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01.
arXiv (quant-ph) 2026-06-16

The Optimal Rate Function in Covariant Quantum State Tomography

arXiv:2606.16948v1 Announce Type: new Abstract: The problem of quantum tomography is to estimate an unknown quantum state $\rho$ from a measurement of $n$ copies of $\rho$. One can ask which tomography protocol, i.e.\ which choice of multi-copy measurement, gives the best possible estimate of $\rho$. To do so, we characterize tomography protocols by their rate function, which governs the exponential rate at which a protocol assigns probability to a particular estimate $\sigma$ of the true state $\rho$. This rate function is a quantum mechanical generalization of the classical relative entropy between the true state and its estimate, and depends on the choice of protocol. It is bounded by the quantum relative entropy, and we show that this bound is sharp: for any $\rho$ and $\sigma$ we construct a family of protocols whose rate functions converge to the quantum relative entropy $D(\sigma\|\rho)$. We consider the family of covariant tomography protocols; these are the basis independent state estimation schemes that assume no prior information about $\rho$ and $\sigma$. Keyl described a specific tomography protocol based on Schur sampling, and conjectured that among all covariant tomography protocols it has the largest possible rate function for all $\sigma$ and $\rho$. We prove this conjecture. The resulting rate function is an annealed version of quantum relative entropy, due to the cost of learning the eigenbasis in covariant quantum state tomography.

02.
bioRxiv (Bioinfo) 2026-06-12

CAREPath: Semantic Context-Aware Reasoning Paths with Mechanism-Augmented Embeddings for Drug Repurposing

Biomedical knowledge graphs (BKGs) that include drugs, genes, and diseases support drug repurposing by connecting drugs to diseases through gene-mediated multi-hop paths, thereby enabling mechanism-of-action reasoning. However, deeper traversal does not necessarily improve mechanistic reasoning: long paths grow combinatorially and frequently pass through hub genes, producing irrelevant gene regulatory signals, whereas overly constrained or sparse paths may miss broader biological context. We propose CAREPath, a KG-LLM framework inspired by depth-first search (DFS)-like and breadth-first search (BFS)-like reasoning to balance mechanistic specificity, scalability, and context recovery. The DFS-like module constrains traversal to short disease-gene-drug paths, converts each path into a structured prompt, and encodes it with a biomedical language model to generate semantic path embeddings. Complementarily, the BFS-like module constructs entity-level mechanism-context embeddings from one-hop gene neighborhoods and enriches them through similarity-guided augmentation using pharmacologically related drugs and gene-signature-similar diseases. Across five biomedical KGs, CAREPath achieves the best overall AUPRC among 18 baselines, improving performance by up to 3.8%. Additional analyses show that semantic short-path encoding contributes most to performance, while mechanism-context augmentation improves robustness under sparse evidence and strengthens Gene Ontology functional agreement. Case studies and recently FDAapproved indications further demonstrate its practical relevance, positioning CAREPath as an interpretable framework for scalable and mechanism-aware drug repurposing. Source code is available at https://github.com/hamppy-song/CAREPath.

03.
arXiv (quant-ph) 2026-06-19

Resolving problems with the continuum limit in coherent-state path integrals

arXiv:2602.02466v2 Announce Type: replace Abstract: The paper solves the problem of continuum limit in bosonic thermal coherent-state path integrals. For this purpose, exact discrete versions of the path integral are constructed for three different orderings of the Hamiltonian: normal, anti-normal and symmetric (Weyl order). Subsequently, their different continuum versions are checked on the harmonic oscillator, to choose the symmetric ordering as a possibly correct choice for all polynomial Hamiltonians. Spotted mathematical subtleties in the simple case serve as a clue to the general solution. Finally, a general justification for the symmetric order is provided by deriving the continuum path integral starting from the exact discrete case using a renormalization procedure in the imaginary time frequency domain. While the role of Weyl order has already been found, the paper provides the missing proof of its suitability for every polynomial Hamiltonian and simplifies the previously established construction by referring only to creation and annihilation operators (without position and momentum operators).

