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To investigate the role of glycosylated hemoglobin in assisting the oral glucose tolerance test for gestational diabetes mellitus (GDM) diagnosis in Asian populations.PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to December 2020. Review Manager was applied to assess the quality of studies and risk of bias. MetaDiSc was used to measure diagnostic odds ratio, sensitivity, specificity, positive and negative likelihood ratios, area under receiving operating characteristic curve, and heterogeneity.A total of 19 original studies (32 669 women) were retrieved. The diagnostic efficiency of glycosylated hemoglobin was quantified from 4.5% to 6.0%. The pooled sensitivity (0.624, 0.609-0.638) and specificity and (0.624, 0.617-0.631) achieved optimal equilibrium at 5.0%. High sensitivity (0.911, 0.902-0.920) and low negative likelihood ratio (0.431, 0.365-0.508) at 4.6% as the rule-out cut-off, while with limited sensitivity, high specificity (0.990, 0.986-0.993) and positive likelihood ratio (8.309, 4.251-16.242) occurred at 5.8% as the rule-in cut-off. Heterogeneity was detected in parts of subgroup analyses (IGlycosylated hemoglobin is a potential tool in assisting GDM diagnosis in Asian populations, which has a better applicability based on the rule-out and rule-in algorithm (4.6%-5.8%), particularly for pregnant women with risk factors.

BACKGROUND: A noninvasive, safe, and economic imaging technique is required to identify epileptogenic lesions in the brain. PURPOSE: Our aim was to perform a meta-analysis evaluating the accuracy of arterial spin-labeling in localizing the epileptic focus in the brain and the changes in the blood perfusion in these regions. DATA SOURCES: Our sources were the PubMed and EMBASE data bases. STUDY SELECTION: English language studies that assessed the diagnostic accuracy of arterial spin-labeling for detecting the epileptogenic zone up to July 2019 were included. DATA ANALYSIS: The symptomatogenic foci of seizures in the brain were determined and used as the references. The relevant studies were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The outcomes were evaluated using the pooled sensitivity, pooled specificity, pooled accuracy, diagnostic odds ratio, area under the summary receiver operating characteristic curve, and likelihood ratio. DATA SYNTHESIS: Six studies that included 174 patients qualified for this meta-analysis. The pooled sensitivity, pooled specificity, and area under the summary receiver operating characteristic curve were 0.74 (95% CI, 0.65–0.82), 0.35 (95% CI, 0.03–0.90), and 0.73 (95% CI, 0.69–0.76), respectively. The accuracy of arterial spin-labeling for localizing the epileptic focus was 0.88 (accuracy in arterial spin-labeling/all perfusion changes in arterial spin-labeling) in cases of a positive arterial spin-labeling result. The epileptogenic zone exhibited hyperperfusion or hypoperfusion. LIMITATIONS: Only a few studies were enrolled due to the strict inclusion criteria. CONCLUSIONS: Arterial spin-labeling can be used for assessing, monitoring, and reviewing, postoperatively, patients with epilepsy. Blood perfusion changes in the brain may be closely related to the seizure time and pattern.

The success of gene therapy depends largely on the development of gene vectors and effective gene delivery systems. It has been demonstrated that cationic microbubbles can be loaded with negatively charged plasmid DNA and thus improve gene transfection efficiency. In this study, we developed dual-targeting cationic microbubbles conjugated with iRGD peptides(Cyclo(Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys)) and CCR2 (chemokine (C-C motif) receptor 2) antibodies (MBiRGD/CCR2) for ultrasound molecular imaging and targeted tumor gene therapy. The ultrasound molecular imaging experiments showed that there were significantly enhanced ultrasound molecular imaging signals in the tumor that received MBiRGD/CCR2, compared with those that received MBiRGD, MBCCR2, or MBcontrol. As a therapy plasmid, pGPU6/GFP/Neo-shAKT2, carrying an expression cassette for the human AKT2 RNA interference sequence, was used. Our results demonstrated that MBiRGD/CCR2 had a significantly higher gene transfection efficiency than MBiRGD, MBCCR2, or MBcontrol under ultrasound irradiation, resulting in much lower AKT2 protein expression and stronger tumor growth inhibition effects in vivo and in vitro. In conclusion, our study demonstrated a novel gene delivery system via MBiRGD/CCR2 for ultrasound molecular-imaging-guided gene therapy of breast cancer.

To develop a nomogram model for distinguishing benign from malignant ampullary lesions more intuitive and accurate.A total of 124 patients with periampullary lesions from January 2016 to June 2020 were enrolled in this retrospective study. Their clinical information, ultrasound (US), dual contrast-enhanced ultrasound (DCEUS) and MRI image features were used for research. Twenty features were collected in our study. Random forest was used to select the first five most important indicators to construct the prediction model.Patients' age, common bile duct (CBD) diameter, the shape, vascularity, and boundary of lesion, lesion size with or without enlarged after CEUS, the enhancement patterns of arterial phase, the washout patterns of venous phase, CEUS diagnosis, and MRI diagnosis were statistically significant (p 0.05). After screening for statistically significant indicators by random forest, the first five most important indicators were age, CBD diameter, the enhancement patterns of arterial phase, the washout patterns of venous phase, lesion size with or without enlarged after CEUS, which were used to construct nomogram. The area under curves (AUC) and 95% confidence intervals (CI) for nomogram, MRI + MRCP + DCEUS, DCEUS, MRI + MRCP were 0.98(0.94-1.00), 0.91(0.84-0.97), 0.89(0.80-0.98), 0.68(0.60-0.77), respectively. The sensitivity and specificity were 100.00% and 84.62% for nomogram, 88.29% and 92.31% for MRI + MRCP+DCEUS, 86.49% and 92.31% for DCEUS, 51.35%, and 100.00% for MRI + MRCP.We combined clinical indicators, gray-scale ultrasound characteristics, and CEUS characteristics to build the nomogram, which can be intuitively and accurately used for preoperative malignant prediction of ampullary lesion patients, worthy of clinical generalizability and application.

