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02.
arXiv (quant-ph) 2026-06-11

Clifford disentanglers for entanglement reduction in molecular electronic structure simulations

arXiv:2606.12056v1 Announce Type: new Abstract: Entanglement is a key bottleneck limiting the efficiency of tensor-network and quantum simulations of molecular electronic structures. Here, we systematically assess and extend Clifford disentanglers as a structure-preserving approach to entanglement reduction: they can modify the entanglement structure of qubit wavefunctions while retaining the Pauli-string form of qubit Hamiltonians. To enable a practical search over Clifford transformations, we classify Clifford operators by their action on the Schmidt spectrum across a bipartition, reducing the two- and four-qubit search spaces to 20 and 91392 representatives, respectively. Embedded in an iterative Clifford-augmented matrix product state framework, these transformations reduce the energy errors at fixed bond dimension for the molecular test cases studied and mitigate the dependence on orbital orderings and fermion-to-qubit mappings. We further show that Clifford disentanglers can also benefit quantum simulations such as the shallow-circuit variational quantum eigensolver calculations. Together, these results establish Clifford disentanglers as a useful structure-preserving entanglement-engineering tool for tensor-network and quantum simulations of molecular electronic structure, while also clarifying their correlation dependence and motivating future developments.

03.
arXiv (CS.AI) 2026-06-15

CADET: Physics-Grounded Causal Auditing and Training-Free Deconfounding of End-to-End Driving Planners

Authors:

arXiv:2606.14438v1 Announce Type: cross Abstract: End-to-end (E2E) autonomous-driving planners trained by imitation are prone to statistical shortcuts: they associate scene elements that merely co-occur with expert actions (a roadside object, a building facade) with driving decisions, rather than the variables that causally determine them. Such causal confusion silently compromises reliability in long-tail scenarios, and it is difficult to detect, because prevailing open-loop metrics (L2 displacement and collision rate) are dominated by ego status and do not indicate whether a planner depends on spurious cues. Existing remedies based on causal-intervention training require retraining large models and cannot audit a planner that is already deployed. We present CADET, a training-free framework that audits, benchmarks, and repairs spurious reliance in pretrained E2E planners without any parameter update.

04.
arXiv (CS.CL) 2026-06-15

The Coin Flip Judge? Reliability and Bias in LLM-as-a-Judge Evaluation

Authors:

LLM-as-a-Judge is now widely used to rank model outputs, train reward models, and populate public leaderboards, but its run-to-run reliability remains under-characterized. We study repeated identical evaluations on 29 tasks spanning 10 categories using two OpenAI judge models (GPT-4o-mini and GPT-4.1-mini), with 50 pairwise trials and 50 pointwise trials per question, supplemented by temperature and prompt-sensitivity ablations. Across judges, pairwise preferences flip on average 13.6% of the time, with 28% of questions exceeding a 20% flip rate and one question reaching 56%. GPT-4o-mini also exhibits a significant first-position bias (72% A-majority, p = 0.024). At the same time, mean pointwise score gaps are small (0.19–0.36 on a 10-point scale) and not statistically significant in aggregate, producing a pairwise–pointwise gap: judges frequently choose a winner even when their own scalar scores provide little evidence of a meaningful quality difference. Beyond within-judge instability, cross-judge agreement is only 76% ($\kappa = 0.51$), semantically equivalent prompt templates change majority outcomes in 25% of tested cases, and deterministic decoding reduces but does not eliminate inconsistency. A reliability curve analysis shows that, in our dataset, 11 repeated trials are needed for a majority vote to recover the 50-trial reference verdict with 95% probability on average, rising to 15 for high-variance questions. These findings suggest that single-trial LLM judging is often too noisy for high-stakes evaluation, and that multi-trial aggregation, position randomization, and explicit uncertainty reporting should be standard practice. Because both judges are from a single provider, cross-provider replication remains an important next step.

