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01.
arXiv (math.PR) 2026-06-17

Diffuse Interface Energies with Microscopic Heterogeneities II: Rare Events

arXiv:2606.17968v1 Announce Type: cross Abstract: We analyze Allen-Cahn functionals with stationary ergodic coefficients in the regime where the length scale $\delta$ of the heterogeneities is much smaller (microscopic) than the interface width $\epsilon$ (mesoscopic). In a companion paper, we show that if the ratio $\epsilon^{-1} \delta$ vanishes fast enough as $\epsilon \to 0$, then the functionals converge to an effective surface energy where the energy density is determined by homogenization effects originating at microscopic scales. Here we prove that if the ratio $\epsilon^{-1} \delta $ vanishes too slowly, the limit of the functional may actually be smaller than this homogenized energy. We refer to this as the rare events regime. In the case of the random checkerboard in dimension one, we use large deviations techniques to give a complete description of the rare events regime, showing that the limiting energy depends in a nontrivial way on the limit of $\epsilon^{-1} \delta | \log \epsilon |$. We further construct, in any dimension, examples of random media in which rare events become relevant at algebraic scales $\delta \approx \epsilon^{1 + \alpha}$ for an arbitrary $\alpha > 0$, as well as almost periodic examples in which atypical configurations play the same role as rare events.

02.
medRxiv (Medicine) 2026-06-17

Cross-Device Adaptation of Mirai for Mammography-Based Breast Cancer Risk Prediction

Fine-tuning can adapt pretrained medical imaging models to new clinical datasets, but device-specific domain shifts may limit generalizability. We evaluated Mirai, a mammography-based deep learning model for breast cancer risk prediction, in a large screening cohort containing Hologic and General Electric (GE) full-field digital mammography systems, including GE Premium View (GE PV) and Tissue Equalization (GE TE) post-processing software. Native Mirai showed lower performance on TE images than on Hologic or PV images. Fine-tuning on TE images improved TE performance, particularly for short-term risk prediction, but substantially reduced performance on Hologic images, consistent with catastrophic forgetting. To mitigate this effect, we developed a device-invariant model using interleaved multi-device sampling and conditional adversarial training. This approach largely restored Hologic performance while maintaining improved TE performance, providing better robustness across heterogeneous imaging platforms. Comparison of cumulative and annual risk AUCs over a five-year time horizon further showed that performance gains were driven mainly by short- and intermediate-term predictions. These findings highlight both the value and dangers of device-specific fine-tuning and support balanced domain-adaptation strategies for deploying mammography-based risk models across diverse clinical imaging environments.

03.
arXiv (quant-ph) 2026-06-16

Real-space spectral functions of three-dimensional billion-size topological non-Hermitian matter with tensor networks

arXiv:2606.16424v1 Announce Type: cross Abstract: Non-Hermitian systems host a wide range of unconventional topological phenomena while large-scale simulations in finite three dimensional systems remain challenging because of the rapidly growing number of sites. In particular, higher-order topological corner modes are often studied only in small lattices, where strong finite-size effects can mask their intrinsic behavior. Here, we develop a tensor-network framework that combines quantics tensor cross interpolation with the kernel polynomial method, enabling compact representations of large non-Hermitian tight-binding Hamiltonians and direct calculations of real-space spectral functions for systems exceeding one billion lattice sites. Using this approach, we investigate three-dimensional non-Hermitian higher-order topological insulators with with structured real-space geometries. The unprecedented system size enables direct access to the macroscopic regime and allows corner-mode spectral responses to be resolved in genuinely three-dimensional systems.By tuning the loss strength, we identify distinct in-gap corner modes across weak- and strong-loss regimes.Our results establish tensor-network algorithms as a powerful strategy to perform real-space spectral calculations in exceptionally large non-Hermitian systems.

