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01.
medRxiv (Medicine) 2026-06-18

Development and Initial Validation of the Quality of life Evaluation in NF2-related Schwannomatosis Trials (QUEST) Assessment

Individuals with NF2-related schwannomatosis (NF2-SWN) experience a complex constellation of physical, emotional, and social symptoms that substantially impact quality of life (QoL). Although disease-specific patient-reported outcome measures are increasingly important for evaluating treatment benefit in clinical trials, existing NF2-SWN QoL measures have limitations in content coverage and sensitivity to change. This study describes the development and initial validation a new disease-specific QoL assessment – the Quality of Life Evaluation in NF2-related Schwannomatosis Trials (QUEST). Using a three-phase, mixed-methods approach, items were generated through concept elicitation interviews with individuals with NF2-SWN and clinicians, prioritized via patient survey data, and refined through iterative cognitive debriefing procedures. The resulting 21-item QUEST assesses the extent to which NF2-SWN has negatively impacted a persons daily life over the past seven days. Initial psychometric evaluation was conducted in an international sample of 174 individuals with NF2-SWN aged 15 years and older (117 women (67%), 158 White individuals (89%)). Exploratory factor analysis supported a four-factor structure, and the total score demonstrated excellent internal consistency and strong test-retest reliability. Evidence of construct validity was demonstrated through hypothesized associations with disease-specific, generic, and domain-specific QoL measures, as well as known-groups validity based on self-reported disease severity and number of prior surgeries. Incremental validity analyses indicated that QUEST explained unique variance beyond existing measures. Together, findings support the QUEST as a reliable and valid disease-specific QoL measure with strong content validity and feasibility for use as a clinical trial endpoint in NF2-SWN.

02.
medRxiv (Medicine) 2026-06-17

Trends in Suicide Mortality by Method among US Individuals aged 10-24 Years from 1999 to 2024

Background: Suicide is the second leading cause of death in US adolescents aged 10-24. Method use strongly influences lethality and design of prevention strategies, but recent trends remain unclear. We therefore aimed to investigate trends in suicide mortality rates by method, age group, and sex. Methods: This cross-sectional study used suicide mortality data from the National Center for Health Statistics for a quarter-century period, between 1999 and 2024. All individuals aged 10-24 years at the time of death, with suicide as the underlying cause, were included. We estimated suicide mortality rates (i.e., the number of suicide deaths per 100,000 people) and annual percent change by method (firearm, asphyxiation, poisoning, other), age group (10-14, 15-19, 20-24), and sex. Changing trend time points were determined using Joinpoint regression models Results: From 1999 to 2024, 159,241 suicide deaths occurred among individuals aged 10-24. While suicide rates declined across all age groups between 2017 and 2024, the male-to-female gap narrowed by 18.9%. Among 10-14-year-olds, declining rates among males masked a consistent increase in female suicide rates since 2011. Although asphyxiation-related suicides decreased across all groups since 2018, firearm suicide rates increased for females in the 10-14 and 20-24 age groups. Albeit not as common as firearms or asphyxiation, poisoning suicide rates increased in the 15-19 and 20-24 age groups. Since 1999, suicide rates by other less common methods (e.g., jumping) showed significant increases, for both sexes, especially among individuals aged 20-24. Suicide rates were consistently highest in the 20-24 age group across all study years. Conclusion: The decrease in suicide mortality rates among individuals aged 10-24 was largely driven by declines in males and reductions in asphyxiation-related suicides. However, increasing female suicide rates in the 10-14 age group, as well as increasing rates of death by less common means, warrant close attention. While suicide prevention efforts like structural interventions and means restriction have shown effectiveness among male adolescents, priority should now be given to adapting these approaches for female adolescents, particularly those aged 10-14.

03.
arXiv (CS.LG) 2026-06-12

A Privacy-Preserving Framework Using Remote Data Science for Inter-Institutional Student Retention Prediction

arXiv:2606.12845v1 Announce Type: cross Abstract: This study explores privacy-preserving machine learning (PPML) techniques using the PySyft platform to enable collaborative prediction of student retention between institutions. We developed a remote data science (RDS) framework with a semi-air-gapped architecture consisting of high-side and low-side servers, allowing researchers from three universities to build predictive models on sensitive student data without direct data access. Using historical data from a small private university (N=720), we evaluated three synthetic data generation approaches and validated the framework through inter-institutional collaboration. The results demonstrate consistent classification performance across institutions (Macro F1: 0.690–0.695) while maintaining strict Family Educational Rights and Privacy Act (FERPA) compliance. We also propose Data-Type-Aware Templates, a novel synthetic data method that prioritizes privacy over distributional fidelity. Our findings confirm that RDS-based PPML is technically feasible for educational settings and offers a practical alternative to federated learning for small-scale inter-institutional collaborations. The code is available at https://github.com/jtfields/NAIRR240195-Privacy-Preserving-Machine-Learning.

