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01.
medRxiv (Medicine) 2026-06-13

Projected population level impact and cost-effectiveness of clinic and community-based tuberculosis screening approaches

The South Africa National Department of Health have set ambitious targets to scale up TB testing, focusing primarily on clinic attendees. In the context of declining funding for TB care and prevention, the most cost-effective approaches for targeting testing should be identified. We developed a mathematical model of TB in South Africa, explicitly incorporating clinic attendance by sex and HIV/ART status. We simulated six screening approaches over 2026-2035 (individually and in combination): three clinic-based (symptom screening, intensified targeted universal TB testing [TUTT, symptom-agnostic sputum testing of clinic attendees in key risk groups], and intensified TUTT allowing saliva samples) and three targeted community-based (community radiographic screening, symptom screening, and universal Xpert Ultra testing), each implemented at a range of coverage levels. Model outputs were combined with a mechanistic cost function to estimate potential impact and cost-effectiveness from a societal perspective. The most cost-effective standalone approach was community radiographic screening at 10% annual population coverage, with an incremental cost-effectiveness ratio (ICER) of $421 per disability-adjusted life year (DALY) averted. 10/11 scenarios along the expansion path included community radiographic screening at progressively higher coverage, combined with a clinic-based approach. Combining complementary approaches to reach both groups at increased risk of TB (e.g. clinic-based screening) and groups with lower screening coverage (e.g. community-based screening) may increase cost-effectiveness of TB screening, compared to standalone approaches. When designing TB screening strategies, both population risk and existing screening coverage should be considered.

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

KCSAT-ML: Probing Reasoning Models with Nationwide-Cohort Human Difficulty

Math reasoning benchmarks have proliferated, yet most lack a per-item difficulty signal grounded in actual human performance. We introduce KCSAT-ML, a decade (2014-2025) of Korean College Scholastic Ability Test (KCSAT; Suneung) mathematics: 664 problems with a 339-item core set carrying official per-item error rates from nationwide cohorts of hundreds of thousands of examinees. We pair the benchmark with Difficulty-aligned Reasoning Gain (DRG): a score-orthogonal metric that asks whether a model's mistakes concentrate on the items humans found hard, or on items humans found easy. Together they expose, across a wide range of VLMs (and LLMs via OCR), three patterns: (i) low-budget accuracy collapses on the high-human-error tail at every model size; (ii) test-time scaling (TTS) raises token use roughly linearly with cohort error rate, while accuracy gains follow a non-monotonic curve; (iii) within a single family, TTS flips between anti-scaling on the hardest items and overthinking on easier ones – two faces of the same alignment failure. On DRG, models with near-identical accuracy can sit at near-opposite values: one model gets wrong what humans also find hard, while another solves the hardest items yet fails on items humans find easy – a contrast that aggregate accuracy hides. Our code and dataset builder will be open-sourced at https://github.com/naver-ai/KCSAT-ML.

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

One-Step Generalization Ratio Guided Optimization for Domain Generalization

arXiv:2606.16301v1 Announce Type: new Abstract: Domain Generalization (DG) aims to train models that generalize to unseen target domains but often overfit to domain-specific features, known as undesired correlations. Gradient-based DG methods typically guide gradients in a dominant direction but often inadvertently reinforce spurious correlations. Recent work has employed dropout to regularize overconfident parameters, but has not explicitly adjusted gradient alignment or ensured balanced parameter updates. We propose GENIE (Generalization-ENhancing Iterative Equalizer), a novel optimizer that leverages the One-Step Generalization Ratio (OSGR) to quantify each parameter's contribution to loss reduction and assess gradient alignment. By dynamically equalizing OSGR via a preconditioning factor, GENIE prevents a small subset of parameters from dominating optimization, thereby promoting domain-invariant feature learning. Theoretically, GENIE balances convergence contribution and gradient alignment among parameters, achieving higher OSGR while retaining SGD's convergence rate. Empirically, it outperforms existing optimizers and enhances performance when integrated with various DG and single-DG methods.

