Evaluation of physician performance using a concurrent-read artificial intelligence system to support breast ultrasound interpretation.

PURPOSE: The purpose of this study was to compare the diagnostic performance and the interpretation time of breast ultrasound examination between reading without and with the artificial intelligence (AI) system as a concurrent reading aid. MATERIAL AND METHODS: A fully crossed multi-reader and multi-case (MRMC) reader study was conducted. Sixteen participating physicians were recruited and retrospectively interpreted 172 breast ultrasound cases in two reading scenarios, once without and once with the AI system (BU-CAD™, TaiHao Medical Inc.) assistance for concurrent reading. Interpretations of any given case set with and without the AI system were separated by at least 5 weeks. These reading results were compared to the reference standard and the area under the LROC curve (AUCLROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for performance evaluations. The interpretation time was also compared between the unaided and aided scenarios. RESULTS: With the help of the AI system, the readers had higher diagnostic performance with an increase in the average AUCLROC from 0.7582 to 0.8294 with statistically significant. The sensitivity, specificity, PPV, and NPV were also improved from 95.77%, 24.07%, 44.18%, and 93.50%-98.17%, 30.67%, 46.91%, and 96.10%, respectively. Of these, the improvement in specificity reached statistical significance. The average interpretation time was significantly reduced by approximately 40% when the readers were assisted by the AI system. CONCLUSION: The concurrent-read AI system improves the diagnostic performance in detecting and diagnosing breast lesions on breast ultrasound images. In addition, the interpretation time is effectively reduced for the interpreting physicians.

Interference with orco gene expression affects host recognition in Diorhabda tarsalis.

Introduction: Diorhabda tarsalis Weise is an important insect pest of the Chinese licorice Glycyrrhiza uralensis Fisch. Behavior of the beetle, including host location, oviposition site selection, self-defense, and aggregation, were regulated by plant volatiles or insect pheromones. Aim: In this study, Identification of ORs and function research on orco were carried out, these could lead to the development of understand for olfaction mechanism in D. tarsalis. Methods: ORs were identified by PacBio RS II platform to sequence the antennas of adult D. tarsalis, the function of orco was explored by dsRNA interference. Results: 29 odorant receptor candidate genes of D. tarsalis were obtained, which code for 130-479 amino acids. Phylogenetic trees of olfactory receptors were constructed with 243 ORs from eight Coleoptera species. DtarORco, DtarOR7 and DtarOR26 are specifically expressed in the antenna, and the expression levels were significantly higher than other DtarORs in antenna, there were no differential expression between male and female beetles. An odorant coreceptor gene (DtarORco) has characteristics of an odorant receptor family member, the encoded mature protein has a predicted molecular weight of 53.898 kDa, dsRNA L4440 expression vectors were constructed and successfully transformed into ribonuclease III-deficient Escherichia coli strain HT115 DE3. After interference treatment, the relative expression level of DtarORco in D. tarsalis antennae significantly decreased and electrophysiological responses to host localization odor signals significantly decreased. At the same time, beetles lost the ability to locate hosts. Discussion: The research on its mechanism of olfaction may lead to the development of new control measures that are environmentally friendly.

Evaluation of TP53/PIK3CA mutations using texture and morphology analysis on breast MRI.

