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

Intrinsic 4D Gaussian Segmentation from Scene Cues

Dynamic 4D Gaussian Splatting reconstructs deforming scenes with high fidelity and is increasingly adopted as a representation for dynamic 3D scenes. Putting such a scene to use, for editing, manipulation or motion analysis, first requires segmenting it: grouping the Gaussian primitives into coherent objects. Current pipelines obtain this grouping by importing 2D masks from foundation models such as SAM and lifting or distilling them into the Gaussian representation. In dynamic scenes these masks must be generated across many frames and views, which is costly, and the resulting segmentation can depend strongly on the quality and consistency of those external masks. We ask how much object-level structure can instead be recovered from the Gaussians themselves, and propose Intrinsic-GS, a training-free, mask-free method that builds a sparse affinity graph over Gaussian primitives from appearance, orientation, scale, deformation-trajectory and non-learned rendered-boundary cues. The graph is partitioned with Leiden community detection, requiring no foundation model and no learned feature field. On the standard 4D Gaussian segmentation benchmarks, Neu3D and HyperNeRF, Intrinsic-GS recovers substantial object structure without mask supervision, reaching 0.746 mIoU on Neu3D and 0.575 on HyperNeRF; on Neu3D, a geometry-only variant reaches 0.902 mIoU, matching SAM-supervised TRASE. On HyperNeRF, Intrinsic-GS runs 12.5x faster than the mask-generation and feature-rendering stages used by mask-supervised pipelines. These results suggest that much of the segmentation signal is already encoded in the Gaussians themselves, offering a fast, mask-free direction for 3D and 4D Gaussian segmentation that may also point toward more generalizable, robust segmentation in settings where external masks are unreliable or expensive.

02.
arXiv (CS.CL) 2026-06-15

Verbatim Chunks Beat Extracted Artifacts: A Controlled Ablation of Memory Representations for Long LLM Conversations

作者:

A growing class of conversational-memory systems compresses dialogue history into structured artifacts – extracted facts, decisions, or events – on the premise that distilled structure retrieves better than raw text. We test this premise with a controlled ablation: within one fixed retrieval-rerank-reasoning pipeline, we swap only the stored representation – LLM-extracted typed artifacts versus verbatim conversation chunks – holding the model, retriever, reranker, and judge constant. Verbatim chunks win by 15.9 points on LoCoMo (43.9% vs. 28.0%) and 22.0 points on LongMemEval-S (67.4% vs. 45.4%); a 1-hop semantic graph does not recover the gap, and five confound controls reproduce the effect. The mechanism is lossy distillation: extraction discards verbatim detail that chunks retain for free, and the extracted-artifact pipeline never beats naive RAG in overall accuracy. Concurrent positive results with near-verbatim, provenance-preserving units fit the same account: retrieval accuracy tracks how far the representation departs from the source. For the extraction designs we test, structured memory should augment verbatim text rather than replace it: a chunks $\cup$ artifacts union store matches chunks on both benchmarks while artifacts alone forfeit the gap. Code and data: https://github.com/tao-hpu/cog-canvas

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

MVAD: A Benchmark Dataset for Multimodal AI-Generated Video-Audio Detection

The rapid advancement of AI-generated multimodal video-audio content has raised significant concerns regarding information security and content authenticity. Existing synthetic video datasets predominantly focus on the visual modality alone, while the few incorporating audio are largely confined to facial deepfakes–a limitation that fails to address the expanding landscape of general multimodal AI-generated content and substantially impedes the development of trustworthy detection systems. To bridge this critical gap, we introduce the Multimodal Video-Audio Dataset (MVAD), the first comprehensive dataset specifically designed for detecting AI-generated multimodal video-audio content. Our dataset exhibits three key characteristics: (1) genuine multimodality with samples generated according to three realistic video-audio forgery patterns; (2) high perceptual quality achieved through diverse state-of-the-art generative models; and (3) comprehensive diversity spanning realistic and anime visual styles, four content categories (humans, animals, objects, and scenes), and four video-audio multimodal data types. Our dataset will be available at https://github.com/HuMengXue0104/MVAD.