05.
arXiv (CS.AI) 2026-06-16

MedAI: Evaluating TxAgent's Therapeutic Agentic Reasoning in the NeurIPS CURE-Bench Competition

arXiv:2512.11682v2 Announce Type: replace Abstract: Therapeutic decision-making in clinical medicine constitutes a high-stakes domain in which AI guidance interacts with complex interactions among patient characteristics, disease processes, and pharmacological agents. Tasks such as drug recommendation, treatment planning, and adverse-effect prediction demand robust, multi-step reasoning grounded in reliable biomedical knowledge. Agentic AI methods, exemplified by TxAgent, address these challenges through iterative retrieval-augmented generation (RAG). TxAgent employs a fine-tuned Llama-3.1-8B model that dynamically generates and executes function calls to a unified biomedical tool suite (ToolUniverse), integrating FDA Drug API, OpenTargets, and Monarch resources to ensure access to current therapeutic information. In contrast to general-purpose RAG systems, medical applications impose stringent safety constraints, rendering the accuracy of both the reasoning trace and the sequence of tool invocations critical. These considerations motivate evaluation protocols treating token-level reasoning and tool-usage behaviors as explicit supervision signals. This work presents insights derived from our participation in the CURE-Bench NeurIPS 2025 Challenge, which benchmarks therapeutic-reasoning systems using metrics that assess correctness, tool utilization, and reasoning quality. We analyze how retrieval quality for function (tool) calls influences overall model performance and demonstrate performance gains achieved through improved tool-retrieval strategies. Our work was awarded the Excellence Award in Open Science. Complete information can be found at https://curebench.ai/.

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

Reasoning Text-to-Video Retrieval for Operating Room Clips via Action-Driven Digital Twins

Text-to-video retrieval in operating rooms (OR) is an enabling technology for OR safety, as it allows stakeholders to retrieve and inspect recordings of specific events. However, because the most safety-critical events may not follow the common structure, to unlock its full potential text-to-video retrieval must be able to handle implicit queries that require reasoning to identify the right video (e.g., the step right before clipping). However, existing methods rely on global embeddings that cannot reason over such queries. We propose OR3, a text-to-video retrieval method that converts clips into action-driven digital twins (ActDTs), grouping concurrent subject-action-object triplets under non-overlapping temporal intervals. Moreover, rather than cross-modal matching through paired encoders, OR3 performs imagination-based retrieval where an LLM generates hypothetical ActDTs from queries. This enables intra-modal matching via a single encoder trained with ActDT-tailored hard negatives. Finally, evidence-grounded refinement revises imagined ActDTs based on discrepancies with top candidates to capture procedure-specific patterns. We construct a benchmark from MM-OR with 276 implicit queries across four reasoning categories over 386 clips from robotic knee procedures. OR3 achieves 57.6 R@1 and 77.3 R@5, outperforming the strongest baseline. These results demonstrate that OR3 enables fine-grained discrimination between visually similar OR video clips through temporal action reasoning.

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

Navigating Distribution Shifts in Medical Image Analysis: A Survey

Medical Image Analysis (MedIA) has become indispensable in modern healthcare, enhancing clinical diagnostics and personalized treatment. Despite the remarkable advancements supported by deep learning (DL) technologies, their practical deployment faces challenges posed by distribution shifts, where models trained on specific datasets underperform on others from varying hospitals, or patient populations. To address this issue, researchers have been actively developing strategies to increase the adaptability of DL models, enabling their effective use in unfamiliar environments. This paper systematically reviews approaches that apply DL techniques to MedIA systems affected by distribution shifts. Rather than organizing existing methods by technical characteristics, we explicitly bridge real-world clinical constraints – such as limited data accessibility, strict privacy requirements, and heterogeneous collaboration protocols – with the technical paradigms able to address them. By establishing this connection between operational constraints and methodological evolution, we categorize existing works into Joint Training, Federated Learning, Fine-tuning, and Domain Generalization, each aligned with specific healthcare scenarios. Beyond this taxonomy, our empirical analysis suggests that, as domain information becomes progressively less accessible across these paradigms, performance improvements become increasingly constrained, and further uncovers a gradual shift in methodological focus from explicit distribution alignment toward uncertainty-aware modeling, ultimately pointing to the need for more deployability-aware design in real-world MedIA.

