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

Patients With Personality: Realistic Patient Simulation through Controlled Diversity and Selective Disclosure

arXiv:2606.17441v1 Announce Type: cross Abstract: Simulating realistic patient interactions is a key requirement to testing clinical applications of LLMs at scale without time-consuming and expensive user studies. However, existing approaches often lack realism and controllability, often oversharing information unprompted, and failing to capture the wide variability of patient behavior. Here, we introduce PatientsWithPersonality (PWP), a patient simulation framework that generates realistic yet diverse virtual patient responses through explicit personality parametrization over a latent patient state. Grounded in HEXACO, a six-dimensional personality space used to quantify and parameterize human behavioral traits, our approach enables fine-grained control over conversational style, cooperativeness, and information disclosure within a unified framework. In a clinician evaluation, PWP is judged nearly as realistic as recorded human actors and clearly ahead of prior simulators, while being flagged as "too informative" far less often. Conditioning on HEXACO axes yields personas whose configured traits are recoverable by both clinicians and an autorater, span a substantially wider behavioral footprint than the closest baseline, and prevent oversharing. Altogether, our framework paves the way for more accurate and informative LLM benchmarking through our realistic and steerable patient simulator.

02.
medRxiv (Medicine) 2026-06-16

Adverse Childhood Experiences and Growth Outcomes in Childhood: A Longitudinal EHR-Based Study

Question Are adverse childhood experiences (ACEs) associated with altered growth trajectories in childhood? Findings In this cohort study of 412,549 children and adolescents, ACEs were associated with lower height throughout childhood, earlier pubertal timing, and shorter final stature. Height differences emerged approximately 2 years before ACE documentation and were greatest among those with earlier documentation. Meaning These findings suggest that early adversity affects physical growth in children and may serve as a measurable indicator of the biological consequences of early-life stress, especially in those with documentation of ACEs prior to the onset of typical pubertal growth. Importance Adverse childhood experiences (ACEs) are among the strongest risk factors for long-term mental and physical health complications, yet their impact on physical growth in childhood remains incompletely understood. Objective To determine the association of ACEs on childhood growth trajectories and growth dynamics. Design, Setting and Participants Retrospective cohort study using longitudinal electronic health record data. Data was collected from participants between February 1999 and August 2025. A large academic medical center biobank linked to deidentified electronic health records in the southeastern United States. A total of 412,549 individuals with at least 2 recorded height measurements between the ages of 2 and 20 were included in the primary analysis. Growth curve analyses were performed in a subset of 199,844 individuals with at least 3 height measurements spanning at least 2 years. Genetic analyses were performed in a subset of 10,114 individuals of primarily European ancestry. Exposure(s) Documented exposure to adverse childhood experiences before age 18 years identified through a natural language processing algorithm. Main Outcome(s) and Measure(s) Height-for-age z-scores across childhood, final attained height, and growth curve parameters estimated using SuperImposition by Translation and Rotation (SITAR) modeling. Results Among 412,549 participants, 18,502 (4.5%) had clinically documented ACEs during childhood. ACE documentation was associated with lower height-for-age z-scores throughout childhood and adolescence. Final attained height was significantly lower among ACE-documented individuals, with mean differences of -3.0 cm among males (174.0 cm vs 177.0 cm, p < 0.001) and -1.3 cm among females (161.8 cm vs 163.1 cm, p < 0.001). Height differences emerged approximately 2 years before clinical ACE documentation. Earlier age at first ACE documentation was associated with progressively shorter final attained height, with each year decrease in age at ACE documentation associated with a decrease in final height of -0.20 cm in females and -0.35 cm in males. Those with first ACE documented prior to pubertal age also showed the most pronounced growth dynamic differences, with males demonstrating a mean reduction in size of 5.25 cm (95% CI, -6.79 cm to -3.70 cm) and 1.26-year earlier pubertal timing (95% CI, -1.50 to -1.03 years), and females demonstrating a reduction in growth curve size of 3.62 cm (95% CI, -4.83 to -2.41 cm) and 1.14-year earlier pubertal timing (95% CI, -1.29 to -0.99 years). Conclusions and Relevance In this large clinical cohort, clinically documented ACEs were associated with time-dependent reductions in stature, earlier pubertal timing, and short final attained height. These findings suggest that early childhood adversity may have lasting effects on physical development and highlight growth trajectories as a potential marker of the biological consequences of early-life stress.

