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Precision Medicine in Substance Use Disorders: Integrating Behavioral, Environmental, and Biological Insights.

Guerrin CGJ, Tesselaar DRM, Booij J, Schellekens AFA, Homberg JR

pubmed logopapersJul 31 2025
Substance use disorders (SUD) are chronic, relapsing conditions marked by high variability in treatment response and frequent relapse. This variability arises from complex interactions among behavioral, environmental, and biological factors unique to each individual. Precision medicine, which tailors treatment to patient-specific characteristics, offers a promising avenue to address these challenges. This review explores key factors influencing SUD, including severity, comorbidities, drug use motives, polysubstance use, cognitive impairments, and biological and environmental influences. Advanced neuroimaging, such as MRI and PET, enables patient subtyping by identifying altered brain mechanisms, including reward, relief, and cognitive pathways, and striatal dopamine D<sub>2/3</sub> receptor binding. Pharmacogenetic and epigenetic studies uncover how variations in dopaminergic, serotoninergic, and opioidergic systems shape treatment outcomes. Emerging biomarkers, such as neurofilament light chain, offer non-invasive relapse monitoring. Multifactorial models integrating behavioral and neural markers outperform single-factor approaches in predicting treatment success. Machine learning refines these models, while longitudinal and preclinical studies support individualized care. Despite translational hurdles, precision medicine offers transformative potential for improving SUD treatment outcomes.

Cognitive profiles associated with faster thalamic atrophy in multiple sclerosis.

Amin M, Scullin K, Nakamura K, Ontaneda D, Galioto R

pubmed logopapersJul 31 2025
Cognitive impairment (CI) in people with MS (pwMS) has complex pathophysiology. Neuropsychological testing (NPT) can be helpful, but interpretation may be challenging for clinicians. Thalamic atrophy (TA) has shown correlation for both neurodegeneration and CI. Leverage machine learning methods to link CI and longitudinal neuroimaging biomarkers. Retrospective review of adult pwMS with NPT and ≥2 brain MRIs. Quantitative MRI regional change rates were calculated using mixed effects models. Participants were divided into training and validation cohorts. K-means clustering was done based on first and second NPT principal components (PC1 and PC2). MRI change rates were compared between clusters. 112 participants were included (mean age 48 years, 71 % female, 80 % relapsing remitting). Processing speed and memory were the major contributors to PC1. We identified two clusters based on PC1, one with significantly more TA in both training and validation cohorts (p = 0.035; p = 0.002) and similar rates of change in all other quantitative MRI measures. The most important contributors to PC1 included measures of processing speed (SDMT/WAIS Coding) and memory (List Learning/BVMT immediate and delayed recall). This clustering method identified a profile of NPT results strongly linked to and possibly driven by TA. These results confirm validity of previously established findings using more advanced analyses in addition to offering novel insights into NPT dimensionality reduction.

The retina as a window into detecting subclinical cardiovascular disease in type 2 diabetes.

Alatrany AS, Lakhani K, Cowley AC, Yeo JL, Dattani A, Ayton SL, Deshpande A, Graham-Brown MPM, Davies MJ, Khunti K, Yates T, Sellers SL, Zhou H, Brady EM, Arnold JR, Deane J, McLean RJ, Proudlock FA, McCann GP, Gulsin GS

pubmed logopapersJul 31 2025
Individuals with Type 2 Diabetes (T2D) are at high risk of subclinical cardiovascular disease (CVD), potentially detectable through retinal alterations. In this single-centre, prospective cohort study, 255 asymptomatic adults with T2D and no prior history of CVD underwent echocardiography, non-contrast coronary computed tomography and cardiovascular magnetic resonance. Retinal photographs were evaluated for diabetic retinopathy grade and microvascular geometric characteristics using deep learning (DL) tools. Associations with cardiac imaging markers of subclinical CVD were explored. Of the participants (aged 64 ± 7 years, 62% males); 200 (78%) had no diabetic retinopathy and 55 (22%) had mild background retinopathy. Groups were well-matched for age, sex, ethnicity, CV risk factors, urine microalbuminuria, and serum natriuretic peptide and high-sensitivity troponin levels. Presence of retinopathy was associated with a greater burden of coronary atherosclerosis (coronary artery calcium score ≥ 100; OR 2.63; 95% CI 1.29–5.36; <i>P</i> = 0.008), more concentric left ventricular remodelling (OR 3.11; 95% CI 1.50–6.45; <i>P</i> = 0.002), and worse global longitudinal strain (OR 2.32; 95% CI 1.18–4.59; <i>P</i> = 0.015), independent of key co-variables. Early diabetic retinopathy is associated with a high burden of coronary atherosclerosis and markers of early heart failure. Routine diabetic eye screening may serve as an effective alternative to currently advocated screening tests for detecting subclinical CVD in T2D, presenting opportunities for earlier detection and intervention. The online version contains supplementary material available at 10.1038/s41598-025-13468-4.

