Machine learning-based colorectal cancer prediction using global dietary data.

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Active health screening for CRC yielded detection of an increasingly younger adults. However, current machine learning algorithms that are trained using older adults and smaller datasets, may not perform well in practice for large populations. AIM: To evaluate machine learning algorithms using large datasets accounting for both younger and older adults from multiple regions and diverse sociodemographics. METHODS: A large dataset including 109,343 participants in a dietary-based colorectal cancer ase study from Canada, India, Italy, South Korea, Mexico, Sweden, and the United States was collected by the Center for Disease Control and Prevention. This global dietary database was augmented with other publicly accessible information from multiple sources. Nine supervised and unsupervised machine learning algorithms were evaluated on the aggregated dataset. RESULTS: Both supervised and unsupervised models performed well in predicting CRC and non-CRC phenotypes. A prediction model based on an artificial neural network (ANN) was found to be the optimal algorithm with CRC misclassification of 1% and non-CRC misclassification of 3%. CONCLUSIONS: ANN models trained on large heterogeneous datasets may be applicable for both younger and older adults. Such models provide a solid foundation for building effective clinical decision support systems assisting healthcare providers in dietary-related, non-invasive screening that can be applied in large studies. Using optimal algorithms coupled with high compliance to cancer screening is expected to significantly improve early diagnoses and boost the success rate of timely and appropriate cancer interventions.

Transfusion-associated hyperkalemia in pediatric population: Analyses for risk factors and recommendations.

BACKGROUND: Transfusion-associated hyperkalemia (TAH) is a potentially life-threatening complication of red blood cell (RBC) transfusion. Previously, we reported features of RBC transfusions from 35 pediatric patients (TAH group) who had hyperkalemia with RBC transfusion in one-year period at four facilities. In this study, we used multivariate analyses and artificial intelligence to compare the TAH group to newly collected control group (non-TAH group) to identify factors associated with TAH occurrence. STUDY DESIGN: A review of RBC transfusion with TAH was compared to non-TAH group who did not develop TAH with RBC transfusion at each facility during the same one-year period. The non-TAH group included 12 patients each in 5 age groups. Wilcoxon rank-sum tests recursive feature elimination, least absolute shrinkage, and selection operator (LASSO), and other artificial intelligence techniques were employed to identify the most salient features associated with predicting specific clinical outcomes for TAH occurrence. RESULTS/FINDINGS: Pre-transfusion creatinine, comorbidities of kidney and/or liver dysfunctions, and total transfused volume within 12 h (tV-12) per kg and per estimated total blood volume (eTBV) showed statistically significant differences between TAH and non-TAH groups. Multivariate analysis revealed the biggest factor in TAH occurrence was tV-12/kg followed by age of RBC units. The thresholds of risks were tV-12/kg of 30 ml/kg, tV-12/eTBV of 30%, and RBC unit age of 7.95 days. CONCLUSIONS: The study findings suggest that the biggest factor on TAH occurrence is tV-12/kg. More importantly, 30% of eTBV transfusion could cause TAH in patients with multiple comorbidities.

The clusters of health-risk behaviours and mental wellbeing and their sociodemographic correlates: a study of 15,366 ASEAN university students.

