Detecting amyloid-$β$ (A$β$) positivity is crucial for early diagnosis of Alzheimer's disease but typically requires PET imaging, which is costly, invasive, and not widely accessible, limiting its use for population-level screening. We address this gap by proposing a PET-guided knowledge distillation framework that enables A$β$ prediction from MRI alone, without requiring non-imaging clinical covariates or PET at inference. Our approach employs a BiomedCLIP-based teacher model that learns PET-MRI alignment via cross-modal attention and triplet contrastive learning with PET-informed (Centiloid-aware) online negative sampling. An MRI-only student then mimics the teacher via feature-level and logit-level distillation. Evaluated across four MRI contrasts (T1w, T2w, FLAIR, T2*) and two independent datasets, our approach demonstrates effective knowledge transfer (best AUC: 0.74 on OASIS-3, 0.68 on ADNI) while maintaining interpretability and eliminating the need for clinical variables. Saliency analysis confirms that predictions focus on anatomically relevant cortical regions, supporting the clinical viability of PET-free A$β$ screening. Code is available at https://github.com/FrancescoChiumento/pet-guided-mri-amyloid-detection.
Automated respiratory audio analysis promises scalable, non-invasive disease screening, yet progress is limited by scarce labeled data and costly expert annotation. Zero-shot inference eliminates task-specific supervision, but existing methods apply uniform computation to every input regardless of difficulty. We introduce TRIAGE, a tiered zero-shot framework that adaptively scales test-time compute by routing each audio sample through progressively richer reasoning stages: fast label-cosine scoring in a joint audio-text embedding space (Tier-L), structured matching with clinician-style descriptors (Tier-M), and retrieval-augmented large language model reasoning (Tier-H). A confidence-based router finalizes easy predictions early while allocating additional computation to ambiguous inputs, enabling nearly half of all samples to exit at the cheapest tier. Across nine respiratory classification tasks without task-specific training, TRIAGE achieves a mean AUROC of 0.744, outperforming prior zero-shot methods and matching or exceeding supervised baselines on multiple tasks. Our analysis show that test-time scaling concentrates gains where they matter: uncertain cases see up to 19% relative improvement while confident predictions remain unchanged at minimal cost.
Current fMRI foundation models primarily rely on a limited range of brain states and mismatched pretraining tasks, restricting their ability to learn generalized representations across diverse brain states. We present \textit{Brain-DiT}, a universal multi-state fMRI foundation model pretrained on 349,898 sessions from 24 datasets spanning resting, task, naturalistic, disease, and sleep states. Unlike prior fMRI foundation models that rely on masked reconstruction in the raw-signal space or a latent space, \textit{Brain-DiT} adopts metadata-conditioned diffusion pretraining with a Diffusion Transformer (DiT), enabling the model to learn multi-scale representations that capture both fine-grained functional structure and global semantics. Across extensive evaluations and ablations on 7 downstream tasks, we find consistent evidence that diffusion-based generative pretraining is a stronger proxy than reconstruction or alignment, with metadata-conditioned pretraining further improving downstream performance by disentangling intrinsic neural dynamics from population-level variability. We also observe that downstream tasks exhibit distinct preferences for representational scale: ADNI classification benefits more from global semantic representations, whereas age/sex prediction comparatively relies more on fine-grained local structure. Code and parameters of Brain-DiT are available at \href{https://github.com/REDMAO4869/Brain-DiT}{Link}.
The analysis of DNA sequences has become critical in numerous fields, from evolutionary biology to understanding gene regulation and disease mechanisms. While deep neural networks can achieve remarkable predictive performance, they typically operate as black boxes. Contrasting these black boxes, axis-aligned decision trees offer a promising direction for interpretable DNA sequence analysis, yet they suffer from a fundamental limitation: considering individual raw features in isolation at each split limits their expressivity, which results in prohibitive tree depths that hinder both interpretability and generalization performance. We address this challenge by introducing DEFT, a novel framework that adaptively generates high-level sequence features during tree construction. DEFT leverages large language models to propose biologically-informed features tailored to the local sequence distributions at each node and to iteratively refine them with a reflection mechanism. Empirically, we demonstrate that DEFT discovers human-interpretable and highly predictive sequence features across a diverse range of genomic tasks.
