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02.
arXiv (CS.AI) 2026-06-11

Are Frontier LLMs Ready for Cybersecurity? Evidence for Vertical Foundation Models from Dual-Mode Vulnerability Benchmarks

arXiv:2605.23243v2 Announce Type: replace-cross Abstract: We evaluate whether frontier LLMs are ready for cybersecurity through a dual-mode benchmark: white-box function-level vulnerability detection (VulnLLM-R, across C/Java/Python) and black-box web application security testing (five production-style applications with 118 ground-truth vulnerabilities across 20+ CWE families, which we will open-source). We test six frontier models (GPT-5.4, Codex~5.3, Claude Opus~4.6, Sonnet~4.6, Gemini~3.1~Pro and Gemini~3~Flash) and two domain-specialized models across four testing paradigms. Our findings are sobering: (1)~every frontier model produces 10-50% false positive rates in white-box detection, systematically over-predicting vulnerabilities; (2)~in black-box testing, frontier models achieve only 4-8% ground-truth coverage, improving to just 10-19% even with external security tools (Playwright MCP, Burp Suite MCP); (3)~structured penetration-testing methodology encoded in domain-specialized agents raises per-family detection above 50%, demonstrating that methodology, not scale, is the primary lever; and (4)~a domain-specialized defense model achieves the highest precision (0.904) and lowest false positive rate (9.7%) among all models, on a single GPU. We identify the absence of structured security testing traces end-to-end request/response sequences, failure-heavy data, and multi-step attack chains as the fundamental training data bottleneck, and propose self-play security testing as a data generation strategy. Our results make the case for vertical foundation models purpose-built for cybersecurity.

03.
arXiv (CS.LG) 2026-06-17

CoCoEmo: Composable and Controllable Human-Like Emotional TTS via Activation Steering

arXiv:2602.03420v2 Announce Type: replace-cross Abstract: Emotional expression in human speech is nuanced and compositional, often involving multiple, sometimes conflicting, affective cues that may diverge from linguistic content. In contrast, most expressive text-to-speech systems enforce a single utterance-level emotion, collapsing affective diversity and suppressing mixed or text-emotion-misaligned expression. While activation steering via latent direction vectors offers a promising solution, it remains unclear whether emotion representations are linearly steerable in TTS, where steering should be applied within hybrid TTS architectures, and how such complex emotion behaviors should be evaluated. This paper presents the first systematic analysis of activation steering for emotional control in hybrid TTS models, introducing a quantitative, controllable steering framework, and multi-rater evaluation protocols that enable composable mixed-emotion synthesis and reliable text-emotion mismatch synthesis. Our results demonstrate, for the first time, that emotional prosody and expressive variability are primarily synthesized by the TTS language module instead of the flow-matching module, and also provide a lightweight steering approach for generating natural, human-like emotional speech.

04.
arXiv (CS.LG) 2026-06-18

Optimal scenario design for climate emulation

arXiv:2606.19302v1 Announce Type: cross Abstract: As deep learning for physical systems continues to grow in popularity, efforts to improve generalizability have primarily focused on designing architectures that embed physical constraints. However, for machine-learning surrogate climate models (emulators), we show that the low structural diversity in existing scenarios commonly used to generate training data places a ceiling on predictive skill. Here, we examine whether training datasets themselves can be optimized to improve generalization. We introduce a method to create datasets that produce emulators capable of generalizing to new, structurally different scenarios absent from the training data. We use a differentiable Simple Climate Model (SCM) to calculate the sensitivity of emulator loss to perturbations in the training data, iteratively updating the training data to maximize emulator skill. For an SCM, training on one scenario optimized in this fashion outperforms an emulator trained on six standard ScenarioMIP pathways. We achieve this higher predictive skill despite training on a smaller dataset, finding that our emulator successfully isolates distinct physical behaviors of different climate forcing agents (e.g., greenhouse gases vs. aerosols) without single-forcing runs. We then demonstrate that scenarios optimized using an SCM, when used to drive an intermediate-complexity climate model, produce a training dataset that yields a more skillful emulator than training on ScenarioMIP outputs. Our results suggest that, in the compute-constrained environment of running full-scale climate models, generating a small number of dynamically rich scenarios provides greater marginal value for emulation and characterizing system responses than expanding the suite of traditional emissions pathways.

