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01.

medRxiv (Medicine) 2026-06-19 DOI: HASH:4141ee1023eaceb3a37126d8db8b14a0

Rumination as a cognitive vulnerability factor in perinatal bereavement: evidence from the CARING study

作者:

Ravaldi↗Mosconi↗Raduzzi↗Olmi↗Neri↗Cocchi↗Vannacci↗

Purpose. Perinatal loss is associated with a high risk of persistent psychological distress, including prolonged grief, depression, anxiety, and post-traumatic stress symptoms. Cognitive processes such as rumination may play a crucial role in maintaining and amplifying distress following loss, yet their specific contribution in perinatal bereavement remains underexplored. Methods. The CARING (Cognitive Analysis and Rumination INvestigation in perinatal Grief) study employed a cross-sectional design involving 298 parents who experienced perinatal loss within the previous five years. Participants completed an anonymous online survey including measures of depressive rumination (Ruminative Response Scale, RRS), angry rumination (Anger Rumination Scale, ARS), perinatal grief (Perinatal Grief Scale, PGS), general psychopathology (SCL-90), and post-traumatic stress symptoms (NSESSS). Non-parametric analyses were conducted to examine associations between rumination patterns and psychological outcomes. Results. Higher levels of rumination were significantly associated with greater perinatal grief, depressive and anxiety symptoms, and post-traumatic stress. Depressive rumination showed consistently stronger associations with all outcomes compared to angry rumination. Participants presenting both depressive and angry rumination exhibited the highest levels of grief intensity, psychological distress, and PTSD symptoms, suggesting a graded relationship between rumination patterns and severity of distress. Rumination levels were not significantly associated with gestational age at loss or with having received psychological support. Conclusions. Rumination, particularly in its depressive form, appears to function as a transdiagnostic cognitive vulnerability factor in perinatal bereavement. These findings highlight rumination as a potential target for early screening and tailored psychological interventions aimed at reducing long-term distress following perinatal loss.

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02.

arXiv (CS.CV) 2026-06-19 DOI: arXiv:2606.20488

How Fragile Are Training-Free AI-Generated Image Detectors? A Controlled Audit of Score Direction, Preprocessing, and Compression

作者:

Jingwen Zhou↗Mingzhe Wang↗

Training-free detectors of AI-generated images promise generator-agnostic deployment without classifier training, yet their reported numbers are rarely compared under a single controlled protocol. We audit two representative training-free scores – an autoencoder-reconstruction score (AEROBLADE-style) and a noise-perturbation feature-similarity score (RIGID-style) – plus a naive feature-kNN control, on a common 1,500-image GenImage-derived benchmark spanning seven generators and JPEG compression at quality 70 and 50. The audit yields three cautionary findings. (i) Implementation details masquerade as method differences: replacing the LPIPS backbone (AlexNet -> VGG-16) changes overall AUROC by +0.085, and switching between resize-to-512 and native-resolution preprocessing flips per-generator conclusions by up to 0.38 AUROC. (ii) Score direction is not a property of the method but of its hyperparameters: the RIGID-style score is inverted (AUROC < 0.5) on SD1.5 and Wukong at noise level sigma=0.05, recovers to >0.5 for every generator at sigma=0.01, and collapses to 0.15 at sigma=0.3. (iii) Dataset format bias inflates robustness claims: without unified re-encoding, AUROC under JPEG-50 exceeds the clean condition for the AlexNet-backbone reconstruction score; after bias correction the residual anomaly localizes to a single generator (BigGAN). The audited scores have complementary per-generator failure sets, but naive z-score fusion does not beat the best single score, indicating that exploiting complementarity requires direction-aware combination.

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03.

arXiv (CS.AI) 2026-06-12 DOI: arXiv:2601.00921

Geometric and Quantum Kernel Methods for Predicting Skeletal Muscle Outcomes in chronic obstructive pulmonary disease

作者:

Azadeh Alavi↗Hamidreza Khalili↗Stanley H. Chan↗Fatemeh Kouchmeshki↗Muhammad Usman↗Ross Vlahos↗

arXiv:2601.00921v3 Announce Type: replace-cross Abstract: Chronic obstructive pulmonary disease (COPD) affects hundreds of millions of people worldwide, and skeletal-muscle dysfunction is clinically important. Quantum machine learning is increasingly explored for biomedical prediction, but its value in small biomarker cohorts requires benchmarking against strong classical baselines. We analysed a cigarette-smoke COPD cohort of 213 animals with blood and bronchoalveolar-lavage biomarkers to predict tibialis anterior muscle weight, muscle quality, and force. We developed a kernel-geometric quantum hybrid method in which synthetic symmetric positive definite (SPD) references are mapped through a reproducing kernel Hilbert space, compressed using train-only random projection, normalised, and supplied to low-dimensional quantum regression circuits. We benchmarked this approach against classical ridge/kernel models, SPD relational representations, and quantum-kernel regression (QKR). All methods were evaluated using condition-stratified repeated cross-validation. The largest numerical improvement was observed for muscle weight, where the proposed method had the numerically lowest mean root mean squared error (RMSE), approximately 1.8% below the best classical comparator; paired fold-level testing did not establish statistically significant superiority after Holm adjustment, but the endpoint is biologically meaningful. The method also had the numerically lowest mean RMSE for muscle quality. For force, biomarker-only Ridge performed best, suggesting a more linear endpoint structure.

