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

EpiBench: Verifiable Evaluation of AI Agents on Epigenomics Analysis

arXiv:2606.13602v1 Announce Type: new Abstract: We introduce EpiBench, a verifiable benchmark for short-horizon epigenomics analysis. EpiBench evaluates whether agents can make well-defined analysis decisions from realistic workflow states and return deterministically gradable answers. The benchmark includes 106 evaluations across CUT\&Tag/CUT\&RUN, ATAC-seq, ChIP-seq, and DNA methylation workflows. Across 5,088 valid trajectories from 16 model-harness pairs, no system passed a majority of attempts: GPT-5.5 / Pi led at 45.0\% (143/318 attempts; 95\% confidence interval (CI), 36.3–53.7), followed by GPT-5.5 / OpenAI Codex at 39.9\% (127/318 attempts; 95\% CI, 31.6–48.3). Claude Opus 4.8 Max / Pi and GPT-5.4 / Pi each passed 39.0\% (124/318 attempts; 95\% CI, 30.2–47.8 and 31.0–47.0, respectively). Performance varies across assay types, and many failed runs still contain parts of the correct answer. Agents often found the right files and computed useful intermediate results, but failed when the task required deeper, assay-specific scientific judgment.

02.
arXiv (CS.LG) 2026-06-19

We Need to Rethink Benchmarking in Anomaly Detection

arXiv:2507.15584v2 Announce Type: replace Abstract: Despite the continuous proposal of new anomaly detection algorithms and extensive benchmarking efforts, progress seems to stagnate, with only minor performance differences between established baselines and new algorithms. In this position paper, we argue that this stagnation is due to limitations in how we evaluate anomaly detection algorithms. In current benchmarks, a trivial algorithm that only checks for extreme values in individual features performs competitively with state-of-the-art deep learning methods, despite failing on simple cases such as anomalies within an annulus of normal points. Moreover, existing benchmarks do not adequately reflect the diversity of anomaly detection applications, making it difficult for practitioners to reliably select algorithms for their applications. Consequently, we need to rethink benchmarking in anomaly detection. In our opinion, anomaly detection should be studied using scenarios that group applications sharing relevant characteristics, defined through a common taxonomy. Benchmarking within scenarios enables scenario-specific choices for preprocessing, metrics, and model selection, clarifying which advances transfer across similar applications and providing practitioners with reliable guidance for their specific contexts.

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

Fusing Stylometric and Embedding Systems to Estimate Authorship Likelihood Ratios in Japanese

The likelihood ratio framework is widely recognized as the logically and legally sound basis for evidential analysis across forensic sciences, and its importance is increasingly acknowledged in analyses of authorship in textual evidence. To date, however, its application has been confined to English-language texts. Meanwhile, authorship attribution has traditionally relied on a diverse array of stylometric features, even as the rise of pre-trained large language models enables new contextual-embedding approaches. Combining these diverse approaches through fusion promises enhanced performance, yet it has not been applied to integrate stylometric-feature systems with embedding-based systems within the likelihood ratio paradigm. This study is the first to apply likelihood ratio-based forensic text comparison to Japanese digital texts, using ~1,000-character excerpts from blogs, to 1) evaluate system performance and likelihood ratio magnitudes and 2) assess the impact of fusing stylometric-feature systems with embedding-based systems. The results demonstrate that the fused system maintains excellent calibration while 1) increasing consistent-with-fact likelihood ratio magnitudes; 2) decreasing contrary-to-fact likelihood ratio magnitudes and 3) improving overall discriminability. The best-performing fusion achieved a log-likelihood-ratio cost of 0.32484, illustrating both the feasibility of likelihood ratio framework for Japanese and the benefits of fusion across heterogeneous systems.

