PubMed HealthSearch

SEARCH · PubMed Health

Results for “Risk prediction model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Externally validated risk prediction models for gestational diabetes mellitus: A systematic review and meta-analysis.

INTRODUCTION: Risk prediction models for gestational diabetes mellitus (GDM) offer potential for early identification and targeted prevention. External validation is crucial to assess model performance across diverse populations. Despite the availability of numerous GDM prediction models, limited evidence exists on their external validation frequency, methodological quality, and clinical applicability. This systematic review evaluated externally validated GDM prediction models, focusing on methodological rigor, reporting standards, and clinical relevance to inform future research and implementation. MATERIAL AND METHODS: Databases including Ovid MEDLINE, Embase, Scopus, Emcare, and CINAHL were searched up to May 1, 2025. Studies reporting external validation of GDM risk prediction models were included. Two reviewers independently screened studies. Data were extracted using the CHARMS framework, and risk of bias and applicability were assessed using PROBAST+AI. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251125758). RESULTS: Twenty-six studies validated 33 models, with validation sample sizes ranging from 50 to 75 161. Over half used the IADPSG criteria to define GDM. Discrimination metrics were commonly reported, but calibration, overall performance, and clinical utility were often lacking. Meta-analysis was feasible for only four models: Teede et al., Nanda et al., Naylor et al., and Van Leeuwen et al., each showing fair discrimination. The Teede et al. model was the most widely validated, with 11 external validations across six continents and a pooled AUC of 0.72 (95% CI: 0.67-0.76). Despite fewer validations, the Nanda et al. model achieved the highest pooled discrimination (5 validations; pooled AUC 0.77, 95% CI: 0.74-0.80). The Naylor et al. and van Leeuwen et al. models also underwent meta-analysis, as sufficient external validation studies were available to support comparative performance assessment. Notably, 69.23% of studies had a high risk of bias. CONCLUSIONS: While many models showed acceptable predictive performance, most validations were methodologically weak. Future studies should follow best-practice guidelines and promote scalable validation strategies, such as algorithm sharing, to enhance clinical utility.

Humans

Risk prediction models for blood transfusion in patients undergoing total hip and knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and evaluate published risk prediction models for perioperative blood transfusion in patients undergoing total hip or knee arthroplasty (THA/TKA). METHODS: We systematically searched PubMed, Web of Science, the Cochrane Library, and Embase from inception to May 31, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability using the Prediction model Risk Of Bias Assessment Tool (PROBAST). The area under the receiver operating characteristic curve (AUC) values were pooled via a meta-analysis using Stata 18.0. RESULTS: d Fourteen studies containing 36 prediction models were included. The incidence of blood transfusion among THA/TKA patients ranged from 3.2% to 30.8%. Preoperative hemoglobin (Hb) level, tranexamic acid (TXA) use, operative duration, intraoperative blood loss, and age were the most frequently incorporated predictors. Model sensitivity ranged from 58% to 94.5%, and specificity ranged from 71.3% to 94%. Meta-analysis showed that the pooled AUC value of the 13 validated models was 0.87 (95% CI: 0.85-0.90), suggesting good discriminatory performance. All models were rated as having a high risk of bias. The applicability of four studies was rated as unclear. CONCLUSION: Although the included studies demonstrated promising discriminative ability of prediction models for blood transfusion in THA/TKA, all were assessed as having a high risk of bias using the PROBAST tool. Therefore, future research should prioritize the development of models with larger sample sizes, rigorous study designs, and multicenter external validation.

Humans

Predictive Models for Hypoglycemia Risk in Haemodialysis Patients With Diabetic Kidney Disease: Systematic Review and Meta-Analysis.

