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1.
J Big Data ; 10(1): 92, 2023.
Article in English | MEDLINE | ID: mdl-37303479

ABSTRACT

Nitrogen Dioxide (NO2) is a common air pollutant associated with several adverse health problems such as pediatric asthma, cardiovascular mortality,and respiratory mortality. Due to the urgent society's need to reduce pollutant concentration, several scientific efforts have been allocated to understand pollutant patterns and predict pollutants' future concentrations using machine learning and deep learning techniques. The latter techniques have recently gained much attention due it's capability to tackle complex and challenging problems in computer vision, natural language processing, etc. In the NO2 context, there is still a research gap in adopting those advanced methods to predict the concentration of pollutants. This study fills in the gap by comparing the performance of several state-of-the-art artificial intelligence models that haven't been adopted in this context yet. The models were trained using time series cross-validation on a rolling base and tested across different periods using NO2 data from 20 monitoring ground-based stations collected by Environment Agency- Abu Dhabi, United Arab Emirates. Using the seasonal Mann-Kendall trend test and Sen's slope estimator, we further explored and investigated the pollutants trends across the different stations. This study is the first comprehensive study that reported the temporal characteristic of NO2 across seven environmental assessment points and compared the performance of the state-of-the-art deep learning models for predicting the pollutants' future concentration. Our results reveal a difference in the pollutants concentrations level due to the geographic location of the different stations, with a statistically significant decrease in the NO2 annual trend for the majority of the stations. Overall, NO2 concentrations exhibit a similar daily and weekly pattern across the different stations, with an increase in the pollutants level during the early morning and the first working day. Comparing the state-of-the-art model performance transformer model demonstrate the superiority of ( MAE:0.04 (± 0.04),MSE:0.06 (± 0.04), RMSE:0.001 (± 0.01), R2: 0.98 (± 0.05)), compared with LSTM (MAE:0.26 (± 0.19), MSE:0.31 (± 0.21), RMSE:0.14 (± 0.17), R2: 0.56 (± 0.33)), InceptionTime (MAE: 0.19 (± 0.18), MSE: 0.22 (± 0.18), RMSE:0.08 (± 0.13), R2:0.38 (± 1.35) ), ResNet (MAE:0.24 (± 0.16), MSE:0.28 (± 0.16), RMSE:0.11 (± 0.12), R2:0.35 (± 1.19) ), XceptionTime (MAE:0.7 (± 0.55), MSE:0.79 (± 0.54), RMSE:0.91 (± 1.06), R2: -4.83 (± 9.38) ), and MiniRocket (MAE:0.21 (± 0.07), MSE:0.26 (± 0.08), RMSE:0.07 (± 0.04), R2: 0.65 (± 0.28) ) to tackle this challenge. The transformer model is a powerful model for improving the accurate forecast of the NO2 levels and could strengthen the current monitoring system to control and manage the air quality in the region. Supplementary Information: The online version contains supplementary material available at 10.1186/s40537-023-00754-z.

2.
Nat Commun ; 13(1): 7652, 2022 Dec 10.
Article in English | MEDLINE | ID: mdl-36496454

ABSTRACT

Metformin, a diabetes drug with anti-aging cellular responses, has complex actions that may alter dementia onset. Mixed results are emerging from prior observational studies. To address this complexity, we deploy a causal inference approach accounting for the competing risk of death in emulated clinical trials using two distinct electronic health record systems. In intention-to-treat analyses, metformin use associates with lower hazard of all-cause mortality and lower cause-specific hazard of dementia onset, after accounting for prolonged survival, relative to sulfonylureas. In parallel systems pharmacology studies, the expression of two AD-related proteins, APOE and SPP1, was suppressed by pharmacologic concentrations of metformin in differentiated human neural cells, relative to a sulfonylurea. Together, our findings suggest that metformin might reduce the risk of dementia in diabetes patients through mechanisms beyond glycemic control, and that SPP1 is a candidate biomarker for metformin's action in the brain.