04.
arXiv (CS.CL) 2026-06-15

Cross-Dataset Bloom Question Classification: Supervised Models and Prompted LLMs

Automatic Bloom's taxonomy classification of assessment questions can substantially reduce instructor workload, but labeling is subjective and teacher-dependent. Prior machine learning (ML) and deep learning (DL) approaches reported strong within-dataset results, yet were rarely evaluated in cross-dataset settings, leaving real-world generalizability unclear; meanwhile, LLM effectiveness for Bloom question classification has not been systematically studied. We evaluated the cross-dataset generalization of existing ML/DL methods and assessed LLMs with multiple prompting strategies on five datasets; the best prompting strategy combined in-context examples with course-specific action verbs. Supervised ML/DL models degraded substantially on unseen datasets, whereas LLMs were more stable, suggesting a robust alternative across diverse educational contexts. Based on the best prompting strategy, we also presented a lightweight UI that supports instructors in automatically classifying large question banks; a usability study indicated low workload and high usability.

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

Domain-Guided Prompting of the Segment Anything Model for Seismic Interpretation: The Role of Attributes, Visualization, and Hybrid Prompts

The advent of large pretrained foundation models for computer vision has significantly improved the efficiency of visual data interpretation. The Segment Anything Model (SAM), in particular, offers powerful zero shot segmentation capabilities through prompt based interaction, thus making it a promising tool for seismic interpretation. However, most existing applications of SAM rely on fine tuning for specific geological targets, which requires extensive labeled data, incurs high computational cost, and often compromises the model's generalization capability. In this study, we introduce a principled framework for zero shot adaptation of foundation models to seismic data. The framework is built on two key components: (1) aligning seismic attributes and visualization choices (e.g., colormaps) with the geological target of interest, and (2) employing a hybrid prompting strategy that combines sparse user defined point prompts with dense mask prompts derived from SAM's internal feature activations. We systematically evaluate this framework across multiple geological targets, datasets, prompt configurations, and seismic attribute representations. Our results demonstrate that geologic target aware selection of seismic attributes and colormaps, combined with hybrid prompting, enhances the separability of geological features and improves boundary delineation and segmentation accuracy relative to point based prompting alone. Our findings show that, when these components are jointly applied, SAM can achieve competitive segmentation performance in a fully zero shot setting, thereby eliminating the need to retrain SAM for each geologic feature. This work establishes a practical and scalable pathway to leverage foundation models in seismic interpretation, reducing reliance on labeled data while preserving model generality.

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

BioDivergence: A Benchmark and Evaluation Framework for Hidden Contextual Contradictions in Biomedical Abstracts

Biomedical findings often seem to conflict across studies, but many of these differences are context-dependent rather than true contradictions. Variations in cohort, geography, assay protocol, disease subtype, and clinical setting can make both claims locally valid. Existing NLI and scientific claim-verification benchmarks reduce such cases to entailment, contradiction, or neutral, failing to capture the contextual structure behind divergence. To address this, we introduce BioDivergence, an evaluation framework with a six-class conflict taxonomy, a 13-axis divergence ontology, and four structured outputs per claim pair: conflict type, divergence axes, dominant confounder, and reconciliation explanation. We release BioDivergence-Silver-v1.0, an article-disjoint silver benchmark of 11,865 claim pairs across five biomedical domains, alongside a legacy deduplicated variant for comparison. Results show notable ranking differences between the two variants, with the fine-tuned reference model dropping about 12 points under the article-disjoint setting, while Mistral-7B-Instruct-v0.3 achieves 0.5523 accuracy and 0.3894 contextual-F1 on the 842-example primary test set. BioDivergence offers a more faithful way to distinguish contextual divergence from direct contradiction and to separate article-level memorization from genuine task learning.

