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01.
arXiv (CS.CL) 2026-06-15

Fodor and Pylyshyn's Systematicity Challenge Still Stands

The recent successes of neural networks producing human-like language have caused significant stir in cognitive science, with many researchers arguing that classical puzzles about human cognition and challenges to artificial intelligence are being solved by neural networks. A notable case is the argument from systematicity due to Jerry Fodor and Zenon Pylyshyn, argues that humans display systematic biconditional dependencies. For example, someone can understand the sentence "John saw Mary" just in case that they understand the sentence "Mary saw John." Symbolic systems explain this systematicity of language and thought, while neural networks offer no immediate explanation. Several recent articles argue that this challenge has now been met by neural networks. In particular, Brenden Lake and Marco Baroni argue that their meta-learning for compositionality protocol matches and perhaps explains human systematicity. We demonstrate that these conclusions are premature. Among other results, we found that their model struggles to learn rules that are even slightly out of distribution compared to their training data. Furthermore, the model behaves unsystematically even on many within-distribution problems. We conclude that Fodor and Pylyshyn's challenge to neural networks remains unmet.

02.
PLOS Computational Biology 2026-06-17

Machine learning-driven identification of virulence determinants in <i>Borrelia burgdorferi</i> associated with human dissemination

by Hoa Thanh Nguyen, Catherine A. Brissette Lyme disease, the most common tick-borne infectious disease in the United States, presents with highly variable clinical outcomes, ranging from localized erythema migrans to severe disseminated complications affecting the heart, joints, and nervous system. The bacterial determinants underlying this phenotypic variation remain largely unknown, limiting our ability to predict disease progression and optimize treatment strategies. Here, we applied machine learning (ML) approaches to identify specific amino acid residues within surface-exposed virulence factors that predict human dissemination phenotypes. Utilizing the published whole genome sequences from 299 clinical Borrelia burgdorferi isolates collected from the United States and Slovenia over a 30-year period (1992–2021), we extracted and characterized translated amino acid sequences (variants) of seven known virulence factors (BB_0406, BBK32, DbpA, OspA, OspC, P66, and RevA). Protein variants were classified based on their association with disseminated versus localized infections using clinical metadata. Cramér’s V analysis revealed possible strong associations between dissemination phenotypes and five adhesins: BBK32, DbpA, OspC, P66, and RevA. We developed ML models using five algorithms with multiple feature selection strategies, achieving robust predictive performance for DbpA, OspC, and RevA variants (all performance metrics > 0.7). Feature importance analysis identified 57, 29, and 42 key predictive residues for DbpA, OspC, and RevA, respectively. Notably, B-cell epitope prediction revealed significant enrichment of ML-identified residues within predicted epitope regions for OspC (11 overlapping residues, OR = 3.57, p = 0.006) and RevA (12 overlapping residues, OR = 2.37, p = 0.048), suggesting these residues may influence immune recognition and bacterial persistence. This study establishes the first computational framework linking Borrelia protein sequence variants to clinical dissemination phenotypes, providing molecular insights into Lyme disease pathogenesis that may inform the development of improved diagnostics and therapeutic targets.

03.
arXiv (CS.AI) 2026-06-11

Compiler-First State Space Duality and Portable $O(1)$ Autoregressive Caching for Inference

arXiv:2603.09555v2 Announce Type: replace-cross Abstract: High-throughput Mamba-2 inference is usually tied to fused CUDA and Triton kernels, limiting portability across accelerator backends. We show that the state space duality (SSD) recurrence has a compiler-friendly structure: diagonal per-head dynamics, fixed-size chunking, einsum-dominated compute, and static control flow. Expressing this structure in standard JAX primitives gives a single-source inference path with no custom kernels, a registered JAX PyTree cache, and a compiled on-device autoregressive loop. On a single Google Cloud TPU v6e, batch-1 prefill reaches approximately 140 TFLOPS, or 15% model FLOP utilisation (MFU), the roofline ceiling for this regime, and cached decode reaches up to 64% hardware bandwidth utilisation (HBU). At a 4096-token context, cached decode is 27x–36x faster than full-prefix recomputation across five Mamba-2 checkpoints from 130M to 2.7B parameters. The same source runs unmodified on NVIDIA L40S, where cached decode remains sequence-length independent across all model scales. WikiText-103 validation perplexity matches the Triton reference mamba_ssm v2.2.2 within +/-0.0005 points, and hidden states agree to float32 rounding tolerance. Code is available at https://github.com/CosmoNaught/mamba2-jax.

