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01.
arXiv (CS.CL) 2026-06-12

Rigel: Reverse-Engineering the Metal 4.1 Tensor Compute Path on the Apple M4 Max GPU

Apple's Metal 4.1 exposes a tensor compute path: the Metal Performance Primitives (MPP) matmul2d operation over cooperative_tensor fragments, whose interface is documented but whose hardware behavior is deliberately hidden. The specification states which data-type rows are supported, never whether they are hardware-accelerated, where the operation physically executes, what its accumulator width is, or how it partitions matrix fragments across threads. We present Rigel, an empirical characterization of this path on a single Apple M4 Max (a pre-neural-accelerator generation). Using a checksum-gated, provenance-tracked microbenchmark harness, Rigel recovers eleven facts the v4.1 specification hides or contradicts. The headline finding: the Metal 4.1 fp8 (E4M3) matmul2d is emulated, not accelerated: it sustains 0.94x the throughput of fp16 despite reading half the operand bytes, so on M4 it is a memory-footprint feature, not a performance feature. We further show, via a three-signal triangulation (throughput ceiling, comparison against simdgroup_matrix, and per-rail power attribution), that matmul2d executes entirely on the GPU shader cores with no dedicated matrix datapath and no evidence of Apple Neural Engine routing; that it accumulates in >=fp32; and we reconstruct the opaque 8x8 cooperative_tensor fragment layout Apple documents nowhere. Acting on the characterization, a hand-fused GEMM + bias + GELU kernel beats the decomposed path by +6.5-12.9% in the cache-resident regime. All findings are reproducible from committed MIT-licensed code and per-cell CSVs.

02.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.

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

Where Black-box Drug-Target Interaction Prediction Models Look: Cross-Method Explainability

arXiv:2606.14245v1 Announce Type: new Abstract: Drug-target interaction (DTI) and affinity (DTA) predictors increasingly achieve strong benchmark scores, yet their internal use of sequence, fingerprint, and graph features often remains opaque. We present an interpretability audit of BridgeDPI architecture on three different datasets including Gao, Human, and C.elegans. This study combines gradient-based attributions – integrated gradients, saliency, layer-wise relevance propagation, SmoothGrad, and SmoothGrad-IG – with feature-wise occlusion ablation and strict intersection consensus across methods to reduce single-explainer bias. We summarize sensitivity and signed effects at raw inputs, at the bridge similarity scaffold, and through the graph convolution, including edge-level sensitivities and targeted edge removals. The results show that explainability is most informative when treated as model criticism: it reveals modality dominance, padding and special-token artifacts, dataset-dependent cooperative versus suppressive effects across layers, and chemistry-consistent fragment and composition motifs where methods agree. These analyses do not substitute for structural or experimental ground truth, yet they can provide testable hypotheses for downstream validation in computational drug discovery pipelines. More broadly, applying modern XAI to contemporary DTI/DTA models is still an early pass over the rich structure implicit in trained weights and data – yet even this first layer of scrutiny already helps researchers relate predictions to drug- and target-side representations and to prioritize external validation.

04.
medRxiv (Medicine) 2026-06-18

From Paper Letters to an Integrated Digital Workflow: Improving Efficiency, Reliability, and Engagement in Health Guidance

Background: Post-checkup health guidance in Japan has traditionally relied on paper-based communication and manual administrative processes. These workflows are time-consuming, prone to transcription errors, and can delay timely engagement with health guidance recipients. Objective: To assess whether replacing a paper-based workflow with an integrated digital system using Microsoft Access, robotic process automation (RPA), and web-based responses could improve administrative efficiency, operational reliability, and engagement among health guidance recipients. Methods: This single-site quality improvement initiative redesigned the existing letter-based workflow. Access served as a central interface for managing recipients and generating guidance letters. RPA (EzRobot) automated repetitive clerical and billing-related tasks. A web form accessed via a QR code enabled recipients to respond digitally. Outcomes included manual administrative handling time per case, occurrence of transcription-related errors, health guidance completion rate, and guidance duration distribution. Results: Following implementation, staff active handling time per case decreased from approximately 10 minutes to less than 1 minute (approximately 30 seconds), while automated RPA execution typically required about 4-5 minutes per case without staff input. No transcription-related errors were detected during the post-implementation observation period. Health guidance completion rates improved from 28.3% to 39.2% (chi-square test, P=200 days decreased from 30.5% to 20.9% and cases with >=240 days decreased from 13.6% to 8.9% (R4 n=59, R5 n=158). Conclusion: An integrated Access-RPA-Web workflow was associated with improvements in administrative efficiency and operational reliability in post-checkup health guidance while retaining human verification and exception handling. This pragmatic, non-AI-dependent approach may offer a useful model for process-level improvement in preventive care settings.