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

MamBOA: State-Space Architecture for Video Recognition

Fine-grained action recognition demands temporal reasoning that general-purpose architectures address through different cost-accuracy tradeoffs: 3D dense operators couple computation to the input volume, while difference-based methods approximate motion through rigid, hand-crafted subtraction of uncontextualized features - each reflecting a deliberate design choice with corresponding limitations in expressiveness or flexibility. We present MamBOA, a backbone-agnostic temporal framework built upon a novel interleaved scan structure that recasts the selective state-space recurrence (S6) as a native motion synthesizer. By interleaving consecutive feature representations extracted from a pretrained backbone into a single alternating sequence, the proposed scan structurally drives the recurrence to encode both temporal observations of each position within a shared hidden state, separated by only a single decay step - rendering the inter-frame transition an intrinsic component of the state dynamics rather than an externally computed quantity. A cascade of dedicated alignment and decoding operations then distills this joint encoding into an explicit motion representation, which a dual-path pooling mechanism adaptively aggregates by balancing attention-driven selection with uniform temporal coverage. The framework interfaces seamlessly with CNN, Transformer, and Mamba backbone families, adding only ~2.1 GFLOPs per feature pair. On Diving48, MamBOA achieves 85.02% Top-1 accuracy with an image-pretrained backbone and 86.24% with a video-pretrained backbone processing the entire video in a single forward pass - demonstrating that structurally induced state-space dynamics constitute a principled and general foundation for motion modeling.

09.
arXiv (CS.AI) 2026-06-15

Benchmarking Vision-Language-Action Models on SO-101: Failure and Recovery Analysis

arXiv:2606.08881v2 Announce Type: replace-cross Abstract: Vision-Language-Action (VLA) models have demonstrated strong generalization in robotic manipulation, yet existing evaluations are primarily conducted in simulation or on expensive robotic platforms, leaving their robustness on affordable real-world robots largely unexplored. We present a standardized real-world benchmark for evaluating representative VLA and imitation learning policies on the low-cost SO-101 robotic platform. The benchmark comprises four representative manipulation tasks together with unified evaluation protocols, enabling systematic comparison under embodiment uncertainty. Using real-world teleoperated demonstrations, we fine-tune and evaluate $\pi_{0.5}$, SmolVLA, Wall-X, and ACT directly on the physical platform. Beyond conventional task success rates, the benchmark incorporates a structured failure taxonomy, semantic- and execution-level failure decomposition, and recovery-aware evaluation metrics to characterize policy robustness. Experimental results show that stronger pretrained VLA policies generally outperform the imitation learning baseline, although performance remains highly task-dependent under low-cost robotic deployment conditions. Execution instability emerges as the dominant failure source, while recovery capability varies substantially across architectures. These results highlight the importance of failure and recovery analysis beyond binary task success and establish SO-101 as a practical benchmark for evaluating embodied AI systems under realistic low-cost robotic deployment conditions.

10.
arXiv (CS.CV) 2026-06-19

FrozenDrive: Zero-Shot Text-Guided Driving Scene Generation and Data Augmentation with Parameter-Free Frozen Diffusion Model

Synthetic data for autonomous driving is surging, powered by diffusion models that promise scalable scene generation. Yet key obstacles remain, as enforcing multi-view and temporal consistency often relies on backbone fine-tuning or added layers, which erodes pre-trained knowledge and weakens text alignment. Models also stay close to the training distribution, struggling under adverse weather and unseen configurations, and fidelity favors frequent over rare classes. We address these gaps with FrozenDrive, a controllable generative framework that preserves a pretrained diffusion models knowledge while achieving strong consistency. FrozenDrive conditions on rich driving-stack signals and text prompts, and introduces knowledge-preserving spatio-temporal attention to impose cross-view alignment and temporal coherence in a single pass within a parameter-free frozen diffusion backbone. An additional object-focused constraint improves per-object fidelity for rare categories. Without any weather- or scene-specific fine-tuning, our model synthesizes globally coherent multi-view driving scenes from text, particularly under adverse and rare conditions, and surpasses prior baselines. On nuScenes, FrozenDrive augmented data significantly improves AD models performance, especially at night and in rain, demonstrating stronger robustness when trained with our scenario-targeted data.