04.
arXiv (CS.AI) 2026-06-16

AI-Driven Test Case Generation from Natural Language Requirements: A Survey of Techniques and Research Gaps

arXiv:2606.06563v2 Announce Type: replace-cross Abstract: Software testing is critical for verifying that systems meet specified requirements, yet remains among the most time-consuming and expensive activities in development. Requirements-based test generation allows test cases to be derived early from requirements artifacts, but generating them directly from natural language is challenging due to inherent ambiguity and imprecision. Recent advances in AI, natural language processing (NLP), and large language models (LLMs) have made automating this pipeline increasingly feasible, while introducing new risks including hallucination, reduced traceability, and inconsistent evaluation. This survey addresses four research questions: what AI and NLP techniques have been proposed for generating test cases from natural language requirements; what tools and frameworks support these approaches; how generated test cases are evaluated; and what research gaps remain. Following Kitchenham and Charters' systematic review guidelines, we searched major scholarly databases spanning 2000-2025 and, after applying strict inclusion criteria, identified 21 primary studies. The literature is organized into three evolutionary eras, revealing that no existing approach simultaneously satisfies six key quality dimensions: automation, ambiguity handling, domain applicability, traceability, evaluation thoroughness, and hallucination control. The survey makes three main contributions: a three-era evolutionary synthesis of AI-based test generation; a six-criteria gap analysis showing no current approach fully addresses all quality dimensions; and four actionable research guidelines targeting hallucination, traceability, complexity sensitivity, and compliance.

05.
arXiv (CS.LG) 2026-06-11

Integral Formulation of QENDy for Robust Nonlinear System Identification

arXiv:2606.11629v1 Announce Type: cross Abstract: This manuscript proposes an integral formulation of the newly defined quadratic embedding method for identifying nonlinear systems (QENDy). In the original algorithm, trajectory data points along with their time derivatives are used. Methods for calculating time derivatives make the algorithm sensitive to noise. Our integral formulation does not use the time derivatives. This results in a more robust method to learn the dynamics.

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

Learning the Geometry of Data: A Mathematical Review of Shape Space Analysis

arXiv:2606.17022v1 Announce Type: cross Abstract: A central objective of machine learning is to identify structure and patterns in data. Advances in data acquisition have increasingly produced datasets whose observations possess rich geometric form, giving rise to shape spaces that encode variability in object geometry. Such datasets arise across a wide range of disciplines, including biology, medicine, anthropology, and computer vision, where subtle geometric differences often carry important scientific information. Traditional machine learning methods, however, are frequently ill-equipped to account for the nonlinear geometric structure underlying these data. This survey synthesizes a rapidly growing body of work on shape space analysis, which provides a mathematical and computational framework for the study of geometric data. Drawing on ideas from differential geometry, statistics, and machine learning, we organize the literature around a common analytical pipeline: shape representation and parameterization, the rigorous construction of robust geodesic metrics, statistical analysis on shape spaces, and geometry-aware learning methods. We discuss how these tools enable the characterization of shape variability, the comparison of geometric objects, and the analysis of structural trajectories across populations and time. To illustrate the breadth of the field, we highlight applications spanning multiple scales of biological organization, including studies of subcellular morphology and primate tooth evolution. Across these and many other domains, researchers face common challenges arising from complex, nonlinear, and often unaligned geometric variation. The review concludes by identifying key theoretical and computational challenges, as well as emerging opportunities driven by increasingly large and diverse geometric datasets.

07.
bioRxiv (Bioinfo) 2026-06-11

Revealing trajectories of multi-modal voxel-level changes in neurodegenerative diseases using latent event mapping

Neurodegenerative diseases are driven by pathological mechanisms that can be indirectly measured in vivo using multi-modal neuroimaging. However, current computational methods that aim to reconstruct trajectories of voxel-level changes in the brain are either not computationally scalable or fully interpretable, limiting their ability to reveal associations between disease progression and underlying mechanisms. Here we introduce Latent Event Mapping (LEMING), a generative unsupervised modelling technique that learns a latent map of disease events along a common pseudo-timeline of events. We apply LEMING to amyloid PET and structural MRI data from the Alzheimer's Disease Neuroimaging Initiative to reveal the first voxel-level trajectories of events in Alzheimer's disease. Notably, we show how LEMING can provide new insights into progression-dependent disease mechanisms. We find that acetylcholine receptor density is significantly positively associated with both late-stage amyloid and atrophy events, suggesting that either these receptors are targeted later in disease progression, or that amyloid does not play an active role. This has strong implications for therapeutics that target acetylcholine receptors, particularly for early-stage intervention strategies.