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

Audited Conformal Prediction for Classification under Unknown Distribution Shift

arXiv:2606.14909v1 Announce Type: cross Abstract: We consider the problem of uncertainty quantification for a pretrained classification model deployed under unknown distribution shift. We propose Audited Conformal Prediction (ACP), a method that leverages a small labeled dataset from the target population to train an auxiliary audit model identifying inputs where the legacy model is likely to fail. By integrating the audit model's outputs into the conformal prediction framework, ACP produces prediction sets that guarantee marginal coverage while achieving substantially higher conditional coverage in practice than existing approaches. We develop and analyze two complementary integration strategies – one targeting marginal coverage with improved conditional performance, the other providing explicit group-conditional coverage guarantees – and establish theoretical guarantees for both. Experiments on synthetic and real-world datasets validate the method and illustrate trade-offs between prediction set size and conditional coverage.

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

Towards Personalized Federated Learning for Dysarthric Speech Recognition

arXiv:2606.13253v1 Announce Type: cross Abstract: Speech recognition is challenging for dysarthric speakers. While federated learning (FL)-based ASR can be an effective tool for protecting privacy, it suffers from heterogeneity issues caused by speaker variability. Forcing all speakers to share the same model components can be suboptimal under such heterogeneity, making personalization a promising direction; however, related research on dysarthric speech remains limited. To this end, this paper explores two aggregation strategies to achieve personalization, including the parameter-based averaging strategy and the embedding-based averaging strategy. Experiments on UASpeech and TORGO show that the proposed methods outperform the baseline regularized FedAvg by statistically significant WER reductions of up to 0.99% absolute (3.15% relative) on UASpeech and 0.56% absolute (4.73% relative) on TORGO, respectively.

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

Understanding, Detecting, and Repairing Real-World In-Context-Learning-Based Text-to-SQL Errors

Large language models (LLMs) have been adopted for text-to-SQL tasks, utilizing their in-context learning (ICL) capability to translate natural language questions into SQL queries. However, such a technique faces correctness problems. In this paper, we conduct the first comprehensive study of text-to-SQL errors of ICL-based techniques. Our study covers four representative ICL-based techniques, five basic repairing methods, two benchmarks, and two LLM settings. We find that text-to-SQL errors are widespread and summarize 27 error types of 7 categories. We also find that existing repairing attempts have limited correctness improvement while having high computational overhead and many mis-repairs. Based on these findings, we propose MapleDoctor, a novel text-to-SQL error detection and repairing framework. The evaluation demonstrates that MapleDoctor outperforms existing solutions by repairing 13.8% more queries with a negligible number of mis-repairs and reducing 67.4% repair latency. The artifact is publicly available at GitHub.

08.
arXiv (CS.AI) 2026-06-18

MagpieTTS-LF: Inference-Time Long-Form Speech Generation Without Training on Long-Form data

arXiv:2606.18485v1 Announce Type: cross Abstract: Neural Text-to-Speech (TTS) systems achieve remarkable quality on short utterances but long-form speech generation shows prosodic drift, speaker inconsistencies and sentence boundary artifacts. Existing approaches either compress sequences, increase context length or naively concatenate independently synthesized chunks. We present an inference-time approach called MagpieTTS-LF that enables MagpieTTS to produce coherent long-form speech without model retraining. Our method introduces three key innovations: (1) soft attention priors to guide monotonic alignment while preserving past and future context; (2) a stateful inference algorithm that maintains context across sentence chunks, ensuring prosodic continuity; (3) history-aware text encoding that uses past text for discourse-level prosodic planning. Experiments on long texts show significant improvements in long-range intelligibility, prosodic coherence, speaker consistency, and boundary naturalness compared to other baselines.