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

CoCoGEC: Counterfactual Generation for Robust Grammatical Error Correction

Grammatical error correction (GEC) systems are usually trained and evaluated on GEC benchmarks, but their performance often drops sharply once the surrounding context is slightly perturbed or extended. This indicates that the existing GEC models usually fail to understand the error patterns in the varying contexts. In this paper, we thoroughly investigate the counterfactuals for GEC tasks, where the subtle changes to the contexts could lead to the label flipping issue. We propose CoCoGEC, a counterfactual generation framework that creates copies of training instances with error-irrelevant contexts altered. Our framework systematically generates counterfactuals by (1) generating intra- and inter-sentence counterfactuals that maintain the error patterns as well as syntax of the original instances by altering the word-level and sentence-level contexts; (2) revising the generated counterfactuals by selecting the instances with flipped labels and high GEC Mutual Information (MI) coefficient. Extensive experiments show that our method substantially improves the stability of GEC models, outperforming a set of data augmentation baselines. Particularly, it could achieve absolute F0.5 gains of +9.9, +11.3, and +20.8 points on the perturbed BEA-19*,CoNLL-14*, and TEM-8* data set.Our code is released at https://github.com/Quinnok/CoCoGEC

05.
medRxiv (Medicine) 2026-06-17

Multi-strain Probiotics Alter Gut Microbiota and Estrobolome Pathways in Primary Dysmenorrhea

Background: Exact cause of primary dysmenorrhoea is unknown but recent evidence uncovers a potential link between gut dysbiosis and benign gynaecological disorder via disruption of estrobolome. Methods: A randomized controlled trial to investigate the effects of multi-strain oral probiotics on primary dysmenorrhoea has been conducted. This is a secondary analysis comparing the stool microbiome in women with primary dysmenorrhoea and those without (control), and the effects of treatment with probiotics versus placebo. Results: Although microbial richness and evenness were comparable between groups (alpha diversity, p > 0.05), gut microbial community composition differed significantly (Bray Curtis PERMANOVA, p = 0.015), characterised by reduced Bifidobacterium adolescentis and Blautia and enrichment of Faecalibacterium in dysmenorrhoea, alongside condition-specific core taxa. Post-intervention analysis revealed significant shifts in microbial community structure between pre- and post-treatment groups (PERMANOVA, F = 2.11, p = 0.005), with probiotic supplementation inducing more consistent and directed microbiome changes than placebo, without altering alpha diversity (p > 0.05). Functional prediction showed no significant difference in overall beta glucuronidase pathway abundance (p > 0.05); however, dysmenorrhoea was associated with higher abundance of beta glucuronidase producing taxa (MaAsLin2, q < 0.05) that were differentially modulated by probiotic treatment. Conclusion: This discovery provides evidence on the microbial disruption in primary dysmenorrhoea as well as the benefit of probiotics to modulate the intestinal microbiota to improve the condition.

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

Measurement-Calibrated Multi-Camera Fusion for Vision-Based Indoor Localization

Indoor vision-based localization systems are affected by detection noise, occlusions, and limited camera coverage, leading to uncertainty at multiple stages of the pipeline. While multi-camera data fusion is widely used to mitigate these issues, it is typically treated as a black-box component and evaluated solely end-to-end, obscuring its mechanistic contributions. To address this gap, this work investigates whether explicitly characterizing single-camera localization errors can be leveraged to calibrate and optimize multi-camera data fusion. We introduce a measurement-calibrated fusion approach that integrates component-wise error quantification, specifically isolating homography calibration, human detection, and motion tracking. A component-wise evaluation is conducted to quantify error contributions from homography calibration, human detection, and motion tracking. Experimental results show that data fusion improves localization accuracy compared to single-camera baselines. While measurement-calibrated fusion provides only limited improvement in absolute accuracy over standard fusion, it substantially reduces trajectory variance and improves motion smoothness, which are critical for applications requiring stable and continuous motion estimates. These results highlight the value of explicit error characterization when designing data fusion strategies for vision-based indoor positioning systems.