Subject(s)
Dementia , Diabetes Mellitus, Type 2 , Metformin , Humans , Metformin/pharmacology , Metformin/therapeutic use , Drug Repositioning , Network Pharmacology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Sulfonylurea Compounds , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Dementia/drug therapy , Dementia/etiology , Medical Records
3.
Diagnostics (Basel) ; 12(11)2022 Oct 26.
Article in English | MEDLINE | ID: mdl-36359435

ABSTRACT

Cerebral stroke (CS) is a heterogeneous syndrome caused by multiple disease mechanisms. Ischemic stroke (IS) is a subtype of CS that causes a disruption of cerebral blood flow with subsequent tissue damage. Noncontrast computer tomography (NCCT) is one of the most important IS detection methods. It is difficult to select the features of IS CT within computational image analysis. In this paper, we propose AC-YOLOv5, which is an improved detection algorithm for IS. The algorithm amplifies the features of IS via an NCCT image based on adaptive local region contrast enhancement, which then detects the region of interest via YOLOv5, which is one of the best detection algorithms at present. The proposed algorithm was tested on two datasets, and seven control group experiments were added, including popular detection algorithms at present and other detection algorithms based on image enhancement. The experimental results show that the proposed algorithm has a high accuracy (94.1% and 91.7%) and recall (85.3% and 88.6%) rate; the recall result is especially notable. This proves the excellent performance of the accuracy, robustness, and generalizability of the algorithm.

4.
Pharmacoepidemiol Drug Saf ; 31(9): 944-952, 2022 09.
Article in English | MEDLINE | ID: mdl-35689299

ABSTRACT

With availability of voluminous sets of observational data, an empirical paradigm to screen for drug repurposing opportunities (i.e., beneficial effects of drugs on nonindicated outcomes) is feasible. In this article, we use a linked claims and electronic health record database to comprehensively explore repurposing effects of antihypertensive drugs. We follow a target trial emulation framework for causal inference to emulate randomized controlled trials estimating confounding adjusted effects of antihypertensives on each of 262 outcomes of interest. We then fit hierarchical models to the results as a form of postprocessing to account for multiple comparisons and to sift through the results in a principled way. Our motivation is twofold. We seek both to surface genuinely intriguing drug repurposing opportunities and to elucidate through a real application some study design decisions and potential biases that arise in this context.


Subject(s)
Antihypertensive Agents , Drug Repositioning , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Causality , Databases, Factual , Electronic Health Records , Humans , Randomized Controlled Trials as Topic
5.
Article in English | MEDLINE | ID: mdl-35270766

ABSTRACT

The first wave of COVID-19 in China began in December 2019. The outbreak was quickly and effectively controlled through strict infection prevention and control with multipronged measures. By the end of March 2020, the outbreak had basically ended. Therefore, there are relatively complete and effective infection prevention and control (IPC) processes in China to curb virus transmission. Furthermore, there were two large-scale updates for the daily reports by the National Health Commission of the People's Republic of China in the early stage of the pandemic. We retrospectively studied the transmission characteristics and IPC of COVID-19 in China. Additionally, we analyzed and modeled the data in the two revisions. We found that most cases were limited to Hubei Province, especially in Wuhan, and the mortality rate was lower in non-Wuhan areas. We studied the two revisions and utilized the proposed transmission model to revise the daily confirmed cases at the beginning of the pandemic in Wuhan. Moreover, we estimated the cases and deaths for the same stage and analyzed the effect of IPC in China. The results show that strong and effective IPC with strict implementation was able to effectively and quickly control the pandemic.


Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , China/epidemiology , Humans , Pandemics/prevention & control , Retrospective Studies , SARS-CoV-2
6.
Sensors (Basel) ; 21(23)2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34883854

ABSTRACT

It is found that nodes in Delay Tolerant Networks (DTN) exhibit stable social attributes similar to those of people. In this paper, an adaptive routing algorithm based on Relation Tree (AR-RT) for DTN is proposed. Each node constructs its own Relation Tree based on the historical encounter frequency, and will adopt different forwarding strategies based on the Relation Tree in the forwarding phase, so as to achieve more targeted forwarding. To further improve the scalability of the algorithm, the source node dynamically controls the initial maximum number of message copies according to its own cache occupancy, which enables the node to make negative feedback to network environment changes. Simulation results show that the AR-RT algorithm proposed in this paper has significant advantages over existing routing algorithms in terms of average delay, average hop count, and message delivery rate.