04.
arXiv (CS.CL) 2026-06-11

PoQ-Judge: A Multi-Architecture Evaluation Framework for Cost-Aware Proof-of-Quality in Decentralized LLM Inference

Decentralized LLM inference networks need lightweight, reference-free quality evaluation for Proof of Quality (PoQ). We present PoQ-Judge, a framework that trains dedicated judge models to score query-output pairs without ground-truth references. We study three architectures across the quality-cost tradeoff: a TextCNN judge, a MiniLM cross-encoder, and a DeBERTa judge. Using two-stage training on UltraFeedback plus GPT-labeled in-domain data, the best model reaches 0.747 Pearson correlation with the ground-truth proxy on a held-out test set, outperforming reference-based evaluators from prior work. As a reference-free component in composite scoring, it achieves 0.645 Pearson correlation, matching the best single reference-based evaluator while removing the need for reference answers. We also show that online calibration identifies semantic quality as the dominant dimension and that cascade evaluation reduces cost by 72.7 percent with only modest quality loss. Results are much stronger on QA than summarization, pointing to proxy quality as the main remaining limitation.

05.
arXiv (CS.CV) 2026-06-16

BRITE: A Benchmark for Reliable and Interpretable T2V Evaluation on Implausible Scenarios

The rapid advancement of photorealistic Text-to-Video (T2V) generation brings in an urgent need for up-to-date evaluation methods. Existing benchmarks largely overlooked implausible scenarios and do not measure audio-visual alignment. We introduce BRITE, the first framework that unifies (1) implausible prompting, (2) fine-grained assessment of audio-visual consistency, and (3) QA-based interpretable evaluation into a comprehensive T2V benchmark. Unlike fully automated Multimodal LLM-based pipelines, which are prone to hallucination and prompt ambiguity, BRITE guarantees reliability through a rigorous human-in-the-loop protocol for benchmark creation. Evaluating five state-of-the-art models (Sora 2, Veo 3.1, Runway Gen4.5, Pixverse V5.5, and Qwen3Max), we reveal a critical performance gap: while models excel at static object composition, they exhibit significant degradation in object-action binding and audio-visual synchronization. Our framework offers the community a reliable, interpretable benchmark and evaluation framework that can detect and locate limitations in the next generation of T2V models, especially for off-manifold prompts

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

Generative Molecular Design with Steerable and Granular Synthesizability Control

arXiv:2505.08774v2 Announce Type: replace-cross Abstract: Designing molecules that are both property-optimal and readily synthesizable is a central challenge in drug discovery. Existing works that do consider synthesizability can jointly output predicted synthesis routes for generated molecules. However, there has been minimal attention in addressing the ease of synthesis and with flexibility to incorporate desired reaction constraints. On the other hand, virtual screening searches for commercially available compounds, but imposes challenges when scaling to ultra-large (billion-size and beyond) chemical spaces. Here, we propose a generative design framework that unifies synthesis-constrained molecular design and ultra-large-scale virtual screening through steerable and granular synthesizability control. Generated molecules satisfy arbitrary multi-parameter optimization objectives with predicted synthesis routes satisfying mix-and-match constraints: including or avoiding certain reactions, incorporating specific building blocks, and minimizing synthesis route length. In an end-to-end in-house campaign targeting BRD4, we designed molecules synthesizable with specific selected reactions and building blocks, synthesized all six selected compounds, and identified two micromolar binders. We further demonstrate that reaction control enables efficient navigation of ultra-large make-on-demand chemical spaces to identify property-optimal candidates. By applying our framework to Chemspace's Freedom 4.0 make-on-demand space (142 billion molecules), we generated ~320k molecules (0.00023% of the library) on a single consumer-grade GPU (with only 8 GB GPU memory) and identified a micromolar Wee1 binder amongst 60 synthesized candidates. The single unified framework thus enables generating novel synthesizable molecules and retrieving catalogue-ready candidates, offering a flexible solution to mitigating the synthesizability bottleneck.

07.
arXiv (CS.AI) 2026-06-19

Token Factory: Efficiently Integrating Diverse Signals into Large Recommendation Models

arXiv:2606.19635v1 Announce Type: cross Abstract: Large Recommendation Models (LRMs) have demonstrated promising capabilities in industry-scale recommendation tasks. However, holistically integrating traditional signals into these transformer-based architectures effectively and efficiently remains a major challenge. Conventional approaches that "textualize" these signals directly or create discrete item representations often lead to excessively long prompts, substantial memory footprints, and high computational overhead. To overcome these limitations, we propose "Token Factory", a framework designed to transform traditional signals into "soft tokens" that can be directly processed by LRMs. This approach enables efficient integration and compression of heterogeneous input features, preventing prompt length explosion while enhancing model performance. We detail the architecture of Token Factory and present experimental results validating its effectiveness in a production-scale recommendation environment.