07.
arXiv (CS.CV) 2026-06-15

MooMIns – Monocular 3D Reconstruction and Object Pose Estimation from Multiple Instances

Simultaneous 3D reconstruction and 6D object pose estimation from a single monocular image is an inherently ill-posed problem. In industrial settings, however, multiple instances of an object are often randomly arranged in bins, implicitly providing several views of the same object within a single image. We show that this implicit multi-view geometry can be exploited to simultaneously reconstruct the object in 3D and estimate the 6D pose of each visible object instance. We present MooMIns, a new Gaussian-splatting-based approach that inverts the original Gaussian splatting formulation: instead of rendering a single scene from multiple cameras, we render multiple object instances from a single camera. Our method is initialized with SAM3 instance segmentation masks and a modified Structure from Motion (SfM) pipeline. In contrast to learned monocular depth estimation, we perform true geometry-based reconstruction from image evidence, avoiding hallucinations caused by training data priors. We evaluate MooMIns on synthetic and real bin-picking scenarios, and demonstrate accurate reconstruction of previously unseen objects as well as reliable pose estimation of individual instance

08.
arXiv (CS.CV) 2026-06-11

OpenMedReason: Scientific Reasoning Supervision for Medical Vision-Language Models

High-stakes clinical use of large vision-language models (LVLMs) requires reasoning that is grounded in visual evidence and clinical knowledge, not just correct final answers. We introduce OpenMedReason, a large-scale, open multimodal medical reasoning corpus comprising approximately 450K image-question-answer instances whose reasoning traces are primarily derived from curated biomedical, human-authored scientific articles. OpenMedReason provides high-fidelity supervision beyond synthetic chains of thought, covering diverse medical domain vision modalities such as radiological scans, microscopic images, visible light photographs, charts, and others. We complement it with OpenMedReason-Bench, a held-out benchmark that allows fine-grained evaluation of LVLMs along three complementary axes of capability, including perception, medical knowledge, and rationale, enabling diagnostic evaluation beyond final-answer accuracy. OpenMedReason is a rich training resource that exhibits its effectiveness in both supervised fine-tuning (SFT) and reinforcement-based alignment. Training with OpenMedReason yields a 20% average improvement in VQA accuracy over the base model and achieves performance within 4.2% of the strongest comparable-scale medical LVLMs. Fine-grained performance analysis confirms that the gains are not concentrated in any single axis: OpenMedReason improves perception, medical knowledge, and rationale jointly, and its reasoning traces are preferred over those of the base model in 86.1% of pairwise comparisons. We release the code and dataset at huggingface.co/datasets/neginb/OpenMedReason.

09.
arXiv (quant-ph) 2026-06-16

Ultrastrongly coupled open systems and fine grained time

arXiv:2606.16634v1 Announce Type: new Abstract: We study the dynamics of a d-level quantum system coupled to a bosonic reservoir when the coupling constant is large. It is known that in the limit of infinite coupling strength, the system undergoes an instantaneous nonselective measurement, resulting in the immediate decoherence in the measurement basis, followed by a unitary Zeno dynamics. Here we resolve this dynamical process by introducing a fine grained scaling regime of short times proportional to the inverse coupling. We provide a rigorous derivation of the open system dynamics in this regime of ultrastrong coupling and demonstrate how decoherence unfolds continuously in the new time scale. We show that Markovian dynamics which are not given by semigroups arise naturally, in contrast to what happens in the weak coupling theory.

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

Direct Advantage Estimation for Scalable and Sample-efficient Deep Reinforcement Learning

arXiv:2606.20411v1 Announce Type: new Abstract: Direct Advantage Estimation (DAE) has been shown to improve the sample efficiency of deep reinforcement learning algorithms. However, its reliance on full environment observability limits its applicability in realistic settings, and its requirement to model transition probabilities incurs substantial computational overhead for high-dimensional observations. In the present work, we address both limitations. First, we extend the theoretical framework of DAE to partially observable domains with minimal modifications. Second, we reduce its computational complexity by introducing discrete latent dynamics models that efficiently approximate transition probabilities. We evaluate our approach on the Arcade Learning Environment and find that DAE scales effectively with function approximator capacity while retaining high sample efficiency.

