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01.
medRxiv (Medicine) 2026-06-24

Durability and Seasonal Variation in the Effectiveness of Nirsevimab over Three Seasons in Connecticut

Background Nirsevimab has been widely administered in the United States since 2023 to protect infants and young children from severe disease caused by respiratory syncytial virus (RSV). Although early post-licensure studies have shown high effectiveness against medically attended RSV infection, uncertainty remains about the durability of protection, effectiveness beyond the first RSV season, and the extent to which changing RSV seasonality influences real-world effectiveness. Objective To estimate the effectiveness of nirsevimab against medically attended RSV infection across three consecutive RSV seasons and to examine how effectiveness varies by season and time since immunization. Methods We conducted a test-negative case-control study utilizing electronic health records of infants and young children tested for RSV by polymerase chain reaction in outpatient and inpatient settings within the Yale New Haven Health System between October 1, 2023, and March 1, 2026. Effectiveness of nirsevimab was estimated using multivariable logistic regression, adjusting for age, weekly RSV activity, pre-existing risk factors, and other potential confounders. Variation in effectiveness was examined by season, encounter setting, and time since immunization up to 24 months. Results Overall, 17,755 infants and young children were tested for RSV infection, of whom 2,388 (13.4%) were cases and 15,367 (86.6%) were controls. The overall effectiveness of nirsevimab was 67.3% (95% confidence interval [CI]: 59.8, 73.3%) against all medically-attended RSV infections, 60.2% (95% CI: 49.6, 68.5%) against RSV-associated outpatient visits, and 88.9% (95% CI: 82.3, 93.0%) against RSV-associated hospitalization. Effectiveness against medically attended RSV infection declined across seasons, from 76.7% (95% CI: 60.5, 86.3%) in 2023/24 to 54.4% (95% CI: 33.0, 68.9%) in 2025/26. Lower season-specific effectiveness in later seasons corresponded with progressively delayed RSV activity over. Protection against RSV-associated hospitalization declined with increasing time since immunization, from 92.5% (95% credible interval [CrI]: 85.9, 96.4%) at 1 month, to 77.2% (95% CrI: 60.4, 87.6%) at 6 months, and 39.9% (95% CrI: 2.4, 63.3%) at 12 months post-immunization, after which effectiveness plateaued. Conclusions Nirsevimab remained effective against RSV-associated hospitalization through 6 to 12 months after immunization. Delayed RSV activity was associated with lower effectiveness, highlighting the importance of aligning administration with local RSV circulation.

02.
arXiv (CS.LG) 2026-06-18

Online Distributional Prediction via Latent Cluster Geometry Under Drift and Corruption

arXiv:2606.18778v1 Announce Type: new Abstract: Online learning in non-stationary streams is often formulated as tracking a point estimate, but many applications require predicting the full data-generating distribution. We study online distributional prediction under drift and adversarial corruption. Our approach represents each candidate law through a latent cluster geometry: a variable-size configuration of centers that organizes probability mass and induces a predictive distribution. A Gibbs quasi-posterior over these configurations yields an online predictor by posterior averaging, and the resulting variable-dimensional posterior can be sampled with reversible-jump MCMC. The method therefore avoids specifying a parametric streaming law while retaining a structured latent space for uncertainty, regularization, and comparison. We evaluate performance by cumulative Wasserstein-1 regret against the time-varying true law. The analysis separates two effects: corruption perturbs the loss-based posterior update, whereas drift makes long-horizon posterior memory stale. We address the latter with a restarted variant that temporally localizes the same quasi-Bayesian update. The resulting high-probability bounds decompose into a PAC-Bayesian complexity term, a corruption-sensitive posterior perturbation term, and a dynamic optimal-transport term driven by \(A_T^{\mathrm{OT}}=\sum_{t=2}^T W_2^2(p_{t-1}^*,p_t^*)\). Under bounded support, stable latent geometry, predictive-map regularity, oracle realizability, localized restart windows, sublinear transport action, and sublinear corruption budget, the restarted predictor achieves sublinear cumulative Wasserstein regret. These guarantees require no parametric model for the stream, drift mechanism, or corruption process.

