Improved FCOS for Detecting Breast Cancers.

PURPOSE: Breast cancer ranks first among cancers affecting women's health. Our goal is to develop a fast, high-precision, and fully automated breast cancer detection algorithm to improve the early detection rate of breast cancer. METHODS: We compare different object detection algorithms, including anchor-based and anchor-free object detection algorithms for detecting breast lesions. Finally, we find that the fully convolutional onestage object detection (FCOS) showed the best performance in the detection of breast lesions, which is an anchor-free algorithm. 1) Considering that the detection of breast lesions requires the context information of the ultrasound images, we introduce the non-local technique, which models long-range dependency between pixels to the FCOS algorithm, providing the global context information for the detection of the breast lesions. 2) The variety of shapes and sizes of breast lesions makes detection difficult. We propose a new deformable spatial attention (DSA) module and add it to the FCOS algorithm. RESULTS: The detection performance of the original FCOS is that the average precision (AP) for benign lesions is 0.818, and for malignant lesions is 0.888. The FCOS with a non-local module improves the performance of the breast detection; the AP of benign lesions was 0.819, and that of malignant lesions was 0.894. Combining the DSA module with the FCOS improves the performance of breast detection; the AP for benign lesions and malignant lesions is 0.840 and 0.899, respectively. CONCLUSION: We propose two methods to improve the FCOS algorithm from different perspectives to improve its performance in detecting breast lesions. We find that FCOS combined with DSA is beneficial in improving the localization and classification of breast tumors and can provide auxiliary diagnostic advice for ultrasound physicians, which has a certain clinical application value.

Artificial Intelligence Medical Ultrasound Equipment: Application of Breast Lesions Detection.

Breast cancer ranks first among cancers affecting women's health. Our work aims to realize the intelligence of the medical ultrasound equipment with limited computational capability, which is used for the assistant detection of breast lesions. We embed the high-computational deep learning algorithm into the medical ultrasound equipment with limited computational capability by two techniques: (1) lightweight neural network: considering the limited computational capability of ultrasound equipment, a lightweight neural network is designed, which greatly reduces the amount of calculation. And we use the technique of knowledge distillation to train the low-precision network helped with the high-precision network; (2) asynchronous calculations: consider four frames of ultrasound images as a group; the image of the first frame of each group is used as the input of the network, and the result is respectively fused with the images of the fourth to seventh frames. An amount of computation of 30 GFLO/frame is required for the proposed lightweight neural network, about 1/6 of that of the large high-precision network. After trained from scratch using the knowledge distillation technique, the detection performance of the lightweight neural network (sensitivity = 89.25%, specificity = 96.33%, the average precision [AP] = 0.85) is close to that of the high-precision network (sensitivity = 98.3%, specificity = 88.33%, AP = 0.91). By asynchronous calculation, we achieve real-time automatic detection of 24 fps (frames per second) on the ultrasound equipment. Our work proposes a method to realize the intelligence of the low-computation-power ultrasonic equipment, and successfully achieves the real-time assistant detection of breast lesions. The significance of the study is as follows: (1) The proposed method is of practical significance in assisting doctors to detect breast lesions; (2) our method provides some practical and theoretical support for the development and engineering of intelligent equipment based on artificial intelligence algorithms.

Evaluation of the Oxidative Stress Status in Zebrafish (Danio rerio) Liver Induced by Three Typical Organic UV Filters (BP-4, PABA and PBSA).

Organic UV filters are a kind of emerging pollutants, which have been widely used in personal care products (PCPs). This study evaluated the effects of benzophenone-4 (BP-4), 4-aminobenzoic acid (PABA), and 2-phenylbenzimidazole-5-sulfonic acid (PBSA) on the selected indices of antioxidative responses in zebrafish (Danio rerio) liver. Zebrafish were exposed to two different doses (i.e., 0.5 and 5 mg L-1) of semi-static water with three individual compounds. Liver samples were collected on 7 and 14 days to analyze biochemical indicators, including superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA). Oxidative stress occurred in zebrafish liver with significantly changed indicators during the whole exposure period. Different experimental groups could induce or inhibit the activity of antioxidant enzymes with varying degrees. With a prolonged exposure time and increased exposure dose, the hepatic lipid peroxidation was also obviously observed. Moreover, the toxicity order of three organic UV filters was analyzed using the integrated biomarker response (IBR) index and the results indicate that exposure to PABA for 7 days at 0.5 mg L-1 and PBSA for 7 days at 5 mg L-1 induced the most severe oxidative stress in the liver of zebrafish.

Ultrasonic Diagnosis of Breast Nodules Using Modified Faster R-CNN.

