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"Lin, Eugene"
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Radiation Risk From Medical Imaging
2010
This review provides a practical overview of the excess cancer risks related to radiation from medical imaging. Primary care physicians should have a basic understanding of these risks. Because of recent attention to this issue, patients are more likely to express concerns over radiation risk. In addition, physicians can play a role in reducing radiation risk to their patients by considering these risks when making imaging referrals. This review provides a brief overview of the evidence pertaining to low-level radiation and excess cancer risks and addresses the radiation doses and risks from common medical imaging studies. Specific subsets of patients may be at greater risk from radiation exposure, and radiation risk should be considered carefully in these patients. Recent technical innovations have contributed to lowering the radiation dose from computed tomography, and the referring physician should be aware of these innovations in making imaging referrals.
Journal Article
A deep adversarial variational autoencoder model for dimensionality reduction in single-cell RNA sequencing analysis
by
Lin, Eugene
,
Mukherjee, Sudipto
,
Kannan, Sreeram
in
Adversarial autoencoder
,
Algorithms
,
Analysis
2020
Background
Single-cell RNA sequencing (scRNA-seq) is an emerging technology that can assess the function of an individual cell and cell-to-cell variability at the single cell level in an unbiased manner. Dimensionality reduction is an essential first step in downstream analysis of the scRNA-seq data. However, the scRNA-seq data are challenging for traditional methods due to their high dimensional measurements as well as an abundance of dropout events (that is, zero expression measurements).
Results
To overcome these difficulties, we propose DR-A (Dimensionality Reduction with Adversarial variational autoencoder), a data-driven approach to fulfill the task of dimensionality reduction. DR-A leverages a novel adversarial variational autoencoder-based framework, a variant of generative adversarial networks. DR-A is well-suited for unsupervised learning tasks for the scRNA-seq data, where labels for cell types are costly and often impossible to acquire. Compared with existing methods, DR-A is able to provide a more accurate low dimensional representation of the scRNA-seq data. We illustrate this by utilizing DR-A for clustering of scRNA-seq data.
Conclusions
Our results indicate that DR-A significantly enhances clustering performance over state-of-the-art methods.
Journal Article
Relevant Applications of Generative Adversarial Networks in Drug Design and Discovery: Molecular De Novo Design, Dimensionality Reduction, and De Novo Peptide and Protein Design
by
Lin, Eugene
,
Lane, Hsien-Yuan
,
Lin, Chieh-Hsin
in
Algorithms
,
Artificial Intelligence
,
Computers
2020
A growing body of evidence now suggests that artificial intelligence and machine learning techniques can serve as an indispensable foundation for the process of drug design and discovery. In light of latest advancements in computing technologies, deep learning algorithms are being created during the development of clinically useful drugs for treatment of a number of diseases. In this review, we focus on the latest developments for three particular arenas in drug design and discovery research using deep learning approaches, such as generative adversarial network (GAN) frameworks. Firstly, we review drug design and discovery studies that leverage various GAN techniques to assess one main application such as molecular de novo design in drug design and discovery. In addition, we describe various GAN models to fulfill the dimension reduction task of single-cell data in the preclinical stage of the drug development pipeline. Furthermore, we depict several studies in de novo peptide and protein design using GAN frameworks. Moreover, we outline the limitations in regard to the previous drug design and discovery studies using GAN models. Finally, we present a discussion of directions and challenges for future research.