BACKGROUND: This study investigated, through cluster analysis, the associations between behavioural characteristics, mental wellbeing, demographic characteristics, and health among university students in the Association of Southeast Asian Nations (ASEAN) University Network - Health Promotion Network (AUN-HPN) member universities. METHODS: Data were retrieved from a cross-sectional self-administered online survey among undergraduate students in seven ASEAN countries. A two-step cluster analysis was employed, with cluster labels based on the predominant characteristics identified within the clusters. The 'healthy' cluster was assigned as the reference group for comparisons using multinomial logistic regression analysis. RESULTS: The analytic sample size comprised 15,366 university students. Five clusters of student-types were identified: (i) 'Healthy' (n = 1957; 12.7%); (ii) 'High sugary beverage consumption' (n = 8482; 55.2%); (iii) 'Poor mental wellbeing' (n = 2009; 13.1%); (iv) 'Smoker' (n = 1364; 8.9%); and (v) 'Alcohol drinker' (n = 1554; 10.1%). Being female (OR 1.28, 95%CI 1.14, 1.45) and being physically inactive (OR 1.20, 95%CI 1.04, 1.39) increased the odds of belonging to the 'High sugary beverage consumption' cluster. Being female (OR 1.21, 95%CI 1.04, 1.41), non-membership in a sports club (OR 1.83, 95%CI 1.43, 2.34) were associated with 'Poor mental wellbeing'. Obesity (OR 2.03, 95%CI 1.47, 2.80), inactively commuting to campus (OR 1.34, 95%CI 1.09, 1.66), and living in high-rise accommodation (OR 2.94, 95%CI 1.07, 8.07) were associated with membership in the 'Smoker' cluster. Students living in The Philippines, Singapore, Thailand, and Vietnam had a higher likelihood of being alcohol drinkers, compared with those who lived in Brunei. CONCLUSIONS: ASEAN university students exhibited health-risk behaviours that typically clustered around a specific health behaviour and mental wellbeing. The results provided support for focusing interventions on one dominant health-risk behaviour, with associated health-risk behaviours within clusters being potential mediators for consideration.

Optimal dynamic treatment regime estimation using information extraction from unstructured clinical text.

The wide-scale adoption of electronic health records (EHRs) provides extensive information to support precision medicine and personalized health care. In addition to structured EHRs, we leverage free-text clinical information extraction (IE) techniques to estimate optimal dynamic treatment regimes (DTRs), a sequence of decision rules that dictate how to individualize treatments to patients based on treatment and covariate history. The proposed IE of patient characteristics closely resembles "The clinical Text Analysis and Knowledge Extraction System" and employs named entity recognition, boundary detection, and negation annotation. It also utilizes regular expressions to extract numerical information. Combining the proposed IE with optimal DTR estimation, we extract derived patient characteristics and use tree-based reinforcement learning (T-RL) to estimate multistage optimal DTRs. IE significantly improved the estimation in counterfactual outcome models compared to using structured EHR data alone, which often include incomplete data, data entry errors, and other potentially unobserved risk factors. Moreover, including IE in optimal DTR estimation provides larger study cohorts and a broader pool of candidate tailoring variables. We demonstrate the performance of our proposed method via simulations and an application using clinical records to guide blood pressure control treatments among critically ill patients with severe acute hypertension. This joint estimation approach improves the accuracy of identifying the optimal treatment sequence by 14-24% compared to traditional inference without using IE, based on our simulations over various scenarios. In the blood pressure control application, we successfully extracted significant blood pressure predictors that are unobserved or partially missing from structured EHR.

DataSifterText: Partially Synthetic Text Generation for Sensitive Clinical Notes.

Petabytes of health data are collected annually across the globe in electronic health records (EHR), including significant information stored as unstructured free text. However, the lack of effective mechanisms to securely share clinical text has inhibited its full utilization. We propose a new method, DataSifterText, to generate partially synthetic clinical free-text that can be safely shared between stakeholders (e.g., clinicians, STEM researchers, engineers, analysts, and healthcare providers), limiting the re-identification risk while providing significantly better utility preservation than suppressing or generalizing sensitive tokens. The method creates partially synthetic free-text data, which inherits the joint population distribution of the original data, and disguises the location of true and obfuscated words. Under certain obfuscation levels, the resulting synthetic text was sufficiently altered with different choices, orders, and frequencies of words compared to the original records. The differences were comparable to machine-generated (fully synthetic) text reported in previous studies. We applied DataSifterText to two medical case studies. In the CDC work injury application, using privacy protection, 60.9-86.5% of the synthetic descriptions belong to the same cluster as the original descriptions, demonstrating better utility preservation than the naïve content suppressing method (45.8-85.7%). In the MIMIC III application, the generated synthetic data maintained over 80% of the original information regarding patients' overall health conditions. The reported DataSifterText statistical obfuscation results indicate that the technique provides sufficient privacy protection (low identification risk) while preserving population-level information (high utility).

Modeling and prediction of pressure injury in hospitalized patients using artificial intelligence.