Predicting the functional impact of single amino acid substitutions (SAVs) is central to understanding genetic disease and engineering therapeutic proteins. While protein language models and structure-based methods have achieved strong performance on this task, they systematically neglect protein dynamics; residue flexibility, correlated motions, and allosteric coupling are well-established determinants of mutational tolerance in structural biology, yet have not been incorporated into supervised variant effect predictors. We present TriFit, a multimodal framework that integrates sequence, structure, and protein dynamics through a four-expert Mixture-of-Experts (MoE) fusion module with trimodal cross-modal contrastive learning. Sequence embeddings are extracted via masked marginal scoring with ESM-2 (650M); structural embeddings from AlphaFold2-predicted C-alpha geometries; and dynamics embeddings from Gaussian Network Model (GNM) B-factors, mode shapes, and residue-residue cross-correlations. The MoE router adaptively weights modality combinations conditioned on the input, enabling protein-specific fusion without fixed modality assumptions. On the ProteinGym substitution benchmark (217 DMS assays, 696k SAVs), TriFit achieves AUROC 0.897 +/- 0.0002, outperforming all supervised baselines including Kermut (0.864) and ProteinNPT (0.844), and the best zero-shot model ESM3 (0.769). Ablation studies confirm that dynamics provides the largest marginal contribution over pairwise modality combinations, and TriFit achieves well-calibrated probabilistic outputs (ECE = 0.044) without post-hoc correction.
The biological definition of Alzheimer's disease (AD) relies on multi-modal neuroimaging, yet the clinical utility of positron emission tomography (PET) is limited by cost and radiation exposure, hindering early screening at preclinical or prodromal stages. While generative models offer a promising alternative by synthesizing PET from magnetic resonance imaging (MRI), achieving subject-specific precision remains a primary challenge. Here, we introduce DIReCT$++$, a Domain-Informed ReCTified flow model for synthesizing multi-tracer PET from MRI combined with fundamental clinical information. Our approach integrates a 3D rectified flow architecture to capture complex cross-modal and cross-tracer relationships with a domain-adapted vision-language model (BiomedCLIP) that provides text-guided, personalized generation using clinical scores and imaging knowledge. Extensive evaluations on multi-center datasets demonstrate that DIReCT$++$ not only produces synthetic PET images ($^{18}$F-AV-45 and $^{18}$F-FDG) of superior fidelity and generalizability but also accurately recapitulates disease-specific patterns. Crucially, combining these synthesized PET images with MRI enables precise personalized stratification of mild cognitive impairment (MCI), advancing a scalable, data-efficient tool for the early diagnosis and prognostic prediction of AD. The source code will be released on https://github.com/ladderlab-xjtu/DIReCT-PLUS.
The identification of reliable molecular biomarkers for Parkinson's disease remains challenging due to its multifactorial nature. Although protein sequences constitute a fundamental and widely available source of biological information, their standalone discriminative capacity for complex disease classification remains unclear. In this work, we present a controlled and leakage-free evaluation of multiple representations derived exclusively from protein primary sequences, including amino acid composition, k-mers, physicochemical descriptors, hybrid representations, and embeddings from protein language models, all assessed under a nested stratified cross-validation framework to ensure unbiased performance estimation. The best-performing configuration (ProtBERT + MLP) achieves an F1-score of 0.704 +/- 0.028 and ROC-AUC of 0.748 +/- 0.047, indicating only moderate discriminative performance. Classical representations such as k-mers reach comparable F1 values (up to approximately 0.667), but exhibit highly imbalanced behavior, with recall close to 0.98 and precision around 0.50, reflecting a strong bias toward positive predictions. Across representations, performance differences remain within a narrow range (F1 between 0.60 and 0.70), while unsupervised analyses reveal no intrinsic structure aligned with class labels, and statistical testing (Friedman test, p = 0.1749) does not indicate significant differences across models. These results demonstrate substantial overlap between classes and indicate that primary sequence information alone provides limited discriminative power for Parkinson's disease classification. This work establishes a reproducible baseline and provides empirical evidence that more informative biological features, such as structural, functional, or interaction-based descriptors, are required for robust disease modeling.