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

Detecting Functional Memorization in Code Language Models

Large language models (LLMs) are increasingly used to generate code at scale. Meanwhile, prior work has investigated whether training data may be recoverable from model outputs, by auditing the textual overlap between training examples and model generations. Code, however, can be functionally equivalent while textually dissimilar. In this work, we study functional memorization: extraction of functional logic beyond what verbatim metrics detect. We construct a counterfactual setup for Olmo-3-32B, comparing a midtrained model (exposed to target code) against a pretrained reference (not exposed). We prompt both models with Python function signatures and measure both textual and functional similarity (i.e., LLM-as-a-judge, execution-based). Our results show clear evidence of functional memorization, highlighting the need for auditing metrics that go beyond textual overlap.

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

AthDGC: An Open Diachronic Greek Treebank with Indo-European Parallels

AthDGC ("Athens-PROIEL") is an open, end-to-end workflow and dataset. It is, to the best of our knowledge, the first openly licensed dependency-parsed treebank of Greek that spans eight diachronic periods, namely Archaic, Classical, Koine, Late Antique, Byzantine, Late Byzantine, Early Modern, and Modern Greek, under a single PROIEL XML 2.0 schema, with verse-level cross-alignment of the New Testament to Latin (Vulgate), Gothic (Wulfila), Old Church Slavonic (Marianus), and Classical Armenian. AthDGC builds on the PROIEL Treebank Family (Haug and Johndal 2008; Eckhoff et al. 2018), which established the schema and the Koine-Greek reference set for the project. Annotation uses the Stanford Stanza PROIEL-trained workflow; sentence-level alignment uses LaBSE, a multilingual sentence-embedding model; word-level alignment uses multilingual-BERT attention through the AwesomeAlign procedure. The v0.4 release provides curated samples and the open-source toolkit; the full annotated corpus partitions remain under v0.5 audit on the Greek national HPC. Quantitative scale, per-witness verse counts, and per-period annotated-row counts are reported in the v0.5 release notes, after the audit pass completes. Concept DOI: 10.5281/zenodo.20439182.

13.
medRxiv (Medicine) 2026-06-15

Dysplasia-Stratified Management of Barrett's Esophagus: An Incidence-Based U.S. Cost-Effectiveness Analysis

Authors:

Background and Aims Barrett's esophagus (BE) is the principal precursor of esophageal adenocarcinoma (EAC), whose incidence has risen sharply in Western countries since the 1960s. Effective, dysplasia stratified surveillance strategies are needed to prevent progression. This study evaluated the cost effectiveness of dysplasia stratified surveillance intervals and endoscopic eradication therapy (EET) across the BE spectrum. Methods We developed an incidence-based Markov state transition model of BE progression calibrated to U.S. epidemiologic data from a healthcare sector perspective over a lifetime horizon. Four hypothetical cohorts of 50-year-old individuals with short segment BE (SSBE), nondysplastic BE (NDBE), low grade dysplasia (LGD), or high-grade dysplasia (HGD) were evaluated. Strategies included no surveillance; surveillance at 1-, 2-, 3-, 4-, 5-, or 10-year intervals; standard or AI assisted endoscopy; non endoscopic screening (sponge, breath, miRNA tests); and EET for LGD and HGD. Outcomes included costs, quality adjusted life years (QALYs), incremental cost effectiveness ratios (ICERs), net monetary benefits (NMBs), EAC cases, and EAC-related deaths. Sensitivity analyses used a willingness to pay threshold of US$100,000 per QALY. Results No surveillance was the most cost-effective strategy for SSBE and NDBE. For LGD, upfront EET was more cost effective than all surveillance strategies, with results sensitive to EAC incidence and recurrence. For HGD, EET was cost saving and yielded the greatest QALYs, with findings robust in 99.9% of simulations. EET prevented 12,614 and 44,295 EAC related deaths per 100,000 individuals with LGD and HGD, respectively. Conclusion Dysplasia-stratified management is essential for optimizing surveillance and treatment strategies in BE. Any degree of dysplasia should receive EET followed by targeted post-treatment monitoring, establishing EET as the central therapeutic pathway for dysplastic BE.