04.
arXiv (CS.CL) 2026-06-12

LEDGER: A Long-Context Benchmark of Corporate Annual Reports for Grounded Financial Retrieval and Extraction

Finance reporting is a natural proving ground for large language models, and the very-long-context capabilities of recent models across all sizes make rigorous evaluation in this domain an increasingly pressing need. Yet most public financial resources reduce the task to plain-text SEC 10-K filings paired with a handful of question-answer items. We release LEDGER (Long-context Evaluation of Documents for Grounded Extraction and Retrieval), a corpus of 4,999 digitized corporate annual reports - full documents with figures, tables, and narrative, not just regulatory filings. Each report is labeled with 31 consolidated financial KPIs to be extracted and linked to the market's reaction at the earnings date. From this data we derive three evaluation benchmarks spanning the difficulty spectrum: a pure page-level KPI retrieval task with TREC-style relevance judgments over 118,048 questions in natural language, a conversational "needle-in-a-haystack" single-value lookup, and a full KPI extraction task, both from long, numerically dense reports. We additionally provide human OCR-quality annotations with inter-annotator agreement and the complete extraction, validation, and scoring toolchain. We further demonstrate the dataset's research utility with a case study linking CEO-letter rhetoric to post-publication market impact.

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

From Passive Generation to Investigation: A Proactive Scientific Peer Review Agent

Large language models (LLMs) have shown promise in automating scientific peer review. However, existing approaches often struggle to generate in-depth reviews supported by concrete evidence. We argue that a key limitation is the lack of flexibility to proactively investigate suspicious parts of a paper based on accumulated evidence, as human reviewers do. In this paper, we explore how to enable an LLM-based review agent to perform such proactive investigation. We find that this can be naturally formulated as a Markov Decision Process (MDP), and propose ProReviewer, a scientific peer review agent that proactively reviews a paper guided by a maintained, structured review log. The structured review log serves as a workspace for the agent to track evidence and intermediate findings collected during review. Experiments show that ProReviewer with an 8B backbone, trained by supervised fine-tuning and optimized by reinforcement learning, achieves the highest average score across five quality dimensions, outperforming prompt-based methods with much larger frontier LLMs by up to 39% and the strongest fine-tuned baseline by 16% relatively. It also attains the highest win rates against baselines in human evaluation.

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

Quantum statistical functions

作者:

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

07.
arXiv (CS.AI) 2026-06-19

Toward Calibrated Mixture-of-Experts Under Distribution Shift

arXiv:2606.20544v1 Announce Type: new Abstract: Calibration aligns a model's predictive uncertainty with the frequencies of its empirical outcomes and is important for understanding and trusting reported probabilities. Recent work shows that enforcing calibration at the level of individual predictors can improve ensemble accuracy and calibration, with mixture-of-experts (MoE) models showing strong empirical improvements in particular; however, the conditions under which calibration helps MoE are not well understood. In this work, we study how MoE models behave under distribution shift, focusing on how routing mechanisms interact with expert-level calibration. We show that expert calibration is sufficient to ensure calibration of the overall model under a broad class of distribution shifts in hard-routed models, but is insufficient for calibrating soft-routed models. To address this, we propose an adversarial reweighting that penalizes calibration errors of the routed aggregate under distribution shift, and we demonstrate that it improves the accuracy-calibration tradeoff both on average and on difficult subsets of the data, across model classes, prediction tasks, and distribution shifts.