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

Rethinking Scaffolding in LLM Tutors: The Interactional Mismatch Between Benchmarks and Real-World Deployments

arXiv:2606.15766v1 Announce Type: new Abstract: A central pedagogical value evaluated in AI tutor benchmarks is scaffolding: guiding students through graduated steps toward a solution. Alignment and evaluation methods for embedding scaffolding behaviour into chatbots, however, rest on an implicit assumption: that students will take up the scaffolding and engage in the conversation. To examine whether this assumption holds, we introduce an evaluation pipeline around two metrics - Chatbot Scaffolding and Student Uptake - and apply them across nine datasets of 9,490 chats, spanning AI tutor benchmarks and real-world deployments of educational chatbots. Our analysis reveals that while benchmarks assume a high-scaffolding, high-student-uptake environment, students in real-world settings exhibit lower levels of uptake overall - frequently bypassing the chatbot's pedagogical framing to drive the interaction toward their own learning goals at little interpersonal cost. We argue that bypassing scaffolding is not necessarily detrimental; rather, it frequently highlights a mismatch between a chatbot's pedagogical framing and the student's learning goals. To meaningfully evaluate the effectiveness of a chatbot's assistance, future benchmarks must move beyond the assumption that students will simply take up the scaffolding, and instead evaluate how these chatbots navigate diverse learning contexts and student-driven interaction patterns.

04.
arXiv (math.PR) 2026-06-16

Pricing Excess-of-Loss Reinsurance and CAT Bonds under Climate Uncertainty: A Cox Process Framework with Temperature-Dependent Stochastic Intensity

arXiv:2606.14830v1 Announce Type: cross Abstract: This paper develops a climate-aware pricing framework for excess-of-loss (XL) reinsurance contracts and catastrophe (CAT) bonds under non-stationary catastrophe risk. Catastrophe arrivals are modeled as a Cox process whose stochastic intensity depends exponentially on a temperature-related climate index. To represent climate dynamics, the index is modeled as a mean-reverting Ornstein–Uhlenbeck process around a time-dependent warming trend. Within this setting, aggregate losses follow a compound Cox structure with lognormal severities. Pricing is performed under a reduced-form risk-adjusted measure, which provides a tractable valuation approach for XL reinsurance layers and binary zero-coupon CAT bond payoffs in an incomplete market setting. Because catastrophe losses are not dynamically replicable, the framework emphasizes scenario-based valuation rather than model-independent no-arbitrage bounds. A Monte Carlo valuation scheme is implemented to quantify the economic implications of climate-dependent catastrophe intensity. The numerical results show that climate dependence materially changes the loss-generation mechanism and affects the valuation of catastrophe-linked contracts. In the baseline calibration, the climate-aware model increases the excess-of-loss reinsurance premium and lowers the CAT bond price relative to the stationary benchmark. Furthermore, our analysis of the 99.5\% Tail Value-at-Risk (TVaR) indicates that stationary benchmarks may underestimate economic capital requirements by approximately 13.7\% compared to the climate-aware framework, highlighting the potential regulatory relevance of the proposed model. This finding highlights that benchmark design is critical for interpreting climate-pricing effects.

05.
arXiv (CS.CV) 2026-06-18

SC3-Eval: Evaluating Robot Foundation Models via Self-Consistent Video Generation

Evaluating generalist robot manipulation policies in the real world is expensive, slow, and difficult to scale. Action-conditioned video world models offer a scalable alternative by simulating policy rollouts. Autoregressive rollouts accumulate compounding errors, observations across multiple camera views must remain mutually consistent, and the evaluator must generalize to policies whose behaviors lie outside the training distribution. We address these challenges with SC3-Eval, a self-consistent video generation recipe that adapts a pre-trained video foundation model into an accurate policy evaluator by enforcing three complementary forms of consistency. First, forward-inverse dynamics consistency jointly trains the model to predict frames from actions and to recover actions from frames, anchoring generated rollouts to a physically plausible action manifold and counteracting the drift a forward-only model cannot penalize. Second, cross-view consistency trains the model to inpaint each camera view from the other, keeping the multi-camera observation coherent over long rollouts without any explicit memory mechanism. Third, test-time consistency reuses the inverse dynamics mode at inference as a per-action-chunk uncertainty signal that terminates rollouts whose generated frames drift away from the requested actions. We also demonstrate SC3-Eval rollouts reproduce the failure modes that policies exhibit in real-world rollouts, supporting fine-grained diagnostic comparison rather than aggregate ranking alone. Across seven real-world vision-language-action policies, SC3-Eval attains a closed-loop Pearson correlation of $0.929$ and MMRV of $0.119$, outperforming three strong prior video-model-based baselines, and generalizes to new tasks.

