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01.
bioRxiv (Bioinfo) 2026-06-14

Cellfm-datasets: A Unified Data Infrastructure for Single-Cell and Spatial Transcriptomics Foundation Model Pretraining

Large-scale cell foundation models are increasingly limited not only by model architecture, but also by the data infrastructure required to repeatedly sample sparse transcriptomic profiles from out-of-core cohorts. AnnData/H5AD has become a standard exchange format for single-cell and spatial omics analysis, yet its HDF5-backed layout is not designed for high-frequency random mini-batch loading under multi-worker and distributed pretraining. We present Cellfm-datasets, a data infrastructure artifact that converts H5AD cohorts into a self-describing compressed sparse row (CSR) memmap layout and exposes the resulting corpus through Hugging Face Dataset and IterableDataset interfaces. The artifact stores a shared gene vocabulary, per-sample metadata, optional spatial coordinates, observation metadata, manifests, and checksums, and reconstructs sparse cell or group records at runtime without dense expansion. A unified sampling abstraction supports random-cell groups, manifest-defined biological regions, and coordinate-based spatial blocks, with deterministic sharding across distributed ranks and data-loader workers. Spatial demonstrations on P14 mouse brain transcriptomics sections illustrate region- and block-level sampling over real anatomical structures. In controlled benchmarks on a public heterogeneous ModelScope scRNA-seq subset, Cellfm-datasets reached 60,571 +/- 1,734 samples/s in single-core random loading, scaled to approximately 160,000 samples/s with eight workers, and maintained near-constant process-private memory while reading up to one million cells. By moving sparse single-cell and spatial corpora from model-specific loader code into reusable, validated, and framework-native dataset artifacts, this design may reduce the engineering burden of reproducible cell foundation model pretraining and make repeated training runs, model comparisons, and mixed-modality data reuse easier to standardize.

02.
arXiv (CS.AI) 2026-06-12

Algorithmic Constitutionalism

arXiv:2606.12437v1 Announce Type: cross Abstract: The increasing encroachment of artificial intelligence (AI) on social life raises significant risks for society, particularly within the infospheres created and controlled by companies such as Google, Facebook, Apple, and Amazon. This article examines these risks through an in-depth analysis of Facebook's content moderation regime, which is already partially governed by algorithms. We argue that the idea of ethical engineering, often proposed in the literature as a solution to the governance challenges posed by AI, is inadequate for several reasons. In response, we develop an alternative framework, which we term "algorithmic constitutionalism." Our approach rests on three pillars: (a) a layered architecture consisting of two levels of code: (i) an operative or object level and (ii) a meta level designed to protect the system's core principles from algorithmically initiated change; (b) algorithmic meta-reasoning, which enables the system to operate simultaneously at both levels so that it can monitor, verify, and potentially correct in real time operations at the object level that depart from principles protected at the meta-code level; and (c) correction through deliberation. The article elaborates the concept of algorithmic constitutionalism and demonstrates how it may be applied to Facebook's content moderation regime. As part of this analysis, we examine the tension between societal constitutionalism and algorithmic constitutionalism. Paradoxically, attempts to subject AI systems to external deliberative control may also enable AI agents to intervene in that process, potentially undermining its purpose. The article concludes by considering the implications of this argument for the European Digital Services Act, which entered into force in October 2022.

03.
arXiv (quant-ph) 2026-06-12

Unifying spacetime approaches to quantum mechanics

arXiv:2606.12539v1 Announce Type: new Abstract: Recent efforts to formulate quantum mechanics in a way that treats space and time on a more equal footing have led to a large variety of spacetime-oriented approaches. In this work we present a detailed study of spacetime states, the objects that play the role of quantum states in the recently introduced framework of spacetime quantum mechanics, and show that the main proposals in the literature are different manifestations of the same underlying object. Path integrals, quantum states over time, pseudo-density matrices, the Page and Wootters mechanism, superdensity operators, and timelike-entanglement proposals all arise from spacetime states through particular evaluations, reduced information, linear maps, or quantum channels. This unification provides explicit mathematical representations of these formalisms, reveals relations among them, and clarifies the spacetime information each one captures. We also study the broader relevance of the spacetime-state point of view for Leggett-Garg inequalities, OTOCs, temporal tensor networks, fermionic systems, relativistic QFTs, quantum reference frames, and classical physics, together with additional insights and perspectives revealed by the common unifying framework.