04.
arXiv (math.PR) 2026-06-12

Sphere Packings in Higher Dimension (after Boaz Klartag)

arXiv:2606.13313v1 Announce Type: cross Abstract: Let $\delta_n^L$ be the maximal density of a lattice sphere packing in the $n$-dimensional Euclidean space. We explain how Boaz Klartag proved the inequality $\delta_n^L \geq c n^2 2^{-n}$ where $c>0$ is a universal constant. In higher dimension, even for non-lattice sphere packings, this new lower bound is a substantial improvement. Klartag's proof uses the probabilistic method in two different ways. The first, very standard, relies on the statistical properties of a uniformly chosen random lattice. The second, completely new, studies the stochastic evolution of an ellipsoid constrained to contain non nonzero lattice points in the interior.

05.
arXiv (CS.CV) 2026-06-12

Quality-Preserving Imperceptible Adversarial Attack on Skeleton-based Human Action Recognition

Adversarial attacks on skeletal human action recognition have received significant attention. However, existing methods typically introduce noise-like perturbations that degrade motion quality post-attack, and thereby are inherently perceptible with recent advancements in S-HAR systems. We discover that this degradation stems from the gap between empirical and true risks during the optimization process of previous adversarial attacks. To address this issue, we propose an attack where adversarial motions are obtained without compromising their motion quality. To minimize the risk gap and preserve motion quality, we propose a distribution-based adversarial attack method without introducing noise-like perturbations. To faithfully evaluate the motion quality, we propose a new metric that aligns with human perception on real-world naturalness. Experiments have been conducted on the state-of-the-art S-HAR methods across two datasets, demonstrating the superiority of our method in both the attack success rate and the post-attack motion quality through qualitative and quantitative analyses. The success of our quality-preserving attack application and distribution-based method raises serious concerns about the robustness of action recognizers, highlighting the need for further enhancements in this domain.

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

Hardware- and Vision-in-the-Loop Validation of Deep Monocular Pose Estimation for Autonomous Maritime UAV Flight

arXiv:2606.19176v1 Announce Type: cross Abstract: Autonomous UAV operations on ships require reliable vision-based relative pose estimation, yet at-sea validation is costly, weather-dependent, and risky. This paper presents a hardware-validated vision-in-the-loop framework that enables fully autonomous indoor flight while emulating photorealistic maritime environments. Rendered maritime views are processed onboard by a deep transformer-based monocular pose estimator. Delayed vision measurements are fused with high-rate IMU data using a delayed Kalman filter to provide consistent state estimates for geometric control. The system captures critical embedded effects, including perception latency, asynchronous updates, and computational constraints, that are absent in pure simulation. Autonomous takeoff, trajectory tracking, and landing experiments demonstrate stable closed-loop flight. The results establish a safe and hardware-realistic intermediate stage for developing maritime UAV autonomy prior to shipboard deployment.

07.
medRxiv (Medicine) 2026-06-16

Diurnal variation in brain-derived tau and five other blood-based biomarkers for dementia and their association with cognitive performance

Blood-based biomarkers of dementia are a promising scalable tool for early diagnosis, tracking disease progression, and evaluating therapeutic efficacy. Utility of these biomarkers will not only be dependent on the reliability of their association with pathology but also contingent on their ability to track cognitive status. Previously, we demonstrated diurnal variation in several biomarkers (amyloid beta (A{beta}) 42 and 40, 42/40 ratio, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and phosphorylated-Tau 217 (p-Tau217)) which has implications for their reliability. Here, we extend these observations to a larger cohort, include brain-derived tau (BD-Tau), which is assumed to be produced exclusively in the brain, and report endocrine measures of circadian rhythmicity. We not only assessed whether these biomarkers vary with time of day, but also whether they associate with daytime function and whether these associations vary with cognitive domain and number of repeated assessments. Data collected in 20 PLWA (72.4{+/-}5.9 years, mean{+/-}SD) and 19 controls (68.9{+/-}9.8 years) were analysed. Participants completed 14 days of home monitoring and one laboratory assessment of sleep and daytime function: mood, daytime sleepiness, reaction time, immediate and delayed memory recall, everyday memory errors. During the 27-hour residential laboratory session, 3-hourly blood samples were collected and analysed for the six blood-based biomarkers of dementia as well as melatonin and cortisol. Rhythmicity of melatonin and cortisol did not differ between groups. P-Tau217 and GFAP (p