BackgroundSarcopenia is an age-related clinical condition and associated with an increased risk of adverse outcomes. However, to date, there is no global standard for the diagnosis of sarcopenia, and fewer serum biomarkers have been suggested for the diagnosis of sarcopenia. It is, thus, important that sarcopenia-related serological diagnostic markers be explored. The present study was based on the Asian Working Group on Sarcopenia 2019 (AWGS 2019) criteria to assess whether aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and fasting insulin*prealbumin (INS*PA) product are diagnostic markers associated with sarcopenia in various ethnic groups in western China.MethodsThis cross-sectional study included 4,099 adults (1,471 men and 2,628 women) from the West China Health and Aging Trend (WCHAT) study. The value of serum biomarkers was based on laboratory data. The accompanying metabolic disorders and the associated parameters were evaluated. Logistic regression analysis was used to explore the association between markers and sarcopenia. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic efficacy of the test in differentiating sarcopenia.ResultsBinary regression analysis showed that high serum AST/ALT (OR = 2.247) and adrenal cortisol (PTC, OR = 1.511), low serum INS*PA (OR = 2.970), free triiodothyronine (FT3, OR = 1.313), 25-OH-VitD (VitD, in male participants, OR = 1.817), and diastolic blood pressure (DBP, in female subjects, OR = 1.250) were independent risk factors for sarcopenia (P P P ConclusionAmong middle-aged and older adults of multiple ethnicities in western China, we found that higher AST/ALT and lower INS*PA levels are associated with an increased prevalence of sarcopenia. Since these serum biomarkers are inexpensive and can be obtained easily from biochemical routine, regular follow-up of AST/ALT and INS*PA may be an effective strategy in sarcopenia screening and management.

PURPOSE To investigate if artificial intelligence can identify fetus intracranial structures in pregnancy week 11-14; to provide an automated method of standard and non-standard sagittal view classification in obstetric ultrasound examination METHOD AND MATERIALS A data set of 1842 2D sagittal-view ultrasound images from 1842 females were collected to train and test a newly design scheme based on deep learning (DL) – Fetus Framework to identify nine fetus intracranial structures: thalami, midbrain, palate, 4th ventricle, cisterna magna, nuchal translucency (NT), nasal tip, nasal skin, and nasal bone. Results from Fetus Framework were further used for standard/non-standard (S-NS) plane classification, a key step for NT measurement and Down Syndrome assessment. S-NS classification were also tested with 156 images from a second medical center. Sensitivity, specificity and area under curve (AUC) were evaluated for comparison among Fetus Framework, three classic DL models and human experts with 1-, 3- and 5-year ultrasound training. Furthermore, a dataset of 316 standard images confirmed by the Fetus framework and another dataset of 316 standard images selected by physicians were utilized individually to train a random forest and perform the Fetal malformation classification task. Based on the hypothesis that random forest performs better on more standard dataset, mean AUC of 5-fold cross validation are compared. RESULTS Nine intracranial structures identified by Fetus Framework in validation are all consistent with that of senior radiologists. For S-NS sagittal view identification, Fetus Framework achieved AUC of 0.996 (95%CI: 0.987, 1.000) in internal test, at par with classic DL models. In external test, FF reaches an AUC of 0.974 (95%CI: 0.952, 0.995), while ResNet-50 arrives at AUC~0.883, 95% CI 0.828–0.939, Xception AUC~0.890, 95% CI 0.834–0.946, and DenseNet-121 AUC~0.894, 95% CI 0.839–0.949. For the internal test set, the sensitivity and specificity of the proposed framework is (0.905, 1), while the first-, third-, and fifth-year clinicians are (0.798, 0.986), (0.690, 0.958), and (0.619, 0.986), respectively. For the external test set, the sensitivity and specificity of FF is (0.989, 0.797)，and first-, third-, and fifth-year clinicians are (0.663, 0.781), (0.609, 0.844), and (0.533, 0.875), respectively. In further validation of fetal malformation classification task, mean AUC of random forest in physician dataset is 0.768 (0.724 – 0.812) and in Fetus dataset is 0.806 (0.741 – 0.871), suggesting that Fetus framework identify standard images more accurately. CONCLUSION We proposed a new deep learning-based Fetus Framework for identifying key fetus intracranial structures. The framework was tested in data from two different medical centers. The results show consistency and improvement from classic models and human experts in standard and non-standard sagittal view classification during pregnancy week 11-13+6. CLINICAL RELEVANCE/APPLICATION With further refinement in larger population, the proposed model can improve the efficiency and accuracy in early pregnancy test using ultrasound examination.

Background A noninvasive left ventricular (LV) pressure-strain loop (PSL) provides a new method to quantify myocardial work (MW) by combining global longitudinal strain (GLS) and LV pressure, which exerts potential advantages over traditional GLS. We studied the LV PSL and MW in patients with type 2 diabetes mellitus (T2DM). Methods This cross-sectional study included 201 subjects (54 healthy controls and 147 T2DM patients) who underwent complete two-dimensional echocardiography (2DE), including 2D speckle-tracking echocardiography (STE), as well as brachial artery pulse pressure measurement. The PSL was used to determine the global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) of all study participants. The association between T2DM and LV function was evaluated according to these MW indices. Results The GLS was significantly lower in the T2DM group than in the control group (P P = 0.022) and the GWW was increased (P P = 0.160). In all diabetic patients, age, body mass index, systolic blood pressure, smoking history, and LVEF were correlated with GWI, GWW and GWE. Conclusions The use of LV PSL is a novel noninvasive technique that could help to depict the relationship between LV myocardial damage and MW in patients with T2DM.

Aim:Mitochondria are essential for energy metabolism in the tumor microenvironment and the survival of cancer cells.Background:ADP-ribosylation factor–like GTPase 5b (ARL5B) has been found to be associated with mitochondrial dysfunction and breast cancer (BC) progression, but the underlying mechanism needs to be further understood.Objective:We investigated the effects of ARL5B on the apoptosis and glycolysis of breast cancer cells and its underlying mechanisms.Method:Quantitative reverse transcription-PCR (qRT-PCR) and western blot assays were used to detect the expression of ARL5B in breast cancer tissues and cells. An ARL5B loss-of-function assay was performed to verify its role in BC development.Results:ARL5B was upregulated in breast cancer tissues and cell lines. ARL5B knockdown induced apoptosis and activated the mitochondrial pathway in breast cancer cells. Interestingly, the inhibition of ARL5B repressed the aerobic glycolysis of breast cancer cells. The role of ARL5B in breast cancer cells was exerted by mediating the activation of viral RNA sensor MDA5-evoked signaling. Silencing ARL5B triggered MDA5 signaling by upregulating the key proteins involved in the MDA5 pathway. Importantly, MDA5 silencing reversed the effects of ARL5B knockdown on mitochondrial-mediated apoptosis and glycolysis, whereas poly (I:C), as a ligand for MDA5, further enhanced ARL5B knockdown- facilitated mitochondrial apoptosis and the inhibition of glycolysis.Conclusion:The knockdown of ARL5B activated MDA5 signaling and thus led to the enhanced mitochondrial- mediated apoptosis and glycolysis inhibition in breast cancer cells. Our study suggested that ARL5B might be a potential therapy target for BC.