14.
arXiv (CS.AI) 2026-06-15

A fully GPU-based workflow for building physics emulators of hypersonic flows

arXiv:2606.13742v1 Announce Type: cross Abstract: The ability to resolve complex physical phenomena with high fidelity and at low computational cost is central to addressing key challenges in modern engineering. A prime example lies in hypersonic flows, where the precise prediction of the full flowfield topology, in particular with respect to shock wave location and intensity, is critical. Yet supersonic and hypersonic flows continue to be a stumbling block for traditional reduced-order models and neural emulators that struggle to capture steep gradients in flow states with physical consistency in applications of industrial relevance. To that end, we introduce a fully GPU based workflow that integrates accelerated data generation with the training of neural emulators augmented by uncertainty quantification and physics-aware refinement. Our workflow is enabled by a differentiable high-fidelity solver (JAX-Fluids) which we employ for rapid dataset creation and residual-based improvement of the neural emulator to enhance physical consistency. Building on this framework, we first present a suite of model architectures and analyze their scaling behavior to expose their strengths and shortcomings. We then show that residual-based refinement enables training on cases where only mesh and input parameters are available, substantially reducing residuals and improving physical consistency. Together, differentiable simulation and residual-based refinement yield physics emulators that remain reliable beyond their training distribution, a key requirement for deploying surrogates in real-world engineering design loops.

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

CCKS: Consensus-based Communication and Knowledge Sharing

arXiv:2606.12281v1 Announce Type: cross Abstract: In Decentralized Training and Decentralized Execution (DTDE) for cooperative Multi-Agent Reinforcement Learning (MARL), action-advising-based knowledge sharing promotes interpretable and scalable cooperation among agents. However, current action advising approaches often adhere too much to the teacher's guidance without evaluating teacher-student compatibility, which causes excessive advising, suboptimal stability, and degraded performance. To overcome these challenges, this paper presents a Consensus-based Communication and Knowledge Sharing (CCKS) framework, which allows agents to adopt recommendations based on consensus-derived constraints and to follow the teacher's instructions more smartly. This mechanism enables agents to balance exploration and learning from experienced teachers, improving overall performance. The key is the consensus model construction, for which we propose to employ contrastive learning to construct consensus models based on local observations in the agents' training phase. In action selection, agents score and choose actions based on consensus and shared knowledge. Designed as a plug-and-play solution, CCKS integrates seamlessly with existing DTDE algorithms. Experiments conducted in the Google Research Football environment and the complex StarCraft II Multi-Agent Challenge demonstrate that the integration with CCKS significantly improves cooperation efficiency, learning speed, and overall performance compared with current DTDE baselines. The code is available at https://github.com/yuanxpy/CCKS.

16.
arXiv (CS.AI) 2026-06-17

Gaussian DP for Reporting Differential Privacy Guarantees in Machine Learning

arXiv:2503.10945v3 Announce Type: replace-cross Abstract: Current practices for reporting differential privacy (DP) guarantees for machine learning (ML) algorithms such as DP-SGD provide an incomplete and potentially misleading picture. For instance, if only a single $(\varepsilon, \delta)$ is known about a mechanism, standard analyses show that there could exist highly accurate inference attacks against training data records, when, upon a more careful analysis, such accurate attacks do not exist for most practical mechanisms. In this position paper, we argue that using _non-asymptotic_ Gaussian Differential Privacy (GDP) as the primary means of communicating DP guarantees in ML avoids these potential downsides. Using two recent developments in the DP literature: (i) open-source numerical accountants capable of computing the privacy profile and $f$-DP curves of DP-SGD to arbitrary accuracy, and (ii) a decision-theoretic metric over DP representations, we show how to provide non-asymptotic bounds on GDP using numerical accountants, and show that GDP can capture the entire privacy profile of DP-SGD and related algorithms with virtually no error, as quantified by the metric. To support our claims, we investigate the privacy profiles of state-of-the-art DP large-scale image classification, and the TopDown algorithm for the U.S. Decennial Census, observing that GDP fits their profiles remarkably well in all cases. We conclude with a discussion on the strengths and weaknesses of this approach, and discuss which other privacy mechanisms could benefit from GDP.