Subject(s)
Algorithms , Computer Simulation , Humans
7.
Nano Lett ; 21(19): 8160-8165, 2021 10 13.
Article in English | MEDLINE | ID: mdl-34543039

ABSTRACT

Airborne particular matter (PM) pollution is an increasing global issue and alternative sources of filter fibers are now an area of significant focus. Compared with relatively mature hazardous gas treatments, state of the art high-efficiency PM filters still lack thermal decomposition ability for organic PM pollutants, such as soot from coal-fired power plants and waste-combustion incinerators, resulting in frequent replacement, high cost, and second-hand pollution. In this manuscript, we propose a bottom-up synthesis method to make the first all-thermal-catalyst air filter (ATCAF). Self-assembled from ∼50 nm diameter TiO2 fibers, ATCAF could not only capture the combustion-generated PM pollutants with >99.999% efficiency but also catalyze the complete decomposition of the as-captured hydrocarbon pollutants at high temperature. It has the potential of in situ eliminating the PM pollutants from burning of hydrocarbon materials leveraging the burning heat.


Subject(s)
Air Pollutants , Air Pollutants/analysis , Catalysis , Hot Temperature , Power Plants
8.
AMIA Annu Symp Proc ; 2021: 334-342, 2021.
Article in English | MEDLINE | ID: mdl-35308969

ABSTRACT

The central task of causal inference is to remove (via statistical adjustment) confounding bias that would be present in naive unadjusted comparisons of outcomes in different treatment groups. Statistical adjustment can roughly be broken down into two steps. In the first step, the researcher selects some set of variables to adjust for. In the second step, the researcher implements a causal inference algorithm to adjust for the selected variables and estimate the average treatment effect. In this paper, we use a simulation study to explore the operating characteristics and robustness of state-of-the-art methods for step two (statistical adjustment for selected variables) when step one (variable selection) is performed in a realistically sub-optimal manner. More specifically, we study the robustness of a cross-fit machine learning based causal effect estimator to the presence of extraneous variables in the adjustment set. The take-away for practitioners is that there is value to, if possible, identifying a small sufficient adjustment set using subject matter knowledge even when using machine learning methods for adjustment.


Subject(s)
Models, Statistical , Bias , Causality , Computer Simulation , Humans
9.
Bioinformatics ; 36(9): 2813-2820, 2020 05 01.
Article in English | MEDLINE | ID: mdl-31971581

ABSTRACT

MOTIVATION: Gradual population-level changes in tissues can be driven by stochastic plasticity, meaning rare stochastic transitions of single-cell phenotype. Quantifying the rates of these stochastic transitions requires time-intensive experiments, and analysis is generally confounded by simultaneous bidirectional transitions and asymmetric proliferation kinetics. To quantify cellular plasticity, we developed Transcompp (Transition Rate ANalysis of Single Cells to Observe and Measure Phenotypic Plasticity), a Markov modeling algorithm that uses optimization and resampling to compute best-fit rates and statistical intervals for stochastic cell-state transitions. RESULTS: We applied Transcompp to time-series datasets in which purified subpopulations of stem-like or non-stem cancer cells were exposed to various cell culture environments, and allowed to re-equilibrate spontaneously over time. Results revealed that commonly used cell culture reagents hydrocortisone and cholera toxin shifted the cell population equilibrium toward stem-like or non-stem states, respectively, in the basal-like breast cancer cell line MCF10CA1a. In addition, applying Transcompp to patient-derived cells showed that transition rates computed from short-term experiments could predict long-term trajectories and equilibrium convergence of the cultured cell population. AVAILABILITY AND IMPLEMENTATION: Freely available for download at http://github.com/nsuhasj/Transcompp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Algorithms , Breast Neoplasms , Adaptation, Physiological , Cells, Cultured , Humans
10.
Neuroimage Clin ; 25: 102186, 2020.
Article in English | MEDLINE | ID: mdl-32000101