05.
bioRxiv (Bioinfo) 2026-06-15

Maternal BMI and Placental Transcriptomic Changes: A Meta-Analysis of Gene Expression at the Maternal-Fetal Interface

Objective: Maternal body mass index (BMI) is often used as a measure of metabolic status and increased or decreased maternal BMI is associated with a heightened risk of cardiometabolic diseases across generations. The placenta mediates these maternal metabolic cues; however, its genome wide transcriptional adaptations in response to maternal BMI remain incompletely defined. Methods: To delineate placental genes, pathways, and interaction clusters whose transcript abundance varies with maternal prepregnancy BMI through a genome wide meta analysis of human placental RNA sequencing datasets. Placental RNA seq reads from four publicly available cohorts (n=146) were mapped to the GRCh38 reference genome and differentially expressed genes were identified. An independent microarray cohort (n=19) was reanalysed separately to facilitate cross platform comparison. Functional enrichment employed GO, KEGG, and STRING protein interaction resources. Results: Meta-analysis of 146 RNA seq samples identified eight genes with genome-wide significance in placentae from underweight pregnancies including inflammatory signaling gene MAP4K1 and metabolic enzyme PSPH, while overweight and obese categories revealed nominally significant differential expression. KEGG analysis demonstrated significant downregulation of oxidative phosphorylation with increasing maternal BMI, and protein-protein interaction networks revealed inflammatory mediators as central nodes in overweight and obese groups. Independent microarray validation corroborated key findings, including consistent downregulation of oxidative phosphorylation in obesity. Conclusion: Maternal BMI is associated with placental transcriptomic signatures involving inflammatory, metabolic, and hormonal pathways, with consistent downregulation of oxidative phosphorylation across platforms. This genome-wide meta-analysis provides a reproducible catalogue of BMI-responsive placental transcripts that may contribute to developmental programming of offspring health.

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

Through the PRISM: Preference Representation in Intermediate States of Video Diffusion Models

Evaluating video generation with clean, pixel-based reward models disconnects evaluation from the noisy diffusion process and incurs massive VAE decoding costs. In this paper, we challenge this paradigm by asking a fundamental question: Can a powerful video generator inherently discriminate preferences directly from noisy latents? To answer this, we introduce PRISM (Preference Representation in Intermediate States of Diffusion Models). PRISM employs a lightweight Query-based Aggregation head with a frozen video diffusion backbone to decode preference signals from noisy latents. Surprisingly, PRISM not only achieves SOTA preference accuracy but also unlocks strong noise-robustness, which enables early-stage Best-of-$N$ sampling. This allows for filtering suboptimal candidates at the very beginning of denoising, drastically reducing computation while boosting video quality. We also reveal a strong positive correlation between a backbone's generative performance and its inherent evaluative power, enabling self-improving video backbones.

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

Fluently Lying: Adversarial Robustness Can Be Substrate-Dependent

The primary tools used to monitor and defend object detectors under adversarial attack assume that when accuracy degrades, detection count drops in tandem. This coupling was assumed, not measured. We report a counterexample observed on a single model: under standard PGD, EMS-YOLO, a spiking neural network (SNN) object detector, retains more than 70% of its detections while mAP collapses from 0.528 to 0.042. We term this count-preserving accuracy collapse Quality Corruption (QC), to distinguish it from the suppression that dominates untargeted evaluation. Across four SNN architectures and two threat models (l-infinity and l-2), QC appears only in one of the four detectors tested (EMS-YOLO). On this model, all five standard defense components fail to detect or mitigate QC, suggesting the defense ecosystem may rely on a shared assumption calibrated on a single substrate. These results provide, to our knowledge, the first evidence that adversarial failure modes can be substrate-dependent.

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

Integrating Multi-Label Classification and Generative AI for Scalable Analysis of User Feedback

arXiv:2601.23018v1 Announce Type: cross Abstract: In highly competitive software markets, user experience (UX) evaluation is crucial for ensuring software quality and fostering long-term product success. Such UX evaluations typically combine quantitative metrics from standardized questionnaires with qualitative feedback collected through open-ended questions. While open-ended feedback offers valuable insights for improvement and helps explain quantitative results, analyzing large volumes of user comments is challenging and time-consuming. In this paper, we present techniques developed during a long-term UX measurement project at a major software company to efficiently process and interpret extensive volumes of user comments. To provide a high-level overview of the collected comments, we employ a supervised machine learning approach that assigns meaningful, pre-defined topic labels to each comment. Additionally, we demonstrate how generative AI (GenAI) can be leveraged to create concise and informative summaries of user feedback, facilitating effective communication of findings to the organization and especially upper management. Finally, we investigate whether the sentiment expressed in user comments can serve as an indicator for overall product satisfaction. Our results show that sentiment analysis alone does not reliably reflect user satisfaction. Instead, product satisfaction needs to be assessed explicitly in surveys to measure the user's perception of the product.