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

Beyond Similarity: Temporal Operator Attention for Time Series Analysis

arXiv:2605.11287v2 Announce Type: replace-cross Abstract: A persistent paradox in time-series forecasting is that structurally simple MLP and linear models often outperform high-capacity Transformers. We argue that this gap arises from a mismatch in the sequence-modeling primitive: while many time-series dynamics are governed by global temporal operators (e.g., filtering and harmonic structure), standard attention forms each output as a convex combination of inputs. This restricts its ability to represent signed and oscillatory transformations that are fundamental to temporal signal processing. We formalize this limitation as a simplex-constrained mixing bottleneck in softmax attention, which becomes especially restrictive for operator-driven time-series tasks. To address this, we propose $Temporal Operator Attention (TOA)$, a framework that augments attention with explicit, learnable sequence-space operators, enabling direct signed mixing across time while preserving input-dependent adaptivity. To make dense $N \times N$ operators practical, we introduce Stochastic Operator Regularization, a high-variance dropout mechanism that stabilizes training and prevents trivial memorization. Across forecasting, anomaly detection, and classification benchmarks, TOA consistently improves performance when integrated into standard backbones such as PatchTST and iTransformer, with particularly strong gains in reconstruction-heavy tasks. These results suggest that explicit operator learning is a key ingredient for effective time-series modeling.

09.
arXiv (CS.CV) 2026-06-18

S3OD: Towards Generalizable Salient Object Detection with Synthetic Data

Salient object detection exemplifies data-bounded tasks where expensive pixel-precise annotations force separate model training for related subtasks like DIS and HR-SOD. We present a method that dramatically improves generalization through large-scale synthetic data generation and ambiguity-aware architecture. We introduce S3OD, a dataset of over 139,000 high-resolution images created through our multi-modal diffusion pipeline that extracts labels from diffusion and DINO-v3 features. The iterative generation framework prioritizes challenging categories based on model performance. We propose a streamlined multi-mask decoder that handles the inherent ambiguity in salient object detection by predicting multiple valid interpretations. Models trained only on synthetic data achieve 20-50% error reduction in cross-dataset generalization, while fine-tuned versions reach state-of-the-art performance across DIS and HR-SOD benchmarks.

10.
arXiv (CS.CL) 2026-06-12

CreativeBench: Benchmarking and Enhancing Machine Creativity via Self-Evolving Challenges

The saturation of high-quality pre-training data has shifted research focus toward evolutionary systems capable of continuously generating novel artifacts, leading to the success of AlphaEvolve. However, the progress of such systems is hindered by the lack of rigorous, quantitative evaluation. To tackle this challenge, we introduce CreativeBench, a benchmark for evaluating machine creativity in code generation, grounded in a classical cognitive framework. Comprising two subsets – CreativeBench-Combo and CreativeBench-Explore – the benchmark targets combinatorial and exploratory creativity through an automated pipeline utilizing reverse engineering and self-play. By leveraging executable code, CreativeBench objectively distinguishes creativity from hallucination via a unified metric defined as the product of quality and novelty. Our analysis of state-of-the-art models reveals distinct behaviors: (1) scaling significantly improves combinatorial creativity but yields diminishing returns for exploration; (2) larger models exhibit ``convergence-by-scaling,'' becoming more correct but less divergent; and (3) reasoning capabilities primarily benefit constrained exploration rather than combination. Finally, we propose EvoRePE, a plug-and-play inference-time steering strategy that internalizes evolutionary search patterns to consistently enhance machine creativity.