BACKGROUND: Hospital-acquired pressure injuries (PIs) induce significant patient suffering, inflate healthcare costs, and increase clinical co-morbidities. PIs are mostly due to bed-immobility, sensory impairment, bed positioning, and length of hospital stay. In this study, we use electronic health records and administrative data to examine the contributing factors to PI development using artificial intelligence (AI). METHODS: We used advanced data science techniques to first preprocess the data and then train machine learning classifiers to predict the probability of developing PIs. The AI training was based on large, incongruent, incomplete, heterogeneous, and time-varying data of hospitalized patients. Both model-based statistical methods and model-free AI strategies were used to forecast PI outcomes and determine the salient features that are highly predictive of the outcomes. RESULTS: Our findings reveal that PI prediction by model-free techniques outperform model-based forecasts. The performance of all AI methods is improved by rebalancing the training data and by including the Braden in the model learning phase. Compared to neural networks and linear modeling, with and without rebalancing or using Braden scores, Random forest consistently generated the optimal PI forecasts. CONCLUSIONS: AI techniques show promise to automatically identify patients at risk for hospital acquired PIs in different surgical services. Our PI prediction model provide a first generation of AI guidance to prescreen patients at risk for developing PIs. CLINICAL IMPACT: This study provides a foundation for designing, implementing, and assessing novel interventions addressing specific healthcare needs. Specifically, this approach allows examining the impact of various dynamic, personalized, and clinical-environment effects on PI prevention for hospital patients receiving care from various surgical services.

Machine learning-based lifetime breast cancer risk reclassification compared with the BOADICEA model: impact on screening recommendations.

BACKGROUND: The clinical utility of machine-learning (ML) algorithms for breast cancer risk prediction and screening practices is unknown. We compared classification of lifetime breast cancer risk based on ML and the BOADICEA model. We explored the differences in risk classification and their clinical impact on screening practices. METHODS: We used three different ML algorithms and the BOADICEA model to estimate lifetime breast cancer risk in a sample of 112,587 individuals from 2481 families from the Oncogenetic Unit, Geneva University Hospitals. Performance of algorithms was evaluated using the area under the receiver operating characteristic (AU-ROC) curve. Risk reclassification was compared for 36,146 breast cancer-free women of ages 20-80. The impact on recommendations for mammography surveillance was based on the Swiss Surveillance Protocol. RESULTS: The predictive accuracy of ML-based algorithms (0.843 ≤ AU-ROC ≤ 0.889) was superior to BOADICEA (AU-ROC = 0.639) and reclassified 35.3% of women in different risk categories. The largest reclassification (20.8%) was observed in women characterised as 'near population' risk by BOADICEA. Reclassification had the largest impact on screening practices of women younger than 50. CONCLUSION: ML-based reclassification of lifetime breast cancer risk occurred in approximately one in three women. Reclassification is important for younger women because it impacts clinical decision- making for the initiation of screening.

Age-Related Differences in Brain Morphology and the Modifiers in Middle-Aged and Older Adults.

Brain structural morphology differs with age. This study examined age-differences in surface-based morphometric measures of cortical thickness, volume, and surface area in a well-defined sample of 8137 generally healthy UK Biobank participants aged 45-79 years. We illustrate that the complexity of age-related brain morphological differences may be related to the laminar organization and regional evolutionary history of the cortex, and age of about 60 is a break point for increasing negative associations between age and brain morphology in Alzheimer's disease (AD)-prone areas. We also report novel relationships of age-related cortical differences with individual factors of sex, cognitive functions of fluid intelligence, reaction time and prospective memory, cigarette smoking, alcohol consumption, sleep disruption, genetic markers of apolipoprotein E, brain-derived neurotrophic factor, catechol-O-methyltransferase, and several genome-wide association study loci for AD and further reveal joint effects of cognitive functions, lifestyle behaviors, and education on age-related cortical differences. These findings provide one of the most extensive characterizations of age associations with major brain morphological measures and improve our understanding of normal structural brain aging and its potential modifiers.

Flipping the grant application review process.

