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16 pages, 1423 KB  
Communication
Evaluating Imputation Methods to Improve Prediction Accuracy for an HIV Study in Uganda
by Nadia B. Mendoza, Chii-Dean Lin, Susan M. Kiene, Nicolas A. Menzies, Rhoda K. Wanyenze, Katherine A. Schmarje, Rose Naigino, Michael Ediau, Seth C. Kalichman and Barbara A. Bailey
Stats 2024, 7(4), 1405-1420; https://doi.org/10.3390/stats7040082 - 24 Nov 2024
Viewed by 1091
Abstract
Standard statistical analyses often exclude incomplete observations, which can be particularly problematic when predicting rare outcomes, such as HIV positivity. In the linkage to the HIV care dataset, there were initially 553 complete HIV positive cases, with an additional 554 cases added through [...] Read more.
Standard statistical analyses often exclude incomplete observations, which can be particularly problematic when predicting rare outcomes, such as HIV positivity. In the linkage to the HIV care dataset, there were initially 553 complete HIV positive cases, with an additional 554 cases added through imputation. Imputation methods amelia, hmisc, mice and missForest were evaluated. Simulations were conducted across various scenarios using the complete data to guide imputation for the full dataset. A random forest model was used to predict HIV status, assessing imputation precision, overall prediction accuracy, and sensitivity. While missForest produced imputed values closer to the observed ones, this did not translate into better predictive models. Hmisc and mice imputations led to higher prediction accuracy and sensitivity, with median accuracy increasing from 64% to 76% and median sensitivity rising from 0.4 to 0.75. Hmisc and amelia were the fastest imputation methods. Additionally, oversampling the minority class combined with undersampling the majority class did not improve predictions of new HIV positive cases using only the complete observations. However, increasing the minority class information through imputation enhanced sensitivity for predicting cases in this class. Full article
(This article belongs to the Section Computational Statistics)
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20 pages, 3876 KB  
Article
Characterization of Circulating Protein Profiles in Individuals with Prader–Willi Syndrome and Individuals with Non-Syndromic Obesity
by Devis Pascut, Pablo José Giraudi, Cristina Banfi, Stefania Ghilardi, Claudio Tiribelli, Adele Bondesan, Diana Caroli, Graziano Grugni and Alessandro Sartorio
J. Clin. Med. 2024, 13(19), 5697; https://doi.org/10.3390/jcm13195697 - 25 Sep 2024
Cited by 2 | Viewed by 2013
Abstract
Background: Prader–Willi syndrome (PWS) is a rare genetic disorder characterized by distinctive physical, cognitive, and behavioral manifestations, coupled with profound alterations in appetite regulation, leading to severe obesity and metabolic dysregulation. These clinical features arise from disruptions in neurodevelopment and neuroendocrine regulation, yet [...] Read more.
Background: Prader–Willi syndrome (PWS) is a rare genetic disorder characterized by distinctive physical, cognitive, and behavioral manifestations, coupled with profound alterations in appetite regulation, leading to severe obesity and metabolic dysregulation. These clinical features arise from disruptions in neurodevelopment and neuroendocrine regulation, yet the molecular intricacies of PWS remain incompletely understood. Methods: This study aimed to comprehensively profile circulating neuromodulatory factors in the serum of 53 subjects with PWS and 34 patients with non-syndromic obesity, utilizing a proximity extension assay with the Olink Target 96 neuro-exploratory and neurology panels. The ANOVA p-values were adjusted for multiple testing using the Benjamani–Hochberg method. Protein–protein interaction networks were generated in STRING V.12. Corrplots were calculated with R4.2.2 by using the Hmisc, Performance Analytics, and Corrplot packages Results: Our investigation explored the potential genetic underpinnings of the circulating protein signature observed in PWS, revealing intricate connections between genes in the PWS critical region and the identified circulating proteins associated with impaired oxytocin, NAD metabolism, and sex-related neuromuscular impairment involving, CD38, KYNU, NPM1, NMNAT1, WFIKKN1, and GDF-8/MSTN. The downregulation of CD38 in individuals with PWS (p < 0.01) indicates dysregulation of oxytocin release, implicating pathways associated with NAD metabolism in which KYNU and NMNAT1 are involved and significantly downregulated in PWS (p < 0.01 and p < 0.05, respectively). Sex-related differences in the circulatory levels of WFIKKN1 and GDF-8/MSTN (p < 0.05) were also observed. Conclusions: This study highlights potential circulating protein biomarkers associated with impaired oxytocin, NAD metabolism, and sex-related neuromuscular impairment in PWS individuals with potential clinical implications. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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15 pages, 1316 KB  
Article
Time-to-Treatment Delays and Their Prognostic Implications in Pharyngeal Cancer—An Exploratory Analysis in Western Romania
by Andreea Mihaela Kiș, Roxana Buzatu, Lazar Chisavu, Marioara Poenaru, Claudia Borza, Andrada Iftode, Oana Silvana Sarau, Cristina Adriana Dehelean and Simona Ardelean
Clin. Pract. 2024, 14(4), 1270-1284; https://doi.org/10.3390/clinpract14040103 - 29 Jun 2024
Viewed by 1842
Abstract
Background: Diagnosis and treatment for pharyngeal cancer are decisive in determining prognosis. Diagnosis delays are frequent, representing a significant cause of avoidable mortality, and an important factor in subpar survival across the continuous HNC care delivery. Methods: The present study represents a retrospective [...] Read more.