Impact of large language models and vision deep learning models in predicting neoadjuvant rectal score for rectal cancer treated with neoadjuvant chemoradiation.

Kim HB, Tan HQ, Nei WL, Tan YCRS, Cai Y, Wang F

pubmed logopapersJul 31 2025
This study aims to explore Deep Learning methods, namely Large Language Models (LLMs) and Computer Vision models to accurately predict neoadjuvant rectal (NAR) score for locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACRT). The NAR score is a validated surrogate endpoint for LARC. 160 CT scans of patients were used in this study, along with 4 different types of radiology reports, 2 generated from CT scans and other 2 from MRI scans, both before and after NACRT. For CT scans, two different approaches with convolutional neural network were utilized to tackle the 3D scan entirely or tackle it slice by slice. For radiology reports, an encoder architecture LLM was used. The performance of the approaches was quantified by the Area under the Receiver Operating Characteristic curve (AUC). The two different approaches for CT scans yielded [Formula: see text] and [Formula: see text] while the LLM trained on post NACRT MRI reports showed the most predictive potential at [Formula: see text] and a statistical improvement, p = 0.03, over the baseline clinical approach (from [Formula: see text] to [Formula: see text])). This study showcases the potential of Large Language Models and the inadequacies of CT scans in predicting NAR values. Clinical trial number Not applicable.

Prognostication in patients with idiopathic pulmonary fibrosis using quantitative airway analysis from HRCT: a retrospective study.

Nan Y, Federico FN, Humphries S, Mackintosh JA, Grainge C, Jo HE, Goh N, Reynolds PN, Hopkins PMA, Navaratnam V, Moodley Y, Walters H, Ellis S, Keir G, Zappala C, Corte T, Glaspole I, Wells AU, Yang G, Walsh SL

pubmed logopapersJul 31 2025
Predicting shorter life expectancy is crucial for prioritizing antifibrotic therapy in fibrotic lung diseases, where progression varies widely, from stability to rapid deterioration. This heterogeneity complicates treatment decisions, emphasizing the need for reliable baseline measures. This study focuses on leveraging artificial intelligence model to address heterogeneity in disease outcomes, focusing on mortality as the ultimate measure of disease trajectory. This retrospective study included 1744 anonymised patients who underwent high-resolution CT scanning. The AI model, SABRE (Smart Airway Biomarker Recognition Engine), was developed using data from patients with various lung diseases (n=460, including lung cancer, pneumonia, emphysema, and fibrosis). Then, 1284 high-resolution CT scans with evidence of diffuse FLD from the Australian IPF Registry and OSIC were used for clinical analyses. Airway branches were categorized and quantified by anatomic structures and volumes, followed by multivariable analysis to explore the associations between these categories and patients' progression and mortality, adjusting for disease severity or traditional measurements. Cox regression identified SABRE-based variables as independent predictors of mortality and progression, even adjusting for disease severity (fibrosis extent, traction bronchiectasis extent, and ILD extent), traditional measures (FVC%, DLCO%, and CPI), and previously reported deep learning algorithms for fibrosis quantification and morphological analysis. Combining SABRE with DLCO significantly improved prognosis utility, yielding an AUC of 0.852 at the first year and a C-index of 0.752. SABRE-based variables capture prognostic signals beyond that provided by traditional measurements, disease severity scores, and established AI-based methods, reflecting the progressiveness and pathogenesis of the disease.

Enhanced stroke risk prediction in hypertensive patients through deep learning integration of imaging and clinical data.

