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1.
3D Print Addit Manuf ; 11(4): 1407-1417, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39360143

RESUMO

The ability to jet a wide variety of materials consistently from print heads remains a key technical challenge for inkjet-based additive manufacturing processes. Drop watching is the most direct method for testing new inks and print head designs but such experiments are also resource consuming. In this work, a data-efficient machine learning technique called active learning is used to construct detailed jettability diagrams that identify complex regions corresponding to "no jetting," "jetting," and "desired jetting," rather than only individually sampled points. Crucially, our active learning method has resolved challenges with model selection that previously limited the accuracy of active learning in practical settings with very small experimental budgets. In addition, the key "desired jetting" zone may be quite small which is a challenge for initializing active learning. We leverage the physical intuition that the "desired jetting" zone tends to exist between the "jetting" and "no jetting" zone, to improve the performance of this highly imbalanced classification problem by performing two binary classifications in sequence. The first binary classification aims to map out the "jetting" zone versus the "no jetting" zone, while the second binary classification targets identifying the "desired jetting" zone with primary drops only. Our experiments use a stroboscopic drop watcher to visualize the jetting behavior of two fluids from a piezoelectric print head with different jetting waveforms. The results obtained from active learning were compared to a grid search method, which involves running more than 200 experiments for each fluid. The active learning method significantly reduces the number of experiments by 80% while achieving a test accuracy of more than 95% in the "jetting" zone prediction for the test fluids. The ability to construct these jettability diagrams will further accelerate new ink and print head developments.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39353461

RESUMO

BACKGROUND: The risk of biochemical recurrence (BCR) after radiotherapy for localized prostate cancer (PCa) varies widely within standard risk groups. There is a need for low-cost tools to more robustly predict recurrence and personalize therapy. Radiomic features from pretreatment MRI show potential as noninvasive biomarkers for BCR prediction. However, previous research has not fully combined radiomics with clinical and pathological data to predict BCR in PCa patients following radiotherapy. Purpose: This study aims to predict 5-year BCR using radiomics from pretreatment T2W MRI and clinical-pathological data in PCa patients treated with radiation therapy, and to develop a unified model compatible with both 1.5T and 3T MRI scanners. Methods: A total of 150 T2W scans and clinical parameters were preprocessed. Of these, 120 cases were used for training and validation, and 30 for testing. Four distinct machine learning models were developed: Model 1 used radiomics, Model 2 used clinical and pathological data, and Model 3 combined these using late fusion. Model 4 integrated radiomic and clinical-pathological data using early fusion. Results: Model 1 achieved an AUC of 0.73, while Model 2 had an AUC of 0.64 for predicting outcomes in 30 new test cases. Model 3, using late fusion, had an AUC of 0.69. Early fusion models showed strong potential, with Model 4 reaching an AUC of 0.84, highlighting the effectiveness of the early fusion model. Conclusions: This study is the first to use a fusion technique for predicting BCR in PCa patients following radiotherapy, utilizing pre-treatment T2W MRI images and clinical-pathological data. The methodology improves predictive accuracy by fusing radiomics with clinical-pathological information, even with a relatively small dataset, and introduces the first unified model for both 1.5T and 3T MRI images.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39307322

RESUMO

PURPOSE: To investigate the predictive value of changes in segmental myocardial 18F- fluorodeoxyglucose (FDG) uptake for major adverse cardiac events (MACEs) in patients with locally advanced esophageal cancer undergoing definitive radiation therapy (RT). MATERIALS AND METHODS: Between August 2012 and January 2019, 482 patients with stage II-III esophageal cancer from two institutions were enrolled and divided into the training (n = 285) and external validation (n = 197) cohorts. All patients underwent 18F-FDG PET within 1 week before treatment and within 3 months of treatment. Myocardial delineation was performed using the Carimas software based on the AHA 17-segment model and was automatically divided into basal, middle, and apical regions. The main endpoint was the occurrence of MACEs, including unstable angina, myocardial infarction, coronary revascularization, hospitalization for heart failure or urgent visits, and cardiac death. Analyses included competing risk and Cox regression. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and Brier score. RESULTS: Thirty-four patients (11.9%) developed MACEs at a median follow-up of 78 months. The basal region (median: 19.44 Gy) of the myocardium received the highest radiation dose, followed by the middle (median: 13.02 Gy) and apical regions (median: 9.32 Gy). Multivariate analysis showed that the change ratio in pre- and post-treatment basal myocardial SUVmean (basal ∆SUVRmean) remained significant after adjusting for age, pre-existing cardiac disease, and dosimetric parameters. The AUCs and Brier scores demonstrated favorable predictive accuracies of models integrating variables with significant differences in the multivariate analysis when predicting MACEs in the training and validation cohorts. CONCLUSION: Basal ∆SUVRmean was an independent predictor of MACEs in patients with locally advanced esophageal cancer receiving definitive RT. Changes in basal myocardial FDG uptake are promising biomarkers for predicting radiation-induced cardiotoxicity.