09.
arXiv (CS.LG) 2026-06-17

Meta-classification of one-class classification models using ranking correlation and nearest neighbor

arXiv:2606.17858v1 Announce Type: new Abstract: Machine Learning (ML) techniques have been applied to various problems. However, applying ML to ML models is an unexplored direction. For this purpose, this paper considers a meta-classification of one-class classification (OCC) models, because all ML models could be approximated as OCC models. The proposal represents OCC models as normality rankings and classifies them using nearest-neighbor and ranking-correlation metrics. The experiment classifies OCC models, where classes correspond to training datasets, algorithms, and hyperparameters. The proposal achieves high accuracy when class labels are datasets. Moreover, it can classify algorithms when the training datasets contain the same class. In addition, the discussion highlights that the classification of OCC models is essentially the classification of datasets that treats multiple samples as a single input. The experiment demonstrates the classification of datasets using sleeping records. The proposed method can provide a unified solution for classifying OCC models, datasets, and rankings. Source code is uploaded to the public repository https://github.com/ToshiHayashi/ClassOCC.

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

EgoPhys: Learning Generalizable Physics Models of Deformable Objects from Egocentric Video

Humans naturally understand object physics through everyday interactions, but faithfully predicting complex deformable dynamics, such as elastic materials and fabrics, remains a major challenge for computer vision and robotics. We present EgoPhys, a framework that constructs deformable physical digital twins from egocentric RGB-only video using generalizable priors. EgoPhys overcomes the limitations of existing methods to enable controllable deformable digital twin generation from egocentric videos by distilling per-object inverse-physics solutions into a compact codebook, enabling prediction of dense spring stiffness fields for unseen objects without per-spring test-time optimization. Trained with generalizable priors from diverse egocentric interactions, EgoPhys outperforms baselines in reconstruction, future prediction, and zero-shot generalization. To support training and evaluation, we curate an egocentric interaction dataset covering diverse deformable objects, scenes, and manipulation styles. We deploy EgoPhys on a real xArm6 robot, demonstrating that a digital twin initialized from a single egocentric human play video can serve as an internal world representation to aid in deformable-object planning, highlighting egocentric RGB observations as a scalable path toward real-to-sim pipelines.

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

CASHEW: Stabilizing Multimodal Reasoning via Iterative Trajectory Aggregation

Vision-language models achieve strong performance across a wide range of multimodal understanding and reasoning tasks, yet their multi-step reasoning remains unstable. Repeated sampling over the same input often produces divergent reasoning trajectories and inconsistent final predictions. To address this, we introduce two complementary approaches inspired by test-time scaling: (1) CASHEW, an inference-time framework that stabilizes reasoning by iteratively aggregating multiple candidate trajectories into higher-quality reasoning traces, with explicit visual verification filtering hallucinated steps and grounding reasoning in visual evidence, and (2) CASHEW-RL, a learned variant that internalizes this aggregation behavior within a single model. CASHEW-RL is trained using Group Sequence Policy Optimization (GSPO) with a composite reward that encourages correct answers grounded in minimal yet sufficient visual evidence, while adaptively allocating reasoning effort based on task difficulty. This training objective enables robust self-aggregation at inference. Extensive experiments on 13 image understanding, video understanding, and video reasoning benchmarks show significant performance improvements, including gains of up to +26.2 percentage points on ScienceQA and +9.1 percentage points on EgoSchema.

12.
arXiv (CS.AI) 2026-06-15

The Silent Cost of Artificial Intelligence Assistance: A Theory of Autonomy Surrender, the Recovery Mechanism, and the Restoration of Human Agency

arXiv:2606.13962v1 Announce Type: cross Abstract: The integration of artificial intelligence into human decision-making environments has introduced a previously undertheorized cost: the gradual surrender of human autonomy in exchange for access to information and computational assistance. Building on the Human Identity and Autonomy Gap (HIAG) framework, this paper advances a theoretical model of autonomy surrender as a measurable, cumulative process driven by cognitive bandwidth depletion. The model proposes three interacting mechanisms: the silent cost of AI assistance, in which autonomy is transferred incrementally and without awareness; the surrender threshold, beyond which reclaiming autonomous function becomes cognitively and psychologically difficult; and the recovery mechanism, which establishes the design obligation and the ethical responsibility accompanying deliberate human re-assumption of control. The paper argues that human re-entry into the decision loop is not a passive option but an active cognitive event requiring intentional bandwidth restoration. The design of AI systems must incorporate structured re-entry pathways, here termed recovery mechanisms, that preserve human agency while appropriately distributing responsibility. The model further predicts a terminal state, here termed preference inversion, in which functional dependence on AI assistance is experienced not as a deficit but as a preference, transforming the restoration of autonomy from a design problem into a cultural and political one. Implications are drawn for AI system design, governance frameworks, and human factors research.