Retinal Cysts are formed by leakage and accumulation of fluid in the retina due to the incompetence of retinal vasculature. These cystic spaces have significance in several ocular diseases such as age-related macular degeneration, diabetic macular edema, etc. Optical coherence tomography is one of the predominant diagnosing techniques for imaging retinal pathologies. Segmenting and quantification of intraretinal cysts plays the vital role in predicting visual acuity. In literature, several methods have been proposed for automatic segmentation of intraretinal cysts. As cystoid macular edema becomes a major problem to humankind, we need to quantify it accurately and operate it out, else it might cause many problems later on. Though research is being carried out in this area, not much of progress has been made and accuracy achieved so far is 68\% which is very less. Also, the methods depend on the quality of the image and give very low results for high noise images like topcon. This work uses ResNet CNN (Convolutional Neural Network) approach of segmentation by the way of patchwise classification for training on image set from cyst segmentation challenge dataset and testing on test data set given by 2 different graders for all 4 vendors in the challenge. It also compares these methods using first publicly available novel cyst segmentation challenge dataset. The methods were evaluated using quantitative measures to assess their robustness against the challenges of intraretinal cyst segmentation. The results are found to be better than the previous state of the art approaches giving more than 70\% dice coefficient on all vendors irrespective of their quality.
Accurate and interpretable plant disease diagnosis remains a major challenge for vision-language models (VLMs) in real-world agriculture. We introduce AgriChain, a dataset of approximately 11,000 expert-curated leaf images spanning diverse crops and pathologies, each paired with (i) a disease label, (ii) a calibrated confidence score (High/Medium/Low), and (iii) an expert-verified chain-of-thought (CoT) rationale. Draft explanations were first generated by GPT-4o and then verified by a professional agricultural engineer using standardized descriptors (e.g., lesion color, margin, and distribution). We fine-tune Qwen2.5-VL-3B on AgriChain, resulting in a specialized model termed AgriChain-VL3B, to jointly predict diseases and generate visually grounded reasoning. On a 1,000-image test set, our CoT-supervised model achieves 73.1% top-1 accuracy (macro F1 = 0.466; weighted F1 = 0.655), outperforming strong baselines including Gemini 1.5 Flash, Gemini 2.5 Pro, and GPT-4o Mini. The generated explanations align closely with expert reasoning, consistently referencing key visual cues. These findings demonstrate that expert-verified reasoning supervision significantly enhances both accuracy and interpretability, bridging the gap between generic multimodal models and human expertise, and advancing trustworthy, globally deployable AI for sustainable agriculture. The dataset and code are publicly available at: https://github.com/hazzanabeel12-netizen/agrichain
Chagas disease screening via ECGs is limited by scarce and noisy labels in existing datasets. We propose a biomarker-based pretraining approach, where an ECG feature extractor is first trained to predict percentile-binned blood biomarkers from the MIMIC-IV-ECG dataset. The pretrained model is then fine-tuned on Brazilian datasets for Chagas detection. Our 5-model ensemble, developed by the Ahus AIM team, achieved a challenge score of 0.269 on the hidden test set, ranking 5th in Detection of Chagas Disease from the ECG: The George B. Moody PhysioNet Challenge 2025. Source code and the model are shared on GitHub: github.com/Ahus-AIM/physionet-challenge-2025