4.
J Biomed Inform ; 158: 104723, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299565

RESUMO

OBJECTIVE: Disease severity scores, or endpoints, are routinely measured during Randomized Controlled Trials (RCTs) to closely monitor the effect of treatment. In real-world clinical practice, although a larger set of patients is observed, the specific RCT endpoints are often not captured, which makes it hard to utilize real-world data (RWD) to evaluate drug efficacy in larger populations. METHODS: To overcome this challenge, we developed an ensemble technique which learns proxy models of disease endpoints in RWD. Using a multi-stage learning framework applied to RCT data, we first identify features considered significant drivers of disease available within RWD. To create endpoint proxy models, we use Explainable Boosting Machines (EBMs) which allow for both end-user interpretability and modeling of non-linear relationships. RESULTS: We demonstrate our approach on two diseases, rheumatoid arthritis (RA) and atopic dermatitis (AD). As we show, our combined feature selection and prediction method achieves good results for both disease areas, improving upon prior methods proposed for predictive disease severity scoring. CONCLUSION: Having disease severity over time for a patient is important to further disease understanding and management. Our results open the door to more use cases in the space of RA and AD such as treatment effect estimates or prognostic scoring on RWD. Our framework may be extended beyond RA and AD to other diseases where the severity score is not well measured in electronic health records.

5.
Dent J (Basel) ; 12(9)2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39329854

RESUMO

The science of dental tissue grafting is evolving, with an increased understanding of factors influencing graft behavior. Despite the widespread clinical use of soft tissue grafts, the histological characteristics of different gingival harvesting sites are still underexplored. This study aimed to fill this gap by analyzing 50 tissue samples harvested from 25 patients across three sites: the hard palate, maxillary tuberosity, and palatal rugae. Each sample underwent thorough histological and histomorphometric analysis. Conventional statistical analysis was performed using SPSS, while predictive modeling was conducted with RapidMiner Studio. The study identified significant histological differences among the graft sites, with notable variations in total graft height, epithelial height, and interdigitation perimeter. These findings underscore the importance of donor site selection in influencing graft success. Pair plots and principal component analysis (PCA) further highlighted the distinct histological features of each tissue type. The random forest classifier identified total graft height, epithelial height, and perimeter as the most influential factors in predicting graft site behavior. This study offers valuable insights into the histological characteristics of soft tissue grafts, potentially leading to more predictable clinical outcomes.

