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01.
arXiv (CS.CV) 2026-06-17

Where Should Action Generation Begin? A Learnable Source Prior for Generative Robot Policies

Generative robot policies typically begin action generation from an observation-independent standard Gaussian distribution, leaving the choice of source distribution underexplored. This work asks a simple question: where should action generation begin? We propose LeaP, a Learnable source Prior that replaces the standard Gaussian with a proprioception-conditioned diagonal Gaussian over action chunks. Parameterized by a lightweight MLP, LeaP jointly predicts the mean and state-adaptive variance of the source distribution, while keeping the downstream generator architecture and inference solver unchanged. This design provides an observation-informed yet stochastic initialization, allowing the generator to focus on precise action refinement rather than transporting samples from an uninformed noise source. On 15 RoboTwin manipulation tasks, LeaP achieves an average success rate of 81.6%, outperforming four representative baselines – including deterministic-source methods, a no-prior counterpart, and a diffusion-bridge policy – by 6.5 to 25.5 percentage points. The same prior consistently improves both flow-matching and diffusion-bridge generators, while using fewer parameters and converging faster. The advantage carries over to real-world deployment, where LeaP attains the best performance. These results suggest that the source distribution is an independent and reusable design axis for generative robot policies, complementary to the choice of generative dynamics.

02.
arXiv (CS.CL) 2026-06-16

WavSLM: Single-Stream Speech Language Modeling via WavLM Distillation

Large language models show that simple autoregressive training can yield scalable and coherent generation, but extending this paradigm to speech remains challenging due to the entanglement of semantic and acoustic information. Most existing speech language models rely on text supervision, hierarchical token streams, or complex hybrid architectures, departing from the single-stream generative pretraining paradigm that has proven effective in text. In this work, we introduce WavSLM, a speech language model trained by quantizing and distilling self-supervised WavLM representations into a single codebook and optimizing an autoregressive next-chunk prediction objective. WavSLM jointly models semantic and acoustic information within a single token stream without text supervision or text pretraining. Despite its simplicity, it achieves competitive performance on consistency benchmarks and speech generation while using fewer parameters, less training data, and supporting streaming inference.

03.
arXiv (math.PR) 2026-06-16

Higher-order spectral perturbation expansions II: Kernel matrices and manifold learning

arXiv:2606.16373v1 Announce Type: cross Abstract: We study spectral concentration bounds for kernel matrices as approximation of the corresponding kernel integral operator. Results are established under weak assumptions on the data setting and the reproducing kernel relying only on a Mercer condition and a local Weyl law. This allows us to deal with key features of kernel matrices, such as large multiplicities, large effective dimension, and heavy-tailed distributions. Our results apply to infinite dimensional principal component analysis, manifold learning, and Bayesian nonparametric statistics. We illustrate this via two prototypical examples: The heat kernel on the sphere and a wavelet prior from Bayesian nonparametrics.

04.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

Migratory cells tend to have soft nuclei that deform and penetrate narrow spaces1,2. Extensive nuclear deformation during migration can cause nuclear-envelope rupture and DNA damage in cancer cells, which may contribute to malignant transformation during tumour progression3–6. However, the importance of DNA damage in physiological migration is less well understood. Here we demonstrate that the migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-stranded breaks (DSBs) due to mechanostress during passage through narrow interstitial spaces. In contrast to many other migratory cells, these DSBs occur without detectable nuclear envelope rupture. Confined migration increases topoisomerase-IIβ covalently bound DSBs, and these lesions are repaired through non-homologous end-joining during brain development without causing cell death. Genome sequencing revealed that DSBs tend to occur at transcriptionally inactive regions. The deletion of ligase IV at the onset of neuronal migration leads to persistent DSB accumulation in cerebellar neurons with moderate transcriptional changes in genes related to synaptic function, neuronal development and stress and immune responses. The mutant mouse develops mild motor deficits in later life, suggesting that the DNA damage generated during normal brain development poses a potential disease risk if left unrepaired. The migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-strand breaks due to mechanostress during passage through narrow interstitial spaces.

