[Association between abnormal oral glucose tolerance test patterns in the second trimester and large for gestational age newborns].

Objective: To investigate the impact of abnormal patterns of 75 g oral glucose tolerance test (OGTT) in the second trimester on the risk of large for gestational age (LGA) newborn deliveries. Methods: General clinical data and OGTT results of 66 290 pregnant women who received regular prenatal care and delivered in Guangdong Maternal and Child Health Hospital from December 24, 2016 to July 26, 2022 were collected. According to the results of OGTT, the pregnant women were divided into 8 groups: normal blood glucose group (normal fasting blood glucose, 1-hour and 2-hour after oral glucose, 54 518 cases), gestational diabetes mellitus (GDM) 0 group (only abnormal fasting blood glucose, 1 430 cases), GDM 1 group (only abnormal blood glucose at 1-hour after oral glucose, 2 150 cases), GDM 2 group (only abnormal blood glucose at 2-hour after oral glucose, 3 736 cases), GDM 0+1 group (both fasting blood glucose and 1-hour after oral glucose were abnormal, 371 cases), GDM 0+2 group (both fasting blood glucose and 2-hour after oral glucose were abnormal, 280 cases), GDM 1+2 group (abnormal blood glucose at 1-hour and 2-hour after oral glucose, 2 981 cases) and GDM 0+1+2 group (abnormal fasting blood glucose, 1-hour and 2-hour after oral glucose, 824 cases). Multivariate logistic regression was used to analyze the effects of different abnormal OGTT patterns on LGA. In addition, the blood glucose measurements at the three time points of OGTT were combined and used as continuous variables in the receiver operating characteristic (ROC) curve to evaluate the predictive value of each blood glucose measurement mode for LGA and the area under the curve (AUC) was compared. Results: (1) Multivariate logistic regression analysis showed that the risks of LGA were significantly increased in GDM 0 group (OR=1.76, 95%CI: 1.50-2.08; P<0.001), GDM 0+1 group (OR=2.29, 95%CI: 1.72-3.04; P<0.001), and GDM 0+1+2 group (OR=1.98, 95%CI: 1.61-2.43; P<0.001). (2) ROC curve analysis showed that fasting blood glucose, 1-hour after oral glucose, 2-hour after oral glucose, fasting+1-hour after oral glucose, fasting+2-hour after oral glucose, 1-hour+2-hour after oral glucose, and fasting+1-hour+2-hour after oral glucose had certain predictive value for LGA (all P<0.001). The AUC of fasting blood glucose measurement was higher than that of 2-hour blood glucose measurement in predicting LGA, and the difference was statistically significant (P<0.05). There was no significant difference in the AUC between fasting blood glucose and other blood glucose measurement modes for predicting LGA (all P>0.05). Conclusions: In the abnormal OGTT patterns, pregnant women with abnormal fasting blood glucose, abnormal fasting+1-hour after oral glucose, and abnormal fasting+1-hour+2-hour after oral glucose have an increased risk of LGA. Fasting blood glucose measurement is of great significance for the prediction of LGA, and could be used as an optimal indicator to evaluate the risk of LGA in clinical practice.

[Decolorization of skin and hair-derived melanin by three ligninolytic enzymes].

Objective: To compare the decolorization efficiency of lignin peroxidase (LiP), manganese peroxidase (MnP) and laccase on eumelanin and pheomelanin, and to investigate the effect of topical administration of LiP solution on hyperpigmented guinea pigs skin induced by 308 nm excimer light. Methods: Pheomelanin-enriched specimens were prepared from human hair and cutaneous melanoma tissue using alkaline lysis method.Synthetic eumelanin was purchased from a commercial supplier.The same amount (0.02%) of melanin was incubated with the equal enzyme activity (0.2 U/ml) of ligninolytic enzymes for 3 h respectively.The absorbance at 475 nm (A(475)) in the enzyme-catalyzed solution was measured using ELISA microplate reader.The experimental hyperpigmentation model was established in the dorsal skin of brownish guinea pigs using 308 nm excimer light radiation.LiP and heat-inactivated LiP solution were topically applied at each site.Meanwhile, 3% hydroquinone and vehicle cream were used as control.The skin color (L value) was recorded using a CR-10 Minolta chromameter.Corneocytes were collected using adhesive taping method.The amount and distribution of melanin in the corneocytes and skin tissues was visualized by Fontana-Masson staining. Results: All three ligninolytic enzymes showed various degree of eumelanin and pheomelanin decolorization activity.The decolorization activity of LiP, MnP and laccase was 40%-70%, 22%-42% and 9%-21%, respectively.The similar lightening was shown in the skin treated with LiP solution and 3% hydroquinone.The amount of melanin granules in the corneocytes was 199±11 by LiP, which was less than that in untreated control (923±12) and heat-inactive control (989±13). The amount of melanin was decreased in the whole epidermis treated with hydroquinone, the epidermis thickness was increased as well. In contrast, melanin of LiP group was decreased only in the superficial epidermis, the epidermis thickness seemed to be normal. Conclusion: LiP exerts a potent decolorization activity for hair- or skin-derived pheomelanin as well as eumelanin.It remains to be further investigated whether LiP serves as a substitute for hydroquinone in skin lightening products.