17.
arXiv (CS.LG) 2026-06-11

Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement

arXiv:2606.08493v2 Announce Type: replace-cross Abstract: Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

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

Tree-Structured Orthonormal Decomposition of the Aitchison Simplex

arXiv:2606.11646v1 Announce Type: new Abstract: Compositional data – vectors encoding relative proportions – arise across scientific domains, including ecology, geochemistry, and genomics. The features in these data often come with known hierarchical structure (e.g., taxonomies, phylogenies, ontologies), yet existing methods either ignore this structure, discard the intrinsic Aitchison geometry, are designed for binary trees, or yield incomplete coordinate systems. We describe PolyILR, a canonical orthonormal decomposition of the Aitchison tangent space aligned with any tree topology. Our construction defines a weighted local geometry at each internal node capturing full branching structure, then lifts these to a global orthonormal basis where every coordinate corresponds to a specific tree location. On microbiome and single-cell benchmarks, PolyILR yields stable, interpretable features and enables inference at multiscale tree resolution. We also establish a novel theoretical connection to softmax classifiers, suggesting possible applications to probabilistic modeling.

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

CoRe: A Continuously Reward-Finetuned LLM Query Rewriter for Multi-Stage Context-Aware Relevance in Web-Scale Video Search

LLM-based query rewriters in production face a tension: the training reward must reflect how the rewrite is consumed by the production ranker, yet the training procedure must be cheap enough to support continuous redeployment as data drifts. We present CoRe (Context Relevance), such a system, redeployed weekly for over five months in a major short-video search engine. Our reward uses the deployed multimodal relevance model as its source and a multiplicative ratio form mirroring the production fusion algebra, closing the simulation-production gap that offline reward proxies leave open. A semi-online Mixed Preference Optimization loop makes this reward affordable at multi-million-instance weekly scale: a DPO-style pairwise objective restricts the gradient pass to a small top-k/bottom-k subset of sampled trajectories, and a phase structure reduces trainer/inference-server parameter syncs from per-step to per-phase. An automated promotion gate over reward-like and stability metrics detected and recovered from a real reward-hacking incident in production. Rewriter output is consumed as parallel relevance signals at recall, rawrank, and finerank without displacing the original signals, bounding rewriter-failure blast radius. Online A/B from two sequential production launches, first deploying the rewriter at finerank, then extending consumption to recall and rawrank, delivers statistically significant reductions in change-query rate on rewrite-impacted queries, with all headline relevance and engagement metrics moving in the expected direction.

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

MBABench: Evaluating LLM Agents on End-to-End Spreadsheet Tasks in Finance

arXiv:2605.22664v3 Announce Type: replace Abstract: LLM agents are increasingly expected to carry out end-to-end workflows, producing complete artifacts from high-level user instructions. To meet enterprise needs, frontier AI labs have developed agents that can construct entire spreadsheets from scratch. This is especially relevant in finance, where core workflows such as financial modeling, forecasting, and scenario analysis are commonly conducted through spreadsheets. Yet, existing spreadsheet benchmarks do not measure this advanced capability, focusing instead on question-answering or single-formula edits. To address this gap, we provide one of the first evaluations of agents on end-to-end spreadsheet tasks, focusing on economically critical financial workflows such as modeling and scenario analysis. Since deliverables therein are routinely reviewed and revised by multiple stakeholders, judging their quality necessarily involves high-level criteria such as readability or ease of modification. To reflect the multidimensional nature of solution quality, we develop an evaluation taxonomy comprising three dimensions: Accuracy, Formula, and Format, each comprising fine-grained criteria that reflect professional standards. The Claude family leads the benchmark and produces the most professional-looking outputs in our qualitative review, but even the strongest agents frequently fall short of professional finance standards and degrade sharply as the difficulty increases beyond a few chained calculations. This suggests that current agents are not yet able to reliably produce professional-quality spreadsheets at the level of complexity real-world workflows demand.