05.
medRxiv (Medicine) 2026-06-18

A Novel Correction Method for QT Interval in the Presence of Left Bundle Branch Block Morphology

Background Accurate assessment of the QT interval is challenging in the presence of QRS prolongation, such as during ventricular pacing or bundle branch block. Current correction methods are heterogeneous and lack consensus. To evaluate the relationship between QRS duration and QT interval during ventricular pacing and to develop a practical correction method for QT assessment. Methods In this prospective single-centre study, 94 patients undergoing electrophysiology study for supraventricular tachycardia were included. Standardised pacing was performed at the same cycle length from the right ventricular (RV) apex, high output and low output pacing from His catheter, and coronary sinus (reference). QRS and QT intervals were measured from 12-lead ECGs. Changes in QT (QT) and QRS duration (QRS) were analysed using linear regression and mixed-effects modelling. QT correction formulas of the form QT corrected = QT N x QRS were evaluated using Bland-Altman analysis across multiple coefficients. Results A significant positive correlation between QRS and QT was observed across all pacing sites (r = 0.52-0.74, p < 0.001). In mixed-effects modelling, QRS was a strong independent predictor of QT (0.59, p < 0.001), with no significant interaction between pacing site and QRS, supporting a consistent relationship across pacing locations. Bland-Altman analysis demonstrated that correction coefficients of 0.65-0.70 minimised systematic bias compared with lower coefficients, with similar precision across models (SD 16 ms) and no evidence of proportional bias. A coefficient of 0.65 provided the most balanced performance between bias and variability. Conclusion QT prolongation during ventricular pacing is primarily driven by QRS widening and follows a consistent linear relationship across pacing sites. A simple correction using QT corrected = QT 0.65 x (QRS 100 ms) provides a practical and accurate method for QT assessment, with potential clinical applicability in patients with conduction abnormalities or ventricular pacing.

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

Revisiting LLM Adaptation for 3D CT Report Generation: A Study of Scaling and Diagnostic Priors

Recent advances in multimodal learning, including large language models (LLMs) and vision-language models (VLMs), have demonstrated strong adaptability to natural images. However, extending their use to the medical domain, particularly for volumetric (3D) images, is challenging due to high computational complexity, volumetric dependencies and the semantic gap between visual features and clinical terminology. Naively fine-tuning LLMs on limited medical data often leads to overfitting and clinical hallucination, where linguistic fluency is prioritized over clinical factuality. In this study, we investigate parameter-efficient adaptation strategies for volumetric CT report generation and introduce RAD3D-Prefix, a lightweight diagnostic-prior conditioning framework that minimizes the need for extensive parameter training. This module integrates image embeddings with multi-label diagnostic classification logits, preserving critical clinical details while bridging the semantic gap. By keeping the LLM frozen, our method requires minimal trainable parameters and mitigates the risk of overfitting on small, domain-specific datasets. Through a systematic study spanning LLMs from 96.1M to 1.6B parameters, we find that fine-tuning is most beneficial for smaller LLMs, whereas freezing larger (~1B+ LLMs and training only lightweight projection layers provides a superior trade-off between performance, generalization, and computational efficiency. Across multiple automatic metrics and a clinical reader study, RAD3D-Prefix outperforms comparable parameter-efficient baselines and demonstrates strong out-of-domain generalization while using substantially fewer trainable parameters than fully fine-tuned alternatives.

