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01.
medRxiv (Medicine) 2026-06-15

Therapeutic efficacy study on shoulder impingement syndrome in swimmers: a network meta-analysis

Shoulder impingement syndrome (SIS), including subacromial impingement and rotator cuff tendinitis, is commonly caused by repetitive swimming movements and associated shoulder joint dysfunction. Despite numerous available treatment options, no consensus exists on the most effective treatment option. Therefore, this systematic review and network meta-analysis aimed to investigate treatment methods for SIS in swimmers. Using a frequentist framework and Cochrane PICOS principles, we compared SIS treatments, constructed network evidence diagrams, and assessed heterogeneity. A total of 45 studies were included in the qualitative synthesis, and 42 contributed to the network meta-analysis, comprising 1752 participants, 9 treatment categories, and outcome measures. For pain outcomes, some adjunctive interventions combined with exercise showed favorable ranking probabilities, although several estimates were accompanied by wide confidence intervals. For shoulder range-of-motion outcomes, taping, acupuncture, manual therapy, and sport-specific training showed favorable effects in selected comparisons, particularly for external and internal rotation. According to surface under the cumulative ranking curve (SUCRA) rankings, exercise combined with medium-frequency therapy ranked highly for pain reduction, whereas exercise combined with acupuncture or extracorporeal shock wave therapy ranked highly for shoulder flexion. Exercise combined with taping ranked highly for external rotation, and exercise combined with manual therapy ranked highly for internal rotation. However, the interpretation of ranking results should remain cautious because uncertainty and inconsistency were present in some comparisons. Exercise-based rehabilitation appears to remain central to the management of SIS in swimmers. Several adjunctive interventions showed favorable findings for selected outcomes, especially pain relief and shoulder rotational function. However, the available evidence was affected by heterogeneity, inconsistency, and imprecision across some treatment comparisons. More rigorously designed swimmer-specific randomized controlled trials are needed before firm treatment hierarchies can be established. Trial registration: The protocol for this systematic review is registered with PROSPERO (www.crd.york.ac.uk/PROSPERO; registration number: CRD42024498851). The first submission of PROSPERO was on January 15, 2024, and it was revised and updated on March 25, 2026.

02.
arXiv (CS.CV) 2026-06-19

SketchKeyAnime: Reference-anchored Sparse Key-Sketch Animation Synthesis

Traditional animation production relies heavily on manual drawing and iterative refinement, particularly for key-pose design, in-betweening, and character coloring. While existing animation and video generation methods have made notable progress, they typically depend on RGB boundary frames, dense frame-wise conditions, or complete sketch sequences, limiting their applicability under low-cost input conditions. We present SketchKeyAnime, a video diffusion framework for generating structurally controllable, appearance-consistent, and temporally coherent animations from sparse key-sketch inputs. Given a single reference RGB image and a few temporally indexed key sketches, SketchKeyAnime introduces a dual-branch conditioning mechanism to encode local geometric constraints alongside semantic-temporal context. It leverages Sketch Cross Attention to fuse reference image and sketch conditions with learnable gating, and incorporates an Adaptive Weighted Loss to strengthen supervision on key-sketch frames and line-art regions. Experimental results on the Aesthetic subset of Sakuga-42M show that our approach consistently outperforms representative animation interpolation and sketch-guided generation baselines. Compared to the best-performing baseline, SketchKeyAnime reduces EDMD by 31.9\% and FVD by 9.5\%, demonstrating superior sketch fidelity and temporal coherence, while achieving the best overall performance across most quantitative metrics. These results validate the proposed framework and highlight its potential for low-cost, highly controllable animation creation.