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

ROVE: Unlocking Human Interventions for Humanoid Manipulation via Reinforcement Learning

arXiv:2606.17011v1 Announce Type: cross Abstract: Human interventions provide crucial corrective signals for post-training Vision-Language-Action (VLA) models. However, enabling seamless humanoid interventions is a formidable systems challenge due to complex whole-body kinematics and dexterous-hand control. Consequently, the collected intervention trajectories are often suboptimal, and methods that rely on human interventions as expert supervision can absorb hesitant, inefficient, or even erroneous behaviors. To address both the system and algorithmic challenges, we propose ROVE, a reinforcement learning framework for humanoid VLA post-training with imperfect human interventions. First, ROVE introduces a human-in-the-loop pipeline capable of collecting deployment and intervention data for humanoid manipulation. Second, it utilizes Optimistic Value Estimation (OVE) to prioritize high-value behaviors from mixed-quality trajectories. To further robustify value estimation, we incorporate cross-embodiment human experience videos to provide rich supervision for long-tailed failure and recovery modes. The resulting critic yields informative advantage signals, steering the VLA actor to focus on high-value behaviors rather than indiscriminately imitating all actions. On challenging real-world contact-rich and fine-grained humanoid manipulation tasks, ROVE outperforms experience-learning baselines and consistently improves across multiple rollout-intervention iterations.

07.
bioRxiv (Bioinfo) 2026-06-21

Expanding the GUSome: Structure-guided identification and characterization of gut microbial β-glucuronidases

The gut microbiome-encoded {beta}-glucuronidase (GUS) enzymes have a significant effect on human physiology through their deglucuronidation activity on endogenous and exogenous glucuronides. GUS activity also significantly influences the pharmacokinetics, efficacy and toxicity of various drugs including chemotherapeutic drugs. Given their crucial role in drug metabolism, GUS enzymes have emerged as promising targets for therapeutic intervention. Here, we have identified and characterized 79 unique GUS enzymes through a structure-guided approach. Structural modelling of these GUS enzymes revealed a conserved core and active-site residues with significant variations in the number and nature of the C-terminal domains. A new classification system based on the number and type of additional C-terminal domains is presented for the GUS proteins. Further, GUS enzymes have been categorized into different loop categories linked to their substrate preferences. The relationship between domain architecture and loop-type is explored by sequence similarity network analysis. We could successfully express, purify and validate GUS processing capability of a panel of identified GUS proteins. The nature of oligomer organization has been deciphered by SEC and DLS studies. Further, we have identified additional GUS enzymes capable of processing SN-38G, glucuronidated form of anticancer drug, irinotecan. These newly identified GUS enzymes will offer valuable insights into gut microbial GUS diversity and their role in understanding the population-specific drug-induced adverse effects on human health.

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

FAConformer: Frequency-Aware Convolutional Transformer for Auditory Attention Decoding

arXiv:2606.14120v1 Announce Type: cross Abstract: Auditory attention decoding (AAD) aims to infer the attended speaker from neural responses in multi-speaker acoustic environments and is a key problem for neuro-steered hearing systems. Although recent studies have achieved encouraging progress, existing AAD models still do not fully exploit frequency domain electroencephalography (EEG) information. In particular, most approaches introduce multi-band information through handcrafted feature extraction or direct cross-band feature concatenation, which mainly exploit frequency information at a shallow level and may overlook band-specific patterns and cross-band interactions. To address these limitations, this paper proposes FAConformer, a frequency-aware CNN-Transformer framework for AAD that explicitly integrates band-specific encoding and adaptive cross-band interaction. Specifically, FAConformer first decomposes EEG signals into multiple frequency bands and assigns each band to an independent CNN-Transformer encoder for band-specific modeling. The resulting band-wise features are then adaptively fused by a carefully designed frequency-aware attention (FAA) module that models cross-band dependencies by treating band-wise features as tokens. Further, band-wise auxiliary supervision (BAS) is introduced to prevent weakly contributing branches from being under-optimized during joint training. In this way, FAConformer performs frequency-aware modeling that more effectively exploits frequency domain information. Extensive experiments on two public AAD datasets with three decision-window lengths demonstrated that FAConformer consistently outperformed 12 competitive baselines, surpassing the current state-of-the-art model by 4.9%. Further analyses of band importance, ablation, and parameter sensitivity verify the effectiveness, robustness, and interpretability of the proposed framework. Code is available at https://github.com/wzwvv/FAConformer.