Introduction Antiphospholipid syndrome is a chronic autoimmune disease with a high prevalence in females. Published data have identified that antiphospholipid antibodies (APLA) of antiphospholipid syndrome are risk factors for poor pregnancy outcomes, such as recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia. However, the association between APLA and late fetal loss is not fully understood and remains controversial. The aim of this study is to identify and analyze the recent publications to better understand the association between APLA and late fetal loss. Material and methods The literature was searched on 31 January 2019 using Ovid, Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) to evaluate the association between APLA and late fetal loss, with articles published before January 2019, according to the PRISMA statement. Without imposing regional restrictions, referenced articles were selected. Quality assessment was conducted independently by two reviewers, based on the Newcastle-Ottawa scale. For the meta-analysis, we used odds ratios (random effects model). The between-study heterogeneity was assessed by Q test. Publication bias was assessed by funnel plots. Results Nineteen studies (with 10 265 cases) were included in the final analysis. The odds ratio (OR) for the late fetal loss with lupus anticoagulant was 5.02 (95% confidence interval [CI] 2.14-7.89). Seven included studies reported that lupus anticoagulant had a statistically significant association with late fetal loss. The results did not show a statistically significant association between anticardiolipin antibodies and late fetal loss. The pooled odds ratio for the association of anticardiolipin antibodies with late fetal loss was 3.47 (95% CI 0.68-6.26). However, we did find the relation between anticardiolipin antibodies and late fetal loss among cohort studies (OR 2.27, 95% CI 1.20-3.44). Anti-beta2 glycoprotein 1 antibodies (β2GP1) showed a significant association with late fetal loss (OR 3.13, 95% CI 0.75-5.50). Conclusions Lupus anticoagulant is strongly associated with late fetal loss in antiphospholipid syndrome patients. However, the association between anticardiolipin antibodies and late fetal loss is inconsistent. There are currently insufficient data to support a significant relation between β2GP1 and late fetal loss.

To evaluate if an automatic classification of rheumatoid arthritis (RA) metacarpophalangeal joint conditions in ultrasound images is feasible by deep learning (DL) method, to provide a more objective, automated, and fast way of RA diagnosis in clinical setting.DenseNet-based DL model was used and both training and testing are implemented in TensorFlow 1.13.1 with Keras DL libraries. The area under curve (AUC), accuracy, sensitivity, and specificity values with 95% CIs were reported. The statistical analysis was performed by using scikit-learn libraries in Python 3.7.A total of 1337 RA ultrasound images were acquired from 208 patients, the number of images is 313, 657, 178, and 189 in OESS Grade L0, L1, L2, and L3, respectively. In Classification Scenario 1 SP-no versus SP-yes, three experiments with region of interest of size 192 × 448 (Group 1), 96 × 224 (Group 2), and 96 × 224 stacked with pre-segmented annotated mask of SP area (Group 3) as input achieve an AUC of 0.863 (95% CI: 0.809, 0.917), 0.861 (95% CI: 0.805, 0.916), and 0.886 (95% CI: 0.836, 0.936), respectively. In Classification Scenario 2 Healthy versus Diseased, experiments in Group 1, Group 2 and Group 3 achieve an AUC of 0.848 (95% CI: 0.799, 0.896), 0.864 (95% CI: 0.819, 0.909), and 0.916 (95% CI: 0.883, 0.952), respectively.We combined DenseNet model with ultrasound images for RA condition assessment. The feasibility of using DL to create an automatic RA condition classification system was also demonstrated. The proposed method can be an alternative to the initial screening of RA patients.

Background To assess the stiffness of benign breast masses in ultrasound images with posterior acoustic shadowing (PAS) and malignant lesions, and explore the significance of differential diagnosis using ultrasound real time shear wave elastography. Material and methods All 117 mammary masses (98 patients) with PAS were assessed by using routine ultrasound examination, and elastic modulus values were obtained with the real time shear wave elastography mode. All breast lesions were confirmed by surgery or biopsy. The significance of differences in ultrasound elastography values between breast benign and malignant masses with posterior acoustic shadowing was assessed, and the ROC curves of elasticity modulus values were analyzed. Results Among the 117 masses, 72 were benign and 45 were malignant. The two types of breast masses showed significant differences in size, margin, internal echo, calcification, and blood flow characteristics (P P > 0.05). Emean, Emax and Esd obtained with real time shear wave elastography showed statistically significant differences between benign masses with posterior acoustic shadowing and breast cancer (P Emin showed no significant difference between them (P = 0.633). Ultrasound real time shear wave elastography showed higher sensitivity and specificity than conventional ultrasound. Conclusions Benign and malignant breast masses with PAS show different ultrasound manifestations. Real time shear wave elastography can facilitate the differential diagnosis and treatment planning for these breast masses.

Objective. Antiphospholipid syndrome (APS) is a chronic autoimmune disease with a high prevalence in females. Published data have identified pregnant women with APS may suffer from recurrent miscarriage, fetal death. However, the association between antiphospholipid antibody (aPL) and fetal growth restriction (FGR) remains controversial. This study aims to systematically review the literature on population-based studies investigating an association between aPL and FGR. Methods. The literature was searched on 1 November, 2021, using Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), following the MOOSE checklist. Study inclusion criteria focused on peer-reviewed published articles that reported an association between aPL and FGR. Quality assessment was performed based on the Newcastle-Ottawa scale. The between-study heterogeneity was assessed by the Q test. Publication bias was assessed by funnel plots. Results. Twenty-two studies (with 11745 pregnant women) were included in the final analysis. Pooled odds ratio for association of aPL, anticardiolipin antibodies (ACA), anti-beta2 glycoprotein 1 antibodies (β2GP1), and FGR was 1.26 (95%CI 1.12, 1.40), 2.25 (95%CI 1.55, 2.94), and 1.31 (95% CI 1.12, 1.49), respectively. Lupus anticoagulant (LA) did not increase the chance of FGR (OR 0.82, 95%CI 0.54, 1.10). Conclusions. Our meta-analysis showed that aPL increased the risk of FGR. The risk of FGR varies with the aPL types. ACA and β2GP1 are strongly associated with FGR. There are currently insufficient data to support a significant relationship between LA and FGR.