6.
PeerJ ; 12: e17797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39221276

RESUMO

Numerous aspects of cellular signaling are regulated by the kinome-the network of over 500 protein kinases that guides and modulates information transfer throughout the cell. The key role played by both individual kinases and assemblies of kinases organized into functional subnetworks leads to kinome dysregulation driving many diseases, particularly cancer. In the case of pancreatic ductal adenocarcinoma (PDAC), a variety of kinases and associated signaling pathways have been identified for their key role in the establishment of disease as well as its progression. However, the identification of additional relevant therapeutic targets has been slow and is further confounded by interactions between the tumor and the surrounding tumor microenvironment. In this work, we attempt to link the state of the human kinome, or kinotype, with cell viability in treated, patient-derived PDAC tumor and cancer-associated fibroblast cell lines. We applied classification models to independent kinome perturbation and kinase inhibitor cell screen data, and found that the inferred kinotype of a cell has a significant and predictive relationship with cell viability. We further find that models are able to identify a set of kinases whose behavior in response to perturbation drive the majority of viability responses in these cell lines, including the understudied kinases CSNK2A1/3, CAMKK2, and PIP4K2C. We next utilized these models to predict the response of new, clinical kinase inhibitors that were not present in the initial dataset for model devlopment and conducted a validation screen that confirmed the accuracy of the models. These results suggest that characterizing the perturbed state of the human protein kinome provides significant opportunity for better understanding of signaling behavior and downstream cell phenotypes, as well as providing insight into the broader design of potential therapeutic strategies for PDAC.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Ductal Pancreático , Sobrevivência Celular , Neoplasias Pancreáticas , Proteínas Quinases , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/enzimologia , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos Associados a Câncer/patologia , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/enzimologia , Linhagem Celular Tumoral , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/enzimologia , Proteínas Quinases/metabolismo , Transdução de Sinais , Microambiente Tumoral , Inibidores de Proteínas Quinases/farmacologia
7.
Front Med (Lausanne) ; 11: 1427768, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267965

RESUMO

Introduction: Total Knee Arthroplasty (TKA) is a widely performed procedure that significantly benefits patients with severe knee degeneration. However, the recovery outcomes post-surgery can vary significantly among patients. Identifying the factors influencing these outcomes is crucial for improving patient care and satisfaction. Methods: In this retrospective study, we analyzed 362 TKA cases performed between January 1, 2018, and July 1, 2022. Multivariate logistic regression was employed to identify key predictors of recovery within the first year after surgery. Results: The analysis revealed that Body Mass Index (BMI), age-adjusted Charlson Comorbidity Index (aCCI), sleep quality, Bone Mineral Density (BMD), and analgesic efficacy were significant predictors of poor recovery (p < 0.05). These predictors were used to develop a clinical prediction model, which demonstrated strong predictive ability with an Area Under the Receiver Operating Characteristic (AUC) curve of 0.802. The model was internally validated. Discussion: The findings suggest that personalized postoperative care and tailored rehabilitation programs based on these predictors could enhance recovery outcomes and increase patient satisfaction following TKA.

8.
Brain Cogn ; 181: 106221, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39250856

RESUMO

BACKGROUND: Cognitive control involves flexibly configuring mental resources and adjusting behavior to achieve goal-directed actions. It is associated with the coordinated activity of brain networks, although it remains unclear how both structural and functional brain networks can predict cognitive control. Connectome-based predictive modeling (CPM) is a powerful tool for predicting cognitive control based on brain networks. METHODS: The study used CPM to predict cognitive control in 102 healthy adults from the UCLA Consortium for Neuropsychiatric Phenomics dataset and further compared structural and functional connectome characteristics that support cognitive control. RESULTS: Our results showed that both structural (r values 0.263-0.375) and functional (r values 0.336-0.503) connectomes can significantly predict individuals' cognitive control subcomponents. There is overlap between the functional and structural networks of all three cognitive control subcomponents, particularly in the frontoparietal (FP) and motor (Mot) networks, while each subcomponent also has its own unique weight prediction network. Overall, the functional and structural connectivity that supports different cognitive control subcomponents manifests overlapping and distinct spatial patterns. CONCLUSIONS: The structural and functional connectomes provide complementary information for predicting cognitive control ability. Integrating information from both connectomes offers a more comprehensive understanding of the neural underpinnings of cognitive control.

