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01.
medRxiv (Medicine) 2026-06-17

Cardio Heart Connect: Protocol for a Randomized Trial of a Commercially Available mHealth Fitness Intervention for Cardiac Rehabilitation After Transcatheter Aortic Valve Replacement

Background: Despite ample evidence of the benefits of cardiac rehabilitation (CR), few transcatheter aortic valve replacement (TAVR) patients participate. Commercially available mobile health offers an opportunity to deliver activity-promotion content to populations that are challenged to participate in CR. This study aims to test the efficacy of clinically controlled, commercially available fitness programming for improving physical activity and cardiovascular health outcomes designed to be initiated while patients are on waitlists for traditional CR. Methods: The Cardio Heart Connect study is a hybrid type I effectiveness-implementation trial aiming to enroll N=200 patients who have been placed on a cardiac rehab waitlist following a TAVR procedure from the University of Colorado Hospital Heart and Vascular Center. Participants will be randomized 1:1 to the Cardio Heart Connect intervention with commercially available fitness or attention control, designed to control for technology access. At baseline, post-intervention (8 weeks), and follow-up (12 months), we will assess the primary outcome of participants? daily steps as measured by smartwatch accelerometer and secondary outcomes of interest including functional capacity (Duke Activity Status Index; VO2max), quality of life (Kansas City Cardiomyopathy Questionnaire), and cardiovascular health status (Life Essential 8). In addition, we will use mixed methodologies to evaluate the implementation of intervention using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework. Conclusions: Commercially available fitness programs have the potential to provide more accessible opportunities for patients recovering from TAVR to engage in physical activity and may be preferred due to their customizability, convenience, and ease of scheduling. Overall, this study will provide insight into the use of commercial mHealth to promote activity following TAVR.

02.
PLOS Computational Biology 2026-06-08

Assessing the inference of single-cell phylogenies and population dynamics from CRISPR lineage recordings

by Julia Pilarski, Tanja Stadler, Sophie Seidel Multicellular organisms develop from a single cell by repeated rounds of cell division, differentiation, and death, which can be represented as a single-cell phylogenetic tree. Genetic lineage tracing allows us to investigate this development by tracking the ancestry of individual cells as populations grow and change over time. However, accurate reconstruction of the cell phylogeny and quantification of the corresponding phylodynamic parameters – cell division, differentiation, and death rates – from this tracking data remains challenging and needs to be systematically evaluated. We perform simulations and assess, using the Bayesian framework, the joint inference of time-scaled cell phylogenies and phylodynamic parameters from CRISPR lineage recordings with random or sequential edits. Principally, we characterize the inference improvements as the recorder capacity increases. We observe more accurate phylogenetic reconstruction from sequential compared to random recordings, but no substantial improvement in phylodynamic inference when using the additional information contained in the order of edits. Overall, we find that CRISPR lineage recordings carry a strong signal on the rates of cell division when appropriate models are used. However, we detect biases in the inferred rates of cell division and death under phylodynamic model misspecification, i.e., when fitting classic memoryless birth-death processes to synchronous cell divisions. Moreover, for scenarios when cells differentiate into distinct types, we demonstrate that Bayesian phylodynamic analysis of sparse end-point measurements can resolve these cell differentiation trajectories by lineage and time. Under prototypical dynamics, we recover cell type-specific division and death rates, and cell type transition rates in over 80% of simulations. Overall, this simulation study explores how much information on cellular development can be extracted from state-of-the-art genetic lineage tracing data using phylogenetic and phylodynamic methodology.

03.
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.

04.
arXiv (CS.LG) 2026-06-11

Family-Aware Residual Architecture for Predicting Quantum Circuit Simulation Performance