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04.

bioRxiv (Bioinfo) 2026-06-11 DOI: HASH:f4d4106092322fb96fbad9f8a1c95e90

GermRL: Alleviating The Germline Bias In Autoregressive Antibody Language Models Through Reinforcement Learning

作者:

Ludwig↗Chungyoun↗Gray↗J. J↗

Antibodies are powerful therapeutics whose antigen specificity arises from sequence diversity shaped during development. Recently, language models trained on large antibody repertoire datasets have enabled the generation and screening of novel candidates, but these models retain a strong germline bias. As AI adoption increases in therapeutic workflows, it is crucial to develop models that harness the diversity of antibodies necessary for the discovery of mutations that encode desirable properties. Previous work explored the germline bias in masked antibody language models, yet the bias in generative autoregressive language models has not yet been addressed. Here, we present GermRL, a lightweight and modular reinforcement learning (RL) framework capable of alleviating the germline bias in pre-trained antibody autoregressive language models through group relative policy optimization (GRPO). GermRL achieves consistent one-shot generation of antibodies that satisfy specified mutation thresholds from germline while maintaining structural plausibility. Under the lowest and highest mutation thresholds tested (5 and 35 mutations from germline), GermRL scores 0.992 and 0.950 pass@1, respectively, compared to 0.398 and 0.034 for the pre-trained language model. Within GermRL, we introduce a key pair of modifications to GRPO that increase training efficiency by discouraging reward hacking under our antibody application. Furthermore, comparison of RL generated and natural antibody sequences reveals how RL based optimization can explore alternative evolutionary mutational patterns and residue compositional strategies while preserving key global properties of natural antibodies, including identifiable germline assignments, embedding-level similarity and comparable developability profiles. Thus, RL-trained generative models optimized to promote antibody mutations through diversity from germline provide a promising framework for navigating the antibody sequence landscape, enabling exploration of novel yet biologically plausible candidates for therapeutic design.

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05.

arXiv (CS.LG) 2026-06-17 DOI: arXiv:2606.17603

Expanding SPHERE-JEPA: A Family of Statistical Regularizers for the Hypersphere

作者:

L\'eo Nicollier↗Enric Meinhardt-Llopis↗Max Dunitz↗Marc Pic↗Pablo Mus\'e↗Gabriele Facciolo↗

arXiv:2606.17603v1 Announce Type: new Abstract: In Self-Supervised Learning (SSL), preventing representation collapse by explicitly enforcing a uniform distribution on the unit hypersphere has proven to be effective. However, current frameworks typically rely on sliced statistical regularizers such as SIGReg (used in LeJEPA) and SUSReg (used in SPHERE-JEPA), which approximate this continuous objective via Monte Carlo sampling along random 1D directions. This stochasticity injects projection variance into the training gradients, destabilizing optimization, and hindering convergence. In this work, we first show that analytically integrating out these random projections natively yields a deterministic Maximum Mean Discrepancy (MMD), bypassing the variance of sliced methods. Motivated by this equivalence, we formulate full-dimensional objectives for MMD, Kernel Stein Discrepancy (KSD), and Kullback-Leibler (KL) divergence directly on the sphere to enforce a uniform distribution. To prevent spatial bias, we equip these tests with rotationally invariant kernels constructed via spectral theory, systematically evaluating two canonical families: smooth exponential decay (Heat) and strict frequency cutoff (Bandlimited) filters. Empirically, removing projection-induced noise results in more stable optimization, faster convergence, and consistent improvements over stochastic sliced regularizers on ImageNet and Galaxy10. Furthermore, we reveal that the choice of the statistical test shapes the geometry of the learned latent space: MMD and KSD favor locally clustered organization suitable for object-centric domains, whereas the continuous KDE-based KL divergence promotes fine-grained instance separation, yielding the strongest results on unclustered procedural texture retrieval.