9.
Front Artif Intell ; 7: 1408029, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233890

RESUMO

Introduction: Hemorrhage remains a leading cause of death in civilian and military trauma. Hemorrhages also extend to military working dogs, who can experience injuries similar to those of the humans they work alongside. Unfortunately, current physiological monitoring is often inadequate for early detection of hemorrhage. Here, we evaluate if features extracted from the arterial waveform can allow for early hemorrhage prediction and improved intervention in canines. Methods: In this effort, we extracted more than 1,900 features from an arterial waveform in canine hemorrhage datasets prior to hemorrhage, during hemorrhage, and during a shock hold period. Different features were used as input to decision tree machine learning (ML) model architectures to track three model predictors-total blood loss volume, estimated percent blood loss, and area under the time versus hemorrhaged blood volume curve. Results: ML models were successfully developed for total and estimated percent blood loss, with the total blood loss having a higher correlation coefficient. The area predictors were unsuccessful at being directly predicted by decision tree ML models but could be calculated indirectly from the ML prediction models for blood loss. Overall, the area under the hemorrhage curve had the highest sensitivity for detecting hemorrhage at approximately 4 min after hemorrhage onset, compared to more than 45 min before detection based on mean arterial pressure. Conclusion: ML methods successfully tracked hemorrhage and provided earlier prediction in canines, potentially improving hemorrhage detection and objectifying triage for veterinary medicine. Further, its use can potentially be extended to human use with proper training datasets.

10.
Cancer Manag Res ; 16: 1175-1187, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39258245

RESUMO

Purpose: This study aims to develop a machine learning (ML) model to predict the risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN) after loop electrosurgical excision procedure (LEEP), addressing a critical gap in personalized follow-up care. Methods: A retrospective analysis of 532 patients who underwent LEEP for high-grade CIN at Cangzhou Central Hospital (2016-2020) was conducted. In the final analysis, 99 women (18.6%) were found to have residual or recurrent high-grade CIN (CIN2 or worse) within five years of follow-up. Four feature selection methods identified significant predictors of residual or recurrent CIN. Eight ML algorithms were evaluated using performance metrics such as AUROC, accuracy, sensitivity, specificity, PPV, NPV, F1 score, calibration curve, and decision curve analysis. Fivefold cross-validation optimized and validated the model, and SHAP analysis assessed feature importance. Results: The XGBoost algorithm demonstrated the highest predictive performance with the best AUROC. The optimized model included six key predictors: age, ThinPrep cytologic test (TCT) results, HPV classification, CIN severity, glandular involvement, and margin status. SHAP analysis identified CIN severity and margin status as the most influential predictors. An online prediction tool was developed for real-time risk assessment. Conclusion: This ML-based predictive model for post-LEEP high-grade CIN provides a significant advancement in gynecologic oncology, enhancing personalized patient care and facilitating early intervention and informed clinical decision-making.

11.
Front Pediatr ; 12: 1421775, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39281189

RESUMO

Objective: The purpose of this study is to develop and assess a nomogram risk prediction model for central precocious puberty (CPP) in obese girls. Methods: We selected 154 cases of obese girls and 765 cases of non-obese girls with precocious puberty (PP) who underwent the gonadotropin-releasing hormone stimulation test at the Jiangxi Provincial Children's Hospital. Univariate analysis and multivariate analysis were conducted to identify predictors of progression to CPP in girls with PP. A predictive model was developed and its predictive ability was preliminarily evaluated. The nomogram was used to represent the risk prediction model for CPP in girls with obesity. The model was validated internally using the Bootstrap method, and its efficacy was assessed using calibration curves and clinical decision analysis curves. Results: In obese girls with PP, basal luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels, as well as uterine volume, were identified as independent risk factors for progression to CPP. In non-obese girls, the basal LH level, bone age, and uterine volume were identified as independent risk factors for progression to CPP. With an AUC of 0.896, the risk prediction model for obese girls, was found to be superior to that for non-obese girls, which had an AUC of 0.810. The model displayed strong predictive accuracy. Additionally, a nomogram was used to illustrate the CPP risk prediction model for obese girls. This model performs well in internal validation and is well calibrated, providing a substantial net benefit for clinical use. Conclusion: A medical nomogram model of CPP risk in obese girls comprised of basal LH value, basal FSH value, and uterine volume, which can be used to identify those at high risk for progression of CPP in obese girls and develop individualized prevention programs.