04.
arXiv (quant-ph) 2026-06-15

Dose-efficient Quantum Phase Estimation in Lossy Optical Interferometry

arXiv:2606.14254v1 Announce Type: new Abstract: Optical interferometry is a cornerstone technique for precise phase measurements across various fields. In many applications, for example, biological imaging, it often necessitates stringent limits on light intensity to prevent adverse effects on light-sensitive samples, a condition known as dose-limited regimes. Maximizing the precision per dose is therefore crucial. In quantum metrology, quantum correlations enable high precision in phase estimation while adhering to dose constraints. Nevertheless, photon loss, including absorption by a sample, substantially diminishes the benefits of quantum enhancement in interferometry. In this work, we experimentally investigate a dose-efficient approach to quantum phase estimation using sequential strategies in the presence of loss. Performance of sequential strategies with and without control is evaluated through quantum Fisher information (QFI) per dose. Experimental results show that both sequential strategies exceed the classical limit and outperform the parallel strategy using unbalanced N00N states. Notably, the control-enhanced sequential strategy attains superior QFI per dose, approaching the quantum limit. These results highlight the promise of sequential strategy for imaging and sensing in resource-constrained scenarios, marking a significant step toward practical and efficient quantum metrology in lossy environments.

05.
arXiv (CS.CL) 2026-06-11

Lius: Translation Model Based Instructional Lingustic Using Continual Instruction Tuning In Kupang Malay

Large Language Models (LLMs) offer new potential for translation tasks but often experience performance degradation when handling low-resource languages. To address this limitation, we propose an approach for fine-tuning LLMs on a low-resource language, Kupang Malay. Our approach involves designing a set of instructions by leveraging explicit lexical and semantic features from a bilingual dictionary, and introducing Continual Instruction Tuning (CIT), a training paradigm that enables iterative instruction-based training. Experimental results demonstrate that our model, named Lius, yields notable improvements over standard instruction-tuned models by outperforming 4-6 points, and surpassing both Neural Machine Translation (NMT) and Multilingual LLM models by 10-13 points on several evaluation metrics. These findings highlight the potential of our approach to mitigate the reliance on large-scale parallel data in low-resource language translation.

06.
medRxiv (Medicine) 2026-06-18

Consistency of sleep timing and duration are associated with more physical activity and favorable heart rate metrics in a naturalistic cohort

Background: Regularity of sleep patterns over time has increasingly gained traction as an important axis of sleep health. Since sleep habits are under some degree of behavioral control, understanding such patterns in naturalistic settings is particularly important. We quantified sleep variability and tested the hypothesis that regularity correlates with physical activity, resting heart rate (rHR), and heart rate variability (HRV). Methods: We analyzed real-world digital health data from over 81,000 participants (over 18 million nights) who provided informed consent to participate in the Apple Heart and Movement Study and elected to contribute sleep, activity, and heart rate data to the study. Variability was quantified using the standard deviation (SD) computed from total sleep time (TST), sleep start time (S-start), end time (S-end), and midpoint time (MP), as well as the Sleep Regularity Index (SRI). Results: The SD-based variability metrics correlated with one another (R values 0.74-0.92), and with the SRI metric (R values 0.62-0.64). More consistent sleep, by any metric, was associated with more activity and better rHR and HRV. The most consistent tertile for TST variability had higher median TST (6.9 vs 5.9 hours), more daily exercise (32.8 vs 20.4 minutes), lower rHR (62.4 vs 65.6 beats per minute), and higher HRV (40.6 vs 37.3), all p