08.
arXiv (CS.AI) 2026-06-19

Science Earth: Towards A Planet-Scale Operating System for AI-Native Scientific Discovery

arXiv:2606.01316v2 Announce Type: replace Abstract: Scientific discovery demands intelligence, perseverance, and serendipity across vast search spaces. Today, top scientific capabilities remain siloed–one AI system for biological analysis, another for clinical reasoning, mathematical derivation, or materials simulation–and no pre-designed team can anticipate every skill a question will need. Science Earth is a planet-scale scientific runtime in which any capability–a simulation cluster, a wet-lab robot, a proof engine, a single-cell pipeline–can connect to any other, with collaboration structure emerging from the question itself. Its underlying EACN protocol lets capabilities discover one another, negotiate task ownership, and adjudicate across incompatible evidentiary standards without prior knowledge of who will meet whom. This shifts the organizing challenge from workflow design to open-ended connectivity. Two runs validate this under structurally distinct conditions. In a trans-Pacific higher-order Kuramoto synchronization study, agents identified and corrected a closure-ratio assumption in Ott-Antonsen analytic theory that fails outside the Lorentzian limit, within thirty minutes. In an eight-agent single-cell run on the 4.88M-cell Kang 2024 pan-cancer atlas, heterogeneous capabilities coupled over a 64.9-hour window with one structural external instruction, producing three new result layers and anchoring findings against an independent wet-lab study on an adjacent CCR8- TIGIT+ Treg subset. These cases are a first empirical reading, not a benchmark sweep. They show that when AI capabilities are truly connectable and coordination emerges from the problem, scientific reasoning becomes a distributed, self-correcting process–a step towards scaling AI-native discovery to the planet.

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

Identification and Inference for Algorithmic Frontiers with Selective Labels

arXiv:2606.14977v1 Announce Type: cross Abstract: This paper provides identification results to characterize a fairness-accuracy (FA) frontier, and statistical inference tools to test hypotheses and build a confidence set for the FA-frontier, when outcomes are observed only for selected individuals. When the selection process is unrestricted but loss is measured in specific ways, we provide a characterization of the sharp identification region of the FA-frontier. Under an assumption of unconfoundedness conditional on observables (and unrestricted loss functions), we obtain point identification and propose a debiased machine learning estimator, derive its asymptotic distribution, and show how this can be used to carry out inference for the FA-frontier. In work in progress, we extend the partial identification results to a broader class of loss functions.

10.
bioRxiv (Bioinfo) 2026-06-16

AutoZyme: An Autonomous Agentic Framework to Optimize Bioinformatics Software

Performance bottlenecks in widely used genomics and bioinformatics software present a substantial and growing burden as biological datasets continue to increase in size and number. Relieving these bottlenecks relies largely on expert manual optimization and therefore remains difficult to scale. Here we present AutoZyme, an agentic framework for scientific software optimization. Given a target function, AutoZyme builds benchmarks, identifies bottlenecks, and iteratively tests code changes, retaining only those that improve runtime while preserving output. We evaluated AutoZyme on 45 functions, improving runtime without substantial memory increases in over 95% of cases considered. Across 38 functions from Seurat, Scanpy and related packages in genomics and bioinformatics, AutoZyme reduced runtime by a median of 8.52-fold, with the largest reductions exceeding 676-fold. The optimized functions are distributed through AutoZyme-Library as drop-in replacements for existing analysis pipelines. We also release AutoZyme as a reusable framework for optimizing additional user-specified packages and functions.

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

IMPACTeen: Intentions, Manipulation, Persuasion, Annotations, and Consequences in Teen Communication Dataset

IMPACTeen is a dataset of textual social influence scenarios spanning interpersonal, media-based, and digital settings in an adolescent context. It contains 1,021 texts, 5,100 individual annotation records, and gold labels for social influence techniques, with each text annotated from five distinct perspectives: teenagers, parents, psychologists, communication experts, and teachers. The resource was constructed through constrained LLM generation, followed by a two-step human editing and validation phase aimed at ensuring youth-context realism. A multi-dimensional annotation covered influence presence, techniques, intentions, consequences, resistance, reactions, and annotation confidence. The dataset supports research on social influence detection, annotator disagreement, cross-lingual modeling, and the training and evaluation of language models. The dataset was created in Polish and is accompanied by a corresponding English version.

