suppressing nuisance-induced and sensor-unsupported variation. We introduce the scene-relevant observation quotient, a representation target induced by sensing-supported distinguishability after nuisance canonicalization, and develop Observation-Quotient Tucker-Structured Autoencoding (OQ-TSAE), a scene-nuisance factorized framework with diagnostics for false distinction, false merge, nuisance sensitivity, and latent ordering consistency. Experiments on a controlled benchmark show that quotient-consistent supervision improves representation-correctness diagnostics over reconstruction-oriented, metric-learning, and contrastive-learning baselines. Sensitivity, perturbation, and ablation studies show the importance of quotient-aligned supervision, reliable quotient relations, and quotient geometry. Complementary real-radar experiments show that a reconstruction-only OQ-TSAE variant retains competitive downstream utility, robustness under observation degradation, and low seed-to-seed variability. These results suggest that sensor-conditioned representations should be evaluated not only by predictive utility, but also by whether their latent geometry preserves sensing-justified scene distinctions.

09.
arXiv (CS.AI) 2026-06-19

JustDiag!: A Diagnostic Justification Engine for Accountable Root Cause Analysis

arXiv:2606.19407v1 Announce Type: cross Abstract: Large language models can produce fluent root cause analyses, but fluent final answers alone are insufficient evidence for accountability in high-stakes operations. In real incident response, engineers need to know what evidence supported a diagnosis, which alternatives were considered, where contradictions remained, and whether the system resolved the case or preserved uncertainty. We address this gap with JustDiag, a diagnostic justification engine for RCA that maintains an explicit process state over evidence, findings, competing hypotheses, conflicts, and next checks. We evaluated the system on 66 real-world incidents using a two-layer protocol that separately scores final-answer quality and process quality. Relative to a matched control without diagnostic justification, JustDiag achieved stronger outcome and process scores, while accepting slightly lower terminal completion due to more calibrated non-closure. These results suggest that accountable RCA requires explicit diagnostic justification artifacts and process-aware evaluation, not only fluent final answers.

10.
bioRxiv (Bioinfo) 2026-06-11

Amylo-Pipe: an integrated web server for mechanistic and kinetic prediction of protein and peptide aggregation

Protein aggregation is central to amyloid-related disorders and remains a major developability challenge for protein therapeutics. Over the past two decades, significant advances have been made to predict aggregation-prone regions (APRs) and estimate aggregation propensity in proteins and peptides. In contrast, the prediction of aggregation kinetics has received relatively less attention due to the limited availability and heterogeneity of experimental data. Consequently, aggregation propensities from APR prediction algorithms were widely accepted as a means to predict relative changes in the aggregation kinetics of proteins and mutants. Previous studies have demonstrated, using large-scale datasets, that aggregation propensity shows a weak or inconsistent correlation with aggregation kinetics. In the present study, we have integrated complementary state-of-the-art mechanistic and kinetic prediction tools for protein aggregation into a unified, user-friendly web framework entitled "Amylo-Pipe". Amylo-Pipe also implements practical features that are especially useful for protein engineering, such as gatekeeper-residue mutational scanning to support the design of aggregation-resistant variants. By consolidating multiple prediction tasks in a single interface, Amylo-Pipe enables a more comprehensive assessment of aggregation behavior than APR-only workflows. The web server is freely accessible at: https://web.iitm.ac.in/bioinfo2/amylopipe/.

11.
PLOS Computational Biology 2026-06-11

Robust discovery of mutational signatures using power posteriors

by Catherine Xue, Jeffrey W. Miller, Scott L. Carter, Jonathan H. Huggins Mutational processes, such as the molecular effects of carcinogenic agents or defective DNA repair mechanisms, produce different mutation types with characteristic frequency profiles, known as mutational signatures. Non-negative matrix factorization (NMF) has been successfully used to discover many mutational signatures, yielding novel insights into cancer etiology and informing targeted therapies. However, the NMF model is only a rough approximation to reality, and even small departures from this assumed model can have large negative effects on the accuracy and reliability of the results. We propose BayesPowerNMF, a Bayesian NMF method that provides nonparametric robustness to model misspecification, principled automated selection of the number of latent processes, and uncertainty quantification of model parameters. In extensive simulation studies, we find that our proposed approach recovers more true signatures with greater accuracy than current leading methods. On whole-genome sequencing data for six cancer types from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, we find that our method is able to accurately recover more signatures than the current state-of-the-art.

