Abstract:Diabetic Retinopathy (DR) progresses as a continuous and irreversible deterioration of the retina, following a well-defined clinical trajectory from mild to severe stages. However, most existing ordinal regression approaches model DR severity as a set of static, symmetric ranks, capturing relative order while ignoring the inherent unidirectional nature of disease progression. As a result, the learned feature representations may violate biological plausibility, allowing implausible proximity between non-consecutive stages or even reverse transitions. To bridge this gap, we propose Directed Ordinal Diffusion Regularization (D-ODR), which explicitly models the feature space as a directed flow by constructing a progression-constrained directed graph that strictly enforces forward disease evolution. By performing multi-scale diffusion on this directed structure, D-ODR imposes penalties on score inversions along valid progression paths, thereby effectively preventing the model from learning biologically inconsistent reverse transitions. This mechanism aligns the feature representation with the natural trajectory of DR worsening. Extensive experiments demonstrate that D-ODR yields superior grading performance compared to state-of-the-art ordinal regression and DR-specific grading methods, offering a more clinically reliable assessment of disease severity. Our code is available on https://github.com/HovChen/D-ODR.
Abstract:Test-time compute allocation in large reasoning models (LRMs) is widely used and has applications in mathematical problem solving, code synthesis, and planning. Recent work has addressed this problem by scaling self-consistency and parallel thinking, adding generic ``thinking tokens'' and prompting models to re-read the question before answering. Unfortunately, these approaches either inject task-agnostic tokens or mandate heuristics that do not explain -- and often ignore -- the \emph{spontaneous} repetition that many LRMs exhibit at the head of their internal chains. In contrast, we analyze and harness the model's tendency to restate the question, which we term the \emph{Echo of Prompt (EOP)}, as a front-loaded, compute-shaping mechanism. We formalize its probabilistic cost by casting echo removal as rejection-based conditioning and defining the \emph{Echo Likelihood Gap} $Δ\mathcal{L}$ as a computable proxy. This provides the missing theoretical link that links early repetition to likelihood gains and downstream accuracy. However, it does not by itself specify how to exploit EOP. Consequently, we develop \emph{Echo-Distilled SFT (ED-SFT)} to instill an ``echo-then-reason'' pattern through supervised finetuning, and \emph{Echoic Prompting (EP)} to re-ground the model mid-trace without training. While promising, quantifying benefits beyond verbosity is non-trivial. Therefore, we conduct length and suffix-controlled likelihood analyses together with layer-wise attention studies, showing that EOP increases answer to answer-prefix attention in middle layers, consistent with an \emph{attention refocusing} mechanism. We evaluate on GSM8K, MathQA, Hendrycks-MATH, AIME24, and MATH-500 under identical decoding settings and budgets, and find consistent gains over baselines. Code is available at https://github.com/hhh2210/echoes-as-anchors.



Abstract:Background: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies. Method: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-view variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information. Results: We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved r2-scores > 0.01 for 71.55% of metabolites. Conclusion: The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research.