PURPOSE: Somatic mutations in TP53 and PIK3CA genes, the two most frequent genetic alternations in breast cancer, are associated with prognosis and therapeutic response. This study predicted the presence of TP53 and PIK3CA mutations in breast cancer by using texture and morphology analyses on breast MRI. MATERIALS AND METHODS: A total of 107 breast cancers (dataset A) from The Cancer Imaging Archive (TCIA) consisting of 40 TP53 mutation cancer and 67 cancers without TP53 mutation; 35 PIK3CA mutations cancer and 72 without PIK3CA mutation. 122 breast cancer (dataset B) from Seoul National University Hospital containing 54 TP53 mutation cancer and 68 without mutations were used in this study. At first, the tumor area was segmented by a region growing method. Subsequently, gray level co-occurrence matrix (GLCM) texture features were extracted after ranklet transform, and a series of features including compactness, margin, and ellipsoid fitting model were used to describe the morphological characteristics of tumors. Lastly, a logistic regression was used to identify the presence of TP53 and PIK3CA mutations. The classification performances were evaluated by accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Taking into account the trade-offs of sensitivity and specificity, the overall performances were evaluated by using receiver operating characteristic (ROC) curve analysis. RESULTS: The GLCM texture feature based on ranklet transform is more capable of recognizing TP53 and PIK3CA mutations than morphological feature, especially for the TP53 mutation that achieves statistically significant. The area under the ROC curve (AUC) for TP53 mutation dataset A and dataset B achieved 0.78 and 0.81 respectively. For PIK3CA mutation, the AUC of ranklet texture feature was 0.70. CONCLUSION: Texture analysis of segmented tumor on breast MRI based on ranklet transform is potential in recognizing the presence of TP53 mutation and PIK3CA mutation.

Computer-aided diagnosis of liver tumors on computed tomography images.

BACKGROUND AND OBJECTIVE: Liver cancer is the tenth most common cancer in the USA, and its incidence has been increasing for several decades. Early detection, diagnosis, and treatment of the disease are very important. Computed tomography (CT) is one of the most common and robust imaging techniques for the detection of liver cancer. CT scanners can provide multiple-phase sequential scans of the whole liver. In this study, we proposed a computer-aided diagnosis (CAD) system to diagnose liver cancer using the features of tumors obtained from multiphase CT images. METHODS: A total of 71 histologically-proven liver tumors including 49 benign and 22 malignant lesions were evaluated with the proposed CAD system to evaluate its performance. Tumors were identified by the user and then segmented using a region growing algorithm. After tumor segmentation, three kinds of features were obtained for each tumor, including texture, shape, and kinetic curve. The texture was quantified using 3 dimensional (3-D) texture data of the tumor based on the grey level co-occurrence matrix (GLCM). Compactness, margin, and an elliptic model were used to describe the 3-D shape of the tumor. The kinetic curve was established from each phase of tumor and represented as variations in density between each phase. Backward elimination was used to select the best combination of features, and binary logistic regression analysis was used to classify the tumors with leave-one-out cross validation. RESULTS: The accuracy and sensitivity for the texture were 71.82% and 68.18%, respectively, which were better than for the shape and kinetic curve under closed specificity. Combining all of the features achieved the highest accuracy (58/71, 81.69%), sensitivity (18/22, 81.82%), and specificity (40/49, 81.63%). The Az value of combining all features was 0.8713. CONCLUSIONS: Combining texture, shape, and kinetic curve features may be able to differentiate benign from malignant tumors in the liver using our proposed CAD system.

The Effect of Atorvastatin on the Viability of Ischemic Skin Flaps in Diabetic Rats.

BACKGROUND: Endothelial progenitor cells play a critical role in neovascularization. However, the mobilization, recruitment, and functional capacity of endothelial progenitor cells are significantly impaired in diabetes. Statins have been shown to augment the number and improve the function of endothelial progenitor cells. This study investigated the effects of statins on the viability of ischemic skin flaps in diabetic rats. METHODS: Twenty normal and 40 diabetic Sprague-Dawley rats were included in this study. Atorvastatin (10 mg/kg/day) was administered orally in 20 diabetic rats at 2 weeks before flap surgery for 21 consecutive days. Other rats received equal vehicle. Two weeks after first gavage, a 3 × 10-cm skin flap was established on the backs of rats. The necrotic area of each skin flap was measured at 7 days postoperatively. Capillary density and endothelial progenitor cells recruited to the flaps were analyzed using immunofluorescence staining. Circulating endothelial progenitor cell number was determined by flow cytometry. In vitro migration and tube formation experiments were used to analyze the function of endothelial progenitor cells. RESULTS: Atorvastatin treatment increased flap survival rate and capillary density. In addition, more endothelial progenitor cells were identified in peripheral blood and skin flaps in diabetic rats receiving atorvastatin. Atorvastatin treatment also restored the impaired function of diabetic endothelial progenitor cells in migration and tube formation. CONCLUSION: Atorvastatin notably promoted neovascularization and enhanced the viability of ischemic skin flaps in diabetic rats, which may be mediated at least partially by augmenting the number and restoring the functional capacity of endothelial progenitor cells.