BACKGROUND We aimed to evaluate the efficacy and safety of pneumatic trabeculoplasty (PNT) and selective laser trabeculoplasty (SLT) in the treatment of primary open-angle glaucoma (POAG) and ocular hypertension (OHT). MATERIAL AND METHODS We randomly divided 120 cases (120 eyes) of POAG or OHT into 2 groups: PNT and SLT. The changes in anterior chamber angle, intraocular pressure (IOP), treatment effect, macular retinal ganglion cell complex (GCC) thickness, visual field, adverse reactions, and complications were observed before and 3 months after treatment. RESULTS In the PNT group, the opening range of anterior chamber angle at 1 week, 2 weeks, 1 month, and 3 months after surgery was significantly larger than that before surgery. In the SLT group, the open range of anterior chamber angle was significantly less than that before surgery at 1 week and 2 weeks after surgery. The open range of anterior chamber angle in the PNT group was significantly larger than that in the SLT group at 1 week, 2 weeks, 1 month, and 3 months after surgery. The mean IOP of the 2 groups decreased significantly after surgery. The postoperative mean IOP of the SLT group was significantly higher than that of the PNT group, and the decrease of IOP in the PNT group was significantly greater than that of the SLT group. The effective rate of the PNT group was higher than that of the SLT group. CONCLUSIONS Both PNT and SLT can reduce the IOP of patients with POAG and OHT. PNT appears to have better short-term treatment efficiency than SLT.

Purpose This systematic review and meta-analysis aimed to evaluate the diagnostic performance of ultrasound elastography in the differentiation of benign and malignant breast non-mass lesions (NMLs). Methods PubMed, Cochrane Library, and Embase databases were searched for eligible studies up to end of June 2021. The diagnostic performance of elastography for NMLs was investigated using pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio (DOR), post-test probability, and the area under hierarchical summary receiver operating characteristic curve (HSROC). Results Eleven studies involving 812 NMLs (malignant 414) were included. The pooled sensitivity, specificity, DOR, positive likelihood ratio, and negative likelihood of elastography for the differentiation of benign and malignant breast NMLs were 79% (95 %CI: 71–85), 86% (95 %CI: 79–91), 23.32 (95 %CI: 13.38–40.66), 5.67 (95 %CI: 3.79–8.47), and 0.24 (95 %CI: 0.17–0.34), respectively. No significant publication bias existed. The area under the HSROC curve was 90% (95 %CI: 87–92). Fagan plots demonstrated good clinical utility. However, substantial heterogeneity existed. Country, measurement index, and number of lesions served as potential sources of heterogeneity. Conclusions The results of this study suggest that elastography has high diagnostic accuracy in differentiating between malignant and benign NMLs. Elastography can be a feasible and non-invasive tool for breast NMLs.

Objectives This study retrospectively evaluated the prognostic performance of the ultrasound elastographic Q-analysis score (EQS) combined with the Prostate Imaging Reporting and Data System (PI-RADS) for malignancy risk stratification in prostate nodules based on transrectal ultrasound-magnetic resonance imaging fusion imaging. Methods Sixty-two patients who were suspected to have PCa between October 2017 and May 2018 in our hospital were retrospectively evaluated. The performance of the EQS and PI-RADS was evaluated by patients' receiver operating characteristic curves in differentiating malignant and benign prostate nodules. The combination of the EQS and PI-RADS methods for prostate imaging was evaluated. Results Sixty-two prostate nodules in 62 patients were included. All of the patients underwent biopsy; 29 cases were prostate cancer, and the rest were benign prostate lesions. Both the EQS and PI-RADS were significantly higher in malignant nodules than in benign nodules. The sensitivity, specificity, area under the curve, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value, and Youden index of an EQS cutoff of 2.05 were 86.2%, 81.8%, 85.9%, 4.73, 0.169, 80.6%, 87.1%, and 68%, respectively. The corresponding numbers for a PI-RADS cutoff of 4 were 82.7%, 69.7%, 84.2%, 2.72, 0.25, 70.6%, 82.1%, and 52.4%. The "tandem" method had a higher diagnostic specificity (87.9%), positive likelihood ratio (6.55), and positive predictive value (85.1%). The "parallel" method had a higher diagnostic sensitivity (96.5%), negative likelihood ratio (0.06), and negative predictive value (95.2%). Conclusions both the EQS and PI-RADS had good diagnostic performance in differentiating between malignant and benign prostate lesions. The combination of the EQS and PI-RADS improved the diagnostic performance to a certain degree.

OBJECTIVES Evaluating the value of screening breast masses by separate or combined use of multimodal Sound Touch Elastography. METHODS Women with 159 masses (mean size, 14.86 ± 6.57 mm; range, 5.30-30.00 mm) were enrolled in the study. The pathology results were adopted as diagnostic standards. The abilities of Young's modulus (E), shear modulus (G), and shear wave (C) to differentiate malignant and benign breast masses based on receiver operating characteristic curves were evaluated, and the optimal cutoff values were obtained. Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated. Then, the values were combined to perform an overall analysis of Sound Touch Elastography using evidence-based medicine, construct forest plots, and calculate areas under the summary receiver operating characteristic curves, pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic scores. RESULTS A total of 159 masses with a mean size of 14.86 ± 6.57 mm (range, 5.30-30.00 mm) were included. For the various parameters, the diagnostic values were as follows: Gmax > Emax > Cmax > Csd > Esd > Gsd > Emean > Gmean > Cmean . There were no significant differences in Emin , Gmin , or Cmin . When the 9 parameters were combined, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic scores and areas under the summary receiver operating characteristic curves were 84% (95% confidence interval [CI], 79%-88%), 82% (95% CI, 80%-84%), 4.75 (95% CI, 4.15-5.43), 0.20 (95% CI, 0.15-0.25), 3.19 (95% CI, 2.84-3.54) and 90.2% (95% CI, 87%-92%), respectively. CONCLUSIONS Sound Touch Elastography can be recognized as a new ultrasound-based diagnostic method for differentiation between benign and malignant breast masses.