ABSTRACT

Functional modules in the human brain support its drive for specialization whereas brain hubs act as focal points for information integration. Brain hubs are brain regions that have a large number of both within and between module connections. We argue that weak connections in brain functional networks lead to misclassification of brain regions as hubs. In order to resolve this, we propose a new measure called ambivert degree that considers the node's degree as well as connection weights in order to identify nodes with both high degree and high connection weights as hubs. Using resting-state functional MRI scans from the Human Connectome Project, we show that ambivert degree identifies brain hubs that are not only crucial but also invariable across subjects. We hypothesize that nodal measures based on ambivert degree can be effectively used to classify patients from healthy controls for diseases that are known to have widespread hub disruption. Using patient data for Alzheimer's Disease and Autism Spectrum Disorder, we show that the hubs in the patient and healthy groups are very different for both the diseases and deep feedforward neural networks trained on nodal hub features lead to a significantly higher classification accuracy with significantly fewer trainable weights compared to using functional connectivity features. Thus, the ambivert degree improves identification of crucial brain hubs in healthy subjects and can be used as a diagnostic feature to detect neurological diseases characterized by hub disruption.


Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/physiopathology , Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/physiopathology , Cerebral Cortex/diagnostic imaging , Connectome/methods , Deep Learning , Nerve Net/diagnostic imaging , Adolescent , Adult , Aged , Cerebral Cortex/physiopathology , Child , Humans , Magnetic Resonance Imaging , Nerve Net/physiopathology , Young Adult
11.
PLoS One ; 14(10): e0223161, 2019.
Article in English | MEDLINE | ID: mdl-31603902

ABSTRACT

In many data classification problems, a number of methods will give similar accuracy. However, when working with people who are not experts in data science such as doctors, lawyers, and judges among others, finding interpretable algorithms can be a critical success factor. Practitioners have a deep understanding of the individual input variables but far less insight into how they interact with each other. For example, there may be ranges of an input variable for which the observed outcome is significantly more or less likely. This paper describes an algorithm for automatic detection of such thresholds, called the Univariate Flagging Algorithm (UFA). The algorithm searches for a separation that optimizes the difference between separated areas while obtaining a high level of support. We evaluate its performance using six sample datasets and demonstrate that thresholds identified by the algorithm align well with published results and known physiological boundaries. We also introduce two classification approaches that use UFA and show that the performance attained on unseen test data is comparable to or better than traditional classifiers when confidence intervals are considered. We identify conditions under which UFA performs well, including applications with large amounts of missing or noisy data, applications with a large number of inputs relative to observations, and applications where incidence of the target is low. We argue that ease of explanation of the results, robustness to missing data and noise, and detection of low incidence adverse outcomes are desirable features for clinical applications that can be achieved with relatively simple classifier, like UFA.


Subject(s)
Algorithms , Breast Neoplasms/diagnosis , Diabetes Mellitus/diagnosis , Leukemia, Myeloid, Acute/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Sepsis/diagnosis , Body Temperature , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Datasets as Topic , Diabetes Mellitus/mortality , Diabetes Mellitus/pathology , Female , Humans , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Models, Statistical , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Sepsis/mortality , Sepsis/pathology , Survival Analysis
12.
Sci Rep ; 8(1): 16016, 2018 10 30.
Article in English | MEDLINE | ID: mdl-30375454

ABSTRACT

Current liver fibrosis scoring by computer-assisted image analytics is not fully automated as it requires manual preprocessing (segmentation and feature extraction) typically based on domain knowledge in liver pathology. Deep learning-based algorithms can potentially classify these images without the need for preprocessing through learning from a large dataset of images. We investigated the performance of classification models built using a deep learning-based algorithm pre-trained using multiple sources of images to score liver fibrosis and compared them against conventional non-deep learning-based algorithms - artificial neural networks (ANN), multinomial logistic regression (MLR), support vector machines (SVM) and random forests (RF). Automated feature classification and fibrosis scoring were achieved by using a transfer learning-based deep learning network, AlexNet-Convolutional Neural Networks (CNN), with balanced area under receiver operating characteristic (AUROC) values of up to 0.85-0.95 versus ANN (AUROC of up to 0.87-1.00), MLR (AUROC of up to 0.73-1.00), SVM (AUROC of up to 0.69-0.99) and RF (AUROC of up to 0.94-0.99). Results indicate that a deep learning-based algorithm with transfer learning enables the construction of a fully automated and accurate prediction model for scoring liver fibrosis stages that is comparable to other conventional non-deep learning-based algorithms that are not fully automated.