07.
arXiv (CS.CL) 2026-06-24

Reinforcement Learning Towards Broadly and Persistently Beneficial Models

As AI systems are deployed across increasingly diverse and high-stakes settings, model alignment must generalize beyond the tasks and domains seen during training. This is especially important for reinforcement learning (RL), which can introduce unexpected misalignment through reward hacking, deception, or other unintended strategies. We study whether RL on beneficial behavior, instantiated in realistic domains, can produce broad and persistent alignment generalization beyond the training distribution. We construct a dataset of realistic situations designed to measure and train beneficial traits, such as truthfulness, fairness, risk awareness, and corrigibility, spanning varied domains, including health, science, and education. We then train models with RL on this dataset and evaluate them on more than 50 independent benchmarks of alignment and beneficial behavior. Compared to a compute-matched baseline, beneficial trait RL improves performance on over 80% of these out-of-distribution benchmarks. We observe substantial out-of-distribution alignment transfer: a beneficial-behavior RL intervention entirely limited to one domain, health, produces broad improvements on non-health alignment evaluations, including reduced reward hacking, deception, and general misalignment. Finally, we study alignment persistence: whether behavior remains robustly aligned under attempts to steer models towards misalignment. Models trained with beneficial trait RL show improved persistence, including greater resistance to adversarial prompting and harmful finetuning; further work is required to isolate the sources of these effects. These results suggest that RL to reinforce beneficial behavior in realistic domains can produce models that are more robustly aligned with human flourishing.

08.
arXiv (CS.CV) 2026-06-15

Generation of Maximal Snake Polyominoes Using a Deep Neural Network

Maximal snake polyominoes are difficult to study numerically in large rectangles, as computing them requires the complete enumeration of all snakes for a specific rectangle size, which corresponds to a brute force algorithm. This hinders the study of maximal snakes in larger rectangles. Moreover, most enumerable snakes lie in small rectangles, obscuring large-scale patterns. In this paper, we investigate the contribution of a deep neural network to the generation of maximal snake polyominoes from a data-driven training, where the maximality and adjacency constraints are not encoded explicitly, but learned. To this extent, we experiment with a denoising diffusion model, which we referred as Structured Pixel Space Diffusion (SPS Diffusion). We find that SPS Diffusion generalizes from small rectangles to larger ones, generating valid snakes up to 28x28 squares and producing maximal snake candidates on squares close to the current computational limit. The model is, however, prone to errors such as branching, cycles, or multiple snake components. Overall, the diffusion model is promising and suggests that complex combinatorial objects can be understood by deep neural networks, which is useful in their investigation.

09.
arXiv (CS.LG) 2026-06-25

Efficient Adaptive Data Acquisition via Pretrained Belief Representations

arXiv:2606.25197v1 Announce Type: new Abstract: Learning effective policies for adaptive data acquisition remains challenging: posterior-based methods rely on surrogate models and posterior approximations that can be misspecified or biased, while direct policy-learning methods map from historical observations and fail to exploit available model representations, making learning harder. We introduce policy learning with belief representations (POLAR), based on the insight that optimal data acquisition depends on the observation history only through a sufficient belief state. Specifically, POLAR decouples representation learning from policy learning by leveraging pretrained predictive foundation models as belief-state encoders, training a policy head on top of their representations. This yields a simple, unified amortised policy learning framework for Bayesian experimental design, Bayesian optimisation, and active learning, differing only in the task-specific utility used to train the policy. Empirically, we find that POLAR outperforms state-of-the-art amortised methods across diverse tasks while requiring far fewer training samples, demonstrating a significant step in the scalability and efficiency of amortised data acquisition.

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

Your Privacy My Cloak: Backdoor Attacks on Differentially Private Federated Learning

arXiv:2606.17035v1 Announce Type: new Abstract: Prior research suggests that differential privacy (DP) inherently enhances the robustness of federated learning (FL) against backdoor attacks. In this paper, we challenge this assumption. Through an empirical analysis of two baseline attack strategies, we uncover a fundamental tension in DP-FL: while bypassing DP allows state-of-the-art defenses to detect and filter malicious updates, complying with DP inadvertently masks their distinguishing statistical characteristics. Consequently, existing defenses become ineffective as DP reduces the raw backdoor signal. Building on this masking effect, we propose RING, a novel attack that explicitly exploits DP to conceal malicious contributions while maximizing attack impact. By collaboratively crafting adversarial perturbations, compromised clients reconstruct a strong backdoor signal during aggregation without triggering anomaly detection. RING operates as a perturbation layer that is agnostic to the underlying backdoor technique, making it broadly applicable and composable with existing attacks – a property that significantly amplifies the threat it poses to DP-FL. Extensive evaluations across four image and text datasets under non-iid distributions show that RING achieves an average attack success rate of 90.3% against six state-of-the-art defenses under a moderate privacy budget, an improvement of up to 26.08x over baseline strategies. Finally, we evaluate potential countermeasures and find that mitigating this threat incurs significant utility trade-offs, exposing a fundamental security gap in the deployment of differentially private FL.