10.
arXiv (CS.AI) 2026-06-11

TouchThinker: Scaling Tactile Commonsense Reasoning to the Open World with Large-scale Data and Action-aware Representation

arXiv:2606.11637v1 Announce Type: new Abstract: Touch is a key modality for embodied agents to understand the physical world. Although recent work has incorporated tactile signals into language systems for tactile commonsense reasoning, scaling such systems to realistic open-world settings remains challenging due to two key bottlenecks: (1) current tactile reasoning datasets remain limited in format and scale, providing insufficient supervision for reasoning from tactile observations to physical commonsense and hindering the learning of transferable tactile commonsense; (2) Tactile signals are inherently redundant and action-specific, yet existing methods often overlook these properties, resulting in inefficient representations with limited semantic expressiveness. To address these limitations, we propose TouchThinker, a tactile-language framework that scales tactile commonsense reasoning to the open world from both data and representation perspectives. First, we construct TouchThinker-1M, a million-scale, multi-source tactile reasoning dataset covering 415 objects, 8 scenarios, and 7 sensor types, providing a solid data foundation for open-world generalization. We further introduce TouchThinker-Bench, an open-world benchmark with more realistic and diverse tasks. Then, we propose action-aware modeling mechanism to improve tactile representation efficiency and enable efficient reasoning. Experimental results demonstrate that TouchThinker achieves competitive performance against state-of-the-art models across multiple datasets. Our code and dataset will be made available at: https://github.com/lvkailin0118/TouchThinker.

11.
medRxiv (Medicine) 2026-06-17

Targeted Proteomic Profiling of Nasal Fluid from the Brain-Nose Interface

The brain-nose interface is an anatomical junction where olfactory neurons from the olfactory bulb traverse the cribriform plate into the nasal mucosa, providing minimally invasive access to the central nervous system (CNS). We hypothesized that nasal fluid from this region could enable detection of neurology-relevant proteins using targeted multiplex assays. Using nosecollect, a targeted nasal sampling device, nasal fluid proximal to brain-nose interface was collected from cognitively impaired patients, alongside matched cerebrospinal fluid (CSF) and plasma. After nasal sample-specific dilution optimization and intra-assay precision evaluation, all matrices were profiled with the Olink Target 96 Neurology and NUcleic acid Linked Immuno-Sandwich Assay CNS disease 120 (NULISAseq CNS Disease 120) panels. Nasal fluid showed technically repeatable detection (intra-assay coefficient of variation

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

ScoreGate: Adaptive Chunk Selection for Retrieval-Augmented Generation via Dual-Score Statistical Fusion

Fixed-cardinality retrieval injects a constant top-K chunks into the generator regardless of query complexity, causing over-retrieval for narrow queries and under-retrieval for compositional ones. We describe ScoreGate, a lightweight score-space decision mechanism that controls retrieval cardinality at inference time using two scores already produced by the standard pipeline: bi-encoder similarity s_i and cross-encoder reranker score r_i, with no additional model inference calls required. Its core insight is that cross-encoder affirmation can rescue semantically relevant chunks that bi-encoder retrieval ranks poorly due to vocabulary mismatch – a failure mode unaddressed by fixed-K or single-score thresholding. On MS MARCO (200 dev queries), ScoreGate achieves MRR@10 = 0.401 with 35% fewer retained chunks than Standard Top-K. On an internal benchmark (n=300, Fleiss' kappa=0.87), ScoreGate observed zero false positives (95% CI [96.4%, 100%]) at 97.77-99.34% recall, with 34.8% fewer tokens per query and only 31ms added latency. Results on both MS MARCO and real-world production traffic suggest that adaptive retrieval cardinality can improve retrieval efficiency without degrading retrieval quality.