12.
arXiv (CS.AI) 2026-06-17

Towards Leveraging AutoML for Sustainable Deep Learning: A Multi-Objective HPO Approach on Deep Shift Neural Networks

arXiv:2404.01965v3 Announce Type: replace-cross Abstract: Deep Learning (DL) has advanced various fields by extracting complex patterns from large datasets. However, the computational demands of DL models pose environmental and resource challenges. Deep shift neural networks (DSNNs) offer a solution by leveraging shift operations to reduce computational complexity at inference. Following the insights from standard DNNs, we are interested in leveraging the full potential of DSNNs by means of AutoML techniques. We study the impact of hyperparameter optimization (HPO) to maximize DSNN performance while minimizing resource consumption. Since this combines multi-objective (MO) optimization with accuracy and energy consumption as potentially complementary objectives, we propose to combine state-of-the-art multi-fidelity (MF) HPO with multi-objective optimization. Experimental results demonstrate the effectiveness of our approach, resulting in models with over 80\% in accuracy and low computational cost. Overall, our method accelerates efficient model development while enabling sustainable AI applications.

13.
arXiv (CS.LG) 2026-06-19

Enhancing Graph Neural Networks Using Proximity Graphs for Dust Source Emission Forecasting

arXiv:2606.19825v1 Announce Type: new Abstract: Accurate prediction of dust source emissions is critical for mitigating the significant environmental and health hazards posed by dust storms. Traditional forecasting methods often struggle to capture the complex spatiotemporal dynamics of these phenomena. In this paper, we demonstrate that proximity graphs enable Graph Neural Networks (GNNs) to effectively model the intricate spatial and temporal relationships between data points. Specifically, we use proximity graphs–such as Delaunay triangulation, Gabriel graph, k-Nearest Neighbor graph, and Yao graph–as the input for GNNs (including GraphSAGE, Graph Convolutional Networks, and Graph Attention Networks) to perform message passing. Our approach highlights the effectiveness of integrating proximity graphs with GNNs for robust and accurate dust source forecasting. To emphasize the importance of proximity graph representations, we compare our method against GNNs using random graphs for message passing. The results show that GNNs with proximity graphs significantly outperform those with random graphs and are also far superior to Long Short-Term Memory (LSTM) model in dust source emission forecasting.

14.
arXiv (CS.CL) 2026-06-11

Cross-modal Consistency Guidance for Robust Emotion Control in Auto-Regressive TTS Models

While Text-to-Speech (TTS) systems enable emotional control via natural-language instructions, expressiveness, naturalness, and speech quality degrade when the target emotion conflicts with the textual semantics. We propose a Cross-modal Consistency Guided Classifier-Free Guidance (CCG-CFG) method with dynamic scales based on the degree of inconsistency between the text emotion and the explicit speech emotion, replacing the dropout condition with the text emotion. We also distill the CCG-CFG guidance signal using a hard-sample mining strategy, improving the TTS model's emotional alignment capability. Evaluations on five emotional corpora and two TTS benchmarks show that our approaches applied to CosyVoice2 achieve up to a 12% absolute improvement in emotion-recognition accuracy and a 10% relative improvement in subjective scores, outperforming baselines including HierSpeech++, Qwen3-TTS, and original CosyVoice2, while preserving intelligibility, naturalness, and high speech quality.

15.
arXiv (CS.CL) 2026-06-17

Position: Coding Benchmarks Are Misaligned with Agentic Software Engineering

Coding agents have become a major mode of software engineering, but the benchmarks we use to compare them were designed in a pre-agent era: they collapse model, harness, and environment into a single end-to-end score, typically computed against one reference solution, with no component-level signal for iteration. We argue that current coding benchmarks are misaligned with agentic software engineering. A coding agent in practice is not a model: it is a system harness – a composite of models, harnesses, contexts, environments, and feedback signals, any one of which can move the benchmark score by margins comparable to those between adjacent model generations. We discuss three symptoms: (i) benchmark scores conflate the model with the rest of the harness; (ii) grading against a single reference solution penalises equally valid alternatives; and (iii) the absence of signal at the level of individual harness components makes the end-to-end system score difficult to iterate on.