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06.

arXiv (CS.LG) 2026-06-17 DOI: arXiv:2606.17445

Toward Controllable Catalyst Inverse Design via Large-Scale Autoregressive Pretraining

作者:

Dong Hyeon Mok↗Jonggeol Na↗Seoin Back↗

arXiv:2606.17445v1 Announce Type: new Abstract: Inverse design of heterogeneous catalysts remains challenging because catalyst surfaces exhibit substantial structural complexity with coupled surface-adsorbate interactions across a vast chemical space that is difficult to explore efficiently through conventional screening alone. Although machine learning-based high-throughput screening has accelerated catalyst discovery, its efficiency inevitably declines as the search space grows, motivating the development of generative models that can directly construct catalysts with target properties. Here, we present a conditional catalyst generative model based on the Generative Pretrained Transformer architecture with a numerical embedding layer that enables the generation of catalyst structures conditioned on both categorical and continuous properties within a single autoregressive framework. The model was pretrained on 133 million catalyst structures and subsequently fine-tuned on approximately 460,000 optimized structures with associated categorical properties and binding energies for conditional generation. The resulting model achieved 98% structural validity, 95% optimization validity, and high categorical condition fidelity, with a 93 % joint match rate for adsorbate type and composition. For binding energy conditioning, the match rate of approximately 20% represents a four-fold improvement over the baseline training distribution, and the generated distributions shift systematically toward the target values, enabling a 1.5 to 4-fold improvement in screening efficiency for reaction-targeted catalyst discovery without additional fine-tuning. These results show that large-scale autoregressive pre-training, combined with explicit property conditioning, provides a practical route toward controllable catalyst generation and accelerated catalysts discovery.

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07.

arXiv (CS.CV) 2026-06-17 DOI: arXiv:2506.24121

TextMesh4D: Zero-shot Text-to-4D Mesh Generation

作者:

Sisi Dai↗Xinxin Su↗Kai Xu↗

Large-scale, high-quality dynamic 3D (4D) assets are essential for learning physically grounded representations, but remain costly to capture and annotate at scale. This limits the viability of supervised 4D learning and motivates zero-shot text-to-4D generation leveraging pretrained diffusion priors. To model complex dynamics, prior methods typically adopt implicit 3D representations (e.g., NeRFs or 3DGS) for their deformation capacity. However, their implicit nature provides limited control over surface topology, which hinders high-fidelity geometry and makes temporally coherent surface reconstruction challenging. To address these limitations, we explore zero-shot text-to-4D mesh generation. However, a structural mismatch arises when combining diffusion-based guidance with topology-constrained meshes: the guidance is noisy and spatially inconsistent, while meshes impose severe topological constraints, making direct vertex-level deformation unstable. In this paper, we introduce TextMesh4D, the first zero-shot framework for text-to-4D that directly generates dynamic meshes by addressing the above challenge at two complementary levels. Geometrically, we shift deformation modeling from vertices to faces via a Jacobian Deformation Field (JDF), enabling topology-aware surface reconstruction through an integrability-enforcing integration formulation. Semantically, we propose a Local-Global Semantic Regularizer (LGSR) that preserves identity over time by jointly constraining local deformation plausibility and global shape consistency. Extensive experiments demonstrate state-of-the-art temporal consistency, structural fidelity, and visual quality, while remaining efficient on a single 24GB GPU.

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08.

arXiv (CS.CV) 2026-06-18 DOI: arXiv:2606.19341

Native Active Perception as Reasoning for Omni-Modal Understanding

作者:

Zhenghao Xing↗Ruiyang Xu↗Yuxuan Wang↗Jinzheng He↗Ziyang Ma↗Qize Yang↗Yunfei Chu↗Jin Xu↗Junyang Lin↗Chi-Wing Fu↗Pheng-Ann Heng↗

Passive models for long video understanding typically rely on a "watch-it-all" paradigm, processing frames uniformly regardless of query difficulty, causing computational cost to grow with video duration. Although interactive frameworks have emerged, they often rely on global pre-scanning, and their context cost still scales with video length. We propose OmniAgent, the first native omni-modal agent that formulates video understanding as a POMDP-based iterative Observation-Thought-Action cycle. OmniAgent executes on-demand actions to selectively distill audio-visual cues into a persistent textual memory, effectively decoupling reasoning complexity from raw video duration. To operationalize this, we introduce (1) Agentic Supervised Fine-Tuning to bootstrap native active perception via best-of-N trajectory synthesis with dual-stage quality control, and (2) Agentic Reinforcement Learning with TAURA (Turn-aware Adaptive Uncertainty Rescaled Advantage), which leverages turn-level entropy to steer credit assignment toward pivotal discovery turns. Crucially, OmniAgent exhibits positive test-time scaling, where performance improves as the number of reasoning turns increases, validating the efficacy of active perception. Empirical results across ten benchmarks (e.g., VideoMME, LVBench) demonstrate that OmniAgent achieves state-of-the-art performance among open-source models. Notably, on LVBench, our 7B agent outperforms the 10$\times$ larger Qwen2.5-VL-72B (50.5% vs. 47.3%).