12.
arXiv (quant-ph) 2026-06-17

Impulse Decoding of Quantum LDPC Codes: Equivalence of Degeneracy and Code-Shortening

arXiv:2606.18240v1 Announce Type: new Abstract: Quantum error correction is essential for building scalable quantum computers. Within the stabilizer formalism, the Calderbank-Shor-Steane framework constructs quantum codes from pairs of classical linear codes. A distinctive feature in this setting is degeneracy, where multiple equivalent error estimates exist-a phenomenon that has no classical counterpart, and the lack of a meaningful classical coding-theoretic interpretation of which has remained a gap in the literature. In this paper, we demonstrate that degeneracy is closely related to the classical operation of shortening of a linear block code. Interestingly, the shortening here takes place at the decoder rather than at the encoder. Leveraging this insight, we present a parallel decoding scheme for quantum low-density parity-check codes, which we term impulse decoding, that significantly outperforms belief propagation with ordered statistics decoding, as well as several other existing techniques, under both code-capacity and circuit-level noise, with significantly lesser complexity. We then present another algorithm based on decoding of residual errors, which when combined with impulse decoding achieves further performance improvement under circuit-level noise.

13.
bioRxiv (Bioinfo) 2026-06-18

MorphoStat: A Statistics-Aware Pipeline for Morphological Profiling Analysis

作者:

High-content imaging produces thousands of morphological measurements per cell. Interpreting these measurements requires normalization to remove plate effects, statistical tests selected on the basis of data distribution, and control over false discoveries across many features tested at once. MorphoStat is an open-source Python pipeline that applies this sequence of steps automatically. Given a CSV file from CellProfiler or a compatible imaging platform, it removes low-quality wells, normalizes each plate against DMSO controls using a MAD-scaled z-score, routes each feature to a parametric or nonparametric test based on a distributional check, applies Benjamini Hochberg correction, and writes out results and publication-ready figures. On the BBBC021 benchmark (MCF-7 breast-cancer cells, 632 wells, 473 features), MorphoStat recovered 12 of 13 known mechanism-of-action classes in principal component space, confirming that the normalization and statistical routing work as intended. The tool is available at https://github.com/Almunthir334/morphostat (DOI: 10.5281/zenodo.20354069) under the MIT license.

14.
arXiv (CS.AI) 2026-06-16

AIRMap: AI-Generated Radio Maps for Wireless Digital Twins

arXiv:2511.05522v4 Announce Type: replace-cross Abstract: Accurate, low-latency channel modeling is essential for real-time wireless network simulation and digital-twin applications. Traditional modeling methods like ray tracing are however computationally demanding and unsuited to model dynamic conditions. In this paper, we propose AIRMap, a deep-learning framework for ultra-fast radio-map estimation, along with an automated pipeline for creating the largest radio-map dataset to date. AIRMap uses a single-input U-Net autoencoder that processes only a 2D elevation map of terrain and building heights. Trained on 1.2M Boston-area samples and validated across four distinct urban and rural environments with varying terrain and building density, AIRMap predicts path gain with under 4 dB RMSE in 4 ms per inference on an NVIDIA L40S-over 100x faster than GPU-accelerated ray tracing based radio maps. A lightweight calibration using just 20% of field measurements reduces the median error to approximately 5%, significantly outperforming traditional simulators, which exceed 50% error. Integration into the Colosseum emulator and the Sionna SYS platform demonstrate near-zero error in spectral efficiency and block-error rate compared to measurement-based channels. These findings validate AIRMap's potential for scalable, accurate, and real-time radio map estimation in wireless digital twins.