Breast cancer has become the biggest threat to female health. Ultrasonic diagnosis of breast cancer based on artificial intelligence is basically a classification of benign and malignant tumors, which does not meet clinical demand. Besides, the current target detection method performs poorly in detecting small lesions, while it is clinically required to detect nodules below 2 mm. The objective of this study is to (a) propose a diagnostic method based on Breast Imaging Reporting and Data System (BI-RADS) and (b) increase its detectability of small lesions. We modified the framework of Faster R-CNN (Faster Region-based Convolutional Neural Network) by introducing multi-scale feature extraction and multi-resolution candidate bound extraction into the network. Then, it was trained using 852 images of BI-RADS C2, 739 images of C3, and 1662 images of malignancy (BI-RADS 4a/4b/4c/5/6). We compared our model with unmodified Faster R-CNN and YOLO v3 (You Only Look Once v3). The mean average precision (mAP) is significantly increased to 0.913, while its average detection speed is slightly declined to 4.11 FPS (frames per second). Meanwhile, its detectivity of small lesions is effectively improved. Moreover, we also tentatively applied our model on video sequences and got satisfactory results. We modified Faster R-CNN and trained it partly based on BI-RADS. Its detectability of lesions, as well as small nodules, was significantly improved. In view of wide coverage of dataset and satisfactory test results, our method can basically meet clinical needs.

Major Effect of Oxidative Stress on the Male, but Not Female, SP-A1 Type II Cell miRNome.

Pulmonary surfactant protein A (SP-A) plays an important role in surfactant metabolism and lung innate immunity. In humans there are two proteins, SP-A1 and SP-A2, encoded by SFTPA1 and SFTPA2, respectively, which are produced by the alveolar type II cells (T2C). We sought to investigate the differential influence of SP-A1 and SP-A2 in T2C miRNome under oxidative stress (OxS). SP-A knock out (KO) and hTG male and female mice expressing SP-A1 or SP-A2 as well as gonadectomized (Gx) mice were exposed to O3-induced oxidative stress (OxS) or filtered air (FA). Expression of miRNAs and mRNAs was measured in the T2C of experimental animals. (a) In SP-A1 males after normalizing to KO males, significant changes were observed in the miRNome in terms of sex-OxS effects, with 24 miRNAs being differentially expressed under OxS. (b) The mRNA targets of the dysregulated miRNAs included Ago2, Ddx20, Plcg2, Irs1, Elf2, Jak2, Map2k4, Bcl2, Ccnd1, and Vhl. We validated the expression levels of these transcripts, and observed that the mRNA levels of all of these targets were unaffected in SP-A1 T2C but six of these were significantly upregulated in the KO (except Bcl2 that was downregulated). (c) Gondadectomy had a major effect on the expression of miRNAs and in three of the mRNA targets (Irs1, Bcl2, and Vhl). Ccnd1 was upregulated in KO regardless of Gx. (d) The targets of the significantly changed miRNAs are involved in several pathways including MAPK signaling pathway, cell cycle, anti-apoptosis, and other. In conclusion, in response to OxS, SP-A1 and male hormones appear to have a major effect in the T2C miRNome.

Effect of decabromodiphenyl ether (BDE-209) on a soil-biota system: Role of earthworms and ryegrass.

In the present study, the toxic effect of decabromodiphenyl ether (BDE-209), an important brominated fire retardant, on soil was evaluated by amending with different concentrations (0 mg/kg, 1 mg/kg, 10 mg/kg, and 500 mg/kg dry wt) for 40 d. The activities of 3 soil enzymes (urease, catalase, and alkaline phosphatase) were measured as the principal assessment endpoints. Meanwhile, the effects of natural environmental factors, such as light conditions and soil biota, on BDE-209 intoxication were studied. For the latter, 30 earthworms (Metaphire guillelmi) with fully matured clitella or ryegrass (Lolium perenne) with fully matured leaves were exposed in soil amended with BDE-209. The activities of the soil enzymes were adversely affected by BDE-209, especially for the high-concentration treatments, with greater adverse effects in the dark than in the light. The presence of earthworms reduced toxicity to BDE-209, whereas ryegrass did not. The calculated integrated biomarker response index, which provides a general indicator of the health status of test species by combining different biomarker signals, further validated these findings. Moreover, the antioxidant status (oxidant-antioxidant balance) of these 2 biota was assessed. Results indicated that BDE-209 significantly affected the activities of antioxidant enzymes (superoxide dismutase and catalase) and enhanced the levels of malondialdehyde in both species. The present study may facilitate a better understanding of the toxicity of BDE-209 toward the soil environment. Environ Toxicol Chem 2016;35:1349-1357. © 2015 SETAC.

Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations.

