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Background: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. Methods: Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. Results: Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P <.0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P <.001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P =.001), shorter 6-min walk distance (P =.001), and reduced cardiac performance (cardiac index, P =.016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P =.0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27–5.33; P <.0087). Comparisons of ML–derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62–0.79) for PAH. Conclusions: This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification. [ABSTRACT FROM AUTHOR]

Context: The nature of the relationship between serum thyrotropin (TSH) levels and higher cognitive abilities is unclear, especially within the normal reference range and in the younger population. Objective: To assess the relationship between serum TSH levels and mental health and sleep quality parameters (fluid intelligence [Gf], MMSE (Mini-Mental State Examination), depression scores, and, finally, Pittsburgh Sleep Quality Index (PSQI) scores (working memory, processing speed, and executive function) in young adults. Methods: This was a retrospective analysis of the data from the Human Connectome Project (HCP). The HCP consortium is seeking to map human brain circuits systematically and identify their relationship to behavior in healthy adults. Included were 391 female and 412 male healthy participants aged 22-35 years at the time of the screening interview. We excluded persons with serum TSH levels outside the reference range (0.4-4.5 mU/L). TSH was transformed logarithmically (log TSH). All the key variables were normalized and then linear regression analysis was performed to assess the relationship between log TSH as a cofactor and Gf as the dependent variable. Finally, a machine learning method, random forest regression, predicted Gf from the dependent variables (including alcohol and tobacco use). The main outcome was normalized Gf (nGf) and Gf scores. Results: Log TSH was a significant co-predictor of nGF in females (β = 0.31(±0.1), P < .01) but not in males. Random forest analysis showed that the model(s) had a better predictive value for females (r = 0.39, mean absolute error [MAE] = 0.81) than males (r = 0.24, MAE = 0.77). Conclusion: Higher serum TSH levels might be associated with higher Gf scores in young women. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, radiogenomics has played a significant role and offered a new understanding of cancer's biology and behavior in response to standard therapy. It also provides a more precise prognosis, investigation, and analysis of the patient's cancer. Over the years, Artificial Intelligence (AI) has provided a significant strength in radiogenomics. In this paper, we offer computational and oncological prospects of the role of AI in radiogenomics, as well as its offers, achievements, opportunities, and limitations in the current clinical practices. Radiogenomics, a combination of "Radiomics" and "Genomics," using Artificial Intelligence (AI) has recently emerged as the state-of-the-art science in precision medicine, especially in oncology care. Radiogenomics syndicates large-scale quantifiable data extracted from radiological medical images enveloped with personalized genomic phenotypes. It fabricates a prediction model through various AI methods to stratify the risk of patients, monitor therapeutic approaches, and assess clinical outcomes. It has recently shown tremendous achievements in prognosis, treatment planning, survival prediction, heterogeneity analysis, reoccurrence, and progression-free survival for human cancer study. Although AI has shown immense performance in oncology care in various clinical aspects, it has several challenges and limitations. The proposed review provides an overview of radiogenomics with the viewpoints on the role of AI in terms of its promises for computational as well as oncological aspects and offers achievements and opportunities in the era of precision medicine. The review also presents various recommendations to diminish these obstacles. [ABSTRACT FROM AUTHOR]

Albuminuria and estimated glomerular filtration rate (e-GFR) are early markers of renal disease and cardiovascular outcomes in persons with diabetes. Although body composition has been shown to predict systolic blood pressure, its application in predicting albuminuria is unknown. In this study, we have used machine learning methods to assess the risk of albuminuria in persons with diabetes using body composition and other determinants of metabolic health. This study is a comparative analysis of the different methods to predict albuminuria in persons with diabetes mellitus who are older than 40 years of age, using the LOOK AHEAD study cohort-baseline characteristics. Age, different metrics of body composition, duration of diabetes, hemoglobin A1c, serum creatinine, serum triglycerides, serum cholesterol, serum HDL, serum LDL, maximum exercise capacity, systolic blood pressure, diastolic blood pressure, and the ankle-brachial index are used as predictors of albuminuria. We used Area under the curve (AUC) as a metric to compare the classification results of different algorithms, and we show that AUC for the different models are as follows: Random forest classifier-0.65, gradient boost classifier-0.61, logistic regression-0.66, support vector classifier -0.61, multilayer perceptron -0.67, and stacking classifier-0.62. We used the Random forest model to show that the duration of diabetes, A1C, serum triglycerides, SBP, Maximum exercise Capacity, serum creatinine, subtotal lean mass, DBP, and subtotal fat mass are important features for the classification of albuminuria. In summary, when applied to metabolic imaging (using DXA), machine learning techniques offer unique insights into the risk factors that determine the development of albuminuria in diabetes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is associated with increased cardiovascular disease (CVD) related morbidity, mortality and death. Exercise capacity in persons with type 2 diabetes has been shown to be predictive of cardiovascular events. In this study, we used the data from the prospective randomized LOOK AHEAD study and used machine learning algorithms to help predict exercise capacity (measured in Mets) from the baseline data that included cardiovascular history, medications, blood pressure, demographic information, anthropometric and Dual-energy X-Ray Absorptiometry (DXA) measured body composition metrics. We excluded variables with high collinearity and included DXA obtained Subtotal (total minus head) fat percentage and Subtotal lean mass (gms). Thereafter, we used different machine learning methods to predict maximum exercise capacity. The different machine learning models showed a strong predictive performance for both females and males. Our study shows that using baseline data from a large prospective cohort, we can predict maximum exercise capacity in persons with diabetes mellitus. We show that subtotal fat percentage is the most important feature for predicting the exercise capacity for males and females after accounting for other important variables. Until now, BMI and waist circumference were commonly used surrogates for adiposity and there was a relative under-appreciation of body composition metrics for understanding the pathophysiology of CVD. The recognition of body fat percentage as an important marker in determining CVD risk has prognostic implications with respect to cardiovascular morbidity and mortality. [ABSTRACT FROM AUTHOR]