Quantification of breast tumor heterogeneity for ER status, HER2 status, and TN molecular subtype evaluation on DCE-MRI.

PURPOSE: Recognizing molecular markers is helpful for guiding treatment plans for breast cancer. This study correlated estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and triple-negative breast cancer (TNBC) statuses to the degree of heterogeneity on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: A total of 102 biopsy-proven cancers from 102 patients between October 2010 and December 2012 were used in this study, including ER (59 positive, 43 negative), HER2 (47 positive, 55 negative), and TNBC (22 TNBC, 80 non-TNBC). At first, the tumor region was segmented by using a region growing method. Then, the region-based features were extracted by the proposed regionalization method to quantify intra-tumoral heterogeneity on breast DCE-MRI. The three-dimensional morphological features (texture features and shape feature) and the pharmacokinetic model were also extracted from the segmented tumor region. After feature extraction, a logistic regression was used to classify ER, HER2, and TNBC statuses respectively. The performances were evaluated by using receiver operating characteristic (ROC) curve analysis. RESULTS: The proposed region-based features achieved the accuracy of 73.53%, 82.35%, and 77.45% for ER, HER2, and TNBC classifications. The corresponding area under the ROC curves (Az) achieves 0.7320, 0.8458, and 0.8328 that were better than those of texture features, shape features, and Tofts pharmacokinetic model. CONCLUSION: The intra-tumoral heterogeneity quantified by the region-based features can be used to reflect the vasculature complexity of different molecular markers and to provide prediction information of cell surface receptors on clinical examination.

Volatiles released by Chinese liquorice roots mediate host location behaviour by neonate Porphyrophora sophorae (Hemiptera: Margarodidae).

BACKGROUND: The cochineal scale, Porphyrophora sophorae (Hemiptera: Coccoidea, Margarodidae), is one of the most serious arthropod pests of Chinese liquorice, Glycyrrhiza uralensis (Fabaceae), an important medicinal herb. The adult females tend to deposit the ovisacs in soil relatively far away from liquorice plants. After hatching, neonates move out of the soil and may use chemical cues to search for new hosts. RESULTS: We collected and analysed the volatiles from soils with and without liquorice roots, and chromatographic profiles revealed hexanal, ß-pinene and hexanol as potential host-finding cues for P. sphorae. The attractiveness of these compounds to neonates was studied in the laboratory using four-arm olfactometer bioassays. The larvae showed a clear preference for ß-pinene over hexanal and hexanol, as well as all possible combinations of the three compounds. In addition, a field experiment confirmed that ß-pinene was significantly more attractive than hexanal and hexanol. CONCLUSION: Newly eclosed larvae of P. sphorae exploit root volatiles as chemical cues to locate their host plant. ß-Pinene proved to be the major chemical cue used by P. sphorae neonates searching for roots of their host plant. © 2016 Society of Chemical Industry.

Stimulation of Nitric Oxide Production Contributes to the Antithrombotic Effect of Stromal Cell-Derived Factor-1α in Preventing Microsurgical Anastomotic Thrombosis.

