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01.
arXiv (CS.CV) 2026-06-16

DC-Motion: Decoupling Semantics and Details via Discrete-Continuous Tokens for Human Motion Generation

Text-to-motion generation requires synthesizing physically realistic dynamics that strictly follow complex and long-horizon textual instructions. Existing approaches rely on homogeneous representation spaces that may fail to capture the hierarchical nature of human motion, with diffusion models struggling at compositional semantic reasoning and AR models sacrificing fine-grained physical details due to quantization. To solve it, we introduce DC-Motion, a factorized generative framework designed to explicitly decouple semantics and details via discrete-continuous tokens. A Discrete-Continuous VAE (DC-VAE) first decomposes motion into discrete tokens for semantics and continuous residuals for fine-grained dynamics. Then, a masked AR model predicts the discrete structure from text, and a lightweight residual diffusion model recovers the continuous physical details. Extensive experiments demonstrate that DC-Motion effectively improves the capability to follow complex instructions. By effectively balancing semantic controllability and physical realism, our approach offers a highly adaptable modeling paradigm for human motion generation. On both HumanML3D and KIT-ML datasets, DC-Motion achieves state-of-the-art performance, delivering the best FID for motion realism and R-precision for text alignment.

02.
arXiv (CS.CV) 2026-06-15

BoRAD: Bootstrap your Own Representations for Multi-class Anomaly Detection

Reconstruction-based anomaly detection is attractive for industrial inspection, but scaling it from category-specific training to a one-for-all setting is challenging. A single model must reconstruct diverse normal appearances without copying abnormal details, which exposes two coupled failure modes: identical shortcut, where anomalies pass through the reconstruction path, and mis-reconstruction, where normal categories are confused with one another. We propose BoRAD, a label-free training framework that treats this as a representation-capacity allocation problem. BoRAD uses a shared learnable prototype bank to impose two complementary regularizers: spatial prototype alignment contracts local within-prototype variation to suppress anomaly copying, while prototype-relative global alignment preserves between-prototype structure and improves sensitivity to abnormal angular deviations. The prototype bank and prediction heads are used only during training; inference remains a standard teacher-student feature discrepancy pass, with no class labels, negative pairs, memory retrieval, or prototype lookup. BoRAD achieves competitive one-for-all anomaly detection performance, including 86.2\% mAD on MVTec AD, 80.7\% mAD on VisA and 73.1\% mAD on Real-IAD. Diagnostic analyses further show reduced anomaly leakage, improved normal-category separability, and stronger anomaly-normal score separation.

03.
arXiv (quant-ph) 2026-06-17

Probes of chaos over the Clifford group and approach to Haar values

arXiv:2603.29695v3 Announce Type: replace Abstract: Chaotic behavior of quantum systems can be characterized by the adherence of the expectation values of given probes to moments of the Haar distribution. In this work, we analyze the behavior of several probes of chaos using a technique known as Isospectral Twirling [1]. This consists in fixing the spectrum of the Hamiltonian and picking its eigenvectors at random. Here, we study the transition from stabilizer bases to random bases according to the Haar measure by T-doped random quantum circuits. We then compute the average value of the probes over ensembles of random spectra from Random Matrix Theory, the Gaussian Diagonal Ensemble and the Gaussian Unitary Ensemble, associated with non-chaotic and chaotic behavior respectively. We also study the behavior of such probes over the Toric Code Hamiltonian.

04.
arXiv (CS.AI) 2026-06-17

Ternary Mamba: Grouped Quantization-Aware Training of W1.58A16 State Space Models

arXiv:2606.18114v1 Announce Type: cross Abstract: State Space Models (SSMs) such as Mamba-2 offer linear-time inference but their memory footprint limits edge deployment. Prior ternary SSM work (Slender-Mamba) trains from scratch on 150B tokens; we show a pretrained checkpoint suffices, reducing the marginal token budget by 1,000x. Using grouped quantization-aware training (QAT) with knowledge distillation from a frozen FP16 teacher, we compress Mamba-2 1.3B to 3.61x (2,687 to 744 MB) and achieve 48.1% zero-shot accuracy (7-task average) in just 102M tokens (4 GPU-hours, single H100) – approaching Bi-Mamba's 48.4% (within +/-0.9pp CI). This QAT-from-pretrained setting reveals zero-ratio collapse, a novel instability caused by learnable quantization scales that does not arise in from-scratch training. We further show that post-hoc correction strategies effective for Transformers fail for SSMs due to error accumulation through the recurrence. These results demonstrate that ternary SSMs do not require expensive from-scratch training: QAT from pretrained checkpoints with KD is a data-efficient alternative.