08.
medRxiv (Medicine) 2026-06-22

Brain-gut axis imaging, motion correction with 11C-carfentanil total-body PET

Background: Mu-opioid receptors (MORs) are expressed throughout the body including in the brain and gastrointestinal (GI) tract. Total-body PET imaging of the brain and GI tract offers a promising approach for cross-sectional in vivo evaluation of the MOR brain-GI axis. However, intestinal motility and bladder filling introduce motion throughout the GI tract over the scan window. Here we establish analysis methodology to account for motion for dynamic imaging of the brain-GI axis, to further characterize peripheral MORs throughout the body and provide a framework for semi-automatic total-body PET modeling. Methods: 4 subjects underwent 90-min dynamic [11C]-carfentanil (cfn) total-body PET acquisitions at baseline, after intravenous naloxone (central antagonist) administration, and after orally administered loperamide (peripheral agonist and P-glycoprotein substrate). Thalamic MOR availability was measured using the Logan reference tissue model. Using CT-based segmentation, the GI tract was subdivided into anatomical segments, in addition to other peripheral organs (e.g., liver, psoas muscle). Frame-by-frame semi-automatic motion correction was performed with three distinct reference frames (11-14 min post-injection, p.i., 35-40 min p.i., and 85-90 min p.i.). The performance of these three were compared to manual correction. Compartment modeling and Logan graphical analysis were performed to estimate relevant kinetic parameters (K1, VT, VTLogan). Results: Across the 4 subjects and regions, kinetic parameter estimates were highly correlated (r>0.7) for K1, VT and VT Logan when comparing semi-automatic (reference frame at 35-40 min p.i.) and manual correction. With semi-automatic motion correction, graphical-based estimation of VTLogan in the gastrointestinal tract was significantly decreased with loperamide relative to baseline (p

09.
medRxiv (Medicine) 2026-06-17

Hormonal Contraceptives Drive Genital Lipid Metabolism Reprogramming and Susceptibility to HIV Infection

Heterosexual genital HIV transmission is a major driver of new infections, particularly in women, making them disproportionately vulnerable to HIV acquisition. Previous studies have associated injectable hormonal contraceptives (HC) with increasing susceptibility to HIV. Yet, the underlying molecular mechanism remains incompletely understood. Given the structural and signaling role of lipids in the female genital tract, cervicovaginal lipidomic profiling has the potential to reveal the mechanistic interplay among HC, lipidome, and HIV susceptibility in the female genital tract. We conducted untargeted cervicovaginal lipidomics study in a cohort of high-risk, HIV-negative, Kenyan sex workers who were using injectable depot medroxyprogesterone acetate (DMPA), oral contraceptive pill (OCP), or no hormonal contraception (NH). Genital lipids were quantitatively analyzed using liquid chromatography-mass spectrometry (LC-MS) and bioinformatics platforms. A total of 1045 lipid species were identified in the cervicovaginal lavage samples. Injectable DMPA significantly downregulated major structural and signaling membrane lipids, including phospholipids, ceramides, sphingomyelins, and glycosphingolipids (p

10.
arXiv (CS.CV) 2026-06-15

ViT-Up: Faithful Feature Upsampling for Vision Transformers

Vision Transformers (ViTs) have become a dominant architecture for visual representation learning, providing exceptionally strong and broadly reusable backbone features. However, ViTs are commonly operated on relatively small patch-token grids due to the quadratic cost of global self-attention, which creates a persistent bottleneck for dense prediction tasks such as semantic segmentation and depth estimation. This has motivated the development of task-agnostic feature upsamplers. While recent state-of-the-art methods produce visually sharp dense representations, their reliance on shallow image encoders for guided upsampling can introduce feature leakage, fragmentation, and blur. We introduce ViT-Up, an implicit feature upsampling framework that replaces external image guidance with layer-wise query construction from intermediate ViT hidden states. This enables feature prediction at arbitrary continuous image coordinates while preserving alignment with the backbone feature space. Experiments demonstrate that ViT-Up consistently outperforms state-of-the-art image-guided upsamplers across dense prediction and semantic correspondence. On DINOv3-S+, ViT-Up improves over prior methods by up to +2.07 mIoU on Cityscapes and +4.17 PCK@0.10 on SPair-71k. With the larger DINOv3-B backbone, these gains increase to +3.36 mIoU and +8.09 PCK@0.10, demonstrating that ViT-Up scales favorably with backbone capacity.

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

Recover Semantics First, Generate Better: Improved Latent Modeling for 3D MRI Reconstruction and Cross-Contrast Synthesis