09.
arXiv (CS.LG) 2026-06-12

The Geometry of Phase Transitions in Generative Dynamics via Projection Caustics

arXiv:2606.13191v1 Announce Type: new Abstract: Continuous-state generative samplers, including diffusion and flow-matching models, evolve through continuous reverse-time dynamics, yet their samples often undergo abrupt qualitative changes: trajectories commit to modes, semantic alternatives collapse, and small perturbations in narrow time windows can produce large downstream effects. This paper develops a geometric account of such phase-transition-like behaviour. We view denoising as gradient descent on a free energy landscape and show that sharp transitions arise near projection caustics, where the nearest-point projection onto the data support ceases to be unique. Motivated by this perspective, we introduce the Critical Boundary Detector (CBD), as practical diagnostics for score-direction instability. Across toy models, standard diffusion models, and latent text-to-image diffusion models, CBD localises mode commitment, predicts intervention-sensitive windows, and supports targeted control in geometrically sensitive regions. Our results connect geometry of data and dynamics of diffusion generation.

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

Structure-Semantic Co-optimized Latent Diffusion Model for Fast Visual Anagram Synthesis

Visual anagram is an intriguing form of art creation wherein a single image presents different conceptual interpretations under transformations such as flipping or rotation. Recent work has achieved visual anagram synthesis by leveraging pretrained text-to-image (T2I) diffusion models, yet still suffers from several key limitations including computational inefficiency, suboptimal aesthetic quality, and weak semantic fidelity and expressiveness. This work focuses on generating visual anagrams with substantially improved visual quality at minimal computational cost, thereby advancing intelligent creation of illusionary digital art. To increase image resolution while reducing time overhead, we adapt the cutting-edge parallel denoising algorithm from pixel-based T2I model to the adversarially distilled latent-based one, and accordingly propose a structure-semantic co-optimization (S2CO) framework to counteract the consequent visual degradation. As the core of our approach, S2CO framework comprises three key innovations: (\romannumeral1) null-text structure alignment optimization; (\romannumeral2) semantic enhancement optimization; (\romannumeral3) attention-guided noise fusion. Building upon these components, our method dubbed S2CO-Anagram is able to generate higher-resolution anagram images with noticeably superior visual harmony and semantic faithfulness than related SOTA approaches, all while achieving substantially faster inference speed. Code will be publicly available.

11.
arXiv (quant-ph) 2026-06-17

Quantum statistical functions

Authors:

arXiv:2602.05821v2 Announce Type: replace Abstract: Statistical functions such as the moment-generating, characteristic, cumulant-generating, and second characteristic functions are standard tools in classical statistics and probability theory. They provide a systematic means to analyze the statistical properties of a system and find applications in diverse fields. While these functions are ubiquitous in classical theory, a quantum counterpart has remained underdeveloped because of the noncommutativity of operators. The absence of such a framework has obscured the connections between statistical quantities and the nonclassical features of quantum mechanics. Here, we construct a framework for quantum statistical functions that addresses these limitations and unifies the languages of quantum statistics. We show that the functions reproduce standard statistical quantities such as expectation values, variance, and covariance upon differentiation. By extending the framework to include pre- and post-selection, we define conditional functions that generate conditional statistical quantities, including the weak value and the weak variance. We further show that multivariable functions, defined with specific operator orderings, correspond to the Kirkwood–Dirac, Margenau–Hill, and Wigner distributions. By generalizing Bochner's theorem within the theory of compactly supported distributions, we obtain a criterion that separates classical statistics from quantum statistics, linking the failure of positive definiteness of the multivariable function to the emergence of quasiprobability. As an application, we import the classical method of moments and generalized method of moments into quantum estimation, introducing quantum estimators that exploit the proposed functions. Our framework reproduces quantum statistical quantities and incorporates the nonclassical features of quasiprobability, providing a basis for further study of quantum statistics.