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09.

arXiv (CS.LG) 2026-06-19 DOI: arXiv:2606.19363

When to Trust, How to Distill: Multi-Foundation Model Guidance for Lightweight, Robust Scientific Time Series Forecasting

作者:

Rupasree Dey↗Abdul Matin↗Nathan Orwick↗Yao Zhang↗Shrideep Pallickara↗Sangmi Lee Pallickara↗

arXiv:2606.19363v1 Announce Type: new Abstract: The deployment of Time-Series Foundation Models (TSFMs) in physical sciences is hindered by a critical trade-off: while these models encode rich, universal temporal dynamics, they suffer from severe distributional misalignment when applied zero-shot to specific scientific domains, and their computational cost prohibits deployment in edge-computing sensor networks. We address a fundamental challenge: How can we extract latent structural knowledge from misaligned foundation models (FM) to train lightweight, specialized forecasters? We propose Gated Uncertainty-Aware Routing for Distillation (Guard), a novel framework that reframes multiteacher distillation as an instance-wise decision process with two adaptive mechanisms: (1) a Contextual Router that dynamically selects the most relevant teacher based on local input statistics, exploiting complementarity across diverse foundation models; and (2) an Uncertainty-Gated Temperature mechanism that acts as a "circuit-breaker," automatically attenuating distillation strength when teacher confidence diverges from domain reality. We evaluate our proposed lightweight framework on four climate-critical domains: meteorology, ecosystem carbon flux, soil moisture, and energy grids. Our method significantly reduces RMSE relative to a fixed-weight multi-teacher distillation baseline, successfully distilling knowledge from pretrained FMs (teachers) even when they exhibit suboptimal zero-shot accuracy due to distribution shift between the original and target data domains. We demonstrate that these domain-misaligned teachers can still serve as critical correctives, outperforming the globally superior FMs on 28.5% of the hardest instances. Ultimately, this enables high-precision scientific forecasting suitable for resource-constrained edge deployment. Code is available at https://github.com/RupasreeDey/GUARD-KDD2026.

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10.

arXiv (CS.CV) 2026-06-17 DOI: arXiv:2606.18208

Looped World Models

作者:

Hongyuan Adam Lu↗Z. L. Victor Wei↗Qun Zhang↗Jinrui Zeng↗Bowen Cao↗Lingwei Meng↗Mocheng Li↗Zezhong Wang↗Haonan Yin↗Naifu Xue↗Minyu Chen↗Cenyuan Zhang↗…

Current world models face a fundamental tension: faithful long-horizon simulation demands deep computation, but deeper models are expensive to deploy and prone to compounding errors. We resolve this by introducing Looped World Models (LoopWM), which are the first looped architectures for world modelling. Our method iteratively refines latent environment states through a parameter-shared transformer block. This yield up to 100x parameter efficiency over conventional approaches with adaptive computation that automatically scales depth to match the complexity of each prediction step. Orthogonal to scaling model size and training data, LoopWM establishes iterative latent depth as a new scaling axis for world simulation, which might significantly push the community forward.

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11.

arXiv (quant-ph) 2026-06-11 DOI: arXiv:2606.12297

A post-selected quantum model of cosmic acceleration

作者:

Dimitris Lionas↗Charis Anastopoulos↗Konstantinos Gourgouliatos↗

arXiv:2606.12297v1 Announce Type: cross Abstract: The origin of cosmic acceleration remains a central problem in cosmology, commonly attributed to a cosmological constant within the $\Lambda$CDM model or to dynamical dark energy. Here, we develop an alternative approach in which acceleration emerges from quantum post-selection, a standard feature of quantum theory that is not usually incorporated into cosmological modelling. While quantum theory admits both pre-selected and post-selected ensembles, quantum cosmological models are almost exclusively formulated in terms of initial conditions. Building on previous work on post-selected quasiclassical dynamics, we construct a minimal predictive cosmological model in which post-selection and coarse-graining generate effective late-time acceleration without introducing a cosmological constant, dark energy, or modifications of general relativity. The resulting expansion history is highly constrained theoretically and depends on at most two parameters beyond standard Friedmann evolution. Confrontation with type Ia supernova and cosmic chronometer data yields statistically competitive fits while naturally avoiding the coincidence problem. The model also reproduces the standard radiation- and matter-dominated behaviour at early times and predicts a present-day jerk parameter significantly different from the $\Lambda$CDM value. These results suggest that cosmic acceleration may arise as a macroscopic quantum cosmological effect rather than from additional cosmological fluids or modified gravitational dynamics.