The clinical characteristics and manifestations of cytomegalovirus esophagitis.

Esophagitis is the second most common gastrointestinal manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone transplantation, are on long-term renal dialysis, or who have the human immunodeficiency virus infection. This study aimed to investigate the clinical characteristics and manifestations of CMV esophagitis in patients who underwent diagnostic endoscopy. A total of 16 patients with histologically proven CMV infection were identified from 1539 patients with esophageal ulcers and analyzed retrospectively (January 2006 to December 2013). Patients' personal data (age, smoking, and alcohol consumption), underlying systemic diseases (diabetes mellitus, end-stage renal disease, and chronic obstructive pulmonary disease), malignancy, indication for esophagogastroduodenoscopy, endoscopic characteristics, and diagnostic methods (pathological or serological findings) were collected for further analysis. Among the patients with CMV esophagitis, the mean age was 59.94 years (range, 23-84 years). The male : female ratio was 1.67:1. Odynophagia and epigastralgia were common symptoms. Of the 16 patients, 3 (18.75%) were infected with the human immunodeficiency virus and 9 (56.25%) had an underlying malignancy, including lung cancer (6 patients), esophageal cancer (2 patients), gastric cancer (1 patient), ampulla of Vater cancer (1 patient), and lymphoma (1 patient). Six of the 9 patients (66.7%) with malignancy had been administered concurrent chemoradiotherapy (CCRT). In this study, patients with malignancy who had been administered CCRT were at increased risk for CMV esophagitis, which had not been reported before in the literature. CMV esophagitis should be considered as a potential treatment-related complication of CCRT.

Correlation of endogenous hormonal levels, fibroglandular tissue volume and percent density measured using 3D MRI during one menstrual cycle.

BACKGROUND: We measured breast density (BD) on MRI and correlated with endogenous hormonal levels. PATIENTS AND METHODS: Twenty-four premenopausal women received four weekly breast MRI. A blood sample was collected on the same day of MRI. BD was measured using a computer-based algorithm. The generalized estimation equation method was applied to model mean fibroglandular tissue volume (FV) and mean percent density (PD) from predictor variables including estradiol, progesterone, and week during a cycle. RESULTS: In week 3, a borderline significant correlation between estradiol and PD (r = 0.43, P = 0.04), estradiol and FV (r = 0.40, P = 0.05) and between progesterone and FV (r = 0.42, P = 0.04) was noted. The FV and PD measured in weeks 4 and 1 were higher than in weeks 2 and 3, adjusted for variation in endogenous estradiol and progesterone, indicating that the hormone change could not account for the changes in density. No lag effect of endogenous hormone on the change of FV or PD was noted (all P-values > 0.05). CONCLUSIONS: Our results showed that BD is not strongly associated with the endogenous hormone. Their association with breast cancer risk was likely coming from different mechanisms, and they should be considered as independent risk factors.

Clinical characteristics and biomarkers of breast cancer associated with choline concentration measured by 1H MRS.

This study investigated the association between the total choline (tCho) concentration and the clinical characteristics and biomarker status of breast cancer. Sixty-two patients with breast cancer, 1.5 cm or larger in size on MR images, were studied. The tCho concentration was correlated with the MRI features, contrast enhancement kinetics, clinical variables and biomarkers. Pairwise two-tailed Spearman's nonparametric test was used for statistical analysis. The tCho concentration was higher in high-grade than moderate-/low-grade tumors (p = 0.04) and in tumors with higher K(trans) and k(ep) (p < 0.001 for both). The association of tCho concentration with age (p = 0.05) and triple negative biomarker (p = 0.09) approached significance. tCho was not detected in 17 patients, including 15 with invasive ductal cancer and two with infiltrating lobular cancer. Fifteen of the 17 patients had moderate- to low-grade cancers, and 11 had human epidermal growth factor-2-negative cancer, suggesting that these two factors might lead to false-negative choline. Higher tCho concentration in high-grade tumors and tumors with higher K(trans) and k(ep) indicates that choline is associated with cell proliferation and tumor angiogenesis. The higher choline level in younger women may be caused by their more aggressive tumor type. The results presented here may aid in the better interpretation of (1)H MRS for the diagnosis of breast lesions.