11.
arXiv (quant-ph) 2026-06-16

Optimising Entanglement Distillation Policies

arXiv:2606.14908v1 Announce Type: new Abstract: Entanglement distillation is a fundamental operation in quantum information processing used to obtain higher-fidelity entangled pairs from a supply of less entangled quantum states using local operations aided by classical communication (LOCC). In a physically relevant setting, where states with an initial fidelity of $f_0$, probabilistically generated over multiple, $m$, memory pairs distributed between two parties, Alice and Bob, are pairwise distilled, the optimal policy identifies the system-configuration dependent sequence of entanglement generation and distillation operations that need to be performed in order to minimize the expected time to reach some target fidelity $f_T>f_0$. Here, we formulate and systematically analyze this task as a Markov decision problem and using a value iteration algorithm, obtain optimal deterministic policies that minimize the expected waiting time required to reach a target fidelity. Our results show that the expected waiting time under the optimal policy decreases with increasing generation probability $p$ and number of quantum memories $m$ - as expected. In contrast, it exhibits non-monotonic behavior with respect to $f_0$ for a fixed fidelity gap, $(\Delta f = f_T-f_0)$. While the optimal policy consistently outperforms baseline policies such as the greedy, nested and entanglement pumping policies, its relative advantage is regime-dependent, being determined by the system parameters ($p,f_0,f_T,m$), and exhibits a nontrivial dependence on the fidelity gap $\Delta f$. Our results highlight the value of formulating entanglement distillation as a Markov decision problem, enabling the systematic design of policies that achieve target fidelity thresholds for quantum information tasks in realistic resource-constrained settings.

12.
arXiv (CS.AI) 2026-06-16

Discrete optimal transport is a strong audio adversarial attack

arXiv:2509.14959v3 Announce Type: replace-cross Abstract: In this paper, we investigate discrete optimal transport (DOT) as a black-box attack against modern automatic speaker verification (ASV) and anti-spoofing countermeasure (CM) systems. Our attack operates as a post-processing distribution-alignment step. Frame-level WavLM embeddings of generated speech (or another person speech) are aligned to an unpaired bona fide speech pool using entropic optimal transport and a top-k barycentric projection, followed by neural vocoding. Unlike gradient-based attacks, the proposed method requires no access to model parameters, gradients, or training data. Experiments on ASVspoof2019 and ASVspoof5 demonstrate that DOT attack substantially increases CM EER and substantially degrades ASV performance across multiple spoofing attacks. The attack transfers across datasets and remains effective after CM fine-tuning. Analysis using speaker similarity, Fréchet Audio Distance, and visualization of embedding distributions suggests that DOT succeeds by shifting source speech toward bona fide regions of the representation space rather than by maximizing speaker similarity. These results indicate that optimal-transport-based distribution alignment represents a previously underexplored attack vector for contemporary ASV and anti-spoofing systems.

14.
arXiv (CS.LG) 2026-06-12

Retrieval-Augmented Foundation Models for Water Level Prediction in the Everglades

arXiv:2508.04888v2 Announce Type: replace Abstract: Accurate water level forecasting in the Everglades is essential for flood mitigation, drought management, water resource planning, and biodiversity conservation. While recent time-series foundation models have shown strong performance on generic tasks (represented in their pre-training), their effectiveness in domain-specific applications remains insufficiently understood. In this work, we curate a domain-specific dataset for water-level forecasting in the Everglades and observe that the performance of current state-of-the-art models remains limited. To address this gap, we leverage a retrieval-augmented mechanism that retrieves analogous multivariate hydrological episodes from an external archive of historical observations to enrich the input context of those pre-trained models. We study two retrieval strategies, statistical similarity-based retrieval and mutual information-based retrieval, and analyze how incorporating retrieved historical contexts affects predictive performance. Extensive experiments show that retrieval augmentation consistently improves long-horizon water level forecasts and yields disproportionately larger gains during extreme events, which is particularly critical for environmental decision-making. Our study provides empirical evidence that analog-based retrieval can benefit pretrained time-series foundation models in environmental science, offering practical insights into their strengths, limitations, and failure modes when applied to hydrological forecasting in the Everglades. Although evaluated in the Everglades, the proposed framework is general and can be applied to other hydrological systems given time series data. The code and data have been made publicly available at https://github.com/rahuul2992000/WaterRAF.