The factors that determine Serum Thyrotropin (TSH) levels have been examined through different methods, using different covariates. However, the use of machine learning methods has so far not been studied in population databases like NHANES (National Health and Nutritional Examination Survey) to predict TSH. In this study, we performed a comparative analysis of different machine learning methods like Linear regression, Random forest, Support vector machine, multilayer perceptron and stacking regression to predict TSH and classify individuals with normal, low and high TSH levels. We considered Free T4, Anti-TPO antibodies, T3, Body Mass Index (BMI), Age and Ethnicity as the predictor variables. A total of 9818 subjects were included in this comparative analysis. We used coefficient of determination (r2) value to compare the results for predicting the TSH and show that the Random Forest, Gradient Boosting and Stacking Regression perform equally well in predicting TSH and achieve the highest r2 value = 0.13, with mean absolute error of 0.78. Moreover, we found that Anti-TPO is the most important feature in predicting TSH followed by Age, BMI, T3 and Free-T4 for the regression analysis. While classifying TSH into normal, high or low levels, our comparative analysis also shows that Random forest performs the best in the classification study, performed with individuals with normal, high and low levels of TSH. We found the following Areas Under Curve (AUC); for low TSH, AUC = 0.61, normal TSH, AUC = 0.61 and elevated TSH AUC = 0.69. Additionally, we found that Anti-TPO was the most important feature in classifying TSH. In this study, we suggest that artificial intelligence and machine learning methods might offer an insight into the complex hypothalamic-pituitary -thyroid axis and may be an invaluable tool that guides us in making appropriate therapeutic decisions (thyroid hormone dosing) for the individual patient. [ABSTRACT FROM AUTHOR]

Isolation profoundly influences social behavior in all animals. In humans, isolation has serious effects on health and disease. Drosophila melanogaster is a powerful model to study small-scale, temporally-transient social behavior. However, longer-term analysis of large groups of flies is hampered by the lack of effective and reliable tools. We built a new imaging arena and improved the existing tracking algorithm to reliably follow a large number of flies simultaneously. Next, based on the automatic classification of touch and graph-based social network analysis, we designed an algorithm to quantify changes in the social network in response to prior social isolation. We observed that isolation significantly and swiftly enhanced individual and local social network parameters depicting near-neighbor relationships. We explored the genome-wide molecular correlates of these behavioral changes and found that whereas behavior changed throughout the six days of isolation, gene expression alterations occurred largely on day one. These changes occurred mostly in metabolic genes, and we verified the metabolic changes by showing an increase of lipid content in isolated flies. In summary, we describe a highly reliable tracking and analysis pipeline for large groups of flies that we use to unravel the behavioral, molecular and physiological impact of isolation on social network dynamics in Drosophila. [ABSTRACT FROM AUTHOR]

Importance: Clinical overlap between autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is increasingly appreciated, but the underlying brain mechanisms remain unknown to date.Objective: To examine associations between white matter organization and 2 commonly co-occurring neurodevelopmental conditions, ASD and ADHD, through both categorical and dimensional approaches.Design, Setting, and Participants: This investigation was a cross-sectional diffusion tensor imaging (DTI) study at an outpatient academic clinical and research center, the Department of Child and Adolescent Psychiatry at New York University Langone Medical Center. Participants were children with ASD, children with ADHD, or typically developing children. Data collection was ongoing from December 2008 to October 2015.Main Outcomes and Measures: The primary measure was voxelwise fractional anisotropy (FA) analyzed via tract-based spatial statistics. Additional voxelwise DTI metrics included radial diffusivity (RD), mean diffusivity (MD), axial diffusivity (AD), and mode of anisotropy (MA).Results: This cross-sectional DTI study analyzed data from 174 children (age range, 6.0-12.9 years), selected from a larger sample after quality assurance to be group matched on age and sex. After quality control, the study analyzed data from 69 children with ASD (mean [SD] age, 8.9 [1.7] years; 62 male), 55 children with ADHD (mean [SD] age, 9.5 [1.5] years; 41 male), and 50 typically developing children (mean [SD] age, 9.4 [1.5] years; 38 male). Categorical analyses revealed a significant influence of ASD diagnosis on several DTI metrics (FA, MD, RD, and AD), primarily in the corpus callosum. For example, FA analyses identified a cluster of 4179 voxels (TFCE FEW corrected P < .05) in posterior portions of the corpus callosum. Dimensional analyses revealed associations between ASD severity and FA, RD, and MD in more extended portions of the corpus callosum and beyond (eg, corona radiata and inferior longitudinal fasciculus) across all individuals, regardless of diagnosis. For example, FA analyses revealed clusters overall encompassing 12121 voxels (TFCE FWE corrected P < .05) with a significant association with parent ratings in the social responsiveness scale. Similar results were evident using an independent measure of ASD traits (ie, children communication checklist, second edition). Total severity of ADHD-traits was not significantly related to DTI metrics but inattention scores were related to AD in corpus callosum in a cluster sized 716 voxels. All these findings were robust to algorithmic correction of motion artifacts with the DTIPrep software.Conclusions and Relevance: Dimensional analyses provided a more complete picture of associations between ASD traits and inattention and indexes of white matter organization, particularly in the corpus callosum. This transdiagnostic approach can reveal dimensional relationships linking white matter structure to neurodevelopmental symptoms. [ABSTRACT FROM AUTHOR]