03.
arXiv (CS.AI) 2026-06-19

Bid Farewell to Seesaw: Towards Accurate Long-tail Session-based Recommendation via Dual Constraints of Hybrid Intents

arXiv:2511.08378v4 Announce Type: replace-cross Abstract: Session-based recommendation (SBR) aims to predict anonymous users' next interaction based on their interaction sessions. In the practical recommendation scenario, low-exposure items constitute the majority of interactions, creating a long-tail distribution that severely compromises recommendation diversity. Existing approaches attempt to address this issue by promoting tail items but incur accuracy degradation, exhibiting a "see-saw" effect between long-tail and accuracy performance. We attribute such conflict to session-irrelevant noise within the tail items, which existing long-tail approaches fail to identify and constrain effectively. To resolve this fundamental conflict, we propose HID (Hybrid Intent-based Dual Constraint Framework), a plug-and-play framework that transforms the conventional "see-saw" into "win-win" through introducing the hybrid intent-based dual constraints for both long-tail and accuracy. Two key innovations are incorporated in this framework: (i) Hybrid Intent Learning, where we reformulate the intent extraction strategies by employing attribute-aware spectral clustering to reconstruct the item-to-intent mapping. Furthermore, discrimination of session-irrelevant noise is achieved through the assignment of the target and noise intents to each session. (ii) Intent Constraint Loss, which incorporates two novel constraint paradigms regarding the diversity and accuracy to regulate the representation learning process of both items and sessions. These two objectives are unified into a single training loss through rigorous theoretical derivation. Extensive experiments across multiple SBR models and datasets demonstrate that HID can enhance both long-tail performance and recommendation accuracy, establishing new state-of-the-art performance in long-tail recommender systems.

04.
arXiv (math.PR) 2026-06-11

On the structure of the sandpile identity element on Sierpinski gasket graphs

arXiv:2603.12006v2 Announce Type: replace-cross Abstract: We consider the identity of the abelian sandpile group of finite approximation graphs of the Sierpinski gasket, and we show that the second-order term in the scaling limit converges to the path distance to the nearest corner on the Sierpinski gasket. The proof relies on a decomposition of the identity of the sandpile group into the sum of a constant function and the Laplacian of the graph distance on the approximating graphs.

05.
arXiv (math.PR) 2026-06-16

A tree-free approach to 3D Yang-Mills Langevin dynamic. Analytic estimates and the existence of a model for a regularity structure

arXiv:2605.14616v2 Announce Type: replace Abstract: Using the multi-index approach to regularity structures due to F. Otto et al., we construct a regularity structure and a model for it associated to the stochastic Langevin equation for the 3D Euclidean Yang-Mills functional. For the model we also obtain global stochastic and global pointwise weighted Besov type estimates which hold almost surely. The model is defined as a limit of a sequence of smooth models introduced with the help of a mollified noise. When the mollification is removed the sequence converges in a certain topology defined with the help of the stochastic estimates. To obtain these results we develop the multi-index approach for systems of equations with vector-valued white noises. This project is motivated by the problem for constructing 3D Euclidean Yang-Mills measure and by the earlier results of the author on the related problem of canonical quantization of the Yang-Mills field on the Minkowski space.

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

Accelerated Convex Optimization via Hamiltonian Dynamics with Deterministic Integration Time

arXiv:2606.17260v1 Announce Type: cross Abstract: We develop Hamiltonian dynamics-based algorithms for smooth convex optimization that achieve accelerated rates of convergence. By exploiting contraction of averaged Hamiltonian flow trajectories rather than requiring contraction at trajectory endpoints, we show that Hamiltonian dynamics-based optimization methods admit deterministic and accelerated convergence guarantees, extending prior work that is limited to quadratic objectives or holds only in expectation. We analyze an idealized continuous-time algorithm and derive practical discrete-time implementations with optimal first-order complexity, thereby establishing Hamiltonian dynamics as a useful algorithmic primitive for deterministic accelerated convex optimization.

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

Computational Identifiability

arXiv:2606.19361v1 Announce Type: cross Abstract: Identification conditions describe the computability of a target query or parameter of interest as a function of the type and amount of information available. In causal identification, this information is often expressed in the form of a causal graph, and data are observed or collected for some subset of variables in the graph. Target queries may be for a single effect alone or for a class of effects in a given model. The derivation of an identification algorithm then defines mathematically the process by which the desired causal effect(s) can be uniquely determined, theoretically, in expectation. Identifiability in expectation, or 'theoretical identifiability,' generally assumes asymptotic properties, infinite data, or other mathematically idealized conditions. In this paper, we explore a fundamental distinction between this theoretical, idealized notion of identifiability and a proposed alternative that is computation-bound. The framework we propose - 'computational identifiability' - is to instead define a finite computational search procedure for an empirical estimator. If this process finds an estimator empirically, within a desired error tolerance, then identifiability is satisfied, conditional on the specified assumptions of the search (i.e., a prior distribution over the parameters) and conditional on the search procedure itself. Through several experiments, we demonstrate how this framework allows us to answer fine-grained, practical identification questions, such as identification with small finite samples, with ambiguous graphical criteria, with mixed observational-interventional data, and across counterfactual data and estimands. Code is available at https://github.com/lbynum/metadentify.