08.
arXiv (math.PR) 2026-06-16

Layerwise Terminal Discrepancy in Chen's Reverse-Heat Coupling on the Boolean Cube

arXiv:2606.04573v2 Announce Type: replace-cross Abstract: Recently, Chen [Chen2026] proved that Talagrand's Boolean convolution conjecture holds up to the dimension-free factor \((\log\log\eta)^{3/2}\), namely for every fixed \(\tau>0\), \[ \mu\{P_\tau f>\eta\|f\|_1\} \le C_\tau \frac{(\log\log\eta)^{3/2}}{\eta\sqrt{\log\eta}}, \qquad \eta>e^3. \] We revisit the terminal testing-discrepancy step in Chen's perturbed reverse-heat coupling. Chen estimates this discrepancy globally in terms of the remaining gap to the terminal level. We keep the same coupling and the same reverse-heat formulations, but localize the terminal discrepancy on each remaining-gap layer before summing the layers. This changes the fixed-time anti-concentration cost from order \((\log L)^{3/2}/\sqrt L\) to order \((\log L)/\sqrt L\), where \(L=\log\eta\). Consequently, we obtain a \((\log\log\eta)^{1/2}\) improvement as \[ \mu\{P_\tau f>\eta\|f\|_1\} \le C_\tau \frac{\log\log\eta}{\eta\sqrt{\log\eta}}, \qquad \eta>e^3. \]

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

Utility-Diversity Aware Online Batch Selection for LLM Supervised Fine-tuning

Supervised fine-tuning (SFT) is a commonly used technique to adapt large language models (LLMs) to downstream tasks. In practice, SFT on a full dataset is computationally expensive and sometimes suffers from overfitting or bias amplification. This facilitates the rise of data curation in SFT, which prioritizes the most valuable data to optimze. This work studies the online batch selection family that dynamically scores and filters samples during the training process. However, existing popular methods often (i) rely merely on the utility of data to select a subset while neglecting other crucial factors like diversity, (ii) rely on external resources such as reference models or validation sets, and (iii) incur extra training time over full-dataset training. To address these limitations, this work develops UDS (Utility-Diversity Sampling), a framework for efficient online batch selection in SFT. UDS leverages the nuclear norm of the logits matrix to capture both data utility and intra-sample diversity, while estimating inter-sample diversity through efficient low-dimensional embedding comparisons with a lightweight memory buffer of historical samples. Such a design eliminates the need for external resources and unnecessary backpropagation, securing computational efficiency. Experiments on multiple benchmarks demonstrate that UDS consistently outperforms state-of-the-art online batch selection methods under varying data budgets, and significantly reduces training time compared to full-dataset fine-tuning. Code is available at https://github.com/gfyddha/UDS.

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

Risk-Aware LLM Agents for Geospatial Data Retrieval: Design and Preliminary Adversarial Evaluation

We present an LLM-driven framework for retrieving remote sensing data from cloud-based geospatial catalogues using natural language queries. The system converts user intent into structured API calls, enabling efficient access to satellite imagery and environmental datasets. The architecture integrates three agents: Guardrail for safety and policy enforcement, General-QA for intent interpretation, and Recommender-Analyst for schema-aware API call generation. This coordinated design ensures reliable, semantically aligned interaction with external data services. The modular framework is portable across platforms through API schema substitution and supports applications in environmental monitoring, disaster response, and climate analysis. It establishes a scalable interface between user intent and geospatial infrastructure, enabling streamlined and automated Earth observation workflows. Preliminary experiments under adversarial multi-turn settings show that prompt-level safety instructions improve robustness, although rare high-impact failures persist in API manipulation scenarios and highlight the need for adaptive, system-level defenses that balance safety, usability, and cost efficiency, which motivates the use of our intercept-level Guardrail agent.

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

Exact Many-body Quantum Dynamics in One-Dimensional Baths via Collective Spins

arXiv:2505.00588v2 Announce Type: replace Abstract: Computing the exact dynamics of many-body quantum systems becomes intractable as system size grows. Here, we present a symmetry-based method that provides an exponential reduction in the complexity of a broad class of such problems $\unicode{x2014}$ qubits coupled to one-dimensional electromagnetic baths. We identify conditions under which partial permutational symmetry emerges and exploit it to group qubits into collective multi-level degrees of freedom, which we term ''superspins.'' These superspins obey a generalized angular momentum algebra, reducing the relevant Hilbert space dimension from exponential to polynomial. Using this framework, we efficiently compute many-body superradiant dynamics in large arrays of qubits coupled to waveguides and ring resonators, showing that $\unicode{x2014}$ unlike in conventional Dicke superradiance $\unicode{x2014}$ the total spin length is not conserved. At long times, dark states become populated. We identify configurations where these states exhibit metrologically useful entanglement. Our approach enables exact treatment of complex dissipative dynamics beyond the fully symmetric limit and provides a rigorous benchmark for approximate numerical methods.