03.
arXiv (CS.CV) 2026-06-25

SplatPainter: Interactive Authoring of 3D Gaussians from 2D Edits via Test-Time Training

The rise of 3D Gaussian Splatting has revolutionized photorealistic 3D asset creation, yet a critical gap remains for their interactive refinement and editing. Existing approaches based on diffusion or optimization are ill-suited for this task, as they are often prohibitively slow, destructive to the original asset's identity, or lack the precision for fine-grained control. To address this, we introduce SplatPainter, a state-aware feedforward model that enables continuous editing of 3D Gaussian assets from user-provided 2D view(s). Our method directly predicts updates to the attributes of a compact, feature-rich Gaussian representation and leverages Test-Time Training to create a state-aware, iterative workflow. The versatility of our approach allows a single architecture to perform diverse tasks, including high-fidelity local detail refinement, local paint-over, and consistent global recoloring, all at interactive speeds, paving the way for fluid and intuitive 3D content authoring.

04.
arXiv (CS.CL) 2026-06-16

Pretraining A Large Language Model using Distributed GPUs: A Memory-Efficient Decentralized Paradigm

Pretraining large language models (LLMs) typically requires centralized clusters with thousands of high-memory GPUs (e.g., H100/A100). Recent decentralized training methods reduce communication overhead by employing federated optimization; however, they still need to train the entire model on each node, remaining constrained by GPU memory limitations. In this work, we propose SParse Expert Synchronization (SPES), a memory-efficient decentralized framework for pretraining mixture-of-experts (MoE) LLMs. SPES trains only a subset of experts per node, substantially lowering the memory footprint. Each node updates its local experts and periodically synchronizes with other nodes, eliminating full-parameter transmission while ensuring efficient knowledge sharing. To mitigate limited per-expert data utilization under sparse expert updates, we introduce an expert-merging warm-up strategy, where experts exchange knowledge early in training, to rapidly establish foundational capabilities. With SPES, we train a 2B-parameter MoE LLM using 16 standalone 48GB GPUs over internet connections, which achieves competitive performance with centrally trained LLMs under similar computational budgets. We further demonstrate scalability by training a 7B model from scratch and a 9B model upcycled from a dense checkpoint, both of which match prior centralized baselines. Our code is available at https://github.com/zjr2000/SPES.

05.
arXiv (CS.CV) 2026-06-15

HPSv3++: Scaling Reward Models Across the Full Spectrum of Diffusion Model Capabilities

Reward models guide text-to-image (T2I) systems toward outputs aligned with human preferences. However, typical reward models such as HPSv3 are trained on pre-annotated data from earlier T2I models, without accounting for quality discriminative shifts arising from evolving model capabilities and reinforcement learning (RL) iterations, limiting their broader applicability. In this work, we propose HPSv3++, a reward model framework that elevates the HPSv3 model for varying T2I model capabilities and their RL iteration changes across the full capability-iteration spectrum. Specifically, we first introduce HPDv3++, a 212K dual-dimension preference dataset annotated for text fidelity and aesthetic quality using a recent high-capability (Qwen-Image) model with human supervision. We then propose a two-stage training framework. Stage 1 employs data-aware orthogonal gradient projection to incorporate diverse aesthetic perception from HPDv3++ while preserving the original effective human preference knowledge in HPSv3. Stage 2 further leverages unlabeled data from T2I models spanning different capability levels and RL iterations, and introduces a joint capability-iterations conditioned signal for the reward model together with a standard deviation-driven unsupervised guidance mechanism, strengthening reward model across the capability-iteration spectrum. HPSv3++ achieves state-of-the-art preference prediction, outperforming HPSv3 9.8% on HPDv3, 5.5% on GenAI-Bench, while achieving 79.1%/88.1% on our proposed HPDv3++. When used for T2I RL training, it consistently improves GenEval scores across diverse T2I models, demonstrating its wide-range capabilities. The code is available at https://github.com/PlantPotatoOnMoon/HPSv3-PlusPlus.