Li H, Zhang T, Han G, Huang Z, Xiao H, Ni Y, Liu B, Lin W, Lin Y

pubmed logopapersJul 31 2025
Stroke is one of the leading causes of death and disability worldwide, with a significantly elevated incidence among individuals with hypertension. Conventional risk assessment methods primarily rely on a limited set of clinical parameters and often exclude imaging-derived structural features, resulting in suboptimal predictive accuracy. This study aimed to develop a deep learning-based multimodal stroke risk prediction model by integrating carotid ultrasound imaging with multidimensional clinical data to enable precise identification of high-risk individuals among hypertensive patients. A total of 2,176 carotid artery ultrasound images from 1,088 hypertensive patients were collected. ResNet50 was employed to automatically segment the carotid intima-media and extract key structural features. These imaging features, along with clinical variables such as age, blood pressure, and smoking history, were fused using a Vision Transformer (ViT) and fed into a Radial Basis Probabilistic Neural Network (RBPNN) for risk stratification. The model's performance was systematically evaluated using metrics including AUC, Dice coefficient, IoU, and Precision-Recall curves. The proposed multimodal fusion model achieved outstanding performance on the test set, with an AUC of 0.97, a Dice coefficient of 0.90, and an IoU of 0.80. Ablation studies demonstrated that the inclusion of ViT and RBPNN modules significantly enhanced predictive accuracy. Subgroup analysis further confirmed the model's robust performance in high-risk populations, such as those with diabetes or smoking history. The deep learning-based multimodal fusion model effectively integrates carotid ultrasound imaging and clinical features, significantly improving the accuracy of stroke risk prediction in hypertensive patients. The model demonstrates strong generalizability and clinical application potential, offering a valuable tool for early screening and personalized intervention planning for stroke prevention. Not applicable.

Identification and validation of an explainable machine learning model for vascular depression diagnosis in the older adults: a multicenter cohort study.

Zhang R, Li T, Fan F, He H, Lan L, Sun D, Xu Z, Peng S, Cao J, Xu J, Peng X, Lei M, Song H, Zhang J

pubmed logopapersJul 31 2025
Vascular depression (VaDep) is a prevalent affective disorder in older adults that significantly impacts functional status and quality of life. Early identification and intervention are crucial but largely insufficient in clinical practice due to inconspicuous depressive symptoms mostly, heterogeneous imaging manifestations, and the lack of definitive peripheral biomarkers. This study aimed to develop and validate an interpretable machine learning (ML) model for VaDep to serve as a clinical support tool. This study included 602 participants from Wuhan in China divided into 236 VaDep patients and 366 controls for training and internal validation from July 2020 to October 2023. An independent dataset of 171 participants from surrounding areas was used for external validation. We collected clinical data, neuropsychological assessments, blood test results, and MRI scans to develop and refine ML models through cross-validation. Feature reduction was implemented to simplify the models without compromising their performance, with validation achieved through internal and external datasets. The SHapley Additive exPlanations method was used to enhance model interpretability. The Light Gradient Boosting Machine (LGBM) model outperformed from the selected 6 ML algorithms based on performance metrics. An optimized, interpretable LGBM model with 8 key features, including white matter hyperintensities score, age, vascular endothelial growth factor, interleukin-6, brain-derived neurotrophic factor, tumor necrosis factor-alpha levels, lacune counts, and serotonin level, demonstrated high diagnostic accuracy in both internal (AUROC = 0.937) and external (AUROC = 0.896) validations. The final model also achieved, and marginally exceeded, clinician-level diagnostic performance. Our research established a consistent and explainable ML framework for identifying VaDep in older adults, utilizing comprehensive clinical data. The 8 characteristics identified in the final LGBM model provide new insights for further exploration of VaDep mechanisms and emphasize the need for enhanced focus on early identification and intervention in this vulnerable group. More attention needs to be paid to the affective health of older adults.

An interpretable CT-based machine learning model for predicting recurrence risk in stage II colorectal cancer.