13.
arXiv (quant-ph) 2026-06-11

Diffusive Relaxation of Participation Entropy in U(1)-symmetric Dynamics

arXiv:2606.11561v1 Announce Type: new Abstract: Participation entropy (PE) quantifies the spread of a many-body wavefunction across configuration space. While PE relaxes rapidly in generic chaotic systems, we show that $\mathrm{U}(1)$ conservation laws slow it down by imprinting with the slow hydrodynamic modes. Using a cluster expansion around equilibrium, we show that, after local density inhomogeneities decay, the leading PE deficit is dominated by squared connected density correlations. The long time relaxation is therefore controlled by diffusive correlation spreading, giving $\Delta S(t)\sim t^{-1/2}$ in the hydrodynamic regime and crossing over to $\sim \exp[-O(t/L^2)]$ when $t\geq L^2$. We confirm this entropy correlation relation using exact computation and infinite system tensor network simulations in various quantum $\mathrm{U}(1)$ conserving circuits. Our results establish PE as a sensitive probe of hydrodynamic memory and suggest that slow relaxation is a generic consequence of conservation laws.

14.
arXiv (CS.AI) 2026-06-16

FP8 is All You Need (Part 1): Debunking Hardware FP64 as the HPC Holy Grail (June 13th version)

arXiv:2606.06510v2 Announce Type: replace-cross Abstract: Conventional HPC holds that native hardware FP64 is the irreducible foundation of scientific computing. On AI-optimized GPUs of the NVIDIA B300 generation and beyond, native FP64 throughput has collapsed to ~1.3 TFLOPS even as FP8 tensor throughput has grown to multiple PFLOPS. We argue something stronger than that this is survivable: the FP8 tensor-core matrix-multiply is the sole computational primitive on which double-precision scientific computing needs to be built. Every canonical kernel – dense and sparse linear algebra, spectral transforms, stencils – and every application composing them reduces, via the Chinese Remainder Theorem-based Ozaki Scheme II, to sequences of FP8 matrix operations; the only non-FP8 arithmetic is a bounded, fixed-width integer accumulation at reconstruction. Native FP64 is thereby demoted from a hardware requirement to a derived accuracy guarantee obtained by composition over the FP8 primitive. We organize the claim as a five-layer hierarchy – the FP8 op, Ozaki II, the basic kernels or Berkeley "dwarfs", composite solvers, and full applications – and, because the dwarf taxonomy already spans scientific computing, establish it by exhibiting the reduction for every dwarf rather than a sample. The claim is falsifiable, and we build the instrument that tests it: a Tensor-Memory Equilibrium (TME) model extending the Roofline with emulation parameters (alpha, beta, gamma). We identify register-level fusion as the mechanism that keeps emulation memory-bound, project recovered FP64 performance across B300 and Rubin against an H100 baseline, and close the kernel coverage with a companion FFT analysis and compensated reductions. The model could have returned a negative verdict; instead it passes across the dwarfs and their compositions. This is the analytical half of a two-part program, with a follow-on implementation to validate the thesis on real silicon.

15.
arXiv (quant-ph) 2026-06-11

Magneto-Optical Trapping of a Metal Hydride Molecule

arXiv:2512.22350v2 Announce Type: replace-cross Abstract: We demonstrate a three-dimensional magneto-optical trap (MOT) of a metal hydride molecule, CaH. We are able to scatter $\sim$$10^{4}$ photons with vibrational loss covered up to vibrational quantum number $\nu=2$. This allows us to laser slow the molecular beam near zero velocity with a "white-light" technique and subsequently load it into a radio-frequency MOT. The MOT contains $230(40)$ molecules, limited by beam source characteristics and predissociative loss of CaH. The temperature of the MOT is below one millikelvin. The predissociative loss mechanism could, in turn, facilitate controlled dissociation of the molecule, offering a possible route to optical trapping of hydrogen atoms for precision spectroscopy.

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

Provable quantum speedups for computing persistence in topological data analysis

arXiv:2410.21258v2 Announce Type: replace-cross Abstract: Topological data analysis (TDA) aims to extract noise-robust features from a data set by examining the number and persistence of holes in its topology. We provide an efficient quantum algorithm for a computational problem closely related to a core task in TDA – determining whether a given hole persists across different length scales. Further, we prove the problem itself is $\mathsf{BQP}_1$-hard, implying that a classical solution is extremely unlikely; this stands in contrast to all previous quantum approaches to TDA, where the problems were also intractable for quantum computers, or where a rigorous proof of classical hardness still remains open. This result implies an {exponential} quantum speedup for this problem under standard complexity-theoretic assumptions. Our approach relies on encoding the persistence of a hole in a variant of the guided sparse Hamiltonian problem, where the guiding state is constructed from a harmonic representative of the hole.