16.
arXiv (quant-ph) 2026-06-11

Exact Entanglement Dynamics Beyond Nearest-Neighbor Dual-Unitary Floquet Systems

作者:

arXiv:2606.11311v1 Announce Type: new Abstract: Exact results using dual-unitarity largely rely on nearest-neighbor structures, while finite-range interactions typically lead to complications. Going beyond the usual nearest-neighbor setting, we introduce an analytically tractable family of finite-range kicked Ising models that admit exact closed-form entanglement dynamics. The construction is based on a staggered structure in which dual-unitarity is present on sublattices that are then coupled to each other. The central observation is that these inter-sublattice couplings do not obstruct the dual-unitarity of the resulting model. For the minimal interaction range of $r= 2$, we derive exact expressions for all the $n-$Rényi entanglement entropies at all times and show that the result is the sum of the two coupled sublattice contributions. Our framework extends naturally to larger finite interaction ranges and to systems with heterogeneous local Hilbert spaces, without additional assumptions. It thus provides a controlled setting for studying exact entanglement growth beyond strictly nearest-neighbor dual-unitary models.

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

AnnotateAnything: Automatic Annotation of 3D Assets for Robot Manipulation

Simulation enables scalable robot data collection, but raw 3D assets provide only geometry, lacking the semantic, interactive, and physical knowledge needed to specify where and how robots should act. In this work, we present AnnotateAnything, a general automatic annotation framework that converts passive 3D assets into manipulation-ready assets with structured, diverse, and executable manipulation labels. AnnotateAnything is built around two complementary pipelines. First, a unified visual-language annotation pipeline using vision-language reasoning to infer object semantics, interaction constraints, and 3D-grounded cues, providing human-prior guidance for identifying meaningful interaction regions. Second, a fully automatic and massively parallel physics annotation pipeline grounds these priors in each asset's geometry and physical constraints through candidate generation, geometry optimization and trajectory generation. This pipeline produces diverse and executable action annotations, including grasp poses, dexterous contacts, articulation waypoints, insertion directions, hanging affordances, and navigation targets. Using the generated annotations, we further build an asynchronous parallel simulation data-collection system across diverse objects, tasks, and robot embodiments. Experiments demonstrate that AnnotateAnything achieves superior annotation efficiency, data-collection efficiency, and task success rates over existing annotation and data-generation pipelines, while also supporting downstream tasks such as affordance detection, robotic VQA, and visual instruction finetuning. We provide project materials on the project page and plan to release the full code, annotations, and benchmark to facilitate future research. Videos, code, demo assets, and annotations are provided in supplementary materials Project page: https://tourmaline-caramel-169490.netlify.app.

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

YTClickbait21K: Human-Annotated Multimodal Dataset for YouTube Clickbait Detection Across Diverse Channels and Content Categories

Clickbait content on video-sharing platforms poses a significant challenge to information reliability, yet progress in automated detection has been constrained by the lack of large-scale, high-quality multimodal datasets. We present YTClickbait21K, a human-annotated YouTube clickbait dataset comprising 21,238 videos collected from 40 channels across 29 countries, covering diverse content categories such as news, entertainment, education, and gaming. Each sample includes structured metadata (title, description, engagement statistics) along with associated thumbnail images, enabling comprehensive multimodal analysis. To ensure annotation quality, every video was independently labeled by three annotators using a standardized decision framework that incorporates textual, visual, and cross-modal consistency cues, with final labels determined through majority voting. The dataset exhibits substantial inter-annotator agreement (k=0.65), confirming reliable labeling despite the inherent subjectivity of clickbait detection. By combining scale, annotation rigor, and multimodal richness, this dataset provides a robust benchmark for developing and evaluating machine learning models, facilitating research in cross-modal semantic understanding, and advancing automated content moderation systems.