07.
arXiv (CS.CL) 2026-06-16

Fast-dLLM++: Fr\'{e}chet Profile Decoding for Faster Diffusion LLM Inference

Diffusion large language models promise parallel token generation, yet inference remains bottlenecked by deciding which masked tokens can be safely committed together. Fast-dLLM addressed this with KV caching and confidence-guided parallel decoding, but its decoding theory uses a homogeneous high-confidence assumption that effectively reduces each candidate set to its weakest selected token. We argue that this leaves speed on the table because real decoding steps exhibit heterogeneous confidence profiles. We propose Fast-dLLM++, a training-free extension that introduces Fr\'{echet profile decoding}: selecting parallel commit sets from the full sorted confidence profile rather than a single worst-case confidence. The resulting rule is a heterogeneous-confidence generalization of Fast-dLLM's factor selector and it recovers the previous rule exactly in the equal-confidence case and adds a provable heterogeneity bonus when the selected tokens have uneven confidences. Fast-dLLM++ leaves the model, diffusion process, and cache implementation entirely unchanged, making it a drop-in replacement for existing Fast-dLLM decoding. Experiments on GSM8K, MATH, HumanEval, and MBPP with the LLaDA-8B model show that the theoretical improvement translates directly into empirical gains: profile-aware selection improves the accuracy–throughput frontier by exploiting safe parallelism that weakest-token rules miss, achieving up to 37\% higher throughput at comparable accuracy. Our code release is at https://github.com/Ringo-Star/FastdLLM_plusplus.

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

MolSight: Molecular Property Prediction with Images

Every molecule ever synthesised can be drawn as a 2D skeletal diagram, yet in modern property prediction this universally available representation has received less focus in favour of molecular graphs, 3D conformers, or billion-parameter language models, each imposing its own computational and data-engineering overhead. We present $MolSight$, the first systematic large-scale study of vision-based Molecular Property Prediction (MPP). Using 10 vision architectures, 7 pre-training strategies, and $2\,M$ molecule images, we evaluate performance across 10 downstream tasks spanning physical-property regression, drug-discovery classification, and quantum-chemistry prediction. To account for the wide variation in structural complexity across pre-training molecules, we further propose a $chemistry-informed curriculum$: five structural complexity descriptors partition the corpus into five tiers of increasing chemical difficulty, consistently outperforming non-curriculum baselines. We show that a single rendered bond-line image, processed by a vision encoder, is sufficient for competitive molecular property prediction, i.e. $chemical insight from sight alone$. The best curriculum-trained configuration achieves the top result on $5 of 10$ benchmarks and top two on $all 10$, at $$80$\times$ lower$$ FLOPs than the nearest multi-modal competitor.

09.
arXiv (CS.CV) 2026-06-12

Iterative Tool Usage Exploration for Multimodal Agents via Step-wise Preference Tuning

Multimodal agents, which integrate a controller e.g., a vision language model) with external tools, have demonstrated remarkable capabilities in tackling complex multimodal tasks. Existing approaches for training these agents, both supervised fine-tuning and reinforcement learning, depend on extensive human-annotated task-answer pairs and tool trajectories. However, for complex multimodal tasks, such annotations are prohibitively expensive or impractical to obtain. In this paper, we propose an iterative tool usage exploration method for multimodal agents without any pre-collected data, namely SPORT, via step-wise preference optimization to refine the trajectories of tool usage. Our method enables multimodal agents to autonomously discover effective tool usage strategies through self-exploration and optimization, eliminating the bottleneck of human annotation. SPORT has four iterative components: task synthesis, step sampling, step verification, and preference tuning. We first synthesize multimodal tasks using language models. Then, we introduce a novel trajectory exploration scheme, where step sampling and step verification are executed alternately to solve synthesized tasks. In step sampling, the agent tries different tools and obtains corresponding results. In step verification, we employ a verifier to provide AI feedback to construct step-wise preference data. The data is subsequently used to update the controller for tool usage through preference tuning, producing a SPORT agent. By interacting with real environments, the SPORT agent gradually evolves into a more refined and capable system. Evaluation in the GTA and GAIA benchmarks shows that the SPORT agent achieves 6.41% and 3.64% improvements, underscoring the generalization and effectiveness introduced by our method. The project page is https://SPORT-Agents.github.io.