Aims To investigate differences in the prevalence of left ventricular (LV) and left atrial (LA) remodelling in hypertensive patients using various thresholds defined by international guidelines and data from the Echocardiographic Measurements in Normal Chinese Adults (EMINCA) study and different indexation methods. Methods and results LV mass (LVM), relative ventricular wall thickness, and LA volume (LAV) were measured using 2D echocardiography in 612 healthy volunteers selected from the EMINCA study population and 306 adult Chinese patients with hypertension who were age- and gender-matched using propensity score-matched analysis. LVM and LAV values were indexed to body surface area (BSA), height2.7, height1.7, and height2 recommended by guidelines or investigators. Using a previously reported method, LV geometry was divided into normal geometry, concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. The prevalence of LV hypertrophy (LVH) and LV geometric patterns in hypertensive patients were compared using different thresholds and indexation methods. Echocardiographic thresholds from guidelines and healthy volunteers exhibited notable differences, particularly for LAV indexed to height2 and for LVM indexed to height1.7, which resulted in a significantly lower prevalence of LA dilatation and LVH in healthy volunteers. The total proportion of abnormal LV geometric patterns was significantly lower with thresholds from healthy volunteers than from guidelines when LVM was indexed to BSA, height1.7, and height2,7. Conclusion Using current echocardiographic thresholds and indexing methods recommended by guidelines may lead to significant misdiagnosis of LA dilatation, and abnormal LV geometry in Chinese patients with hypertension, and thresholds based on ethnic-specific normal echocardiographic reference values and an accurate indexing algorithm are warranted.

In biomedical studies, the causal mediation effect might be heterogeneous across individuals in the study population due to each study subject's unique characteristics. While individuals' mediation effects may differ from each other, it is often reasonable and more interpretable to assume that individuals belong to several distinct latent subgroups with similar attributes. In this article, we first show that the subgroup-specific mediation effect can be identified under the group-specific sequential ignorability assumptions. Then, we propose a simple mixture modeling approach to account for the latent subgroup structure where each mixture component corresponds to one latent subgroup in the linear structural equation model framework. Model parameters can be estimated using the standard expectation-maximization (EM) algorithm. Each individual's subgroup membership can be inferred based on the posterior probability. We propose to use the singular Bayesian information criterion to consistently select the number of latent subgroups by recognizing that the Fisher information matrix for mixture models might be singular. We then propose to use nonparametric bootstrap method to compute standard errors and confidence intervals. We conducted simulation studies to evaluate the empirical performance of our proposed method named iMed. Finally, we reanalyzed a DNA methylation data set from the Normative Aging Study and found that the mediation effects of two well-documented DNA methylation CpG sites are heterogeneous across two latent subgroups in the causal pathway from smoking behavior to lung function. We also developed an R package iMed for public use.

Background Placenta previa and accreta are serious obstetric conditions that are associated with a high risk of intraoperative massive hemorrhage, the prophylactic intravascular balloon occlusion technique is increasingly used in managing uncontrolled hemorrhage in cesarean section (CS). We aim to examine the clinical effectiveness of prophylactic balloon occlusion of the internal iliac artery (PBOIIA) during CS in improving maternal outcomes for patients with placenta previa and accreta. Methods A total of 420 women with placenta previa and accreta who underwent CS from January 2014 to December 2018 were included retrospectively. Patients were divided into balloon group in which patients had PBOIIA (n = 248) and the control group in which patients did not have PBOIIA (n = 172). Meanwhile, we performed a subgroup analysis in whether taking parallel transverse uterine incision (PTUI) surgery. Information on conditions of patients and newborns, perioperative blood indicators, surgical outcomes were collected. Results Median estimated blood loss (mEBL) was 2200 mL in the balloon group and 2150 mL in the control group respectively, there was no significant difference between two-groups comparison (P > 0.05), and the rate of patients with hysterectomy was also has no difference between the two groups (36.3% verus 35.5%, P > 0.05), while there is a significant difference between two groups in the amount of PRBCs transfused [3 (0–31.5) verus 3 (0–39), P 8 units in the balloon group is significantly lower than that in control group (11.29% verus 23.26%, P P P >0.05), but it could significantly decrease hysterectomy rates (P Conclusions PBOIIA has no significant effect on reducing intraoperative EBL and hysterectomy rate in patients with placenta previa and accreta. and although it could reduce the intraoperative PRBCs in patients with massive hemorrhage, it significantly increases the financial cost for patients. Therefore, PBOIIA should not be routinely recommended to patients with placenta previa and accreta.

The present study compared the effects of ultrasonic irradiation and SonoVue microbubbles (US) or Lipofectamine 3000 on the transfection of small interfering RNA for PRR11 (siPRR11) and Proline-rich protein 11 (PRR11) overexpression plasmid into breast cancer cells. SiPRR11 and PRR11 overexpression plasmid were transfected into breast cancer MCF7 cells mediated by US and Lipofectamine 3000. PRR11 expressions in breast cancer and normal tissues were determined using Gene Expression Profiling Interactive Analysis (GEPIA). The viability, proliferation, migration, invasion and apoptosis of breast cancer cells were respectively measured by MTT assay, clone formation assay, scratch wound-healing assay, Transwell assay and flow cytometry. PRR11 and epithelial-to-mesenchymal transition (EMT)-related and apoptosis-related (B-cell lymphoma 2, Bcl-2; Bcl-2-associated protein X, Bax) proteins’ expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as appropriate. As ultrasonic intensity increased, the viability of MCF7 cells was decreased. Results from GEPIA suggested that PRR11 was up-regulated in breast cancer. Silencing PRR11 mediated by US showed a higher efficiency than by Lipofectamine 3000. SiPRR11 transfected by Lipofectamine 3000 suppressed cells growth and metastasis, while promoted cell apoptosis. Moreover, E-cadherin (E-cad) and Bax expressions were high but N-cadherin (N-cad), Snail and Bcl-2 expressions were low. However, overexpressed PRR11 caused the opposite effects. More importantly, transfection of siPRR11 and PRR11 overexpression plasmid using US had a higher efficacy than using Lipofectamine 3000. US transfection of PRR11 siRNA showed better effects on inhibiting breast cancer progression. The current findings contribute to a novel treatment for breast cancer.