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

3D Classification of Paramagnetic Rim Lesions in Multiple Sclerosis via Asymmetric QSM-FLAIR Modeling

Paramagnetic rim lesions (Rim$^+$) identified on susceptibility-sensitive MRI have recently emerged as a specific biomarker of chronic active inflammation in Multiple Sclerosis (MS) and are associated with long-term disability progression. However, susceptibility imaging and expert interpretation remain limited to specialized centers, visual assessment is time-consuming and variable, and the low prevalence of Rim$^+$ lesions poses severe class imbalance challenges for automated analysis. We propose a 3D multimodal deep learning framework for lesion-level Rim$^+$/Rim$^-$ classification from Quantitative Susceptibility Mapping (QSM) and FLAIR MRI. The architecture explicitly models modality asymmetry by treating QSM as the primary susceptibility-driven signal and conditioning it with FLAIR-derived structural context. To improve robustness under limited data, we employ self-supervised multimodal pretraining followed by supervised fine-tuning with contrastive regularization. The method was evaluated on a clinically acquired cohort of 88 people with MS with expert lesion annotations as reference standard. Results highlight improved performance compared to prior architectures, supporting the effectiveness of asymmetric multimodal modeling for automated chronic active lesion identification.

22.
medRxiv (Medicine) 2026-06-11

Genetic Susceptibility to Incisional Hernia: Evaluation of Hernia Polygenic Risk Scores

Objectives: Incisional hernia (IH) affects 13-30% of people after abdominal surgery, resulting in substantial morbidity and costs. While clinical risk factors have been studied extensively, genomic risk for IH is incompletely understood. We aimed to evaluate the impact of polygenic risk scores (PRS) on IH risk prediction. Methods] We created and evaluated three PRS for abdominal hernia, ventral hernia and latent hernia susceptibility for prediction of IH in an institutional biobank. The primary outcome was defined as the diagnosis or repair of an IH based on ICD-9/10-CM/PCS and CPT codes. Clinical covariates included age, sex, body mass index (BMI), smoking status, index procedure type, and perioperative surgical site infection. A phenome-wide association study (PheWAS) was performed to assess clinical associations with increased PRS. We then tested the ability of the PRS to improve prediction for IH by modeling clinical covariates with and without PRS in patients who underwent abdominal surgery. Model performance was assessed using 10 iterations of 5-fold cross-validation to estimate Brier scores and area under the receiver operating characteristic curve (AUROC), which were compared using cross-model Bayesian analysis of variance. Results: In 55,809 subjects, assessed PRS was significantly associated with incisional, umbilical, and ventral hernia on PheWAS, with 1.19 greater odds of developing IH per 1-SD increase in PRS (95% CI: 1.13-1.25, P < 0.001). Of 9,909 subjects who underwent qualifying abdominal surgery, 706 developed IH. In this cohort, the latent hernia susceptibility PRS was associated with a 16% increased hazard of developing IH per 1-SD increase (HR 1.16; 95% CI: 1.07-1.26; P < 0.001). Compared to a predictive model using clinical covariates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC = 0.660, 95% CI: 0.653-0.666), addition of the PRS showed similar Brier score and AUROC estimates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC: 0.667, 95% CI: 0.661-0.673) at five years. Cross-model Bayesian analysis demonstrated >99% probability of practical equivalence when trying to detect a difference of [&ge;] 0.02. Conclusion: All three PRS for hernia were independently associated with IH, suggesting that genomic factors contribute significantly to IH development. However, none of the three PRS meaningfully improved clinical IH risk prediction in patients who underwent abdominal surgery. This suggests that clinical comorbidities and surgical techniques may be equally as important as genomic architecture.