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

Activation- and Influence-Aware Ranks (AIR): Function-Preserving SVD Compression for LLMs

arXiv:2606.19993v1 Announce Type: new Abstract: We present Activation- and Influence-Aware Ranks (AIR), an SVD-based LLM compression framework that guides each weight matrix's low-rank approximation with a backward-signal influence metric. Starting from the activation-aware optimum of SVD-LLM(W), AIR runs a single closed-form alternating least squares (ALS) sweep that integrates influence element-wise under a monotone-descent guarantee. AIR is layer-local and composes orthogonally with end-to-end methods: alone it exceeds ACIP, and AIR+LoRA outperforms it further. AIR improves perplexity over SVD-LLM(W) by >18% at

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

3D Classification of Paramagnetic Rim Lesions in Multiple Sclerosis via Asymmetric QSM-FLAIR Modeling

Paramagnetic rim lesions (Rim$^+$) identified on susceptibility-sensitive MRI have recently emerged as a specific biomarker of chronic active inflammation in Multiple Sclerosis (MS) and are associated with long-term disability progression. However, susceptibility imaging and expert interpretation remain limited to specialized centers, visual assessment is time-consuming and variable, and the low prevalence of Rim$^+$ lesions poses severe class imbalance challenges for automated analysis. We propose a 3D multimodal deep learning framework for lesion-level Rim$^+$/Rim$^-$ classification from Quantitative Susceptibility Mapping (QSM) and FLAIR MRI. The architecture explicitly models modality asymmetry by treating QSM as the primary susceptibility-driven signal and conditioning it with FLAIR-derived structural context. To improve robustness under limited data, we employ self-supervised multimodal pretraining followed by supervised fine-tuning with contrastive regularization. The method was evaluated on a clinically acquired cohort of 88 people with MS with expert lesion annotations as reference standard. Results highlight improved performance compared to prior architectures, supporting the effectiveness of asymmetric multimodal modeling for automated chronic active lesion identification.

10.
arXiv (CS.CL) 2026-06-16

KVEraser: Learning to Steer KV Cache for Efficient Localized Context Erasing

Post-hoc context erasing over the KV cache is challenging because a local edit has a global consequence: once a span has been processed, its influence propagates into the cached states of all subsequent tokens. This issue arises naturally in long-context LLM applications, where stale retrieved facts, incorrect tool observations, retracted user preferences, or harmful prompt injections may be identified only after prefill. Exact erasing must then recompute all tokens after the deleted span, making its computational cost depend on suffix length rather than erased-span length. We introduce KVEraser, a learned KV-cache editing method for efficient localized context erasing. Given a processed context and a span to remove, KVEraser replaces only the KV states of the erased interval with learned steering states while reusing the remaining cache unchanged. To learn a transferable erasing mechanism, we build a two-stage training pipeline: generic span-neighbor pre-training teaches the eraser to suppress the influence of the erased span, while task-specific fine-tuning adapts this capability to downstream scenarios. Experiments show that KVEraser nearly matches full recomputation in post-erasure performance on in-domain tasks across 1K–32K context lengths, while its latency increases by only 24% compared with a 17.6x increase for full recomputation. KVEraser also generalizes to unseen long-document QA tasks with harmful factual distractors, achieving the best performance among approximate baselines with a 3–4x speedup over full recomputation.