12.
medRxiv ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39281738

RESUMO

INTRODUCTION: Autosomal Dominant Alzheimer's Disease (ADAD) through genetic mutations can result in near complete expression of the disease. Tracking AD pathology development in an ADAD cohort of Presenilin-1 (PSEN1) E280A carriers' mutation has allowed us to observe incipient tau tangles accumulation as early as 6 years prior to symptom onset. METHODS: Resting-state functional Magnetic Resonance Imaging (fMRI) and Positron-Emission Tomography (PET) scans were acquired in a group of PSEN1 carriers (n=32) and non-carrier family members (n=35). We applied Connectome-based Predictive Modeling (CPM) to examine the relationship between the participant's functional connectome and their respective tau/amyloid-ß levels and cognitive scores (word list recall). RESULTS: CPM models strongly predicted tau concentrations and cognitive scores within the carrier group. The connectivity patterns between the temporal cortex, default mode network, and other memory networks were the most informative of tau burden. DISCUSSION: These results indicate that resting-state fMRI methods can complement PET methods in early detection and monitoring of disease progression in ADAD.

13.
Heliyon ; 10(17): e37459, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39290266

RESUMO

The molecular energy, which is the sum of all eigenvalues, is crucial in determining the total π-electron energy of conjugated hydrocarbon molecules. We used machine learning techniques to calculate the energy, inertia, nullity, signature, and Estrada index of molecular graphs for bismuth tri-iodide and benzene rings embedded in P-type surfaces within 2D networks. We applied MATLAB to extract the actual eigenvalues from the data and developed general equations for these molecular properties. We then used these equations to estimate the values and compared them to the actual values through graphical analysis. Our results demonstrate the potential of data-driven techniques in predicting molecular properties and enhancing our understanding of spectral theory.

14.
J Dairy Sci ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39218059

RESUMO

One suggested approach to improve the reproductive performance of dairy herds is through the targeted management of subgroups of biologically similar animals, such as those with similar probabilities of becoming pregnant, termed pregnancy risk. We aimed to use readily available farm data to develop predictive models of pregnancy risk in dairy cows. Data from a convenience sample of 108 dairy herds in the UK were collated and each herd was randomly allocated, at a ratio of 80:20, to either training or testing data sets. Following data cleaning, there were a total of 78 herds in the training data set and 20 herds in the testing data set. Data were further split by parity into nulliparous, primiparous, and multiparous subsets. An XGBoost model was trained to predict the insemination outcome in each parity subset, with predictors from farm records of breeding, calving and milk recording. Training data comprised 74,511 inseminations in 45,909 nulliparous animals, 86,420 inseminations in 39,439 primiparous animals, and 158,294 inseminations in 32,520 multiparous animals. The final models were evaluated by predicting with the testing data, comprising 31,740 inseminations in 19,647 nulliparous animals, 38,588 inseminations in 16,215 primiparous animals, and 65,049 inseminations in 12,439 multiparous animals. Model discrimination was assessed by calculating the area under receiver operating characteristic curves (AUC); model calibration was assessed by plotting calibration curves and compared across test herds by calculating the expected calibration error (ECE) in each test herd. The models were unable to discriminate between insemination outcomes with high accuracy, with an AUC of 0.63, 0.59 and 0.62 in the nulliparous, primiparous and multiparous subsets, respectively. The models were generally well-calibrated, meaning the model-predicted pregnancy risks were similar to the observed pregnancy risks. The mean (SD) ECE in the test herds was 0.038 (0.023), 0.028 (0.012) and 0.020 (0.008) in the nulliparous, primiparous and multiparous subsets respectively. The predictive models reported here could theoretically be used to identify subgroups of animals with similar pregnancy risk to facilitate targeted reproductive management; or provide information about cows' relative pregnancy risk compared with the herd average, which may support on-farm decision-making. Further research is needed to evaluate the generalizability of these predictive models and understand the source of variation in ECE between herds; however, this study demonstrates that it is possible to accurately predict pregnancy risk in dairy cows using readily available farm data.

15.
Am J Epidemiol ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39277561

RESUMO

To inform public health interventions, researchers have developed models to forecast opioid-related overdose mortality. These efforts often have limited overlap in the models and datasets employed, presenting challenges to assessing progress in this field. Furthermore, common error-based performance metrics, such as root mean squared error (RMSE), cannot directly assess a key modeling purpose: the identification of priority areas for interventions. We recommend a new intervention-aware performance metric, Percentage of Best Possible Reach (%BPR). We compare metrics for many published models across two distinct geographic settings, Cook County, Illinois and Massachusetts, assuming the budget to intervene in 100 census tracts out of 1000s in each setting. The top-performing models based on RMSE recommend areas that do not always reach the most possible overdose events. In Massachusetts, the top models preferred by %BPR could have reached 18 additional fatal overdoses per year in 2020-2021 compared to models favored by RMSE. In Cook County, the different metrics select similar top-performing models, yet other models with similar RMSE can have significant variation in %BPR. We further find that simple models often perform as well as recently published ones. We release open code and data for others to build upon.