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12.

arXiv (CS.CV) 2026-06-18 DOI: arXiv:2512.09185

Learning Patient-Specific Disease Dynamics with Latent Flow Matching for Longitudinal Imaging Generation

作者:

Hao Chen↗Rui Yin↗Yifan Chen↗Qi Chen↗Chao Li↗

Understanding disease progression is a central clinical challenge with direct implications for early diagnosis and personalized treatment. While recent generative approaches have attempted to model progression, key mismatches remain: disease dynamics are inherently continuous and monotonic, yet latent representations are often scattered, lacking semantic structure, and diffusion-based models disrupt continuity with random denoising process. In this work, we propose to treat the disease dynamic as a velocity field and leverage Flow Matching (FM) to align the temporal evolution of patient data. Unlike prior methods, it captures the intrinsic dynamic of disease, making the progression more interpretable. However, a key challenge remains: in latent space, Auto-Encoders (AEs) do not guarantee alignment across patients or correlation with clinical-severity indicators (e.g., age and disease conditions). To address this, we propose to learn patient-specific latent alignment, which enforces patient trajectories to lie along a specific axis, with magnitude increasing monotonically with disease severity. This leads to a consistent and semantically meaningful latent space. Together, we present $\Delta$-LFM, a framework for modeling patient-specific latent progression with flow matching. Across three longitudinal MRI benchmarks, $\Delta$-LFM demonstrates strong empirical performance and, more importantly, offers a new framework for interpreting and visualizing disease dynamics.

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13.

arXiv (CS.AI) 2026-06-15 DOI: arXiv:2606.14210

From Prompts to Responses: Dual-Sided Data Leakage and Defense in Split Large Language Models

作者:

Zixuan Gu↗Xiaojun Ye↗Yang Liu↗

arXiv:2606.14210v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly deployed in privacy-sensitive domains, where users must balance the risk of data exposure through external APIs against the high computational cost of local deployment. Split learning has therefore emerged as a promising paradigm for LLM fine-tuning and inference under limited local resources. However, it introduces new privacy risks. Prior work primarily studies leakage of private input prompts, typically via inversion attacks on intermediate representations, while the potential for sensitive information leakage through generative response outputs remains largely unexplored. In this work, we unveil novel vulnerabilities of Split-LLM by presenting Patched Model Inversion with Dual-Sided Initialization (PIDI), a two-stage attack that simultaneously targets both private input prompts and output responses in Split-LLM settings. It combines dual-sided initialization with a patched inversion strategy to tackle long sequences, substantially outperforming prior inversion methods. To counter threats from both sides, we further propose the Adapter-based DualGuard with Mutual Information Defense (ADMI), which integrates an adapter-based local warmup strategy and mutual information regularization to provide a strong empirical privacy protection with minimal impact on task performance. Extensive experiments across diverse tasks and models demonstrate that ADMI effectively defends against PIDI and other state-of-the-art inversion attacks. Our code is publicly available at https://github.com/FLAIR-THU/VFLAIR-LLM.

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14.

arXiv (CS.CL) 2026-06-11 DOI: arXiv:2606.11766

Fast Speech Foundation Model Distillation Using Interleaved Stacking

作者:

Eungbeom Kim↗Kyogu Lee↗

Distilling a large speech foundation model (SFM) into an efficient student model has been successfully applied to low-resource environments. Although distillation reduces inference latency, it requires an additional student model training. However, the training efficiency of SFM distillation remains underexplored. In this work, we explore training acceleration of SFM distillation to speed up model deployment. We examine the potential of stacking, in which the model depth is progressively increased through training until the target model depth is reached. While existing stacking methods improve training speed, they suffer from performance degradation. To handle this limitation, we propose interleaved stacking, a novel stacking method that consistently preserves layer position throughout the stacking process. This property is particularly critical in SFMs, in which each layer encodes distinct layer-specific knowledge. We validate the effectiveness of the proposed method on SUPERB.

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15.

Nature Biotechnology 2026-06-05 DOI: HASH:3e73bcac3de442b75c61148ec9479e32

Multiplexed, precise genome engineering in monocots with twin prime editing systems

作者:

Hongchao Li↗

Simultaneously introducing diverse genomic edits remains a challenge in crop genome engineering. Here we describe a twin prime editing-based knockout (TKO) system that installs stop codon clusters (SCCs) for precise translational termination with minimal in-frame mutations. TKO achieves knockout efficiencies of up to 70.5%, 58.6% and 75.1% in rice, maize and wheat protoplasts, respectively, and produces heritable knockout alleles in 96.8% of regenerated rice plants. In hexaploid wheat, TKO outperforms Cas9 4.2-fold in generating triple-homolog knockouts, largely by reducing in-frame mutations. Orthogonal TKO editors with sequence-divergent SCCs enable simultaneous knockout of up to ten genes without cross-interference. Integration of TKO with conventional prime editing establishes TRIM1 (TKO editor-enabled gene rupture and development of integrated multitype genome modification system) for simultaneous knockout and precise editing, achieving a 22.8% coediting of four genes in rice. TRIM2 extends this capacity to kilobase-scale modifications through a prime editor–recombinase system, enabling a 4.9-kb insertion (1.2% efficiency) and gene knockout (up to 79.8%) in protoplasts. Plant genome editing is multiplexed with twin prime editing.