12.
arXiv (CS.AI) 2026-06-11

Erased but Not Forgotten: How Backdoors Compromise Concept Erasure

arXiv:2504.21072v3 Announce Type: replace-cross Abstract: The expansion of text-to-image diffusion models has raised concerns about harmful outputs, from fabricated depictions of public figures to sexually explicit imagery. To mitigate such risks, prior work has proposed concept erasure methods that aim to sever unwanted concepts from the model via fine-tuning, yet it remains unclear whether these approaches truly remove all links to the harmful concept or merely conceal superficial connections. In this work, we reveal a critical vulnerability, the Erasure Evasion Backdoor (EEB): an adversary binds a backdoor trigger to a concept slated for removal, and this malicious link survives subsequent erasure. We show that both black-box and white-box adversaries can instantiate this threat. Across six state-of-the-art erasure methods, including robust ones that explicitly search for alternative representations of the target concept, EEB consistently exposes harmful content: up to 82% success against celebrity-identity unlearning, up to 94% for object erasure, and up to 16 times amplification of explicit-content exposure. While EEB uncovers a blind spot in current erasure methods, it also provides a diagnostic tool for stress-testing future concept erasure techniques.

13.
arXiv (CS.AI) 2026-06-16

Rescaling Confidence: What Scale Design Reveals About LLM Metacognition

arXiv:2603.09309v2 Announce Type: replace Abstract: Verbalized confidence, in which LLMs report a numerical certainty score, is widely used to estimate uncertainty in black-box settings, yet the confidence scale itself (typically 0–100) is rarely examined. We show that this design choice is not neutral. Across six LLMs and three datasets, verbalized confidence is heavily discretized, with more than 78\% of responses concentrating on just three round-number values. To investigate this phenomenon, we systematically manipulate confidence scales along three dimensions: granularity, boundary placement, and range regularity, and evaluate metacognitive sensitivity using $meta-d'$. We find that a 0–20 scale consistently improves metacognitive efficiency over the standard 0–100 format, while boundary compression degrades performance and round-number preferences persist even under irregular ranges. These results demonstrate that confidence scale design directly affects the quality of verbalized uncertainty and should be treated as a first-class experimental variable in LLM evaluation.

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

Human Cognition in Machines: A Unified Perspective of World Models

This report of world models distinguishes prior works by the cognitive functions they innovate. Many works claim an almost human-like cognitive capability in their world models. To evaluate these claims requires a proper grounding in first principles from human and machine cognition theory. In moving towards human-like world models we present a conceptual unified framework for world models that fully incorporates all the cognitive functions (i.e., memory, perception, language, reasoning, imagining, motivation, and metacognition) and identify gaps in existing research as a guide for future states of the art. In particular, we find that motivation (especially intrinsic motivation) and metacognition remain drastically under-researched, and we propose concrete directions to address these gaps informed by active inference and global workspace theory. We also introduce epistemic world models, a new category encompassing agent frameworks for scientific discovery that operate over structured knowledge. Our taxonomy, applied to video, embodied, and epistemic world models, suggests research directions where prior taxonomies have not.

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

Cross-Modal Registration Between 3D and 2D Fingerprints via Pose-Aware Unwrapping and Point-Cloud Fusion

Three-dimensional (3D) fingerprints preserve global finger geometry and local ridge structure while avoiding contact-induced deformation, but they remain difficult to integrate with legacy two-dimensional (2D) fingerprint systems. This paper addresses the intermediate stage between 3D acquisition and cross-modal matching, and presents a unified framework for 3D fingerprint preprocessing and registration across contactless and contact-based 2D modalities. The framework combines four components: 1) a nonparametric visualization and unwrapping method that converts a 3D fingerprint point cloud into a rolled-equivalent 2D representation without relying on a global finger-shape model; 2) a point-cloud fusion pipeline that registers and mosaics multiple partial 3D captures into a more complete fingerprint model; 3) an ellipse-based pose normalization method for canonical finger alignment; and 4) a pose-aware cross-modal registration strategy that improves compatibility between 3D fingerprints and both contactless and contact-based 2D fingerprints. Experiments on a self-collected multimodal fingerprint database containing 150 fingers show that the proposed framework achieves ridge-level 3D registration accuracy, robust pose estimation, and consistent gains in 2D compatibility. In particular, the 3D fusion error is concentrated around 0.09 mm, contactless 2D–3D registration reaches ridge-scale projection accuracy, and pose-aware unwrapping improves genuine matching scores relative to generic 3D unwrapping. These results support the use of 3D fingerprints as an effective geometric bridge across heterogeneous fingerprint modalities. The baseline implementation has been publicly released at https://github.com/XiongjunGuan/3DFpVisual.