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

DRFLOW: A Deep Research Benchmark for Personalized Workflow Prediction

arXiv:2606.18191v1 Announce Type: new Abstract: Deep research (DR) systems are increasingly used for complex information-seeking tasks, but existing works mainly focus on generating reports and summaries. In contrast, many enterprise tasks instead require an agent to identify concrete workflows which is a sequence of action-steps. For example, rather than summarizing budgeting policies, an agent should be able to determine the steps needed to answer a question such as: "How do I request new headcount given a fixed budget?". Therefore, we introduce DRFLOW, a benchmark for evaluating personalized workflows predicted by agents from heterogeneous sources. Each task requires the agent to identify relevant evidence from scattered sources, then use that evidence to predict the correct action-step sequence for the user's task. DRFLOW contains 100 tasks across five domains, with 1,246 reference workflow steps grounded in more than 3,900 sources. We define seven diagnostic metrics covering factual grounding, step recovery, structural ordering, condition resolution, and personalization. We further present DRFLOW-Agent (DRFA), a workflow-oriented reference agent to predict personalized workflow. We show that although DRFA improves over strong baseline agents (upto 10.02% average F1 score), there is substantial room for improvement remains across these workflow metrics, indicating that predicting complete and correct personalized workflows remains a challenging frontier for deep research.

13.
arXiv (CS.CV) 2026-06-17

Seeing Is Not Screening: Multimodal Hidden Instruction Attacks on Agent Skill Scanners

Agent skills are emerging as an important attack surface in LLM-based systems. Through an empirical study of existing skill scanners, we find that current defenses primarily rely on textual descriptions, manifests, and source code as the main signals for security analysis, which can leave visually conveyed malicious intent insufficiently examined. This creates a practical blind spot: harmful operational instructions hidden in images may bypass scanning while still being recoverable by multimodal agents during deployment. To systematically investigate this threat, we propose SkillCamo, a document-mediated multimodal instruction attack that conceals malicious instructions within images bundled with a skill while rewriting the surrounding documentation to naturally reference those images as part of the normal workflow. Thus, the attack does not rely on the image alone, but on the joint interpretation of textual guidance and visual payload at execution time. To defend against such attacks, we further propose ExecScan, an execution-grounded multimodal scanning module that performs intent extraction, behavior reconstruction, abuse assessment, and deliberative execution simulation over skill artifacts. ExecScan jointly analyzes documentation, code, referenced resources, and visual content to recover hidden instructions, reconstruct executable behavior chains, and identify downstream risks such as exfiltration, destruction, persistence, deception, and privilege escalation. Extensive experiments show that image-hidden malicious instructions challenge existing skill scanners, while ExecScan can improve the skill scanning performance.

14.
arXiv (CS.LG) 2026-06-19

Spectral DPPs via NEPv: A Scalable Continuous Relaxation of Determinantal MAP for Diversity-Aware Data Selection

arXiv:2606.19411v1 Announce Type: new Abstract: Selecting a small, diverse, high-quality subset from a massive pool of candidates is a recurring primitive in modern machine learning – data curation and coreset selection for training and fine-tuning large models, active-learning batch acquisition, prompt and exemplar selection for in-context learning, retrieval diversification, and experimental design. Determinantal Point Processes (\operatorname{DPP} s) give a principled, well-calibrated notion of diversity for this task, but their MAP objective – pick a size-$k$ subset $S$ maximizing $\logdet(L_S)$ – is NP-hard, and the standard greedy and sampling algorithms scale superlinearly in the ground-set size $n$. This cost is prohibitive precisely in the data-centric regime where diversity matters most, where $n$ ranges over millions to billions of candidate examples, features, or embeddings. We recast \operatorname{DPP}-MAP as a continuous optimization problem over the Stiefel manifold, and show that its first-order optimality conditions form a Nonlinear Eigenvalue Problem with eigenvector dependency (\operatorname{NEP}v) of a previously unstudied form. This \operatorname{NEP}v\ admits a self-consistent field (\operatorname{SCF}) iteration with a spectral-gap-based local contraction guarantee, giving a principled iterative solver where the diversity objective drives an eigenvector-dependent operator. The resulting algorithm, \OurMethod, requires only matrix-vector products with the kernel and runs in time $O\!\big((ndk+nk^2)\,t\big)$ for a small number of iterations $t$, scaling near-linearly in $n$ and integrating directly with low-rank and feature-map kernels common in ML. This paper focuses on the relaxation, solver, and scaling analysis; full real-data benchmarking is left to a planned empirical study.