Background Intimal injury plays a critical role in initiating the pathogenesis of thrombosis formation after microsurgical anastomosis. Application of stromal cell-derived factor-1α (SDF-1α) is reported to promote early regeneration of injured intima through migration of endothelial cells and mobilization of endothelial progenitor cells. We therefore hypothesized that local transfer of SDF-1α gene would inhibit microsurgical anastomotic thrombosis. Methods Sixty Sprague-Dawley rats were used and divided randomly into three groups (SDF-1α group, plasmid group, and saline group) in this study. Plasmid DNA encoding SDF-1α, empty plasmid, and saline were injected into the left femoral muscles of rats from each group, respectively. Seven days after injection, peripheral blood samples were obtained to measure the plasma levels of SDF-1α and nitric oxide (NO). The left femoral artery of each rat was crushed, transected, and repaired by end-to-end microsurgical anastomosis. Vascular patency was assessed at 15, 30, and 120 minutes after reperfusion using milk test. Thrombosis formation was assessed with hematoxylin and eosin staining and scanning electron microscopy at 120 minutes postoperatively. Results The plasma levels of SDF-1α and NO in SDF-1α group were significantly higher than those in plasmid group and saline group (p < 0.01). The patency rate in SDF-1α group was significantly higher than that in control groups at 120 minutes after reperfusion (p < 0.05). Treatment of SDF-1α significantly reduced the size of thrombotic occlusion when compared with controls (p < 0.05). All SDF-1α recipients exhibited decreased thrombosis under scanning electron microscopy. Conclusions The current study demonstrated that local transfer of SDF-1α gene increases arterial patency and inhibits microsurgical anastomotic thrombosis in a crush model of femoral artery in rat. The antithrombotic effect of SDF-1α may be mediated through increased production of endogenous NO. These findings provide a novel approach for inhibition of microsurgical anastomotic thrombosis.

[Mechanism of genuineness of Glycyrrhiza uralensis based on SNP of ß-Amyrin synthase gene].

ß-Amyrin synthase (ß-AS) genes of Glycyrrhiza uralensis from 6 different regions were analyzed by PCR-SSCP and sequenced, then the correlationship between ß-AS SNP and regions of Glycyrrhiza uralensis were determined. According to the 1 coding single nucleotide polymorphism on the first exon of ß-AS gene at 94 bp site, Glycyrrhiza uralensis could be divided into 3 genotypes. In these genotypes, the percentage of 94A type in genuine regions was much higher, and it had significant differences with the percentage in non-genuine regions (P < 0.001). The results of the experiment proved that different ß-AS genotypes at 94 bp site from different regions may be one of the important reasons to result in the genuineness of Glycyrrhiza uralensis.

Combined Anterolateral Thigh and Anteromedial Thigh Flap for Extensive Extremity Reconstruction: Vascular Anatomy and Clinical Application.

BACKGROUND: The combined anterolateral thigh (ALT) and anteromedial thigh (AMT) flap has been previously reported for use in complicated head and neck reconstruction. However, it has not gained popularity due to the vascular variation. Here, we explore the vascular basis of this combined flap, and report its application in extremity reconstruction. METHODS: This study was divided into two parts: vascular anatomy and clinical application. In the anatomical study, 52 sides of adult thighs were dissected to identity vascular perforators supplying the combined ALT and AMT flap, with focus on sizeable perforators (larger than 0.5 mm) arising from the descending branch of the lateral circumflex femoral artery.Clinically, five male patients were treated by combined ALT and AMT flaps for extensive extremity reconstruction from January 2006 to December 2010. The mean age was 32 years (range, 23-45 years). The combined flap was used for covering large soft-tissue defects in forearm (n = 3) and calf (n = 2). For each patient, esthetic and functional results were recorded. RESULTS: The anatomical study showed that sizeable perforators supplying the ALT flap were present in 50 thighs (96.2%), and the perforators supplying the AMT flap were present in 32 thighs (61.5%). The combined ALT and AMT flaps were available in 30 thighs (57.7%).All five combined flaps survived completely. Skin grafts covering the donor sites healed uneventful. The mean follow-up was 9.6 months (range, 6-12 months). No complications were recorded during the follow-up. CONCLUSION: The combined ALT and AMT flap may be used for extensive extremity reconstruction in selected patients for its great maneuverability and acceptable donor-site morbidity.

Evaluation of the treatment response to neoadjuvant chemotherapy in locally advanced breast cancer using combined magnetic resonance vascular maps and apparent diffusion coefficient.