arXiv:2606.11620v1 Announce Type: cross Abstract: Approximate tensor-network simulators enable classical simulation of quantum circuits beyond the reach of exact methods, but selecting optimal approximation parameters – such as bond dimension thresholds – remains a costly trial-and-error process. We present a family-aware neural architecture that predicts both the minimum approximation threshold required to achieve target fidelity and the expected wall-clock runtime for quantum circuit simulation, given only the circuit's OpenQASM description and execution context. Our key insight is that quantum circuits from different algorithmic families (e.g., QFT, Grover, VQE) exhibit fundamentally distinct simulation cost profiles due to their differing entanglement structures. We employ family-conditioned residual corrections – additive, family-specific adjustments atop a shared backbone, drawing on established conditional computation techniques – enabling the model to capture both universal circuit properties and algorithmic nuances. The architecture incorporates a pretrained family classifier (97.5% accuracy) and domain-informed algorithm fingerprint features derived from gate-composition heuristics. Evaluated on circuits spanning 7–130 qubits across 10 algorithm families, our system achieves 79.5% exact threshold accuracy (91.2% within one rung) and $R^2 = 0.82$ runtime correlation, with inference completing in approximately 50 ms – replacing trial-and-error simulation runs that may take minutes to hours. Ablation studies confirm that family-aware modeling provides the single largest performance improvement (+3.2 percentage points), validating the hypothesis that algorithm family is a first-class feature for simulation cost prediction.

05.
arXiv (CS.LG) 2026-06-15

Structured Noise Adaptation for Sequential Bayesian Filtering with Embedded Latent Transfer Operators

arXiv:2606.14195v1 Announce Type: new Abstract: Kalman filters based on the Embedded Latent Transfer Operators (ELTO) emerge as novel statistical tools for sequential state estimation. However, a critical limitation stems from their use of simplified noise models, which fail to dynamically adapt to non-stationary processes. To address this limitation, we introduce an ELTO-based Bayesian filtering approach with a new structured parameterization for the filter's noise model. This parameterization enables structured noise adaptation, which couples the data-driven learning of an optimal time-invariant noise model with dynamic parameter adaptation that responds to changes in dynamics within non-stationary processes. Empirical results show that our structured noise adaptation improves the filter's dynamic state estimation performance in noisy, time-varying environments.

06.
medRxiv (Medicine) 2026-06-18

Device assessed 24-hour movement behaviour and cardiovascular disease mortality amongst cancer survivors.

Background: Cancer survivors face elevated risks of mortality from cardiovascular disease (CVD). The potential importance of physical activity (PA) and other behaviours across the 24-hour day (e.g. sedentary behaviour (SB) and sleep) for CVD-mortality risk is not well understood in this at-risk population. Objectives: To assess the importance of 24-hour movement behaviour, using a compositional approach, for mitigating CVD-mortality amongst cancer survivors. Methods: Participants with a prior cancer diagnosis were drawn from the UK Biobank accelerometry sub-study (n=6,158). Accelerometer-derived movement (moderate-to-vigorous PA (MVPA), vigorous PA (VPA), moderate PA (MPA), light PA (LPA), SB, sleep) was examined in relation to CVD-mortality, identified from health record linkage data (using Fine-Gray Cox proportional-hazards models adjusted for demographic, health, lifestyle covariates). Results: Median follow-up was 8.0 years (Q1-Q3: 7.4-8.5), with n=500 (8.2%) deaths (CVD-deaths: n=118). Greater MVPA, in place of any other behaviour, was inversely associated with CVD-mortality with e.g. 10% lower hazard if MVPA theoretically replaced 7 minutes (mins)/day SB (Hazard ratio (HR): 0.91, (95% Confidence Interval: 0.86-0.95)), 9 mins/day LPA (HR: 0.90, 0.83-0.97), or 11 mins/day sleep (HR: 0.90, 0.83-0.97). The VPA component of MVPA proved critical, requiring only ~1-2 additional mins/day for equivalent hazard reduction. Sleep duration, was also inversely associated with CVD-mortality. A 10% lower hazard required replacing 29 mins/day of SB with sleep (HR: 0.90, 0.84-0.96); no other behavioural replacement amongst SB, sleep or LPA could provide an equivalent risk reduction. Conclusions: Among cancer survivors, the most potent reduction in CVD-mortality followed theoretically reallocating time to higher intensity movement.

07.
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.