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

VibeThinker-3B: Exploring the Frontier of Verifiable Reasoning in Small Language Models

This technical report introduces VibeThinker-3B, a compact dense model with 3B parameters developed to investigate how far verifiable reasoning can be pushed within a strictly small-model regime. Building upon the Spectrum-to-Signal post-training paradigm, we systematically enhance the model through an optimized pipeline that includes curriculum-based supervised fine-tuning, multi-domain reinforcement learning, and offline self-distillation. Experimental evaluations demonstrate that VibeThinker-3B achieves frontier-level performance on highly demanding verifiable tasks. Specifically, it attains a score of 94.3 on AIME26 (improving to 97.1 with claim-level test-time scaling), an 80.2 Pass@1 on LiveCodeBench v6, and exhibits strong out-of-distribution generalization with a 96.1\% acceptance rate on recent unseen LeetCode contests. This effectively places it in the performance band of first-tier reasoning systems, matching or exceeding flagship models that are orders of magnitude larger, such as DeepSeek V3.2, GLM-5, and Gemini 3 Pro. Furthermore, a score of 93.4 on IFEval confirms that this extreme reasoning enhancement does not compromise strict instruction controllability. Extending our previous 1.5B work, these findings motivate the Parametric Compression-Coverage Hypothesis, which views verifiable reasoning as compressible into compact reasoning cores, while open-domain knowledge and general-purpose competence require broad parameter coverage over facts, concepts, and long-tail scenarios. This perspective suggests that compact models are not merely deployment-efficient substitutes, but a complementary path toward frontier-level performance in parameter-dense capability regimes.

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

PCS-UQ: Uncertainty Quantification via the Predictability-Computability-Stability Framework

arXiv:2505.08784v2 Announce Type: replace-cross Abstract: As machine learning (ML) enters high-stakes domains, trustworthy uncertainty quantification (UQ) is essential for safety. In this paper we introduce PCS-UQ, a framework based on the Predictability, Computability, and Stability (PCS) principles for veridical data science. Starting with a candidate set of models or algorithms, PCS-UQ integrates a rigorous prediction-check to screen out unsuitable models in the set and utilizes bootstrap samples, in order to capture both inter-sample variability and algorithmic instability for the prediction-checked algorithms. We then introduce a novel multiplicative calibration scheme to enhance local adaptivity, which basically corresponds to a new score in conformal prediction. Moreover, we produce a compilation of 17 real-world regression datasets with manually-constructed subgroups. On this benchmark, PCS-UQ maintains the target coverage while outperforming or matching conformal methods equipped with oracle-selected algorithms in interval width. PCS-UQ achieves consistent subgroup coverage, outperforming these oracle-selected conformal methods. Notably, PCS-UQ stands out in achieving both competitive interval widths and consistent subgroup coverage.Across 6 classification datasets, PCS-UQ reduces prediction set sizes by 20\%. To scale the framework for deep learning, we propose computationally efficient variants that bypass expensive retraining. On three computer vision benchmarks, these variants reduce prediction set sizes by 20\% over conformal baselines. Finally, we provide theoretical proof that a modified PCS-UQ algorithm preserves valid coverage under exchangeability as a form of split conformal inference.

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

AI for Social Good: An Investigation of the Causal Relationship Between Environmental Regulations and Their Effects on Air Pollution in London, UK