AIM: To provide evidence for selecting and developing reliable clinical assessment tools for hypoglycemia in diabetic kidney disease patients during haemodialysis. DESIGN: Review. METHODS: Systematic searches were performed in 9 Chinese and English databases to collect literature regarding the development of hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease. Two reviewers independently performed literature screening, data extraction, risk-of-bias assessment, and applicability evaluation. The Prediction Model Risk of Bias Assessment Tool was used to assess the risk of bias and applicability of the included studies. Meta-analysis was conducted using R software. DATA SOURCES: CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, EMbase, Web of Science, and CINAHL. The search period covered from the establishment date of each database to December 2025. RESULTS: Six studies, comprising six prediction models, were included. Two studies performed internal validation, and three conducted external validation. All models reported the area under the curve, ranging from 0.813 to 0.866, and calibration measures. Four studies were rated as having a high risk of bias, while all six demonstrated good overall applicability. The meta-analysis showed that the pooled AUC value of the six studies was 0.846 (95% CI: 0.823-0.867). CONCLUSION: Research on hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease remains in the developmental stage. Although the included prediction models exhibited satisfactory apparent discriminatory ability and clinical applicability, most of the original studies suffered from a high risk of bias and lacked adequate validation. The true predictive performance and clinical application value of these models remain to be further verified. Accordingly, routine and unconditional clinical application is not recommended at this stage. Future studies should include more high-quality, multicenter external validation and develop models with high generalizability, favourable clinical applicability, and robust predictive performance to facilitate early identification of hypoglycemia risk in this population. IMPACT: This study systematically evaluated the hypoglycemia risk prediction models for diabetic kidney disease patients during haemodialysis, and the research on hypoglycemia risk prediction models for maintenance haemodialysis patients during dialysis is still in the development stage. This study provides a reference for clinical medical staff to select or develop hypoglycemia risk prediction and assessment tools for diabetic kidney disease patients during haemodialysis. REPORTING METHOD: This study was conducted in accordance with the relevant guidelines of the EQUATOR Network and followed the TRIPOD-SRMA Checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. TRIAL REGISTRATION: PROSPERO: CRD420251243352.

Humans

The Progress of Gout Prediction Models Based on Multi-source Data.

INTRODUCTION: Gout, a highly serious inflammatory disease that is caused by monosodium urate crystals, is becoming an increasingly significant health concern. Artificial Intelligence and multi-omics-based research have made significant gains for the early detection and prevention of gout based on diverse approaches. This review intends to summarize current advances in forecasting gout susceptibility and gout-related symptoms, evaluate the predictive efficacy of different features, and ascertain which clinical and omics characteristics are most effective in these prediction models. METHODS: We explored the PubMed database after 2010 using keywords such as "gout", "predictive model", "risk prediction", and "machine learning", and confined our search to Englishlanguage articles. The original peer-reviewed research articles that developed gout models were selected. Research that was not original or lacked internal validation was excluded. RESULTS: Clinical features, genomics, microbiomics, radiomics, and metabolomics have been utilized to construct models related to gout and have demonstrated excellent predictive performance. Multisource data prediction models usually exhibit better effectiveness. DISCUSSION: Gout-oriented models performed excellently in predictive performance but present limitations in certain clinical and omics domains. However, if they are to affect actual patient care, they must overcome some external confirmation roadblocks and the fiscal and practical implications they will face ahead of time. CONCLUSION: This review indicates that clinical and multi-omics models of gout are significant instruments for clinical decision-making. The models constructed in these studies may be crucial for the treatment of gout and its practical benefits.

Gout

Breast Cancer Risk Stratification in Black Women: Current Status and Potential Solutions to Improve Accuracy.

Breast cancer risk stratification models identify individuals at increased risk, allowing earlier screening than for those at average risk and potentially improving health outcomes. Due to the increasing rates of breast cancer in individuals aged <40 years, especially among Black females, the American College of Radiology now recommends all females initiate breast cancer risk assessment by age 25 years. Several breast cancer risk prediction models are readily available, including the Gail Model, Breast Cancer Surveillance Consortium Risk Calculator, BOADICEA, and Tyrer-Cuzick Model. However, because these models were primarily developed using data from White women of European ancestry, they may underestimate risk in Black women. Indeed, current evidence suggests that these models underpredict breast cancer risk among Black women, particularly those of African ancestry. Although cancer risk prediction models typically incorporate personal characteristics, family history of cancer, and hormonal and lifestyle factors, inherited breast cancer genes can also increase risk for breast cancer. Beyond monogenic inherited breast cancer genes that increase breast cancer risk, emerging data suggest that single nucleotide polymorphisms identified through genome-wide association studies (GWAS) may be used to generate polygenic risk scores, which may further refine breast cancer risk. However, GWAS data are also primarily gathered from European ancestry females, further reducing the ability to accurately stratify breast cancer risk in non-European ancestry populations. Current data highlight the importance of ensuring representation from all populations in developing cancer risk prediction models, conducting genomics research, and designing effective implementation strategies to enhance the use of these models in routine clinical care. Although new analytic methods and models are being developed to improve breast cancer risk stratification across populations, it remains critical to assess the utility and calibration of existing and new models to ensure applicability across non-European ancestry populations.