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

Aligning Quantum Operators with Large Language Models

arXiv:2606.13811v1 Announce Type: cross Abstract: Can Large Language Models (LLMs) understand and reason about quantum operators? Despite their remarkable capabilities in mathematics and symbolic reasoning, LLMs remain inherently blind to quantum representations such as unitary matrices. In this work, we take a step toward bridging this gap by introducing an approach that maps unitary operators into the latent space of an LLM, enabling unified modeling over quantum and linguistic inputs. We instantiate this idea on Clifford+T circuit synthesis over a Pauli rotation gate set, where our model achieves results competitive with state-of-the-art methods and scales consistently with training data, with no signs of saturation. Our approach further enables language-conditioned synthesis, allowing gate constraints unseen during training to be specified directly in natural language. This work suggests a path toward quantum–aware foundation models that can natively interpret and reason about quantum operations, which could have broader implications reaching across quantum compilation and algorithm discovery.

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

An adaptive framework for the axisymmetric pulsar magnetosphere using physics-informed Kolmogorov-Arnold networks

arXiv:2606.10686v2 Announce Type: replace-cross Abstract: The pulsar magnetosphere has only recently been addressed using Physics-Informed Neural Networks (PINNs), by deploying a domain-decomposition approach and treating the separatrix and equatorial current sheet as infinitesimally thin discontinuities. However, this baseline requires extensive manual hyperparameter tuning, achieves limited final accuracy and demands several hours of training. We refine this framework by introducing domain-specific neural architectures based on Kolmogorov-Arnold networks, an automated adaptive training pipeline and a physics-based convergence criterion that eliminate the need for manual calibration. The proposed methodology delivers self-consistent axisymmetric magnetosphere solutions with mean squared errors of the PDE residuals at O(1e-6) in double precision - an improvement of two orders of magnitude over the baseline - while achieving convergence in under 20 minutes in single precision. Importantly, the method reliably resolves stellar radii reduced by up to 80% compared to the baseline, overcoming the severe spatial scale disparities that also challenge traditional solvers. Furthermore, by varying the flux that opens to infinity, we provide a correction to the equation that connects it to the equatorial T-point's position. The complete framework is released as the open-source library PulsarX.

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

RLRC: Reinforcement Learning-based Recovery for Compressed Vision-Language-Action Models

arXiv:2506.17639v2 Announce Type: replace-cross Abstract: Vision-Language-Action models (VLA) have demonstrated remarkable capabilities and strong potential in complex robotic manipulation. However, their large parameter sizes and high inference latency hinder real-world deployment, especially on resource-constrained platforms. To address this, we conduct a systematic empirical study of model compression for VLAs. Building on these insights, we present RLRC, a three-stage compression and recovery pipeline consisting of structured pruning, performance recovery via SFT and RL, and subsequent quantization. The RL stage incorporates a critic warm-up strategy and BC loss regularization to stabilize training and preserve policy behavior. RLRC achieves up to an 8 times memory reduction and 2.3 times inference speedup while maintaining the original task success rate. Extensive experiments across multiple VLA backbones show that RLRC consistently outperforms existing compression baselines, highlighting its effectiveness for on-device deployment. Project website: https://rlrc-vla.github.io

19.
medRxiv (Medicine) 2026-06-15

Multi-domain AD risk burden and plasma biomarkers in cognitively unimpaired adults

Introduction: Alzheimer's disease (AD) pathology accumulates decades before symptom onset, yet how the cumulative effect of genetic, familial, and modifiable lifestyle risk burden jointly affects plasma biomarker levels and trajectories in cognitively unimpaired older adults remains unknown. Methods: We analyzed data from 261 participants in the PREVENT-AD cohort. A composite risk score integrating APOE e4 status, polygenic score, family history, and modifiable/lifestyle risk was examined against six plasma biomarkers using linear regression and linear mixed-effects models. Results: APOE e4 was the strongest predictor of plasma biomarker levels. Higher composite risk burden was associated with elevated ptau181, ptau217, ptau217/Ab42, and GFAP levels, and lower Ab42/40 levels. A higher risk burden was predictive of accelerated ptau181 accumulation. Discussion: Cumulative AD risk burden is broadly associated with plasma biomarker levels and specifically predicts accelerated ptau181 accumulation in cognitively unimpaired older adults, supporting structured composite risk profiling as a framework for AD risk stratification.