arXiv:2606.15257v1 Announce Type: new Abstract: Air pollution regulation is central to urban public health governance, but estimating its effects is difficult because policies are implemented non-randomly and pollution trajectories are shaped by meteorology, socioeconomic change, temporal trends, and overlapping interventions. This study develops an uncertainty-aware Bayesian deep learning framework to estimate the aggregate effect of air pollution regulations on PM$_{2.5}$ concentrations in London from 2010 to 2020. The framework integrates daily PM$_{2.5}$ observations from Inner London monitoring stations, meteorological covariates, annual socioeconomic indicators, month-of-year and day-of-week indicators, and daily regulation status data for 32 policy measures. A Bayesian LSTM captures temporal dependencies in environmental and socioeconomic covariates, Bayesian embedding layers represent temporal and regulation status inputs, and a regulation status prediction branch supports propensity score-based adjustment for non-random policy implementation. Regulatory effects are estimated by comparing observed PM$_{2.5}$ concentrations with counterfactual predictions under a hypothetical no-regulation scenario, with uncertainty summarized across repeated Bayesian training runs and bootstrap resampling. Results show that London's regulations were associated with an average PM$_{2.5}$ reduction of 1.88 $\mu$g/m$^3$, a relative reduction of 12.35%, with a 95% confidence interval of 1.64-2.12 $\mu$g/m$^3$. Estimated effects were limited before 2013, became clearer from 2013 to 2017, and were strongest in 2018 and 2019. The findings suggest that sustained and cumulative regulatory interventions contributed to measurable improvements in London's air quality. This study demonstrates how uncertainty-aware causal AI can support environmental accountability, public health protection, and evidence-based governance for environmental decision-making.

08.
arXiv (quant-ph) 2026-06-11

Nonlocal continuous-variable gates by amplified optical connections

arXiv:2603.12866v2 Announce Type: replace Abstract: Nonlocal quantum gates, coupling quantum systems located at a distance, are crucial for distributed quantum computing. To this aim, high-capacity optical noiseless connections between different processing units are essential for transmitting large amounts of information per mode. Simultaneously, optical quantum computing offers future high-speed multimode quantum processors. We propose a library of feasible protocols to implement a necessary nonlocal continuous-variable (CV) quantum nondemolition (QND) gate between two distant users sharing a quantum channel and exploiting classical communication. The users are endowed with a newly achieved high-fidelity and large-bandwith element - single-pass phase-sensitive optical parametric amplifier (OPA), that allows for both online squeezing and channel-loss compensation. The use of OPAs enhances quality of the resulting gate in terms of both excess noise and entangling capability. The proposed schemes are also applicable to CV cluster state fusion, providing a first step towards development of distributed CV measurement-based quantum computation.

09.
arXiv (CS.LG) 2026-06-17

A Generalized Sinkhorn Algorithm for Mean-Field Schrödinger Bridge

arXiv:2604.06531v3 Announce Type: replace-cross Abstract: The mean-field Schrödinger bridge (MFSB) problem concerns designing a minimum-effort controller that guides a diffusion process with nonlocal interaction to reach a given distribution from another by a fixed deadline. Unlike the standard Schrödinger bridge, the dynamical constraint for MFSB is the mean-field limit of a population of interacting agents with controls. It serves as a natural model for large-scale multi-agent systems. The MFSB is computationally challenging because the nonlocal interaction makes the problem nonconvex. We propose a generalization of the Hopf-Cole transform for MFSB and, building on it, design a Sinkhorn-type recursive algorithm to solve the associated system of integro-PDEs. Under mild assumptions on the interaction potential, we discuss convergence guarantees for the proposed algorithm. We present numerical examples with repulsive and attractive interactions to illustrate the theoretical contributions.

11.
medRxiv (Medicine) 2026-06-17

A non-invasive liquid biopsy resolves the diagnostic blind spot in chronic kidney disease

Chronic kidney disease is a major global health burden, and its early detection is critical for delaying progression to kidney failure using recently developed targeted therapies. However, current diagnostic screening relies heavily on blood markers that are confounded by muscle mass, and on urine tests that frequently miss structural damage occurring without protein leakage. This creates a critical diagnostic blind spot that hinders timely intervention. Here we show a non-invasive liquid biopsy platform that quantifies a specific protein marker, MUC1, on urinary extracellular vesicles to accurately assess renal parenchymal integrity. By bypassing the systemic metabolic noise of traditional blood tests, our assay provides a remarkably stable, person-specific functional signature. Following extensive validation across diverse cohorts, our longitudinal analysis demonstrated that the discrepancy between this novel urine-based readout and standard blood tests unmasks hidden renal vulnerability, successfully predicting rapid functional decline. By comprehensively evaluating both tubular and glomerular integrity from a single spot urine sample, these findings establish a completely non-invasive, highly scalable prescreening tool that resolves the diagnostic blind spot, enabling broader early detection strategies and ushering in a new era of proactive risk management.