11.
arXiv (CS.AI) 2026-06-15

TabKD: Tabular Knowledge Distillation through Interaction Diversity of Learned Feature Bins

arXiv:2603.15481v2 Announce Type: replace-cross Abstract: Data-free knowledge distillation enables model compression without original training data, critical for privacy-sensitive tabular domains. However, existing methods does not perform well on tabular data because they do not explicitly address feature interactions, the fundamental way tabular models encode predictive knowledge. We identify interaction diversity, systematic coverage of feature combinations, as an essential requirement for effective tabular distillation. To operationalize this insight, we propose TabKD, which learns adaptive feature bins aligned with teacher decision boundaries, then generates synthetic queries that maximize pairwise interaction coverage. Across 4 benchmark datasets and 4 teacher architectures, TabKD achieves highest student-teacher agreement in 14 out of 16 configurations, outperforming 5 state-of-the-art baselines. We further show that interaction coverage strongly correlates with distillation quality, validating our core hypothesis. Our work establishes interaction-focused exploration as a principled framework for tabular model extraction.

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

Are Neuro-Inspired Multi-Modal Vision-Language Models Resilient to Membership Inference Privacy Leakage?

In the age of agentic AI, the growing deployment of multi-modal models (MMs) has introduced new attack vectors that can leak sensitive training data in MMs, causing privacy leakage. This paper investigates a black-box privacy attack, i.e., membership inference attack (MIA) on multi-modal vision-language models (VLMs). State-of-the-art research analyzes privacy attacks primarily to unimodal AI-ML systems, while recent studies indicate MMs can also be vulnerable to privacy attacks. While researchers have demonstrated that biologically inspired neural network representations can improve unimodal model resilience against adversarial attacks, it remains unexplored whether neuro-inspired MMs are resilient against privacy attacks. In this work, we introduce a systematic neuroscience-inspired topological regularization (tau) framework to analyze MM VLMs resilience against image-text-based inference privacy attacks. We examine this phenomenon using three VLMs: BLIP, PaliGemma 2, and ViT-GPT2, across three benchmark datasets: COCO, CC3M, and NoCaps. Our experiments compare the resilience of baseline and neuro VLMs (with topological regularization), where the tau > 0 configuration defines the NEURO variant of VLM. Our results on the BLIP model using the COCO dataset illustrate that MIA attack success in NEURO VLMs drops by 24% mean ROC-AUC, while achieving similar model utility (similarities between generated and reference captions) in terms of MPNet and ROUGE-2 metrics. This shows neuro VLMs are comparatively more resilient against privacy attacks, while not significantly compromising model utility. Our extensive evaluation with PaliGemma 2 and ViT-GPT2 models, on two additional datasets: CC3M and NoCaps, further validates the consistency of the findings. This work contributes to the growing understanding of privacy risks in MMs and provides evidence on neuro VLMs privacy threat resilience.

13.
arXiv (math.PR) 2026-06-11

Feynman–Kac formula for the heat equation with a one-center point interaction in $d=3$