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

Reconstructing Template-Memorized Images from Natural Prompts

arXiv:2507.07947v4 Announce Type: replace-cross Abstract: Recent advances in generative models, such as diffusion models, have raised concerns related to privacy, copyright infringement, and data stewardship. To better understand and control these risks, prior work has introduced techniques and attacks that reconstruct images, or parts of images, from training data. While these results demonstrate that training data can be recovered, existing methods often rely on high computational resources, partial access to the training set, or carefully engineered prompts. In this work, we present a new attack that requires low resources, assumes little to no access to the training data, and identifies seemingly benign prompts that can lead to potentially risky image reconstruction. We further show that such reconstructions may occur unintentionally, even for users without specialized knowledge. For example, we observe that for one existing model, the prompt ``blue Unisex T-Shirt'' generates the face of a real individual. Moreover, by combining the identified vulnerabilities with real-world prompt data, we discover prompts that reproduce memorized visual elements. Our approach builds on insights from prior work and leverages domain knowledge to expose a fundamental vulnerability arising from the use of scraped e-commerce data, where templated layouts and images are closely tied to pattern-like textual prompts. The code for our attack is publicly available at https://github.com/TheSolY/lr-tmi.

14.
arXiv (quant-ph) 2026-06-17

Probing PbTe-Pb nanowire devices with radio-frequency reflectometry

arXiv:2606.04544v2 Announce Type: replace-cross Abstract: We report the implementation of radio-frequency (rf) reflectometry on selective-area-grown PbTe-Pb nanowire devices on a CdTe substrate. These nanowires are predicted to host Majorana zero modes. We demonstrate the compatibility of the rf technique, including both resistive and capacitive sensing, with these nanowires. The effect of dielectric loss from the CdTe substrate is quantitatively characterized. Furthermore, the feasibility of rf reflectometry is verified under finite magnetic fields where zero-energy modes can emerge. Our results establish the fast control of PbTe quantum devices, paving the way for their applications in topological quantum computation.

15.
arXiv (CS.CL) 2026-06-12

Agentic MPC for Semantic Control System Resynthesis

While MPC effectively handles structured, diverse, and low-level specifications, it lacks the capability to dynamically incorporate high-level contextual information such as social norms, user intent, or natural language instructions. To address this limitation, this manuscript introduces an agentic MPC framework that enables context-aware, semantically adaptive control synthesis by integrating with large language model-based agents. The agent interprets heterogeneous inputs, including natural language messages, environmental observations, and external knowledge, to resynthesize the control specifications. The effectiveness of the framework is demonstrated in an autonomous driving scenario, where the system aligns with personal preferences or responds to social situations such as emergency vehicle yielding.

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

DC-Motion: Decoupling Semantics and Details via Discrete-Continuous Tokens for Human Motion Generation

Text-to-motion generation requires synthesizing physically realistic dynamics that strictly follow complex and long-horizon textual instructions. Existing approaches rely on homogeneous representation spaces that may fail to capture the hierarchical nature of human motion, with diffusion models struggling at compositional semantic reasoning and AR models sacrificing fine-grained physical details due to quantization. To solve it, we introduce DC-Motion, a factorized generative framework designed to explicitly decouple semantics and details via discrete-continuous tokens. A Discrete-Continuous VAE (DC-VAE) first decomposes motion into discrete tokens for semantics and continuous residuals for fine-grained dynamics. Then, a masked AR model predicts the discrete structure from text, and a lightweight residual diffusion model recovers the continuous physical details. Extensive experiments demonstrate that DC-Motion effectively improves the capability to follow complex instructions. By effectively balancing semantic controllability and physical realism, our approach offers a highly adaptable modeling paradigm for human motion generation. On both HumanML3D and KIT-ML datasets, DC-Motion achieves state-of-the-art performance, delivering the best FID for motion realism and R-precision for text alignment.