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

Audited Conformal Prediction for Classification under Unknown Distribution Shift

arXiv:2606.14909v1 Announce Type: cross Abstract: We consider the problem of uncertainty quantification for a pretrained classification model deployed under unknown distribution shift. We propose Audited Conformal Prediction (ACP), a method that leverages a small labeled dataset from the target population to train an auxiliary audit model identifying inputs where the legacy model is likely to fail. By integrating the audit model's outputs into the conformal prediction framework, ACP produces prediction sets that guarantee marginal coverage while achieving substantially higher conditional coverage in practice than existing approaches. We develop and analyze two complementary integration strategies – one targeting marginal coverage with improved conditional performance, the other providing explicit group-conditional coverage guarantees – and establish theoretical guarantees for both. Experiments on synthetic and real-world datasets validate the method and illustrate trade-offs between prediction set size and conditional coverage.

13.
arXiv (quant-ph) 2026-06-12

Steady-State Noise Signatures of Lindbladian Exceptional Points

arXiv:2606.13377v1 Announce Type: new Abstract: Exceptional points (EPs) are non-Hermitian degeneracies at which two or more eigenvalues and their corresponding eigenvectors coalesce. In open quantum systems, exceptional points can arise in the Lindbladian governing the dissipative dynamics. Their signatures have so far been mainly identified in finite-time observables, such as transient currents, while steady-state average currents generally provide no direct evidence of the underlying exceptional-point structure. In this work, we demonstrate that signatures of Lindbladian EPs can nevertheless be accessed in the steady-state regime through current noise. We derive general expressions for current correlation functions within a Lindblad master-equation framework and show, in particular, how exceptional points affect their behaviour as a function of the time delay. We illustrate these results with the paradigmatic example of two interacting qubits coupled to two reservoirs, where the steady-state noise clearly distinguishes overdamped, underdamped, and critical regimes. Our results establish current correlation functions as a steady-state probe of Lindbladian EPs in open quantum systems.

14.
arXiv (CS.AI) 2026-06-19

FlowFake: Liquid Networks for Audio Deepfake Detection

arXiv:2606.19579v1 Announce Type: cross Abstract: Audio deepfakes generated by neural text-to-speech and voice-cloning systems threaten speaker verification and public discourse at scale. The core challenge is cross-dataset generalization: detectors trained on one synthesis pipeline collapse on unseen forgeries. We argue that this failure is primarily because of structural synthetic speech artifacts which are multi-timescale trajectory anomalies. Though every existing detector aggregates a fixed-window frame statistics, this misaligns the architecture with the signal. We propose FlowFake, a Liquid Time-Constant (LTC) architecture whose hidden state evolves via a learned ODE, with per-neuron adaptive time constants simultaneously resolving spectral (10ms) and prosodic (2s) cues. At only 34K parameters FlowFake achieves formal BIBO stability and O(dt^4) integration error. On a four-dataset cross domain benchmark (ASVspoof2019-LA, FakeOrReal, InTheWild, MLAAD), FlowFake reaches 75.29% on ASVspoof2019 trained only on FakeOrReal and 79.97% trained only on MLAAD. It outperforms RawGAT-ST and Whisper-DF on every evaluated pair and matching SSL Wav2vec2 (300x larger) at 0.01% of its parameter count. The source code is available on : https://github.com/GhostRider2023/FlowFake

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

Merged amplitude encoding for Chebyshev quantum Kolmogorov–Arnold networks: trading qubits for circuit executions

arXiv:2603.02818v3 Announce Type: replace Abstract: Quantum Kolmogorov–Arnold networks based on Chebyshev polynomials (CCQKAN) evaluate each edge activation function as a quantum inner product, creating a trade-off between qubit count and the number of circuit executions per forward pass. We introduce merged amplitude encoding, a technique that packs the element-wise products of all $n$ input-edge vectors for a given output node into a single amplitude state, reducing circuit executions by a factor of $n$ at a cost of only 1–2 additional qubits relative to the sequential baseline. The merged and original circuits compute the same mathematical quantity exactly; the open question is whether they remain equally trainable within a gradient-based optimization loop. We address this question through numerical experiments on 10 network configurations under ideal, finite-shot, and noisy simulation conditions, comparing original, parameter-transferred, and independently initialized merged circuits over 16 random seeds. Wilcoxon signed-rank tests show no significant difference between the independently initialized merged circuit and the original ($p > 0.05$ in 28 of 30 comparisons), while parameter transfer yields significantly lower loss under ideal conditions ($p < 0.001$ in 9 of 10 configurations). On 10-class digit classification with the $8\times8$ MNIST dataset using a one-vs-all strategy, original and merged circuits achieve comparable test accuracies of 53–78\% with no significant difference in any configuration. These results provide empirical evidence that merged amplitude encoding preserves trainability under the simulation conditions tested.