Multi-contrast magnetic resonance imaging (MRI) provides complementary information for clinical diagnosis. However, acquiring all MRI sequences is often time-consuming and costly. Recent generative models perform cross-contrast synthesis to address this issue by inferring absent contrasts from the available ones. Nevertheless, synthesizing 3D MRI presents significant challenges. Due to the massive volume sizes, operating directly in the pixel space is computationally prohibitive; therefore, a common approach is to first compress the 3D volumes into a latent space and subsequently train generative models in that space. We observe that existing compression architectures face several critical issues: they under-preserve long-range anatomical coherence, discard clinically meaningful semantics, and rely on optimization objectives that lead to over-smoothed reconstructions. Ultimately, these shortcomings compromise the performance of subsequent generative models. In this work, we propose a semantics-first latent modeling framework for 3D MRI reconstruction and cross-contrast synthesis. Specifically, we introduce a Latent Harmonization Encoder (LHE) to capture global anatomical dependencies, ensuring coherent volumetric representations. To mitigate semantic degradation during latent compression, we further design a Semantic Recovery Block (SRB) that injects high-level priors from a self-supervised semantic teacher, enhancing contrast-aware separability in the latent space. Additionally, we propose an Anatomy-aware Frequency Loss (AFL) to adaptively preserve diagnostically relevant high-frequency structures. Extensive experiments on two public multi-contrast MRI datasets demonstrate consistent improvements in reconstruction fidelity and cross-contrast synthesis quality. Our code is available at https://github.com/script-Yang/RSF.

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

Parthenon Law: A Self-Evolving Legal-Agent Framework

arXiv:2606.04602v3 Announce Type: replace Abstract: As agents grow more capable, legal-domain LLM agents promise to turn document-heavy matters into reviewable work products – yet reliable deployment faces three obstacles: no large-scale evidence on how today's strongest model-and-harness combinations behave on end-to-end legal matters; no agent architecture adapted to the legal vertical, only general-purpose harnesses; and, in a setting that keeps shifting with new facts, authorities, and deadlines, no mechanism for systems to learn from their own outcomes. We address each. A large-scale empirical study on Harvey LAB – $12{,}510$ agent trajectories – shows that even frontier agents remain far from completing matters in a single pass: per-criterion accuracy climbs with stronger models while strict matter completion stalls. We then introduce \textsc{Parthenon}, a self-evolving legal-agent framework that factors Model, Harness, Agent roles, legal Knowledge, deterministic Tools, and procedural Skills into auditable surfaces for source traceability, date and number grounding, deliverable compliance, and issue closure. Finally, an anti-leakage learning loop converts scored failures into task-agnostic edits to skills, tools, and knowledge, letting the system improve with experience – as a firm refines its checklists and playbooks after each matter – without touching model weights. Across our large-scale empirical analysis, \textsc{Parthenon} substantially improves the performance of state-of-the-art models and harnesses on legal-matter tasks.

13.
arXiv (CS.AI) 2026-06-11

Making Models Unmergeable via Scaling-Sensitive Loss Landscape

arXiv:2601.21898v2 Announce Type: replace Abstract: The rise of model hubs has made it easier to access reusable model components, making model merging a practical tool for combining capabilities. Yet, this modularity also creates a governance gap: downstream users can recompose released weights into unauthorized mixtures that bypass safety alignment or licensing terms. Because existing defenses are largely post-hoc and architecture-specific, they provide inconsistent protection across diverse architectures and release formats in practice. To close this gap, we propose Trap$^2$, an architecture-agnostic protection framework that encodes protection into updates during fine-tuning, regardless of whether they are released as adapters or full models. Instead of relying on architecture-dependent approaches, Trap$^2$ uses weight re-scaling as a simple proxy for the merging process. It keeps released weights effective in standalone use, but degrades them under re-scaling that often arises in merging, undermining unauthorized recomposition.

14.
arXiv (math.PR) 2026-06-16

The Backward Stochastic Partial Differential Integral Equations: Solvability and Comparison Principle

arXiv:2606.16237v1 Announce Type: new Abstract: The paper is concerned with the well-posedness of backward stochastic partial differential equations with jumps, also called backward stochastic partial differential integral equations. We start from the proof for the existence and uniqueness of solution to backward stochastic evolution equation with jump in the Gelfand triple framework. Then the well-posedness of both weak solution and strong solution to backward stochastic partial differential integral equation is obtained with the Gelfand triple replaced by specific Sobolev spaces. Finally, the comparison principle for backward stochastic partial differential integral equation is proved, which has potential applications in financial mathematics.