Humans

Integrating Imaging-Derived Clinical Endotypes with Plasma Proteomics and External Polygenic Risk Scores Enhances Coronary Microvascular Disease Risk Prediction.

Coronary microvascular disease (CMVD) is an underdiagnosed but significant contributor to the burden of ischemic heart disease, characterized by angina and myocardial infarction. The development of risk prediction models such as polygenic risk scores (PRS) for CMVD has been limited by a lack of large-scale genome-wide association studies (GWAS). However, there is significant overlap between CMVD and enrollment criteria for coronary artery disease (CAD) GWAS. In this study, we developed CMVD PRS models by selecting variants identified in a CMVD GWAS and applying weights from an external CAD GWAS, using CMVD-associated loci as proxies for the genetic risk. We integrated plasma proteomics, clinical measures from perfusion PET imaging, and PRS to evaluate their contributions to CMVD risk prediction in comprehensive machine and deep learning models. We then developed a novel unsupervised endotyping framework for CMVD from perfusion PET-derived myocardial blood flow data, revealing distinct patient subgroups beyond traditional case-control definitions. This imaging-based stratification substantially improved classification performance alongside plasma proteomics and PRS, achieving AUROCs between 0.65 and 0.73 per class, significantly outperforming binary classifiers and existing clinical models, highlighting the potential of this stratification approach to enable more precise and personalized diagnosis by capturing the underlying heterogeneity of CMVD. This work represents the first application of imaging-based endotyping and the integration of genetic and proteomic data for CMVD risk prediction, establishing a framework for multimodal modeling in complex diseases.

Cardiovascular Disease

Exploring China's Clean Air Act and associated cardiovascular disease risk: a prospective, quasi-experimental, and causal inference modelling study.

BACKGROUND: Substantial improvements in air quality have been recorded following the implementation of China's Clean Air Act (CCAA) in 2013. However, the association between CCAA implementation and individual-level cardiovascular disease (CVD) risk remains unclear. We aimed to examine the long-term association between CCAA implementation and individual-level predicted CVD risk. METHODS: In this prospective, quasi-experimental study, we used data from the China Kadoorie Biobank, a prospective cohort study that recruited participants from five urban and five rural areas across China between 2004 and 2008, with three resurveys conducted after the baseline survey (in 2008, 2013-14, and 2020-21). We included 34&#x2009;862 individuals (mean age 51&#xb7;3 years) who participated in at least one resurvey and had no history of CVD at baseline. Participants were classified into intervention (n=25&#x2009;497) and control (n=9365) groups based on the local government's targets for particulate matter reduction. We estimated the 10-year risk of incident CVD morbidity or mortality using a validated risk prediction model. We used a difference-in-difference model to assess the long-term association between CCAA implementation and predicted risk, with adjustments made for regional confounders and individual-level characteristics, including demographics, lifestyle factors, medical history, and indoor air pollution exposure. The relationship between changes in long-term exposure to PM2&#xb7;5, PM10, and O3 and predicted risk after CCAA implementation was analysed using a linear model. The estimated risk differences associated with air pollutant changes were estimated based on the magnitude of changes and their corresponding effect sizes. FINDINGS: After the CCAA was implemented, PM2&#xb7;5 and PM10 concentrations declined in both groups, but O3 concentrations increased. The intervention group showed a 3&#xb7;95% (95% CI 3&#xb7;18-4&#xb7;72%) lower increase in predicted risk than the control group, with larger estimated differences under stricter enforcement. Between 2013 and 2021, each 10 &#x3bc;g/m3 change in PM2&#xb7;5 concentration was positively associated with a 1&#xb7;80 (1&#xb7;34-2&#xb7;27) percentage point change in predicted CVD risk, whereas each 10 &#x3bc;g/m3 change in PM10 concentration was associated with a 1&#xb7;24 (0&#xb7;84-1&#xb7;63) percentage point change and each 10 &#x3bc;g/m3 change in O3 concentration with a 0&#xb7;58 (0&#xb7;33-0&#xb7;83) percentage point change. Overall, the observed changes in air pollutants during the study period were associated with an average 6&#xb7;6 percentage point reduction in predicted CVD risk. INTERPRETATION: The CCAA and improved air quality were associated with a slower increase in predicted CVD risk, supporting the necessity for stricter, multipollutant air quality policies to maximise public health benefits. FUNDING: National Natural Science Foundation of China, Kadoorie Charitable Foundation, Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, Chinese Ministry of Science and Technology, and UK Wellcome Trust.