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

A Unified Latent Space Disentanglement VAE Framework with Robust Disentanglement Effectiveness Evaluation

arXiv:2603.11242v2 Announce Type: replace-cross Abstract: Evaluating and interpreting latent representations, such as variational autoencoders (VAEs), remains a significant challenge for diverse data types, especially when ground-truth generative factors are unknown. To address this, we unify several state-of-the-art disentangled VAE approaches for latent space disentanglement into one framework – bfVAE. To assess the effectiveness of a disentangled VAE model and enhance latent space interpretability, we propose Feature Variance Heterogeneity via Latent Traversal (FVH-LT) and Dirty Block Sparse Regression in Latent Space (DBSR-LS). To ensure robust interpretability of learned latent space, we develop a greedy alignment strategy (GAS) that mitigates label switching and aligns latent dimensions across runs to set the foundation of result aggregation. We also introduce a convenient scalar latent space separation index (LSSI) based on the GAS-aligned outputs of FVH-LT and DBSR-LS to summarize the overall latent structural separation without knowledge of the ground-truth generative factors. We compare bfVAE to five VAE models and validate the effectiveness FVH-LT, DBSR-LS, and LSSI in on seven tabular and image datasets. Under our examined experimental settings, bfVAE provides a more flexible disentanglement framework achieves more favorable overall trade-off between disentanglement and reconstruction than the benchmark VAE models; FVH-LT and DBSR-LS reliably uncover semantically meaningful and domain-relevant latent structures and generally yield consistent results; and LSSI makes an effective quantitative summary of latent structural separation.

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

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

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

18.
medRxiv (Medicine) 2026-06-18

Effectiveness and Safety of Bempedoic Acid Across Clinically Relevant Subgroups: Insights from the CLEAR Taiwan Study

Background Despite available lipid-lowering therapies (LLT), many patients fail to achieve low-density lipoprotein cholesterol (LDL-C) targets. This gap persists across clinically relevant subgroups. Bempedoic acid has demonstrated effective LDL-C lowering with a favorable safety profile in the CLEAR Taiwan study; however, its effects across subgroups in Asian populations remains limited. Methods The phase IV CLEAR Taiwan study (NCT06925100) enrolled patients with inadequately controlled hypercholesterolemia who received bempedoic acid for 12 weeks in addition to background LLT. This analysis evaluated changes in lipid parameters, high-sensitivity C-reactive protein (hsCRP), and safety outcomes in clinically relevant subgroups, including cardiovascular risk, diabetes, age, statin tolerance, and sex. Results A total of 180 patients were included. Bempedoic acid achieved significant LDL-C reductions in all subgroups. Numerically greater LDL-C reductions were observed in primary prevention, statin-intolerant, younger (< 65 years), and female patients, while comparable reductions were observed across diabetes status. Reductions in non-high-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B were consistent with LDL-C findings. Significant decreases in hsCRP were observed in all subgroups, with numerically greater reductions in patients aged < 65 years and those without diabetes. Bempedoic acid was well tolerated, with a low incidence of adverse events and no new safety signals identified. Changes in liver enzymes, renal function, and uric acid were minimal within subgroups. Conclusion Subgroup analyses from the CLEAR Taiwan study demonstrate consistent efficacy and safety of bempedoic acid across clinically relevant subgroups and support its use as a flexible option to address residual gaps in lipid management.

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

GAS-Leak-LLM: Genetic Algorithm-Based Suffix Optimization for Black-Box LLM Jailbreaking

arXiv:2606.15788v1 Announce Type: cross Abstract: Large Language Models (LLMs) constitute pivotal components within the AI-dominated information technology ecosystem. To mitigate risks associated with harmful or policy-violating outputs, commercial systems employ advanced alignment strategies and multi-layered content moderation mechanisms. Despite these safeguards, recent research has demonstrated that LLMs remain vulnerable to adversarial manipulation, particularly through jailbreaking and prompt injection techniques. In this work, we propose GAS-Leak-LLM a novel jailbreaking attack based on a genetic algorithm that systematically evolves adversarial suffix to bypass safety constraints. Operating in a strict black-box setting, our method requires no access to model parameters or internals, thereby reflecting realistic threat scenarios in deployed systems. Through the iterative application of selection, mutation, and crossover heuristics, the framework systematically explores the discrete prompt space to identify high-fitness adversarial suffixes. Empirical findings reveal critical shortcomings in existing safety enforcement mechanisms and confirm the effectiveness and practical viability of the proposed attack.