15.
arXiv (CS.AI) 2026-06-19

The Algorithmic-Human Manager: AI, Apps, and Workers in the Indian Gig Economy

arXiv:2606.19975v1 Announce Type: cross Abstract: This paper examines the impact of artificial intelligence and digital technologies on the blue-collar gig economy in India, focusing on algorithmic management. This paper examines the impact of artificial intelligence and digital technologies on the blue collar gig economy in India, focusing on algorithmic management he use of automated systems to allocate, monitor, and evaluate work in location-based services such as ride sharing and delivery. Using a social justice framework and a mixed-methods approach comprising interviews with 16 gig workers and 21 key stakeholders, the study uncovers a dual reality: while AI-powered systems expand access to work and generate operational efficiencies, they simultaneously introduce significant challenges related to fairness, transparency, and worker dignity. Key findings reveal that algorithmic systems are opaque by design, produce inequitable outcomes, and are not structured to reward additional labour with proportionate pay. The study advocates for a pragmatic hybrid governance model an Algorithmic Human Manager framework in which technological efficiency and human accountability operate together rather than in opposition. The findings carry implications for policymakers, platform companies, and civil society organizations working to design equitable AI governance frameworks for the gig economy in India and across the Global South.

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

Let LLMs Judge Each Other: Multi-Agent Peer-Reviewed Reasoning for Medical Question Answering

Objective: To enhance the accuracy, interpretability, and robustness of large language models (LLMs) in medical question answering (MedQA). Method: We designed a multi-agent peer-reviewed reasoning method in which multiple LLM agents independently generate chain-of-thought reasoning with candidate answers, then act as peer reviewers to evaluate each other's reasoning for factual correctness and logical soundness. The highest-rated reasoning chain is selected to produce the final answer. Experiments were conducted with five state-of-the-art LLMs (Llama-3.1-8B, Qwen2.5-7B, Phi-4, DeepSeek-LLM-7B, GPT-oss-20B) on three benchmark datasets: HeadQA, MedQA-USMLE, and PubMedQA. Performance was compared against single-model chain-of-thought reasoning and chain-of-thought-based majority voting. Results: Peer-reviewed reasoning consistently outperformed both baselines. The best model combination achieved an average accuracy of 0.820 across datasets, exceeding the strongest single model (0.777) and majority voting ensembles (up to 0.789). The method also scaled effectively with more participating models, while peer assessments reliably distinguished high- from low-quality reasoning chains. Conclusion: The proposed multi-agent peer-reviewed reasoning method enables LLMs to act as both solvers and evaluators, yielding superior performance in MedQA. By emphasizing reasoning quality rather than answer agreement alone, this approach improves accuracy, interpretability, and robustness, offering a promising direction for trustworthy biomedical AI systems.

17.
arXiv (math.PR) 2026-06-11

The Geometry of Admissible Short Selling in Discrete-Time Stochastic Portfolio Theory

arXiv:2606.11191v1 Announce Type: cross Abstract: While discrete-time Stochastic Portfolio Theory (SPT) provides a robust framework for market analysis, existing work on functional generation has predominantly focused on long-only portfolios defined on the entire unit simplex. This paper extends the geometric framework of functional generation to the broader class of bankruptcy-proof long-short portfolios defined on local market state spaces. We establish that, within this admissible setting, pseudo-arbitrage is fully characterized by the concavity of the generating function on the market state space, thereby relaxing the usual global domain requirement. A central contribution of this work is a geometric characterization of the short-selling mechanism. We prove that the presence of short selling is equivalent to the negativity of the maximal concave extension of the generating potential. This phenomenon is linked to the steepness of the logarithmic gradient as the market approaches a zero boundary nested inside the simplex. To systematically exploit this mechanism, we introduce the barycentric scaling transformation, a constructive methodology that maps classical long-only generating functions onto restricted domains to engineer admissible strategies with controlled short-selling exposure. Finally, through the analysis of specific shrunken portfolios, we identify a geometric phase transition: under suitable boundary conditions, admissible strategies exhibit a long-only core and a short-selling region in a qualitative sense (without asserting an exact partition of the state space). This provides a unified geometric perspective on relative arbitrage beyond the long-only constraint.