05.
arXiv (CS.AI) 2026-06-17

A Gradient-based Causal Discovery Framework with Applications to Complex Industrial Processes

arXiv:2507.11178v3 Announce Type: replace-cross Abstract: With the advancement of deep learning technologies, various neural network-based Granger causality models have been proposed. Although these models have demonstrated notable improvements, several limitations remain. Most existing approaches adopt the component-wise architecture, necessitating the construction of a separate model for each time series, which results in substantial computational costs. In addition, imposing the sparsity-inducing penalty on the first-layer weights of the neural network to extract causal relationships weakens the model's ability to capture complex interactions. To address these limitations, we propose Gradient Regularization-based Neural Granger Causality (GRNGC), which requires only one time series prediction model and applies $L_{1}$ regularization to the gradient between model's input and output to infer Granger causality. Moreover, GRNGC is not tied to a specific time series forecasting model and can be implemented with diverse architectures such as KAN, MLP, and LSTM, offering enhanced flexibility. Numerical simulations on DREAM, Lorenz-96, fMRI BOLD, and CausalTime show that GRNGC outperforms existing baselines and significantly reduces computational overhead. Meanwhile, experiments on real-world DNA, Yeast, HeLa, and bladder urothelial carcinoma datasets further validate the model's effectiveness in reconstructing gene regulatory networks.

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

Code Correctness Signals in LLM Hidden States: Pre-Generation Probing and Repair Geometry

arXiv:2606.14530v1 Announce Type: new Abstract: Large language models encode rich information in their hidden states. This work asks whether code correctness is legible in the hidden states of Qwen3-4B-Instruct-2507, before it generates and as it repairs a failed attempt, studied on 444 LiveCodeBench tasks. It reports two findings connected by a single confound-control tool: residualization. First, the correctness of the model's first-attempt code is linearly decodable from the prompt-final hidden state, with a leakage-free held-out AUC of 0.931 +/- 0.008 across 50 outer splits. After the linear effect of prompt length is removed from each hidden state dimension, the probe still reaches 0.911 +/- 0.010, well above a prompt-length baseline of 0.754 +/- 0.014. Second, on 236 cleaned cases where the model attempts to repair a failed first attempt, the hidden state shift from the failing attempt to its repair carries a statistically detectable contrastive direction, significant on both a magnitude and a split-half test against label-shuffled nulls. This direction does not survive a conditional residualization against repair-context covariates that differ between successful and failed repairs, marking it as a correlate of repair success driven by the repair context rather than an isolated repair-comprehension feature. The probe layer is selected by nested cross-validation, and the same residualization approach that upholds the pre-generation correctness result overturns the repair-direction interpretation. The contribution is as much methodological as empirical: a diagnostic honest enough to report a negative result alongside a positive one.

07.
medRxiv (Medicine) 2026-06-15

Quantitative insights into the role of phages and plasmids in the persistence of nontuberculous mycobacteria in chloraminated drinking water

Nontuberculous mycobacteria (NTM) are opportunistic pathogens that persist in chloraminated drinking water systems, yet the roles of phages and plasmids in their persistence remain largely unexplored. Using genome-resolved and quantitative metagenomics, we characterized NTM, phages, prophages, and plasmids in a chloraminated building plumbing system. Bacterial metagenome-assembled genomes (MAGs) and viral operational taxonomic units (vOTUs) were quantified at mean concentrations of 8.41 * 10^7 and 8.00 * 10^8 copies/L, respectively, including seven NTM MAGs at a mean total concentration of 4.01 * 10^5 copies/L. NTM concentrations were highest at the site with the lowest bacterial and viral diversity. Predicted NTM-infecting virus concentrations were inversely related to NTM concentrations across sites, suggesting complex phage-host dynamics that warrant direct experimental investigation. NTM, putative phages, prophages, and plasmids encoded functions related to disinfectant tolerance, stress response, metal resistance, and secretion. These findings identify phage interactions, prophages, and plasmids as overlooked genomic and ecological dimensions of NTM persistence in engineered water systems.