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16.

bioRxiv (Bioinfo) 2026-06-14 DOI: HASH:af0d08b0eefa74a7ba6367fc17594a0f

Transposable elements as evolutionary substrates of proteindisorder in the human proteome

作者:

Mac Donagh↗Vergesio↗Aguilar↗Nores↗Lagares↗Fornasari↗M. S↗Parisi↗

Intrinsically disordered regions (IDRs) are central contributors to protein function, evolution and human disease, yet the evolutionary routes that seed new disordered segments within pre-existing proteins are still poorly understood. Sequence insertions provide a powerful mechanism for disorder expansion, but the genomic donors of inserted IDR and its long-term conformational fate remain largely unknown. Transposable elements (TEs), abundant mobile genetic elements with distinctive compositional biases, represent compelling candidates for generating disorder within proteins. Here, we systematically mapped TE-derived segments across human proteins and isoforms, and we found that these insertions are strongly enriched in intrinsic disorder. The structural consequences of their insertion are shaped by TE class and family, reflecting the sequence biases of the elements from which they originate. Recent, Primate specific insertions preferentially generate disordered segments, whereas older insertions more frequently occupy ordered structural contexts, revealing an age-dependent transition in the conformational state of TE-derived sequences. TE-containing isoforms are expressed at lower levels than TE-free isoforms, particularly when insertions are young and disorder-rich, suggesting that intrinsic disorder may constrain the cellular tolerance of newly exonized sequences. These findings identify TEs as a major evolutionary mechanism linking genome mobility to the emergence of new disordered conformational ensembles in the human proteome.

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17.

medRxiv (Medicine) 2026-06-15 DOI: HASH:59c5937aaae90c7532317152b28ab35a

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

作者:

ElSherif↗M. S↗Redden↗K. L↗Langley↗J. M↗Ye↗Blanchard↗Smith↗Wang↗Abu-Raya↗Filliter↗…

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).

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18.

arXiv (CS.LG) 2026-06-19 DOI: arXiv:2606.20416

On the Redundancy of Timestep Embeddings in Diffusion Models

作者:

Jos\'e A. Ch\'avez↗

arXiv:2606.20416v1 Announce Type: new Abstract: Diffusion models rely heavily on explicit timestep embeddings to modulate the denoising process across various noise scales. In this work, we challenge the necessity of these temporal signals by analyzing their impact on U-Net and Diffusion Transformer architectures. Beyond empirical evidence, we provide a theoretical framework demonstrating that, under certain conditions, the global minimizer of the diffusion training objective can be achieved without explicit timestep conditioning. Our findings reveal a surprising robustness when timestep embeddings are completely removed. Extensive ablation studies on the CelebA and CIFAR-10 datasets show that these time-agnostic models can maintain high structural fidelity and even surpass their conditioned counterparts in competitive metrics, including FID, precision, and recall. Our analysis suggests these architectures can implicitly infer noise scales from the corrupted input under specific assumptions, rendering explicit temporal conditioning redundant. This study challenges long-standing temporal conditioning paradigms and paves the way for more efficient and structurally focused generative architectures.

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19.

arXiv (CS.CV) 2026-06-18 DOI: arXiv:2606.19053

Benchmarking Large Vision-Language Models on Fine-Grained Image Tasks: From Evaluation to Diagnosis

作者:

Hong-Tao Yu↗Chen-Wei Xie↗Yuxin Peng↗Serge Belongie↗Xiu-Shen Wei↗

Recent advancements in Large Vision-Language Models (LVLMs) have demonstrated remarkable multimodal perception and reasoning capabilities. While numerous benchmarks have evaluated LVLMs from holistic or task-specific perspectives, their capabilities on fine-grained image tasks-fundamental to computer vision-remain insufficiently understood. To address this gap, we introduce FG-BMK, a comprehensive fine-grained evaluation benchmark containing 1.01 million questions and 0.28 million images, covering diverse scenarios from common object-centric domains to specialized domains. FG-BMK jointly evaluates dialogue-level fine-grained semantic recognition and feature-level visual discriminability through human-oriented and machine-oriented paradigms, enabling diagnostic analysis of whether LVLM failures arise from insufficient visual representations, weak visual-to-semantic grounding, or limited fine-grained knowledge. Through extensive experiments on a diverse set of representative LVLMs/VLMs, we find that current LVLMs remain inadequate fine-grained recognizers, with failures arising from intertwined bottlenecks in visual representations, semantic grounding, modality alignment, and category-level knowledge. We further analyze training design factors for improving fine-grained capabilities and examine how visual and linguistic perturbations affect LVLM predictions. These findings provide diagnostic insights into the limitations of current LVLMs and offer guidance for future data construction and model design in developing more reliable LVLMs for fine-grained visual tasks. Our code is open-source and available at https://fg-bmk.github.io/.