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

An Empirical Investigation of Pre-Trained Deep Learning Model Reuse in the Scientific Process

arXiv:2603.13584v2 Announce Type: replace-cross Abstract: Deep learning has achieved recognition for its impact within natural sciences, yet the prohibitive financial and technical cost of training models from scratch inhibit adoption. Following software engineering community guidance, natural scientists are reusing pre-trained deep learning models (PTMs) to amortize these costs. While prior works recommend PTM reuse patterns, we present the first empirical study of PTM reuse patterns in the natural sciences, quantifying the utilization and impact of PTM reuse within the scientific process across 17,718 peer reviewed, open access papers. Our results show that "Biochemistry, Genetics and Molecular Biology" has outpaced other natural scientific fields in PTM reuse, "adaptation" reuse is the most prevalent PTM reuse pattern identified across all natural science fields, and the "testing" stage of the scientific process has been most impacted by PTM integration.

08.
arXiv (CS.CV) 2026-06-15

SA4Depth: Consistent Pose-Depth Scale Alignment for Self-Supervised Monocular Depth Estimation

Self-supervised depth estimation from monocular sequences relies on the joint learning of a depth and a pose network. Despite abundant research done to improve the depth network, efforts on the pose remain limited. In this context, even when depth is estimated up to scale, we highlight the importance of the alignment between the scene scales estimated by the pose and depth nets. Then, we introduce SA4Depth, an approach to improve this alignment and boost the depth predictions while keeping the inference time unchanged. Our proposed method uses the depth estimated during training to reproject learnable visual features across consecutive frames and refine the pose estimates by reducing feature alignment residuals. With our method, the estimated scene scales by the separate depth and pose networks are aligned, and the prediction scale consistency is improved across different sequences. Our differentiable refinement integrates seamlessly into existing self-supervised pipelines and substantially improves their depth estimates. We demonstrate this with extensive experiments both outdoors and indoors on KITTI, Cityscapes, and NYUv2. Additionally, results on KITTI Odometry confirm the effectiveness of our pose refinement. Our code is available at https://github.com/Runningchauncey/SA4Depth .

10.
arXiv (CS.LG) 2026-06-11

Efficient Multinomial Logistic Bandit via Frequent Directions

arXiv:2606.11968v1 Announce Type: new Abstract: This paper studies efficient online algorithms for multinomial logistic bandits (MLogB), where the feedback distribution over $K+1$ outcomes follows a multinomial logistic model of $d$-dimensional action vectors. A representative UCB-type algorithm, OFUL-MLogB, achieves a regret bound of $\tilde{\mathcal{O}}(Kd\sqrt{T})$, but still requires $\mathcal{O}(K^3d^3)$ time and $\mathcal{O}(K^2d^2)$ space per round due to parameter estimation and optimistic reward construction, which is prohibitive in high-dimensional settings. To address this limitation, we propose EOFD-MLogB, which integrates frequent directions matrix sketching into OFUL-MLogB. By maintaining a low-rank SVD sketch of the accumulated Hessian, constrained online Newton updates in parameter estimation and $Kd \times K$ spectral-norm computations in the reward bonus are reduced to one-dimensional root-finding tasks and $K \times K$ eigenvalue computations, respectively. This yields dominant per-round time complexity $\mathcal{O}(Kd(m+K)^2)$ and space complexity $\mathcal{O}(Kd(m+K))$, where $m \ll d$ is the sketch size. We further prove a regret bound of $\tilde{\mathcal{O}}(\Delta_T(Kd\ln\Delta_T+m)\sqrt{T})$, where the sketching error factor $\Delta_T$ is controlled by the $m$-truncated spectral tail of the Hessian. Thus, when the Hessian is approximately low-rank, the regret is close to that of OFUL-MLogB. Experiments validate the computational efficiency and competitive performance.

11.
arXiv (CS.AI) 2026-06-19

GLARE: A Natural Language Interface for Querying Global Explanations

arXiv:2606.19735v1 Announce Type: new Abstract: While global explanations are crucial for understanding vision models across datasets, classes, and decision contexts, their complex and monolithic nature often hinders practical exploration. Because users typically seek targeted answers to specific questions rather than static artifacts, we present an LLM-based interactive interface that provides natural language access to global explanations for black-box image classifiers. The system's core LLM acts as a mediator, translating natural language questions into structured SQL queries over local explanation data. This enables flexible aggregation without exposing users to low-level representations. For each query, the interface outputs statistics-augmented natural language responses, supporting local explanations, and intent-aligned visualizations. We evaluate the system on intent interpretation, query mapping accuracy, generalization to novel queries and datasets, and robustness to linguistic errors. Our results demonstrate that LLM-mediated querying substantially improves the accessibility and usability of global explanations for human-centered XAI.