15.
arXiv (CS.CV) 2026-06-11

DeceptionX: Explainable Deception Detection with Multimodal Large Language Models

Deception detection is a critical and highly challenging task within affective computing and behavioral analysis. Existing deep learning methods typically treat this task as a straightforward classification problem; however, this black-box approach lacks interpretability and fails to capture the complex logical deduction processes utilized by human experts when identifying lies. While Multimodal Large Language Models (MLLMs) have shown potential, applying them effectively requires a bridge between low-level audiovisual cues and high-level logical reasoning. In this paper, we propose DeceptionX, a novel MLLM framework that shifts the paradigm of deception detection from black-box classification to an interpretable Observe-Think-Summarize reasoning process. To address the scarcity of high-quality reasoning data, we first constructed DeceptChain, a high-quality dataset developed through a human-in-the-loop process. This dataset synthesizes fine-grained visual and auditory evidence (such as micro-expressions and vocal tremors) into structured chain-of-thought reasoning data. Furthermore, we propose a three-stage training pipeline and a Discrepancy-Aware Redundancy Elimination~(DARE) strategy for DeceptionX to further enhance the model's generalization capabilities. Extensive experiments demonstrate that DeceptionX not only outperforms existing MLLM baselines and state-of-the-art methods on standard real-world benchmarks but also provides transparent, expert-level reasoning paths, bridging the critical gap between accuracy and interpretability in multimodal deception detection.

16.
arXiv (CS.LG) 2026-06-17

Operator Boosting Produces Pareto-Efficient PDE Surrogates

arXiv:2606.17460v1 Announce Type: new Abstract: Neural operators are widely used as surrogate solution maps for partial differential equations (PDEs), but full-size models can be costly to store, deploy, and evaluate in many-query scientific workflows. This work introduces Operator Boosting, a stagewise residual-learning framework for constructing compact neural-operator surrogates directly, rather than training a large model and compressing it afterward. Starting from the empirical mean predictor in normalized output coordinates, the method trains a sequence of tiny same-family neural operators on residual fields and incorporates each correction through validation-selected shrinkage. We instantiate the framework with Fourier neural operators (FNOs), DeepONets, and convolutional neural operators (CNOs), and compare boosted tiny stacks against full-size monolithic baselines across one-, two-, and three-dimensional PDE benchmarks from PDEBench, APEBench, and The Well. Across 30 dataset-architecture pairs, 21 show positive mean accuracy gains and 17 have positive confidence intervals, while all boosted stacks reduce trainable parameter count by approximately 72-95%. Best-model comparisons show empirical Pareto improvements on 7 of 10 completed PDE benchmarks, including two-dimensional Navier-Stokes, shallow-water dynamics, Darcy flow, one-dimensional transport and reaction systems, and three-dimensional compressible Navier-Stokes. These results show that Operator Boosting often improves the empirical accuracy-parameter Pareto frontier of neural PDE surrogates, while also exposing PDE- and architecture-dependent regimes where residual boosting fails to offset compression.

17.
arXiv (CS.CL) 2026-06-18

Beyond Reward Engineering: A Data Recipe for Long-Context Reinforcement Learning

Long-context reasoning is an essential capability for large language models, particularly when they are deployed as autonomous agents that must reason over lengthy trajectories. Reinforcement learning (RL) has recently emerged as a dominant paradigm for improving this ability, yet existing work largely focuses on reward engineering while diverse training data remains scarce. We revisit this problem from a data-centric perspective and show that a simple yet effective data recipe alone, paired with a minimal outcome-based GRPO setup, suffices to substantially improve long-context reasoning. Our recipe targets three complementary task families – retrieval, multi-evidence synthesis, and reasoning – for which we construct and curate eight datasets totaling ~14K examples. Experiments on three models (Qwen3-4B/8B/30B-A3B) yield average gains of +7.2/+3.2/+6.4 points across seven long-context benchmarks, surpassing prior RL training sets. We further demonstrate that these gains transfer to agentic tasks, where continuing RL training on an agent-tuned model with our data recipe improves GAIA by +4.8 and BrowseComp by +7.0 points. We will release our datasets to facilitate future research.