PURPOSE: To evaluate the treatment response of locally advanced breast cancer (LABC) to neoadjuvant chemotherapy using magnetic resonance (MR) vascular maps and apparent diffusion coefficient (ADC) at 3T. Materials and Methods Thirty-one patients with LABC who underwent breast MR studies before, after the first course, and after completing neoadjuvant chemotherapy were enrolled. Vascular morphology was retrieved via Hessian matrix and the voxels of the vessels and volume of vessels were measured automatically. Whole tumor mean ADC values were calculated. Clinical responders were defined as >50% tumor reduction in the final MR studies. Pathologically complete responders were also recorded. RESULTS: There were 21 clinical responders and 10 nonresponders. Compared to the nonresponders after the first course, the responders were characterized by more vascular reduction of the breast lesion and decreased bilateral vascular discrepancy (voxels and volume), and increments in the ADC value and ADC percentage of the lesions (all P < 0.05). There were three pathological complete responders who showed more apparent early vascular reduction of the lesion breast (voxels and volume) and increments in the ADC value than others (P = 0.02, 0.01 and 0.02, respectively). CONCLUSION: The early changes of MR vascular maps and ADC are associated with the final treatment response of LABC.

Enhancing the accumulation of beta-amyrin in Saccharomyces cerevisiae by co-expression of Glycyrrhiza uralensis squalene synthase 1 and beta-amyrin synthase genes.

Glycyrrhiza uralensis Fisch. ex DC is widely used in traditional Chinese medicine (TCM). Among its various active components, glycyrrhizic acid is believed to be the marker component. Squalene synthase (SQS) and beta-amyrin synthase (beta-AS) are key enzymes in the biosynthetic pathway of glycyrrhizic acid in G uralensis. To reveal the effects of co-expression of SQS1 and beta-AS genes on this pathway, 7 yeast expression vectors harboring different SQS1 variants and beta-AS were constructed and expressed in Saccharomyces cerevisiae as fusion proteins. TLC and GC-MS results showed that co-expression of SQS1 and beta-AS enhanced the accumulation of beta-amyrin. The effects of SQS12 were more obvious than the other two SQS1 variants. This study is significant for further investigations concerned with exploring the biosynthesis of glycyrrhizic acid in vitro and strengthening the efficacy of G. uralensis by means of increasing the content of glycyrrhizic acid.

Cloning and characterization of a cDNA coding 3-hydroxy-3-methylglutary CoA reductase involved in glycyrrhizic acid biosynthesis in Glycyrrhiza uralensis.

The roots of Glycyrrhiza uralensis are widely used in Chinese medicine for their action of clearing heat, detoxicating, relieving cough, dispelling sputum and tonifying spleen and stomach. The reason why Glycyrrhiza uralensis has potent and significant actions is that it contains various active secondary metabolites, especially glycyrrhizic acid. In the present study, we cloned the cDNA coding 3-hydroxy-3-methylglutary CoA reductase (HMGR) involved in glycyrrhizic acid biosynthesis in Glycyrrhiza uralensis. The corresponding cDNA was expressed in Escherichia coli as fusion proteins. Recombinant HMGR exhibited catalysis activity in reduction of HMG-CoA to mevalonic acid (MVA) just as HMGR isolated from other species. Because HMGR gene is very important in the biosynthesis of glycyrrhizic acid in Glycyrrhiza uralensis, this work is significant for further studies concerned with strengthening the efficacy of Glycyrrhiza uralensis by means of increasing glycyrrhizic acid content and exploring the biosynthesis of glycyrrhizic acid in vitro.

[Researches on influence of squalene synthase gene polymorphism on catalytic efficiency of its encode enzyme in Glycyrrhiza uralensis].

OBJECTIVE: To analyse the polymorphism of squalene synthase gene and reveal the influence of squalene synthase (SQS) gene polymorphism on the catalytic efficiency of its encode enzyme in Glycyrrhiza uralensi. METHOD: The total RNA was extracted. PCR was used to amplify the coding sequences of squalene synthase gene, which were sequenced and analysed. The expression vectors containing different SQS gene sequences, including SQS1C, SQS1F, SQS2A, SQS2B, were constructed and transformed into Escherichia coli BL21. The fusion protein was induced to express by IPTG, then was isolated, purified and used to carry out the enzymatic reaction in vitro. GC-MS was used to analyse the production. RESULT: There were three kinds of gene polymorphism existing in SQS1 gene of G. uralensis, including single nucleotide polymorphism (SNPs), insertion/deletion length polymorphism (InDels) and level of amino acid, the proportion of conservative replace of SQS1 was 53.94%, and there were 2 mutational sites in structural domains. The proportion of conservative replace of SQS2 was 60%, and there was 1 mutational site in structural domains. The production squalene could be detected by GC-MS in all the 4 kinds of enzymatic reactions. The capacity of accumulating squalene of SQS1F was higher than other SQS genes. CONCLUSION: The polymorphism of SQS gene was quite abundant in G. uralensis, which maybe the molecular foundation of the formation of high-quality liquorice.