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

The Scaffold Effect: How Prompt Framing Drives Apparent Multimodal Gains in Clinical VLM Evaluation

arXiv:2603.28387v2 Announce Type: replace Abstract: Trustworthy clinical AI requires that performance gains reflect genuine evidence integration rather than surface-level artifacts. We evaluate 12 open-weight vision-language models (VLMs) on binary classification across two clinical neuroimaging cohorts, \textsc{FOR2107} (affective disorders) and \textsc{OASIS-3} (cognitive decline). Both datasets come with structural MRI data that carries no reliable individual-level diagnostic signal. Under these conditions, smaller VLMs exhibit gains of up to 58\% F1 upon introduction of neuroimaging context, with distilled models becoming competitive with counterparts an order of magnitude larger. A contrastive confidence analysis reveals that merely mentioning MRI availability in the task prompt accounts for 70-80\% of this shift, independent of whether imaging data is present, a domain-specific instance of modality collapse we term the scaffold effect. Expert evaluation reveals fabrication of neuroimaging-grounded justifications across all conditions, and preference alignment, while eliminating MRI-referencing behavior, collapses both conditions toward random baseline. Our findings demonstrate that surface evaluations are inadequate indicators of multimodal reasoning, with direct implications for the deployment of VLMs in clinical settings.

13.
arXiv (CS.LG) 2026-06-15

Traditional machine learning vs. deep learning from dynamic graph representations of proteins' 3D folds in the task of protein structure classification

arXiv:2605.29228v2 Announce Type: replace Abstract: Protein structure classification (PSC) uses supervised learning to predict a protein's CATH/SCOP(e) class from the protein's sequence or 3D structural feature(s). We already modeled 3D structures as (static) protein structure networks (PSNs), demonstrating the competitiveness of PSN-based features to sequence or direct (i.e. non-network) 3D structural features in the PSC task. More recently, we demonstrated the power of features extracted from dynamic PSNs over features extracted from static PSNs (and thus by transitivity over sequence and direct 3D structural features) in the same task. That dynamic PSN approach used traditional machine learning (ML), combining manual (pre-engineered) features with an off-the-shelf classifier. Here, we evaluate whether automatic deep learning (DL) from the dynamic PSNs yields improvements. Our evaluation on 72 datasets spanning ~44,000 CATH- or SCOPe-labeled dynamic PSNs reveals that in terms of PSC accuracy, traditional ML and DL are (close to) tied for a large majority of the datasets, while DL is on average 10+ times slower. We are the first to evaluate traditional ML vs. DL in the dynamic PSN-based PSC task.

14.
arXiv (CS.LG) 2026-06-11

Seeing Below the Limit of Detection: A Censored-Poisson Bayesian Latent-Growth Change-Point Detector (the Span Detector) for Serial ctDNA in HR+/HER2- Metastatic Breast Cancer

arXiv:2606.11876v1 Announce Type: cross Abstract: Circulating-tumour DNA (ctDNA) carries evidence of drug resistance months before imaging shows it, but the earliest evidence lives below the assay's limit of detection (LoD): a nascent subclone is detected only intermittently, producing a flickering sequence of faint detects and non-detects. Commercial liquid biopsies treat each draw as an independent snapshot and a non-detect as nothing. We argue a non-detect is a left-censored observation, and the pattern of non-detects and faint detects over time carries actionable evidence of growth before any single value is trustworthy. We introduce Span, a censored-Poisson Bayesian latent-growth change-point detector that models the binary detection process, accumulates a sequential generalised-likelihood-ratio statistic for an upward change-point in the per-variant detection rate, and raises a competing-risks alarm with calibrated false-alarm control. Span has no learned weights, so there is nothing to overfit. On a synthetic cohort of HR+/HER2- metastatic breast cancer on first-line CDK4/6-inhibitor plus endocrine therapy, at a matched 10% false-alarm rate, Span roughly doubles the fraction of impending progressions caught three months ahead (indolent regime: 25% vs 11% for the snapshot), with a falsifiable dose-response: large for indolent emergence, vanishing for fast emergence. A value-trajectory baseline performs identically to the snapshot, isolating the gain to the censored detection model. The survival backbone matches a Cox baseline on real breast-cancer data (GBSG-2, n=686; C-index 0.67 vs 0.68), and on a real longitudinal cohort with clean biomarkers (PBC2, n=312) the same pipeline correctly declines to win, a falsifiable boundary test confirming the mechanism is regime-specific. All ctDNA trajectories are synthetic.