08.
medRxiv (Medicine) 2026-06-18

Looked but didn't see: inattentional blindness and yes-bias confabulation in vision-language models

Previous work showed that many participants fail to notice a gorilla in a video of people playing basketball. Another study found that 83% of trained radiologists failed to report a gorilla figure inserted into a chest CT nodule-search task, even though eye-tracking revealed that most observers had foveated the figure. We ask whether a similar phenomenon exists in contemporary vision-language models (VLMs). We find that (i) VLMs are capable of spotting the gorilla in both still-frame images and videos of lung CT scans; (ii) models display inattentional blindness, which varies according to model generation and type of stimulus presented; (iii) Gemini-3.1-Pro outperforms most other flagship and open-weight VLMs at identifying the presence or absence of the gorilla. We additionally ran a segmentation experiment utilizing two different model classes: a generalist (SAM 3), which found the gorilla but produced little to no results for anatomy-based prompts; a medical specialist (BiomedParse), which produced more promising anatomy-based results but flagged "gorilla" on gorilla-free control videos on 82% of frames. The behavioral signature of inattentional blindness reproduces in VLMs, but a unique confabulation failure mode means that any "did the model see X" claim requires signal-detection analysis with a matched-control false-alarm baseline.

09.
medRxiv (Medicine) 2026-06-15

Repurposing cardiovascular disease risk models to predict incident and co-occurring cardiovascular, cardiometabolic and neurocognitive outcomes.

Background: Cardiovascular disease (CVD), cardiometabolic and neurocognitive conditions share risk factors and frequently co-occur. We evaluated whether four established CVD risk prediction models (QRISK3, PCE, SCORE2, SCORE2-OP) can be repurposed to predict 10-year risk of these conditions and their co-occurrence with CVD. Methods: The models were recalibrated using 20% of the UK Biobank (UKB) and evaluated in the remaining 80%. We performed external validation using data from Clinical Practice Research Datalink (CPRD) Aurum, assessing model discrimination (c-statistics) and calibration (intercept and slope). We used permuted feature importance to determine the influence of each individual predictor in the models. Results: Depending on the model, the c-statistics for incident CVD ranged from 0.71 to 0.74 in the UKB test set (16,137 events). Discrimination was equal to or higher than CVD when evaluated against non-traditional CVD outcomes: 0.74 to 0.77 for heart failure (3,471 events), 0.72 to 0.73 for atrial fibrillation (9,213 events), 0.73 to 0.75 for peripheral arterial disease (1,927 events) and 0.80 to 0.82 for abdominal aortic aneurysm (595 events). For the multimorbidity endpoints, model discrimination ranged from 0.74 for the composite of CVD and T2DM (SCORE2-OP) to 0.83 for the composite of CVD and dementia or Parkinson's disease (QRISK3). When considering the onset of any cardiovascular, cardiometabolic, or neurocognitive outcome discrimination ranged from 0.71 to 0.72. The repurposed models slightly underestimated the predicted risk in the CPRD compared to the UKB: average difference in calibration intercept was at most -0.64. After age and sex, smoking status and systolic blood pressure contributed most to model predictions. Conclusions: Repurposed CVD models can be used to identify 10-year risk of many CVD-related conditions and their multimorbidity. These may be used to support risk-based approaches to prevention and screening. The repurposed models have been made available at: https://repurposed-cvd-risk-models.shinyapps.io/cvd_cmd_dementia_app/ Keywords: Risk prediction; cardiovascular disease; cardiometabolic disease; dementia; disease prevention.

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

Capturing Intransitive Dominance in Tennis Forecasting: A Graph Neural Network Approach

arXiv:2510.20454v2 Announce Type: replace Abstract: Intransitive player dominance, where player A beats B, B beats C, but C beats A, is common in competitive tennis. Yet, there are few known attempts to incorporate it within forecasting methods. We address this problem with a graph neural network approach that explicitly models these intransitive relationships through temporal directed graphs, with players as nodes and their historical match outcomes as directed edges. Our model (65.7% accuracy, 0.214 Brier score) forecasts competitively with established rating systems such as Weighted Elo. Although it does not improve on the baseline in unconditional accuracy, a forecast-encompassing test shows that it carries complementary information. A combined forecast significantly outperforms Weighted Elo, and there is some indication that the gain grows more strongly on the intransitive matchups our model targets. A graph-based representation of player interactions thus captures a forecasting signal that transitive rating systems discard, even between players who share no common opponents.