10.
medRxiv (Medicine) 2026-06-16

Infections and suicide and self-harm: a population-based matched cohort study

Background Infections have been associated with adverse mental health outcomes, including suicide, but evidence beyond severe or central nervous system infections is limited. We investigated associations between a range of acute infections and subsequent suicide/self-harm outcomes. Methods We conducted six infection-specific matched cohort studies using English primary care records from the Clinical Practice Research Datalink Aurum (2007-2024), linked to hospital admissions and mortality data. Adults ([&ge;]18 years) with a primary care record of infection (gastroenteritis, lower respiratory tract [LRTI], skin/soft-tissue [SSTI], urinary tract [UTI], sepsis, meningitis/encephalitis [positive control]) were matched (age, sex, practice, calendar period) to up to five comparators without infection. We estimated hazard ratios (HRs) for suicide/self-harm outcomes using Cox regression, stratified by matched set and implicitly adjusting for matching factors, with additional adjustment for deprivation, lifestyle factors, and comorbidities. We examined whether associations varied over time, by infection severity, antimicrobial treatment, sex, and prior mental health conditions. Findings Cohorts ranged from 18,192 individuals with meningitis/encephalitis (matched to 90,915 without) to 398,099 with SSTI (matched to 1,743,747). After adjustment, individuals with infection had a higher hazard of suicide/self-harm outcomes than comparators across all cohorts: sepsis (HR 1.79, 95% CI 1.65-1.93), gastroenteritis (1.62, 1.55-1.70), meningitis/encephalitis (1.56, 1.32-1.84), UTI (1.41, 1.33-1.50), SSTI (1.37, 1.31-1.43), and LRTI (1.37, 1.31-1.44). Risk was highest in the year post-infection, attenuating over time, and was higher among severe infections and those without prior mental health conditions. Interpretation Common acute infections recorded in primary care are associated with increased risk of suicide and self-harm, particularly following severe infections and in the year post-infection. Findings support suicide risk monitoring following acute infection, particularly among individuals without prior mental health conditions, and highlight infection prevention as a potentially modifiable strategy in vulnerable populations. Funding Wellcome and La Caixa. Copyright This work is licensed under a Creative Commons Attribution (CC BY) licence.

11.
arXiv (quant-ph) 2026-06-19

Applications of quantum annealing to magnetic dipole hyperfine structure constants: First results beyond energies for atoms

arXiv:2606.20166v1 Announce Type: new Abstract: We report the first results of the magnetic dipole hyperfine structure (HFS) constants of neutral $\mathrm{Li}$, Li-like $\mathrm{Be}$, neutral $\mathrm{Na}$, and Na-like $\mathrm{Mg}$ using a modified version of the Quantum Annealer Eigensolver (QAE) algorithm on D-Wave's quantum hardware. The results are benchmarked against relativistic configuration interaction with multiconfiguration Dirac Hartree-Fock (MCDHF) calculations using the General-purpose Relativistic Atomic Structure Package (GRASP), and simulated annealing. In our modified QAE, a zooming-and-sigma-annealing approach with a floating-point encoding scheme is adopted to estimate the ground-state eigenvalue and eigenvector of the relativistic Dirac-Coulomb Hamiltonian matrices ($H_{\mathrm{DC}}$) constructed from 11 or fewer configuration state functions (CSFs). For calculations with extended correlation orbital sets, we applied a CSF truncation scheme, retaining only CSFs (up to 12) that make significant contributions to the ground-state wavefunction. Our modified QAE precision is kept limited to three decimal places (up to 10 qubits). Hardware demonstrations on the D-Wave quantum processing unit (QPU) yielded results that were completely consistent with GRASP (at the chosen precision) in determining the magnetic dipole HFS constants, with accuracy varying across systems and $H_{\mathrm{DC}}$ matrix dimensions.

12.
Nature (Science) 2026-06-17

Structure of the pre-initiation complex explains CMGE biogenesis

When cells enter S phase, bidirectional DNA replication is initiated through the kinase-regulated recruitment of three activators (Cdc45, GINS and Pol ε) to a duplex-DNA-loaded double hexamer of minichromosome maintenance (MCM) ATPases. Together, these proteins form two CMGE helicases that establish divergent replication forks as they become separated1. Here, to gain an understanding of CMGE biogenesis, we reconstituted the pre-initiation complex with purified yeast proteins. The cryo-electron-microscopy structure shows a set of firing factors caught in the act of assembling two symmetrical CMGEs. We show how stepwise complex formation reshapes MCM in preparation for DNA opening, and we explain how ATP promotes firing-factor ejection and CMGE maturation. We find that although Sld2 facilitates&nbsp;the recruitment of GINS to MCM, as expected, it also aids the efficient separation of the CMGE dimer, and is essential for the ejection of the lagging strand from MCM. These findings have direct implications for our understanding of the metazoan Sld2 orthologue, RECQL4, and point to a replication-fork establishment mechanism that is conserved across eukaryotes. Cryo-electron microscopy and biochemical reconstitution experiments in yeast provide insight into the assembly of the CMGE complex, a helicase that establishes bidirectional DNA replication in eukaryotic cells, and elucidate the role of the firing factor Sld2.