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

Authorship Attribution in Multilingual Machine-Generated Texts

As Large Language Models (LLMs) have reached human-like fluency and coherence, distinguishing machine-generated text (MGT) from human-written content becomes increasingly difficult. While early efforts in MGT detection have focused on binary classification, the growing landscape and diversity of LLMs require a more fine-grained yet challenging authorship attribution (AA), i.e., being able to identify the precise generator (LLM or human) behind a text. However, AA remains nowadays confined to a monolingual setting, with English being the most investigated one, overlooking the multilingual nature and usage of modern LLMs. In this work, we introduce the problem of Multilingual Authorship Attribution, which involves attributing texts to human or multiple LLM generators across diverse languages. Focusing on 18 languages – covering multiple families and writing scripts – and 8 generators (7 LLMs and the human-authored class), we investigate the multilingual suitability of monolingual AA methods in terms of their cross-lingual transferability, and the impact of generators on attribution performance. Our results reveal that while certain monolingual AA methods can be adapted to multilingual settings, significant limitations and challenges remain, particularly in transferring across diverse language families, underscoring the complexity of multilingual AA and the need for more robust approaches to better match real-world scenarios.

12.
arXiv (CS.AI) 2026-06-19

Grounded Inference: Principles for Deterministically Encapsulated Generative Models

arXiv:2606.19753v1 Announce Type: new Abstract: The incorporation of generative models into traditional computational systems presents both enormous opportunity and tremendous peril. Although many early adopters have realized these perils at great expense, the field still requires foundational frameworks to de-risk incorporation of AI into traditional systems. This manuscript establishes this foundation through the definition of four specific primitives of AI blended architecture, designed to enable deterministic encapsulation of probabilistic models. It further establishes two overarching anti-patterns broadly represented across industry to serve as warnings for engineers in this field. This framework was designed to enable successful integration of AI into traditional systems while providing a foundation upon which generative model providers could build the next generation of generative model interfaces.

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

Olmo Hybrid: From Theory to Practice and Back

Recent work has demonstrated the potential of non-transformer language models, especially linear recurrent neural networks (RNNs) and hybrid models that mix recurrence and attention. Yet there is no consensus on whether the potential benefits of these new architectures justify the risk and effort of scaling them up. To address this, we provide evidence for the advantages of hybrid models over pure transformers on several fronts. First, theoretically, we show that hybrid models do not merely inherit the expressivity of transformers and linear RNNs, but can express tasks beyond both, such as code execution. Putting this theory to practice, we train Olmo Hybrid, a 7B-parameter model largely comparable to Olmo 3 7B but with the sliding window layers replaced by Gated DeltaNet layers. We show that Olmo Hybrid outperforms Olmo 3 across standard pretraining and mid-training evaluations, demonstrating the benefit of hybrid models in a controlled, large-scale setting. We find that the hybrid model scales significantly more efficiently than the transformer, explaining its higher performance. However, its unclear why greater expressivity on specific formal problems should result in better scaling or superior performance on downstream tasks unrelated to those problems. To explain this apparent gap, we return to theory and argue why increased expressivity should translate to better scaling efficiency, completing the loop. Overall, our results suggest that hybrid models mixing attention and recurrent layers are a powerful extension to the language modeling paradigm: not merely to reduce memory during inference, but as a fundamental way to obtain more expressive models that scale better during pretraining.

14.
medRxiv (Medicine) 2026-06-20

EpiLink: a simulation-based compatibility model for genomic transmission clustering in infectious disease surveillance

Identifying recently linked infections from pathogen genome sequences is central to infectious disease surveillance, yet many clustering approaches rely on fixed genetic distance thresholds whose relationship to transmission is often unclear. This limitation is especially important in rapidly growing outbreaks and superspreading events, where many cases may be sampled close together in time and share little genetic variation, making true transmission links difficult to distinguish from other closely related infections. Supervised models can improve discrimination, but they require labelled transmission data that are rarely available during outbreak response. We developed EpiLink, a threshold-free method that estimates whether two cases are compatible with recent transmission. Here, compatibility means how well the observed genetic distance and sampling-time difference between two cases fit what would be expected if they were linked by defined recent transmission scenarios. EpiLink simulates plausible recent transmission histories while accounting for uncertainty in infection timing, testing delay, and mutation accumulation, then assigns higher scores to pairs whose observed differences are typical of those simulations. EpiLink was evaluated using both synthetic and empirical SARS-CoV-2 outbreak data from the 2020 Boston epidemic. Two EpiLink variants were compared to a logistic regression model trained on labelled transmission data. One EpiLink variant assumed deterministic mutation accumulation, with genetic differences proportional to elapsed evolutionary time; the other accounted for stochasticity by sampling mutation counts from a Poisson distribution. The logistic regression model performed better at distinguishing linked from unlinked pairs, but EpiLink achieved comparable clustering accuracy. In the Boston data, EpiLink recovered clusters enriched for documented conference and skilled nursing facility outbreaks. EpiLink thus provides an interpretable, simulation-based approach for identifying recent transmission clusters when fixed thresholds are difficult to justify and labelled transmission data are unavailable.