Journal Article
Applying a bagging ensemble machine learning approach to predict functional outcome of schizophrenia with clinical symptoms and cognitive functions
2021
It has been suggested that the relationship between cognitive function and functional outcome in schizophrenia is mediated by clinical symptoms, while functional outcome is assessed by the Quality of Life Scale (QLS) and the Global Assessment of Functioning (GAF) Scale. To determine the outcome assessed by QLS and GAF, we established a bagging ensemble framework with a feature selection algorithm resulting from the analysis of factors such as 3 clinical symptom scales and 11 cognitive function scores of 302 patients with schizophrenia in the Taiwanese population. We compared our bagging ensemble framework with other state-of-the-art algorithms such as multilayer feedforward neural networks, support vector machine, linear regression, and random forests. The analysis revealed that the bagging ensemble model with feature selection performed best among predictive models in predicting the QLS functional outcome by using 20-item Scale for the Assessment of Negative Symptoms (SANS20) and 17-item Hamilton Depression Rating Scale (HAMD17). Moreover, to predict the GAF outcome, the bagging ensemble model with feature selection performed best among predictive models by using SANS20 and the Positive and Negative Syndrome Scale-Positive (PANSS-Positive) subscale. The study indicates that there are synergistic effects between negative (SANS20) and depressive (HAMD17) symptoms as well as between negative and positive (PANSS-Positive) symptoms in influencing functional outcome of schizophrenia using the bagging ensemble framework with feature selection.
Journal Article
Prediction of functional outcomes of schizophrenia with genetic biomarkers using a bagging ensemble machine learning method with feature selection
2021
Genetic variants such as single nucleotide polymorphisms (SNPs) have been suggested as potential molecular biomarkers to predict the functional outcome of psychiatric disorders. To assess the schizophrenia’ functional outcomes such as Quality of Life Scale (QLS) and the Global Assessment of Functioning (GAF), we leveraged a bagging ensemble machine learning method with a feature selection algorithm resulting from the analysis of 11 SNPs (
AKT1
rs1130233,
COMT
rs4680,
DISC1
rs821616,
DRD3
rs6280,
G72
rs1421292,
G72
rs2391191,
5-HT2A
rs6311,
MET
rs2237717,
MET
rs41735,
MET
rs42336, and
TPH2
rs4570625) of 302 schizophrenia patients in the Taiwanese population. We compared our bagging ensemble machine learning algorithm with other state-of-the-art models such as linear regression, support vector machine, multilayer feedforward neural networks, and random forests. The analysis reported that the bagging ensemble algorithm with feature selection outperformed other predictive algorithms to forecast the QLS functional outcome of schizophrenia by using the
G72
rs2391191 and
MET
rs2237717 SNPs. Furthermore, the bagging ensemble algorithm with feature selection surpassed other predictive algorithms to forecast the GAF functional outcome of schizophrenia by using the
AKT1
rs1130233 SNP. The study suggests that the bagging ensemble machine learning algorithm with feature selection might present an applicable approach to provide software tools for forecasting the functional outcomes of schizophrenia using molecular biomarkers.
Journal Article
Small Molecule Accurate Recognition Technology (SMART) to Enhance Natural Products Research
by
Gerwick, William H.
,
Idelbayev, Yerlan
,
Duggan, Brendan M.
in
140/131
,
639/638/630
,
639/638/92/349
2017
Various algorithms comparing 2D NMR spectra have been explored for their ability to dereplicate natural products as well as determine molecular structures. However, spectroscopic artefacts, solvent effects, and the interactive effect of functional group(s) on chemical shifts combine to hinder their effectiveness. Here, we leveraged Non-Uniform Sampling (NUS) 2D NMR techniques and deep Convolutional Neural Networks (CNNs) to create a tool, SMART, that can assist in natural products discovery efforts. First, an NUS heteronuclear single quantum coherence (HSQC) NMR pulse sequence was adapted to a state-of-the-art nuclear magnetic resonance (NMR) instrument, and data reconstruction methods were optimized, and second, a deep CNN with contrastive loss was trained on a database containing over 2,054 HSQC spectra as the training set. To demonstrate the utility of SMART, several newly isolated compounds were automatically located with their known analogues in the embedded clustering space, thereby streamlining the discovery pipeline for new natural products.