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

AudioX-Turbo: A Unified Framework for Efficient Anything-to-Audio Generation

Audio and music generation based on flexible multimodal control signals is a widely applicable topic, with the following key challenges: 1) a unified multimodal modeling framework, 2) large-scale, high-quality training data, and 3) the prohibitive inference cost of multi-step diffusion sampling. As such, we propose AudioX-Turbo, a unified and efficient framework for anything-to-audio generation that integrates varied multimodal conditions (i.e., text, video, and audio signals) in this work. AudioX-Turbo follows a teacher-student paradigm. The teacher AudioX-Base is built on a Multimodal Diffusion Transformer with a Multimodal Adaptive Fusion module that aligns diverse multimodal inputs for high-fidelity synthesis, and is then distilled into the few-step student AudioX-Turbo via Distribution Matching Distillation adapted to flow matching, complemented by a diffusion-based discriminator for high-quality few-step generation. To support the training of AudioX-Turbo, we construct a large-scale, high-quality dataset, IF-caps-Pro, comprising approximately 9.2M samples curated through a two-stage data collection and annotation pipeline. We benchmark AudioX-Turbo across a wide range of tasks, finding that our model achieves superior performance, especially on text-to-audio and text-to-music generation, while operating at only 4 sampling steps and requiring approximately 25x fewer function evaluations (NFE) than multi-step baselines. These results demonstrate that our method is capable of audio generation under flexible multimodal control, showing efficient and powerful instruction-following capabilities. The code and datasets will be available at https://zeyuet.github.io/AudioX-Turbo/.

20.
arXiv (CS.CV) 2026-06-17

UoU: A Universal Fingerprint Foundation Model Based on Large-Scale Unsupervised Learning

Fingerprint recognition is still dominated by task-specific pipelines, where enhancement, structural parsing, alignment, and matching are optimized in isolation. Although effective in narrow settings, this design limits representation reuse across sensors, qualities, and downstream applications. We therefore present UoU, short for ``a Universal fingerprint foundation model based on large-scale Unsupervised learning,'' which reframes fingerprint feature extraction as a domain-specific foundation-model problem. UoU is organized around a multi-level representation hierarchy spanning image restoration, structural fields, semantic tokens, point-level biometric entities, and compact global descriptors. Its training recipe combines a supervised cold start on precise annotations, large-scale weakly supervised refinement, and large-scale unsupervised consolidation, with the latter two stages iterated during large-scale training so that weak supervision broadens semantic coverage while unsupervised learning stabilizes correspondences, invariances, and representation geometry. Rather than treating fingerprint imagery as generic texture, UoU exploits domain-specific symmetries and intermediate structure, including orientation flow, periodic ridge patterns, sparse biometric entities, and spatial equivariance. The framework is intentionally architecture-agnostic: while the present study includes an initial transformer-based structured-prediction instantiation, the broader design supports multi-task learning, scalable model configurations, and downstream specialization for matching, alignment, enhancement, registration, and related fingerprint applications. This paper presents the technical motivation, system design, and validation protocol of UoU, and part of the baseline implementation is publicly available at https://github.com/XiongjunGuan/UoU.

21.
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).

22.
arXiv (CS.CV) 2026-06-15

Optimizing Rank for High-Fidelity Implicit Neural Representations

Implicit Neural Representations (INRs) based on vanilla Multi-Layer Perceptrons (MLPs) are widely believed to be incapable of representing high-frequency content. This has directed research efforts towards architectural interventions, such as coordinate embeddings or specialized activation functions, to represent high-frequency signals. In this paper, we challenge the notion that the low-frequency bias of vanilla MLPs is an intrinsic, architectural limitation to learn high-frequency content, but instead a symptom of stable rank degradation during training. We empirically demonstrate that regulating the network's rank during training substantially improves the fidelity of the learned signal, rendering even simple MLP architectures expressive. Extensive experiments show that using optimizers like Muon, with high-rank, near-orthogonal updates, consistently enhances INR architectures even beyond simple ReLU MLPs. These substantial improvements hold across a diverse range of domains, including natural and medical images and novel view synthesis, with up to +9 dB PSNR over the same architecture. Code is available at (https://rank-inrs.github.io).

23.
arXiv (CS.CV) 2026-06-15

Explaining RhythmFormer: A Systematic XAI Analysis of Periodic Sparse Attention for Remote Photoplethysmography