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

Explaining Attention with Program Synthesis

arXiv:2606.19317v1 Announce Type: cross Abstract: A longstanding goal of research on interpretable deep learning is to replace opaque neural computations with human-meaningful symbolic descriptions. In this paper, we propose an approach for approximating the behavior of components of deep networks with executable programs. We focus on attention heads in transformer language models. For a given head, we first compute its associated attention matrices on a collection of randomly selected training examples. Next, we prompt a pre-trained language model with a summary of these matrices, and instruct it to generate a set of Python programs that can reproduce the associated attention patterns given only text from the input sentence. Finally, we re-rank programs according to how well our final set of programs predict behavior on held-out inputs. We demonstrate that a set of fewer than 1,000 such generated programs can reproduce the attention patterns of heads in GPT-2, TinyLlama-1.1B, and Llama-3B, achieving an average Intersection-over-Union similarity above 75% on TinyStories. Moreover, the best-fit programs can replace neural attention heads without substantially affecting model behavior: replacing 25% of attention heads with programmatic surrogates across the three models incurs only a 16% average perplexity increase, while maintaining performance on a variety of downstream question answering benchmarks. This work contributes a scalable pipeline for reverse-engineering attention heads in transformer models using human-readable, executable code, advancing a path toward symbolic transparency in neural models.

16.
bioRxiv (Bioinfo) 2026-06-21

Expanding the GUSome: Structure-guided identification and characterization of gut microbial β-glucuronidases

The gut microbiome-encoded {beta}-glucuronidase (GUS) enzymes have a significant effect on human physiology through their deglucuronidation activity on endogenous and exogenous glucuronides. GUS activity also significantly influences the pharmacokinetics, efficacy and toxicity of various drugs including chemotherapeutic drugs. Given their crucial role in drug metabolism, GUS enzymes have emerged as promising targets for therapeutic intervention. Here, we have identified and characterized 79 unique GUS enzymes through a structure-guided approach. Structural modelling of these GUS enzymes revealed a conserved core and active-site residues with significant variations in the number and nature of the C-terminal domains. A new classification system based on the number and type of additional C-terminal domains is presented for the GUS proteins. Further, GUS enzymes have been categorized into different loop categories linked to their substrate preferences. The relationship between domain architecture and loop-type is explored by sequence similarity network analysis. We could successfully express, purify and validate GUS processing capability of a panel of identified GUS proteins. The nature of oligomer organization has been deciphered by SEC and DLS studies. Further, we have identified additional GUS enzymes capable of processing SN-38G, glucuronidated form of anticancer drug, irinotecan. These newly identified GUS enzymes will offer valuable insights into gut microbial GUS diversity and their role in understanding the population-specific drug-induced adverse effects on human health.

17.
arXiv (CS.LG) 2026-06-12

Physics-Informed Neural Networks and Radial Basis Functions for PDEs with Dirac Delta Sources

arXiv:2606.12735v1 Announce Type: new Abstract: Physics-Informed Neural Networks (PINNs) are a machine learning method for solving forward and inverse Partial Differential Equations (PDEs). When applied to PDEs with Dirac delta functions in the forcing terms, boundary conditions, or initial conditions, PINNs require approximating them with smooth surrogate functions, a practice that can introduce significant modeling errors. In this work, we exploit the interpretation of PINNs as Residual Least Squares (RLS) methods and show that this perspective enables direct treatment of Dirac delta terms by integrating the weak-form equation. Among RLS formulations other than PINN, we focus on the Radial Basis Function (RBF) expansion (also known as a single-layer RBF Network). We show that while integrating out the Dirac delta in PINNs causes residuals to fail to converge to zero, RBF-RLS consistently provides good forward and inverse solutions to transport problems. We explain this finding using the Neural Tangent Kernel (NTK) theory. We test both approaches on linear PDEs that represent groundwater flow and transport in porous media and rivers. We solve inverse problems to fit synthetic data, noisy synthetic data, and real-world measurements.

