As a fundamental component of health care, disease screening is of highly importance. Oftentimes, two screening tests for a specific disease are compared in order to determine an optimal screening ...policy, for example, the digital rectal examination (DRE) and serum prostate specific antigen (PSA) level for screening prostate cancer. Ideally, if a gold standard test is given to each individual being screened to establish their true disease status, the difference in accuracy measures between two tests can be evaluated. In practice, however, it is common that only individuals who test positive on at least one screening test are to receive gold standard tests, which are often invasive and cannot be applied to those with negative results on both tests due to ethical reasons. Under such circumstances, estimates of the differences in accuracy measures between two tests cannot be determined, thus the inference problem within this framework is challenging. In this article, using sensitivity and specificity as measures of test accuracy, we show that their difference between two tests is interval‐identified, as bounded by estimable sharp bounds. Here, we develop the asymptotic normality for the estimators of the bounds and construct confidence intervals for the difference by utilizing the method for solving inference problem for partially identified parameters. The performance of constructed confidence intervals for the difference and their sharp bounds are evaluated via simulation studies. We also apply the proposed method to the prostate cancer example to compare the accuracy of DRE and PSA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Reverse time migration (RTM) is a seismic imaging method to map the subsurface reflectivity using recorded seismic waveforms. The practice in exploration seismology has long established a two-fold ...approach of seismic imaging: Using velocity modeling building to establish the long-wavelength reference velocity models, and using seismic migration to map the short-wavelength reflectivity structures. Among various seismic migration methods for different situations, RTM is the only method that is capable to use all seismic wave types that can be computed numerically. Being initiated in early 1980's, RTM seeks an image of the subsurface reflectivity as the best match in an image space between the extrapolation of time-reversed waveform data and the prediction based on estimated velocity model and source parameters. Judging the image quality in the same space of forming the images is more advantageous than the approaches of modeling and inversion which seek the solution in the model space but judge its fitness in data space. Considering that most seismic migration applications today still use primary reflection as the only signal, the capability of RTM to use all computable wave types is unique and helpful reducing the imaging artifacts due to mistaking non-primary waves as primary reflections. Hence, we refer to those RTM algorithms using only primary reflections as the first-generation RTM methods, and the RTM algorithms making a full use of primary reflections, multiple reflections and other non-primary waveform data as the second-generation RTM methods. This paper reviews the development history of the RTM along with its major challenges, current solutions, and future perspectives.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study proposes novel estimation and inference approaches for heterogeneous local treatment effects using high‐dimensional covariates and observational data without a strong ignorability ...assumption. To achieve this, with a binary instrumental variable, the parameters of interest are identified on an unobservable subgroup of the population (compliers). Lasso estimation under a non‐convex objective function is developed for a two‐stage generalized linear model, and a debiased estimator is proposed to construct confidence intervals for treatment effects conditioned on covariates. Notably, this approach simultaneously corrects the biases due to high‐dimensional estimation at both stages. The finite sample performance is evaluated via simulation studies, and real data analysis is performed on the Oregon Health Insurance Experiment to illustrate the feasibility of the proposed procedure.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Acute liver failure (ALF) is a syndrome of severe hepatocyte injury with high rate of mortality. Hepatitis B virus (HBV) infection is the major cause of ALF worldwide, however, ...the underlying mechanism by which HBV infection leads to ALF has not been fully disclosed.
Methods
D-GalN-induced hepatocyte injury model and LPS/D-GalN-induced ALF mice model were used to investigate the effects of HBV X protein (HBx) in vitro and in vivo, respectively. Cell viability and the levels of Glutathione (GSH), malondialdehyde (MDA) and iron were measured using commercial kits. The expression of ferroptosis-related molecules were detected by qRT-PCR and western blotting. Epigenetic modification and protein interaction were detected by chromatin immunoprecipitation (ChIP) assay and co-immunoprecipitation (co-IP), respectively. Mouse liver function was assessed by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histological changes in liver tissues were monitored by hematoxylin and eosin (H&E) staining, and SLC7A11 immunoreactivity was assessed by immunohistochemistry (IHC) analysis.
Results
D-GalN triggered ferroptosis in primary hepatocytes. HBx potentiated D-GalN-induced hepatotoxicity and ferroptosis in vitro, and it suppressed SLC7A11 expression through H3K27me3 modification by EZH2. In addition, EZH2 inhibition or SLC7A11 overexpression attenuated the effects of HBx on D-GalN-induced ferroptosis in primary hepatocytes. The ferroptosis inhibitor ferrostatin-1 (Fer-1) protected against ALF and ferroptosis in vivo. By contrast, HBx exacerbates LPS/D-GalN-induced ALF and ferroptosis in HBx transgenic (HBx-Tg) mice.