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

No One Knows the State of the Art in Geospatial Foundation Models

Geospatial foundation models (GFMs) have been proposed as generalizable backbones for disaster response, land-cover mapping, food-security monitoring, and other high-stakes Earth-observation tasks. Yet the published work about these models does not give reviewers or users enough information to tell which model fits a given task. We argue that nobody knows what the current state of the art is in geospatial foundation models. The methods may be useful, but the GFM literature does not standardize evaluations, training and testing protocols, released weights, or pretraining controls well enough for anyone to compare or rank them. In a 152-paper audit, we find 46 cross-paper disagreements of at least 10 points for the same model, benchmark, and protocol; 94/126 papers with extractable pretraining data use a configuration no other paper uses; and 39% of GFM papers release no model weights. This lack of community standards can be solved. We propose six concrete expectations: named-license weight release, shared core evaluations, copied-versus-rerun baseline annotations, variance reporting, one shared evaluation harness, and data-vs-architecture-vs-algorithm controls. These gaps are a coordination failure, not a fault of any individual lab; the authors of this paper, like many others in the GFM community, have contributed to them. Rather than just critiquing the community, we aim to provide concrete steps toward a shared understanding of how to innovate GFMs.

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

Bridging the Usability Gap: Lessons from Interpreting Studies for Machine Interpreting Design

Machine interpreting (MI), the live, real-time branch of speech translation, has achieved remarkable progress on standard benchmarks, with some systems approaching human parity on textual fidelity. Yet the user experience remains far inferior to interpreter-mediated communication, revealing what we term the accuracy illusion: systems that appear accurate on paper but fail in practice to support smooth, goal-oriented interaction. This paper defines MI as a distinct subfield of speech translation, with its own characteristics and the need for evaluation methods grounded in communicative effectiveness rather than isolated fidelity metrics. Drawing on insights from interpreting studies, we identify critical dimensions of professional interpreting practice that are overlooked by current systems, and consolidate them into three interdependent design priorities for future MI: agency (context-sensitive initiative and repair), grounding (multimodal and discourse-level situational awareness), and experience (adaptive improvement through real interaction). Together, these priorities chart a path toward closing the usability gap and enabling systems that can sustain authentic multilingual communication in real time.

14.
arXiv (quant-ph) 2026-06-19

Electrical Noise Produced by Micron-Sized Particles above a Surface Paul Trap

arXiv:2606.19585v1 Announce Type: new Abstract: Electric field noise produced by the surface of ion trap electrodes reduces the fidelity of quantum computing operations. Despite decades of investigation its microscopic origins remain unclear. Here, we measure electric field noise at trapping locations along the symmetry axis of a linear surface Paul trap. We find that noise levels vary by three orders-of-magnitude in one 600$\,\mu$m section of the trap. Optical and scanning electron microscope images show micron-sized particles close to the trapping locations with the highest noise levels. We find that modeling the particles as a lossy dielectric with a effective loss tangent $\tan\theta=0.33(0.06)$ describes the magnitude of the noise, as well as its spatial and frequency dependence. Our observations may explain the large variation of reported noise levels in literature.

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

Toward Preference-aligned Large Language Models via Residual-based Model Steering

Preference alignment is a critical step in making Large Language Models (LLMs) useful and aligned with (human) preferences. Existing approaches such as Reinforcement Learning from Human Feedback or Direct Preference Optimization typically require curated data and expensive optimization over billions of parameters, and eventually lead to persistent task-specific models. In this work, we introduce Preference alignment of Large Language Models via Residual Steering (PaLRS), a training-free method that exploits preference signals encoded in the residual streams of LLMs. From as few as one hundred preference pairs, PaLRS extracts lightweight, plug-and-play steering vectors that can be applied at inference time to push models toward preferred behaviors. We evaluate PaLRS on various small-to-medium-scale open-source LLMs, showing that PaLRS-aligned models achieve consistent gains on mathematical reasoning and code generation benchmarks while preserving baseline general-purpose performance. Moreover, when compared to models aligned with DPO and SimPO, they perform better with great time-savings. Our findings highlight that PaLRS offers an effective, much more efficient and flexible alternative to standard preference optimization pipelines, offering a training-free, plug-and-play mechanism for alignment with minimal data.