Journal Article

A prediction model for metachronous colorectal cancer: development and validation.

BACKGROUND: Being able to estimate the risk of metachronous disease in a patient with colorectal cancer (CRC) could enable risk-appropriate surveillance. The aim of this study was to develop a risk-prediction model to estimate individual 10-year risk of metachronous disease following a CRC diagnosis. METHODS: A population-based cohort of patients with CRC was recruited soon after diagnosis between 1997 and 2012 from the United States, Canada, and Australia. Cox regression with the least absolute shrinkage and selection operator penalization was used to identify factors that predicted the risk of a new primary CRC diagnosed at least 1 year after the initial CRC diagnosis. Potential predictors included demography, anthropometry, lifestyle factors, comorbidities, personal and family cancer history, medication use, age at diagnosis, and pathological features of the first CRC. Internal validation through bootstrapping was used to evaluate the discrimination and calibration. RESULTS: We included 6085 CRC cases; 138 (2.3%) of these cases were diagnosed with metachronous disease over a median of 12&#x2009;years (IQR&#x2009;=&#x2009;5-17&#x2009;years). Metachronous CRC risk was predicted by body mass index; smoking status; level of physical activity; family history of cancer and synchronous CRC; stage, grade, histological type, and DNA mismatch repair status; and age at diagnosis of the first CRC. The model was valid with a C statistic of 0.65 (95% CI&#x2009;=&#x2009;0.63 to 0.68) and a calibration slope of 0.873 (SD = 0.087). CONCLUSIONS: Metachronous CRC can be predicted with reasonable accuracy using a prediction model that consists of clinical variables collected as part of routine practice.

Humans

Diagnostic performance of machine learning models versus established risk stratification for intracranial aneurysm rupture: a systematic review and bivariate meta-analysis.

BACKGROUND: Machine learning (ML) models have been proposed to improve the discrimination of intracranial aneurysm rupture status beyond established clinical risk stratification tools. However, reported performance is heterogeneous and the relative contribution of model architecture and feature dominance remains unclear. METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-diagnostic test accuracy systematic review and diagnostic meta-analysis of studies evaluating ML models for intracranial aneurysm rupture discrimination. PubMed, Embase and CENTRAL were searched to February 2026. Sensitivity and specificity were pooled using a bivariate random-effects model, with summary receiver operating characteristic curves generated across training, internal testing and external validation datasets. Models were compared with regression-based approaches and Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid haemorrhage, Site of aneurysm (PHASES) scores. Subgroup and meta-regression analyses explored associations between algorithm family and feature domain. RESULTS: Sixty-two retrospective cohorts (29&#x2009;709 patients 209 models) met the inclusion criteria. In training datasets, pooled sensitivity and specificity for ML were 0.81 (95% CI 0.75 to 0.85)&#x2009;and 0.83 (0.80-0.86), with an area under the curve (AUC) of 0.878, exceeding PHASES (AUC 0.667). In testing datasets, ML retained higher discrimination (AUC 0.837) than regression models (0.806) and PHASES (0.646). In external validation, sensitivity was preserved (0.82), but specificity declined (0.66). Deep learning demonstrated the highest AUCs (training and testing). Incorporation of haemodynamic or radiomic features improved pooled discrimination relative to morphology alone. Evidence of small-study effects and mostly unclear Prediction Model Risk Of Bias Assessment Tool ratings were observed. CONCLUSIONS: ML approaches demonstrate higher pooled discrimination for aneurysm rupture status than conventional risk scores in retrospective datasets, but reduced external validation specificity and heterogeneity limit confidence for clinical translation. Prospective, externally validated, calibrated models are required before integration into routine cerebrovascular risk stratification.

Humans

Telomere Length Dynamics as a Biomarker of Individual Radiation Sensitivity and Pneumonitis in Lung Cancer Patients Receiving Thoracic Radiation Therapy.