17.
Nature (Science) 2026-06-17

A 98-qubit trapped-ion quantum computer with all-to-all connectivity

Quantum computers require both high-fidelity operations and large qubit numbers to surpass classical capabilities1. Trapped-ion platforms have demonstrated the highest gate fidelities of any modality2–6 but scaling to larger qubit numbers while preserving performance has remained a central challenge. We report on Quantinuum Helios, a 98-qubit trapped-ion quantum processor based on the quantum charge-coupled device (QCCD) architecture7. Helios features 137Ba+ hyperfine qubits8,9, all-to-all connectivity enabled by a rotatable ion storage ring connecting two quantum operation regions by a junction10,11, speed improvements from parallelized operations12 and a new software stack with real-time compilation of dynamic programs13. Averaged over all operational zones in the system, we achieve average infidelities of 2.5(1) × 10−5 for single-qubit (1Q) gates, 7.9(2) × 10−4 for two-qubit (2Q) gates and 3.3(5) × 10−4 for state preparation and measurement (SPAM), none of which are fundamentally limited and probably able to be improved. These component infidelities are predictive of system-level performance in both random Clifford circuits and random circuit sampling (RCS), the latter demonstrating that Helios operates well beyond the reach of classical simulation and establishes a new frontier of fidelity and complexity for quantum computers14. A new quantum computer, Quantinuum Helios, which is a 98-qubit trapped-ion quantum processor built on the QCCD architecture, demonstrates performance well beyond classical capabilities and provides a path for scaling up quantum computing.

18.
arXiv (CS.LG) 2026-06-18

QUIVER: Cost-Aware Adaptive Preference Querying in Surrogate-Assisted Evolutionary Multi-Objective Optimization

arXiv:2605.04267v2 Announce Type: replace Abstract: Interactive multi-objective optimization systems face a budget allocation dilemma: one can spend resources on expensive objective evaluations or on eliciting decision-maker preferences that identify the relevant region of the Pareto set. Moreover, preference elicitation itself spans modalities with different information content and cognitive burden, ranging from cheap, noisy pairwise preference statements (PS) to richer but costlier indifference adjustments (IA). We study cost-aware optimization under an unknown scalarization and introduce QUIVER (Query-Informed Value Estimation for Regret), a surrogate-assisted evolutionary multi-objective optimizer that adaptively chooses between objective evaluations and heterogeneous preference queries. At each step, QUIVER selects the next action by maximizing the expected decision-quality improvement per unit total cost. Across DTLZ and WFG benchmarks under synthetic decision-maker models, QUIVER achieves the lowest final utility regret on challenging WFG problems (utility regret of 2.14 on WFG4, 2.82 on WFG9: a 25% improvement over baselines), outperforming all single-modality baselines. We analyze how the optimal mix of PS and IA adapts to problem difficulty: on easy problems (DTLZ2), QUIVER selects 80\% PS queries; on hard problems (WFG9), it shifts to 35% IA queries. This adaptive modality selection demonstrates cost-aware preference learning in action.

19.
arXiv (CS.CV) 2026-06-16

Variational Test-time Optimization for Diffusion Synchronization

Collaborative generation, which coordinates multiple diffusion trajectories to extend the capabilities of pretrained priors, has emerged as a powerful paradigm for extending the applicability of diffusion models. Among existing approaches, diffusion synchronization provides a scenario-agnostic solution by introducing general guidance mechanisms. However, current synchronization approaches rely heavily on heuristics and still require task-specific tailoring, which limits their generalizability and performance. In this work, we mathematically derive a synchronization framework based on optimal control, providing a principled explanation of diffusion synchronization. During sampling, we optimize control variables to guide multiple trajectories toward coherent solutions while remaining close to the underlying diffusion prior. Our method operates entirely at test-time without additional training, thereby enabling broad applicability across diverse generation scenarios when combined with strong pretrained priors. We demonstrate consistent improvements over baselines on three representative collaborative generation tasks, covering a wide range of modalities and applications. Beyond performance gains, our work establishes a novel foundation for collaborative generation, opening a principled path toward extending pretrained generative models to new collaborative generation settings.