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

Auditing Machine Unlearning: A Systematic Research on Whether Models Truly Forget

arXiv:2606.16110v1 Announce Type: new Abstract: Machine unlearning has been extensively studied in response to growing privacy concerns and regulatory requirements. However, auditing whether unlearning algorithms have truly erased the influence of specific data remains an open challenge. The lack of reliable and practical auditing mechanisms can lead to critical privacy risks, such as residual information leakage. This paper initiates a systematic investigation into whether existing unlearning algorithms can truly forget the designated data. We propose the first practical and general-purpose auditing framework for machine unlearning, inspired by the concept of proof of ignorance. Our framework addresses the key practicality limitations of existing methods by eliminating the need for retraining-from-scratch baselines, avoiding the training of large numbers of shadow models, and requiring no intrusive intervention in the original training process. To evaluate the effectiveness of our framework, we first conduct validation experiments to verify its soundness and completeness. We then perform comprehensive experiments across six datasets and ten representative unlearning methods. The results demonstrate that our framework reliably distinguishes between successful and failed unlearning. In particular, we observe that retraining-based and fine-tuning-based methods can achieve effective unlearning, even when the target data remain in the original dataset. In contrast, de-optimization-based methods fail to achieve true unlearning and instead degrade the model's performance. Fisher/Hessian-based methods also fail to unlearn requested data, even formal certification is provided. Moreover, we show that our framework is robust against fake unlearning attempts and generalizes well to large language models.

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

Beyond Layer Importance in Layer-wise Sparsity: An Inter-Layer Perturbation-Absorption Perspective

The considerable layer-wise redundancy in large language models (LLMs) has established non-uniform sparsity allocation across layers as the standard pruning approach for efficient compression. Existing layer-wise allocation methods that estimate allocation strategy from local signals such as activation outliers or weight spectra mainly derive from local layer importance, whereas the final post-pruning performance is also influenced by the network's subsequent compensatory capacity. In this paper, we directly characterize this property through controlled perturbation experiments. We make the following empirical findings. First, layers exhibit highly heterogeneous responses to pruning-scale perturbations. In most cases, early layers amplify perturbations, while middle and late layers actively absorb them, with relative L2 drift decreasing monotonically across depth and direction realigning toward the unperturbed hidden-state trajectory. Second, absorption is a large-perturbation phenomenon. Under small perturbations the network exhibits amplification across all layers, and the transition to absorption occurs smoothly as perturbation magnitude grows to pruning scale. This enriches the linearized accumulation theory underlying related works. Building on these findings, we define an absorption coefficient per layer and propose absorption-aware correction, an orthogonal augmentation that improves OWL and AlphaPruning by reducing perplexity by 7.13% and boosting zero-shot accuracy by 1.02% across multiple model families at 70% sparsity.

20.
arXiv (CS.CV) 2026-06-11

On the Study of Biometric Spoofing Detection using Deep Learning

Biometric systems are increasingly deployed in security applications; however, they remain vulnerable to spoofing attacks, in which attackers exploit counterfeit biometric data to gain unauthorized access. This research evaluates the effectiveness of state-of-the-art machine learning models, MobileNetV2, DenseNet-121, Inception-v3, and Spoof Trace Disentanglement (STD) in detecting spoofing attacks within facial recognition systems. Using the CelebA-Spoof dataset, the study evaluates model effectiveness using metrics such as accuracy, precision, recall, and F1 Score. Cross-dataset validation is carried out on the MSU-MFSD dataset to assess generalizability. The results show MobileNetV2 as the most efficient model, achieving 92% accuracy while balancing computational effectiveness, making it appropriate for real-life applications. Inception-v3 shows moderate robustness, while DenseNet-121 and STD struggle with generalization. The findings highlight the need for advances in domain adaptation and hybrid architectures to enhance biometric security systems.

21.
medRxiv (Medicine) 2026-06-16

Reporting patterns of adverse drug withdrawal events using individual case safety reports in United States and European databases