BACKGROUND: There is a significant clinical need for effective treatment of iron deficiency. A number of compounds that can be administered intravenously have been developed. This study examines how the compounds are handled by macrophages and their relative potential to provoke oxidative stress. METHODS: Human kidney (HK-2) cells, rat peritoneal macrophages and renal cortical homogenates were exposed to pharmaceutical iron preparations. Analyses were performed for indices of oxidative stress and cell integrity. In addition, in macrophages, iron uptake and release and cytokine secretion was monitored. RESULTS: HK-2 cell viability was decreased by iron isomaltoside and ferumoxytol and all compounds induced lipid peroxidation. In the renal cortical homogenates, lipid peroxidation occurred at lowest concentrations with ferric carboxymaltose, iron dextran, iron sucrose and sodium ferric gluconate. In the macrophages, iron sucrose caused loss of cell viability. Iron uptake was highest for ferumoxytol and iron isomaltoside and lowest for iron sucrose and sodium ferric gluconate. Iron was released as secretion of ferritin or as ferrous iron via ferroportin. The latter was blocked by hepcidin. Exposure to ferric carboxymaltose and iron dextran resulted in release of tumor necrosis factor α. CONCLUSIONS: Exposure to iron compounds increased cell stress but was tissue and dose dependent. There was a clear difference in the handling of iron from the different compounds by macrophages that suggests in vivo responses may differ.

Subacute oral toxicity of BDE-15, CDE-15, and HODE-15 in ICR male mice: assessing effects on hepatic oxidative stress and metals status and ascertaining the protective role of vitamin E.

The present study examined the effects of oral exposure of 4,4'-dibromodiphenyl ether (BDE-15), 4,4'-dichlorodiphenyl ether (CDE-15), and 4,4'-dihydroxydiphenyl ether (HODE-15) on hepatic oxidative stress (OS) and metal status in Institute of Cancer Research (ICR) male mice. Furthermore, the role of vitamin E in ameliorating potential OS caused by BDE-15, CDE-15, and HODE-15 was investigated. Three groups of mice were exposed to 1.20 mg/kg(body weight)/day of each of the three toxicants for 28 days. Results showed that none of the three toxicants altered growth rates of mice, but significantly increased (P<0.05) relative liver weights and decreased relative kidney weights. Pathological changes including cell swelling, inflammation and vacuolization, and hepatocellular hypertrophy in livers were observed. Significant decreases (P<0.05 and P<0.01) in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and glutathione (GSH) levels, together with increases in malondialdehyde (MDA) content were recorded in all toxicant-treated groups. Hepatic copper levels increased in all toxicant-treated groups. Hepatic zinc levels decreased in the liver of BDE-15-treated mice, whereas they increased in the livers of CDE-15-treated and HODE-15-treated mice. In conclusion, daily exposure to the three toxicants perturbed metal homeostasis and increased OS in mouse liver. Experimental data indicated the hepatic oxidative toxicity of the three toxicants followed the order BDE-15

Acute oral toxicity and liver oxidant/antioxidant stress of halogenated benzene, phenol, and diphenyl ether in mice: a comparative and mechanism exploration.

The lethal doses (LD50s) of fluorinated, chlorinated, brominated, and iodinated benzene, phenol, and diphenyl ether in mice were ascertained respectively under the consistent condition. The acute toxicity of four benzenes orders in fluorobenzene (FB) < iodobenzene < chlorobenzene≈bromobenzene, that of four phenols orders in 4-iodophenol≈4-bromophenol < 4-chlorophenol (4-MCP) < 4-fluorophenol (4-MFP), and that of four diphenyl ethers orders in 4,4'-iododiphenyl ether < 4,4'-difluorodiphenyl ether < 4,4'-dichlorodiphenyl ether≈4,4'-dibromodiphenyl ether. General behavior adverse effects were observed, and poisoned mouse were dissected to observe visceral lesions. FB, 4-MCP, and 4-MFP produced toxic faster than other halogenated benzenes and phenols, as they had lower octanol-water partition coefficients. Pathological changes in liver and liver/kidney weight changes were also observed. Hepatic superoxide dismutase, catalase activities, and malondialdehyde level were tested after a 28-day exposure, which reflects a toxicity order basically consistent with that reflected by the LD50s. By theoretical calculation and building models, the toxicity of benzene, phenol, and diphenyl ether were influenced by different structural properties.

H-ferritin is the major source of iron for oligodendrocytes.