07.
arXiv (CS.CL) 2026-06-11

The Structural Attention Tax: How Retrieval Format Hijacks In-Context Learning Independent of Content

Retrieval-augmented generation (RAG) systems inject external knowledge to improve LLM outputs, yet the format of injected content – distinct from its semantic relevance – can independently distort the model's attention distribution. We identify and formalise a phenomenon we term the structural attention tax: knowledge graph (KG) triples, due to their relational delimiters and repeated slot patterns, capture 2-3x more attention per token than semantically equivalent natural-language text ($\hat{o}$(KG) $\approx$ 0.70 vs. $\hat{o}$(neutral) $\approx$ 0.25), compressing demonstration attention by up to 42% – regardless of whether the triples are relevant or noise. We develop a formal framework decomposing attention scores into semantic and structural components (Eq. 2), derive a compression bound (Proposition 1) connecting token-level format bias to demonstration attention loss, and show that the structural term governs how much attention is diverted while the semantic term governs whether this helps or hurts. This decoupling reveals two orthogonal axes for improving retrieval-augmented ICL: optimising retrieval quality (semantic axis) and reducing format-driven attention capture (structural axis). Empirically, across two model families (Mistral-7B, LLaMA-3-8B) and three QA benchmarks, we observe that source-task alignment dominates: task-matched BM25 retrieval achieves 58-62% on HotpotQA vs. ConceptNet's 25-27%, a >30 pp gap that dwarfs all gating strategies ($\leq$2 pp). We derive five structure-aware mitigation strategies from the framework, ranging from zero-cost prompt modifications to training-time regularisation; format flattening (S3) is validated by both accuracy and attention-level evidence from a verbalized-triple control, while structural dispersal (S1) yields mixed results that illuminate the challenges of format-level intervention.

08.
arXiv (CS.AI) 2026-06-11

SPEA2$^+$: Improved Density Estimation in SPEA2 with Provable Runtime Guarantees

arXiv:2606.12382v1 Announce Type: cross Abstract: The Strength Pareto Evolutionary Algorithm 2 (SPEA2) is a popular and prominent evolutionary algorithm for solving multi-objective optimisation problems. Despite its popularity, theoretical analyses of SPEA2 have only appeared recently. Moreover, these analyses focus exclusively on how SPEA2 handles non-dominated solutions and disregard the algorithmic components responsible for handling dominated solutions. We conduct a first runtime analysis of SPEA2 for which these components are analysed. We prove that, unlike other prominent algorithms, including NSGA-II, NSGA-III and SMS-EMOA under the same setting of constant population size and duplicate elimination, SPEA2 is unable to cover the Pareto front of the OneTrapZeroTrap benchmark efficiently. Our results indicate that using k-th nearest-neighbour distance in the fitness assignment provides an insufficient signal to maintain diversity among dominated individuals. To address this issue, we propose an improved variant, SPEA2$^+$, that considers all pairwise distances. The new algorithm achieves the same performance guarantees as the other prominent algorithms on OneTrapZeroTrap, while matching the performance of the original SPEA2 on simpler problems. Experimental results complement our theoretical findings.

09.
Nature Medicine 2026-06-22

<b>PROTEUS trial heralds perioperative therapy for prostate cancer</b>

Perioperative androgen-deprivation therapy plus apalutamide could represent a new treatment option for patients with high-risk, localized prostate cancer. Perioperative androgen-deprivation therapy plus apalutamide could represent a new treatment option for patients with high-risk, localized prostate cancer.

10.
arXiv (CS.CL) 2026-06-24

Are LLM Evaluators Really Narcissists? Sanity Checking Self-Preference Evaluations

Recent research has shown that large language models (LLMs) favor their own outputs when acting as judges, undermining the integrity of automated post-training and evaluation workflows. However, it is difficult to disentangle which behaviors are explained by narcissism versus experimental confounds. Specifically, LLM evaluators may deliver self-preferring verdicts when comparing responses to questions they fail on; these verdicts may not depend on the identity of the author, but on evaluator quality. We correct this by directly comparing the judge's voting distribution in cases where it evaluates itself versus another model. This evaluator quality baseline reveals that only 51% of examples in previous findings retain statistical significance against this null hypothesis, covering 89.6% of total self-preference probability mass. Finally, we compare the entropy of voting distributions, suggesting uncertainty-driven overlap, and show that our procedure enables more careful documentation against the backdrop of judge-bias research.