Remote photoplethysmography (rPPG) transformers achieve low heart-rate error on benchmarks, yet their decisions remain opaque–a growing concern as rPPG moves toward clinical heart rate estimation. Existing rPPG XAI is dominated by qualitative heatmap inspection without quantitative faithfulness metrics or physiology-grounded validation, leaving a gap between visual plausibility and auditable evidence. We address this gap. First, we adapt four attribution methods (raw attention, rollout, flow, Beyond Intuition) to RhythmFormer's bi-level routing attention with top-$k$ selection. Second, we introduce a skin coverage metric quantifying how much attribution mass falls on skin regions. Third, we adapt the SaCo faithfulness coefficient from its original classification setting to rPPG regression by using the MAE between original and perturbed predicted rPPG waveforms as the perturbation impact. Applying these tools, we quantify a multi-hop leakage effect under sparse top-$k$ routing: attention rollout and flow almost completely restores the connections that individual refined-attention layers explicitly set to zero. Beyond Intuition mitigates this via its value-projection-weighted rollout and gradient-supported mask, attaining the highest median refined skin coverage ($0.83$ vs. $0.57$ for vanilla rollout) and faithfulness ($F=0.92$) among the evaluated methods on UBFC-rPPG. Validation across diverse datasets and model variants is needed. A case study on a low-SaCo outlier further shows all four methods recovering consistently once an artefactual region is replaced, suggesting consistent SaCo behavior across attribution families in this illustrative case. Together, these metrics move XAI for rPPG toward auditable numerical evidence about spatial alignment and perturbation faithfulness, i.e. trustworthy rPPG XAI.

24.
bioRxiv (Bioinfo) 2026-06-19

HTS-Oracle v2: Prospective AI-Guided Discovery and Experimental Validation of Small Molecule Modulators Across Multiple Targets

High-throughput screening (HTS) remains the cornerstone of early-phase small molecule discovery yet consistently underperforms against immunotherapy targets, yielding validated hit rates below 0.1%. Here we introduce HTS-Oracle v2, which features rigorous cross-validation that ensures honest performance estimates. HTS-Oracle v2 was trained and validated across four clinically significant immune checkpoint targets (CD28, ICOS, LAG-3, and TIGIT) achieving ROC-AUC values of 0.968, 0.969, 0.875, 0.928 respectively under rigorous cross-validation. For prospective experimental validation, HTS-Oracle v2 was applied to an 8,960-compound Enamine Protein Mimetic Library, selecting only 25 compounds per target for experimental testing using temperature-related intensity change (TRIC) technology, a 99.7% reduction in screening burden. HTS-Oracle v2 identified 4, 5, 4, and 6 validated binders from 25 prospectively selected compounds per target, corresponding to validated hit rates of 16%, 20%, 16%, and 24%, respectively. Notably, 67-80% of all experimentally confirmed hits across the full 8,960-compound library were captured within just 25 model-selected compounds per target. For CD28, this represents a 28-fold improvement over HTS-Oracle v1 (239x versus 8.4x), establishing HTS-Oracle v2 as an efficient platform for AI-guided prospective hit discovery across immunotherapy targets.

25.
arXiv (CS.CL) 2026-06-19

Omnilingual SONAR: Cross-Lingual and Cross-Modal Sentence Embeddings Bridging Massively Multilingual Text and Speech

Cross-lingual sentence encoders typically cover only a few hundred languages and often trade downstream quality for stronger alignment, limiting their adoption. We introduce OmniSONAR, a new family of omnilingual, cross-lingual and cross-modal sentence embedding models that natively embed text, speech, code, and mathematical expressions in a single semantic space, while delivering state-of-the-art downstream performance at the scale of thousands of languages, from high-resource to extremely low-resource varieties. To reach this scale without representation collapse, we use progressive training. We first learn a strong foundational space for 200 languages with an LLM-initialized encoder-decoder, combining token-level decoding with a novel split-softmax contrastive loss and synthetic hard negatives. Building on this foundation, we expand to several thousands language varieties via a two-stage teacher-student encoder distillation framework. Finally, we demonstrate the cross-modal extensibility of this space by seamlessly mapping 177 spoken languages into it. OmniSONAR halves cross-lingual similarity search error on the 200-language FLORES dataset and reduces error by a factor of 15 on the 1,560-language BIBLE benchmark. It also enables strong translation, outperforming NLLB-3B on multilingual benchmarks and exceeding prior models (including much larger LLMs) by 15 chrF++ points on 1,560 languages into English BIBLE translation. OmniSONAR also performs strongly on MTEB and XLCoST. For speech, OmniSONAR achieves a 43% lower similarity-search error and reaches 97% of SeamlessM4T speech-to-text quality, despite being zero-shot for translation (trained only on ASR data). Finally, by training an encoder-decoder LM, Spectrum, exclusively on English text processing OmniSONAR embedding sequences, we unlock high-performance transfer to thousands of languages and speech for complex downstream tasks.