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

Constitutional On-Policy Safe Distillation

arXiv:2606.03089v2 Announce Type: replace-cross Abstract: On-policy self-distillation (OPSD) has emerged as an efficient post-training paradigm by using a teacher conditioned on privileged information to provide dense token-level supervision. Prior work has shown that OPSD can collapse in verifiable reasoning tasks, but safety alignment differs in that it is guided by high-level constitutions rather than explicit target answers, making it a natural setting to revisit dense distillation. However, our pilot study show that safety OPSD still suffers from severe collapse: constitutional conditioning contracts the teacher distribution toward short and overly conservative responses, and Reverse KL further amplifies this contraction into reduced expressiveness. We formalize this effect as geometric leakage under safety boundaries in a non-orthogonal semantic space, where safety pressure transfers into the expressiveness dimension. Based on this analysis, we propose Constitutional On-Policy Safe Distillation (COPSD), which first calibrates the teacher through a Cross-SFT cold-start and then performs constitution-conditioned on-policy distillation. Experiments on 12 benchmarks show that COPSD achieves a consistently stronger safety–helpfulness trade-off than baselines while substantially reducing the safety tax on general reasoning ability.

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

Green AI Carbon Optimizer: Carbon-Efficient Training Location Recommendation and Global AI Energy Demand Forecasting

arXiv:2606.14707v1 Announce Type: cross Abstract: AI training and deployment consume substantial electricity, but carbon outcomes remain weakly integrated into routine model development decisions. This paper presents Green AI Carbon Optimizer with two primary contributions: (i) a carbon aware cloud region recommendation method for training workloads, and (ii) a power law forecasting pipeline for global AI energy demand. For location recommendation, we combine regional grid carbon intensity, renewable share, and data center Power Usage Effectiveness (PUE) into a unified scoring model across 100+ regions from major cloud providers. For a reference workload (8*A100, 100h), estimated emissions in our sampled regions range from 7.74kg to 272.00kg CO2. Selecting the best region instead of the worst corresponds to a 97.2% reduction relative to the worst case. Ablation shows that ranking by renewable share alone can select regions with higher CO2 emissions than rankings that include grid carbon intensity. For forecasting, we fit a power law relation between parameter count and training energy using 26 anchor models. We combine this fit with scenario assumptions on model growth, hardware efficiency, and training frequency, and evaluate sensitivity to inference ratio and ecosystem scaling. Across scenarios, projected 2030 demand ranges from 7TWh to 1,436TWh under the stated assumptions, highlighting the importance of deployment choices, model scaling discipline, and transparent energy reporting.

19.
arXiv (quant-ph) 2026-06-17

Photon anti-bunching in high harmonic generation

arXiv:2606.17620v1 Announce Type: new Abstract: Photon anti-bunching is the direct evidence for the existence of photons without having a classical counterpart. Unlike bunching of photons, which can have a semi-classical description, the effect of photon anti-bunching can only be understood with quantized electromagnetic fields. However, for the process of high harmonic generation (HHG), where many photons of the driving field are upconverted to a single photon of higher energy, there is yet no clear evidence for the presence of individual photon emission. The key result of this work is the prediction of photon anti-bunching in the process of HHG, marking it the first theoretical discovery of non-classicality in the temporal correlations of HHG photons. While other non-classical signatures in HHG, such as sub-Poissonian statistics or squeezing, have been discussed for an ensemble of photons, the anti-bunching signature reported here is a signature of a single photon. This is achieved by using the recently developed Heisenberg picture approach for quantum optical HHG, revealing clear anti-bunching signatures in the intensity correlation function across the entire harmonic spectrum.

21.
PLOS Medicine 2026-05-20

Associations between hematologic dynamics during pregnancy and obstetric complications: A retrospective observational study