11.
PLOS Computational Biology 2026-06-10

A mean-field model of neural networks with PV and SOM interneurons reveals connectivity-based mechanisms of gamma oscillations

by Farzin Tahvili, Martin Vinck, Matteo Di Volo Classic theoretical models of cortical oscillations are based on the interactions between two populations of excitatory and inhibitory neurons. Nevertheless, experimental studies and network simulations suggest that interneuron subclasses such as parvalbumin (PV) and somatostatin (SOM) exert distinct control over oscillatory dynamics. Yet, we lack a theoretical understanding of the mechanisms underlying oscillations in E-PV-SOM circuits and of the differences with respect to the classical mechanisms for oscillations in simpler E–I networks. Here, we derive a biologically realistic mean-field model of a canonical three-population E-PV-SOM circuit. This model robustly generates oscillations whose features are consistent with experimental observations, including the relative timing of PV and SOM activity and the effects of optogenetic perturbations. By reducing the model to a linear analytical form, we demonstrate that gamma oscillations emerge directly from the cell-specific connectivity of the three-population circuit. This connectivity motif alone accounts for experimentally observed phase relationships, with PV activity consistently leading that of SOM neurons. Together, this mean field model identifies a distinct structural mechanism giving rise to oscillations in canonical E–PV–SOM circuits and provides theoretical primitives for constructing large-scale, cell-type-specific models of cortical dynamics.

12.
medRxiv (Medicine) 2026-06-19

A soluble bi-specific fusion protein for the improved expansion of human CD8+ CAR-T cells

The success of Chimeric Antigen Receptor (CAR) T cell therapy is heavily dependent on the quality of the final cellular product. Current expansion protocols often rely on reagents that require removal from cell culture media, posing logistical challenges in manufacturing, and can also lead to terminal differentiation. Here, we evaluate the use of a soluble, bead-free T cell activator, T cell expansion protein (T-CEP), as a streamlined alternative for generating potent CAR-T cells. Human T cells were activated with T-CEP or known T cell activators (Dynabeads and TransAct) and transduced with either CD19 or interleukin-13 (IL-13) mutein (tetravariant-13; TV-13)-based CAR lentiviral vectors. Our results demonstrate that T-CEP supports robust CAR-T cell expansion and achieves transduction efficiencies comparable to commercial reagents for both types of CAR-T cells. Notably, T-CEP significantly favored the expansion of CD8+ T cells, yielding an enhanced CD27+ phenotype and a lower CD4:CD8 ratio compared to TransAct. Cytotoxicity assays confirmed that T-CEP-expanded CAR-T cells possess cytolytic function equivalent to commercial reagents for both CARs, while exhibiting lower levels of inflammatory cytokine secretion. In summary, T-CEP represents a competitive alternative to existing expansion agents, as it does not require its removal during CAR-T manufacturing and generates a CD8+ dominant, less-differentiated phenotype without compromising efficacy.

13.
arXiv (CS.AI) 2026-06-25

Weight Space Representation Learning via Neural Field Adaptation

arXiv:2512.01759v3 Announce Type: replace-cross Abstract: We investigate the potential of weights to serve as effective representations, focusing on neural fields. Our key insight is that constraining the optimization space through a pre-trained base model and low-rank adaptation (LoRA) can induce structure in weight space. Across reconstruction, generation, and analysis tasks on 2D and 3D data, we find that multiplicative LoRA weights achieve high representation quality while exhibiting distinctiveness and semantic structure. When used with latent diffusion models, multiplicative LoRA weights enable higher-quality generation than existing weight-space methods.