08.
arXiv (quant-ph) 2026-06-16

Complete Relational Description of Spin in a Quantum Background

arXiv:2606.15873v1 Announce Type: new Abstract: The standard description of the state of a spin in quantum mechanics presupposes externally fixed directions – a classical background. Can a spin be fully described instead in relation to other quantum mechanical systems? Poulin suggested twenty years ago group averaging over rotations the joint state of a fundamental spin and a reference spin with large angular momentum which, however, yields a classical bit in a probabilistic mixture. We revisit this idea and show that when the quantum reference system is augmented to two large spins, the standard quantum mechanical description of a spin is recovered in the limit of large quantum numbers for the reference system.

09.
medRxiv (Medicine) 2026-06-23

Attention and memory in Parkinson's disease: a discriminant analysis approach

Background. Cognitive impairment in Parkinson's disease (PD) is highly prevalent and heterogeneous. Assessing multiple cognitive domains is challenging and risks redundancy. This study evaluated whether a discriminant analysis approach could optimize the selection of specific tasks and measures for identifying attention and memory deficits in PD. Methods. Thirty PD patients and 25 cognitively unimpaired (CU) controls completed four experimental tasks: two assessing attention (flanker and spatial Stroop), one for recognition memory, one for working memory (n-back). Following group-level difference analyses, a discriminant analysis was performed to identify which tasks, and performance metrics possessed the highest sensitivity for distinguishing PD patients from CU individuals. Results. At the group level, PD patients exhibited significantly worse conflict costs in both attention tasks and lower sensitivity scores (d') in the recognition memory task compared to CU controls. The discriminant analysis revealed that time-based measures from the spatial Stroop task and the sensitivity score from the recognition memory task provided the highest discriminating power to differentiate between the two groups. Conclusion. These findings suggest that cognitive deficits in PD can be identified with high diagnostic accuracy using a targeted subset of metrics, eliminating the need for extensive and redundant neuropsychological testing batteries for attention and memory, without needing an extensive number of cognitive tasks for attention and memory.

10.
arXiv (CS.CV) 2026-06-18

SegmentAnyTreeV2: Scaling Transformer-Based Tree Instance Segmentation Across Sensors, Platforms, and Forests

We present SegmentAnyTreeV2, a sensor- and platform-agnostic framework for semantic and instance segmentation of forest point clouds. The model combines a serialization-based Point Transformer v3 backbone with a lightweight semantic head and a tree-focused cross-attention mask decoder. Semantic predictions restrict instance decoding to tree-class voxels, while instance-aware query initialization, one-to-many seed supervision, and asymmetric mask scoring improve separation in dense and structurally complex stands. We further introduce FOR-instance v3, an expanded benchmark comprising 427 scenes and 26,496 annotated trees across diverse biomes, forest structures, and LiDAR platforms. On the FOR-instanceV2 test split, SegmentAnyTreeV2 achieves 90.5% precision, 80.2% recall, 85.0% F1, 90.7% coverage, and 87.6% semantic mIoU, outperforming previous learning-based methods in both instance detection and mask completeness. Zero-shot evaluation on independent sites further demonstrates strong cross-domain generalization.

11.
arXiv (CS.CV) 2026-06-18

Test-Time Adaptation in Optical Coherence Tomography Using Trajectory-Aligned Time-Independent Flow

Optical coherence tomography (OCT) is essential in ophthalmology, but inconsistent image quality especially in low-cost devices hinders automated analysis. To address this, we introduce a flow-matching-based test-time adaptation method that generates high-quality surrogate images from noisy inputs. Typically, domain gaps between test and training data cause pixel distribution mismatches during the denoising process. We overcome this by matching the test image's histogram to synthetic reference trajectories, successfully aligning the input with expected distributions. Additionally, we remove the network's time conditioning to account for slight deviations in real-world noise distributions. Our approach achieves state-of-the-art performance in segmenting critical biomarkers for two stages of Age-related Macular Degeneration (AMD). Code is available: https://github.com/Veit21/tta-flow.