13.
arXiv (math.PR) 2026-06-12

Pathwise integration beyond Young via Faber–Schauder energy spaces

作者:

arXiv:2606.13331v1 Announce Type: cross Abstract: We develop a pathwise integration theory based on Faber–Schauder energy spaces. The approach replaces the classical Hölder–Young and finite-variation Young conditions by dyadic summability conditions expressed in terms of Faber–Schauder coefficients. On the normalized interval $[0,1]$, these conditions define Banach spaces $\mathcal{E}^p$, which we call Faber–Schauder energy spaces. For $p,q>1$ satisfying $1/p+1/q\ge1$, we prove that every pair $f\in\mathcal{E}^p$ and $g\in\mathcal {E}^q$ admits a continuous pathwise integral $I_{f,g}$, constructed from dyadic left Riemann sums. We call $I_{f,g}$ the Faber–Schauder integral, and show that it depends boundedly and bilinearly on $(f,g)$ in the corresponding energy norms. The integral satisfies additivity, integration by parts, and a dyadic Young–Loève estimate. It is also the uniform limit of classical Riemann–Stieltjes integrals of finite Faber–Schauder approximations. The Faber–Schauder integral agrees with the classical Young integral whenever the latter is available, but also applies to deterministic and Gaussian examples for which neither the Hölder–Young condition nor the finite-variation Young condition can be verified. In this sense, it provides a Faber–Schauder coefficient-based extension of Young's framework.

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

Ouroboros-Spatial: Closing the Data-Model Loop for Spatial Reasoning

Spatial reasoning remains a persistent challenge for multimodal large language models (MLLMs). Existing approaches largely rely on large-scale, statically curated datasets, where all training samples are treated uniformly regardless of the model's evolving capabilities. This static paradigm is inherently data-inefficient: training capacity is often spent on samples that are either trivial or overly difficult for the model at its current stage. To address this limitation, we propose Ouroboros-Spatial, a self-evolving training framework in which the model plays dual roles as a proposer and a solver. In each iteration, a frozen proposer generates spatial question-answer (QA) pairs from 3D scene metadata and raw video frames, together with executable code for deriving reliable ground truth. A learnable solver is then fine-tuned on the accepted samples, and its per-sample prediction confidence is used as a difficulty signal. This signal is fed back to the proposer in the next iteration, guiding it to generate questions better matched to the solver's current capabilities. Through this closed-loop design, the training distribution co-evolves with model ability, reducing redundant trivial examples while filtering out ambiguous or uninformative samples with limited learning value. Across six spatial reasoning benchmarks, Ouroboros-Spatial substantially improves Qwen3-VL-4B and Qwen3-VL-8B while using an order of magnitude fewer training examples than recent large-scale curated datasets. On VSI-Bench, it yields absolute gains of 9.9 and 6.8 points for the 4B and 8B models, respectively, enabling both to outperform a wide range of strong open-source and proprietary baselines.

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

TaFD: Threat-Aware Frequency Decoupling for Adversarial Robustness against Heterogeneous Attacks