20.
medRxiv (Medicine) 2026-06-22

COVID-19 containment policies and hyperglycemia in pregnancy: correlation with the Stringency Index in a nationwide Belgian cohort

Background During the COVID-19 pandemic, gestational diabetes (GD) prevalence showed variable changes across regions, with most reporting increases and others decreases; however, its association with perinatal outcomes in Belgium remains unknown. We aimed to compare the prevalence of hyperglycemia in pregnancy (HIP) in 2020 versus 2019 and examined the correlation between HIP prevalence and pandemic-related restrictions measured by the Stringency Index (SI) and evaluate neonatal weight percentiles changes. Methods: We included all singleton live births in Belgium in 2019 and 2020 from Belgian birth registry data. We compared monthly proportions of HIP prevalence and Small for gestational age (SGA) and Large for gestional age (LGA) newborns in 2019 and 2020. Crude and adjusted odds ratios (ORs, aORs) were estimated with logistic and multinomial regression. The Spearman correlation coefficient was used to assess the correlation between the monthly average SI and the monthly aORs of HIP. Results: For deliveries from January to June 2020, no significant differences in HIP prevalence were observed compared with 2019. From July to December 2020, there was a significant increase in HIP, with peaks in July (GD screening in April) (aOR 1.41, 1.26-1.58) and November (GD screening in August) (aOR 1.33, 95% CI 1.18-1.49). There was no significant change in neonatal weight percentiles. The Spearman correlation coefficient between the SI and HIP aORs was 0.86 (p = 0.02). Conclusion During the pandemic, we observed an increase in the prevalence of HIP, compared to 2019, without a measurable impact on LGA or SGA newborns. The aOR of HIP in a given month was strongly correlated with the corresponding SI.

21.
bioRxiv (Bioinfo) 2026-06-11

Machine Learning-Guided Discovery of Bacterial-Selective Membrane-Active Compounds Reveals Mechanistic Bias in Antibiotic Training Datasets

The rise of antibiotic resistance necessitates the discovery of antibacterial compounds with novel mechanisms of action (MoAs). Recent machine learning approaches have shown promise in antibacterial compound discovery, but often identify derivatives of known antibiotic classes rather than mechanistically novel compounds. Previous approaches applied Tanimoto similarity filters at the end of screening pipelines, but this method has substantial drawbacks: Tanimoto similarity can be misleading in chemical space, and post-hoc filtering does not influence what activity models learn to prioritize. Here, we present a machine learning pipeline that addresses chemical novelty upfront by employing an XGBoost-based MoA classifier to explicitly prioritize compounds predicted to have mechanisms distinct from known antibiotic classes, combined with graph neural networks for antibacterial activity and toxicity prediction. Applied to the Zinc20 database, our approach successfully identified non-toxic antibacterial compounds structurally distinct from known antibiotics. Notably, the majority of these hits exhibited membrane-targeting activity with selectivity for bacterial cells over mammalian cells, suggesting potential for next-generation membrane-active antibiotics. However, we did not identify compounds with novel protein targets. Systematic analysis revealed that this limitation stems from mechanistic bias in training data rather than model architecture. Specifically, our activity model learned to preferentially score compounds similar to specific groups in the training data, thus overrepresenting certain MoA classes including membrane-active compounds. Even substantial model architecture and training data enhancements did not overcome this constraint. Our findings demonstrate that the primary bottleneck for discovering mechanistically novel antibiotics is the scarcity of diverse, mechanistically-annotated training data. This work provides both a methodological framework for mechanism-aware screening and critical insights into data requirements for genuinely novel antibiotic discovery.

23.
arXiv (CS.CV) 2026-06-11

Weakly Supervised Segmentation as Semantic-Based Regularization

Weakly supervised semantic segmentation (WSSS) trains dense pixel-level segmentation models from partial or coarse annotations such as bounding boxes, scribbles, or image-level tags. While recent work leverages foundation models such as the Segment Anything Model (SAM) to generate pseudo-labels, these approaches typically depend on heuristic prompt choices and offer limited ways to incorporate prior knowledge or heterogeneous labels. We address this gap by taking a neurosymbolic perspective: integrating differentiable fuzzy logic with deep segmentation models. Weak annotations and domain-specific priors are unified as continuous logical constraints that fine-tune SAM under weak supervision. The refined foundation model then produces improved pseudo-labels, from which we train a second-stage prompt-free segmentation model. Experiments on Pascal VOC 2012 and the REFUGE2 optic disc/cup segmentation dataset show that our logic-guided fine-tuning yields higher-quality pseudo-labels, leading to state-of-the-art segmentation accuracy that often exceeds densely supervised baselines.