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20.

arXiv (CS.CL) 2026-06-12 DOI: arXiv:2606.13507

Leveraging Audio-LLMs to Filter Speech-to-Speech Training Data

作者:

Qixu Chen↗Satoshi Nakamura↗

Large-scale mined corpora provide abundant training data for end-to-end speech-to-speech translation (S2ST) but may contain noise, misalignment, and semantic errors. Filtering noisy data is crucial to maintain robust speech translation performance. We study how to train an audio-language model to make keep/drop decisions on paired speech directly from audio. To obtain reliable supervision without manual labels, we adopt a scalable two-stage Rank-to-Distill strategy. A lightweight ranker generates keep/drop pseudo-labels from noisy speech pairs, then trains an audio large language model to predict keep/drop directly from raw paired speech. The resulting model jointly captures acoustic fidelity and cross-lingual semantic consistency for the selection of speech-conditioned data. Experiments on CVSS-C and SpeechMatrix show consistent improvements over unfiltered training, yielding up to +1.4 ASR-BLEU for end-to-end S2ST.

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21.

Nature (Science) 2026-06-10 DOI: HASH:4fbb7cb6e335b78a92704d7eb1f1509e

Diverse binding poses of agonistic neurotoxins on human Na_v1.6

作者:

Xiao Fan↗

Voltage-gated sodium (Nav) channels are key targets of various venomous toxins. Deciphering the binding poses and mechanisms of action of representative toxins will help to dissect the functional mechanism of the channels and facilitate therapeutic development targeting Nav channels1,2. Here we present cryo-electron microscopy&nbsp;(cryo-EM) structures of distinct binding poses of three agonistic peptide toxins on the human Nav1.6–β1 channel complex. The globular β-scorpion toxin Cn2 nestles between the extracellular segment of voltage-sensing domain (VSD)&nbsp;in the second repeat of the Nav1.6 core α-unit (VSDII) and the pore extracellular loops in the third repeat of the Nav1.6 core α-unit (ECLIII), where it is stabilized by interactions with both protein regions and the branched N1372-glycan. Cone&nbsp;snail ι-conotoxin RXIA adopts an elongated conformation, spanning VSDI and VSDIV to wrap around the shoulder of the pore domain (PD). The bullet&nbsp;ant-derived toxin δ-paraponeritoxin-Pc1a exists as a transmembrane helix that stands between VSDII and PDIII. Our findings, corroborated by functional characterizations, illustrate the diversity in peptide toxin binding poses and mechanisms of action, link stabilization of the up state of VSDI or VSDII to channel activation, and provide clues to the rational design of selective Nav channel modulators. Structures of the distinct binding poses of three agonistic peptide toxins—bullet-ant-derived toxin δ-paraponeritoxin-Pc1a, cone&nbsp;snail ι-conotoxin RXIA and the globular β-scorpion toxin Cn2—on the human Nav1.6–β1 channel complex illustrate a diversity in binding poses and mechanisms of action.

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22.

arXiv (CS.CL) 2026-06-15 DOI: arXiv:2606.13852

Hybrid Classical-Quantum Variational Autoencoder for Neural Topic Modeling

作者:

Ivan Kankeu↗

Neural topic models enable scalable semantic discovery, but their integration with quantum hardware remains largely unexplored. We present a proof-of-concept hybrid classical-quantum variational autoencoder (VAE) for topic modeling, embedding parameterized quantum circuits within the VAE inference network while retaining a classical topic-word decoder. To address the resource constraints of quantum hardware, we propose a modified Gaussian Softmax posterior that decouples latent space dimensionality from the number of topics to be extracted, enabling the model to operate with a low-resource 10-qubit quantum device. On the AgNews dataset, the hybrid VAE outperforms state-of-the-art neural topic models (NTMs), reaching a $C_v$ coherence score of 0.71 and an NPMI score of 0.20 while preserving high topic diversity. For comparison, we also construct a fully classical variant, which also outperforms state-of-the-art models on AgNews and exhibits clear class separation in the latent space. These results demonstrate that hybrid VAEs are computationally viable even on NISQ-era devices and represent a promising direction for quantum-enhanced topic modeling.