Introduction: Adverse drug withdrawal events (ADWEs) are a key safety concern with deprescribing but are infrequently reported in trials. Although pharmacovigilance systems have advanced our understanding of medication-related harms, it is unclear how extensively these systems have been used for ADWEs. Objectives: To examine the reporting patterns of ADWEs for all drugs recorded in United States and European pharmacovigilance databases between 2004 and 2023. Methods: A retrospective study was conducted using two pharmacovigilance databases, the publicly available FDA-FAERS dataset and EMA-EV Level 2A (individual-level) dataset. ADWE cases were identified using relevant MedDRA preferred terms. Data on patient characteristics, reporter type, drugs, indication, ADWE outcomes, dechallenge/rechallenge, seriousness criteria, time to onset, duration, and causality were summarised. Results: A total of 158,505 ADWE reports were analysed (FDA-FAERS: 145,514; EMA-EV: 12,987), with mean ages of 46.1 (FDA; 55.3% female) and 45.5 years (EMA; 57.1% female). The frequently reported drug classes were opioids (FDA: oxycodone, 29.8%; EMA: buprenorphine, 19%), antidepressants (FDA: duloxetine, 32%; EMA: venlafaxine, 25.9%) and gabapentinoids (FDA: pregabalin, 6.7%; EMA: pregabalin, 6.0%). The most common adverse outcomes were other serious medical conditions (FDA=63.9%; EMA=46.0%), hospitalisation (FDA=15.9%; EMA=28.3%), and disability (FDA=13.3%; EMA=6.2%) and these outcomes varied significantly based on sex and age group (p

22.
Science (Express) 2026-05-07

Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design | Science

作者: 未知作者

A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.

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

AI Economist Agent: An Agentic Framework for Model-Grounded Economic Analysis with RAG, Knowledge Graphs, and Large Language Models

arXiv:2606.20041v1 Announce Type: cross Abstract: We propose a model-grounded RAG-based AI economist with an agentic framework for economic scenario analysis using large language models (LLMs) and knowledge graphs. While LLMs can generate fluent economic narratives, economists are often required to make economic claims grounded by economic theory and real-world data. Based on this motivation, this study proposes an RAG-based AI economist, which utilizes knowledge graphs including economic data and theory and LLM-based agents to plan the analysis, retrieve relevant evidence, select appropriate models, and generate reports. In our framework, we do not produce quantitative claims directly with the language model alone; instead, we generate narratives grounded in explicit model-based computations and linked to the retrieved evidence via AI agents. We refer to our framework as an AI economist agent. We evaluate the AI economist agent in two applications: economist report generation for U.S. inflation persistence and Federal Reserve policy, and bank stress-test narrative generation for U.S. commercial real estate refinancing stress. The results illustrate how grounding the generated reports improves their economic coherence and traceability.

24.
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.

25.
medRxiv (Medicine) 2026-06-22

Multi-omics data fusion reveals divergent molecular signatures of intra-articular micro-fragmented adipose tissue and hyaluronic acid treatment in inflammatory-phenotype knee osteoarthritis

Knee osteoarthritis (KOA) affects an estimated 374 million people worldwide and has no approved disease-modifying treatment. Intra-articular micro-fragmented adipose tissue (MFAT) outperformed hyaluronic acid (HA) on patient-reported outcomes in our recent double-blind randomized trial (ISRCTN88966184), yet the molecular basis of this differential efficacy is unknown, and the two interventions have not previously been compared at the level of their in vivo molecular response in human KOA. Here we apply an interpretable artificial-intelligence data-fusion framework, based on non-negative matrix tri-factorization, to longitudinally collected plasma from this cohort, integrating proteomics, N-glycomics, miRNA transcriptomics and patient genetics with prior protein-protein and miRNA-gene regulatory networks at baseline, one and six months. The framework jointly decomposes all data modalities at each timepoint into shared, interpretable factors, from which we derive data-driven pathways of genes and of miRNAs and recover new patient-gene and patient-miRNA associations. These pathways were biologically coherent, showing significant enrichment in Gene Ontology Biological Process and Reactome Pathway annotations. By six months, the two treatments left clearly distinct molecular signatures: HA remained dominated by canonical OA pathogenic processes, including cartilage-degrading effectors such as MMP13 and LIMK2 and markers of synovial inflammation, whereas MFAT shifted the systemic landscape toward chondroprotection, anti-inflammatory signalling and bone-cartilage homeostasis, with prioritized effectors including SIRT7 and NDUFC1. To our knowledge, these are the first systems-level molecular data directly comparing the in vivo response to the two treatments in human KOA, providing initial evidence that MFAT acts as a disease-modifying intervention and demonstrating the value of interpretable data fusion for uncovering treatment mechanisms in small translational cohorts.