by Veronica Tozzo, Rachel Petherbridge, Kaitlyn James, Sarah Hsu, Deepti Pant, Chloe Michalopoulos, Brody H. Foy, Tanayott Thaweethai, Christopher Mow, Jacqueline Maya, Carolina Batlle Camero, Lydia Shook, Kathryn J. Gray, Logan Mauney, John M. Higgins, Camille E. Powe Background Pregnancy alters hematologic state as measured by complete blood count (CBC), but the longitudinal changes in CBC indices that define healthy pregnancies are not well established. In a large cohort based at an academic health system in the United States, we aimed to define reference intervals and typical longitudinal changes in CBC indices during pregnancy. We then tested for associations between extreme CBC values for gestational age or extreme longitudinal changes in CBC indices and obstetric complications. Methods and findings We studied nine CBC indices in individuals with singleton pregnancies who delivered after 30 weeks’ gestation and presented for prenatal care prior to 20 weeks. The electronic health record (EHR)-based Maternal Health Cohort (Massachusetts General Hospital; 1998–2016) formed our discovery cohort of 45,992 pregnancies, 18% of which had relevant complications. We developed a validation cohort of 48,868, 27% with complications from EHR data in the Mass General Brigham healthcare system from 2016 to 2024. In pregnancies without complications in the discovery cohort, we derived gestational-age-specific reference intervals (2.5th–97.5th percentile) and established typical intra-pregnancy longitudinal changes. In the validation cohort, we then tested CBC values outside of the 26–29 weeks’ gestation reference interval and CBC rare changes (uncommon changes in magnitude and direction) between 7–14 and 26–29 weeks’ gestation for association with a composite outcome (hypertensive disorders of pregnancy, small for gestational age birthweight, preterm birth) and its individual components using generalized estimating equations. Derived reference intervals differed from those in the literature for mean red cell volume, mean red cell hemoglobin, red cell count, and mean red cell hemoglobin concentration; reference intervals for other indices were similar to those previously published. In validation, hematocrit, hemoglobin, and red cell count values above their gestational-age specific reference intervals were associated with increased risk of the composite obstetric outcome: odds ratios (ORs) of 1.4 (95% CI [1.2, 1.5] p 

22.
arXiv (CS.LG) 2026-06-11

How Low Can You Go? Active Learning for Sparse Model Discovery in the Ultra-Low-Data Limit

arXiv:2606.12182v1 Announce Type: new Abstract: Identifying the governing equations of complex dynamical systems remains a fundamental challenge across science and engineering. While early approaches relied on empirical data and heuristics, modern data-driven methods offer greater flexibility and fewer assumptions. However, data acquisition in real-world settings is often expensive. This work addresses this challenge by introducing an active learning strategy for dynamics discovery in the ultra-low data limit. Rather than sampling randomly, our method iteratively prioritizes regions that are most informative for model identification. This approach builds on Sparse Identification of Nonlinear Dynamics (SINDy), and utilizes an ensemble extension, E-SINDy, to estimate epistemic uncertainty and guide the sampling for both ordinary and partial differential equations (ODEs/PDEs). For ODEs, an exhaustive analysis is conducted on the Lorenz system across varying data budgets and noise levels. For PDEs, two systems with contrasting dynamical characteristics are examined: the Burgers' equation, where a sharp shock front creates a distinction between informative and uninformative regions, and the Kuramoto-Sivashinsky equation, which presents a more spatially complex sampling landscape. Across all scenarios, the proposed method accurately identifies the governing dynamics with significantly fewer data samples than random sampling.

23.
medRxiv (Medicine) 2026-06-15

A controlled human infection model for symptomatic pertussis in North America using the pertactin-producing clinical isolate D420