Endoscopic management of suspected esophageal foreign body in adults.

Foreign bodies should not be allowed to remain in the esophagus beyond 24 hours after presentation. However, some patients with esophageal foreign body ingestion do not come to the hospital immediately and may delay medical intervention from the time of ingestion. The aim of this study was to investigate the outcomes of adults with suspected esophageal foreign body ingestion according to the time of ingestion and types of foreign bodies. A total of 326 adult patients (151 men and 175 women) were analyzed, and divided into two groups according to the time period: within or beyond 24 hours from ingestion to endoscopic intervention. A total of 172 patients (52.7%) were found to have ingested foreign bodies; 73.5% were removed smoothly, 10.3% were treated by push technique and 16.0% with failed retrieval received alternative treatments. A higher proportion of patients in the beyond-24 hours group suffered from odynophagia (25.9 vs. 12.9%, P < 0.05). Negative identification of esophageal foreign bodies was more frequent in the beyond-24 hours group (67 vs. 40.2%, P < 0.05), but these patients showed higher proportions of esophageal ulcers (21.1 vs. 7.2%, P < 0.05). The beyond-24 hours group also showed a significantly higher rate of foreign bodies in the lower esophagus (40.0 vs. 15.3%, P < 0.05). Patients with esophageal food bolus impaction had significant delayed endoscopic intervention, longer therapeutic endoscopic time, higher proportions of esophageal cancer, stricture and fewer complications. Endoscopic intervention within 24 hours from the time of ingestion should be considered early in adults, because delaying intervention may produce more symptomatic esophageal ulcerations with odynophagia.

Clinical manifestation of esophageal carcinosarcoma: a Taiwan experience.

Carcinosarcoma of the esophagus is a rare neoplasm with both carcinomatous and sarcomatous components. This study aimed to investigate its clinicopathologic features and endoscopic characteristics. The data of patients diagnosed to have esophageal carcinosarcoma pathologically in the past 30 years (January 1976-December 2007) were reviewed. Of 3318 cases of esophageal malignancy, 12 were diagnosed as esophageal carcinosarcoma, with an incidence of 0.36%. All of the cases were male with a mean age of 62.3 years. Of the 12 tumors, 8 were polypoid type, and 4 were ulcerative type. In the endoscopic ultrasonography examination, the tumors show heterogeneous hypoechoic lesions with irregular outer margins and internal multicystic components. Four patients (33.3%) had previous head and neck squamous cell carcinoma that occurred metachronously. This is the first report about the characteristics of esophageal carcinosarcoma under endoscopic ultrasonography examination. The relationship between esophageal carcinosarcomas and head and neck cancer needs further investigation.

Hybrid 3D/2D Convolutional Neural Network for Hemorrhage Evaluation on Head CT.

BACKGROUND AND PURPOSE: Convolutional neural networks are a powerful technology for image recognition. This study evaluates a convolutional neural network optimized for the detection and quantification of intraparenchymal, epidural/subdural, and subarachnoid hemorrhages on noncontrast CT. MATERIALS AND METHODS: This study was performed in 2 phases. First, a training cohort of all NCCTs acquired at a single institution between January 1, 2017, and July 31, 2017, was used to develop and cross-validate a custom hybrid 3D/2D mask ROI-based convolutional neural network architecture for hemorrhage evaluation. Second, the trained network was applied prospectively to all NCCTs ordered from the emergency department between February 1, 2018, and February 28, 2018, in an automated inference pipeline. Hemorrhage-detection accuracy, area under the curve, sensitivity, specificity, positive predictive value, and negative predictive value were assessed for full and balanced datasets and were further stratified by hemorrhage type and size. Quantification was assessed by the Dice score coefficient and the Pearson correlation. RESULTS: A 10,159-examination training cohort (512,598 images; 901/8.1% hemorrhages) and an 862-examination test cohort (23,668 images; 82/12% hemorrhages) were used in this study. Accuracy, area under the curve, sensitivity, specificity, positive predictive value, and negative-predictive value for hemorrhage detection were 0.975, 0.983, 0.971, 0.975, 0.793, and 0.997 on training cohort cross-validation and 0.970, 0.981, 0.951, 0.973, 0.829, and 0.993 for the prospective test set. Dice scores for intraparenchymal hemorrhage, epidural/subdural hemorrhage, and SAH were 0.931, 0.863, and 0.772, respectively. CONCLUSIONS: A customized deep learning tool is accurate in the detection and quantification of hemorrhage on NCCT. Demonstrated high performance on prospective NCCTs ordered from the emergency department suggests the clinical viability of the proposed deep learning tool.