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

UNIEGO: Proxies as Mediators for Unified Egocentric Video Representation Learning

arXiv:2606.20559v1 Announce Type: cross Abstract: Egocentric video understanding is inherently limited by the narrow perspective of wearable cameras: a single viewpoint, a single modality, a single model cannot capture the full richness of human action. We argue that a truly expressive egocentric representation must subsume complementary knowledge across viewpoints, modalities, and foundation model representations, yet remain deployable from egocentric video alone. To this end, we introduce a hierarchical multi-teacher distillation framework that produces UNIEGO, a unified egocentric encoder trained with nine teachers spanning ego-exo viewpoints, RGB, depth, and skeleton modalities, and four foundation models. Rather than distilling directly from heterogeneous teachers whose incompatible architectures and feature geometries induce conflicting gradients, our framework interposes a layer of representation-specific Proxy models that translate diverse teacher knowledge into a homogeneous egocentric space. A second distillation stage, Selective Proxy Distillation (SPD), then adaptively selects, for each training sample, the subset of proxies that are both correct and confident, distilling exclusively from reliable supervision and suppressing erroneous signals. SPD is further stabilized by initializing UNIEGO as a learned convex combination of proxy parameters, placing the unified model in a well-conditioned region of the loss landscape before distillation begins. UNIEGO achieves state-of-the-art performance across three egocentric video understanding tasks - action recognition, video retrieval, and action segmentation on three challenging ego-exo benchmarks, outperforming naive multi-teacher distillation baselines and demonstrating that structured, proxy-mediated knowledge transfer yields richer and more discriminative egocentric representations.

17.
medRxiv (Medicine) 2026-06-11

Computer Vision Scoring of Figure Copy and Recall

Objective. Figure copy and recall tests are sensitive measures of visuoconstruction and visual episodic memory, but their clinical is constrained by labor-intensive manual scoring. We developed and validated an automated, element-level scoring pipeline using Vertex AI object detection for the tablet-based figure copy and recall tasks in the California Cognitive Assessment Battery (CCAB). The automated scoring pipeline duplicated the scoring procedures used by expert manual raters. Methods. A normative sample of 2,011 community-dwelling adults aged 18-90 completed figure copy and delayed recall trials at baseline, with subsamples retested at 1 day and at 6, 18, and 30 months. Participants completed the drawings with their index finger on a tablet computer with finger position digitized to analyze the speed and timing of individual drawing strokes A convolutional object-detection model trained on the Vertex AI AutoML Vision platform identified each of twelve canonical figure elements in rendered drawings. Separate element presence and location scores were computed after homographically warping drawings onto a canonical template to produce trial-level Element, Location, and Total scores. To compare Vertex and human scores, Vertex AI and expert human raters independently scored 1500 randomly selected drawings to evaluate inter-rater agreement, including a common subset of 100 drawings scored by Vertex AI and all raters. Results. Total scores were virtually indistinguishable (r = 0.966) from human-human agreement (mean r = 0.971) as were Element presence scores (mean r = 0.959 vs. r = 0.963). Location-score agreement (r = 0.951) was slightly below the human-human mean (r = 0.972) due to pixel-level analysis by Vertex AI that was impossible for human raters. The Vertex pipeline showed no preferential advantage for the single expert rater who categorized Elements during training. Automated scores showed strong demographic gradients, age effects on Recall (r = -0.32) were approximately twice those in Copy conditions (r = -0.16). A Memory Cost score (Recall - Copy) showed a monotonic age-related decline from +0.40 z in the youngest subjects to -0.54 z in the oldest. Kinetic analysis revealed that drawing speed and efficiency showed significant age-related changes. Overnight test-retest reliability was high (Recall r = 0.72) and the Recall trial showed a large overnight learning effect ({Delta} = +1.18) that continued with repeated tests up to 30 months ({Delta} = +0.75).

