Abstract Gallbladder cancer (GBC) is one of the deadliest cancers, with a 5-year-survival-rate of less than 5 percent for late-stage disease. The response rate to chemotherapy among GBC patients is generally poor. Recent research has attempted to identify diagnostic, prognostic, and predictive biomarkers, however, currently, no biomarkers can accurately diagnose GBC and predict patients’ prognosis. Integrative analysis of molecular and clinical characterization has not been fully established, and minimal improvement has been made to the survival of these patients, in part due to the heterogeneity of GBC. Machine learning techniques have been proven to empower analysis of big data in oncology, allowing for improvement in the generation of biomarkers to predict patient outcomes. Using machine learning, we can utilize high-throughput RNA sequencing with clinicopathologic data to develop a predictive tool for GBC prognosis. Current predictive models for GBC outcomes often utilize clinical data only, with the highest C-statistic reported being 0.71. C-statistic values over 0.7 generally indicate good models, however 0.8 is the threshold for strong predictive models. We aim to build a superior algorithm to predict overall survival in GBC patients with advanced disease, using machine learning approaches to prioritize biomarkers for GBC prognosis. We have identified over 80 fresh frozen GBC tissue samples from Mayo Clinic Rochester, Dongsan Medical Center in Daegu, Korea, University of the Witwatersrand, in Johannesburg, South Africa, Lithuanian University of Health Science in Vilnius, Lithuania, and University of Calgary in Calgary, Canada, from patients enrolled between 2012 and 2021. We will perform next-generation RNA sequencing on these tissue samples. The patients’ clinical, pathologic and survival data will be abstracted from the medical record uniformly across sites. Feature engineering and dimensionality reduction will be performed. Then random forests, support vector machines, and gradient boosting machines will be applied to train the data. Variable importance will prioritize multi-omic markers. Standard 5-fold cross validation will be used to assess performance of each ML algorithm. If overall survival can be better predicted with the addition patients’ transcriptional sequencing data compared to using clinical profiles alone, we can gain a greater understanding of key biomarkers driving the tumor phenotype. Citation Format: Linsey Jackson, Loretta Allotey, Valles Kenneth, Gavin Oliver, Asha Nair, Daniel O'Brien, Rondell Graham, Mitesh Borad, Arjun Athreya, Lewis Roberts. Prognostic biomarkers for gallbladder cancer: A machine learning approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1944.
Introduction: Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill. This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance. Methods: This single center study evaluated adults hospitalized in an ICU who received intravenous meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort (N = 19) and an opportunistically sampled qualification cohort (N = 32). A non-linear mixed effects model was developed using parametric methods to estimate meropenem serum concentrations. Results: The best fit structural model in the richly-sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70 kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best predicted meropenem clearance. The mean (standard error) Vd in the final model was 17.4 (3.07) L and clearance was 11.5 (1.55) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias. Conclusions: Contemporary eGFR equations which use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared to creatinine only or cystatin C only eGFR equations in adult critically ill patients.
Connected embedded systems in the realm of smart infrastructures comprise ubiquitous end-point devices supported by a communication infrastructure. Device, energy supply and network failures are a reality and provisioned communications could fail. Self-organization is a process where network devices cooperate with each other to restore network connectivity on detecting network connectivity failures. Self-organized networks are envisioned to be hierarchical, implying that a root device is expected to spend more energy to forward the entire network's data. This leads to battery exhaustion and therefore a single point of failure in the system. In this paper we address this problem by proposing an energy-governed resilient networking framework. Our framework enforces a policy to throttle upstream network traffic to maintain energy drain at the root device. To demonstrate the effectiveness of the proposed policy, we designed our experiment framework using Nano-RK and FireFly; a lightweight operating system and sensing platform respectively.
BACKGROUND Mental health disorders are a leading cause of medical disabilities across an individual’s lifespan. This burden is particularly substantial in children and adolescents because of challenges in diagnosis and the lack of precision medicine approaches. However, the widespread adoption of wearable devices (eg, smart watches) that are conducive for artificial intelligence applications to remotely diagnose and manage psychiatric disorders in children and adolescents is promising. OBJECTIVE This study aims to conduct a scoping review to study, characterize, and identify areas of innovations with wearable devices that can augment current in-person physician assessments to individualize diagnosis and management of psychiatric disorders in child and adolescent psychiatry. METHODS This scoping review used information from the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of several databases from 2011 to June 25, 2021, limited to the English language and excluding animal studies, was conducted. The databases included Ovid MEDLINE and Epub ahead of print, in-process and other nonindexed citations, and daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; Web of Science; and Scopus. RESULTS The initial search yielded 344 articles, from which 19 (5.5%) articles were left on the final source list for this scoping review. Articles were divided into three main groups as follows: studies with the main focus on autism spectrum disorder, attention-deficit/hyperactivity disorder, and internalizing disorders such as anxiety disorders. Most of the studies used either cardio-fitness chest straps with electrocardiogram sensors or wrist-worn biosensors, such as watches by Fitbit. Both allowed passive data collection of the physiological signals. CONCLUSIONS Our scoping review found a large heterogeneity of methods and findings in artificial intelligence studies in child psychiatry. Overall, the largest gap identified in this scoping review is the lack of randomized controlled trials, as most studies available were pilot studies and feasibility trials.