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

ChLogic: Evaluating Robustness of Logical Reasoning in Chinese Expressions

Large language models perform increasingly well on standardized logical reasoning benchmarks, but whether this ability remains robust beyond English is unclear. We introduce ChLogic, an English–Chinese aligned benchmark that tests whether models preserve logical reasoning performance when the same latent logical structure is expressed in English and diverse Chinese surface realizations. Built from formal logical templates, the benchmark contains three data sets: (i) the General aligned set, derived from 60 General Propositions across nine template families; (ii) the Difficult aligned set, derived from 40 Difficult Problems; and (iii) the Chinese-only set, covering 15 language-specific phenomenon types. Each aligned item pairs one English reference expression with five Chinese realizations. Experiments on Qwen3, Ministral, and GLM models reveal a persistent English–Chinese performance gap. Back-translation from standard Chinese into English often improves performance on the General aligned set, but produces mixed effects on the Difficult aligned set, where Qwen3-32B and GLM-5.1 perform worse after translation. These results indicate that Chinese surface realization, translation artifacts, and model-specific behavior jointly affect multilingual logical reasoning. Overall, ChLogic provides a useful stress test for the robustness of multilingual reasoning.

13.
arXiv (CS.CL) 2026-06-19

Code-Switching Reveals Language Anchoring in Multilingual LLMs

Multilingual Large Language Models (MLLMs) are increasingly expected to handle Code-Switched (CS) inputs, yet mixing languages frequently degrades performance relative to source- or target-language monolingual counterparts. To understand this degradation, we use grammar-forced CS as a controlled diagnostic setting for locating CS representations relative to their source and target counterparts. We introduce Anchor Bias, a geometric measure that quantifies language anchoring, whether a CS hidden state aligns closer to its source or target language counterpart. Across diverse MLLMs, Anchor Bias reveals a consistent grammar-frame effect: source-framed CS stays source-anchored, whereas target-framed CS shifts target-ward and shows larger Question Answering (QA) degradation. Motivated by this representational pattern, we propose CANVAS (Contextual Anchor-based Neural Vector Alignment Steering), an inference-time intervention that extracts a source-side canvas from the input and softly steers target-language hidden states toward the source anchor during prefill. CANVAS consistently recovers QA F1 across MLLMs and CS conditions, showing that internal anchoring signals provide an actionable target for mitigating CS inference failures.

14.
arXiv (quant-ph) 2026-06-16

Morphology-resolved scrambling in a chaotic quantum billiard

arXiv:2606.16865v1 Announce Type: new Abstract: Chaotic quantum systems can retain spatial memory through scarred eigenstates, but whether these static structures control scrambling remains unclear. This work establishes a morphology-resolved connection between scarred eigenstates and eigenstate-resolved OTOCs in a peanut-shaped quantum billiard. Scalar localisation diagnostics, including differential entropy and continuum participation ratios, detect anomalous concentration but discard spatial architecture. A scale-normalised density overlap, in contrast, directly compares probability density profiles, revealing families of orthogonal eigenstates with nearly identical spatial morphology. Comparing the complete OTOC time traces of these orthogonal eigenstates reveals that morphological recurrence has dynamical content: moderate density overlap yields no universal prediction, whereas strongly recurring morphologies exhibit nearly identical OTOC growth and saturation. Thus, scarred structures act as spatial templates for operator growth, not merely static violations of ergodicity. This morphology-resolved framework turns eigenstate shape into a quantitative predictor of scrambling and provides a scale-controlled diagnostic of weak ergodicity breaking in quantum chaos.