Conclusion
HBx facilitates ferroptosis in ALF via EZH2/H3K27me3-mediated SLC7A11 suppression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Multi-Label Learning with Emerging New Labels Zhu, Yue; Ting, Kai Ming; Zhou, Zhi-Hua
IEEE transactions on knowledge and data engineering,
10/2018, Volume:
30, Issue:
10
Journal Article
Peer reviewed
Open access
In a multi-label learning task, an object possesses multiple concepts where each concept is represented by a class label. Previous studies on multi-label learning have focused on a fixed set of class ...labels, i.e., the class label set of test data is the same as that in the training set. In many applications, however, the environment is dynamic and new concepts may emerge in a data stream. In order to maintain a good predictive performance in this environment, a multi-label learning method must have the ability to detect and classify instances with emerging new labels. To this end, we propose a new approach called Multi-label learning with Emerging New Labels (MuENL). It has three functions: classify instances on currently known labels, detect the emergence of a new label, and construct a new classifier for each new label that works collaboratively with the classifier for known labels. In addition, we show that MuENL can be easily extended to handle sparse high dimensional data streams by simply reducing the original dimensionality, and then applying MuENL on the reduced dimensional space. Our empirical evaluation shows the effectiveness of MuENL on several benchmark datasets and MuENLHD on the sparse high dimensional Weibo dataset.
This study was aimed at investigating the effects of lncRNA AK139328 on myocardial ischaemia/reperfusion injury (MIRI) in diabetic mice. Ischaemia/reperfusion (I/R) model was constructed in normal ...mice (NM) and diabetic mice (DM). Microarray analysis was utilized to identify lncRNA AK139328 overexpressed in DM after myocardial ischaemia/reperfusion (MI/R). RT‐qPCR assay was utilized to investigate the expressions of lncRNA AK139328 and miR‐204‐3p in cardiomyocyte and tissues. Left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and fractioning shortening (FS) were obtained by transthoracic echocardiography. Haematoxylin‐eosin (HE) staining and Masson staining were utilized to detect the damage of myocardial tissues degradation of myocardial fibres and integrity of myocardial collagen fibres. Evans Blue/TTC staining was used to determine the myocardial infarct size. TUNEL staining was utilized to investigate cardiomyocyte apoptosis. The targeted relationship between lncRNA AK139328 and miR‐204‐3p was confirmed by dual‐luciferase reporter gene assay. MTT assay was used for analysis of cardiomyocyte proliferation. Western blot was utilized to investigate the expression of alpha smooth muscle actin (α‐SMA), Atg7, Atg5, LC3‐II/LC3‐I and p62 marking autophagy. Knockdown of lncRNA AK139328 relieved myocardial ischaemia/reperfusion injury in DM and inhibited cardiomyocyte autophagy as well as apoptosis of DM. LncRNA AK139328 modulated miR‐204‐3p directly. MiR‐204‐3p and knockdown of lncRNA AK139328 relieved hypoxia/reoxygenation injury via inhibiting cardiomyocyte autophagy. Silencing lncRNA AK139328 significantly increased miR‐204‐3p expression and inhibited cardiomyocyte autophagy, thereby attenuating MIRI in DM.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Current machine learning techniques have achieved great success; however, there are many deficiencies. First, to train a strong model, a large amount of training examples are required, whereas ...collecting the data, particularly data with labels, is expensive or even difficult in many real tasks. Second, once a model has been trained, if environment changes, which often happens in real tasks, the model can hardly perform well or even become useless. Third,
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In prognosis studies to evaluate association between a continuous biomarker and a survival outcome, investigators often classify subjects into two subclasses of the high‐ and low‐expression groups ...and apply simple survival analysis techniques of the Kaplan‐Meier method and the logrank test. The high‐ and low‐expressions are defined according to whether or not the observation of the biomarker is higher than the cut‐off value, which is heterogeneous across studies. The heterogeneous definitions of the cut‐off value make it difficult to apply the standard meta‐analysis techniques. We propose a method to estimate the concordance index for a survival outcome synthesizing published prognosis studies, in which the Kaplan‐Meier estimates for the high‐ and low‐expression groups are reported. We illustrate our proposed method with a real dataset for meta‐analysis of prognosis studies evaluating Ki‐67 in early breast cancer and evaluate its performance with a simulation study.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Plastics–microorganism interactions have aroused growing environmental and ecological concerns. However, previous studies concentrated mainly on the direct interactions and paid little attention to ...the ecotoxicology effects of phthalates (PAEs), a common plastic additive that is continuously released and accumulates in the environment. Here, we provide insights into the impacts of PAEs on the dissemination of antibiotic resistance genes (ARGs) among environmental microorganisms. Dimethyl phthalate (DMP, a model PAE) at environmentally relevant concentrations (2–50 μg/L) significantly boosted the plasmid-mediated conjugation transfer of ARGs among intrageneric, intergeneric, and wastewater microbiota by up to 3.82, 4.96, and 4.77 times, respectively. The experimental and molecular dynamics simulation results unveil a strong interaction between the DMP molecules and phosphatidylcholine bilayer of the cell membrane, which lowers the membrane lipid fluidity and increases the membrane permeability to favor transfer of ARGs. In addition, the increased reactive oxygen species generation and conjugation-associated gene overexpression under DMP stress also contribute to the increased gene transfer. This study provides fundamental knowledge of the PAE–bacteria interactions to broaden our understanding of the environmental and ecological risks of plastics, especially in niches with colonized microbes, and to guide the control of ARG environmental spreading.
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IJS, KILJ, NUK, PNG, UL, UM
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