Journal Article
Competing with a pandemic: Trends in research design in a time of Covid-19
by
Lin, Eugene
,
Bian, Shelly X.
in
Betacoronavirus - isolation & purification
,
Clinical trials
,
Coronavirus Infections - epidemiology
2020
During the Covid-19 pandemic, major journals have published a significant number of Covid-19 related articles in a short period of time. While this is necessary to combat the worldwide pandemic, it may have trade-offs with respect to publishing research from other disciplines.
To assess differences in published research design before and after the Covid-19 pandemic.
We performed a cross-sectional review of all 322 full-length research studies published between October 1, 2019 and April 30, 2020 in three major medical journals. We compared the number of randomized controlled trials (RCTs) and studies with a control group before and after January 31, 2020, when Covid-19 began garnering international attention.
The number of full-length research studies per issue was not statistically different before and after the Covid-19 pandemic (from 3.7 to 3.5 per issue, p = 0.17). Compared to before January 31, 2020, 0.7 fewer non-Covid-19 studies per issue were published versus after January 31, 2020 (p<0.001), a change that was offset by Covid-19 studies. Among non-Covid-19 studies, 0.9 fewer studies with a control group per issue were published after January 31, 2020, with RCTs contributing to nearly all the decline (p<0.001, p = 0.001, respectively). In the same timeframe, non-Covid-19 studies without a control group and non-Covid-19 studies without randomization experienced relatively small changes that did not meet our threshold for statistical significance (increases of 0.1 and 0.1 per issue, p = 0.80, p = 0.88, respectively).
Using a simple heuristic for assessing research design and lack of generalizability to the general medical literature.
In summary, the increase in Covid-19 studies coincided with a decrease of mostly non-Covid-19 RCTs.
Journal Article
Impact of the COVID-19 pandemic on the kidney community: lessons learned and future directions
by
Varnell, Charles
,
Tesar, Vladimir
,
Tannor, Elliot K
in
Coronaviruses
,
COVID-19
,
Kidney diseases
2022
The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected patients with kidney disease, causing significant challenges in disease management, kidney research and trainee education. For patients, increased infection risk and disease severity, often complicated by acute kidney injury, have contributed to high mortality. Clinicians were faced with high clinical demands, resource shortages and novel ethical dilemmas in providing patient care. In this review, we address the impact of COVID-19 on the entire spectrum of kidney care, including acute kidney injury, chronic kidney disease, dialysis and transplantation, trainee education, disparities in health care, changes in health care policies, moral distress and the patient perspective. Based on current evidence, we provide a framework for the management and support of patients with kidney disease, infection mitigation strategies, resource allocation and support systems for the nephrology workforce.In this Review, the authors summarize the challenges associated with the care of patients with kidney disease during the COVID-19 pandemic. They describe the major challenges and missed opportunities, global inequalities in health care, and offer a framework for future pandemic preparedness.
Journal Article
Hospitalizations among adults with chronic kidney disease in the United States: A cohort study
by
Lash, James P.
,
Jepson, Christopher
,
Kanthety, Radhika
in
Adult
,
Aged
,
Biology and Life Sciences
2020
Adults with chronic kidney disease (CKD) are hospitalized more frequently than those without CKD, but the magnitude of this excess morbidity and the factors associated with hospitalizations are not well known.