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

Superhuman Safe and Agile Racing through Multi-Agent Reinforcement Learning

arXiv:2605.22748v2 Announce Type: replace-cross Abstract: Autonomous systems have achieved superhuman performance in isolation or simulation, yet they remain brittle in shared, dynamic real-world spaces. This failure stems from the dominant single-agent paradigm for physical applications, where other actors are ignored or treated as environmental noise, preventing effective coordination. Here we show that multi-agent reinforcement learning provides the essential safety scaffolding required for real-world interaction. Using high-speed quadrotor racing as a high-stakes testbed, we train agents to navigate complex aerodynamic interactions and strategic maneuvering with a variable number of racers. Through league-based self-play, agents evolve sophisticated anticipatory behaviors, including proactive collision avoidance, overtaking, and handling multi-agent physical interactions, including aerodynamic downwash. Our agents outperform a champion-level human pilot in multi-player races at speeds exceeding 22 m/s, while simultaneously reducing collision rates by 50 % compared to state-of-the-art single-agent baselines. Crucially, training with diverse artificial agents enables zero-shot generalization to safer human interaction. These results suggest that the path to robust robotic co-existence lies not in isolated safety constraints, but in the rigorous demands of multi-agent interaction. Multimedia materials are available at: https://rpg.ifi.uzh.ch/marl

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

The Art of Interrogation: Consistency Amplifies Factuality in Spatial Reasoning

arXiv:2606.11918v1 Announce Type: new Abstract: Current Large Reasoning Models (LRMs) exhibit remarkable general capabilities but significantly underperform in spatial reasoning tasks. Existing approaches treat this gap as a knowledge deficit, relying on supervised fine-tuning (SFT) to ingest labeled spatial data from external vision sources or synthetic engines. In contrast, we argue that for many tasks, spatial reasoning capabilities are already present in pre-trained LRMs but require alignment through logical coherence under geometric 2D and 3D constraints. In this work, we propose a self-supervised reinforcement learning (RL) framework that targets the internal reasoning process without requiring ground-truth annotations. By formalizing the notion of consistency verifiers – reward functions that check for geometric and semantic consistency under transformations – we demonstrate that models can improve their spatial reasoning abilities. We use both image transformations, like flipping, and textual transformations, like swapping the order of objects in the question, and propose a new optimal transport-based RL strategy, OT-GRPO, which is a minimal-matching variant of group relative policy optimization tailored to pairwise verifiers. We show that this label-free consistency training approaches the accuracy of models trained with ground-truth supervision and achieves similar generalization across diverse tasks and data domains.

17.
medRxiv (Medicine) 2026-06-22

Study protocol: Feasibility and clinical implications of real-time cerebral autoregulation monitoring in major noncardiac surgery with the Medtronic Cotrending algorithm (AUTOREGULATE-NONCARDIAC-COTRENDING)

Background: Perioperative hypotension is associated with postoperative organ injury. However, trials of hypotension avoidance have not found meaningful improvements in postoperative cardiovascular, renal, neurological or functional outcomes. One possible explanation is that organ perfusion depends on patients individual autoregulatory ranges. Hence, technology enabling monitoring of the autoregulatory status of vital organs, e.g. the brain, could provide a physiologic basis for personalising of blood pressure targets. However, current established methodologies for monitoring cerebral autoregulation in noncardiac surgery, e.g. the cerebral oximetry index (COx), are limited by performance and usability. The Medtronic Cotrending algorithm has been developed to provide automated, near real-time assessment of cerebral autoregulation. While feasibility was demonstrated in cardiac surgery, its applicability in major noncardiac surgery remains unknown. This study aims to evaluate the technical feasibility and clinical implications of Cotrending-based cerebral autoregulation monitoring in major noncardiac surgery. Objectives: Primary objective: To evaluate the technical feasibility of using the Medtronic Cotrending algorithm to monitor intraoperative cerebral autoregulation in real-time during major noncardiac surgery, drawing comparisons to the COx algorithm. Secondary objectives: to investigate the potential clinical implications of Cotrending-based cerebral autoregulation monitoring. Design: Single-centre, prospective cohort study. Setting: Swiss tertiary care centre Patients: Patients enrolled in AUTOREGULATE-NONCARDIAC who were monitored intraoperatively with the Medtronic INVOS(TM) 5100 near-infrared spectroscopy (NIRS) system. Outcomes: Technical feasibility outcomes include success rate of determination of the lower limit of cerebral autoregulation, intraoperative uptime, time to first estimate of the lower limit of cerebral autoregulation, sensitivity to external factors and to data artefacts; agreement of Cotrending-derived lower limit of cerebral autoregulation with COx-derived lower limit of cerebral autoregulation. Conclusions: N/A Trial registration: Clinicaltrials.gov NCT07630129