arXiv:2606.11677v1 Announce Type: new Abstract: We study Schrödinger operators with a one-center point interaction, formally defined by \begin{align*} -\Delta_\alpha=-\Delta+\alpha\,\delta_0(\cdot), \end{align*} for $\alpha\in\mathbb{R}$, and the associated heat equation \begin{align} \partial_t u=\tfrac{1}{2}\Delta_{\alpha} u,\quad u(0,x)=u_0(x)\in C_c^{\infty}(\mathbb{R}^3\setminus\{0\}).\label{eq:HEapp} \end{align} Here $\Delta$ denotes the Laplacian (self-adjoint on $L^2(\mathbb{R}^3)$) and $\delta_x$ the Dirac measure at $x$. The operator $-\Delta_\alpha$ can be realized either as a self-adjoint extension of $-\Delta|_{C_0^{\infty}(\mathbb{R}^3\setminus\{0\})}$ in $L^2(\mathbb{R}^3)$, or as the norm-resolvent limit of $-\Delta+\lambda_\varepsilon V(\cdot/\varepsilon)$ for suitable $\lambda_\varepsilon$ and $V:\mathbb{R}^3\to\mathbb{R}$. In this paper we construct, for each $t>0$ and $x\in\mathbb{R}^3\setminus\{0\}$, a probability law on path space and a normalizing function $G_t^\alpha(x)$ giving the following probabilistic representation of the solution to the associated equation: \begin{align*} u(t,x)=G_t^\alpha(x)\,\mathbb{E}\bigl[u_0\bigl(W^{t,x}(t)\bigr)\bigr], \end{align*} where $\{W^{t,x}(s):0\le s\le t\}$ is a continuous process depending on $(t,x,\alpha)$. The result provides a Feynman–Kac type formula for the heat equation with a one-point interaction in three dimensions.

14.
medRxiv (Medicine) 2026-06-10

Gendered pathways to adolescent mental health: An empirical assessment of a new conceptual framework

Introduction Gender norms and roles are important determinants of physical and mental health in the key period of adolescence. Yet, the gendered pathways to mental health in adolescents are not fully understood. Using a conceptual framework for global adolescent mental health that we developed based on a Delphi process, we empirically investigated the associations between six gender-related constructs and adolescent mental health. Methods We used cross-sectional Gender and Adolescence: Global Evidence (GAGE) data from Ethiopia (2020) to explore the associations between sex, gender norms, psychological competencies, gender attitudes, gender roles, with the latter two also serving as mediators, and psychological distress (GHQ-12), using Structural Equation Modelling (SEM). Results The SEM model contained measurements from 1,584 adolescents, including 843 girls and 741 boys, with a median age of 13 years. Out of 14 pathways tested, we found statistically significant associations between psychological competencies and psychological distress; sex and gender attitudes; and between gender norms and psychological competencies, gender attitudes, and gender roles. Hence, the gender-related constructs were mostly associated with each other, rather than with psychological distress. Conclusion The gender-related constructs are strongly interrelated, thereby attenuating their individual effects on psychological distress. The interplay of gender-related constructs should be considered when developing interventions to promote mental health in adolescents.

15.
arXiv (CS.LG) 2026-06-25

Do Prompt-Elicited Trajectories Reflect Training-Time Reward Hacking? A Systematic Study on Monitoring Trainig-Time Reward Hacking in Code Generation

arXiv:2604.23488v2 Announce Type: replace Abstract: Reward hacking in code generation, where models exploit evaluation loopholes to obtain high reward without correctly solving the intended task, poses a critical challenge for Reinforcement Learning (RL) and the deployment of reasoning models. Existing studies often rely on explicitly prompted hacking trajectories, but it remains unclear whether monitors trained on such data can detect reward hacks that arise without direct hacking instructions during RL training. In this work, we introduce Trace-and-Amplify, a framework for scalable curation of reward-hacking trajectories that arise during RL training without explicit hacking instructions. The framework uses unit-test tracers to identify hacking solutions when they occur and retains such trajectories for monitor training and evaluation. Through controlled comparisons between monitors trained on prompt-elicited hacking trajectories and training-time reward-hacking trajectories collected by Trace-and-Amplify, we find that (1) prompt-elicited-data-trained monitors often fail to generalize to trajectories curated by our framework, and (2) monitors trained on our Trace-and-Amplify trajectories demonstrate stronger generalizability to unseen hacking types. Our results indicate that prompted reward hacking data may not fully reflect training-time reward-hacking behaviors, and that relying solely on these data can lead to misleading conclusions. Codebase is available at https://github.com/LichenLillc/CoTMonitoring.git

16.
arXiv (CS.CV) 2026-06-17

GeoDisaster: Benchmarking Orchestrated Agents for Operational Disaster Geo-Intelligence

