Pathological Evidence Exploration in Deep Retinal Image Diagnosis

Though deep learning has shown successful performance in classifying the label and severity stage of certain disease, most of them give few evidence on how to make prediction. Here, we propose to exploit the interpretability of deep learning application in medical diagnosis. Inspired by Koch's Postulates, a well-known strategy in medical research to identify the property of pathogen, we define a pathological descriptor that can be extracted from the activated neurons of a diabetic retinopathy detector. To visualize the symptom and feature encoded in this descriptor, we propose a GAN based method to synthesize pathological retinal image given the descriptor and a binary vessel segmentation. Besides, with this descriptor, we can arbitrarily manipulate the position and quantity of lesions. As verified by a panel of 5 licensed ophthalmologists, our synthesized images carry the symptoms that are directly related to diabetic retinopathy diagnosis. The panel survey also shows that our generated images is both qualitatively and quantitatively superior to existing methods.Comment: to appear in AAAI (2019). The first two authors contributed equally to the paper. Corresponding Author: Feng L

Identification of Soat1 as a Quantitative Trait Locus Gene on Mouse Chromosome 1 Contributing to Hyperlipidemia

We previously identified two closely linked quantitative trait loci (QTL) on distal chromosome 1 contributing to major variations in plasma cholesterol and triglyceride levels in an intercross derived from C57BL/6 (B6) and C3H/HeJ (C3H) apolipoprotein E-deficient (apoE−/−) mice. Soat1, encoding sterol o-acyltransferase 1, is a functional candidate gene located underneath the proximal linkage peak. We sequenced the coding region of Soat1 and identified four single nucleotide polymorphisms (SNPs) between B6 and C3H mice. Two of the SNPs resulted in amino-acid substitutions (Ile147Val and His205Tyr). Functional assay revealed an increased enzyme activity of Soat1 in peritoneal macrophages of C3H mice relative to those of B6 mice despite comparable protein expression levels. Allelic variants of Soat1 were associated with variations in plasma cholesterol and triglyceride levels in an intercross between B6.apoE−/− and C3H.apoE−/− mice. Inheritance of the C3H allele resulted in significantly higher plasma lipid levels than inheritance of the B6 allele. Soat1 variants were also significantly linked to major variations in plasma esterified cholesterol levels but not with free cholesterol levels. Trangenic expression of C3H Soat1 in B6.apoE−/− mice resulted in elevations of plasma cholesterol and triglyceride levels. These results indicate that Soat1 is a QTL gene contributing to hyperlipidemia

Identification of Matrix Metalloproteinase-2 and 9 as Biomarker of Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disease uniquely occurring during pregnancy. In this study we aimed to identify novel biomarker for the diagnosis of ICP in Chinese population. 50 healthy pregnant women, 50 mild ICP patients and 48 severe ICP patients were enrolled for this study. Liver function tests, including serum total bilirubin, direct bilirubin, alanine transami-nase, aspartate aminotransferase and cholyglycine, were performed in all participants. After an overnight fast serum levels of total bile acids (TBA), matrix metalloproteinase (MMP)-2 and MMP-9 were measured, and their correlation with liver function tests were analyzed. The observed increase in serum TBA in ICP patients was not statistically significant which made it unreliable for diagnosis of ICP in Chinese population. On the other hand, both MMP-2 and MMP-9 serum levels exhibited a progressive and significant elevation in mild and severe ICP patients compared with healthy pregnant women, which also positively correlated with liver function tests. Serum levels of both MMP-2 and MMP-9 could be reliably used as laboratory abnormalities for accurate diagnosis and sensitive grading of ICP in Chinese population

Comparison of <i>Soat1</i> enzyme activity in peritoneal macrophages harvested from B6.apoE^−/− and C3H.apoE^−/− mice (A).

<p>Cell homogenates were prepared from five individual mice of each strain and kept at concentrations of 2–4 mg/ml in a buffer (50 mM Tris, 1 mM EDTA at pH 7.8 with protease inhibitors). To solubilize the enzyme, 1 M KCl and various concentrations of CHAPS were added. The enzyme was assayed in duplicate in taurochoate/cholesterol/PC mixed micelles. *<i>P</i><0.05. C3H had significantly higher <i>Soat1</i> activity levels than B6. Western blot analysis of <i>Soat1</i> expression in peritoneal macrophages derived from B6.apoE^−/− and C3H.apoE^−/− mice (B). Each lane represents an individual mouse. There was no significant difference in <i>Soat1</i> expression between the two strains.</p

Characterization of <i>Soat1</i> transgenic mice.

<p>A, expression of <i>Soat1</i> protein in transgenic mice. PC, positive control: lane loaded with <i>Soat1</i> protein; NC, negative control: lane loaded with buffer only. B, real-time PCR analysis of <i>Soat1</i> mRNA expression in the liver of transgenic and non-transgenic (control) littermates. The expression level of <i>Soat1</i> was expressed as copy number relative to 10,000 copies of GAPDH mRNA. Results are means ± SE of 6 and 5 transgenic and non-transgenic mice, respectively. C, expression of <i>Soat1</i> protein in the liver of transgenic and non-transgenic littermates. Each lane represents an individual mouse.</p