Multi-threat robustness remains a fundamental challenge in deep learning. Although joint adversarial training (JAT) is widely adopted, it suffers from negative transfer under heterogeneous threats, particularly between $\ell_p$-bounded and semantic attacks. Through first-order gradient analysis, we formalize this as gradient incompatibility and theoretically establish the necessity of decoupled optimization. We further reveal that these conflicting threats exhibit separable spectral characteristics in the frequency domain. Motivated by this observation, we propose Threat-aware Frequency Decoupling (TaFD), a two-stage defense framework that reformulates JAT as a frequency-domain divide-and-conquer paradigm. TaFD first discovers latent threat domains via unsupervised clustering of attack spectral prototypes and trains a lightweight classifier for inference-time threat domain identification. Conditioned on the prediction, TaFD employs a Frequency-Conditional Convolution that learns threat-domain-specific spectral masks and routes each sample to the corresponding expert, enforcing structural parameter separation and alleviating optimization conflicts. We validate TaFD on three representative image-classification benchmarks (CIFAR-10, CIFAR-100, and Tiny-ImageNet) and on two representative architectures (the convolutional ResNet and the hybrid-transformer MobileViT). Extensive results demonstrate that TaFD achieves more balanced robustness against heterogeneous attacks than existing JAT and frequency-domain baselines, improving average robust accuracy by approximately 11\% over the strongest baseline while maintaining leading clean accuracy.

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

AdsMind: A Physics-Grounded Multi-Agent System for Self-Correcting Discovery of Adsorption Configurations on Heterogeneous Catalyst Surfaces

arXiv:2606.19152v1 Announce Type: cross Abstract: Identifying the lowest-energy surface-adsorbate configuration is critical for modeling heterogeneous catalysis, yet exhaustive exploration with ab initio calculations is computationally prohibitive. Machine-learning force fields (MLFFs) accelerate structural relaxation but leave the search over the vast configurational space a major bottleneck, and open-loop large language model (LLM) agents lack a physics-grounded feedback mechanism to correct erroneous initial guesses. We propose AdsMind (Adsorption configuration discovery with Machine intelligence and relaxation feedback), a closed-loop multi-agent framework that enables autonomous error correction through MLFF relaxation feedback. Across four LLM backends, AdsMind achieves consistently high search reliability, with success rates of 100% and 98.8% on the benchmarks AA20 and OCD-GMAE62. Relative to its single-pass (1-Shot) ablation it reduces cross-backend energy dispersion, and it uses only 4.11 and 4.67 MLFF relaxations per case, respectively – an approximately 14-fold reduction over heuristic enumeration baselines. Density functional theory (DFT) validation using VASP/PBE on six representative AA20 systems shows that the reported open-loop Adsorb-Agent outputs exhibit qualitative adsorption-energy sign errors for molecular adsorbates, whereas AdsMind preserves the correct sign in all tested cases with closer quantitative agreement. AdsMind thus delivers reliability, self-reflection, and interpretability simultaneously, supporting more DFT-informed autonomous chemistry workflows.

17.
bioRxiv (Bioinfo) 2026-06-18

Bioinf-Farma: supervised integration of epitope prediction and recombinant protein developability for automated vaccine candidate prioritization

Vaccine antigen discovery requires prioritizing protein candidates according to both immunogenic potential and recombinant expression feasibility. These properties are typically evaluated using separate computational tools, requiring researchers to integrate heterogeneous outputs through ad hoc workflows. Here, we present BIOINF-farma, a modular platform integrating epitope prediction and developability assessment for rational antigen selection within a unified environment. Candidates can be submitted as amino acid sequences or three-dimensional structures. When experimental structures are unavailable, BIOINF-farma automatically searches for models in AlphaFold DB or performs structure prediction using Boltz-2, ensuring a standardized structural representation for downstream analyses. Antigenicity is quantified by combining structure-based conformational epitope signals (MLCE/REBELOT-BEPPE) and sequence-based linear epitope propensity scores (BepiPred 3.0) into a protein-level Antigenicity Score, with a classification threshold optimized on a manually curated validation dataset. Developability is evaluated through two supervised Random Forest meta-learners that integrate three solubility predictors (DeepSoluE, SoluProt, Protein-Sol) and three thermal stability predictors (TemStaPro, ProLaTherm, BertThermo), whose outputs are combined into an Expression Efficiency Score (EES). By integrating complementary predictive signals, the meta-learning framework achieves greater accuracy and robustness than individual predictors while maintaining performance across a broad range of sequence identities. The Antigenicity Score effectively discriminates antigenic from non-antigenic proteins with a large effect size, whereas EES successfully distinguishes soluble from insoluble outcomes on an independent panel of recombinant proteins expressed in Escherichia coli. BIOINF-farma jointly assesses antigenicity and expression feasibility within a single framework. Its modular architecture facilitates the incorporation of future predictive methods, while its web-based interface makes the full pipeline accessible to users without programming expertise, supporting rapid candidate triage in vaccine research and emerging pathogen responses.