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

ChartFI: Benchmarking Faithfulness and Insightfulness of Chart Descriptions from Multimodal Large Language Models

Chart descriptions are essential for accessibility, cross-modal retrieval, and assisting readers in extracting insights from complex visualizations. As multimodal large language models (MLLMs) are increasingly adopted for automated chart description generation, a critical question arises: how faithfully and insightfully do these models actually describe charts? Current benchmarks fall short on two fronts: existing datasets consist of simple, homogeneous charts paired with shallow, fact-enumerating descriptions; and prevailing metrics fail to capture the multi-faceted nature of description quality. To address these gaps, we present the Chart Faithfulness and Insightfulness Benchmark (ChartFI-Bench). We first summarize four dimensions that characterize high-quality chart descriptions: factual accuracy, salient feature emphasis, domain-informed guidance, and chart-text complementarity. Guided by these dimensions, we construct a high-quality benchmark comprising 896 chart-description pairs, which feature visually complex charts and semantically rich descriptions. Furthermore, we design four aligned evaluation metrics – Faithfulness, Coverage, Informativeness, and Acuity – to systematically assess the quality of descriptions across these dimensions. Experiments conducted on mainstream MLLMs demonstrate the effectiveness of the proposed framework and reveal common weaknesses among existing models.

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

LLM-Powered Personalized Glycemic Assessment in Type 2 Diabetes with Wearable Sensor Data

arXiv:2606.12699v1 Announce Type: cross Abstract: Type 2 Diabetes (T2D) poses an increasing global health threat, demanding effective glycemic assessment to support personalized and improved diabetes care. Wearable sensors such as continuous glucose monitors (CGM) and fitness trackers offer many valuable insights for glycemic assessment. However, effectively analyzing these data requires integration with essential individual-level context. Existing methods are often based on traditional machine learning (ML) and rely primarily on historical blood glucose measurements and overlook personalized information, which limits their performance across diverse diabetes populations. Recent advances in large language models (LLMs) have demonstrated their ability to integrate diverse data modalities while modeling sequential dependencies, motivating the exploration of their potential for personalized glycemic assessment. In this paper, we propose GlyLLM, an LLM-powered framework for modeling CGM-based glycemic dynamics through the integration of wearable sensor data and structured metadata. GlyLLM can leverage the extensive prior knowledge of pre-trained LLMs and achieve sensor-text semantic abstraction at decision time. Experiments on two related tasks on the AI-READI dataset demonstrate that our model outperforms traditional ML methods by an average of 13.66\% in Root Mean Squared Error (RMSE) for glucose forecasting and 13.08\% in Area Under the Receiver Operating Characteristic (AUROC) for diabetes categorization. Additionally, our ablation study shows that diabetes surveys and biometric tests are more critical than other health information for glycemic assessment. Our work presents a promising step toward harnessing the power of LLMs to advance personalized glycemic assessment in T2D care.

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

ARVO: Atlas of Reproducible Vulnerabilities for Open-Source Software

arXiv:2606.17283v1 Announce Type: cross Abstract: Achieving reproducibility, quantity, and diversity in vulnerability datasets has long been viewed as an inherent three-way trade-off, where improving one dimension often comes at the cost of the others. In practice, reproducibility has been the dimension most often neglected. This has limited what can be automatically extracted from historical bug datasets, and has reduced their utility for downstream security research. In this work, we propose a method to produce a new security dataset which ensures reproducibility for diverse vulnerabilities at scale by identifying the key obstacles to large-scale bug reproduction and addressing them with general solutions. Using this method, we introduce full reproducibility to the largest open source software vulnerability dataset (OSS-Fuzz) and construct the ARVO dataset (an Atlas of Reproducible Vulnerabilities in Open-source software). ARVO is a large-scale dataset consisting of over 6,100 real-world vulnerabilities across 311 projects. Focusing on reproducibility, ARVO differs from existing datasets by providing each vulnerability in a form that can be consistently rebuilt, triggered, and analyzed across versions. Reproducibility also enables automatic identification of the corresponding patch for each vulnerability and supports direct interaction with vulnerabilities after code changes, capabilities that existing large-scale datasets do not provide. In our evaluation, ARVO successfully reproduces 81% of vulnerabilities and achieves 89.4% accuracy on the located patches. We also discuss ARVO's influence on both upstream practices and downstream security research.