Wu Z, Gong L, Luo J, Chen X, Yang F, Wen J, Hao Y, Wang Z, Gu R, Zhang Y, Liao H, Wen G

pubmed logopapersJul 31 2025
This study aimed to develop an interpretable 3-year disease-free survival risk prediction tool to stratify patients with stage II colorectal cancer (CRC) by integrating CT images and clinicopathological factors. A total of 769 patients with pathologically confirmed stage II CRC and disease-free survival (DFS) follow-up information were recruited from three medical centers and divided into training (n = 442), test (n = 190), and validation cohorts (n = 137). CT-based tumor radiomics features were extracted, selected, and used to calculate a Radscore. A combined model was developed using artificial neural network (ANN) algorithm, by integrating the Radscore with significant clinicoradiological factors to classify patients into high- and low-risk groups. Model performance was assessed using the area under the curve (AUC), and feature contributions were qualified using the Shapley additive explanation (SHAP) algorithm. Kaplan-Meier survival analysis revealed the prognostic stratification value of the risk groups. Fourteen radiomics features and five clinicoradiological factors were selected to construct the radiomics and clinicoradiological models, respectively. The combined model demonstrated optimal performance, with AUCs of 0.811 and 0.846 in the test and validation cohorts, respectively. Kaplan-Meier curves confirmed effective patient stratification (p < 0.001) in both test and validation cohorts. A high Radscore, rough intestinal outer edge, and advanced age were identified as key prognostic risk factors using the SHAP. The combined model effectively stratified patients with stage II CRC into different prognostic risk groups, aiding clinical decision-making. Integrating CT images with clinicopathological information can facilitate the identification of patients with stage II CRC who are most likely to benefit from adjuvant chemotherapy. The effectiveness of adjuvant chemotherapy for stage II colorectal cancer remains debated. A combined model successfully identified high-risk stage II colorectal cancer patients. Shapley additive explanations enhance the interpretability of the model's predictions.

Recovering Diagnostic Value: Super-Resolution-Aided Echocardiographic Classification in Resource-Constrained Imaging

Krishan Agyakari Raja Babu, Om Prabhu, Annu, Mohanasankar Sivaprakasam

arxiv logopreprintJul 30 2025
Automated cardiac interpretation in resource-constrained settings (RCS) is often hindered by poor-quality echocardiographic imaging, limiting the effectiveness of downstream diagnostic models. While super-resolution (SR) techniques have shown promise in enhancing magnetic resonance imaging (MRI) and computed tomography (CT) scans, their application to echocardiography-a widely accessible but noise-prone modality-remains underexplored. In this work, we investigate the potential of deep learning-based SR to improve classification accuracy on low-quality 2D echocardiograms. Using the publicly available CAMUS dataset, we stratify samples by image quality and evaluate two clinically relevant tasks of varying complexity: a relatively simple Two-Chamber vs. Four-Chamber (2CH vs. 4CH) view classification and a more complex End-Diastole vs. End-Systole (ED vs. ES) phase classification. We apply two widely used SR models-Super-Resolution Generative Adversarial Network (SRGAN) and Super-Resolution Residual Network (SRResNet), to enhance poor-quality images and observe significant gains in performance metric-particularly with SRResNet, which also offers computational efficiency. Our findings demonstrate that SR can effectively recover diagnostic value in degraded echo scans, making it a viable tool for AI-assisted care in RCS, achieving more with less.

A privacy preserving machine learning framework for medical image analysis using quantized fully connected neural networks with TFHE based inference.

Selvakumar S, Senthilkumar B

pubmed logopapersJul 30 2025
Medical image analysis using deep learning algorithms has become a basis of modern healthcare, enabling early detection, diagnosis, treatment planning, and disease monitoring. However, sharing sensitive raw medical data with third parties for analysis raises significant privacy concerns. This paper presents a privacy-preserving machine learning (PPML) framework using a Fully Connected Neural Network (FCNN) for secure medical image analysis using the MedMNIST dataset. The proposed PPML framework leverages a torus-based fully homomorphic encryption (TFHE) to ensure data privacy during inference, maintain patient confidentiality, and ensure compliance with privacy regulations. The FCNN model is trained in a plaintext environment for FHE compatibility using Quantization-Aware Training to optimize weights and activations. The quantized FCNN model is then validated under FHE constraints through simulation and compiled into an FHE-compatible circuit for encrypted inference on sensitive data. The proposed framework is evaluated on the MedMNIST datasets to assess its accuracy and inference time in both plaintext and encrypted environments. Experimental results reveal that the PPML framework achieves a prediction accuracy of 88.2% in the plaintext setting and 87.5% during encrypted inference, with an average inference time of 150 milliseconds per image. This shows that FCNN models paired with TFHE-based encryption achieve high prediction accuracy on MedMNIST datasets with minimal performance degradation compared to unencrypted inference.
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