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

TxBench-PP: Analyzing AI Agent Performance on Small-Molecule Preclinical Pharmacology

arXiv:2606.19245v1 Announce Type: new Abstract: Artificial intelligence (AI) agents promise to accelerate drug discovery by compressing interpretation and decision-making loops, but practical deployment requires trusted evaluation on realistic program decisions. We introduce TherapeuticsBench Preclinical Pharmacology (TxBench-PP), a verifiable benchmark for small-molecule preclinical pharmacology and the first focused slice of a broader TherapeuticsBench effort across drug-discovery stages and therapeutic modalities. TxBench-PP tests whether agents can recover accurate conclusions from real-world assay data rather than memorized facts from literature. The benchmark contains 100 evaluations indexed by program stage, assay type, and task structure, spanning mechanism-of-action (MoA) and pharmacodynamic (PD) reasoning, compound-target engagement, causal target validation, developability and safety, and translational efficacy. Agents receive realistic workflow snapshots, inspect files in a coding environment, and return structured answers graded deterministically. Across 16 model-harness configurations, comprising 11 models and 4,800 trajectories, no system reliably recovered preclinical pharmacology decisions. The strongest configuration, Claude Opus 4.8 / Pi, passed 59.3\% of endpoint attempts (178/300; 95\% CI, 51.1-67.6), followed by GPT-5.5 / Pi at 55.3\% (166/300; 47.0-63.6).

19.
arXiv (CS.AI) 2026-06-17

Understanding LLMs in Title-Abstract Screening: From Disagreements to Recommendations

arXiv:2606.17588v1 Announce Type: cross Abstract: Several studies have examined the use of large language models (LLMs) for title-abstract screening in systematic reviews (SRs), reporting mixed accuracy. However, questions of reliability remain largely unaddressed. In this study, we go beyond quantitative LLM-human agreement metrics and qualitatively investigate how and why LLMs fail. We also propose actionable recommendations. We analyzed disagreements between LLMs and researchers across six software engineering SRs and over 1,000 primary study papers. For each SR, papers were screened independently by human experts and LLMs in zero-shot mode, resulting in Kappa values ranging from 0.52 to 0.77. Qualitative analysis suggests that human-LLM disagreement results from recurring, identifiable causes, such as boundary ambiguity in key terms, keyword overemphasization, and incorrect topic inference. Based on these findings, we propose recommendations such as validating semantic understanding before deployment, running multiple LLMs, and focusing validation efforts on borderline cases. Future studies are needed to validate the impact of our recommendations, and community efforts are needed to develop normative guidelines on LLM usage in SRs.

20.
arXiv (quant-ph) 2026-06-11

A Pfaffian quantum Hall state of ultracold bosons

arXiv:2606.12409v1 Announce Type: cross Abstract: Fractional quantum Hall states are a cornerstone of topological physics, hosting fractionally charged quasiparticles with exotic statistics that promise to enable topologically protected quantum information processing. Among these, the Pfaffian state introduced by Moore and Read implements a p-wave pairing structure that supports excitations with non-Abelian exchange statistics. Despite extensive study in electronic systems, direct access to its pairing structure has remained limited. Here we realize a three-particle bosonic Pfaffian state of ultracold $^{87}\mathrm{Rb}$ atoms in an optical lattice subject to a Floquet-engineered synthetic magnetic field. Using a Bayesian-optimized adiabatic protocol, we prepare a state exhibiting Pfaffian pairing correlations. Site-resolved measurements of multi-point density correlations reveal a pronounced suppression of short-range three-body coincidences, reflecting the underlying pairing structure. We further probe the state's transport response through Hall drift measurements. Our results establish a bottom-up approach to engineering non-Abelian topological order and lay the groundwork for future explorations of anyonic braiding in synthetic matter.