Subject(s)
Diagnostic Imaging , Image Processing, Computer-Assisted/methods , Liver Cirrhosis/diagnostic imaging , Algorithms , Animals , Biomarkers , Biopsy , Collagen/metabolism , Deep Learning , Diagnostic Imaging/methods , Image Processing, Computer-Assisted/standards , Liver Cirrhosis/pathology , Machine Learning , Magnetic Resonance Imaging , Male , Microscopy , Neural Networks, Computer , Rats , Reproducibility of Results , Tomography, X-Ray Computed
13.
PLoS One ; 13(5): e0195518, 2018.
Article in English | MEDLINE | ID: mdl-29734327

ABSTRACT

Research on temporal characteristics of human dynamics has attracted much attentions for its contribution to various areas such as communication, medical treatment, finance, etc. Existing studies show that the time intervals between two consecutive events present different non-Poisson characteristics, such as power-law, Pareto, bimodal distribution of power-law, exponential distribution, piecewise power-law, et al. With the occurrences of new services, new types of distributions may arise. In this paper, we study the distributions of the time intervals between two consecutive visits to QQ and WeChat service, the top two popular instant messaging services in China, and present a new finding that when the value of statistical unit T is set to 0.001s, the inter-event time distribution follows a piecewise distribution of exponential and power-law, indicating the heterogeneous character of IM services users' online behavior in different time scales. We infer that the heterogeneous character is related to the communication mechanism of IM and the habits of users. Then we develop a combination model of exponential model and interest model to characterize the heterogeneity. Furthermore, we find that the exponent of the inter-event time distribution of the same service is different in two cities, which is correlated with the popularity of the services. Our research is useful for the application of information diffusion, prediction of economic development of cities, and so on.


Subject(s)
Internet , Models, Statistical , Social Behavior , Text Messaging/statistics & numerical data , Humans , Time Factors
14.
Gastric Cancer ; 19(2): 453-465, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26205786

ABSTRACT

BACKGROUND: Gastric cancer, a leading cause of cancer death worldwide, has been little studied compared with other cancers that impose similar health burdens. Our goal is to assess genomic copy-number loss and the possible functional consequences and therapeutic implications thereof across a large series of gastric adenocarcinomas. METHODS: We used high-density single-nucleotide polymorphism microarrays to determine patterns of copy-number loss and allelic imbalance in 74 gastric adenocarcinomas. We investigated whether suppressor of tumorigenesis and/or proliferation (STOP) genes are associated with genomic copy-number loss. We also analyzed the extent to which copy-number loss affects Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes-genes that may be attractive targets for therapeutic inhibition when partially deleted. RESULTS: The proportion of the genome subject to copy-number loss varies considerably from tumor to tumor, with a median of 5.5 %, and a mean of 12 % (range 0-58.5 %). On average, 91 STOP genes were subject to copy-number loss per tumor (median 35, range 0-452), and STOP genes tended to have lower copy-number compared with the rest of the genes. Furthermore, on average, 1.6 CYCLOPS genes per tumor were both subject to copy-number loss and downregulated, and 51.4 % of the tumors had at least one such gene. CONCLUSIONS: The enrichment of STOP genes in regions of copy-number loss indicates that their deletion may contribute to gastric carcinogenesis. Furthermore, the presence of several deleted and downregulated CYCLOPS genes in some tumors suggests potential therapeutic targets in these tumors.


Subject(s)
Adenocarcinoma/genetics , Gene Dosage , Gene Expression Regulation, Neoplastic , Stomach Neoplasms/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Cell Proliferation , Genes, Tumor Suppressor , Humans , Loss of Heterozygosity , Polymorphism, Single Nucleotide , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology
15.
J Biophotonics ; 9(4): 351-63, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26131709