14.
arXiv (CS.CL) 2026-06-16

Oops, Wait: Discourse Tokens Matter in Reasoning Model

Recent studies suggest that even data-efficient training with ($\simeq$1K) reasoning trajectories can induce non-trivial reasoning capabilities in large language models through post-training. Such training corpora often contain iconic tokens such as "wait", "so", and "alternatively", which frequently appear in reasoning trajectories and may play a role in this process. This paper focuses on characterizing observable token-level patterns in post-training and a case study of how data-efficient supervised fine-tuning (SFT) differs from, and falls short of, large-scale post-training. To this end, we first identify tokens that correlate with correct answers along reasoning trajectories across models and training setups. We then focus on the distribution and (functional) roles of the "wait" token to primarily study the model trained in a data-efficient manner compared with the counterpart. Our study finds that discourse tokens are associated with correctness and a reasoning accuracy jump, even in data-efficient SFT. This suggests data-efficient SFT can partially reproduce discourse-token patterns to mimic meaningful reasoning behavior, but the patterns are less aligned with high-confidence answer transitions than those from large-scale post-training.

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

PrefSQA: Pairwise Preference Prediction for Speech Quality Assessment and the Critical Role of High Quality Datasets

arXiv:2606.19597v1 Announce Type: cross Abstract: Mean opinion scores (MOS) are widely used for speech quality assessment, yet scalar labels are sensitive to rater variability and listening test differences. This introduces labeling noise, which limits the reliability of MOS prediction. Preference prediction reduces this variability as listeners compare signals directly, producing cleaner labels. We study MOS-free preference prediction and propose PrefSQA, which incorporates uncertainty-aware logits, an impairment attention head, and a module based on non-matching-reference comparisons. We use and refine five datasets, including MOS-derived and low-noise simulated sets with matching and non-matching content, experiment with human preference sets, and test on unseen data. Experiments show small improvements on MOS-derived data, while other sets reveal clear improvement over the baselines, highlighting the value of high-quality preference data and demonstrating the effectiveness of the proposed method.

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

Think Again or Think Longer? Selective Verification for Budget-Aware Reasoning

Test-time reasoning is increasingly used as a serving-time control knob, but extra reasoning is not uniformly valuable: it can repair failed attempts, waste compute on already-correct answers, or introduce harmful answer changes. We study this as a deployment allocation problem rather than a new-verifier problem. We introduce \sevra, Selective Verification for Reasoning Allocation, a serving-layer controller that decides whether to preserve a frozen solver's initial answer or invoke active verification. Using a frozen Qwen3-4B solver, we log intervention outcomes and train recoverability-aware gates from serving-visible attempt state. On \mathfive, selective verification reaches 76.3\% accuracy, compared with 75.5\% for always verifying, while reducing post-generation tokens by 26.8\% and harmful flips from 2.2\% to 1.0\%. However, an 8,192-token initial solve reaches 76.0\% accuracy with 28\% fewer total model tokens, showing that selective recovery is useful but not the best tested cost frontier. In frozen transfer to \gsm, the selective policy verifies only 3.0\% of examples, improves accuracy from 93.4\% to 94.5\%, and reduces verification tokens by 91.2\% relative to always verifying; again, a longer initial solve matches its accuracy with fewer realized tokens. On CommonsenseQA, always-on verification hurts, while Self-Consistency@5 improves accuracy at about five times the realized token cost. The resulting deployment rule is: tune the initial budget first, then use selective recovery when explicit checks, bounded retries, auditability, or regression-risk control matter.

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

Null-Space Diffusion Distillation Unlocks Speed, Fidelity and Realism in Lensless Imaging

Lensless imaging reconstructs scenes from highly multiplexed measurements, resulting in a severely ill-posed inverse problem. In this work, we identify a fundamental trade-off between measurement consistency, perceptual quality, and inference speed across lensless reconstruction paradigms. Traditional methods favor consistency but produce perceptually degraded results, supervised approaches achieve high-quality reconstructions with fast inference but may violate physical constraints, and diffusion-prior methods achieve high perceptual quality and consistency–particularly when structured constraints such as range-null decomposition are used–but remain slow due to iterative sampling. Motivated by this observation, we propose Null-Space Diffusion Distillation (NSDD), a single-pass reconstruction model that distills structured diffusion-prior inference into an efficient feed-forward network. NSDD learns to produce high-quality reconstructions that preserve measurement consistency while avoiding costly iterative sampling. Experimental results demonstrate that NSDD achieves perceptual quality and consistency competitive with diffusion-prior methods, while providing significantly faster inference and offering a favorable balance across all three objectives. Furthermore, ablation experiments show that distilling the range–null decomposition improves reconstruction quality and robustness over unstructured full-reconstruction distillation, including on unseen real scenes. These results highlight the potential of structure-aware distillation for efficient lensless imaging. Code is available at github.com/JRCSAVSN/NullSpaceDiffusionDistillation.