PURPOSE: Telomere shortening is a biomarker for genome instability and aging, and the vulnerability of telomeric DNA to oxidative damage suggests its potential role in mediating radiation therapy (RT) side effects. This study evaluates telomere length (TL) as a biomarker for clinical radiosensitivity and adverse outcomes in thoracic RT-treated patients. METHODS AND MATERIALS: Patients with cancer receiving thoracic RT (2019-2022) were prospectively enrolled at Brigham and Women's Hospital, Boston, Massachusetts. Peripheral blood mononuclear cells (PBMCs) were collected pre-RT and &#x2264;12 months post-RT. TL was measured using quantitative PCR, and multipathway DNA repair capacity (DRC) was simultaneously assessed by fluorescence multiplex host cell reactivation assays. RT outcomes included patient-reported quality of life and radiation pneumonitis. Linear mixed-effects models were used to analyze TL dynamics; risk prediction models for RT outcomes were evaluated using area under the curve. RESULTS: Pre-RT TL decreased with age (0.44% lower per year; 95% CI, 0.12%-0.77%) and advanced cancer stage (6.87% lower per step increase of stage; 95% CI, 3.45%-10.16%). Radical RT was associated with telomere shortening (3.7% lower; 95% CI, 0.27%-7.07%) in PBMCs, detectable &#x2264;6 months post-RT. Pre-RT TL strongly predicted post-RT changes, and TL dynamics outperformed static measures in predicting symptom burden and radiation pneumonitis. Positive associations were observed between TL and DRC against oxidative lesions, with A:8-oxoG repair capacity mediating 12.8% of RT-induced TL shortening. CONCLUSIONS: Lymphocyte TL can reflect individual radiosensitivity and interact with oxidative damage repair. Longitudinal assessment of TL dynamics provides additional predictive value for adverse RT outcomes compared with static measures. Further studies are needed to fully determine the clinical utility of TL.

Humans

Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification.

BACKGROUND AND AIMS: Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for potentially life-threatening arrhythmic events (AEs) even while treated with &#x3b2;-blockers. The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediated CPVT on &#x3b2;-blocker monotherapy. METHODS: The derivation and independent validation cohorts included 743 and 129 patients, respectively. AEs were defined as arrhythmic syncope, appropriate implantable cardioverter-defibrillator shock, sudden cardiac arrest (SCA), and sudden cardiac death. Near-fatal or fatal AEs (nf/fAEs) included all AEs except for arrhythmic syncope. Prediction models using Cox regression were developed and internally and externally validated. RESULTS: A total of 102 (13.7%) patients in the derivation cohort and 24 (18.6%) patients in the validation cohort experienced &#x2265;1 AE over a median follow-up of 5.1 [interquartile range (IQR), 7.7] and 2.4 (IQR, 4.4) years, respectively. Predictors of AE were arrhythmic syncope or SCA prior to diagnosis and age at &#x3b2;-blocker initiation. In the derivation and validation cohorts, the optimism-corrected C-indices of the models for AE were 0.67 [95% confidence interval (CI) 0.62-0.72] and 0.59 (95% CI 0.48-0.71), respectively. For nf/fAEs, ventricular arrhythmia severity before &#x3b2;-blocker initiation was a fourth independent predictor, and C-indices of the models in the derivation and validation cohorts were 0.74 (95% CI 0.68-0.80) and 0.60 (95% CI 0.47-0.72), respectively. In the derivation cohort, calibration slopes were 1.00 (95% CI 0.59-1.41) for AE and 1.00 (95% CI 0.69-1.32) for nf/fAE. CONCLUSIONS: These externally validated risk prediction models using clinical parameters accurately distinguished CPVT patients on &#x3b2;-blocker monotherapy at low and high risk for future AEs while treated with &#x3b2;-blockers. These models provide guidance for implementation of clinical management therapies to prevent AEs in patients with CPVT.

Humans

Evaluating the impact of modeling choices on the performance of integrated genetic and clinical models.

PURPOSE: The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results. We performed multiple modeling experiments integrating clinical and demographic data from electronic health records with genetic data to understand which decisions may affect performance. METHODS: Clinical data in the form of structured diagnostic codes, medications, procedural codes, and demographics were extracted from 2 large independent health systems, and polygenic risk scores (PRS) were generated across all patients of European ancestry with genetic data in the corresponding biobanks. Crohn's disease was studied based on its substantial genetic component, established electronic health records-based definition, and sufficient prevalence for training and testing. We investigated the impact of choices regarding the PRS integration method, training sample, model complexity, and performance metrics. RESULTS: Overall, our results showed that including PRS resulted in higher performance, but this gain was only robust in situations with limited clinical information. We found consistent performance increases from more compute-intensive models, such as random forest, but the impact of other decisions varied by site. CONCLUSION: This work highlights the importance of considering methodological decision points in interpreting the impact of PRS on prediction performance in clinical models.