ABSTRACT

Liver surface is covered by a collagenous layer called the Glisson's capsule. The structure of the Glisson's capsule is barely seen in the biopsy samples for histology assessment, thus the changes of the collagen network from the Glisson's capsule during the liver disease progression are not well studied. In this report, we investigated whether non-linear optical imaging of the Glisson's capsule at liver surface would yield sufficient information to allow quantitative staging of liver fibrosis. In contrast to conventional tissue sections whereby tissues are cut perpendicular to the liver surface and interior information from the liver biopsy samples were used, we have established a capsule index based on significant parameters extracted from the second harmonic generation (SHG) microscopy images of capsule collagen from anterior surface of rat livers. Thioacetamide (TAA) induced liver fibrosis animal models was used in this study. The capsule index is capable of differentiating different fibrosis stages, with area under receiver operating characteristics curve (AUC) up to 0.91, making it possible to quantitatively stage liver fibrosis via liver surface imaging potentially with endomicroscopy.


Subject(s)
Liver Cirrhosis/diagnostic imaging , Liver/diagnostic imaging , Microscopy , Animals , Collagen/metabolism , Liver/metabolism , Liver/pathology , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Male , Rats , Rats, Wistar , Surface Properties
16.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 3887-3890, 2016 Aug.
Article in English | MEDLINE | ID: mdl-28269135

ABSTRACT

Quantitative co-localization analysis with fluorescent microscopy is a common approach to assess the spatial co-ordination of molecules and thus to understand their functions in biological processes. However, the co-localization analysis results might not be consistent due to various imaging conditions and different quantification methods used. We propose a novel method to separate a co-localization event into two aspects: co-occurrence and intensity correlation, which are usually combined as one parameter in other quantitative co-localization analyses. By examining co-localization through both co-occurrence and intensity correlation, the co-localization analysis provides accurate and interpretable results. Furthermore, the co-occurrence pixels can be visualized in an additional image channel to provide an intuitive impression of the quantity and locations of the co-localization events occurring.


Subject(s)
Image Processing, Computer-Assisted , Microscopy, Fluorescence , Algorithms , Animals , Computers , Embryonic Stem Cells/cytology , Humans , Mice , Normal Distribution , Software
17.
Aerosp Med Hum Perform ; 86(7): 606-13, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26102140

ABSTRACT

INTRODUCTION: Shoulder injuries due to working inside the space suit are some of the most serious and debilitating injuries astronauts encounter. Space suit injuries occur primarily in the Neutral Buoyancy Laboratory (NBL) underwater training facility due to accumulated musculoskeletal stress. We quantitatively explored the underlying causal mechanisms of injury. METHODS: Logistic regression was used to identify relevant space suit components, training environment variables, and anthropometric dimensions related to an increased propensity for space-suited injury. Two groups of subjects were analyzed: those whose reported shoulder incident is attributable to the NBL or working in the space suit, and those whose shoulder incidence began in active duty, meaning working in the suit could be a contributing factor. RESULTS: For both groups, percent of training performed in the space suit planar hard upper torso (HUT) was the most important predictor variable for injury. Frequency of training and recovery between training were also significant metrics. The most relevant anthropometric dimensions were bideltoid breadth, expanded chest depth, and shoulder circumference. Finally, record of previous injury was found to be a relevant predictor for subsequent injury. The first statistical model correctly identifies 39% of injured subjects, while the second model correctly identifies 68% of injured subjects. DISCUSSION: A review of the literature suggests this is the first work to quantitatively evaluate the hypothesized causal mechanisms of all space-suited shoulder injuries. Although limited in predictive capability, each of the identified variables can be monitored and modified operationally to reduce future impacts on an astronaut's health.


Subject(s)
Accidents, Occupational/statistics & numerical data , Aerospace Medicine/methods , Arm Injuries/epidemiology , Astronauts/statistics & numerical data , Shoulder Injuries , Space Flight/instrumentation , Space Suits/statistics & numerical data , Arm Injuries/etiology , Humans , Logistic Models , Models, Theoretical , ROC Curve , Space Suits/adverse effects
18.
J Biophotonics ; 8(10): 804-15, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25597396