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

Active Learning with Low-Rank Structure for Data Selection

arXiv:2606.16045v1 Announce Type: new Abstract: In the data selection problem, the objective is to choose a small, representative subset of data that can be used to efficiently train a machine learning model. Sener and Savarese [ICLR 2018] showed that, given an embedding representation of the data and suitable geometric assumptions, heuristics based on $k$-center clustering can be used to perform data selection. This perspective was further explored by Axiotis et. al. [ICML 2024], who proposed a data selection approach based on $k$-means clustering and sensitivity sampling. However, these methods rely on the assumption that the dataset exhibits intrinsic geometric structure that can be effectively captured by clustering, whereas many modern datasets instead possess global algebraic structure that is better exploited by low-rank approximation or principal component analysis. In this paper, we introduce a new data selection framework based on low-rank approximation and residual-based sampling, formulated through the lens of row subset selection and loss-preserving coreset construction. Given an embedding representation of the data satisfying mild regularity conditions, which can be interpreted as algebraic or angular notions of Lipschitz continuity, we show that it is possible to select a weighted subset of $\tilde{O}\left(k + \frac{1}{\varepsilon^2}\right)$ data points whose average loss approximates the average loss over the full dataset within a $(1+\varepsilon)$ relative error, up to an additive $\varepsilon \Phi_k$ term, where $\Phi_k$ denotes the optimal rank-$k$ approximation cost of the embedding matrix. We complement these theoretical guarantees with empirical evaluations, demonstrating that on a range of real-world datasets, our data selection approach achieves improved performance over prior strategies based on uniform sampling or clustering-based sensitivity sampling.

19.
arXiv (quant-ph) 2026-06-16

Fully Quantum Algorithm for the 1-dimensional linear Lattice Boltzmann Method

arXiv:2606.16514v1 Announce Type: new Abstract: A fully quantum algorithm for solving the one-dimensional linear advection-diffusion equation using the Lattice Boltzmann method as a numerical procedure is presented in this work. We start by presenting a state of the art of the current usage of quantum algorithms for solving ordinary and partial differential equations. We then describe two algorithms for the one-dimensional Lattice Boltzmann method with two degrees of freedom. The first one is an existing hybrid quantum-classical algorithm with measurements at each time step, and the second one is our improved version, viz. a fully quantum algorithm where only one measurement is needed at the end of the algorithm. The fully quantum algorithm is first executed on a quantum simulator and then compared with a classical approach. Subsequently, the fully quantum algorithm is run on a quantum system with 133 qubits to investigate the effect of noise and the depth of the circuit on the output state. We find fluctuations in the final result due to the decoherence noise of the qubits.

20.
arXiv (CS.CV) 2026-06-17

Looped World Models

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

21.
arXiv (CS.AI) 2026-06-11

Estimating Tail Risks in Language Model Output Distributions

arXiv:2604.22167v2 Announce Type: replace-cross Abstract: Language models are increasingly capable and are being rapidly deployed on a population-level scale. As a result, the safety of these models is increasingly high-stakes. Fortunately, advances in alignment have significantly reduced the likelihood of harmful model outputs. However, when models are queried billions of times in a day, even rare worst-case behaviors will occur. Current safety evaluations focus on capturing the distribution of inputs that yield harmful outputs. These evaluations disregard the probabilistic nature of models and their tail output behavior. To measure this tail risk, we propose a method to efficiently estimate the probability of harmful outputs for any input query. Instead of naive brute-force sampling from the target model, where harmful outputs could be rare, we operationalize importance sampling by creating unsafe versions of the target model. These unsafe versions enable sample-efficient estimation by making harmful outputs more probable. On benchmarks measuring misuse and misalignment, these estimates match brute-force Monte Carlo estimates using 10-20x fewer samples. For example, we can estimate probability of harmful outputs on the order of 10^-4 with just 500 samples. Additionally, we find that these harmfulness estimates can reveal the sensitivity of models to perturbations in model input and predict deployment risks. Our work demonstrates that accurate rare-event estimation is both critical and feasible for safety evaluations. Code is available at https://github.com/rangell/LMTailRisk

22.
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.