There is a critical relationship between oligodendrocyte development, myelin production, and iron bioavailability. Iron deficiency leads to hypomyelination both in humans and animal models, and the neurological sequelae of hypomyelination are significant. Therefore, understanding molecular mechanisms of iron import into oligodendrocytes is necessary for devising effective strategies for iron supplementation. Although transferrin has been considered as an essential component of oligodendrocyte media in culture, oligodendrocytes in vivo lack transferrin receptors. We have established that receptors for H-ferritin (HF) exist on cells of oligodendroglial lineage and that uptake of extracellular HF by oligodendrocyte progenitors is via receptor mediated endocytosis. These data strongly argue that ferritin is a major source of iron for oligodendrocytes. In this study, we demonstrate that media deficient in transferrin results in loss of viability of oligodendrocyte progenitors in culture. Cell loss could be prevented by supplementing the media with HF. Moreover, the addition of extracellular HF stimulates development of oligodendrocyte progenitor cells (OPCs) by increasing expression of myelin basic protein (MBP) and olig2 proteins without increasing their proliferation. The effect of HF on the OPCs could be mimicked by addition of membrane permeable 3,5,5-trimethylhexanoyl ferrocene (TMH-Fe) as an iron source to the media, but not membrane-impermeable ferric ammonium citrate. Overall, therefore, our results demonstrate the importance of iron for OPCs viability and differentiation and identify extracellular HF as a critical source of iron for oligodendrocytes. Given that ferritin receptors, but not transferrin receptors can be demonstrated on oligodendrocytes in vivo, the delivery of iron to oligodendrocytes via ferritin may be the more biological relevant delivery system.

The mechanism of vanadium-mediated developmental hypomyelination is related to destruction of oligodendrocyte progenitors through a relationship with ferritin and iron.

The second post-natal week in rat is the period of the most intense oligodendrocyte development and myelination. This period coincides with peak iron import by oligodendrocytes. During that time oligodendrocyte progenitors (OPCs) are sensitive to agents that may disturb normal iron homeostasis and assimilation of iron into these cells. One mechanism by which iron homeostasis can be disrupted is by environmental exposure to other metals. Vanadium is a transition metal, and exposure to vanadium during early brain development produces hypomyelination with variety of related neuro-behavioral phenotypes. In the current study, we investigated mechanisms of hypomyelination induced by vanadium exposure in developing rat brain. We demonstrate that both in vivo and in vitro, OPCs are more sensitive to vanadium exposure than astrocytes or mature oligodendrocytes. Vanadium exposure in OPCs resulted in increased ROS generation and increased annexinV labeling suggestive of apoptosis. Because ferritin is a major iron delivery protein for oligodendrocytes, we exposed the cells to recombinant ferritin and iron both of which exacerbated vanadium cytotoxicity, while the iron chelator desferroxamine (DFO) prevented cytotoxic/apoptotic effects of vanadium. To illustrate relationship between ferritin and vanadium, we demonstrate that vanadium exacerbated DNA nicking produced by iron-rich spleen ferritin, but not iron-poor apoferritin, resulting in a single and double strand breaks in a DNA relaxation assay. We propose that developmental exposure to vanadium interferes with normal iron assimilation into oligodendrocytes resulting in oxidative stress and apoptosis. Therefore, depletion of OPCs due to vanadium exposure in early post-natal period may be an important mechanism of vanadium-induced hypomyelination.

Cytokine toxicity to oligodendrocyte precursors is mediated by iron.

Inflammatory processes play a key role in the pathogenesis of a number of common neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Abnormal iron accumulation is frequently noted in these diseases and compelling evidence exists that iron is involved in inflammatory reactions. Histochemical stains for iron repeatedly demonstrate that oligodendrocytes, under normal conditions, stain more prominently than any other cell type in the brain. Therefore, we examined the hypothesis that cytokine toxicity to oligodendrocytes is iron mediated. Oligodendrocytes in culture were exposed to interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). Toxicity was observed in a dose-dependent manner for IFN-gamma and TNF-alpha. IL-1beta was not toxic in the concentrations used in this study. The toxic concentration of IFN-gamma, and TNF-alpha was lower if the cells were iron loaded, but iron loading had no effect on the toxicity of IL-1beta. These data provide insight into the controversy regarding the toxicity of cytokines to oligodendrocytes by revealing that iron status of these cells will significantly impact the outcome of cytokine treatment. The exposure of oligodendrocytes to cytokines plus iron decreased mitochondrial membrane potential but activation of caspase 3 is limited. The antioxidant, TPPB, which targets mitochondria, protected the oligodendrocytes from the iron-mediated cytotoxicity, providing further support that mitochondrial dysfunction may underlie the iron-mediated cytokine toxicity. Therapeutic strategies involving anti-inflammatory agents have met with limited success in the treatment of demyelinating disorders. A better understanding of these agents and the contribution of cellular iron status to cytokine toxicity may help develop a more consistent intervention strategy.