ABSTRACT

Cancer initiating cells (CICs) have been the focus of recent anti-cancer therapies, exhibiting strong invasion capability via potentially enhanced ability to remodel extracellular matrices (ECM). We have identified CICs in a human breast cancer cell line, MX-1, and developed a xenograft model in SCID mice. We investigated the CICs' matrix-remodeling effects using Second Harmonic Generation (SHG) microscopy to identify potential phenotypic signatures of the CIC-rich tumors. The isolated CICs exhibit higher proliferation, drug efflux and drug resistant properties in vitro; were more tumorigenic than non-CICs, resulting in more and larger tumors in the xenograft model. The CIC-rich tumors have less collagen in the tumor interior than in the CIC-poor tumors supporting the idea that the CICs can remodel the collagen more effectively. The collagen fibers were preferentially aligned perpendicular to the CIC-rich tumor boundary while parallel to the CIC-poor tumor boundary suggesting more invasive behavior of the CIC-rich tumors. These findings would provide potential translational values in quantifying and monitoring CIC-rich tumors in future anti-cancer therapies. CIC-rich tumors remodel the collagen matrix more than CIC-poor tumors.


Subject(s)
Breast Neoplasms/pathology , Extracellular Matrix/pathology , Neoplastic Stem Cells/pathology , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Transformation, Neoplastic , Collagen/metabolism , Doxorubicin/metabolism , Doxorubicin/pharmacology , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Female , Humans , Mice , Mice, SCID , Microscopy , Mitoxantrone/metabolism , Mitoxantrone/pharmacology , Neoplasm Invasiveness , Neoplastic Stem Cells/drug effects
19.
Sci Rep ; 4: 4636, 2014 Apr 10.
Article in English | MEDLINE | ID: mdl-24717650

ABSTRACT

The accurate staging of liver fibrosis is of paramount importance to determine the state of disease progression, therapy responses, and to optimize disease treatment strategies. Non-linear optical microscopy techniques such as two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) can image the endogenous signals of tissue structures and can be used for fibrosis assessment on non-stained tissue samples. While image analysis of collagen in SHG images was consistently addressed until now, cellular and tissue information included in TPEF images, such as inflammatory and hepatic cell damage, equally important as collagen deposition imaged by SHG, remain poorly exploited to date. We address this situation by experimenting liver fibrosis quantification and scoring using a combined approach based on TPEF liver surface imaging on a Thioacetamide-induced rat model and a gradient based Bag-of-Features (BoF) image classification strategy. We report the assessed performance results and discuss the influence of specific BoF parameters to the performance of the fibrosis scoring framework.


Subject(s)
Liver Cirrhosis/diagnosis , Microscopy, Fluorescence, Multiphoton/methods , Animals , Disease Progression , Image Processing, Computer-Assisted , Liver/pathology , Liver Cirrhosis/classification , Male , Rats , Rats, Wistar , Thioacetamide
20.
J Hepatol ; 61(2): 260-269, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24583249

ABSTRACT

BACKGROUND & AIMS: There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients. METHODS: qFibrosis was established as a combined index based on 87 parameters of architectural features. Images acquired from 25 Thioacetamide-treated rat samples and 162 CHB core biopsies were used to train and test qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed employing Metavir and Ishak fibrosis staging as standard references, and collagen proportionate area (CPA) measurement for comparison. RESULTS: qFibrosis faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify differences between all stages in both animal samples (p<0.001) and human biopsies (p<0.05). It is robust to sampling size, allowing for discrimination of different stages in samples of different sizes (area under the curve (AUC): 0.93-0.99 for animal samples: 1-16 mm(2); AUC: 0.84-0.97 for biopsies: 10-44 mm in length). qFibrosis can significantly predict staging underestimation in suboptimal biopsies (<15 mm) and under- and over-scoring by different pathologists (p<0.001). qFibrosis can also differentiate between Ishak stages 5 and 6 (AUC: 0.73, p=0.008), suggesting the possibility of monitoring intra-stage cirrhosis changes. Best of all, qFibrosis demonstrates superior performance to CPA on all counts. CONCLUSIONS: qFibrosis can improve fibrosis scoring accuracy and throughput, thus allowing for reproducible and reliable analysis of efficacies of anti-fibrotic therapies in clinical research and practice.


Subject(s)
Hepatitis B, Chronic/complications , Liver Cirrhosis, Experimental/diagnosis , Animals , Biopsy , Collagen/analysis , Disease Models, Animal , Humans , Liver/pathology , Liver Cirrhosis, Experimental/pathology , Rats
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