18.
arXiv (CS.CV) 2026-06-19

OTCHA: Optimal Transport-driven Confidence-aware Latent Hub Alignment for Multi-View Medical Image Classification

Multi-view imaging, such as mammography and chest radiography, is a standard component of clinical practice. However, medical images are often unregistered and contain view-specific artifacts or irrelevant background cues that can obscure diagnostically relevant findings. Many existing methods directly fuse per-view representations, allowing such irrelevant content to contaminate the fused embedding and reducing robustness under varying view configurations. We propose OTCHA, a confidence-aware latent hub token alignment module based on optimal transport (OT) that refines patch tokens before fusion for multi-view classification. OTCHA introduces a set of learnable latent hub tokens shared across views. For each view, we compute an OT plan between patch tokens and hub tokens that jointly considers feature similarity and geometry, and augment the OT formulation with token-conditional dustbins to enable partial matching and discard irrelevant tokens. The resulting transport plan provides token-wise matching confidence, which gates hub-mediated message passing and weights a novel optimal-transport-based representation alignment loss to stabilize refinement. Experiments on three multi-view medical image datasets demonstrate consistent improvements over competing baselines across diverse anatomies and view configurations. Our code is available at https://github.com/labhai/OTCHA.

19.
medRxiv (Medicine) 2026-06-22

Multisite Real-World Validation of an Electronic Health Record-Integrated Generative Artificial Intelligence Tool for Venous Thromboembolism Risk Stratification

Background: Guiding risk-appropriate inpatient thromboprophylaxis requires venous thromboembolism (VTE) risk stratification; however, reliable risk determination remains inconsistent in routine care. Health systems increasingly pilot artificial intelligence (AI) tools, yet few studies demonstrate rigorous evaluation in the context of a learning health system (LHS). We evaluated the performance of a pilot electronic health record (EHR)-integrated generative AI (GenAI) system, inHealth General Reasoner (iHGR), for VTE risk stratification versus clinician order set classifications and physician-adjudicated chart review. Methods: This multisite retrospective validation study included adult inpatient admissions at Johns Hopkins Medicine between June 21, 2025, and Dec 18, 2025 (checklist-based order set from June 21, 2025 - November 19, 2025, and clinician judgement-based order set from November 29 - December 18, 2025). From 758 eligible admissions, we randomly sampled 500 balanced by site and order set periods. iHGR and clinician-selected order set classifications were compared with the reference standard (RS). Primary outcomes were iHGR sensitivity and specificity. Secondary analyses compared the order sets with the same RS to evaluate workflow comparators and error patterns. Results: iHGR achieved 81.8% sensitivity (95% CI 77.3-85.6) and 70.9% specificity (63.6-77.3). The checklist-based order set had 61.3% sensitivity (53.7-68.5) and 86.2% specificity (77.4-91.9). The clinician judgement-based order set had 78.1% sensitivity (71.3-83.7) and 65.4% specificity (54.3-75.0). False-negative iHGR classifications were associated with missed narrative risk factors. Conclusion: iHGR showed higher sensitivity for VTE risk than checklist-based order sets and clinician judgement without introducing systematic bias. In silico evaluation of pilot AI systems within LHSs can identify clinically important performance trade-offs and implementation targets before operational scale-up. Narrative clinical data abstraction remained a key limitation, supporting the use of GenAI to support rather than supplant clinician judgement.

20.
PLOS Computational Biology 2026-06-08

Assessing the inference of single-cell phylogenies and population dynamics from CRISPR lineage recordings

by Julia Pilarski, Tanja Stadler, Sophie Seidel Multicellular organisms develop from a single cell by repeated rounds of cell division, differentiation, and death, which can be represented as a single-cell phylogenetic tree. Genetic lineage tracing allows us to investigate this development by tracking the ancestry of individual cells as populations grow and change over time. However, accurate reconstruction of the cell phylogeny and quantification of the corresponding phylodynamic parameters – cell division, differentiation, and death rates – from this tracking data remains challenging and needs to be systematically evaluated. We perform simulations and assess, using the Bayesian framework, the joint inference of time-scaled cell phylogenies and phylodynamic parameters from CRISPR lineage recordings with random or sequential edits. Principally, we characterize the inference improvements as the recorder capacity increases. We observe more accurate phylogenetic reconstruction from sequential compared to random recordings, but no substantial improvement in phylodynamic inference when using the additional information contained in the order of edits. Overall, we find that CRISPR lineage recordings carry a strong signal on the rates of cell division when appropriate models are used. However, we detect biases in the inferred rates of cell division and death under phylodynamic model misspecification, i.e., when fitting classic memoryless birth-death processes to synchronous cell divisions. Moreover, for scenarios when cells differentiate into distinct types, we demonstrate that Bayesian phylodynamic analysis of sparse end-point measurements can resolve these cell differentiation trajectories by lineage and time. Under prototypical dynamics, we recover cell type-specific division and death rates, and cell type transition rates in over 80% of simulations. Overall, this simulation study explores how much information on cellular development can be extracted from state-of-the-art genetic lineage tracing data using phylogenetic and phylodynamic methodology.