[Researches on the influence of 3-hydroxy-3-methylglutary-coenzyme A reductase gene polymorphism on catalytic efficiency of its encode enzyme in Glycyrrhiza uralensis].

OBJECTIVE: To analyse the effect of expression proteins containing different escherichia coli of 3-hydroxy-3-methylglutary-coenzyme A reductase(HMGR) genic mutation on the conversion efficiency of MVA with GC-MS method, in order to lay a foundation for revealing the function of HMGR gene polymorphism of Glycyrrhiza uralensis in the production of high-quality G. uralensis medicines. METHOD: The expression carrier was established from four HMGR genic mutation types cloned from G. uralensis and transformed into Escherichia coli BL21. The protein was induced to express, detected and purified. The purified protein was adopted for in vitro enzymatic reaction. TLC and GC-MS were used for qualitative and quantitative analysis on reaction products. RESULT: The catalytic activity of L/V genotype(-HSL and -HSV) was similar, and so was the catalytic activity of the genotype with GA insertion (GALLV and GALSV), but the catalytic activity of the latter was around 2 times higher than that of the former. CONCLUSION: The functional gene polymorphism of G. uralensis may be the molecular foundation for the production of high-quality G. uralensi medicines.

[Analysis on correlation between 3-hydroxy-3-methylglutary-coenzyme A reductase gene polymorphism of Glycyrrhiza uralensis and content of glycyrrhizic acid].

OBJECTIVE: To reveal the 3-hydroxy-3-methylglutary-coenzyme A reductase (HMGR) gene polymorphism of Glycyrrhiza uralensis, and the correlation between HMGR gene polymorphism and the content of glycyrrhizic acid. METHOD: Liquorice plants containing different content of glycyrrhizic acid were used as materials. RT-PCR was used to amplify their HMGR gene sequences, which were connected with vector pMD19-T for clone sequencing. Multiple alignments were performed to analyse HMGR gene polymorphism of G. uralensis. Then the correlation between HMGR gene polymorphism and the content of glycyrrhizic acid was revealed. RESULT: HMGR gene sequences polymorphism included codon mutation, base substitution mutation, copy number polymorphism and allele heterozygosity. There were 4 types of mutations in HMGR gene coding amino acid sequences, namely -HSL, -HSV, GALLV, GALSV. Among them, -HSV type was common in liquorice plants, -HSL type only existed in liquorice plants with low content of glycyrrhizic acid, and GALSV type only existed in liquorice plants with high content of glycyrrhizic acid. CONCLUSION: HMGR gene sequences of G. uralensis are highly polymorphic and related to the content of glycyrrhizic acid.

[Spatial structure and distribution simulation of Aphis gossipii Glover population based on GIS].

Based on geographic information system (GIS) and geostatistical analysis, this paper studied the spatial structure of Aphis gossipii Glover population in Xiangshan District of Zhongwei City, Ningxia Province, with the spatial distribution of the population simulated by ordinary Kriging interpretation. The spatial structure of A. gossipii population varied with its occurrence stage (initial, blossom, and final stage). The semivariograms of A. gossipii could be described by exponential or Gaussian model, indicating that A. gossipii had an aggregated spatial arrangement. The aggregation degrees at different occurrence stages were all beyond 45%, and the spatial correlation ranged from 10.37 km to 29.11 km. The spatial variance was greatly affected by spatial autocorrelation. The population dynamics of A. gossipii at its different occurrence stages could be easily analyzed and intuitively simulated from the two aspects of time and space by spatial distribution simulation, and thus, the occurrence position and degree of A. gossipii could be easily determined.