21.
medRxiv (Medicine) 2026-06-15

Shortened blastocyst vitrification achieves live birth rates comparable to standard protocols: an analysis of 3168 cryotransfers

Study question Do shortened blastocyst vitrification and warming protocols provide comparable live birth rates (LBR) and obstetrical and perinatal outcomes to traditional vitrification and warming protocols? Summary answer Shortened vitrification and warming protocols provide comparable LBR, obstetric and perinatal outcomes to traditional protocols. Shortened vitrification coupled with traditional multi step warming benefitted women >35yrs. What is known already Embryo viability following cryopreservation is dependent on blastomere survival and functional integrity, both impacted by ice crystal formation and osmotic gradients. Recent innovations in cryopreservation challenge the need for stepwise dehydration and rehydration protocols. While one step ''fast'' blastocyst warming protocols seem to provide equivalent clinical outcomes to traditional ''slow'' protocols, fewer studies investigate whether blastocyst dehydration rates can be similarly increased. A thorough safety and effectiveness evaluation remains necessary for both treatment success and offspring health. Study design, size, duration Three clinics within a network participated in this retrospective consecutive cohort study, with cycle data collected for 3603 warmed blastocysts resulting in 3168 frozen blastocyst transfers in 2170 patients between 2023 and 2025. We modelled the relationship between ''fast'' versus ''slow'' protocols and outcomes with Generalized Additive Models, and linear and logistic regressions where appropriate. Two tailed chi square with Yates correction was used to examine pregnancy loss and obstetrical and perinatal outcomes; p0.05). Importantly, women 35yrs or older at vitrification (n=1715 transfers) profited from a F/S strategy, which provided a significant increase in live birth rates (OR:1.42 [1.02-1.98] p=0.038) compared to S/S. The same improved live birth following a F/S strategy were also seen in embryos of lower quality (OR:1.78 [1.12-2.83] p=0.015), suggesting of a protective effect of this cryopreservation strategy on the developmental competence of impaired germplasm. Limitations, reasons for caution Factors affecting the results may be unaccounted for by the study retrospective nature. Wider implication of the findings Overall, shortened, ''faster'' vitrification and warming protocols provide comparable reproductive outcomes to traditional ones. The combination of shorter exposure to cryoprotectant (CPA) during vitrification and stepwise osmotic gradient during warming provided significant clinical benefits specifically to patients >35 and lower quality embryos, pointing to the possibility of adapting vitrification protocols to specific patients populations and optimizing their clinical outcomes.

22.
medRxiv (Medicine) 2026-06-10

A Three-Tier Operational Benchmark for Evaluating Large Language Models on Hospital Medication Safety

Objective. To introduce PsiBench, a clinically validated medication-safety benchmark for evaluating large language models (LLMs) against the standards used to certify hospital computerized provider order entry (CPOE) and electronic health record (EHR) systems, and a non-overlapping three-tier evaluation framework separating highest-stakes discrimination, the operational CDS regime, and category-correct alerting. Materials and Methods. PsiBench comprises 492 medication-safety scenarios across 11 safety categories, created by clinical pharmacology experts whose work underpins an annualized testing procedure used by more than 2,000 U.S. hospitals. The three-tier framework partitions the scenarios non-overlappingly: Discrimination (98 scenarios, 50 fatal vs 48 deception, near-balanced 51%/49%); Operational (394 scenarios, 261 serious unsafe plus 133 safe including 41 Excessive Alerts reclassified as operational negatives); and Attribution (311 alert-required scenarios). We evaluated 40 frontier LLMs from 10 providers over 3 runs per scenario at temperature 0.2 (or the provider default where temperature is not configurable), yielding 59,040 evaluations conducted April 21-23, 2026. Results. Headline binary performance on the full benchmark spans a wide range across the 40 models: F1 78.5%-92.3%, accuracy 65.4%-89.8%, sensitivity 81.4%-100.0%, specificity 6.1%-81.8%. Leading models by F1 (o4-mini 92.3%; o3 92.2%) pair high sensitivity with meaningful specificity; three models saturate sensitivity at 100% but fall below 25% specificity, indistinguishable from a naive always-alert classifier. The wide spread on a single headline metric motivates tier-specific analyses, developed in a separate clinical paper. Discussion and Conclusion. PsiBench and the three-tier framework operationalize a rigorous evaluation rubric for LLM medication safety, grounded in two decades of national hospital audit experience. The framework generalizes to any binary medication-safety classifier (rule-based, conventional ML, or LLM-driven), supporting tier-aware model selection and post-deployment surveillance.