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

Metabolic cost of information processing in Poisson variational autoencoders

arXiv:2602.13421v2 Announce Type: replace-cross Abstract: Computation in biological systems is fundamentally energy-constrained, yet standard theories of computation treat energy as freely available. Here, we argue that variational free energy minimization under a Poisson assumption offers a principled path toward an energy-aware theory of computation. Our key observation is that the Kullback-Leibler (KL) divergence term in the Poisson free energy objective becomes proportional to the prior firing rates of model neurons, yielding an emergent metabolic cost term that penalizes high baseline activity. This structure couples an abstract information-theoretic quantity – the *coding rate* – to a concrete biophysical variable – the *firing rate* – which enables a trade-off between coding fidelity and energy expenditure. Such a coupling arises naturally in the Poisson variational autoencoder (P-VAE) – a brain-inspired generative model that encodes inputs as discrete spike counts and recovers a spiking form of *sparse coding* as a special case – but is absent from standard Gaussian VAEs. To demonstrate that this metabolic cost structure is unique to the Poisson formulation, we compare the P-VAE against Grelu-VAE, a Gaussian VAE with ReLU rectification applied to latent samples, which controls for the non-negativity constraint. Across a systematic sweep of the KL term weighting coefficient $\beta$ and latent dimensionality, we find that increasing $\beta$ monotonically increases sparsity and reduces average spiking activity in the P-VAE. In contrast, Grelu-VAE representations remain unchanged, confirming that the effect is specific to Poisson statistics rather than a byproduct of non-negative representations. These results establish Poisson variational inference as a promising foundation for a resource-constrained theory of computation.

24.
medRxiv (Medicine) 2026-06-17

Real-World Effectiveness and Safety of Avacopan in ANCA-Associated Vasculitis: A Systematic Literature Review and Meta-analysis

Background: The efficacy and safety of avacopan in ANCA-associated vasculitis (AAV) has been established in randomized trials of of avacopan as a glucocorticoid (GC) sparing therapy. However, real world evidence (RWE) has an important role in confirming effectiveness and evaluating safety in more generalizable settings. This study aimed to synthesize RWE on the effectiveness and safety of avacopan in adults with AAV. Methods: A systematic literature review and meta analysis of non interventional real world studies was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Eligible studies included adults with AAV treated with avacopan in routine clinical practice. Pooled estimates of effectiveness and safety outcomes were calculated using random effects meta-analyses. Primary outcomes included remission at 6 and 12 months and sustained remission at 12 months. Secondary outcomes included relapse, GC use and dosing, hepatotoxicity, infections, and treatment discontinuation. Exploratory outcomes included changes in estimated glomerular filtration rate (eGFR) and dialysis related endpoints. Results: A total of 71 studies were included and contributed to quantitative analyses. Pooled remission for patients on avacopan was 87% (95% CI: 75%-94%) at 6 months and 93% (95% CI: 86%-97%) at 12 months, and sustained remission was 86% (95% CI: 74%-93%) at 12 months. Relapse at 12 months was low (7%; 95% CI: 4%-11%). GC use was 36% at both 6 and 12 months. Improvements in eGFR were observed at 6 months (18 mL/min/1.73 m2) and 12 months (18 mL/min/1.73 m2), and dialysis liberation was 66% in a limited subset. Among avacopan patients, 11% experienced any hepatotoxicity, including 7% with serious (defined as directly reported or requiring hospitalization) hepatotoxicity, while 7% experienced serious (defined as directly reported or requiring hospitalization) infection. Conclusions: In real world clinical practice, avacopan is associated with high remission rates, low relapse rates, and a consistent GC sparing effect, with effectiveness comparable to standard of care regimens. Findings support its clinical use with appropriate safety monitoring; however, the observed heterogeneity in hepatotoxicity and the limited comparative effectiveness evidence highlight areas requiring further investigation.

25.
arXiv (math.PR) 2026-06-18

First to reach $n$ game

arXiv:2506.08782v4 Announce Type: replace Abstract: We consider a game with two players, consisting of a number of rounds, where the first player to win $n$ rounds becomes the overall winner. Who wins each individual round is governed by a certain urn having two types of balls (type 1 and type 2). At each round, we randomly pick a ball from the urn, and its type determines which of the two players wins. We study the game under three regimes. In the first and the third regimes, a ball is taken without replacement, whilst in the second regime, it is returned to the urn with one more ball of the same colour. We study the properties of the random variables equal to the properly defined overall net profits of the players, and the results are drastically different in all three regimes.