15.
arXiv (quant-ph) 2026-06-17

Entanglement transition in unitary system-bath dynamics

arXiv:2512.06081v3 Announce Type: replace Abstract: The evolution of a system coupled to baths is commonly described by a master equation that, in the long-time limit, yields a steady-state density matrix. However, when the same evolution is unraveled into quantum trajectories, it is possible to observe a transition in the scaling of entanglement within the system as the system-bath coupling increases - a phenomenon that is invisible in the trajectory-averaged reduced density matrix of the system. Here, we go beyond the paradigm of trajectories from master equations and explore whether a qualitatively analogous entanglement-scaling transition emerges in a single unitary evolution of the combined system-bath setup, without monitoring the dynamics of the system. We investigate the scaling of entanglement in a unitary quantum setup composed of a two-dimensional lattice of free fermions, where each site is coupled to a fermionic bath. As the system-bath coupling increases, the logarithmic fermionic negativity reveals an entanglement transition from logarithmic-law to area-law scaling. This occurs while the system's steady-state properties are trivial, highlighting that the signatures of these different scalings are within the bath-bath correlations. Evidence of the transition is also found in the mutual information and the correlations of the full system-bath setup, suggesting that the entanglement transition is underpinned by a change in the spatial structure of quantum information.

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

Efficient Flow Matching using Latent Variables

Flow matching models have shown great potential in image generation tasks among probabilistic generative models. However, most flow matching models in the literature do not explicitly utilize the underlying clustering structure in the target data when learning the flow from a simple source distribution like the standard Gaussian. This leads to inefficient learning, especially for many high-dimensional real-world datasets, which often reside in a low-dimensional manifold. To this end, we present $\texttt{Latent-CFM}$, which provides efficient training strategies by conditioning on the features extracted from data using pretrained deep latent variable models. Through experiments on synthetic data from multi-modal distributions and widely used image benchmark datasets, we show that $\texttt{Latent-CFM}$ exhibits improved generation quality with significantly less training and computation than state-of-the-art flow matching models by adopting pretrained lightweight latent variable models. Beyond natural images, we consider generative modeling of spatial fields stemming from physical processes. Using a 2d Darcy flow dataset, we demonstrate that our approach generates more physically accurate samples than competing approaches. In addition, through latent space analysis, we demonstrate that our approach can be used for conditional image generation conditioned on latent features, which adds interpretability to the generation process.

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

Narrative Theory-Driven LLM Methods for Automatic Story Generation and Understanding: A Survey

Applications of narrative theories using large language models (LLMs) deliver promising methods in automatic story generation and understanding tasks. Our survey examines how natural language processing (NLP) research uses LLM methods to engage with diverse concepts from narrative studies. We use established distinctions from narratology to categorise ongoing efforts and discover the following: \redtext{(a) narrative texts come from diverse sources beyond just literature, (b) theoretical synthesis and validation are potential outcomes, (c) generation tasks lag behind understanding in several ways: theoretical application, post-training methods, exploring non-fiction narratives and addressing narrative levels beyond fabula and discourse.} For future directions, instead of the pursuit of a single, generalised benchmark for `narrative quality', we believe that progress can benefit from efforts that focus on the following: defining and improving theory-based metrics for individual narrative attributes; continue conducting large-scale, theory-driven literary/social/cultural analysis; generating narratives in situated contexts; and continuing experiments where outputs can be used to validate or refine narrative theories. This work provides a contextual foundation for more systematic and theoretically informed narrative research in NLP by providing an overview to ongoing research efforts and the broader narrative studies landscape.

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

Task-Restricted Symmetries in Recurrent Weight Space

arXiv:2606.18457v1 Announce Type: new Abstract: Recurrent networks can contain substantial functional redundancy in weight space: changing a recurrent matrix may leave the input-output rollout nearly unchanged on a task distribution, while similar-scale changes can destroy the same behavior. We study this redundancy in one-layer tanh RNNs using ordered real Schur coordinates. The Schur form separates spectral blocks from directed nonnormal couplings, giving a diagnostic basis for structured ablations that keep the input and readout maps fixed. In a fixed-length copy task, selected nonnormal Schur couplings can be removed with little loss in some trained solutions, whereas other couplings are necessary for accurate autonomous replay. Across flip-flop, sine generation, and context-dependent integration, the loss-preserving ablation profile varies across tasks and trained solutions. These results identify candidate approximate functional invariances, not universal symmetries of recurrent weight space. Schur-coordinate ablations provide a practical diagnostic for which structured perturbations preserve a trained recurrent solution and which ones disrupt its computation.