15.
arXiv (CS.LG) 2026-06-18

Lifecycle-Aware Dynamic Analysis for Secure ML Model Execution

arXiv:2606.19023v1 Announce Type: cross Abstract: The growing reliance on pre-trained Machine Learning (ML) models has introduced new attack surfaces. Recent vulnerabilities demonstrate that malicious behavior can be embedded within model artifacts, often bypassing existing defenses. Current model-scanning solutions primarily rely on static, format-specific rules or known attack signatures, which limit their ability to generalize across frameworks and to detect novel exploitation paths. In contrast, we propose a solution that focuses on the effects an attack has on the host system executing the model and builds on foundational intuitions about ML model execution. In particular, we observe that ML models operate within well-defined lifecycle phases and that, within each phase, interactions with the host system are highly structured and predictable. We translate these intuitions into Moat, a dynamic lifecycle-aware approach for securing ML model execution, and instantiate this design in Re-Moat, our reference implementation. We evaluate Re-Moat across multiple ML frameworks using 77,974 real-world model artifacts from the Hugging Face Hub, 31 Proofs-of-Concept (PoCs) from CVEs, and 334 models from a state-of-the-art dataset, and compare it against state-of-the-art model-scanning solutions. Our results show that our approach detects all evaluated attack classes while maintaining a close-to-zero false-positive rate, validating our intuitions and motivating dynamic analysis for securing ML model execution.

16.
arXiv (quant-ph) 2026-06-15

Electromagnetic Wightman functions and vacuum densities for a brane intersecting the AdS boundary

arXiv:2604.17583v2 Announce Type: replace-cross Abstract: We investigate the combined effects of a brane intersecting the AdS boundary and background gravitational field on the local characteristics of the electromagnetic vacuum. Two types of boundary conditions on the brane are considered, which are higher-dimensional generalizations of the perfect electric (PEC) and perfect magnetic (PMC) boundary conditions in Maxwell's electrodynamics. The brane-induced contributions to the Wightman functions of the vector potential and field tensor are explicitly extracted. Simple expressions in terms of elementary functions are provided. The behavior of the vacuum expectation values (VEVs) is mimicked by a scalar field with a negative effective mass squared determined by the radius of the AdS spacetime. The expectation values of the electric and magnetic fields squares and of the energy-momentum tensor are investigated as local characteristics of the vacuum state. The brane-induced contributions to these VEVs have opposite signs for the PEC and PMC conditions. For the PMC condition, this contribution is negative for the electric field squared and positive for the magnetic field squared. The VEV of the energy-momentum tensor has a nonzero off-diagonal component. The brane-induced vacuum energy density is positive for PMC condition, whereas the normal and parallel stresses change sign as functions of the distance from the brane. Unlike the problem involving a planar boundary in the Minkowski bulk, the vacuum energy-momentum tensor does not vanish in (3+1)-dimensional AdS spacetime.