The Internet of Things is a paradigm that allows the interaction of ubiquitous devices through a network to achieve common goals. This paradigm like any man-made infrastructure is subject to disasters, outages and other adversarial conditions. Under these situations provisioned communications fail, rendering this paradigm with little or no use. Hence, network self-organization among these devices is needed to allow for communication resilience. This paper presents a survey of related work in the area of self-organization and discusses future research opportunities and challenges for self-organization in the Internet of Things. We begin this paper with a system perspective of the Internet of Things. We then identify and describe the key components of self-organization in the Internet of Things and discuss enabling technologies. Finally we discuss possible tailoring of prior work of other related applications to suit the needs of self-organization in the Internet of Things paradigm.
Introduction: Identifying patients at risk for ischemic events after percutaneous coronary intervention (PCI) relies on traditional analysis of limited clinical and imaging variables. Machine learning (ML) has shown promise in effectively predicting cardiovascular risk in population studies. While existing ML models mainly predict mortality and incorporate clinical variables, there is a lack of tools that have utilized genetic data and that predict ischemic events. Aims: This study aims to develop and validate a ML model incorporating genotyping and clinical data to enhance prediction of ischemic outcomes for PCI patients utilizing large prospectively derived diverse datasets. Methods: Patients from the TAILOR-PCI trial (n=5302) were utilized for model development. 50% of the sample was utilized for Boruta feature selection and 50% for training and testing using cross validation. Features included demographics, medical history, medications, PCI characteristics, and genetic data (specifically, CYP2C19 *2, *3, *17 alleles). The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. Multiple ML classification algorithms, including Support Vector Machine (SVM) polynomial, Random Forest, Light gradient boost, XG Boost, among others, were benchmarked for their prediction performance on rare events. The top performing classifiers were externally validated on an independent dataset from the PRECISION PCI study (n=3,745). Results: Mean participant age of the training set was 64.2 ± 11.0 years, with 75.4% being male. During follow-up of 12 months, among 4,572 patients in the entire cohort 343 (7.5%) met the primary outcome. The SVM polynomial model demonstrated the highest area under the curve (AUC) of 0.67 for predicting the primary outcome with test dataset. The sensitivity, specificity, precision, and recall were 0.87, 0.28, 0.07, and 0.87 respectively (Figure). Peripheral arterial disease, body mass index, and age were among the top variables by feature importance. Conclusion: ML models incorporating both clinical and genetic data are feasible and highly promising in predicting major adverse cardiac events that may help guide use of anti-platelet drug therapy. The AUC values are reasonable given imbalances and misclassifications in datasets, and further model optimization with prospective utilization of the model will be paramount.
This paper proposes a data-driven longitudinal model that brings together factor graphs and learning methods to demonstrate a significant improvement in predictability in clinical outcomes of patients with major depressive disorder treated with antidepressants. Using data from the Mayo Clinic PGRN-AMPS trial and the STAR*D trial for validation, this work makes two significant contributions in the context of predictability in psychiatric therapeutic outcomes. First, we establish symptom dynamics in response to antidepressants by using the forward algorithm on a factor graph. Symptom dynamics are the changes in the symptom severity that are most likely to occur because of the antidepressants taken during the trial, and the associated clinical outcomes at 4 weeks and 8 weeks into the trial. The structure of the factor graph is inferred by using unsupervised learning to stratify patients by the similarity of their overall symptom severity. Second, by using metabolomics data as an accurate biological measure in addition to symptom survey data and other patient history information, the prediction of clinical outcomes such as response and remission significantly improved from 30% to 68% in men, and from 35% to 72% in women. This work demonstrates a significant difference in how men and women respond to antidepressants in terms of their symptom dynamics, and also shows that top predictors of clinical outcomes for men and women are significantly different and known to play a role in behavioral sciences.
Introduction: The Clinical Global Impressions-Improvement (CGI-I) scale is widely used in clinical research to assess symptoms and functioning in the context of treatment. The correlates of the CGI-I with efficacy scales for adolescent major depressive disorder are poorly understood. This study focused on benchmarking CGI-I scores with changes in the Children's Depression Rating Scale-Revised (CDRS-R) and the Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report (QIDS-A17-SR). Methods: We examined three datasets with the clinician-rated CDRS-R to ascertain equivalent percent changes in total scores and CGI-I ratings. Exploratory analyses examined corresponding percentage changes in the QIDS-A17-SR and the CGI-I ratings. The CGI-I was the reference scale for nonparametric equipercentile linking with the Equate package in R. Results: CGI-I scores of 1 mapped to ≥78%–95% change in CDRS-R scores at 4–6 weeks across three datasets. CGI-I scores of 2 mapped to 56%–94% change in CDRS-R scores at 4–6 weeks across three studies. CGI-I scores of 3 mapped to 30%–68% changes in CDRS-R scores at 4–6 weeks across three studies. CGI-I scores of 4 mapped to a range of 29%–44% at 4–6 weeks across three studies. There was no significant difference (p ≥ 0.6) between treatment groups in both the Treatment of Adolescents with Depression and Treatment of Resistant Depression in Adolescents studies, for each CGI-I score ( = 1, or = 2 or = 3, or ≥4), associated mapping of total depression severity score, or associated percent change from baseline for corresponding follow-up visits. There was no significant sex difference (p > 0.2) in CGI-I linkages to CDRS-R total or percentage changes. Conclusions: These findings establish clear relationships among CGI-I scores and the CDRS-R and the QIDS-A17-SR. These benchmarks have utility for clinical trial study design, inter-rater reliability training, and clinical implementation.
Interpatient variability in bipolar I depression (BP-D) symptoms challenges the ability to predict pharmacotherapeutic outcomes. A machine learning workflow was developed to predict remission after 8 weeks of pharmacotherapy (total score of ≤8 on the Montgomery Åsberg Depression Rating Scale [MADRS]).