The return on research investment resulting from new breakthrough scientific discoveries may be decreasing over time due to the law of diminishing returns, the relative decrease of research funding in terms of purchasing power parity, and various activities gaming the system. By altering the grant-review process, the scientific community may directly address the third problem. There is evidence that peer reviews of research proposals may lack reliability and may produce invalid or inconsistent ratings. In addition, extreme focus on grantsmanship threatens to uproot a cornerstone principle that scientific-value should be the key driver in funding decision-making. This opinion provides (1) a justification of the need to consider alternative strategies to boost the impact of public investment in innovative scientific discovery, (2) proposes a framework for flipping the traditional front-loaded peer-review approach to allocation of research funding, into a new back-loaded assessment of scholarly return on investment, and (3) provokes the scientific community to accelerate the debate on alternative funding mechanisms, as the stakes of inaction may be very high.

Machine learning techniques for personalized breast cancer risk prediction: comparison with the BCRAT and BOADICEA models.

BACKGROUND: Comprehensive breast cancer risk prediction models enable identifying and targeting women at high-risk, while reducing interventions in those at low-risk. Breast cancer risk prediction models used in clinical practice have low discriminatory accuracy (0.53-0.64). Machine learning (ML) offers an alternative approach to standard prediction modeling that may address current limitations and improve accuracy of those tools. The purpose of this study was to compare the discriminatory accuracy of ML-based estimates against a pair of established methods-the Breast Cancer Risk Assessment Tool (BCRAT) and Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) models. METHODS: We quantified and compared the performance of eight different ML methods to the performance of BCRAT and BOADICEA using eight simulated datasets and two retrospective samples: a random population-based sample of U.S. breast cancer patients and their cancer-free female relatives (N = 1143), and a clinical sample of Swiss breast cancer patients and cancer-free women seeking genetic evaluation and/or testing (N = 2481). RESULTS: Predictive accuracy (AU-ROC curve) reached 88.28% using ML-Adaptive Boosting and 88.89% using ML-random forest versus 62.40% with BCRAT for the U.S. population-based sample. Predictive accuracy reached 90.17% using ML-adaptive boosting and 89.32% using ML-Markov chain Monte Carlo generalized linear mixed model versus 59.31% with BOADICEA for the Swiss clinic-based sample. CONCLUSIONS: There was a striking improvement in the accuracy of classification of women with and without breast cancer achieved with ML algorithms compared to the state-of-the-art model-based approaches. High-accuracy prediction techniques are important in personalized medicine because they facilitate stratification of prevention strategies and individualized clinical management.

Impact of using a broad-based multi-institutional approach to build capacity for non-communicable disease research in Thailand.

Thailand's transition to high middle-income country status has been accompanied by demographic changes and associated shifts in the nation's public health challenges. These changes have necessitated a significant shift in public health focus from the treatment of infectious diseases to the more expensive and protracted management of non-communicable diseases (NCDs) in older adults.In 2010, in response to this shift in focus, the University of Michigan and colleagues at the Praboromarajchanok Institute for Health Workforce Development in Thailand began work on a broad-based multi-institutional programme for NCD research capacity-building in Thailand.To begin to build a base of intervention research we paired our programme's funded Thai postdoctoral fellows with United States mentors who have strong programmes of intervention research. One direct impact of the programme was the development of research 'hubs' focused upon similar areas of investigative focus such as self-management of cancer symptoms, self-management of HIV/AIDS and health technology information applications for use in community settings. Within these hubs, interventions with proven efficacy in the United States were used as a foundation for culturally relevant interventions in Thailand. The programme also aimed to develop the research support structures necessary within departments and colleges for grant writing and management, dissemination of new knowledge, and ethical conduct of human subject research.In an effort to capitalise on large national health datasets and big data now available in Thailand, several of the programme's postdoctoral fellows began projects that use data science methods to mine this asset. The investigators involved in these ground-breaking projects form the core of a network of research hubs that will be able to capitalise on the availability of lifespan health data from across Thailand and provide a robust working foundation for expansion of research using data science approaches.Going forward, it is vitally important to leverage this groundwork in order to continue fostering rapid growth in NCD research and training as well as to capitalise upon these early gains to create a sustaining influence for Thailand to lead in NCD research, improve the health of its citizens, and provide ongoing leadership in Southeast Asia.

Hypothesis: Caco-2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts.

Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco-2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco-2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium. Single- to multi-cell ring/torus-shaped genomes were observed prior to complex fractal Turing patterns extending from a rotating torus centre in a spiral pattern consistent with a gene morphogen motif. These features may contribute to the well-described differentiation from stem cells at the crypt base to the luminal colon epithelium along the crypt axis. This observation may be useful to study the role of mechanogenomic processes and the underlying molecular mechanisms as determinants of cellular and tissue architecture in space and time, which is the focal point of the 4D nucleome initiative. Mathematical and bioengineer modelling of gene circuits and cell shapes may provide a powerful algorithm that will contribute to future precision medicine relevant to a number of common medical disorders.

Neuroanatomical morphometric characterization of sex differences in youth using statistical learning.

Exploring neuroanatomical sex differences using a multivariate statistical learning approach can yield insights that cannot be derived with univariate analysis. While gross differences in total brain volume are well-established, uncovering the more subtle, regional sex-related differences in neuroanatomy requires a multivariate approach that can accurately model spatial complexity as well as the interactions between neuroanatomical features. Here, we developed a multivariate statistical learning model using a support vector machine (SVM) classifier to predict sex from MRI-derived regional neuroanatomical features from a single-site study of 967 healthy youth from the Philadelphia Neurodevelopmental Cohort (PNC). Then, we validated the multivariate model on an independent dataset of 682 healthy youth from the multi-site Pediatric Imaging, Neurocognition and Genetics (PING) cohort study. The trained model exhibited an 83% cross-validated prediction accuracy, and correctly predicted the sex of 77% of the subjects from the independent multi-site dataset. Results showed that cortical thickness of the middle occipital lobes and the angular gyri are major predictors of sex. Results also demonstrated the inferential benefits of going beyond classical regression approaches to capture the interactions among brain features in order to better characterize sex differences in male and female youths. We also identified specific cortical morphological measures and parcellation techniques, such as cortical thickness as derived from the Destrieux atlas, that are better able to discriminate between males and females in comparison to other brain atlases (Desikan-Killiany, Brodmann and subcortical atlases).

Complete hazard ranking to analyze right-censored data: An ALS survival study.

Survival analysis represents an important outcome measure in clinical research and clinical trials; further, survival ranking may offer additional advantages in clinical trials. In this study, we developed GuanRank, a non-parametric ranking-based technique to transform patients' survival data into a linear space of hazard ranks. The transformation enables the utilization of machine learning base-learners including Gaussian process regression, Lasso, and random forest on survival data. The method was submitted to the DREAM Amyotrophic Lateral Sclerosis (ALS) Stratification Challenge. Ranked first place, the model gave more accurate ranking predictions on the PRO-ACT ALS dataset in comparison to Cox proportional hazard model. By utilizing right-censored data in its training process, the method demonstrated its state-of-the-art predictive power in ALS survival ranking. Its feature selection identified multiple important factors, some of which conflicts with previous studies.

HDDA: DataSifter: statistical obfuscation of electronic health records and other sensitive datasets.

There are no practical and effective mechanisms to share high-dimensional data including sensitive information in various fields like health financial intelligence or socioeconomics without compromising either the utility of the data or exposing private personal or secure organizational information. Excessive scrambling or encoding of the information makes it less useful for modelling or analytical processing. Insufficient preprocessing may compromise sensitive information and introduce a substantial risk for re-identification of individuals by various stratification techniques. To address this problem, we developed a novel statistical obfuscation method (DataSifter) for on-the-fly de-identification of structured and unstructured sensitive high-dimensional data such as clinical data from electronic health records (EHR). DataSifter provides complete administrative control over the balance between risk of data re-identification and preservation of the data information. Simulation results suggest that DataSifter can provide privacy protection while maintaining data utility for different types of outcomes of interest. The application of DataSifter on a large autism dataset provides a realistic demonstration of its promise practical applications.

Comparison of genomic data via statistical distribution.