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

Learning High Coverage Discriminative Parsimonious Rulesets

arXiv:2606.14156v1 Announce Type: cross Abstract: Learning systems based on IF-THEN rule representations readily offer interpretability, making them a crucial focus in contemporary AI research. A key objective for such rule sets is to achieve both high discriminative power and interpretability. While existing state-of-the-art algorithms implicitly prioritize predictive accuracy, they often fall short on one or more quality metrics that ensure interpretability, such as coverage and parsimony of rule sets. Motivated by this, this paper propose the development of CDPR, which aims to create highly accurate and interpretable rule sets for classification problems. To the best of our knowledge, this represents the first attempt to establish such an approach. In this study, we introduce two algorithms rooted in submodular maximization, which not only provide provable guarantees on coverage but also yield rule sets that are both discriminative and parsimonious. We empirically demonstrate that rule sets learned through our approaches achieve higher accuracy and interpretability and has more than a 2.5-fold improvement in average coverage rates when compared to the next best algorithm.

20.
arXiv (CS.CV) 2026-06-17

HRDX: A Large-Scale Vector HD-Map Dataset

Reliable autonomous driving requires vectorized HD maps that are geometrically accurate, semantically rich, and scalable to long-horizon driving. However, existing public HD map datasets are limited in scale, provide sparse semantic attributes, and lack modalities such as aerial imagery that could enable new research directions. We present HRDX, a large-scale dataset for vector HD-map construction, spanning about 40 hours (1,400 km) of minimally overlapping drives, which is several times larger than prior public HD map datasets. Data is captured using six synchronized surround cameras, a 128-beam LiDAR, and centimeter-level RTK GNSS/IMU, and is further complemented by precisely aligned aerial orthoimagery. Annotations cover 10 vector map classes, complemented with over 20 semantic and topological attributes. To evaluate this richer ontology, we introduce the Composite Score (CS) to jointly assess geometric fidelity and attribute correctness. Benchmark experiments show that HRDX's scale improves online vector-map construction, and that aligned aerial imagery provides a useful structural prior: using aerial imagery at training and/or inference improves geometric map quality, while aerial-augmented teachers can transfer part of this benefit to camera-only students without increasing inference-time sensor requirements. HRDX is intended to support reproducible research on large-scale HD-map learning, multimodal BEV fusion, and training-time privileged information. HRDX dataset and benchmarks are available at https://github.com/honda-research-institute/HRDX

21.
arXiv (quant-ph) 2026-06-19

Random Local Stabilizer Codes in Three Dimensions without String or Self-Similar Fractal Logical Operators

作者:

arXiv:2606.19873v1 Announce Type: new Abstract: Quantum error-correcting codes (QECs) are essential components quantum computation and have deep connections to quantum phases of matter. A key obstruction to passive self-correcting QECs is the presence of string logical operators, which can generate logical errors through constant-energy-barrier processes. Haah's Codes (fracton codes) showed that three-dimensional stabilizer codes can forbid such string logical operators, but their translation-invariant structure supports self-similar fractal logical operators with a logarithmic energy barrier. We introduce the qutrit random cubic codes, a family of local qutrit Calderbank-Shor-Steane stabilizer Hamiltonians with similar cube-check structure as Haah's Code 1 but built from spatially varying stabilizers. We prove that these models retain the no-string property and numerically observe that they have properties distinct from translation-invariant fracton codes: the smallest ground-state degeneracy exponent is $k=2$ for odd $L$ and $k=4$ for even $L$; noncontractible plane-logical operators span the entire logical space; and charge-push diagnostics show that the self-similar fractal operators are absent. These results demonstrate that constrained randomness can fundamentally change the nature of stabilizer codes and improve their self-correction properties. They further point to broader families of quantum error-correcting codes and quantum phases beyond canonical topological and fracton orders.