14.
arXiv (CS.AI) 2026-06-25

Are Tabular Foundation Models Robust to Realistic Query Distribution Shifts in Microbiome Data?

arXiv:2606.24995v1 Announce Type: cross Abstract: Tabular foundation models (TFMs) achieve strong performance on microbiome abundance data, yet their robustness under realistic distribution shift remains poorly characterized. We introduce a benchmark that evaluates the robustness of TFMs to biologically inspired perturbations across six gut microbiome datasets spanning four disease contexts. In this in-context learning setting, models receive unperturbed support sets as context and are evaluated on perturbed query samples. To isolate robustness beyond "shortcut" features, we preserve the most discriminative taxa and apply three controlled perturbation strategies: (i) removal of high-abundance (uninformative) taxa, (ii) sparsification via increased zero-inflation, and (iii) zero-imputation via spurious non-zero injections. Our results show that protecting discriminative features is insufficient to guarantee stability under support-query shift: across datasets, all perturbations degrade model performance, with zero-imputation consistently the most harmful, indicating that corrupting global feature structure can break generalization even when key taxa are retained. Sparsification disproportionately affects TFMs relative to a classical random forest baseline, suggesting greater sensitivity to zero-inflation-type shifts. The code is publicly available at: https://github.com/UMMISCO/metagenomics-fm/.

15.
arXiv (CS.CL) 2026-06-16

A Unified Definition of Hallucination: It's The World Model, Stupid!

Despite numerous attempts at mitigation since the inception of language models, hallucinations remain a persistent problem even in today's frontier LLMs. Why is this? We review existing definitions of hallucination and fold them into a single, unified definition wherein prior definitions are subsumed. We argue that hallucination can be unified by defining it as simply inaccurate (internal) world modeling, in a form where it is observable to the user. For example, stating a fact which contradicts a knowledge base OR producing a summary which contradicts the source. By varying the reference world model and conflict policy, our framework unifies prior definitions. We argue that this unified view is useful because it forces evaluations to clarify their assumed reference "world", distinguishes true hallucinations from planning or reward errors, and provides a common language for comparison across benchmarks and discussion of mitigation strategies. Building on this definition, we also connect our framework to HalluWorld, a complementary benchmark that instantiates fully specified reference world models for stress-testing model hallucinations.

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

Workflow-GYM: Towards Long-Horizon Evaluation of Computer-use Agentic tasks in Real-World Professional Fields

arXiv:2606.11042v2 Announce Type: replace Abstract: Recent years have witnessed the rapid evolution of AI agents toward handling increasingly complex, real-world tasks. However, existing benchmarks rarely evaluate whether agents can operate graphical user interfaces to complete long-horizon, high-value professional workflows across diverse domains. Current GUI benchmarks still predominantly focus on general-purpose software, relatively simple applications, and short-horizon tasks, leaving it largely unknown whether modern agents can follow user instructions to autonomously operate domain-specific professional software and accomplish economically valuable work in an end-to-end manner. To bridge this gap, we introduce Workflow-GYM, a benchmark for long-horizon GUI tasks centered on professional domains and specialized software environments. Through extensive experiments on state-of-the-art models, we find that even the strongest models achieve only slightly above 30% success rates, highlighting that professional long-horizon GUI workflows remain highly challenging for current GUI agents. Further analysis reveals that current agents struggle to maintain long-horizon workflow consistency, frequently exhibiting workflow stage omission, error propagation, objective drift, and insufficient understanding of professional software environments. Our findings provide important insights into the limitations of current agent systems and suggest key directions for the next generation of GUI-agent research.

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

Smoothing Dark Areas in Molecular Latent Diffusion

arXiv:2606.13955v1 Announce Type: new Abstract: Latent diffusion is a promising framework for scalable 3D molecular generation, but it requires a latent space that remains smooth, valid, and navigable beyond posterior samples. Existing molecular VAEs, however, are typically learned through reconstruction-based objectives, which do not guarantee such a latent space. We show that this leads to dark areas: regions of latent space that are reachable during diffusion sampling but decode to disconnected or chemically invalid molecules. Unlike in image generation, molecular decoding requires strict structural and chemical precision, so even small latent perturbations can produce catastrophic failures. We therefore propose TopVAE, a topology-optimized VAE that reduces dark areas by making the decoder internalize structural and chemical constraints during training, eliminating the need for test-time chemical correction. TopVAE greatly improves off-posterior robustness, and when paired with a standard DiT, achieves $77\%$ lower FCD-3D on QM9, the highest V&C, $52\%$ lower FCD-3D on GEOM-Drugs, and $1.29{\times}$ more stable and connected molecules on zero-shot scaffold inpainting.