Remote-sensing vision-language models (RS-VLMs) have advanced Earth-observation analysis toward visual interpretation and instruction-following, yet fall short of operational geo-intelligence, which demands tool-grounded spatial reasoning and structured, evidence-backed decisions. We introduce GeoDisaster, an operational geospatial disaster reasoning benchmark with 2,921 verified instances across 43 question types and five task families: deforestation monitoring, multi-hazard analysis, building-damage assessment, flood-safe routing, and Sentinel-1 SAR flood monitoring. Instances integrate heterogeneous EO/GIS evidence-optical and SAR imagery, raster masks, vector geometries, road networks, and exposure layers-spanning hazard detection, damage assessment, exposure estimation, and diagnostic report generation. Ground-truth answers are grounded in executable geospatial workflows and deterministic consistency checks, removing the need for language-model annotation. We further propose an orchestrated multi-agent framework with 18 disaster-oriented tools, where role-specialized agents coordinate through explicit execution contracts, aligned via Role-Contract Expectation Alignment (RCEA): failure-aware supervised fine-tuning combined with contract-grounded reinforcement learning over dense step-level signals. Experiments show that GeoDisaster challenges existing RS-VLMs and agentic systems, while RCEA improves tool use, evidence grounding, state consistency, and decision generation.

17.
arXiv (quant-ph) 2026-06-16

Quantum Measurement and Continuous Markov Processes

arXiv:2606.15958v1 Announce Type: new Abstract: These are the lecture notes for a course on diffusive quantum measuring instruments. They were prepared and delivered at the Perimeter Institute on Mondays and Thursdays, from 2:30 to 4:00 PM, beginning October 27th, 2025 and ending December 11th, 2025. These lectures were recorded and can be found at https://pirsa.org/c25038.

18.
arXiv (CS.CV) 2026-06-16

BBR-Net: Boundary-Balanced Replay for Continual Medical Image Segmentation

Continual learning for medical image segmentation remains challenging under domain shift because replay-based methods often preserve appearance information without explicitly modeling anatomical structure. This study investigates whether structural consistency governs knowledge retention in continual cardiac ultrasound segmentation. We propose the Boundary-Balanced Replay Network (BBR-Net), which selects replay samples using boundary-aware priority and class balance to preserve anatomically informative regions. The method is evaluated on CAMUS and CardiacNet under forward (CAMUS to CardiacNet) and reverse (CardiacNet to CAMUS) task orders. In the forward setting, BBR-Net retains source-task performance close to an offline joint-training reference, while markedly reducing catastrophic forgetting and preserving competitive target-task adaptation. Ablation results show that boundary-aware prioritization contributes to retention and improves the balance between source-task preservation and target-task adaptation when combined with class-aware sampling. In contrast, the reverse setting reveals that structure-aware replay fails when initial representations are learned from noisy and structurally inconsistent data. To isolate this effect, we conduct a controlled structural perturbation analysis by progressively corrupting source-task boundaries while keeping the dataset, architecture, and training protocol fixed. Forgetting increases consistently as structural reliability decreases, suggesting that replay effectiveness is strongly influenced by the quality of stored structural information, rather than by memory capacity alone. These findings indicate that preserving anatomical structure under domain shift is a central factor in continual medical image segmentation, and that replay mechanisms should account for structural reliability to support robust knowledge retention.

19.
bioRxiv (Bioinfo) 2026-06-12

Deciphering cross-omics complexity of tissues via diagonal integration of unpaired spatial multi-omics data

Recent spatial multi-omics technologies enable the simultaneous in situ profiling of multiple omics modalities on the same tissue section; however, they face challenges in experimental complexity and high costs. This technical limitation can be circumvented by diagonal integration methods, which integrate omics data from different modalities. However, existing single-cell diagonal integration approaches overlook spatial information, causing unreliable anchoring across omics layers. Here, we introduce STAMO, a graph attention neural network model for spatially aware integration of unpaired spatial slices from different omics. Systematic benchmarking on spatial epigenome-transcriptome slices proves that STAMO outperforms the state-of-the-art methods in generating aligned embeddings and identifying consensus spatial domains across omics. We apply STAMO to integrate unpaired data from diverse spatial omics types (transcripts, epigenetics, DNA, and proteins), including slices from spatial RNA and four different epigenomic modalities, spatial ATAC and RNA slices across embryonic stages, spatial protein and RNA slices, and spatial DNA and RNA slices. In addition, the integration capability of STAMO can be further used to achieve cross-omics generation, offering a solution for exploring spatial region-specific gene regulatory mechanisms.