20.
arXiv (CS.CL) 2026-06-16

Human genetic evidence is associated with drug approval across therapeutic areas: an observational analysis of 26,278 target-disease pairs with temporal validation and feature ablation

Genetic evidence is enriched among approved drug targets: in an observational analysis of 26,278 target-disease pairs from Open Targets and ChEMBL, targets with any genetic association had a 3.25-fold higher approval rate than those without (OR = 3.25, 95% CI 2.79-3.79, p = 1.91e-42). A target-level analysis accounting for non-independence of pairs sharing the same gene gave OR = 2.79 (bootstrap 95% CI 2.22-3.53); the oncology pair-level OR of 6.72 attenuates to 2.71 at the target level, illustrating how non-independence inflates area-specific estimates. The enrichment replicated in post-2015 approvals (OR = 3.51, p = 1.72e-8). Feature ablation across six evidence types revealed that literature mining alone accounts for most classifier performance (AUPRC = 0.099 versus 0.109 for all features), consistent with temporal leakage from post-approval publications. Excluding literature, remaining evidence types retain above-baseline signal (AUPRC = 0.084, 1.63x baseline). Sensitivity analyses bracket the pair-level OR between 3.25 and 4.93. Genetic evidence alone yields only a 1.0-percentage-point absolute AUPRC gain and the best model has poor calibration; the classifier has limited practical predictive value. We catalogue 1,433 genetically supported Phase 1/2 pairs as a hypothesis-generating resource. All findings are observational.

21.
medRxiv (Medicine) 2026-06-22

Survival differences and artemisinin resistance in severe malaria among HIV coinfected patients: data from Mozambique

Abstract Background Malaria remains a significant cause of morbidity and mortality, especially in sub-Saharan Africa, where rates of HIV coinfection are high. This study aimed to determine whether Plasmodium falciparum malaria treatment outcomes and rates of antimalarial resistance markers differ according to HIV serostatus in Mozambique. Methodology We conducted an observational study of non-pregnant adults, with and without HIV coinfection, admitted to the Hospital Central de Maputo for treatment of severe malaria. Plasmodium falciparum DNA was extracted from whole blood and sequenced to identify single-nucleotide polymorphisms. Statistical analyses to compare clinical outcomes and rates of nonsynonymous mutations in genes associated with drug resistance were performed in R version 4.2. Results We recruited 149 study participants aged between 18-62 years, 72 (48.3%) were female, and 59 (39.6%) were infected with HIV. Comparing clinical outcomes, we found a significant difference in anemia (hemoglobin

22.
arXiv (CS.LG) 2026-06-15

Hybrid Uncertainty Sensitivity Analysis Based on the HSIC for High-Dimensional Responses with Aleatory–Epistemic Separation

arXiv:2606.14053v1 Announce Type: cross Abstract: Quantifying the influence of hybrid aleatory and epistemic uncertainties on high-dimensional system responses remains a major challenge in global sensitivity analysis (GSA). Existing Hilbert–Schmidt Independence Criterion (HSIC)-based approaches are primarily restricted to single-output settings and lack a rigorous decomposition of heterogeneous uncertainty sources and their interactions. To address this limitation, a novel double-space tensor-product RKHS framework is proposed for sensitivity analysis under hybrid uncertainty. By constructing factorized kernels over both the latent input space and the multidimensional output space, a concurrent double Möbius inversion is derived to orthogonally decompose the global dependence measure into pure aleatory effects, pure epistemic effects, and their interaction contributions. The resulting dimension-wise sensitivity indices preserve the uncertainty attribution structure across all output dimensions. To satisfy the independence assumptions required by the decomposition, an auxiliary-variable representation based on the inverse probability integral transform is introduced, enabling the treatment of hierarchical uncertainties and Copula-induced correlations within a unified latent space. A fully vectorized single-loop implementation is further developed to avoid the computational burden of nested Monte Carlo simulation. Statistical significance and estimation uncertainty are quantified through permutation testing and Bootstrap confidence intervals. Numerical studies on a modified multi-output Ishigami function and an aerodynamic pressure-field problem demonstrate the accuracy, scalability, and practical applicability of the proposed framework.