19.
medRxiv (Medicine) 2026-06-19

Reassessing Instrument Strength in Two-Sample Mendelian Randomization Analysis

Mendelian randomization (MR) analysis is widely used to estimate causal relationships between risk factors and outcomes of interest. Two-sample MR approaches have gained increasing attention in genetic epidemiology due to the growing availability of Genome-Wide Association Study (GWAS) summary statistics from public databases. A critical step in two-sample MR is the selection of genetic variants as instrumental variables (IVs). Although genome-wide significant variants are typically preferred, the inclusion of variants with weaker association p-values is considered, as they may potentially improve power through an increased instrument number of instruments, while they may introduce weak instrument bias and attenuate effect estimates towards the null. Our simulation results show that even modest levels of pleiotropy substantially increase the variability of causal effect estimates, while the inclusion of weak IVs does not substantially affect the direction and variability of causal effect estimates in most cases. In real data analyses, we used two released versions of FinnGen GWAS summary statistics with different sample sizes as exposure GWASs to assess the influence of weak IVs. Here, the inclusion of IVs with higher exposure-association p-values resulted in weakened estimated effect sizes, particularly when the exposure GWAS sample size was small. These findings suggest that incorporating weak IVs is reasonable when the exposure GWAS sample size is large, but it poses a risk of falsely concluding null associations when the exposure GWAS sample size is small.

20.
arXiv (CS.AI) 2026-06-15

ChronoID: Infusing Explicit Temporal Signals into Semantic IDs for Generative Recommendation

arXiv:2606.14260v1 Announce Type: cross Abstract: Semantic IDs are crucial in generative recommendation, but with a fundamental limitation: temporal information is not well incorporated into semantic IDs. Instead, time influences recommendation only implicitly (e.g., through session construction heuristics, preference alignment, or sequence order), while existing semantic ID learning remains entirely time-agnostic. This design conflates interactions occurring under distinct temporal contexts into identical semantic representations, implicitly assuming that item semantics and user intent are temporally stationary. Such an assumption is misaligned with real-world recommendation scenarios, where evolving interaction rhythms play a central role. In this work, we investigate where and how the explicit time should be incorporated into semantic ID for generative recommendation. First, we systematically characterize the design space along three orthogonal dimensions of temporal signals and present a unified framework, ChronoID, for time-aware semantic ID learning. Then, by contributing a new time-explicit generation recommendation benchmark, ChronoID answers the questions: what is the effective way of infusing time, how to design the architecture, and where does the gain come from.

21.
medRxiv (Medicine) 2026-06-10

Towards the Virtual Amyotrophic Lateral Sclerosis Patient: Inferring Cortical Excitability through Whole-Brain Dynamical Modeling

Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem neurodegenerative disorder in which motor-neuron degeneration is accompanied by widespread alterations in cortical dynamics. Among its most reproducible neurophysiological signatures is cortical hyperexcitability, yet how this local excitability imbalance shapes distributed whole-brain activity remains poorly understood. Here, we combined source-reconstructed resting-state MEG data, tractography-informed whole-brain modeling, and simulation-based inference to investigate whether ALS-related alterations in large-scale brain dynamics can be mechanistically explained by changes in cortical excitability. First, we characterized empirical brain dynamics using complementary features spanning regional activity amplitude and variability, functional connectivity, and avalanche-based metrics. These analyses revealed significant alterations in ALS patients relative to healthy controls, as well as associations with clinical impairment and disease staging. To mechanistically interpret these changes, we employed a reduced Wong-Wang whole-brain model in which local recurrent excitation modulates emergent large-scale neural dynamics. Simulations showed that increasing excitability systematically reproduced the empirical dynamical signatures observed in ALS. We then applied a simulation-based inference framework to estimate latent excitability parameters directly from empirical observations. Whole-brain model inversion revealed increased excitability in ALS patients compared with controls. The recovered excitability parameter was associated with disease staging, supporting its clinical relevance as a model-derived descriptor of ALS progression. Finally, by extending the model to estimate frontal and non-frontal excitability separately, we found that ALS-related alterations were predominantly associated with increased frontal excitability, whereas non-frontal regions appeared comparatively less affected. The recovered parameters related to disease staging. Together, these findings provide a mechanistic framework linking altered large-scale brain dynamics in ALS to selective cortical hyperexcitability, explaining how local excitability changes can give rise to global network reorganization. More broadly, they show how computational model inversion can recover latent multiscale pathophysiological processes from empirical neural recordings, offering a non-perturbative alternative to complex experimental paradigms typically required to causally probe local-to-global mechanisms.