16.
Breast Cancer Res ; 26(1): 132, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39272208

RESUMO

BACKGROUND: Despite evidence indicating the dominance of cell-of-origin signatures in molecular tumor patterns, translating these genome-wide patterns into actionable insights has been challenging. This study introduces breast cancer cell-of-origin signatures that offer significant prognostic value across all breast cancer subtypes and various clinical cohorts, compared to previously developed genomic signatures. METHODS: We previously reported that triple hormone receptor (THR) co-expression patterns of androgen (AR), estrogen (ER), and vitamin D (VDR) receptors are maintained at the protein level in human breast cancers. Here, we developed corresponding mRNA signatures (THR-50 and THR-70) based on these patterns to categorize breast tumors by their THR expression levels. The THR mRNA signatures were evaluated across 56 breast cancer datasets (5040 patients) using Kaplan-Meier survival analysis, Cox proportional hazard regression, and unsupervised clustering. RESULTS: The THR signatures effectively predict both overall and progression-free survival across all evaluated datasets, independent of subtype, grade, or treatment status, suggesting improvement over existing prognostic signatures. Furthermore, they delineate three distinct ER-positive breast cancer subtypes with significant survival in differences-expanding on the conventional two subtypes. Additionally, coupling THR-70 with an immune signature identifies a predominantly ER-negative breast cancer subgroup with a highly favorable prognosis, comparable to ER-positive cases, as well as an ER-negative subgroup with notably poor outcome, characterized by a 15-fold shorter survival. CONCLUSIONS: The THR cell-of-origin signature introduces a novel dimension to breast cancer biology, potentially serving as a robust foundation for integrating additional prognostic biomarkers. These signatures offer utility as a prognostic index for stratifying existing breast cancer subtypes and for de novo classification of breast cancer cases. Moreover, THR signatures may also hold promise in predicting hormone treatment responses targeting AR and/or VDR.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Receptores Androgênicos , Receptores de Calcitriol , Receptores de Estrogênio , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Prognóstico , Receptores de Estrogênio/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Estimativa de Kaplan-Meier , Transcriptoma
17.
Front Toxicol ; 6: 1402630, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39238878

RESUMO

Neurotoxicants are substances that can lead to adverse structural or functional effects on the nervous system. These can be chemical, biological, or physical agents that can cross the blood brain barrier to damage neurons or interfere with complex interactions between the nervous system and other organs. With concerns regarding social policy, public health, and medicine, there is a need to ensure rigorous testing for neurotoxicity. While the most common neurotoxicity tests involve using animal models, a shift towards stem cell-based platforms can potentially provide a more biologically accurate alternative in both clinical and pharmaceutical research. With this in mind, the objective of this article is to review both current technologies and recent advancements in evaluating neurotoxicants using stem cell-based approaches, with an emphasis on developmental neurotoxicants (DNTs) as these have the most potential to lead to irreversible critical damage on brain function. In the next section, attempts to develop novel predictive model approaches for the study of both neural cell fate and developmental neurotoxicity are discussed. Finally, this article concludes with a discussion of the future use of in silico methods within developmental neurotoxicity testing, and the role of regulatory bodies in promoting advancements within the space.