21.
arXiv (CS.LG) 2026-06-16

Tail-Shape Estimation in LLM Evaluation Is Fragile: A Protocol for Diagnosing False Positives

Authors:

arXiv:2606.16511v1 Announce Type: new Abstract: Recent work motivates moving large language model (LLM) evaluation from mean-based to tail-aware metrics, including conditional value-at-risk and tail-index estimates of reward-model error. We ask whether the canonical extreme-value-theory tail-index parameter, which isolates how heavy a tail is from how large the tail mass is, adds discriminative information beyond the mean and a standard tail-magnitude statistic in LLM evaluation. We pre-register a protocol covering admissibility, goodness-of-fit, threshold-stability, and effect-size requirements for any positive tail-shape claim. The protocol is the contribution of this paper; the empirical study below is a demonstration of what its gates catch. Applied to a standard LLM toxicity-evaluation setup under two structurally different scorer families, the protocol catches three distinct modes of false positives that a naive analysis would have published, and rejects the headline tail-shape claim on both scorers. We conclude that tail-shape estimation in the LLM toxicity-evaluation setups we examined is more fragile than the recent literature suggests, and recommend the protocol as a starting point for tail-index claims in similar setups.

22.
arXiv (math.PR) 2026-06-15

Stationary measures for higher spin vertex models on a strip

Authors:

arXiv:2309.04897v2 Announce Type: replace-cross Abstract: We introduce a higher spin vertex model on a strip with fused vertex weights. This model can be regarded as a generalization of both the unfused six-vertex model on a strip arXiv:2212.09111 and an 'integrable two-step Floquet dynamics' model introduced in arXiv:1711.08884. We solve for the stationary measure using a fused version of the matrix product ansatz and then characterize it in terms of the Askey-Wilson process. Using this characterization, we obtain the limits of the mean density along an arbitrary down-right path. It turns out that all these models share a common phase diagram, which, after an appropriate mapping, matches the phase diagram of open ASEP. This provides evidence for the universality of this phase diagram.

23.
arXiv (CS.CV) 2026-06-15

FBSDiff++: Improved Frequency Band Substitution of Diffusion Features for Efficient and Highly Controllable Text-Driven Image-to-Image Translation

With large-scale text-to-image (T2I) diffusion models achieving significant advancements in open-domain image creation, increasing attention has been focused on their natural extension to the realm of text-driven image-to-image (I2I) translation, where a source image acts as visual guidance to the generated image in addition to the textual guidance provided by the text prompt. We propose FBSDiff, a novel framework adapting off-the-shelf T2I diffusion model into the I2I paradigm from a fresh frequency-domain perspective. Through dynamic frequency band substitution of diffusion features, FBSDiff realizes versatile and highly controllable text-driven I2I in a plug-and-play manner (without need for model training, fine-tuning, or online optimization), allowing appearance-guided, layout-guided, and contour-guided I2I translation by progressively substituting low-frequency band, mid-frequency band, and high-frequency band of latent diffusion features, respectively. In addition, FBSDiff flexibly enables continuous control over I2I correlation intensity simply by tuning the bandwidth of the substituted frequency band. To further promote image translation efficiency, flexibility, and functionality, we propose FBSDiff++ which improves upon FBSDiff mainly in three aspects: (1) accelerate inference speed by a large margin (8.9$\times$ speedup in inference) with refined model architecture; (2) improve the Frequency Band Substitution module to allow for input source images of arbitrary resolution and aspect ratio; (3) extend model functionality to enable localized image manipulation and style-specific content creation with only subtle adjustments to the core method. Extensive qualitative and quantitative experiments verify superiority of FBSDiff++ in I2I translation visual quality, efficiency, versatility, and controllability compared to related advanced approaches.