Deep-Learning Convolutional Neural Networks Accurately Classify Genetic Mutations in Gliomas.

BACKGROUND AND PURPOSE: The World Health Organization has recently placed new emphasis on the integration of genetic information for gliomas. While tissue sampling remains the criterion standard, noninvasive imaging techniques may provide complimentary insight into clinically relevant genetic mutations. Our aim was to train a convolutional neural network to independently predict underlying molecular genetic mutation status in gliomas with high accuracy and identify the most predictive imaging features for each mutation. MATERIALS AND METHODS: MR imaging data and molecular information were retrospectively obtained from The Cancer Imaging Archives for 259 patients with either low- or high-grade gliomas. A convolutional neural network was trained to classify isocitrate dehydrogenase 1 (IDH1) mutation status, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation status. Principal component analysis of the final convolutional neural network layer was used to extract the key imaging features critical for successful classification. RESULTS: Classification had high accuracy: IDH1 mutation status, 94%; 1p/19q codeletion, 92%; and MGMT promotor methylation status, 83%. Each genetic category was also associated with distinctive imaging features such as definition of tumor margins, T1 and FLAIR suppression, extent of edema, extent of necrosis, and textural features. CONCLUSIONS: Our results indicate that for The Cancer Imaging Archives dataset, machine-learning approaches allow classification of individual genetic mutations of both low- and high-grade gliomas. We show that relevant MR imaging features acquired from an added dimensionality-reduction technique demonstrate that neural networks are capable of learning key imaging components without prior feature selection or human-directed training.

Correction: Tensor based multichannel reconstruction for breast tumours identification from DCE-MRIs.

[This corrects the article DOI: 10.1371/journal.pone.0172111.].

Tensor based multichannel reconstruction for breast tumours identification from DCE-MRIs.

A new methodology based on tensor algebra that uses a higher order singular value decomposition to perform three-dimensional voxel reconstruction from a series of temporal images obtained using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is proposed. Principal component analysis (PCA) is used to robustly extract the spatial and temporal image features and simultaneously de-noise the datasets. Tumour segmentation on enhanced scaled (ES) images performed using a fuzzy C-means (FCM) cluster algorithm is compared with that achieved using the proposed tensorial framework. The proposed algorithm explores the correlations between spatial and temporal features in the tumours. The multi-channel reconstruction enables improved breast tumour identification through enhanced de-noising and improved intensity consistency. The reconstructed tumours have clear and continuous boundaries; furthermore the reconstruction shows better voxel clustering in tumour regions of interest. A more homogenous intensity distribution is also observed, enabling improved image contrast between tumours and background, especially in places where fatty tissue is imaged. The fidelity of reconstruction is further evaluated on the basis of five new qualitative metrics. Results confirm the superiority of the tensorial approach. The proposed reconstruction metrics should also find future applications in the assessment of other reconstruction algorithms.

Comparative analysis of human milk and infant formula derived peptides following in vitro digestion.

It has long been recognised that there are differences between human milk and infant formulas which lead to differences in health and nutrition for the neonate. In this study we examine and compare the peptide profile of human milk and an exemplar infant formula. The study identifies both similarities and differences in the endogenous and postdigestion peptide profiles of human milk and infant formula. This includes differences in the protein source of these peptides but also with the region within the protein producing the dominant proteins. Clustering of similar peptides around regions of high sequence identity and known bioactivity was also observed. Together the data may explain some of the functional differences between human milk and infant formula, while identifying some aspects of conserved function between bovine and human milks which contribute to the effectiveness of modern infant formula as a substitute for human milk.

Magnetic resonance imaging of anatomic and vascular characteristics in a canine model of human aging.