23.
arXiv (math.PR) 2026-06-18

Extrema of microscopically slowed-down Gaussian fields

Authors:

arXiv:2606.19207v1 Announce Type: new Abstract: We introduce a family of Gaussian fields whose covariance structure exhibits an inhomogeneous, microscopic slowdown and it interpolates between a $\log$ profile (for a certain interpolation parameter $\alpha=0$) and a $\log\log$ profile (when the interpolation parameter is $\alpha=1/2$). We consider both one dimensional such objects (which we call {\it Branching Brownian Motions in a cooling environment}) as well as higher dimensional, spatial fields. We identify the correct centering of the maximum at time $T$ and prove tightness of the recentered maximum. While the exponent in the first-order growth varies linearly with $\alpha$, giving a leading order of $T^{1-\alpha}$, the second-order correction exhibits a phase transition at $\alpha=1/3$.

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

Noise-Driven Escape from Metastable Phases explains Grokking in Deep Neural Networks

arXiv:2606.17120v1 Announce Type: new Abstract: Deep neural networks (DNNs) exhibit first order phase transitions under variations of the L2 regularization strength, with each transition marking the onset of a new learnable feature. Below a critical regularization strength, all features are in principle learnable, but coexisting metastable states, separated by energy barriers, can trap the network and impede convergence. A strength of DNNs is their ability to generalize. But many open questions remain, among them the origin of so called grokking: the abrupt, delayed onset of generalization after prolonged apparent overfitting. We show for linear DNNs that grokking is consistent with hysteresis in first-order L2 phase transitions: using L2 regularization to engineer deliberate trapping, we demonstrate that a model in a low-accuracy metastable state escapes only when SGD noise drives it across an energy barrier, with escape times following Arrhenius scaling. We reproduce grokking-like delayed convergence across two orders of magnitude in escape time by deliberately trapping models in metastable phases. Using sparse sub-sampling we also reproduce the canonical grokking curve where test error eventually approaches the final training error. Our work suggests that the number of metastable states equals the number of learnable features – one per singular value of the data covariance – the potential for hysteresis grows naturally with task complexity. We provide evidence that the same mechanism likely operates in general nonlinear DNNs. Our results provide routes toward more efficient learning schemes.

25.
bioRxiv (Bioinfo) 2026-06-22

HTS-Oracle X: AI-Guided Prospective Discovery of Small Molecule Immune Checkpoint Binders

Targeting immune checkpoint protein-protein interactions (PPIs) using small molecules remains limited by the shallow, featureless binding surfaces of co-stimulatory and co-inhibitory receptors and the characteristically low hit rates of conventional high-throughput screening against these interfaces. Here we report HTS-Oracle X, a multimodal deep learning platform that integrates bidirectional cross-attention fusion of ChemBERTa SMILES embeddings with extended RDKit descriptors, trains on continuous biophysical binding signals rather than binary labels, and employs Monte Carlo Dropout uncertainty quantification for uncertainty-adjusted compound selection. Trained on 45,760 Dianthus TRIC-screened compounds per target under scaffold-aware cross-validation, HTS-Oracle X was applied prospectively to a 100,160-compound Enamine library against CD28, TIM-3, and VISTA. From 150 model-selected compounds, 45 dose-response confirmed binders were identified (30.0% overall hit rate), yielding enrichment factors of 234-408x over experimentally established random prospective baselines and 16 sub-micromolar hits. The top hits, HX-CD28-1 (KD = 233 nM), HX-TIM3-1 (KD = 249 nM), and HX-VISTA-1 (KD = 345 nM), demonstrated on-target functional activity in immune cell and tumor co-culture assays. HTS-Oracle X represents a scalable AI-guided framework for small molecule discovery against non-enzymatic immune checkpoint targets.