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

A homotopy-type-theoretic generalization of neurosymbolic inference

arXiv:2606.17851v1 Announce Type: new Abstract: A wide range of neurosymbolic (NeSy) systems compute one functional: a belief-weighted sum of a logical quantity over a space of $\sigma$-structures, of which weighted model counting, fuzzy logic, and probabilistic logic are special cases. This account is built on sets, and a set deliberately forgets two things that are important for NeSy: when two $\sigma$-structures are the same up to a symmetry of the theory, and how many distinct proofs witness a query. Replacing the underlying sets by types, in the sense of homotopy type theory, preserves this information, and turns this functional into a belief-weighted homotopy cardinality, a notion of size that counts each object in inverse proportion to its symmetries. We develop the framework from scratch for NeSy systems, prove a conservativity theorem that recovers the classical functional when symmetries are trivial, and show that the symmetry our framework exposes is exactly the one behind reasoning shortcuts. The payoff is concrete: the shortcut-aware concept posterior that recent methods reach by ensembling or expressive density estimation is the only symmetry-invariant point of the confusion-set simplex, computable in closed form by averaging a single model over the symmetry group. On MNIST reasoning-shortcut benchmarks this single-model wrapper is better calibrated than a diversity-trained ensemble, while leaving label accuracy and identifiable concepts untouched. Code is freely available at https://github.com/bio-ontology-research-group/hott-nesy.

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

Toward Preference-aligned Large Language Models via Residual-based Model Steering

Preference alignment is a critical step in making Large Language Models (LLMs) useful and aligned with (human) preferences. Existing approaches such as Reinforcement Learning from Human Feedback or Direct Preference Optimization typically require curated data and expensive optimization over billions of parameters, and eventually lead to persistent task-specific models. In this work, we introduce Preference alignment of Large Language Models via Residual Steering (PaLRS), a training-free method that exploits preference signals encoded in the residual streams of LLMs. From as few as one hundred preference pairs, PaLRS extracts lightweight, plug-and-play steering vectors that can be applied at inference time to push models toward preferred behaviors. We evaluate PaLRS on various small-to-medium-scale open-source LLMs, showing that PaLRS-aligned models achieve consistent gains on mathematical reasoning and code generation benchmarks while preserving baseline general-purpose performance. Moreover, when compared to models aligned with DPO and SimPO, they perform better with great time-savings. Our findings highlight that PaLRS offers an effective, much more efficient and flexible alternative to standard preference optimization pipelines, offering a training-free, plug-and-play mechanism for alignment with minimal data.

20.
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.

21.
arXiv (CS.AI) 2026-06-15

An interpretable unsupervised representation learning for high precision measurement in particle physics

arXiv:2511.22246v2 Announce Type: replace-cross Abstract: Unsupervised learning has been widely applied to various tasks in particle physics. However, existing models lack precise control over their learned representations, limiting physical interpretability and hindering their use for accurate measurements. We propose the Histogram AutoEncoder (HistoAE), an unsupervised representation learning network featuring a custom histogram-based loss that enforces a physically structured latent space. Applied to silicon microstrip detectors, HistoAE learns an interpretable two-dimensional latent space corresponding to the particle's charge and impact position. After simple post-processing, it achieves a charge resolution of $0.25\,e$ and a position resolution of $3\,\mu\mathrm{m}$ on beam-test data, comparable to the conventional approach. These results demonstrate that unsupervised deep learning models can enable physically meaningful and quantitatively precise measurements. Moreover, the generative capacity of HistoAE enables straightforward extensions to fast detector simulations.

22.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.