24.
arXiv (CS.CV) 2026-06-19

Scaling Self-Play for End-to-End Driving

End-to-end autonomous driving models are typically trained on offline human-demonstration datasets that provide limited state coverage and often no closed-loop feedback, making them prone to compounding errors when deployed in closed-loop and brittle to long-tail agent interactions. To overcome these limitations, we propose an alternative strategy for training end-to-end driving models: large-scale self-play directly from pixels in simulation. While prior self-play approaches have shown promising transfer to real-world driving, they typically assume vectorized Bird's-Eye-View (BEV) observations that are incompatible with end-to-end policies operating directly on sensor observations. To this end, we introduce Gigapixel, a high-throughput batched driving simulator with perspective rendering, enabling scalable self-play directly from pixel observations. Rather than targeting compute-costly photorealistic sensor simulation, Gigapixel renders a simplified bounding-box world that preserves essential scene structure while achieving throughput at 50k agent steps per second. Since direct pixel-space self-play RL is prohibitively sample-inefficient at end-to-end model scale, we propose self-play DAgger training: we train pixel-based policies in self-play via on-policy distillation from a privileged RL teacher. To bridge the sim-to-real gap, we subsequently transfer the self-play trained policies to real-world sensor data through lightweight perception adaptation. Policies trained in Gigapixel and adapted to real-world sensor data achieve competitive performance on the HUGSIM and NAVSIM-v2 benchmarks without human trajectory supervision. Moreover, scaling self-play training yields proportional gains in policy performance, establishing self-play as a practical and scalable strategy for training end-to-end models.

25.
PLOS Medicine 2026-05-22

Differences in tuberculosis prevalence by sex in low- and middle-income countries over 1993–2025: A systematic review and meta-analysis

by Nicole A. Swartwood, Nanki Singh, Seyed Alireza Mortazavi, Melike Hazal Can, Hening Cui, Do Kyung Ryuk, Peter MacPherson, Katherine C. Horton, Nicolas A. Menzies Background Global and national initiatives to combat tuberculosis (TB) have expanded over recent years. Despite this, the TB burden remains high in some population groups, with men recognized as having elevated TB risks. Summary measures of sex differences in TB prevalence were last estimated in 2016. Since then, many additional prevalence surveys have been conducted, including in the highest TB burden countries. We conducted a systematic review of sex-stratified TB prevalence survey data published over 1993–2025, to provide updated estimates of male-to-female (M:F) TB prevalence ratios and determine whether sex-related disparities in TB burden have closed over time. Methods and findings We identified surveys reporting community-representative, sex-stratified estimates of pulmonary TB prevalence in low- and middle-income countries (LMICs), including surveys from an earlier review (covering January 1993–March 2016) and a new systematic review (covering 1st December 2015–13th October 2025). This review was prospectively registered with PROSPERO (CRD42024503853) and included searches of PubMed, Embase, Global Health, the Cochrane Library, Africa Index Medicus, LILACS, and SciELO. We extracted data on bacteriologically confirmed and smear-positive TB prevalence among adults (aged ≥ 15 years), stratified by sex. Risk of bias was evaluated using eight criteria specific to prevalence surveys. We fit multi-level Bayesian regression models with study- and country-level random effects to estimate the M:F ratio of TB prevalence (male prevalence divided by female prevalence), overall and for key subgroups. In meta-regression analyses, we estimated how prevalence ratios varied over time and according to known TB risk factors and TB case definitions.We identified 10,124 publications and extracted data from 100 eligible studies representing 102 unique prevalence surveys and 4,658,310 participants (45.6% male) in 33 LMICs. TB prevalence was higher in men than women in 90/102 of the included surveys, with a pooled M:F prevalence ratio of 2.02 (95% credible interval (CrI): 1.71, 2.34) for bacteriologically confirmed TB and 2.38 (95% CrI: 1.91, 2.90) for smear-positive TB. Time trend analyses showed a 2.0% (95% CrI: −0.2, 4.5%) average annual change in the M:F ratio of bacteriologically confirmed TB over the study period. The M:F prevalence ratio was estimated to be higher for countries with greater excess HIV prevalence among men, and countries with greater gender equity (as measured by the United Nation’s Gender Development Index). The estimated M:F prevalence ratio was also higher for surveys that did not restrict testing to individuals reporting TB symptoms. Study limitations include heterogeneity in survey methods and definitions, as well as limited data from the Americas, Eastern Mediterranean, and Europe WHO world regions and post-COVID-19 period. Conclusions Men in LMICs consistently experience TB at a higher prevalence than women. Time trend estimates are uncertain, but consistent with widening sex differences in TB prevalence over the last three decades, despite efforts to address the risk factors underlying this excess TB burden.