17.
arXiv (math.PR) 2026-06-16

Exact Label Recovery in Euclidean Random Graphs

arXiv:2407.11163v3 Announce Type: replace-cross Abstract: In this paper, we propose a family of label recovery problems on weighted Euclidean random graphs. The vertices of a graph are embedded in $\mathbb{R}^d$ according to a Poisson point process, and are assigned to a discrete community label. Our goal is to infer the vertex labels, given edge weights whose distributions depend on the vertex labels as well as their geometric positions. Our general model provides a geometric extension of popular graph and matrix problems, including submatrix localization and $\mathbb{Z}_2$-synchronization, and includes the Geometric Stochastic Block Model (proposed by Sankararaman and Baccelli) as a special case. We study the fundamental limits of exact recovery of the vertex labels. Under a mild distinctness of distributions assumption, we determine the information-theoretic threshold for exact label recovery, in terms of a Chernoff-Hellinger divergence criterion. Impossibility of recovery below the threshold is proven by a unified analysis using a Cramér lower bound. Achievability above the threshold is proven via an efficient two-phase algorithm, where the first phase computes an almost-exact labeling through a local propagation scheme, while the second phase refines the labels. The information-theoretic threshold is dictated by the performance of the so-called genie estimator, which decodes the label of a single vertex given all the other labels. This shows that our proposed models exhibit the local-to-global amplification phenomenon.

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

Natural-Language Temporal Grounding in Hour-Long Videos is a Search Problem: A Benchmark and Empirical Decomposition

Temporal grounding–returning the interval $[t_s, t_e]$ for a natural-language query over a video–is the language interface to long-form video, yet has been studied on short videos; the dynamics of hour-scale natural-language grounding remain underexplored. We take the position that at hour-scale, the binding constraint is search, not recognition: Video-LLMs are bottlenecked not by localizing a nearby event, but–given a natural-language query–by searching for the relevant region of a long video. To test this, we release ExtremeWhenBench, the first open hour-scale grounding benchmark (2,273 queries over 194 videos, mean 75.7 min, max 9 hr) with an open-form query distribution. Every open Video-LLM collapses while a frame-level retrieval baseline outperforms them; a failure taxonomy attributes 85% of failures to search; and a retrieve-then-ground hybrid recovers 6.7x over the monolithic Video-LLM–mirroring retrieve-then-read in open-domain QA.

19.
arXiv (CS.CL) 2026-06-12

MDForge: Agentic Molecular Dynamics Pipeline Design under Sparse Simulator Feedback

Molecular dynamics (MD) is the canonical in-silico method for atomistic molecular science, simulating molecular behavior from first-principle physics. Designing an MD pipeline for a new system requires substantial expert knowledge: running it on even one molecule is expensive, ruling out trial-and-error. We automate this expert pipeline-design process with an LLM agent. Unlike existing MD agents that orchestrate a predefined tool set, we treat pipeline design as open-ended code generation in which the agent's behavior is reshaped online by verbal reward. Specifically, we build MDForge, an LLM agent whose in-context update rule densifies the sparse reward via a multi-agent debate among physics experts. On three SAMPL host-guest binding free-energy benchmarks, MDForge automatically designs MD pipelines competitive with human experts. Deployed on a library of unseen candidate guests, its CB[7] pipeline discovers a novel binder that wet-lab competition NMR confirms is a high-affinity, picomolar CB[7] binder. Our data and code are available at https://github.com/Zehong-Wang/MDForge.

20.
arXiv (quant-ph) 2026-06-17

Cumulant expansion approach to the decay dynamics of interacting Mössbauer nuclei after strong impulsive excitation

arXiv:2510.00970v2 Announce Type: replace Abstract: Recent progress in accelerator-based x-ray sources brings higher excitation of ensembles of Mössbauer nuclei closer to experimental feasibility. Yet, a theoretical modeling of the decay dynamics of the interacting nuclear ensemble after the impulsive excitation is still an open challenge. Here, we derive a set of nonlinear equations which is capable of efficiently modeling large nuclear ensembles for arbitrary degrees of excitation. As key signature for higher excitation, we identify a non-linear time-evolution of the nuclear dipole phase, which can be tuned via the scattering geometry, and interferometrically be measured. Furthermore, we identify interesting finite-size effects in the nuclear dynamics of small ensembles. Our results provide important guidance for future experiments aiming at the non-linear excitation of nuclei. We further envision the exploration of finite size-effects in Mössbauer spectroscopy with highest spatial resolution, i.e., small sample volumes.