20.
Nature Medicine 2026-06-25

Neoadjuvant stereotactic body radiation therapy with durvalumab and oleclumab in ER<sup>+</sup>HER2<sup>−</sup> breast cancer: a randomized phase 2 trial

Patients with estrogen receptor-positive (ER+), HER2-negative, early breast cancer (BC) have low pathologic complete response (pCR) rates following neoadjuvant chemotherapy. Immune checkpoint inhibitors (ICIs) provide limited benefit in programmed death-ligand 1 (PD-L1)-negative tumors, characterized by an immune-cold tumor microenvironment. Here we hypothesized that immune-modulating stereotactic body radiation therapy (iSBRT; 3 × 8 Gy) could enhance response through tumor microenvironment reprogramming, and that CD73 blockade could further improve efficacy. We conducted a phase 2, randomized, multicenter trial (Neo-CheckRay) in 147 female patients with high-risk, ER+HER2− early BC. Patients received neoadjuvant chemotherapy plus iSBRT alone (No_ICI), with anti-PD-L1 durvalumab (Single_ICI) or with durvalumab plus anti-CD73 oleclumab (Double_ICI). In the intention-to-treat population, the primary endpoint, residual cancer burden 0/1 rate, was 35.4% with No_ICI, 45.1% with Single_ICI and 47.9% with Double_ICI, without statistically significant differences. pCR rates were 16.7%, 29.4% and 33.3%, respectively (P = 0.059). In the per-protocol population (MammaPrint High Risk, n = 131), pCR rates were 16.3%, 32.6% and 35.6%, respectively (P = 0.040). Among PD-L1-negative tumors (n = 91), pCR rates were 3.4%, 28.1% and 30.0%, respectively. No new safety signals were observed. Baseline transcriptomic analysis showed low immune signature expression in PD-L1-negative tumors. Paired baseline and on-treatment biopsies obtained 1 week after iSBRT demonstrated tumor microenvironment reprogramming toward an inflamed phenotype in the iSBRT + anti-PD-L1 arms. These findings suggest that iSBRT + anti-PD-L1 may convert immune-cold ER+HER2− BC into more inflamed tumors and improve response, particularly in PD-L1-negative disease. ClinicalTrials.gov registration: NCT03875573 . In the randomized phase 2 Neo-CheckRay trial, patients with early-stage ER+HER2− breast cancer received neoadjuvant immune-modulating stereotactic body radiation therapy with or without durvalumab, and with or without the anti-CD73 antibody oleclumab, leading to encouraging clinical responses when durvalumab was added including in patients with PD-L1-negative tumors.

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

Pretrained self-supervised speech models can recognize unseen consonants

Modern pretrained self-supervised automatic speech recognition models are trained on large-scale audio data to encode speech into contextualized representations. However, their training data are heavily skewed toward high-resource languages with little data from low-resource languages, raising concerns about the potential underrepresentation of typologically uncommon speech sounds such as click consonants primarily found in Khoisan languages. This leads to our central research question: Can these models recognize click consonants as accurately as other speech sounds? To address this question, we fine-tune and compare pretrained self-supervised speech models (Wav2Vec2 and HuBERT) on data from two click-rich Khoisan languages (G|ui and West !Xoon). Our results reveal that the fine-tuned models consistently recognize clicks more accurately than non-clicks, suggesting that self-supervision enables generalization across human speech sounds including rare phonemes.