18.
arXiv (CS.AI) 2026-06-25

The Token Not Taken: Sampling, State, and the Stochasticity of AI Agents

arXiv:2606.08998v2 Announce Type: replace Abstract: Agentic AI systems can behave differently across runs: the same request may produce a different plan, a different tool call, a different code edit, or a different final answer. Such variability arises from several layers that are often conflated. At the core of many current agents is a foundation model, a large pretrained model adaptable to many downstream tasks, embedded in an orchestration loop that plans, calls tools, observes results, and updates state. One explicit intrinsic source of variability in such systems is token generation: the model computes scores over possible next tokens, the scores are converted into probabilities, and a decoder may sample tokens using a pseudo-random number generator. A small sampled token difference can then propagate upward into a different tool call, code path, search query, or agent state. Other sources of variability are extrinsic to token sampling, including changing environments, live data, serving infrastructure, batch effects, and numerical details. By separating these layers, this tutorial clarifies what it means to call agentic AI systems stochastic, when such variability can be reproduced under matched conditions, and why deterministic execution need not imply identical behavior in deployed settings.

19.
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.

20.
medRxiv (Medicine) 2026-06-15

Reaching out-of-school girls with HPV vaccination: A qualitative evaluation in six low- and middle-income countries using the RE-AIM framework

Background Infection with human papillomavirus (HPV), the primary cause of cervical cancer, disproportionately affects women in low- and middle-income countries (LMICs). While school-based vaccination of adolescent girls against HPV is highly effective, this strategy systematically excludes out-of-school (OOS) girls. Using the RE-AIM framework, we explored strategies to reach OOS girls with HPV vaccination across six African and Asian LMICs. Methods We conducted semi-structured key informant interviews with 32 vaccination program stakeholders from Cambodia, Cameroon, Kenya, Malawi, Mozambique, and Uganda between May and September 2024. Interviews explored countries implementation successes, challenges, and strategies to reach OOS girls with HPV vaccination and sustainability considerations. Data were analyzed using a hybrid team-based thematic analysis approach guided by the RE-AIM framework. Results Community outreach-based strategies, typically integrated into routine immunization outreach, were identified as the most effective approach to reach OOS girls with HPV vaccination. Targeted strategies, such as locating outreach clinics in community venues frequented by OOS girls (e.g., churches, markets) enhanced implementation. Perceived effectiveness of these strategies varied across participants, and formal assessment of effectiveness was constrained by the absence of disaggregated vaccination coverage data by school enrollment status. Some subpopulations of OOS girls (i.e., girls in nomadic or migrant communities, urban OOS girls) were not readily reached through standard outreach approaches, prompting implementation of adapted and tailored strategies for these subpopulations. Costs associated with conducting outreach in harder-to-reach areas were major barriers to reaching OOS girls, presenting challenges to the sustainability and cost-effectiveness of these approaches. Conclusions Routine community outreach platforms were widely perceived as most effective for reaching OOS girls. Strengthening disaggregated monitoring systems, adapting outreach for harder-to-reach subpopulations of OOS girls, and financing delivery models for tailored outreach strategies will be critical to improving equitable HPV vaccine coverage among OOS girls.

21.
PLOS Medicine 2026-05-14

First-trimester nonsteroidal anti-inflammatory drugs exposure and risk of major congenital malformations: A retrospective register-based cohort study