22.
arXiv (CS.LG) 2026-06-16

DP-Hype: Federated Differentially Private Hyperparameter Search

arXiv:2510.04902v3 Announce Type: replace Abstract: Tuning hyperparameters in federated machine learning can substantially impact model performance. When hyperparameters are tuned on sensitive data, privacy becomes an important challenge and to this end, differential privacy has emerged as the de facto standard for provable privacy. A standard setting in federated learning is that clients agree on a shared setup, i.e., find a compromise from a set of hyperparameters, like a model's learning rate. Yet, prior work on privacy-preserving hyperparameter tuning is tailored to specific learning tasks, does not account for the privacy leakage of aggregated results, or offers a sub-optimal privacy-utility trade-off. In this work, we present our algorithm DP-Hype, which performs a federated and privacy-preserving hyperparameter search by conducting a federated voting based on local hyperparameter evaluations of clients. In this way, DP-Hype selects hyperparameters that lead to a compromise supported by a majority of clients, while maintaining scalability and independence from specific learning tasks. We prove that DP-Hype preserves the strong notion of differential privacy called client-level differential privacy and, importantly, show that its privacy guarantees do not depend on the number of hyperparameters. We also provide bounds on its utility guarantees, that is, the probability of finding good hyperparameters, and implement DP-Hype as a submodule in the popular Flower framework for federated machine learning. In addition, we evaluate performance on multiple benchmark data sets in iid as well as multiple non-iid settings and demonstrate high utility of DP-Hype even under small privacy budgets.

23.
Nature (Science) 2026-06-18

Daily briefing: The proteins that protect us from deadly mutations

作者:

Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States. Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States.

24.
arXiv (CS.LG) 2026-06-11

On Regret Bounds of Thompson Sampling for Bayesian Optimization

arXiv:2603.09276v2 Announce Type: replace-cross Abstract: We study a widely used Bayesian optimization method, Gaussian process Thompson sampling (GP-TS), under the assumption that the objective function is a sample path from a GP. Compared with the GP upper confidence bound (GP-UCB) with established high-probability and expected regret bounds, most analyses of GP-TS have been limited to expected regret. Moreover, whether the recent analyses of GP-UCB for the lenient regret and the improved cumulative regret upper bound can be applied to GP-TS remains unclear. To fill these gaps, this paper shows several regret bounds: (i) a regret lower bound for GP-TS, which implies that GP-TS suffers from a polynomial dependence on $1/\delta$ with probability $\delta$, (ii) an upper bound of the second moment of cumulative regret, which directly suggests an improved regret upper bound on $\delta$, (iii) expected lenient regret upper bounds, and (iv) an improved cumulative regret upper bound on the time horizon $T$. Along the way, we provide several useful lemmas, including a relaxation of the necessary condition from recent analysis to obtain improved regret upper bounds on $T$.

25.
arXiv (CS.LG) 2026-06-16

Empirical Study of Pop and Jazz Mix Ratios for Genre-Adaptive Chord Generation

作者:

arXiv:2605.04998v2 Announce Type: replace-cross Abstract: This revision updates a pop-to-jazz chord-generation rehearsal study. Best-epoch metrics still show that modest pop rehearsal preserves pop accuracy while improving jazz prediction, but v2 corrects released-checkpoint selection: the released F1 equals Phase 0, F2 had a transcription error, and ft-pop80-v2 restores a hash-distinct jazz-adapted F1 across 3 seeds.