A flexible class of semiparametric partly linear frailty transformation models is considered for analyzing clustered interval-censored data, which arise naturally in complex diseases and dental research. This class of models features two nonparametric components, resulting in a nonparametric baseline survival function and a potential nonlinear effect of a continuous covariate. The dependence among failure times within a cluster is induced by a shared, unobserved frailty term. A sieve maximum likelihood estimation method based on piecewise linear functions is proposed. The proposed estimators of the regression, dependence, and transformation parameters are shown to be strongly consistent and asymptotically normal, whereas the estimators of the two nonparametric functions are strongly consistent with optimal rates of convergence. An extensive simulation study is conducted to study the finite-sample performance of the proposed estimators. We provide an application to a dental study for illustration.

Cardiovascular diseases are the biggest threat to human being’s health all over the world, and carotid atherosclerotic plaque is the leading cause of ischemic cardiovascular diseases. To determine the location and shape of the plaque, it is of great significance to detect the intima-media (IM). In this paper, a new IM detection method based on convolution neural network (IMD-CNN) is proposed for the detection of IM of blood vessels in longitudinal ultrasonic images. In IMD-CNN, firstly the region of interest (ROI) is automatically extracted by morphological processing, then the patch-wise training data are constructed, and finally a simple CNN is trained to detect the IM. The experimental results obtained on 23 images show that the test accuracy of IMD-CNN is over 86% and the performance of IMD-CNN is also visually proved to be effective.

Objectives To review the diagnostic accuracy of transvaginal ultrasound (TVS) in the preoperative detection of uterosacral ligaments (USL) in patients with clinical suspicion of deep infiltrating endometriosis (DIE). Methods Extensive searches were conducted in PubMed, EMBASE and Cochrane libraries to search studies published between January 1989 and September 2, 2019. The inclusion criteria were the preoperative assessment of USL endometriosis by TVS in patients with clinically suspected DIE, using laparoscopy and histological results as the reference standard. The assessment of research quality uses preferred reporting items, including the System Review and Meta Analysis (PRISMA) guidelines, as well as the quality assessment of diagnostic accuracy study 2 (QUADAS-2) tools. Results During our advanced search, 7562 studies were identified. Finally, 11 of which were recognized as qualified and incorporated into this study. The pooled sensitivity, specificity, positive probability ratio (LR+) and negative probability ratio(LR-) of TVS for detecting DIE in the USL were 65 %(95 %CI:43−83), 92 %(95 %CI:84−96), 7.80 (95 %CI:4.7–13.0) and 0.38(95 %CI:0.22−0.66), respectively. There was significant heterogeneity in sensitivity (I2: 97.40 %; Cochran Q, 385.09; P Conclusion TVS provides an excellent comprehensive diagnostic performance for DIE of the USL. However, further research is required to improve the diagnostic quality.

BACKGROUND This study aimed to compare the predictive role of two-dimensional transthoracic echocardiography (2D-TTE) and three-dimensional transthoracic echocardiography (3D-TTE) on in-hospital all-cause mortality in patients with heart failure and reduced ejection fraction (HFrEF) due to ischemic heart disease (IHD). MATERIAL AND METHODS Patients (N-224) with HFrEF due to IHD who had a left ventricular ejection fraction (LVEF)

Aims: In this systematic review and meta-analysis, we discuss the value of grey-scale ultrasonography (US) in diagnosing adhesive capsulitis of the shoulder (ACS).Material and methods: We retrieved relevant studies from PubMed, Cochrane Library, and Embase before 8 April 2019. We selected 7 studies concerning 446 patients (490 shoulders) that used grey-scale US to diagnose ACS and magnetic resonance imaging (MRI) or arthroscopy as the reference standard. We assessed the diagnostic accuracy of US on the basis of combined sensitivity, specificity, likelihood ratio (LR), and the area under the summary receiver operating characteristic (SROC) curve (AUC).Results: The combined sensitivity, specificity, positive LR and negative LR were found to be 88% (95%CI: 74–95), 96% (95%CI: 88–99), 23.89 (95%CI: 6.31–90.51) and 0.12 (95%CI: 0.05–0.29), respectively. The AUC was 0.97 (95%CI: 0.96–0.98). ACS was diagnosed on the basis of four US features: coracohumeral ligament thickening, inferior capsule/axillary recess capsule thickening, rotator interval abnormality, and restriction of the range of motion. The corresponding sensitivities were 64.4 (95%CI: 48.8–78.1), 82.1 (95%CI: 73.8–88.7), 82.6 (95%CI: 74.1–89.2) and 94.3 (95%CI: 84.3–98.8), respectively, and specificities were 88.9 (95%CI: 76.0–96.3), 95.7 (95%CI: 90.3–98.6), 93.9 (95%CI: 89.8–96.7), and 90.9 (95%CI: 75.7–98.1), respectively.Conclusions: Our meta-analysis showed that grey-scale US plays a significant role in the diagnosis of ACS. Because of its high sensitivity and specificity, US can be added to the existing clinical diagnosis program.

Previous meta-analyses that found an inverse association between coffee consumption and metabolic syndrome pooled data from cross-sectional and longitudinal studies, which could lead to potentially misleading conclusions. Hence, this work aimed to reassess this association by analyzing data from the 2 types of studies separately and including recent studies. Online databases including PubMed, Scopus, Embase, The Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, and Science Direct were searched for relevant studies published up to July 2020. Both cross-sectional and longitudinal studies were included if published after 1999, reported both effect estimates and CIs, and presented results adjusted for confounding variables. Data of the highest coffee consumption level in each study, as well as those of medium consumption levels in studies with ≥3 consumption categories, were pooled using random-effect models, with sex-stratified and sex-adjusted results being analyzed separately. Results were obtained based on data from 13 cross-sectional studies involving 280,803 participants and 2 longitudinal studies involving 17,014 participants. The overall sex-adjusted association of the highest consumption level was not significant (n = 9 studies; OR: 0.88; 95% CI: 0.70, 1.10; I(2): 91.5%) and the 2 longitudinal studies both yielded no association. Subgroup analysis revealed inverse associations in both males and females, as well as in Caucasians with medium coffee consumption (n = 4 studies, OR: 0.88; 95% CI: 0.84, 0.93; I(2): 0%). Although residual confounding could affect the results of this meta-analysis, our findings suggested with a low certainty that coffee consumption may not be associated with metabolic syndrome, a finding that is different from those of previous meta-analyses and could be due to variation in characteristics of study participants. More longitudinal studies are also needed to further assess the temporal association between coffee consumption and metabolic syndrome. This meta-analysis was registered at https://www.crd.york.ac.uk/prospero as CRD42018110650.