24.
arXiv (CS.CL) 2026-06-17

Toward Accessible Psychotherapy Training Using AI-Driven Interactive Patient Avatars

Training psychotherapists in evidence-based interventions such as Acceptance and Commitment Therapy (ACT) requires repeated practice with meaningful feedback, yet opportunities for safe, standardized training are limited by ethical, logistical, and resource constraints. We introduce a system designed to support ACT-oriented psychotherapy training through spoken dialogue with an embodied virtual patient. The system uses large language models to simulate patient behavior conditioned on profiles derived from real therapy sessions and configurable clinical scenarios, while a separate automated evaluator provides turn-by-turn feedback on therapist responses based on established ACT fidelity criteria. Rather than aiming to replace supervision, the system is intended to support deliberate practice by enabling experimentation, reflection, and immediate feedback in low-risk settings. Expert evaluation with practicing psychologists confirmed high realism in patient behavior and demonstrated that immediate turn-by-turn ACT feedback increased therapists' awareness of intervention choices and enabled effective experimentation with alternative responses. Quantitative evaluation across 49 therapy transcripts identified GPT-4o-mini as the optimal feedback model, achieving the lowest mean absolute error (MAE = 6.12) in replicating human supervisor ACT fidelity ratings with statistically significant agreement. This work demonstrates the potential of fidelity-aware simulated patients as a scalable complement to psychotherapy training.

25.
medRxiv (Medicine) 2026-06-16

Investigating naming error patterns after non-invasive brain stimulation and language treatment in persons with aphasia

Abstract Background: Transcranial direct current stimulation (tDCS) paired with behavioral language therapy can improve naming in persons with aphasia (PWA), yet naming errors persist. Little is known about how naming error patterns change after non-invasive brain stimulation is combined with language treatment. Aims: To examine whether right cerebellar tDCS plus computerized aphasia therapy changes the types of naming errors in people with chronic aphasia across timepoints, and to determine whether effects differ by cerebellar tDCS polarity (anode vs. cathode). Methods and Procedures: In a randomized, double-blind, sham-controlled, within-subject crossover study, we retrospectively analyzed behavioral data from 24 individuals with post-stroke aphasia. Each participant completed two 15-session intervention periods (3-5 sessions/week) with active cerebellar tDCS + computerized aphasia therapy and sham + computerized aphasia therapy, separated by a two-month washout. General linear models (GLMs) assessed longitudinal changes in six error types (semantic, phonological real word, phonological nonword, no response, mixed, unrelated) on an untrained picture naming task (Philadelphia Naming Test; PNT) and a trained task (Naming 80; N80). Additional GLMs evaluated polarity effects with 2 (Group: anode vs. cathode) x 2 (Treatment) interactions, and treatment-order effects with 2 (Group: tDCS-first vs. sham-first) x 2 (Treatment) interactions. Outcomes and Results: Active cerebellar tDCS did not significantly change error types for trained items (N80). For untrained items (PNT), active tDCS reduced several error types relative to sham, with the clearest and most durable reduction in phonological nonword errors; more moderate reductions occurred for phonological real word and unrelated errors. Mixed errors showed a marginally opposite pattern, tending to increase after tDCS and decrease after sham. Polarity analyses indicated broadly similar effects across anodal and cathodal stimulation overall, but only the anode group showed a reliable treatment effect for phonological nonword errors on the PNT. Treatment-order analyses revealed no significant order effects. Conclusions: Our results indicate a shift in naming error types, particularly after tDCS treatment for the untrained naming task (PNT). These findings may help guide the course of treatment approaches of those with aphasia and what error naming pattern types may show changes post stroke when combining non-invasive brain stimulation and computerized aphasia therapy. Clinical Trial Registration: Cerebellar Transcranial Direct Current Stimulation and Aphasia Treatment [NCT02901574] Keywords: aphasia, naming errors, non-invasive brain stimulation, cerebellar tDCS, computerized aphasia treatment