22.
bioRxiv (Bioinfo) 2026-06-11

DModE: An end-to-end framework for Differential Modification and Expression Analysis of Nanopore direct RNA sequencing data

Summary: Nanopore direct RNA sequencing (DRS) enables simultaneous quantification of transcript abundance and RNA modifications from native RNA molecules, providing a unique opportunity to study transcriptional and epitranscriptomic regulation within a single experiment. However, comprehensive analysis of DRS data remains challenging, as existing workflows typically focus on individual processing steps and often require manual integration of multiple software packages for expression analysis, modification detection, statistical testing, and visualization. Furthermore, integrated differential expression and differential RNA modification analysis at both gene and isoform resolution remains poorly supported by current workflows. Here, we present DModE (Differential Modification and Expression Analysis), an end-to-end framework for integrated analysis of Nanopore DRS data. DModE combines an Epi2ME-compatible Nextflow preprocessing workflow with a dedicated Python package for downstream statistical analysis, visualization, and reporting. The framework supports differential gene and isoform expression analysis, differential RNA modification analysis at genome and transcript level, metagene profiling, exploratory epitranscriptomic analyses, and integrated assessment of relationships between expression and modification dynamics. Results are automatically summarized in interactive HTML reports, facilitating reproducible and accessible data interpretation. By integrating transcriptomic and epitranscriptomic analyses within a single framework, DModE substantially simplifies comprehensive DRS data analysis and lowers the barrier for studying RNA modification biology using Nanopore sequencing.

23.
medRxiv (Medicine) 2026-06-18

Urinary Creatine Riboside Complements PSA to Improve Disease Detection in the Diagnostic Gray Zone of Prostate Cancer

Circulating prostate-specific antigen (PSA) discriminates poorly in the diagnostic gray zone (3.0-9.99 ng/mL), where ~75% of biopsies yield no clinically significant prostate cancer (PCa). We evaluated whether urinary creatine riboside (CR), a tumor-derived metabolite excreted through the prostatic urethra, complements PSA for gray-zone detection and independently predicts prostate-cancer-specific mortality (PCSM). In the NCI-Maryland PCa Case-Control Study (951 cases, 962 controls; 47.6% African American men; median follow-up 11.5 years), urinary CR was quantified by UPLC-MS/MS. Within the PSA gray zone (n = 668), urinary CR was complementary to PSA, with markedly higher single-marker discrimination than PSA (AUC 0.93, 95% CI 0.88-0.98 vs 0.77, 0.66-0.89) and additive when combined ({Delta}AUC +0.17, p < 0.001; 91.4% sensitivity at 80% specificity). After adjustment for 11 clinical and sociodemographic covariates, urinary CR independently predicted PCSM complementary to PSA (Fine-Gray SHR 1.72, 1.35-2.19 for CR; 1.35, 1.08-1.68 for PSA; Harrell's C 0.85 for CR + PSA vs 0.77 for PSA alone), with strongest signal in African American men (SHR 2.43, 1.57-3.75 for CR). We conclude that urinary CR is a candidate non-invasive biomarker complementary to PSA - improving gray-zone triage and predicting PCSM; prospective validation in biopsy-referred cohorts is warranted.

24.
bioRxiv (Bioinfo) 2026-06-19

Children's DNA Methylation and Family Dynamics in a Congo Basin Subsistence Community: Links with Parental Conflict and Fathers' Caregiving

Family environments may contribute to children's long-term health through biological processes, including epigenetic regulation such as DNA methylation (DNAm). However, most studies in this area focus on Euro-American populations while also rarely including fathering data. The current study investigated children's blood DNAm associations with positive (father caregiving) and negative (parental conflict) family dynamics in a smaller-scale subsistence society living in the Congo Basin rainforest. We measured DNAm from dried blood spots of 54 children (mean age=8.48 years) and conducted three epigenome-wide association studies aimed at discovering differential co-methylated regions (CMRs) associated with family dynamics. Via path models, we investigated the health implications and shared contribution of family factors of the identified CMRs. Differential DNAm associated with family dynamics was localized to genes related to stress, immunology, development, and aging, thus possibly linking to children's physical health and were simultaneously connected to other family factors such as number of siblings. Our findings suggested similarities in biological embedding of family factors across socio-ecologically diverse contexts.

25.
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.