Data from 3,939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 and 2008 at 7 clinical centers in the United States were used to estimate primary causes of hospitalizations, hospitalization rates, and baseline participant factors associated with all-cause, cardiovascular, and non-cardiovascular hospitalizations during a median follow up of 9.6 years. Multivariable-adjusted Poisson regression was used to identify factors associated with hospitalization rates, including demographics, blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria. Hospitalization rates in CRIC were compared with rates in the Nationwide Inpatient Sample (NIS) from 2012. Of the 3,939 CRIC participants, 45.1% were female, and 41.9% identified as non-Hispanic black, with a mean age of 57.7 years, and the mean eGFR is 44.9 ml/min/1.73m2. CRIC participants had an unadjusted overall hospitalization rate of 35.0 per 100 person-years (PY) [95% CI: 34.3 to 35.6] and 11.1 per 100 PY [95% CI: 10.8 to 11.5] for cardiovascular-related causes. All-cause, non-cardiovascular, and cardiovascular hospitalizations were associated with older age (≥65 versus 45 to 64 years), more proteinuria (≥150 to <500 versus <150 mg/g), higher systolic blood pressure (≥140 versus 120 to <130 mmHg), diabetes (versus no diabetes), and lower eGFR (<60 versus ≥60 ml/min/1.73m2). Non-Hispanic black (versus non-Hispanic white) race/ethnicity was associated with higher risk for cardiovascular hospitalization [rate ratio (RR) 1.25, 95% CI: 1.16 to 1.35, p-value < 0.001], while risk among females was lower [RR 0.89, 95% CI: 0.83 to 0.96, p-value = 0.002]. Rates of cardiovascular hospitalizations were higher among those with ≥500 mg/g of proteinuria irrespective of eGFR. The most common causes of hospitalization were related to cardiovascular (31.8%), genitourinary (8.7%), digestive (8.3%), endocrine, nutritional or metabolic (8.3%), and respiratory (6.7%) causes. Hospitalization rates were higher in CRIC than the NIS, except for non-cardiovascular hospitalizations among individuals aged >65 years. Limitations of the study include possible misclassification by diagnostic codes, residual confounding, and potential bias from healthy volunteer effect due to its observational nature.
In this study, we observed that adults with CKD had a higher hospitalization rate than the general population that is hospitalized, and even moderate reductions in kidney function were associated with elevated rates of hospitalization. Causes of hospitalization were predominantly related to cardiovascular disease, but other causes contributed, particularly, genitourinary, digestive, and endocrine, nutritional, and metabolic illnesses. High levels of proteinuria were observed to have the largest association with hospitalizations across a wide range of kidney function levels.
Journal Article
Cost-effectiveness of multidisciplinary care in mild to moderate chronic kidney disease in the United States: A modeling study
2018
Multidisciplinary care (MDC) programs have been proposed as a way to alleviate the cost and morbidity associated with chronic kidney disease (CKD) in the US.
We assessed the cost-effectiveness of a theoretical Medicare-based MDC program for CKD compared to usual CKD care in Medicare beneficiaries with stage 3 and 4 CKD between 45 and 84 years old in the US. The program used nephrologists, advanced practitioners, educators, dieticians, and social workers. From Medicare claims and published literature, we developed a novel deterministic Markov model for CKD progression and calibrated it to long-term risks of mortality and progression to end-stage renal disease. We then used the model to project accrued discounted costs and quality-adjusted life years (QALYs) over patients' remaining lifetime. We estimated the incremental cost-effectiveness ratio (ICER) of MDC, or the cost of the intervention per QALY gained. MDC added 0.23 (95% CI: 0.08, 0.42) QALYs over usual care, costing $51,285 per QALY gained (net monetary benefit of $23,100 at a threshold of $150,000 per QALY gained; 95% CI: $6,252, $44,323). In all subpopulations analyzed, ICERs ranged from $42,663 to $72,432 per QALY gained. MDC was generally more cost-effective in patients with higher urine albumin excretion. Although ICERs were higher in younger patients, MDC could yield greater improvements in health in younger than older patients. MDC remained cost-effective when we decreased its effectiveness to 25% of the base case or increased the cost 5-fold. The program costed less than $70,000 per QALY in 95% of probabilistic sensitivity analyses and less than $87,500 per QALY in 99% of analyses. Limitations of our study include its theoretical nature and being less generalizable to populations at low risk for progression to ESRD. We did not study the potential impact of MDC on hospitalization (cardiovascular or other).
Our model estimates that a Medicare-funded MDC program could reduce the need for dialysis, prolong life expectancy, and meet conventional cost-effectiveness thresholds in middle-aged to elderly patients with mild to moderate CKD.
Journal Article