20.
arXiv (CS.CL) 2026-06-11

AI Coding Agents in Social Science: Methodologically Diverse, Empirically Consistent, Interpretively Vulnerable

The deployment of LLM-based agents in scientific analysis raises opposing concerns: that agents may reduce methodological diversity, or that they may amplify the analytic flexibility through which researchers reach motivated conclusions. We argue these worries target two empirically separable layers: a design layer of methodological choices, and a verdict layer in which a decision rule maps estimates to a substantive claim. We test both by running 20 independent executions of Claude Code and Codex on a prominent immigration and social-policy against a many-analysts human baseline. At the design layer, Codex matches human methodological diversity and Claude Code produces nearly three times as many specifications; both agents' effect estimates remain broadly aligned with the human consensus, and no agent model exactly matches any human model. A prompt-induced anti-immigration researcher prior reorganizes each agent's methodological decisions but, unlike for biased human analysts in the same data, does not shift aggregate estimates or final verdicts; nor do agents reroute along the methodological axes humans use to bias their estimates. At the verdict layer, an explicit confirmatory prompt flips Claude Code's verdicts from 10% to 90% support while leaving its coefficient distribution essentially unchanged, operating through rule omission rather than rule softening. AI agents can rival or exceed human methodological diversity at the design layer while remaining vulnerable at the verdict layer. In our setting, the locus of AI bias is not estimation but interpretation.

21.
bioRxiv (Bioinfo) 2026-06-11

PhyloZoo: a unified framework for phylogenetic network analysis in Python

Authors:

Reticulate evolutionary processes (events in which lineages merge, such as hybridization, recombination, and horizontal gene transfer) are widespread across nature but cannot be represented by phylogenetic trees alone. Phylogenetic networks have therefore become an important modelling tool, yet existing software is typically tied to specific inference paradigms and provides limited support for working with multiple network representations in a unified and programmable environment. PhyloZoo is an open-source Python framework that lowers the barrier to developing practical, easy-to-use software for phylogenetic network analysis. It provides data structures and algorithms covering the main representations used in the field, together with dedicated visualization tools and robust I/O for all major phylogenetic file formats. A particular emphasis lies on semi-directed phylogenetic networks, which explicitly represent root uncertainty and have so far received limited support in existing software. By offering a shared foundation for developing interoperable tools and a combinatorial layer that supports computational proofs and theoretical exploration, PhyloZoo enables reproducible workflows for applied, methodological, and theoretical studies of reticulate evolution. Availability and implementation: PhyloZoo is implemented in Python and installable from PyPI, with source code, documentation, and examples available at https://github.com/nholtgrefe/phylozoo.

22.
bioRxiv (Bioinfo) 2026-06-14

Systematic AI-Driven Drug Repurposing via Clinical Trial Data Mining: A Framework and Six Cross-Therapeutic Case Studies.

Authors:

Drug repurposing, the application of approved or shelved compounds to new therapeutic indications, offers a cost- and time-efficient alternative to de novo drug discovery. However, the systematic identification of repurposing candidates from the rapidly expanding body of clinical trial data remains a significant challenge. Here we present a publicly accessible AI-powered tool that mines the ClinicalTrials.gov registry to identify approved drugs with under-explored therapeutic potential in high-value disease areas. The tool integrates natural language processing, mechanism-of-action pathway analysis, and trial density scoring to surface candidates where biological plausibility is high and clinical trial coverage is sparse. We demonstrate the tool's utility across six cross-therapeutic case studies spanning oncology, cardiology, neurology, rare diseases, immunology, and infectious disease. Key findings include: the identification of Zonisamide as an under-explored combination candidate for obesity alongside GLP-1 receptor agonists; mechanistic validation of SGLT2 inhibitors in heart failure with preserved ejection fraction (HFpEF); and a novel cross-domain mapping of anti-TNF biologics to early-stage neurodegeneration via shared neuroinflammatory pathways. The tool is freely accessible and designed to lower the barrier for academic and industry researchers to systematically pursue repurposing opportunities.