23.
arXiv (CS.AI) 2026-06-16

When in Doubt, Plan It Out: Committed Small Language Model Deliberation for Reactive Reinforcement Learning

arXiv:2606.16995v1 Announce Type: new Abstract: Reinforcement Learning (RL) policies often degrade in unfamiliar environments because they lack explicit deliberation. We propose Plan, Align, Commit, Think (PACT), a hybrid architecture that combines a fast, reactive RL policy with a slow, deliberative Small Language Model (SLM) planner. PACT invokes the SLM asynchronously to generate and validate candidate action plans. Once a plan is verified through simulation as safe, feasible, and complete, it is executed directly, bypassing the RL policy without retraining or modifying it. Evaluated on three FrozenLake configurations of increasing difficulty, PACT outperforms all baselines while relying on a 2B-parameter SLM backbone, suggesting that deliberative planning and reactive execution are more powerful in concert than either is alone in these settings.

24.
arXiv (CS.CV) 2026-06-18

Zero-Shot Cross-City Generalization in End-to-End Autonomous Driving: Self-Supervised versus Supervised Representations

End-to-end autonomous driving models are typically trained on multi-city datasets using supervised ImageNet-pretrained backbones, yet their ability to generalize to unseen cities remains largely unexamined. When training and evaluation data are geographically mixed, models may implicitly rely on city-specific cues, masking failure modes that would occur under real-world domain shifts when generalizing to new locations. In this work, we formulate zero-shot cross-city transfer as a controlled representation-level stress test for end-to-end autonomous driving and ask how visual pretraining affects transfer behavior under geographic domain shift. We conduct a comprehensive study by integrating self-supervised backbones I-JEPA, DINOv2, and MAE into planning frameworks. We evaluate performance under strict geographic splits on nuScenes in the open-loop setting and on NAVSIM in the closed-loop evaluation protocol. Our experiments reveal a substantial generalization gap when transferring models across cities with different road topologies, traffic conventions, and visual environments. In open-loop evaluation, a supervised backbone exhibits severe degradation when transferring between cities, yet some domain-specific self-supervised methods can substantially reduce both displacement and collision degradation. In closed-loop evaluation, self-supervised pretraining improves average out-of-distribution PDMS in several single-city training settings. Our results provide empirical evidence that representation learning influences the robustness of cross-city planning and motivate zero-shot geographic transfer as an important stress test for evaluating end-to-end autonomous driving systems.

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

The Proxy Knows Too Much: Sealing LLM API Routers with Attested TEEs

arXiv:2606.16358v1 Announce Type: cross Abstract: Agents increasingly access large language models (LLMs) through API routers. A router terminates the client's transport-layer security session and opens a separate upstream session, so it holds the full interaction in plaintext. This makes the router an application-layer man-in-the-middle: it can rewrite agent tool calls, swap dependencies for typosquatted packages, trigger attacks only under audit-evading conditions, and passively exfiltrate secrets. Existing client-side defenses are evadable. We propose AEGIS, a provider-transparent attested API router whose data path is a client-verified faithful passthrough. AEGISconfines plaintext handling to a small hardware-enclave component while leaving authentication, scheduling, accounting, and management on the untrusted host. The client verifies the enclave before releasing plaintext. The host can neither read nor alter the interaction, and plaintext leaves only toward destinations fixed by the measured image. We show that all four malicious-router attack classes succeed against a plaintext-access baseline and are blocked by AEGIS, including adaptive tests against the same boundary. The trusted path is $851$ lines, carries three provider-native APIs without conversion, and completes every request under real-provider workload and concurrency. In a seeded audit pilot, two commodity coding agents find eight and ten of ten planted invariant violations. The local relay overhead is about six milliseconds per request.