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

Cost-Optimal LLM Routing with Limited User Feedback under User Satisfaction Guarantees

arXiv:2606.19376v1 Announce Type: cross Abstract: Inference costs for large language model (LLM) applications are rapidly growing, driven by surging demand and rising infrastructure cost. Users expect high-quality responses, and in commercial settings this is formally codified in Service Level Agreements (SLAs), creating a fundamental tension between cost and quality. Recent progress on cost-aware LLM request routing has shown potential to resolve this tension, but existing approaches rely on complete feedback signals, offline training, extensive per-workload tuning, and most lack SLA guarantees or inference-time adaptivity. We introduce SLARouter, an online routing algorithm that learns a cost-optimal policy from the sparse, one-sided user feedback available in production systems. SLARouter provides theoretical guarantees for both cost optimality and strict SLA compliance. Experiments across a wide range of LLM benchmarks show that SLARouter satisfies SLA constraints without the need for per-benchmark tuning, reducing operating cost by up to 2.2x over existing baselines.

16.
arXiv (quant-ph) 2026-06-15

Emission of time-ordered photon pairs from a coherently-driven Kerr microcavity

arXiv:2601.06468v2 Announce Type: replace-cross Abstract: Weakly-interacting many-body systems possess remarkable quantum properties that are essential components of quantum technologies, and constitute a topic of fundamental interest. Here we show that in a solid-state nonlinear microcavity embedding discrete modes of exciton-dressed photons, we can isolate a single eigenmode of quantum fluctuations from the much brighter coherent fraction of the field. In this regime, we perform frequency- and time-resolved correlations measurements between photons on the red and blue side of the fluctuations spectrum. When the average number of fluctuation quanta is smaller than one, we observe the formation of large pairwise time-ordered correlations: red photon first and blue photon second. We show that this peculiar time-ordering correlation emerges spontaneously from the interplay between frequency-resolved detection, and the non-trivial internal quantum structure of the elementary fluctuations.

17.
bioRxiv (Bioinfo) 2026-06-15

Inferring Cell Fate Trajectories in Time-Resolved Metabolic RNA Labeling data

Single-cell RNA sequencing provides high-resolution snapshots of cellular states but lacks direct information about transcriptional dynamics. Metabolic RNA labeling addresses this limitation by distinguishing newly synthesized RNA, offering insight into the direction of cell state changes, and providing valuable information when attempting to recover the underlying continuous dynamics from static snapshots of cell distributions. However, existing trajectory inference methods do not fully exploit this additional signal. Here, we propose FLOWSATATE, a framework for single-cell trajectory inference that leverages time-resolved RNA labeling within an Optimal Transport setting. We model cell dynamics as a gradient flow in an inferred potential landscape parameterized by a neural network, integrating both total and labeled RNA across time points. The learned potential enables identification of key genes and transcription factors driving cell fate decisions and supports prediction of future cellular states. We benchmark our approach on its ability to generalize unseen data and recover coherent trajectories. We also apply it to study colorectal cancer response to demethylation treatment as well as neuronal differentiation of embryonic stem cells.

18.
Science (Express) 2026-05-07

Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design | Science

作者: 未知作者

A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.

19.
arXiv (CS.CV) 2026-06-16

A Survey on 3D Gaussian Splatting Applications: Segmentation, Editing, and Generation

In the context of novel view synthesis, 3D Gaussian Splatting (3DGS) has recently emerged as an efficient and competitive counterpart to Neural Radiance Field (NeRF), enabling high-fidelity photorealistic rendering in real time. Beyond novel view synthesis, the explicit and compact nature of 3DGS enables a wide range of downstream applications that require geometric and semantic understanding. This survey provides a comprehensive overview of recent progress in 3DGS applications. It first reviews the reconstruction preliminaries of 3DGS, followed by the problem formulation, 2D foundation models, and related NeRF-based research areas that inform downstream 3DGS applications. We then categorize 3DGS applications into three foundational tasks: segmentation, editing, and generation, alongside additional functional applications built upon or tightly coupled with these foundational capabilities. For each, we summarize representative methods, supervision strategies, and learning paradigms, highlighting shared design principles and emerging trends. Commonly used datasets and evaluation protocols are also summarized, along with comparative analyses of recent methods across public benchmarks. To support ongoing research and development, a continually updated repository of papers, code, and resources is maintained at https://github.com/heshuting555/Awesome-3DGS-Applications.