Humans

Evaluating the impact of modeling choices on the performance of integrated genetic and clinical models.

The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results across studies. Here, we performed multiple modeling experiments integrating clinical and demographic data from electronic health records (EHR) and genetic data to understand which decision points may affect performance. Clinical data in the form of structured diagnostic codes, medications, procedural codes, and demographics were extracted from two large independent health systems and polygenic risk scores (PRS) were generated across all patients with genetic data in the corresponding biobanks. Crohn's disease was used as the model phenotype based on its substantial genetic component, established EHR-based definition, and sufficient prevalence for model training and testing. We investigated the impact of PRS integration method, as well as choices regarding training sample, model complexity, and performance metrics. Overall, our results show that including PRS resulted in higher performance by some metrics but the gain in performance was only robust when combined with demographic data alone. Improvements were inconsistent or negligible after including additional clinical information. The impact of genetic information on performance also varied by PRS integration method, with a small improvement in some cases from combining PRS with the output of a clinical model (late-fusion) compared to its inclusion an additional feature (early-fusion). The effects of other modeling decisions varied between institutions though performance increased with more compute-intensive models such as random forest. This work highlights the importance of considering methodological decision points in interpreting the impact on prediction performance when including PRS information in clinical models.

Preprint

Large-Scale Plasma Proteomics Identifies Early Molecular Deviations and Improves Risk Prediction for Heart Failure Among Individuals With Obesity.

AIMS: Heart failure (HF) is a major global public health challenge, with obesity being one of its key risk factors. Although several HF risk prediction models have been developed in the general population, few are specifically tailored to individuals with obesity. This underscores the urgent need for precise biomarkers to improve individual risk stratification and enable personalized prevention strategies. We aimed to develop and validate a plasma proteomics-based protein risk score (PRS) to predict incident HF among individuals with obesity. MATERIALS AND METHODS: We analysed 9831 participants with obesity (BMI &#x2265;&#x2009;30&#x2009;kg/m2) from the UK Biobank with baseline measurements of 2911 circulating proteins and up to 16&#x2009;years of follow-up. Multivariable Cox regression identified proteins associated with incident HF after comprehensive covariate adjustment. A PRS was constructed using LASSO regression and evaluated in a held-out test set. Protein trajectories before HF onset were reconstructed using LOESS modelling. To enhance clinical feasibility, a minimal protein panel was identified using LightGBM with forward feature selection. RESULTS: A total of 727 participants developed HF during follow-up. Multivariable cox analyses identified 578 proteins significantly associated with HF. LASSO regression further selected 81 proteins to build the PRS, which showed a strong association with HF risk in both training (HR 3.57; 95% CI 3.19-4.00) and test cohorts (HR 2.45; 95% CI 2.20-2.74). Adding the PRS improved prediction beyond age and sex (&#x394;C&#x2009;=&#x2009;0.091) and beyond the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) model (&#x394;C&#x2009;=&#x2009;0.052), with consistent gains in NRI and IDI. Proteomic deviations were detectable up to 16&#x2009;years before diagnosis. A four-protein panel (GDF15, NT-proBNP, TNFRSF10B, CTHRC1) achieved robust discrimination (AUC 0.789), outperforming NT-proBNP alone (AUC 0.695) and complementing the PCP-HF model (combined AUC 0.803). DISCUSSION: Large-scale plasma proteomics substantially improves HF risk prediction in individuals with obesity and reveals long-standing molecular alterations preceding clinical onset. A simplified four-protein panel maintains robust predictive accuracy and provides a practical approach for the early detection and targeted prevention of obesity-related HF.