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23.

arXiv (CS.CV) 2026-06-16 DOI: arXiv:2606.15534

Track2View: 4D-Consistent Camera-Controlled Video Generation via Paired 3D Point Tracks

作者:

Feng Qiao↗Zhaochong An↗Zhexiao Xiong↗Serge Belongie↗Nathan Jacobs↗

Re-rendering an existing video from a novel camera viewpoint requires the output to follow the prescribed camera trajectory while preserving the appearance and dynamics of the original scene across every frame. Existing methods rely on per-frame pose embeddings, noisy point-cloud renderings, or implicit learned correspondences, none of which provides an explicit, temporally continuous link between source and target pixels. We propose Track2View, which conditions a video diffusion transformer on paired 3D point tracks: sparse trajectories of scene points projected into both the source and target camera views. These tracks provide explicit spatiotemporal correspondences that are temporally continuous by construction, encoding what content should appear where and when. At the core of Track2View is a dual-view track conditioner that transfers visual context from source to target view through parameter-free geometric operations and learned temporal aggregation, ensuring generalization to arbitrary camera trajectories without memorizing specific motions. We further introduce a data curation pipeline that extracts one-to-one track correspondences by running a 3D point tracker on temporally concatenated multi-camera view pairs. On a 400-video benchmark spanning static and dynamic scenes, Track2View achieves state-of-the-art results across visual quality, view synchronization, and camera accuracy, reducing rotation error by 30-65% and translation error by 61-72% relative to leading baselines. Project page is available at this https URL: https://qjizhi.github.io/track2view

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24.

arXiv (CS.CL) 2026-06-12 DOI: arXiv:2606.13662

EurekAgent: Agent Environment Engineering is All You Need For Autonomous Scientific Discovery

作者:

Amy Xin↗Jiening Siow↗Junjie Wang↗Zijun Yao↗Fanjin Zhang↗Jian Song↗Lei Hou↗Juanzi Li↗

LLM-based agents have shown increasing potential in automating scientific discovery. Given an optimizable metric and an execution environment, they can propose, validate, and iterate scientific solutions, and have produced results that outperform human-designed approaches. As model capabilities continue to improve, we argue that the bottleneck for autonomous scientific discovery is shifting from prescribing agent workflows to designing agent environments: the resources, constraints, and interfaces that shape agent behavior. We frame this as environment engineering: building environments that amplify productive behaviors, such as open-ended exploration, systematic artifact management, and inter-agent collaboration, while suppressing harmful behaviors, such as reward hacking and high-friction human oversight. We present EurekAgent, an environment-engineered agent system for metric-driven autonomous scientific discovery. EurekAgent engineers the environment along four dimensions: permissions engineering for bounded agent execution and isolated evaluation; artifact engineering for filesystem and Git-based collaboration; budget engineering for budget-aware exploration; and human-in-the-loop engineering for easy human supervision and intervention. EurekAgent sets new state-of-the-art results on multiple mathematics, kernel engineering, and machine learning tasks, including new state-of-the-art 26-circle packing results discovered with less than $11 in total API cost. We open-source our code and results, and call for environment engineering as a core research direction for developing reliable autonomous research agents.

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25.

arXiv (CS.CL) 2026-06-18 DOI: arXiv:2606.19218

RECOM: A Validity Discrimination Tradeoff in Automatic Metrics for Open Ended Reddit Question Answering

作者:

Pushwitha Krishnappa↗Amit Das↗Vinija Jain↗Aman Chadha↗Tathagata Mukherjee↗

Automatic metrics are the default for evaluating LLM-generated text, yet a metric is quietly asked to do two jobs: tell genuine content alignment from surface coincidence (validity), and tell a better system from a worse one (discriminative power). On open-ended, opinion-driven question answering, the two are in tension. We introduce RECOM (Reddit Evaluation for Correspondence of Models), a contamination-free evaluation dataset of 15,000 r/AskReddit questions (September 2025), each paired with its authentic community replies, which postdate every evaluated model's training cutoff. Scoring five open-source LLMs (7–10B) against every reply each metric paired with a random-derangement noise floor we find that no metric does both jobs well. Cosine similarity separates real from random answers (Cohen's $d \approx 2$) but cannot rank the five models ($|d| < 0.1$); BERTScore precision appears to rank the models (raw $|d|$ up to 0.63), but once response length is controlled this collapses to $|d| = 0.09$ and its validity is weak ($d \approx 0.8$, versus cosine's $\approx 2$). Because every metric scores the same outputs, this validity–discrimination tradeoff is a property of the metrics, not the models, and we argue it stems from representation design. Three independent LLM judges reproduce the validity gap and likewise separate the five models only weakly. We recommend reporting metrics on both axes, with an explicit random-baseline floor. RECOM is publicly available at https://anonymous.4open.science/r/recom-D4B0

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