by Ariel Avraham Hasidim, Itamar Ben Shitrit, Daphna Idan, Tal Michael, Amalia Levy, Gali Pariente, Eitan Lunenfeld, Sharon Daniel Background Pain and fever are common in early pregnancy, yet their management poses a major clinical dilemma. Although not confirmed, recent studies have raised safety concerns regarding acetaminophen. Evidence on the use of nonsteroidal anti-inflammatory drugs (NSAID) in the first trimester remains inconclusive. This uncertainty has left clinicians with limited evidence to guide treatment decisions. This study evaluated the association between first-trimester NSAID exposure and the risk of major congenital malformations (MCMs) in a large, population-based cohort of pregnancies. Methods and findings We conducted a population-based retrospective cohort study within the Southern Israeli Pregnancy Registry (siPREG) project, including all singleton pregnancies of women aged 15–45 years resulting in live births, stillbirths, or elective terminations for fetal malformations at a Soroka University Medical Center between 1998 and 2018. Pregnancies exposed to established teratogens, multiple gestations, and those with documented genetic or chromosomal anomalies were excluded. First-trimester NSAID exposure was defined by pharmacy dispensations (overall and by specific agents). MCMs were identified from linked clinical, hospitalization, and termination records through the first postnatal year.Propensity scores were estimated using covariates selected via a directed acyclic graph, including maternal age, ethnicity, diabetes, medical indication for NSAID use, exposure to other antipyretics, obesity, smoking, folic-acid use, gravidity, perinatal care, and year of pregnancy. Generalized full matching was used to balance covariates. Adjusted risk ratios were derived using weighted Poisson regression with G-computation, and two-way cluster-robust standard errors, jointly clustering by maternal identifier and matching subclass. Sensitivity analyses included a dose–response assessment across defined-daily-dose (DDD) categories and a tipping-point analysis evaluating the impact of potential misclassification from unrecorded over-the-counter NSAID use.A total of 264,858 singleton pregnancies were included in the final cohort; 20,202 (7.6%) were exposed to NSAID, most commonly ibuprofen (5.1%), diclofenac (1.6%), and naproxen (1.2%). NSAID exposure, in total and as individual agents, was not associated with MCMs overall (8.2% versus 7.0%; matched-adjusted-Relative Risk (aRR) = 0.99 (95% CI [0.90,1.10])) or with organ-system-specific MCMs, including cardiovascular (matched-aRR = 1.05 (95% CI [0.92,1.20]), musculoskeletal (matched-aRR = 1.03 (95% CI [0.77,1.39])), central nervous system (matched-aRR = 0.77 (95% CI [0.53,1.11])), cleft palate (matched-aRR = 0.95 (95% CI [0.47–1.91])), gastrointestinal (matched-aRR = 1.03 (95% CI [0.64–1.63])), and genitourinary (matched-aRR = 0.99 (95% CI [0.72,1.35])) malformations. Dose–response analyses showed no significant association with MCMs across cumulative NSAID exposure: short-term (1–7 DDD, matched-aRR = 1.06 (95% CI [0.97,1.15]), medium-term (8–21 DDD, matched-aRR = 1.10 (95% CI [0.99,1.22]), and long-term (>21 DDD, matched-aRR = 1.24 (95% CI [0.94,1.63])). The main limitation was the potential for minor exposure misclassification due to over-the-counter availability of ibuprofen, although sensitivity analyses simulating such misclassification suggested minimal impact on the risk estimates. Conclusion In this large, population-based cohort, we found no evidence supporting an association between first-trimester exposure to NSAID and MCMs, providing reassuring evidence regarding their fetal safety in early pregnancy.

22.
arXiv (CS.AI) 2026-06-18

EMORSION: Examining the Impact of Audio Parameters on Emotional Responses and Immersion in Film

arXiv:2606.18266v1 Announce Type: cross Abstract: EMORSION is an exploratory proof-of-concept study examining how film audio design shapes audience emotion and immersion in acinema setting. Four film scenes were selected across the horror (2) and drama (2) genres, balanced between mainstream and independent productions. For each scene, multiple alternative audio mixes were created by systematically manipulating three core aspects of audio design, frequency (pitch), dynamics (loudness), and directionality (spatial placement). Three audience groups viewed the scenes, with each group exposed to one manipulated mix alongside a control mix for each scene. Audience responses were assessed through a triangulated multimodal framework combining self-reported emotion and immersion via a questionnaire, physiological measures including heart rate monitoring, and video-based motion tracking. The protocol successfully captured measurable, interpretable differences across audio conditions, indicating that even subtle changes in audio design can shape emotional perception and immersion. Unconventional mixes tended to produce greater variability in audience interpretation, while conventional immersive mixes were associated with stronger cross-audience agreement. These findings establish the feasibility of the EMORSION protocol and motivate larger-scale studies to characterise the role of specific audio parameters in shaping audience experience.