Sequence comparison has become an essential tool in bioinformatics, because highly homologous sequences usually imply significant functional or structural similarity. Traditional sequence analysis techniques are based on preprocessing and alignment, which facilitate measuring and quantitative characterization of genetic differences, variability and complexity. However, recent developments of next generation and whole genome sequencing technologies give rise to new challenges that are related to measuring similarity and capturing rearrangements of large segments contained in the genome. This work is devoted to illustrating different methods recently introduced for quantifying sequence distances and variability. Most of the alignment-free methods rely on counting words, which are small contiguous fragments of the genome. Our approach considers the locations of nucleotides in the sequences and relies more on appropriate statistical distributions. The results of this technique for comparing sequences, by extracting information and comparing matching fidelity and location regularization information, are very encouraging, specifically to classify mutation sequences.

Probability Distributome: A Web Computational Infrastructure for Exploring the Properties, Interrelations, and Applications of Probability Distributions.

Probability distributions are useful for modeling, simulation, analysis, and inference on varieties of natural processes and physical phenomena. There are uncountably many probability distributions. However, a few dozen families of distributions are commonly defined and are frequently used in practice for problem solving, experimental applications, and theoretical studies. In this paper, we present a new computational and graphical infrastructure, the Distributome, which facilitates the discovery, exploration and application of diverse spectra of probability distributions. The extensible Distributome infrastructure provides interfaces for (human and machine) traversal, search, and navigation of all common probability distributions. It also enables distribution modeling, applications, investigation of inter-distribution relations, as well as their analytical representations and computational utilization. The entire Distributome framework is designed and implemented as an open-source, community-built, and Internet-accessible infrastructure. It is portable, extensible and compatible with HTML5 and Web2.0 standards (http://Distributome.org). We demonstrate two types of applications of the probability Distributome resources: computational research and science education. The Distributome tools may be employed to address five complementary computational modeling applications (simulation, data-analysis and inference, model-fitting, examination of the analytical, mathematical and computational properties of specific probability distributions, and exploration of the inter-distributional relations). Many high school and college science, technology, engineering and mathematics (STEM) courses may be enriched by the use of modern pedagogical approaches and technology-enhanced methods. The Distributome resources provide enhancements for blended STEM education by improving student motivation, augmenting the classical curriculum with interactive webapps, and overhauling the learning assessment protocols.

A role for ephrin-A5 in axonal sprouting, recovery, and activity-dependent plasticity after stroke.

Stroke causes loss of neurological function. Recovery after stroke is facilitated by forced use of the affected limb and is associated with sprouting of new connections, a process that is sharply confined in the adult brain. We show that ephrin-A5 is induced in reactive astrocytes in periinfarct cortex and is an inhibitor of axonal sprouting and motor recovery in stroke. Blockade of ephrin-A5 signaling using a unique tissue delivery system induces the formation of a new pattern of axonal projections in motor, premotor, and prefrontal circuits and mediates recovery after stroke in the mouse through these new projections. Combined blockade of ephrin-A5 and forced use of the affected limb promote new and surprisingly widespread axonal projections within the entire cortical hemisphere ipsilateral to the stroke. These data indicate that stroke activates a newly described membrane-bound astrocyte growth inhibitor to limit neuroplasticity, activity-dependent axonal sprouting, and recovery in the adult.

An automatic framework for quantitative validation of voxel based morphometry measures of anatomical brain asymmetry.

The study of anatomical brain asymmetries has been a topic of great interest in the neuroimaging community in the past decades. However, the accuracy of brain asymmetry measurements has been rarely investigated. In this study, we propose a fully automatic methodology for the quantitative validation of brain tissue asymmetries as measured by Voxel Based Morphometry (VBM) from structural magnetic resonance (MR) images. Starting from a real MR image, the methodology generates simulated 3D MR images with a known and realistic pattern of inter-hemispheric asymmetry that models the left-occipital right-frontal petalia of a normal brain and the related rightward bending of the inter-hemispheric fissure. As an example, we generated a dataset of 64 simulated MR images and applied this dataset for the quantitative validation of optimized VBM measures of asymmetries in brain tissue composition. Our results suggested that VBM analysis strongly depended on the spatial normalization of the individual brain images, the selected template space, and the amount of spatial smoothing applied. The most accurate asymmetry detections were achieved by 9-degrees of freedom registration to the symmetrical template space with 4 to 8mm spatial smoothing.