Background Despite widespread vaccination, pertussis remains a poorly controlled disease globally and results in substantial annual morbidity and mortality, particularly in young children. Controlled human infection models (CHIMs) using the causative agent Bordetella pertussis are promising systems to enable the study of pertussis disease pathogenesis and immunology and to rapidly assess vaccines and therapeutics. While a pertussis CHIM that produces asymptomatic infection has been established in Europe, the development of a CHIM that leads to symptomatic illness would be advantageous for evaluating vaccine efficacy against both infection and disease. Methods Healthy participants 18-40 years of age were inoculated intranasally with one of eight doses (ranging from 104 to 108 colony forming units (CFU)) of the pertactin-producing B. pertussis isolate D420 at the challenge facility within the Canadian Center for Vaccinology (Nova Scotia, Canada). The study occurred in two stages. In stage one, the B. pertussis dose was escalated in cohort groups of five to six participants until reaching an endpoint where 70-90% of participants exhibited mild (non-severe, Grade 1 or 2) symptomatic infection, defined as the Human Infectious Dose 70-90 (HID70-90). In stage two, additional challenges were conducted for doses below, at, and above the identified HID70-90 to characterize the emerging pertussis model. For all challenge doses, participants were closely monitored during an inpatient stay of up to 24 days and post-discharge for laboratory-confirmed infection, pertussis symptoms, safety, and IgG antibody responses to four B. pertussis antigens including pertussis toxin, filamentous hemagglutinin, fimbriae, and pertactin. All participants received a five-day course of azithromycin, where timing of initiation depended on B. pertussis testing and symptoms. The study was conducted between July 4, 2022 and March 19, 2025. Findings Seventy-five participants were inoculated with one of the eight B. pertussis D420 challenge doses and completed the inpatient stay. From the stage-one dose escalation, we found that 107 CFU of B. pertussis D420 was the lowest dose that achieved the HID70-90, where 9 of 12 participants (75.0%) exhibited mild symptomatic infection. Following stage-two challenges, 16 of 22 total participants at 107 CFU (72.7%) developed mild symptomatic infection, thus verifying the HID70-90. The symptomatic infection rate below the HID70-90 at 5x106 CFU of D420 was 20.0% and above the HID70-90 at 5x107 and 108 CFU were 58.3% and 55.6%, respectively. Symptoms with elevated frequency for symptomatic infection (relative to background symptoms in non-infected) included nasal congestion, runny nose, fatigue, malaise, and cough. At the HID70-90, 50% of symptomatic infections included cough. Serological analyses of the four highest (stage-two) challenge doses (5x106, 107, 5x107, 108 CFU) revealed that antibody titres increased over time post-challenge. Seroconversion for at least one of the four studied antibodies was nearly twice as common for symptomatic (70.0%) than asymptomatic (35.7%) infection and was absent (0%) for non-infected. All infections were cleared following azithromycin treatment (100%) and there were no study-related serious adverse events. Interpretation A safe and reproducible symptomatic pertussis CHIM was achieved, providing a model for research on pertussis disease pathogenesis and immunology and for assessing vaccines and therapeutics. (Clinicaltrials.gov, NCT05136599).

24.
arXiv (CS.AI) 2026-06-16

CAP: Towards PPG Universal Representation Learning with Patient-level Supervision

arXiv:2606.15284v1 Announce Type: cross Abstract: Photoplethysmography (PPG) plays a central role in wearable health monitoring and clinical decision support. Yet existing approaches to universal PPG representation learning largely focus on signal-level objectives and often overlook patient-level health context, which limits generalization to complex clinical tasks and heterogeneous cohorts. To address this gap, we construct a large-scale paired PPG-EHR multimodal dataset by distilling fragmented medical histories and clinical records into cohesive, patient-level electronic health records (EHR). Building on this resource, we propose Clinical Anchored Pretraining for PPG (CAP). During pretraining, CAP performs cross-modal contrastive alignment that anchors PPG representations to patient-level clinical semantics, guiding the encoder beyond waveform fitting toward modeling consistency in a patient's overall physiological state. During downstream adaptation, the pretrained PPG encoder provides clinically grounded representations that strengthen inductive bias and improve robustness and transferability. Experiments demonstrate that CAP consistently outperforms strong baselines on four diverse downstream tasks. CAP achieves a particularly large gain on respiratory rate prediction (up to +87.6% relative improvement over the state-of-the-art baseline) and delivers an average relative +26.7% across all tasks. We further enhance the interpretability of our approach through comprehensive analyses, including ablations and multiple complementary visualizations of the learned representations. The code for our experiments is available at: https://github.com/gody123gody/CAP .

25.
medRxiv (Medicine) 2026-06-10

Human genetic evidence links serine biosynthesis to diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is a common and disabling condition for which no disease-modifying therapies are available. Glycemic and metabolic drivers do not fully explain why only a subset of individuals with diabetes develop DPN, and genetic contributors remain poorly defined. We aimed to perform a multi-population genome-wide association study (GWAS) of DPN to highlight potential new etiological pathways and therapeutic targets. Methods We performed a multi-population GWAS of neuropathy in people with and without diabetes using the VA Million Veteran Program and UK Biobank, followed by replication in the All of Us Research Program (AoU), and gene-based and gene-set analyses to identify implicated pathways. Causal relationships between circulating serine levels and DPN were further tested using two sample Mendelian randomization. To further evaluate pathogenic potential, we analyzed rare, high impact variants in GWAS implicated genes among individuals with unresolved inherited neuropathies using the GENESIS platform. Findings Among individuals with type 2 diabetes, we identified seven genome wide significant loci (p