22.
medRxiv (Medicine) 2026-06-24

MedGenesis: Toward a World Model for Autonomous Clinical and Translational Research

Clinical research advances slowly because its core tasks, from evidence synthesis to mechanistic validation, remain fragmented. We present MedGenesis, a clinical artificial intelligence (AI) scientist built on a world-model reasoning loop that jointly updates a Latent Hypothesis Space and a Latent Action Space under expected information gain (EIG), uncertainty reduction (UR), and a safety prior P(safe), and integrates longitudinal electronic health records (EHRs) via the Virtual Clinical Trajectory and Observation Representation (ViCTOR) for cohort retrieval, trajectory stratification, and time-to-event analysis. On two benchmarks - ClinicalResBench (1,697 expert-curated questions) and ClinicalRepBench (40 paper-reproduction tasks) - MedGenesis outperformed frontier language models and biomedical AI systems while reducing hallucination. Across 1 million patient observations spanning five clinical evidence formats, it generated traceable outputs across meta-analysis, randomized controlled trials, real-world trajectories, case-control studies, and case reports, with one wet-lab-coupled run nominating a 3-hydroxybutyrate - neutrophil axis modulating antitumor immunity. These results compress hypothesis-to-evidence cycles from years to hours, creating a continuous clinical discovery process.

23.
arXiv (CS.AI) 2026-06-17

MoCo-AIS: A Contrastive Learning Framework for Similarity Computation of Vessel Trajectories

arXiv:2606.17978v1 Announce Type: new Abstract: Trajectory similarity is a fundamental task in analyzing mobility patterns, essential for applications such as route pattern extraction, mobility prediction, and anomaly detection. Traditional distance-based measures for computing similarity incur high computational cost, driving the adoption of lightweight learning-based approaches. Supervised methods rely on extensive labels derived from traditional distance measures and often reproduce these metrics, which limits generalization. While self-supervised learning addresses this issue through contrastive learning, it lacks a unified framework, making it difficult to compare deep learning (DL) models for consistent trajectory representation. Accordingly, this paper presents MoCo-AIS, a unified framework for learning vessel trajectory embeddings based on the Momentum Contrast (MoCo) paradigm, which formulates similarity learning through positive and negative trajectory pairs. Within this framework, we evaluate a diverse set of leading DL models on large-scale, real-world vessel-tracking AIS datasets that capture diverse navigation behaviors and operating conditions. Results demonstrate that our framework significantly improves similarity learning over existing baselines, while providing a benchmarking platform for evaluating trajectory representation models.

24.
medRxiv (Medicine) 2026-06-15

Entity-Aware Generation of Synthetic Clinical Progress Notes for Prostate Cancer using Large Language Model

Objectives: This study investigates large language models (LLMs) for clinical entity projection across substantial textual transformation. Specifically, we evaluate whether entities annotated in Spanish prostate cancer case reports can be preserved and explicitly projected when the source narratives are transformed into hospital-style clinical progress notes. Entity projection is treated as a generation-driven task, allowing paraphrase, condensation and narrative reorganisation, providing that clinically relevant entities remain recoverable as structured annotations. Methods: A corpus of 109 Spanish prostate cancer case reports was annotated using a silver-standard pipeline combining Spanish biomedical named-entity recognition with rule-based prostate-specific antigen (PSA) and Gleason extractors. The resulting silver-standard annotations were validated on a subset of generated notes against a gold-standard consensus produced by medical experts in prostate cancer. Four LLMs were evaluated for note generation and entity projection: GPT-5.4 Nano, Qwen 3.5:35B-A3B, GLM5 and Claude Sonnet 4.6. Entity-to-Entity (E2E) generation used XML-annotated cases as RAG-supported input, whereas Text-to-Entity (T2E) generation required models to generate and annotate notes directly from plain text cases. Zero-shot and few-shot prompting were tested. Projection quality was measured using precision, recall and F1-score, and complemented by LLM-as-a-judge evaluation using Kimi K2.6. Results: E2E consistently outperformed T2E, indicating that explicit entity-enriched in- put substantially facilitates entity preservation and localisation. GLM5 achieved the best E2E zero-shot result (F1 = 0.915), followed by Claude Sonnet 4.6 (F1 = 0.896). In T2E, few-shot prompting improved performance, with Claude Sonnet 4.6 reaching the highest score (F1 =0.718). Age, Gleason, Disease, Procedure, Duration and negation-related entities were robustly projected, whereas PSA and Dose showed less stable behaviour. Conclusion: LLMs can generate clinically plausible synthetic prostate cancer evolution notes while preserving a substantial proportion of source entities, particularly when explicit semantic annotations are provided as input. However, the lower and more variable performance observed in T2E highlights the difficulty of jointly generating clinical narratives and projecting entities without source-side information, especially for numerical and measure-related entities.