23.
bioRxiv (Bioinfo) 2026-06-20

Systematic Evaluation of Feature Representations for Cancer-Associated sORF Prediction in Non-coding RNA

Short open reading frames (sORFs) within non-coding RNAs (ncRNAs) have arisen as a hidden layer of gene regulation, encoding small peptides that represent a new class of cancer regulators with diagnostic and therapeutic potential. However, inferring associations between sORFs to specific cancer types remains challenging and requires computational approaches for accurate prediction. Recently, the CoraL framework introduced the first computational approach for predicting cancer-associated peptides, focusing primarily on model architecture while overlooking how feature extraction strategies influence predictive accuracy. We present a systematic evaluation of machine learning models and feature extraction approaches to predict cancer-associated sORFs across 15 cancer types. We benchmarked seven traditional machine learning algorithms combined with three feature extraction methods: k-mer frequency, Word2Vec embeddings, and genomic language model (gLM)-based embeddings. To our knowledge, this is the first study applying gLM-derived embeddings to the prediction of cancer-associated sORFs in ncRNA. Our results show that traditional machine learning models with appropriate feature extraction outperform the CoraL baseline across all cancer types, achieving up to 10% higher accuracy in some of the 15 evaluated datasets. Interestingly, k-mer features consistently outperformed gLM embeddings without fine-tuning, suggesting that local sequence composition may provide more discriminative information for this task and that pre-trained genomic representations may require task-specific adaptation to fully capture these patterns. Additionally, we observed that the way sequences are tokenized, such as the k-mer length, can affect performance: longer fragments (e.g., k=7) sometimes reduced accuracy for Random Forest but had a smaller effect on MLP. Our findings suggest that appropriate feature engineering can provide greater improvements than increasing model complexity.

24.
medRxiv (Medicine) 2026-06-10

Impact of Early Treatment on Symptom Improvement and Procedural Events among Men with BPH and Bothersome Lower Urinary Tract Symptoms: A Contemporary Analysis of the American Urological Association Quality (AQUA) Registry

PURPOSE: As the armamentarium of BPH therapies continues to expand, it remains imperative to maximize patient satisfaction and minimize decisional regret. We sought to determine the impact of time from BPH diagnosis to index treatment on symptom improvement and subsequent procedural events. MATERIALS AND METHODS: We queried the American Urological Association Quality Registry for men [&ge;] 40 years old with BPH, available IPSS data, and no receipt of prior BPH treatment. Index treatment included medication, surgery, or minimally invasive surgical therapy (MIST). Outcomes included IPSS over 3 years of follow-up, change in percentage of mild lower urinary tract symptoms (LUTS) by 3 months, and time to procedural event. Patients were stratified by time from index diagnosis to treatment by 3 years. Outcomes were compared across time-to-treatment cohorts with appropriate statistical tests with p < 0.05 as significant. RESULTS: 43,919 patients met criteria with 19,642 pursuing treatments. Patients pursued treatment at comparably lower baseline IPSS compared to prior prospective series. Patients undergoing surgery and MIST had significantly higher baseline IPSS, while medical comorbidities were significantly more common among men initiating pharmacotherapy. Early surgery and MIST were associated with significant improvement in IPSS within 6-12 months and an increase in mild LUTS by 3 months. All forms of early treatment were associated with delayed time to procedural events, including catheterization and fulguration. CONCLUSIONS: Early procedural intervention for BPH is associated with early symptom improvement and delayed time to procedural events among real-world, contemporary practice.

25.
arXiv (CS.LG) 2026-06-16

Scalable Pairwise Kernel Learning with Stochastic Vec Trick

arXiv:2606.16979v1 Announce Type: new Abstract: Pairwise learning is a specialized form of supervised learning that focuses on predicting outcomes for pairs of objects. In this work, we introduce SPaiK, a new scalable kernel learning method tailored for pairwise settings. Our approach preserves the expressive power of kernel methods while substantially reducing computational and memory requirements. The key innovation is the stochastic generalized vec trick (sGVT), a stochastic extension of the sparse Kronecker product multiplication algorithm, which enables efficient large-scale training with pairwise kernels. By incorporating sGVT, SPaiK makes it possible to apply kernel-based pairwise learning to datasets of a size previously out of reach. We evaluate the performance of SPaiK on seven real-world drug-target affinity datasets and compare the results with state-of-the-art methods in pairwise learning.