20.
medRxiv (Medicine) 2026-06-11

Computer Vision Scoring of Figure Copy and Recall

Objective. Figure copy and recall tests are sensitive measures of visuoconstruction and visual episodic memory, but their clinical is constrained by labor-intensive manual scoring. We developed and validated an automated, element-level scoring pipeline using Vertex AI object detection for the tablet-based figure copy and recall tasks in the California Cognitive Assessment Battery (CCAB). The automated scoring pipeline duplicated the scoring procedures used by expert manual raters. Methods. A normative sample of 2,011 community-dwelling adults aged 18-90 completed figure copy and delayed recall trials at baseline, with subsamples retested at 1 day and at 6, 18, and 30 months. Participants completed the drawings with their index finger on a tablet computer with finger position digitized to analyze the speed and timing of individual drawing strokes A convolutional object-detection model trained on the Vertex AI AutoML Vision platform identified each of twelve canonical figure elements in rendered drawings. Separate element presence and location scores were computed after homographically warping drawings onto a canonical template to produce trial-level Element, Location, and Total scores. To compare Vertex and human scores, Vertex AI and expert human raters independently scored 1500 randomly selected drawings to evaluate inter-rater agreement, including a common subset of 100 drawings scored by Vertex AI and all raters. Results. Total scores were virtually indistinguishable (r = 0.966) from human-human agreement (mean r = 0.971) as were Element presence scores (mean r = 0.959 vs. r = 0.963). Location-score agreement (r = 0.951) was slightly below the human-human mean (r = 0.972) due to pixel-level analysis by Vertex AI that was impossible for human raters. The Vertex pipeline showed no preferential advantage for the single expert rater who categorized Elements during training. Automated scores showed strong demographic gradients, age effects on Recall (r = -0.32) were approximately twice those in Copy conditions (r = -0.16). A Memory Cost score (Recall - Copy) showed a monotonic age-related decline from +0.40 z in the youngest subjects to -0.54 z in the oldest. Kinetic analysis revealed that drawing speed and efficiency showed significant age-related changes. Overnight test-retest reliability was high (Recall r = 0.72) and the Recall trial showed a large overnight learning effect ({Delta} = +1.18) that continued with repeated tests up to 30 months ({Delta} = +0.75).

21.
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.

22.
bioRxiv (Bioinfo) 2026-06-20

MIRATS framework: Normative multiscale characterization of brain regulatory systems across sex and age using multimodal MRI

作者:

Deep brain systems involved in arousal, autonomic regulation, sensory integration, and homeostatic control remain underrepresented in conventional whole-brain neuroimaging frameworks. In particular, diencephalic and brainstem nuclei are often insufficiently represented in cortex-centered analyses, limiting the normative references needed to interpret systems-level variation in health and disease. To address this gap, we developed a unified multiscale framework with explicit representation of deep nuclei. By integrating cerebral, cerebellar, diencephalic, and brainstem atlases in standard space, we constructed a 220-region whole-brain parcellation and extracted complementary features at three analytical scales: nodal properties, edge-wise connectivity, and persistent-homology-based topological descriptors. We applied this framework to healthy adults from the Human Connectome Project-Aging cohort to characterize normative multiscale organization and test sex- and age-related variation. Applied to this cohort, our framework revealed pronounced heterogeneity across anatomical systems. Brainstem and diencephalic nuclei showed multiscale feature profiles distinct from those of cerebral and cerebellar regions across nodal, edge-wise, and higher-order topological scales. Sex comparisons identified selective differences across different scales, whereas age modeling revealed widespread but feature- and system-dependent variation across adulthood. Together, these findings show that normative whole-brain organization in this deep-system-aware space is structured by system-specific rather than globally uniform patterns. These findings establish a normative multiscale framework for characterizing brainstem-diencephalic-cerebellar-cerebral organization in healthy adults and provide a quantitative reference for future translational studies of disease-related abnormalities in deep regulatory systems.