23.
arXiv (CS.LG) 2026-06-19

UltraEP: Unleash MoE Training and Inference on Rack-Scale Nodes with Near-Optimal Load Balancing

arXiv:2606.04101v3 Announce Type: replace-cross Abstract: Large-scale expert parallelism (EP) is becoming pivotal for training and serving frontier MoE models, but it also amplifies device-level expert load imbalance into compute stragglers, token all-to-all bottlenecks, and activation-memory spikes. Existing balancers redistribute experts periodically based on historical load, which becomes unreliable for production deployments with non-stationary load patterns. We present UltraEP, the first exact-load, real-time balancer for large-EP MoE training and serving prefill on rack-scale nodes (RSNs). Leveraging the extended scale-up connectivity among dozens of GPUs within RSNs, UltraEP rebalances every microbatch and layer on critical paths, which requires nontrivial co-design of plan solving and expert replication communication to minimize exposed overhead. To this end, UltraEP eagerly reacts to post-gating load with an efficient quota-driven planner, and executes the resulting irregular expert-state transfers with RSN-native persistent tile streaming and relay-based fan-out mitigation. We evaluate UltraEP in a multi-RSN deployment of up to 256 GPUs, using cutting-edge MoE models from 106B to 671B parameters. Averaged across training and serving, UltraEP achieves 94.3% of the force-balanced ideal throughput, delivering 1.49$\times$ improvement over no-balancing, while reducing the final inter-rank imbalance from 1.30$-$4.01 to 1.01$-$1.04.

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

PreAct: Computer-Using Agents that Get Faster on Repeated Tasks

作者:

arXiv:2606.17929v1 Announce Type: new Abstract: Computer-using agents drive real software through the screen – clicking and typing – but they solve every task from scratch: asked to repeat a task, an agent re-reads the screen, re-reasons every tap, and pays the full cost again. We present PreAct, which lets such an agent get faster on tasks it has done before. The first time it succeeds, PreAct compiles the run into a small state-machine program-states that check the screen, transitions that act-and on later runs replays it directly instead of invoking the agent 8.5-13x faster, with no per-step language-model calls. Replay is not blind: at each step PreAct checks that the screen matches what the program expects before acting, and hands control back to the agent the moment something is off. PreAct applies the same discipline when deciding what to keep: a freshly compiled program enters the store only if, re-run from a clean state, an independent evaluator confirms it solved the task-catching programs that replay to their last step yet leave the task undone. Across a mobile, a desktop, and a web benchmark, this store-time check separates repeated runs that improve from ones that degrade as faulty programs accumulate, worth 1.75-2.6 tasks per benchmark, the same direction on all three; a fallback that explores afresh when no program fits brings PreAct level with a strong record-and-replay baseline. We also report what did not matter: prompt wording, runtime guardrails, and whether a language model or a plain embedding retriever selects which program to reuse.

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arXiv (CS.AI) 2026-06-16

Guiding Federated Graph Recommendation with LLM-encoded knowledge

arXiv:2606.15277v1 Announce Type: cross Abstract: Graph-based recommender systems are highly effective at extracting collaborative signals from user–item interactions, and federated learning (FL) allows these models to be trained while preserving user privacy. However, aggregating graph representations across distributed, non-IID clients remains a challenge; structural embeddings learned locally often misalign, and naive averaging fails to capture meaningful cross-client relationships. Most existing federated graph methods rely exclusively on structural aggregation, neglecting the rich, global semantic context available in large language models (LLMs). In this paper, we propose a novel framework that uses LLM-encoded knowledge to guide federated graph recommendation. Specifically, clients learn structural representations from local graphs while simultaneously summarizing their typical interaction patterns into compact semantic vectors via a frozen LLM. The central server then uses these LLM-encoded semantic signals to discover related preference patterns across clients, guiding the selective aggregation of their structural representations. This enables semantically informed cross-client collaboration without exposing raw data. Extensive experiments on standard benchmarks show that guiding structural alignment with LLM-encoded knowledge consistently improves recommendation accuracy over existing federated graph baselines.