Genome-wide association studies (GWAS) using longitudinal phenotypes collected over time is appealing due to the improvement of power. However, computation burden has been a challenge because of the complex algorithms for modeling the longitudinal data. Approximation methods based on empirical Bayesian estimates (EBEs) from mixed-effects modeling have been developed to expedite the analysis. However, our analysis demonstrated that bias in both association test and estimation for the existing EBE-based methods remains an issue. We propose an incredibly fast and unbiased method (simultaneous correction for EBE, SCEBE) that can correct the bias in the naive EBE approach and provide unbiased P-values and estimates of effect size. Through application to Alzheimer’s Disease Neuroimaging Initiative data with 6 414 695 single nucleotide polymorphisms, we demonstrated that SCEBE can efficiently perform large-scale GWAS with longitudinal outcomes, providing nearly 10 000 times improvement of computational efficiency and shortening the computation time from months to minutes. The SCEBE package and the example datasets are available at https://github.com/Myuan2019/SCEBE.

Nonlinear mixed-effects modeling is a popular approach to describe the temporal trajectory of repeated measurements of clinical endpoints collected over time in clinical trials, to distinguish the within-subject and the between-subject variabilities, and to investigate clinically important risk factors (covariates) that may partly explain the between-subject variability. Due to the complex computing algorithms involved in nonlinear mixed-effects modeling, estimation of covariate effects is often time-consuming and error-prone owing to local convergence. We develop a fast and accurate estimation method based on empirical Bayes estimates from the base mixed-effects model without covariates, and simple regressions outside of the nonlinear mixed-effect modeling framework. Application of the method is illustrated using a pharmacokinetic dataset from an anticoagulation drug for the prevention of major cardiovascular events in patients with acute coronary syndrome. Both the application and extensive simulations demonstrated that the performance of this high-throughput method is comparable to the commonly used maximum likelihood estimation in nonlinear mixed-effects modeling.

Smoking is a major preventable risk factor for atherosclerosis. However, the causative link between cigarette smoke and atherosclerosis remains to be established. The objective of this study is to characterize the role of GTP cyclohydrolase 1 (GTPCH1), the rate‐limiting enzyme for de novo tetrahydrobiopterin (BH4) synthesis, in the smoking‐accelerated atherosclerosis and the mechanism involved. In vitro, human umbilical vein endothelial cells were treated with nicotine, a major component of cigarette smoke, which reduced the mRNA and protein levels of GTPCH1 and led to endothelial dysfunction. GTPCH1 overexpression or sepiapterin could attenuate nicotine‐reduced nitric oxide and ‐increased reactive oxygen species levels. Mechanistically, human antigen R (HuR) bound with the adenylateuridylate‐rich elements of the GTPCH1 3′ untranslated region and increased its stability; nicotine inhibited HuR translocation from the nucleus to cytosol, which downregulated GTPCH1. In vivo, nicotine induced endothelial dysfunction and promoted atherosclerosis in ApoE−/− mice, which were attenuated by GTPCH1 overexpression or BH4 supplement. Our findings may provide a novel and promising approach to atherosclerosis treatment.

The prevalence and significance of right ventricular dysfunction (RVD) in patients with cardiogenic shock due to acute myocardial infarction (AMI-CS) have not been well characterized. We hypothesized that RVD is common in AMI-CS and associated with worse clinical outcomes.We retrospectively analyzed patients with available hemodynamics enrolled in the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial (n = 139) and registry (n = 258) to identify RVD in AMI-CS. RVD was defined by an elevated central venous pressure (CVP), elevated CVP-pulmonary capillary wedge pressure (PCWP) ratio, decreased pulmonary artery pulsatility index, and decreased right ventricular stroke work index. A P value of.01 was used to infer significance. In the SHOCK trial and registry, respectively, 38% and 37% of patients had RVD, but RVD was not associated with 30-day or 6-month survival (hazard ratio [HR] 1.51, (99% CI 0.92-2.49; P = .10). RV failure with the use of inclusion criteria from the Recover Right Trial for RV Failure (RR-RVF) requiring percutaneous mechanical circulatory support included elevated CVP and CVP/PCWP and a low cardiac index despite ≥1 inotrope or vasopressor. In the SHOCK trial and registry, respectively, 45% (n = 63/139) and 38% (n = 98/258) of patients met RR-RVF criteria. The RR-RVF criteria were not significantly associated with 30-day mortality in the registry cohort (HR 1.44, 99% CI 1.01-2.04; P = .04), or in the trial cohort (HR 1.51, 99% CI 0.92-2.49; P = .10).Hemodynamically defined RVD is common in AMI-CS. Routine assessment with pulmonary artery catherization allows detection of RVD; however, further work is needed to identify interventions that will result in improved outcomes for these patients.

Purpose To evaluate the efficacy of additional treatment with hydroxychloroquine (HCQ) for pregnant women with persistent positive antiphospholipid antibodies or antiphospholipid antibody syndrome (APS). Method We conducted a systematic search of the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases from inception to 31th December 2019. Two authors performed study selection, data collection, and data analysis independently. Result Five retrospective studies involving 477 pregnancies were selected. The live birth rate was significantly improved in the experimental group (OR, 3.29; 95 % CI, 1.45–7.49; P = 0.004). Additionally, pregnancy loss was associated with the additional use of HCQ (OR, 0.30;95 % CI, 0.13–0.69; P = 0.004). However, HCQ had no significant association with preterm delivery (OR, 0.43; 95 % CI, 0.13–1.37; P = 0.16) and fetal growth restriction showed an OR of 0.22 (95 % CI, 0.13–1.88; P = 0.55). Conclusion These data suggest that receiving HCQ as an additional treatment can improve the live birth rate in pregnant women with persistent antiphospholipid antibodies.