Background: Diagnosis and treatment for pharyngeal cancer are decisive in determining prognosis. Diagnosis delays are frequent, representing a significant cause of avoidable mortality, and an important factor in subpar survival across the continuous HNC care delivery. Methods: The present study represents a retrospective analysis of medical records from Western Romania, which included 180 patients, to evaluate the impact of time-to-treatment delay on patients diagnosed with pharyngeal cancer. The data analyses were performed using the Kaplan–Meier method R (version 3.6.3) packages, including tidyverse, final-fit, mcgv, survival, stringdist, janitor, and Hmisc. Results: The mean days from diagnosis until the end of treatment were higher for the nasopharynx group. Cox regression analysis regarding diagnosis to treatment duration categories showed an increased risk mortality by 3.11 times (95%CI: 1.51–6.41, p = 0.0021) with a Harrell’s C-index of 0.638 (95%CI: 0.552–0.723). The hypopharynx and oropharynx locations increased risk mortality by 4.59 (95%CI: 1.55–13.55) and 5.49 times (95%CI: 1.79–16.81) compared to the nasopharynx location. Conclusions: The findings of this study led to the conclusion that it seems there is a trend of mortality risk for oropharynx and hypopharynx cancers due to delays in the time to treatment over 70 days, standing as a basis for further research as there is an imperative need for prospective multicenter studies. Full article
(This article belongs to the Special Issue Clinical Outcome Research in the Head and Neck)
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14 pages, 4628 KB  
Article
Development and Validation of Nomograms Predicting the 5- and 8-Year Overall and Cancer-Specific Survival of Bladder Cancer Patients Based on SEER Program
by Peng Wen, Jiao Wen, Xiaolong Huang and Fengze Wang
J. Clin. Med. 2023, 12(4), 1314; https://doi.org/10.3390/jcm12041314 - 7 Feb 2023
Cited by 8 | Viewed by 2156
Abstract
Background: Bladder cancer is often prone to recurrence and metastasis. We sought to construct nomogram models to predict the overall survival (OS) and cancer-specific survival (CSS) of bladder cancer patients. Methods: A reliable random split-sample approach was used to divide patients into two [...] Read more.
Background: Bladder cancer is often prone to recurrence and metastasis. We sought to construct nomogram models to predict the overall survival (OS) and cancer-specific survival (CSS) of bladder cancer patients. Methods: A reliable random split-sample approach was used to divide patients into two groups: modeling and validation cohorts. Uni-variate and multivariate survival analyses were used to obtain the independent prognostic risk factors based on the modeling cohort. A nomogram was constructed using the R package, “rms”. Harrell’s concordance index (C-index), calibration curves and receiver operating characteristic (ROC) curves were applied to evaluate the discrimination, sensitivity and specificity of the nomograms using the R packages “hmisc”, “rms” and “timeROC”. A decision curve analysis (DCA) was used to evaluate the clinical value of the nomograms via R package “stdca.R”. Results: 10,478 and 10,379 patients were assigned into nomogram modeling and validation cohorts, respectively (split ratio ≈ 1:1). For OS and CSS, the C-index values for internal validation were 0.738 and 0.780, respectively, and the C-index values for external validation were 0.739 and 0.784, respectively. The area under the ROC curve (AUC) values for 5- and 8-year OS and CSS were all greater than 0.7. The calibration curves show that the predicted probability values of 5- and 8-year OS and CSS are close to the actual OS and CSS. The decision curve analysis revealed that the two nomograms have a positive clinical benefit. Conclusion: We successfully constructed two nomograms to forecast OS and CSS for bladder cancer patients. This information can help clinicians conduct prognostic evaluations in an individualized manner and tailor personalized treatment plans. Full article
(This article belongs to the Section Oncology)
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