23.
medRxiv (Medicine) 2026-06-11

Vascular Phenotyping in Parkinson's Disease: Diabetes Mellitus Operationalizes a Microvascular Metabolic Syndrome Cluster Across PPMI Diagnostic Cohorts

Background: Diabetes mellitus elevates Parkinson's disease (PD) risk, via hypothesized cerebrovascular mediation. Whether the diabetes/prediabetes vascular-risk phenotype concentrates in cardiometabolic risk or macrovascular events across prodromal and clinically diagnosed PD remains unresolved. Objectives: To quantify the vascular-risk burden associated with diabetes/prediabetes across the PPMI diagnostic cohorts to test whether this association differs by cohort. Methods: Cross-sectional analysis of 413 PPMI participants (76 healthy controls, 145 prodromal PD, 192 clinically diagnosed PD) examined diabetes/prediabetes (n = 73) and seven vascular risk factors. The Vascular Burden Score (0 to 7) was a priori partitioned into microvascular and macrovascular sub-scores. Modified Poisson regression estimated adjusted prevalence ratios (aPR), adjusted for age, sex, and body mass index. A cohort-by-diabetes interaction tested cross-cohort consistency. Sensitivity analyses incorporated nigral diffusion tensor imaging (PD-risk biomarker) and FreeSurfer white matter hypointensity volume (cerebrovascular marker). Results: Diabetes/prediabetes elevated Vascular Burden Score ({beta} = 0.53, 95% CI 0.29 to 0.77, p < 0.001) versus non-diabetic participants, with a non-significant cohort-by-diabetes interaction (F = 0.29, p = 0.747). Three microvascular factors survived false discovery rate correction: obesity (aPR 2.28), hypertension (aPR 1.60), and hyperlipidemia (aPR 1.45). Macrovascular events showed no diabetic amplification ({beta} = -0.06, p = 0.25). In the imaging-phenotyped subset, Vascular Burden Score components contributed classifier variance distinct from nigral microstructure. Conclusions: Diabetes/prediabetes operationalize a microvascular cluster stable across prodromal and idiopathic PD. Cardiometabolic phenotyping may complement established PD-risk biomarkers (dopamine transporter SPECT, nigral diffusion), pending longitudinal validation linking vascular phenotype to dopaminergic markers.

24.
arXiv (CS.LG) 2026-06-15

Minimum Distance Summaries for Robust Neural Posterior Estimation

arXiv:2602.09161v2 Announce Type: replace-cross Abstract: Simulation-based inference (SBI) enables amortized Bayesian inference by first training a neural posterior estimator (NPE) on prior-simulator pairs, typically through low-dimensional summary statistics, which can then be cheaply reused for fast inference by querying it on new test observations. Because NPE is estimated under the training data distribution, it is susceptible to misspecification when observations deviate from the training distribution. Many robust SBI approaches address this by modifying NPE training or introducing error models, coupling robustness to the inference network and compromising amortization and modularity. We introduce minimum-distance summaries, a plug-in robust NPE method that adapts queried test-time summaries independently of the pretrained NPE. Leveraging the maximum mean discrepancy (MMD) as a distance between observed data and a summary-conditional predictive distribution, the adapted summary inherits strong robustness properties from the MMD. We demonstrate that the algorithm can be implemented efficiently with random Fourier feature approximations, yielding a lightweight, model-free test-time adaptation procedure. We provide theoretical guarantees for the robustness of our algorithm and empirically evaluate it on a range of synthetic and real-world tasks, demonstrating substantial robustness gains with minimal additional overhead.

25.
arXiv (CS.CL) 2026-06-19

CzechDocs: A Multiway Parallel Dataset of Formatted Documents for Minority Languages in Czechia

We present CzechDocs, a multiway parallel dataset of formatted documents (HTML, DOCX, and PDF) covering Czech and minority languages used in Czechia-primarily Ukrainian and English, with smaller portions of Vietnamese, Russian and other languages. The dataset is designed to support the evaluation of machine translation systems that aim to preserve document formatting during translation. We provide a comparison of the most common approaches to format-preserving machine translation on a validation subset of the dataset. This validation split, together with the evaluation toolkit, is publicly released for further research. A held-out test split will be reserved for a future shared task focused on document-level translation with formatting preservation.