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

FlexPooling with Simple Auxiliary Classifiers in Deep Networks

In computer vision, the basic pipeline of most convolutional neural networks consists of multiple feature extraction layers, where the input signal is downsampled to a lower resolution in each subsequent layer. This downsampling process is commonly referred to as pooling, which is an essential operation in CNNs. Pooling improves robustness against transformations, reduces the number of trainable parameters, increases the receptive field, and lowers computation time. Since pooling is a lossy process but remains important for extracting high-level information from low-level representations, it is important to preserve the most prominent information from previous activations to improve network discriminability. Standard pooling is usually performed using dense pooling methods, such as max pooling or average pooling, or through strided convolutional kernels. In this paper, we propose a simple yet effective adaptive pooling method, called FlexPooling, which generalizes average pooling by learning a weighted average over activations jointly with the rest of the network. We further show that attaching Simple Auxiliary Classifiers (SAC) to the CNN improves performance and demonstrates the effectiveness of the proposed method compared with standard pooling methods. Experiments on multiple popular image classification datasets show that FlexPooling consistently outperforms baseline networks, achieving approximately 1 to 3 percent improvement in accuracy.

22.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

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

Characterizing Admissible Objective Functions for Hierarchical Clustering

arXiv:2604.23628v2 Announce Type: replace-cross Abstract: Hierarchical clustering is a fundamental task in data analysis, but classical methods have long lacked a principled objective function. Dasgupta [STOC~2016] took an important step toward addressing this gap by proposing a well-motivated objective function for cluster trees. Cohen-Addad et al. [J. ACM 2019] subsequently introduced the notion of admissibility: an objective function is admissible if, whenever the input similarity matrix admits generating trees, its minimizers are precisely those generating trees.They also gave a necessary and sufficient condition for admissibility within a family of objective functions based on aggregate intercluster similarity. We refer to this family as sum-type objective functions. However, apart from Dasgupta's original objective function, no explicit admissible objective functions in this family were provided. In this paper, we study admissible objective functions for hierarchical clustering in two directions. For sum-type objective functions, we give a complete characterization when the scaling function is a symmetric polynomial of degree at most two, and we derive sufficient conditions for degree-three polynomials. We also show that the recursive sparsest cut algorithm achieves an O$(\phi)$-approximation ratio for the admissible objective functions covered by our characterization, where $\phi$ is the approximation factor of the sparsest cut subroutine. We then introduce max-type objective functions, where cluster interaction is measured by maximum, rather than aggregate, intercluster similarity. For this class, we characterize which objective functions are admissible for arbitrary symmetric scaling functions and give a complete characterization when the scaling function is a symmetric polynomial of degree at most two.

24.
arXiv (quant-ph) 2026-06-11

Fun with Graph States: Nonlocal Bell Pairs and the Arf Invariant

arXiv:2606.06582v2 Announce Type: replace Abstract: We study inner products and partial amplitudes of graph states–a commonly employed class of quantum states, which are specified by graphs. We find that the magnitudes of these quantities are simply related to the rank of the adjacency matrix of the graph over F_2 while the phase is determined by the Arf invariant of its quadratic refinement. These facts motivate a nonlocal tensor factorization of the Hilbert space, with respect to which all graph states are products of Bell pairs with unentangled ancillae. These results may illuminate the quantum advantage in the framework of Measurement-Based Quantum Computation and suggest that graph states can be usefully visualized in the language of algebraic topology. In addition, we develop a specialized technique for computing expectation values of qubit-wise permutations in graph states, which is useful for calculating multi-invariants.

25.
PLOS Medicine 2026-06-12

Placenta accreta spectrum in the 21st century: Challenging dogma and redefining disorder

by Eric Jauniaux, Helena C. Bartels, Yalda Afshar Placenta accreta spectrum (PAS) is a serious pregnancy complication caused by abnormal placental attachment to the uterus. In this Perspective, Eric Jauniaux and colleagues discuss emerging evidence that challenges our long-held pathophysiological understanding of PAS, and argue that a critical reassessment of definition, diagnosis, and management is overdue. In this Perspective, Jonathan Evans and colleagues discuss why restricting access to joint replacement surgery based on BMI alone is not supported by evidence, and highlight how such rest rictions risk exacerbating stigma, inequity and avoidable harm to those who would benefit from surgery.