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

CogniFold: Always-On Proactive Memory via Cognitive Folding

Existing agent memory remains predominantly reactive and retrieval-based, lacking the capacity to autonomously organize experience into persistent cognitive structure. Toward genuinely autonomous agents, we introduce CogniFold, a brain-inspired "always-on" agent memory designed for the next generation of proactive assistants. CogniFold continuously folds fragmented event streams into self-emerging cognitive structures, bootstrapping progressively higher-level cognition from incoming events and accumulated knowledge. We ground this by extending Complementary Learning Systems (CLS) theory from two layers (hippocampus, neocortex) to three, adding a prefrontal intent layer. Emulating the prefrontal cortex as the locus of intentional control and decision-making, CogniFold achieves this through graph-topology self-organization: cognitive structures proactively assemble under the stream, merge when semantically similar, decay when stale, relink through associative recall, and surface intents when concept-cluster density crosses a threshold. We evaluate structural formation using CogEval-Bench, demonstrating that CogniFold uniquely produces memory structures that match cognitive expectations and concept emergence. Furthermore, across eight downstream benchmarks – two probing long-term conversational memory (LoCoMo, LongMemEval) and six spanning other cognitive domains – we validate that CogniFold simultaneously performs robustly on conventional memory tasks. Our code is available at https://github.com/OpenNorve/CogniFold.

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

MOSAIC: Modality-Specific Adaptation for Incremental Continual Learning in Parkinson's Disease Gait Assessment

arXiv:2606.13258v1 Announce Type: new Abstract: Gait-based Parkinson's disease assessment increasingly relies on heterogeneous sensors, but clinical systems rarely collect all modalities simultaneously. New sensors may arrive through device upgrades, protocol changes, or multi-center deployment, while historical patient data are often unavailable because of privacy and storage constraints. This modality-incremental setting faces three challenges: unreliable cross-modal distillation, modality-specific statistical shifts, and reduced plasticity after preservation. We propose MOSAIC, a compact continual learning framework. First, we identify the Toxic Teacher phenomenon and introduce Modality-Specific Warm-Up to stabilize newly learned modality representations before distillation. Second, we propose a statistics-decoupled MSBN architecture that isolates sensor statistics while maintaining a shared semantic backbone. Third, we design a curriculum-guided repulsive objective for Plasticity Recovery, preserving legacy knowledge while recovering modality-specific capacity. Experiments on three multimodal Parkinson's gait datasets show that MOSAIC improves final performance and mitigates forgetting. Project code is available at: https://github.com/minlinzeng/MOSAIC_Modality-Specific-Adaptation-for-Incremental-Continual-Learning-in-PD-Gait-Assessment.git

20.
arXiv (CS.CV) 2026-06-18

Geometry-Aware Dataset Condensation for Diffusion Model Training

Dataset condensation aims to construct compact datasets from real data via synthesis or selection. However, existing approaches are ill-suited for diffusion model training: synthetic data generation often yields low-fidelity samples unsuitable for authentic modeling, while real subset selection typically fails to preserve the distributional geometry required by diffusion likelihood objectives. To address this, we propose to reformulate real subset selection as a geometry-aware distribution alignment problem. By incorporating one-sided partial optimal transport, our method selectively aligns a compact subset with the full data distribution while allowing unmatched mass in low-density regions, ensuring the preserved geometric structure necessary for effective diffusion model training. To further ensure distributional fidelity, we complement geometric alignment with lightweight feature-statistics and semantic consistency regularization. An efficient two-stage discrete optimization strategy is proposed to achieve this alignment objective. Extensive experiments across diffusion variants, subset sizes, image resolutions, and training rounds show that our method achieves superior fidelity and distributional coverage in diffusion model training. Codes are available at https://github.com/2018cx/GADC.