23.
arXiv (math.PR) 2026-06-16

Balanced affine Motzkin paths: Pearson geometry and global endpoint asymptotics

arXiv:2601.17634v2 Announce Type: replace Abstract: We study endpoint distributions of balanced affine weighted Motzkin paths. In the balanced case, the generating-function equation has Pearson-type characteristic geometry. We show that this geometry controls the terminal-height law globally: the characteristic escape time determines the limiting cumulant generating function, the large-deviation rate function, and the ray-scale asymptotics. Thus the usual Gaussian window is only the local quadratic approximation to a global Pearson-driven profile. For finite sizes, we prove a uniform Daniels saddlepoint approximation in the one-dominant-singularity regimes and identify the exceptional antipodal case requiring a lattice/interference correction.

24.
arXiv (CS.LG) 2026-06-16

CADO: From Imitation to Cost Minimization for Heatmap-based Solvers in Combinatorial Optimization

arXiv:2602.08210v2 Announce Type: replace Abstract: Heatmap-based solvers have emerged as a promising paradigm for Combinatorial Optimization (CO). However, we argue that the dominant Supervised Learning (SL) training paradigm suffers from a fundamental objective mismatch: minimizing imitation loss (e.g., cross-entropy) does not guarantee solution cost minimization. We dissect this mismatch into two deficiencies: Decoder-Blindness (being oblivious to the non-differentiable decoding process) and Cost-Blindness (prioritizing structural imitation over solution quality). We empirically demonstrate that these intrinsic flaws impose a hard performance ceiling. To overcome this limitation, we propose CADO (Cost-Aware Diffusion models for Optimization), a streamlined Reinforcement Learning fine-tuning framework that formulates the diffusion denoising process as an MDP to directly optimize the post-decoded solution cost. We introduce Label-Centered Reward, which repurposes ground-truth labels as unbiased baselines rather than imitation targets, and Hybrid Fine-Tuning for parameter-efficient adaptation. CADO achieves state-of-the-art performance across diverse benchmarks, validating that objective alignment is essential for unlocking the full potential of heatmap-based solvers.

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

Medical Heuristic Learning: An LLM-Driven Framework for Interpretable and Auditable Clinical Decision Rules

arXiv:2606.16337v1 Announce Type: new Abstract: Predictive modeling for clinical tabular data is central to clinical decision support and therefore requires not only strong predictive performance but also transparent decision logic. Although deep learning and tree-based ensemble methods can achieve high accuracy, their black-box nature remains a major obstacle to clinical deployment. This challenge is further compounded by common characteristics of medical data, including limited sample sizes, severe class imbalance, and feature evolution arising from changes in diagnostic criteria and clinical documentation. To address these issues, we propose Medical Heuristic Learning (MHL), an instantiation of the learning-beyond-gradients paradigm for clinical tabular prediction. Instead of relying on neural network weight updates, MHL uses a large language model (LLM)-driven workflow that integrates statistical probes, medical knowledge probes, rule synthesis, and code-level iterative refinement to optimize a deterministic and executable decision system. The resulting model is expressed not as opaque parameters, but as versioned pure-Python decision rules that are explicitly interpretable, fully auditable, and clinically grounded. MHL also supports continual learning by starting from previously validated rules and iteratively revising them using updated feature information under data drift or feature evolution. Comprehensive experiments on medical datasets show that MHL achieves performance comparable to state-of-the-art methods while maintaining strong behavior in small-sample and highly imbalanced settings. The results further indicate that this explicit rule update mechanism can help alleviate catastrophic forgetting under feature evolution. Overall, these findings suggest that non-gradient-based heuristic systems offer a transparent and adaptable alternative for high-stakes clinical decision support.