18.
J Clin Med ; 13(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39274293

RESUMO

Background: Parkinson's Disease significantly impacts health-related quality of life, with the Parkinson's Disease Questionnaire-39 extensively used for its assessment. However, predicting such outcomes remains a challenge due to the subjective nature and variability in patient experiences. This study develops a machine learning model using accessible clinical data to enable predictions of life-quality outcomes in Parkinson's Disease and utilizes explainable machine learning techniques to identify key influencing factors, offering actionable insights for clinicians. Methods: Data from the Parkinson's Real-world Impact Assessment study (PRISM), involving 861 patients across six European countries, were analyzed. After excluding incomplete data, 627 complete observations were used for the analysis. An ensemble machine learning model was developed with a 90% training and 10% validation split. Results: The model demonstrated a Mean Absolute Error of 4.82, a Root Mean Squared Error of 8.09, and an R2 of 0.75 in the training set, indicating a strong model fit. In the validation set, the model achieved a Mean Absolute Error of 11.22, a Root Mean Squared Error of 13.99, and an R2 of 0.36, showcasing moderate variation. Key predictors such as age at diagnosis, patient's country, dementia, and patient's age were identified, providing insights into the model's decision-making process. Conclusions: This study presents a robust model capable of predicting the impact of Parkinson's Disease on patients' quality of life using common clinical variables. These results demonstrate the potential of machine learning to enhance clinical decision-making and patient care, suggesting directions for future research to improve model generalizability and applicability.

19.
PNAS Nexus ; 3(9): pgae412, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39323982

RESUMO

Socioeconomic resources (SER) calibrate the developing brain to the current context, which can confer or attenuate risk for psychopathology across the lifespan. Recent multivariate work indicates that SER levels powerfully relate to intrinsic functional connectivity patterns across the entire brain. Nevertheless, the neuroscientific meaning of these widespread neural differences remains poorly understood, despite its translational promise for early risk identification, targeted intervention, and policy reform. In the present study, we leverage graph theory to precisely characterize multivariate and univariate associations between SER across household and neighborhood contexts and the intrinsic functional architecture of brain regions in 5,821 youth (9-10 years) from the Adolescent Brain Cognitive Development Study. First, we establish that decomposing the brain into profiles of integration and segregation captures more than half of the multivariate association between SER and functional connectivity with greater parsimony (100-fold reduction in number of features) and interpretability. Second, we show that the topological effects of SER are not uniform across the brain; rather, higher SER levels are associated with greater integration of somatomotor and subcortical systems, but greater segregation of default mode, orbitofrontal, and cerebellar systems. Finally, we demonstrate that topological associations with SER are spatially patterned along the unimodal-transmodal gradient of brain organization. These findings provide critical interpretive context for the established and widespread associations between SER and brain organization. This study highlights both higher-order and somatomotor networks that are differentially implicated in environmental stress, disadvantage, and opportunity in youth.

20.
Behav Brain Res ; : 115255, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39326636

RESUMO

OBJECTIVES: Maladaptive risky decision-making is a common pathological behavior among patients with various psychiatric disorders. Brain entropy, which measures the complexity of brain time series signals, provides a novel approach to assessing brain health. Despite its potential, the dynamics of brain entropy have seldom been explored. This study aimed to construct a dynamic model of brain entropy and examine its predictive value for risky decision-making in patients with mental disorders, utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: This study analyzed the rs-fMRI data from a total of 198 subjects, including 48 patients with bipolar disorder (BD), 47 patients with schizophrenia (SZ), 40 patients with adult attention deficit hyperactivity disorder (ADHD), as well as 63 healthy controls (HC). Time series signals were extracted from 264 brain regions based on rs-fMRI. The traditional static entropy and dynamic entropy (coefficient of variation, CV; rate of change, Rate) were constructed, respectively. Support vector regression was employed to predict risky decision-making utilizing leave-one-out cross-validation within each group. RESULTS: Our findings showed that CV achieved the best performances in HC and BD groups (r = -0.58, MAE = 6.43, R2 = 0.32; r = -0.78, MAE = 12.10, R2 = 0.61), while the Rate achieved the best in SZ and ADHD groups (r = -0.69, MAE = 10.20, R2 = 0.47; r = -0.78, MAE = 7.63, R2 = 0.60). For the dynamic entropy, the feature selection threshold rather than the time window length and overlapping ratio influenced predictive performance. CONCLUSIONS: These results suggest that dynamic brain entropy could be a more effective predictor of risky decision-making than traditional static brain entropy. Our findings offer a novel perspective on exploring brain signal complexity and can serve as a reference for interventions targeting risky decision-making behaviors, particularly in individuals with psychiatric diagnoses.

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