21.
bioRxiv (Bioinfo) 2026-06-11

DivQuant: Estimation of Species Richness and Entropy from Small Samples

Estimating diversity properties of discrete distributions from a small observed sample is a fundamental problem in algorithmic statistics that has applications in many fields, in particular bioinformatics, but also in ecology or linguistics. The two most common diversity measures are the number of distinct elements in a multiset, also referred to as species richness in ecology or alpha diversity in microbial analysis, and the Shannon entropy, also referred to as evenness. Estimating these properties from a small sample is particularly challenging for distributions with many rare elements. Thus, many estimators have been proposed in the past that, in practice, work well for different types of distributions. We present DivQuant, an optimization-based, extrapolating richness and entropy estimator with three contributions. First, we formulate the upsampling problem as a convex quadratic program with a Neyman {chi}2 objective. Unlike the linear program of its predecessor RichnEst, DivQuant admits confidence intervals via {chi}2 test inversion that are empirically well-calibrated. Second, we replace RichnEst's fixed-threshold fingerprint truncation with the rare/abundant fingerprint split of Valiant and Valiant, which strongly reduces problem size and preserves enough degrees of freedom for the confidence-interval program to remain valid and feasible. Third, we plug the optimal population fingerprint returned by the program into Shannon's entropy formula to obtain an entropy estimate. DivQuant attains close-to-nominal 95% confidence intervals in essentially all tested regimes, including six simulated distribution families, Tara Oceans microbiome data, and 10X Genomics scRNA-seq data, while competing state-of-the-art methods (RichnEst, iNext, PreSeq) miss the true richness in up to 80% of instances, well above the nominal 5%. In addition, DivQuant outperforms classical asymptotic entropy estimators (Miller-Madow, CAE) and the extrapolating iNext estimator. Running times remain competitive, with DivQuant typically completing in seconds. DivQuant is available as a command-line tool at https://gitlab.com/rahmannlab/divquant.

22.
arXiv (CS.AI) 2026-06-17

CausalT5k: Diagnosing Refusal and Failure Modes in Trustworthy Causal Reasoning Across Causal Rungs

arXiv:2602.08939v2 Announce Type: replace Abstract: Large language models increasingly produce fluent causal explanations, yet they often fail in ways aggregate accuracy cannot diagnose: confusing association with intervention, abandoning correct judgments under pressure, over-refusing valid claims, or answering when evidence is underdetermined. We introduce CTK, a diagnostic benchmark of 5,147 cases and growing, across 10 domains and all three levels of Pearl's Ladder of Causation. Unlike benchmarks that only score correctness, CTK reveals why a model failed by annotating causal rung, trap type, pressure sensitivity, refusal quality, and Utility-Safety tradeoffs. Its Sheep/Wolf taxonomy separates valid causal designs from inferential traps; paired neutral/pressure variants measure sycophantic drift through Bad Flip Rate; and Wise Refusal fields test whether a model identifies the missing information needed before endorsing a claim. CTK exposes failure modes hidden by aggregate accuracy: the Skepticism Trap, Rung Collapse under scaling, pressure-induced drift, Detection-Correction gaps, and counterfactual error modes. Rather than prescribing a correction method, it provides the diagnostic substrate for studying causal-reasoning failure profiles.

23.
bioRxiv (Bioinfo) 2026-06-10

APOSM: Pairwise preference learning improves generative small-molecule design

Small-molecule lead refinement is constrained by the cost of synthesizing and assaying candidates, making the surrogate models that prioritize compounds for experimental testing central to the design process. The reliability of such surrogates is limited by the noise and sparsity of screening measurements. We show that training the surrogate on pairwise comparisons between candidate molecules, rather than on absolute predicted scores, yields a substantially more reliable signal for active candidate selection in this regime. We develop APOSM, an active-learning algorithm that combines a fragment-based generator, a pairwise message-passing graph neural network surrogate, and probabilistic ranking inside a batched acquisition loop. On the Practical Molecular Optimization benchmark and a GPCR ligand rediscovery task, APOSM improves target attainment and sampling efficiency over unguided fragment-based optimization, the Graph-GA genetic algorithm, and a pointwise-regression ablation, with the largest gains on tasks where absolute scores are hardest to calibrate.

24.
arXiv (CS.AI) 2026-06-16

PH-KAN: Port-Hamiltonian Kolmogorov-Arnold Network

arXiv:2606.14708v1 Announce Type: cross Abstract: Data-driven machine learning approaches have become increasingly attractive for nonlinear system identification, but standard models often fail to preserve the underlying physical structure and remain difficult to interpret, especially when no analytical model is available. In this context, port-Hamiltonian (pH) models provide a natural physics-informed representation. However, when these models are parameterized with standard multilayer perceptrons (MLPs), the learned constitutive components often remain poorly interpretable. In this paper, we propose a structure-preserving identification framework for nonlinear port-Hamiltonian systems based on Kolmogorov-Arnold Networks (KANs). The proposed PH-KAN model parameterizes the interconnection matrix, dissipation matrix, Hamiltonian, and input mapping using dedicated KAN blocks, while enforcing the port-Hamiltonian constraints by construction. This yields constitutive representations in which the nonlinear functions defining the identified pH components can be explicitly inspected, leading to a more interpretable model than with standard MLP-based parameterizations.