23.
bioRxiv (Bioinfo) 2026-06-10

Bias-mitigated microbiome inference refines coronary artery disease signature

作者:

Roughly half the cells in the human body are microbial, and changes in these communities are increasingly implicated in cardiovascular, metabolic, and oncological diseases. Yet identifying which taxa truly differ in abundance, differential abundance (DA), is distorted by four major sources of bias: loss of total microbial load, taxa measurement efficiencies, arbitrary pseudocounts required to handle pervasive zeros, and contamination which has recently driven retractions. No existing DA method accounts for all four. Here we introduce BootDA, a non-parametric bootstrap-based method that explicitly models each bias source without data transformations, pseudocounts, parametric assumptions, or assuming that most taxa are non-DA. In semi-parametric simulations preserving the sparsity (>70% zeros) and correlation structure of real 16S amplicon data, BootDA achieved the highest sensitivity among tested methods, including ANCOM-BC2, LinDA, MaAsLin 3, and Wilcoxon tests, while controlling the false discovery rate. Performance was retained in low biomass settings when contamination contributed ~50% of counts, and without negative controls, indicating de novo decontamination capability. Applied to a coronary artery disease cohort, BootDA refined the original signature to two co-enriched genera, Klebsiella and Gemmiger, and excluded likely contaminants. BootDA is available as an R package and could generalise to other sparse, high dimensional biological data.

24.
arXiv (CS.AI) 2026-06-17

Combating Data Laundering in LLM Training

arXiv:2604.01904v3 Announce Type: replace-cross Abstract: Post-hoc unauthorized-training data detection for large language models (LLMs) typically assumes a query-with-originals regime: rights holders query a target LLM with raw proprietary data and assess whether the model assigns them stronger memorization-based detection signals, e.g., higher confidence or lower loss, than held-out non-training reference texts. We show that this regime becomes brittle under data laundering, where the target LLM is trained on semantics-preserving but stylistically or structurally transformed surrogates of proprietary data to obfuscate provenance. Since training-time exposure occurs in the laundered form, memorization signals may no longer appear on the originals, collapsing the candidate-reference signal separation that standard detectors rely on. We counter this threat by studying laundering-aware detection with raw proprietary data, a held-out reference corpus, and query access to the target LLM, while the laundering transformation is undisclosed. Since exact recovery of the laundered corpus is infeasible, we infer a detection-useful synthesis process via an auxiliary LLM that maps originals into training-like queries. To make this search tractable, we introduce Synthesis Data Reversion (SDR), which constrains the unbounded space of natural-language transformations through a goal-details abstraction: a high-level transformation goal, e.g., "lyrical rewriting", and fine-grained details, e.g., "with vivid imagery". SDR identifies the most likely goal and iteratively refines details so synthesized queries elicit stronger target-model detection signals. Evaluated on the MIMIR benchmark against diverse laundering practices and target LLM families (Pythia, Llama2, and Falcon), SDR consistently restores detection signals, offering a practical auditing layer against data laundering.

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arXiv (CS.CV) 2026-06-16

GridVQA-X: A Framework for Evaluating Multimodal Explainability Methods

With the increasing development of Vision-Language Models, it becomes imperative that their predictions are readily explainable to relevant stakeholders. However, the field of explainability has not kept pace with the multimodal surge. While recent Multimodal Explainable AI (MxAI) methods generate explanations to attribute the interaction between different modalities, current evaluation protocols lack the ground truth required to distinguish between true cross-modal reasoning (e.g., spatial composition) and shallow cross-modal shortcuts (e.g., Bag-of-Words attribute matching). It remains unknown whether MxAI methods faithfully capture synergistic interactions or merely hallucinate reasoning on models acting as simple feature detectors. In this paper, we introduce GridVQA-X, the first diagnostic framework specifically designed to evaluate cross-modal explainability. Unlike natural datasets, GridVQA-X leverages a closed-world synthesis logic to generate unique, mathematically guaranteed explanations. We utilize this controlled environment to train paired ground-truth models on identical architectures: $M_{pure}$, which learns robust spatial-relational reasoning and $M_{spur}$, which is structurally forced to rely on cross-modal shortcuts. This behavioral divergence creates a rigorous testbed: a faithful explainer must report distinct reasoning pathways for each model. Our findings reveal that widely used methods fail to distinguish between models relying on genuine spatial-relational reasoning and those exploiting cross-modal shortcuts, highlighting a critical gap in capturing true cross-modal synergy and misrepresenting how multimodal models actually make decisions.