Dogs exhibit both neuroanatomical and cognitive changes as a function of age that parallel those seen in aging humans. This study describes in vivo changes in neuroanatomical and cerebrovascular characteristics of the canine brain as a function of age in a group of dogs ranging from 4 to 15 years old. Dynamic contrast-enhanced magnetic resonance imaging (MRI) was used to measure the kinetics of contrast agents in the brain. Measures of vascular volume and blood-brain barrier (BBB) permeability were derived from a pharmacokinetic analysis. Cortical atrophy and ventricular enlargement were characteristic features of the aged canine brain. Vascular volume did not vary as a function of age and BBB permeability exhibited a nonsignificant increasing trend with age. However, BBB dysfunction was detected in one middle-aged dog that in addition to having unusually large ventricles, demonstrated an early onset of diffuse senile plaques at postmortem. These findings indicate that BBB dysfunction detected by magnetic resonance imaging may be useful for predicting and potentially diagnosing early pathological conditions.

Applications of dynamic contrast enhanced MRI in oncology: measurement of tumor oxygen tension.

A new model based on an extension of the Krog's cylindrical model was developed to calculate tumor oxygen tension (pO(2)) from the H-1 dynamic contrast enhanced MRI (DCE-MRI) measurements. The model enables one to calculate the tumor pO(2) using the vascular volume fraction (f(b)) obtained by the DCE-MRI. The proposed model has three parameters. For small values of f(b) one assumes that there exists a linear relationship between and f(b). The constant of proportionality in this case is given by C(1) - the oxygen tension per vascular volume fraction. For larger values of f(b) a modified version of Krogh model using two parameters is developed and here C(2) - is the integrated blood oxygen tension, and C(3) - given by the combination of the oxygen diffusion coefficient, solubility of oxygen in the tissue, capillary radius, and tissue metabolic consumption rate. The parameters of the model can be determined by performing simultaneous in-vivo F-19 MRI oxygen tension measurement and dynamic Gd-DTPA enhanced MRI on the same tumor. Dynamic MRI data can be used with a compartmental model to calculate tumor vascular volume fraction on a pixel by pixel basis. Then tumor oxygen tension map can be calculated from the vascular volume fraction by the extended Krogh model as described above. In the present work, the model parameters were determined using three rats bearing Walker-256 tumors and performing simultaneous F-19 and DCE MRI on the same tumor. The parameters obtained by fitting the model equation to the experimental data were: C(1) = 983.2 +/- 133.2torr, C(2) = 58.20 +/- 2.4 torr, and C(3) = 1.7 +/- 0.1 torr. The performance of the extended Krogh model was then tested on two additional rats by performing both F-19 and DCE-MRI studies and calculating the pO(2) (H-1) using the model and comparing it with the pO(2) (F-19) obtained from the F-19 MRI. It was found that the measurements obtained by both techniques had a high degree of correlation [pO(2) (H-1) = (1.01 +/- 0.07) pO(2) (F-19) + (0.91 +/- 0.05) and r=0.96], indicating the applicability of the proposed model in determining pO(2) from the DCE-MRI.

Prediction of gene therapy-induced tumor size changes by the vascularity changes measured using dynamic contrast-enhanced MRI.

We studied the changes of tumor size after gene therapy treatment and its relationship with the changes of vascular volume as measured by dynamic contrast-enhanced magnetic resonance imaging (MRI), to investigate whether the vascular changes is predictive of tumor regression. The study was carried out using a spontaneously regressing rat tumor model (C6 Glioma grown subcutaneously in rats). Three rats were treated with recombinant adenoviruses expressing three genes, mouse interleukin 1-alpha (IL1-alpha), mouse interferon gamma (IFN-gamma), and human transforming growth factor beta (TGF-beta), one from each kind. Two rats were treated with saline as controls. Longitudinal studies were performed to monitor the changes of tumor volume (based on T(2)-weighted images) and the vascular volume (based on dynamic contrast enhanced images). In untreated animals, tumor regression was preceded by several days with a decrease in vascular volume. When the tumor growth was perturbed by expression of mouse IL-1alpha, the increase in vascular volume was correlated with the continuing growth in size, and the decrease in vascular volume was predictive of the onset of tumor regression. As new advances in immunotherapy in cancer treatment emerge, the ability to determine the efficacy of therapy as early as possible will enable optimization of treatment regiments. The vascularity changes measured by dynamic MRI may provide a means to serve for this purpose.