Humans

Multiple features of cell-free mtDNA for predicting transarterial chemoembolization response in hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is the primary treatment modality for advanced HCC, yet its efficacy assessment and prognosis prediction largely depend on imaging and serological markers that possess inherent limitations in terms of real-time capability, sensitivity, and specificity. Here, we explored whether multiple features of cell-free mitochondrial DNA (cf-mtDNA), including copy number, mutations, and fragmentomics, could be used to predict the response and prognosis of patients with HCC undergoing TACE treatment. METHODS: A total of 60 plasma cell-free DNA samples were collected from 30 patients with HCC before and after the first TACE treatment and then subjected to capture-based mtDNA sequencing and whole-genome sequencing. RESULTS: Comprehensive analyses revealed a clear association between cf-mtDNA multiple features and tumor characteristics. Based on cf-mtDNA multiple features, we also developed HCC death and progression risk prediction models. Kaplan-Meier curve analyses revealed that the high-death risk or high-progression-risk group had significantly shorter median overall survival (OS) and progression-free survival than the low-death risk or low-progression-risk group (all p<0.05). Moreover, the change in cf-mtDNA multiple features before and after TACE treatment exhibited an exceptional ability to predict the risk of death and progression in patients with HCC (log-rank test, all p<0.01; HRs: 0.36 and 0.33, respectively). Furthermore, we observed the consistency of change between the cf-mtDNA multiple features and copy number variant burden before and after TACE treatment in 40.00% (12/30) patients with HCC. CONCLUSIONS: Altogether, we developed a novel strategy based on profiling of cf-mtDNA multiple features for prognosis prediction and efficacy evaluation in patients with HCC undergoing TACE treatment.

Humans

Risk Factors and Predictive Model for Postoperative High Myopia in Children Undergoing Congenital Cataract Surgery With Intraocular Lens Implantation.

PURPOSE: To identify risk factors associated with the development of high myopia following congenital cataract surgery and to establish a robust predictive model. DESIGN: Retrospective clinical cohort study. SUBJECTS: This retrospective study included 106 pediatric patients who underwent congenital cataract surgery with primary IOL implantation (mean follow-up 8.19 years). The model was externally validated in an independent cohort of 72 patients with a mean follow-up of 7.83 years. METHODS: Preoperative and postoperative ocular biometric parameters were collected. Risk factors for postoperative high myopia were analyzed using Cox proportional hazards regression, which served as the basis for model construction. The predictive performance of the model was rigorously evaluated for discrimination and calibration. Discriminative ability was quantified using Harrell's C-index and the area under the receiver operating characteristic curve (AUC). Model calibration was assessed via calibration plots by comparing predicted probabilities with actual observed outcomes. Internal validation was performed using a bootstrapping method (500 iterations) to ensure model stability and adjust for potential overfitting. RESULTS: An initial postoperative refraction of <+0.75D, and a higher IOL Power to Axial length Ratio (IOL/AL ratio) were identified as significant risk factors for the development of postoperative high myopia. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. The predictive model demonstrated robust performance, achieving a C-index of 0.711 (internal validation C-index: 0.713). The area under the receiver operating characteristic curve (AUC) values for predicting high myopia at 5 and 10 years were 0.858 and 0.745, respectively. Furthermore, calibration curves demonstrated excellent agreement between the predicted and observed outcomes throughout the follow-up period. In external validation, the model achieved a C-index of 0.825, 5-year AUC of 0.833, and 10-year AUC of 0.713. CONCLUSIONS: Our analysis established that initial postoperative refraction <+0.75D, and an elevated IOL/AL ratio are key determinants of high myopia risk following surgery. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. This predictive framework provides clinicians with a practical tool to optimize preoperative IOL selection and identify high-risk infants who require vigilant myopia prevention and balanced amblyopia management.

Humans

Prognostic value of genes associated with metastasis and propionate metabolism in rectal cancer.

BACKGROUND: Research indicates that alterations in propionate metabolic pathways play a critical role in cancer development and invasion. Postoperative metastatic recurrence remains a major cause of mortality in patients with rectal cancer. However, propionate metabolism-related genes (PMRGs) in rectal cancer remain insufficiently characterized. Therefore, this study aimed to identify prognostic biomarkers associated with lymph node metastasis and propionate metabolism and construct a risk&#x2011;prediction model for rectal cancer via bioinformatic analyses. METHODS: The Cancer Genome Atlas-Rectum Adenocarcinoma (TCGA-READ) and GSE87211 datasets, together with a curated PMRGs gene set, were used in this study. Pearson correlation analysis was performed to assess associations between overlapping genes (differentially expressed genes between READ and normal tissues, as well as between N0 and N1-N2 stages) and PMRGs, leading to the identification of candidate genes. Functional enrichment analyses were subsequently conducted to characterize the biological roles of these candidates. Prognostic biomarkers were identified using univariate Cox regression combined with least absolute shrinkage and selection operator (LASSO) regression, and a prognostic model was constructed accordingly. Independent prognostic validation was then performed. In addition, immune checkpoint profiling and immunotherapy response analyses were conducted across risk subgroups. Single-gene Gene Set Enrichment Analysis (GSEA) was applied to elucidate the pathways associated with the identified biomarkers. Finally, drug sensitivity analyses were performed. RESULTS: A total of 157 candidate genes were identified through the analytical pipeline. Functional enrichment analysis indicated that these genes were primarily involved in inflammatory response regulation and tumor necrosis factor (TNF) signaling pathways. Five prognostic biomarkers were subsequently identified and incorporated into a predictive model. External validation using the GSE87211 cohort confirmed the robustness of the model. Risk score and disease status were identified as independent prognostic factors. Six immune checkpoint molecules exhibited differential expression between risk groups. Correlation analyses revealed that the risk score was positively associated with most immune checkpoint genes. Single-gene GSEA demonstrated that the biomarkers were mainly enriched in ribosomal biogenesis and cell adhesion molecule-related pathways. Furthermore, 51 therapeutic agents exhibited significantly different half-maximal inhibitory concentration (IC50) values between risk subgroups. CONCLUSIONS: This study identified five biomarkers (CCL24, IGFBP3, ODC1, PYGM, and VKORC1) associated with lymph node metastasis and propionate metabolism pathways, providing a potential foundation for prognostic prediction in patients with rectal cancer.

Rectal cancer

Identification and evaluation of glutamine-related gene characteristics based on multi-omics to predict the prognosis of patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), a prevalent malignancy of the gastrointestinal tract, ranks among the leading causes of cancer-related morbidity and mortality. Its clinical course is marked by high fatality and poor prognosis. Elucidating the mechanisms underlying CRC initiation and recurrence is therefore critical for identifying novel therapeutic targets. METHODS: This study incorporated two datasets, TCGA-CRC and GSE17537. A total of 84 glutamine metabolism-related genes (GMRGs) were identified, and differential expression analysis was conducted using the TCGA-CRC dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to determine gene modules most strongly associated with GMRG scores. Single-cell RNA sequencing (scRNA-seq) was utilized to characterize key cellular clusters and to identify differentially expressed genes (DEGs) between high and low glutamine metabolism (GM) groups. Overlapping GMRGs were visualized using the ggVennDiagram package in R. A CRC risk prediction model was developed through Cox proportional hazards and LASSO regression analyses, with performance evaluated by ROC curves. Cell type enrichment across 64 immune and stromal populations was assessed via xCell, and intergroup differences were tested using the Wilcoxon rank-sum test. TIDE scores were used to estimate immunotherapy responsiveness, while oncoPredict facilitated drug sensitivity profiling. PCOLCE2 expression in CRC was validated by RT-qPCR and Western blotting. Its functional role was examined through CCK-8 assays, invasion and migration tests, flow cytometry, and glutamate quantification. RESULTS: ScRNA-seq analysis identified two key cell populations and 437 DEGs associated with GM status. WGCNA pinpointed the MEgreen module as most significantly correlated with GMRG scores, encompassing 1075 genes. Integration of DEGs, module genes, and GM-related DEGs yielded 60 candidate genes for downstream analysis. A GMRG-based prognostic model comprising six genes (SRPX, CXCL1, GPX3, PCOLCE2, CLU, SEMA3E) demonstrated strong predictive performance. Prognostic gene expression correlated with immune and stromal infiltration patterns, as indicated by Spearman correlation analysis. The high-risk group exhibited diminished predicted response to immunotherapy (TIDE scores). Drug sensitivity analysis identified four compounds&#x2014;Dasatinib-51, WH-4-023-56, TWS-119-366, and LDN-193189-478&#x2014;with elevated efficacy in high-risk CRC cases. PCOLCE2 expression was significantly reduced in CRC tissues. Functional assays revealed that PCOLCE2 knockdown did not substantially affect cell proliferation but significantly impaired invasion and migration in CRC cells, increased apoptosis, and suppressed both glutamine uptake and glutamate production&#x2014;highlighting its oncogenic role. CONCLUSION: Six GMRGs&#x2014;SRPX, CXCL1, GPX3, PCOLCE2, CLU, and SEMA3E&#x2014;were identified as key components of a robust prognostic model for CRC. These findings offer valuable insights into CRC pathogenesis and potential therapeutic strategies. Notably, this study provides the first evidence implicating PCOLCE2 as a tumor-promoting factor in CRC.

Glutamine