// Jian Fang 1 , Fuhao Qiao 1 , Jingjing Tu 1 , Jinfeng Xu 1 , Fangfang Ding 1 , Yun Liu 1 , Bufugdi Andreas Akuo 1 , Jianpeng Hu 2 and Shihe Shao 1 1 Department of Pathogenic Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China 2 Department of Urinary Surgery, Zhenjiang First People’s Hospital, Zhenjiang, Jiangsu 212013, China Correspondence to: Shihe Shao, email: 351564372@qq.com Keywords: NEAT1, cancer, OS, meta-analysis, poor prognosis Received: September 07, 2016 Accepted: April 11, 2017 Published: April 26, 2017 ABSTRACT The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA. Many studies have reported that NEAT1 plays critical oncogenic roles and facilitates tumorigenesis of various human cancers. High NEAT1 expression is associated with a poor prognosis in cancer patients. This meta-analysis was conducted to assess the association between NEAT1 levels and survival times of cancer patients. Overall survival (OS) was the primary endpoint. Thirteen publications with 1,496 cancer patients from 5 databases (PubMed, EMBASE, Cochrane Library, Wiley Online Library, and Medline) met the criteria for this meta-analysis. Results of the analysis showed that NEAT1 expression in human cancer was significantly associated with OS (hazard ratio [HR]=1.53, 95% confidence interval [CI]: 1.39–1.68), including digestive system tumor (HR=1.54, 95% CI: 1.37–1.73) and respiratory carcinomas (HR=1.44, 95% CI: 1.11–1.85). The results also indicated that NEAT1 expression was highly associated with tumor size (>3 cm vs. ≤3 cm; odds ratio [OR]=2.51, 95% CI: 1.27–4.99; p =0.009), TNM stage (III+IV vs. I+II; OR=4.17, 95% CI: 2.42–7.18; p =0.00001), and distant metastasis (OR=2.73, 95% CI: 1.28–5.79; p =0.01). However, there was no significant association with differentiation (poor vs. well + moderate, OR=1.45, 95% CI: 0.72–2.91) and lymph node metastasis (OR=1.39, 95% CI: 0.54–3.60). This meta-analysis showed that NEAT1 expression may be a useful biomarker for predicting a poor prognosis in patients with cancer.

Oxidative stress is thought to play an important role in the pathophysiology of pre-eclampsia. Polymorphism of Glutathione S-transferase P1 (GSTP1) protect cells against the cytotoxic effects of reactive compounds. Published data on the association between the GSTP1 polymorphism and pre-eclampsia risk are controversial. A meta-analysis was performed to assess whether the polymorphisms of GSTP1 are associated with pre-eclampsia risk. Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases were searched to identify eligible studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for GSTP1 polymorphism and pre-eclampsia were appropriately derived from fixed-effects or random effects models. A total of six studies were enrolled in this meta-analysis. The pooled analyses revealed that GSTP1 polymorphism was not associated with pre-eclampsia risk. Heterogeneity among studies was founded in allele contrast. Galbraith plot analyses were performed to assess the source of heterogeneity and one study was found to be contributor of heterogeneity. The heterogeneity decreased significantly after excluding that study. Present meta-analysis demonstrates that GSTP1 polymorphism may be not correlated with pre-eclampsia risk.

Osteoporosis is a major health problem, making bones fragile and susceptible to fracture. Previous works showed that mechanical loading stimulated bone formation and accelerated fracture healing. Focusing on the role of Wnt3a (wingless/integrated 3a), this study was aimed to assess effects of mechanical loading to the spine, using ovariectomized (OVX) mice as a model of osteoporosis. Two‐week daily application of this novel loading (4N, 10Hz, 5 min/d) altered bone remodeling with an increase in Wnt3a. Spinal loading promoted osteoblast differentiation, endothelial progenitor cell migration, and tube formation and inhibited osteoclast formation, migration, and adhesion. A transient silencing of Wnt3a altered the observed loading effects. Spinal loading significantly increased bone mineral density, bone mineral content, and bone area per tissue area. The loaded OVX group showed a significant increase in the number of osteoblasts and reduction in osteoclast surface/bone surface. Though expression of osteoblastic genes was increased, the levels of osteoclastic genes were decreased by loading. Spinal loading elevated a microvascular volume as well as VEGF expression. Collectively, this study supports the notion that Wnt3a‐mediated signaling involves in the effect of spinal loading on stimulating bone formation, inhibiting bone resorption, and promoting angiogenesis in OVX mice. It also suggests that Wnt3a might be a potential therapeutic target for osteoporosis treatment. —Li, X., Liu, D., Li, J., Yang, S., Xu, J., Yokota, H., Zhang, P. Wnt3a involved in the mechanical loading on improvement of bone remodeling and angiogenesis in a postmenopausal osteoporosis mouse model. FASEB J. 33, 8913–8924 (2019). www.fasebj.org

Background Placenta previa and accreta are serious obstetric conditions that are associated with a high risk of intraoperative massive hemorrhage. Purpose To develop a scoring system for intraoperative massive hemorrhage combining MRI and clinical characteristics to predict the risk of massive hemorrhage in placenta previa and accreta STUDY TYPE: Retrospective cohort study. Subjects In all, 374 patients consisting of 259 patients with placenta previa and accreta after previous cesarean section (CS) for the derivation cohort and 115 patients for the validation cohort. Field strength/sequence 1.5T single-shot fast spin-echo sequence. [Correction added on October 23, 2019, after first online publication: The field strength in the preceding sentence was corrected.] ASSESSMENT: Using the derivation cohort, clinical and MRI data were collected and multivariable logistic regressions analysis was conducted to develop a scoring system for prediction of intraoperative massive bleeding (blood loss volume > 2000 mL). Finally, the scoring system was validated on 115 patients. Statistical tests Student's t-test, Mann-Whitney U-test, X 2 statistics, multivariable analysis, and receiver operating characteristic (ROC) analysis. Results Ten indicators, including clinically maternal age (1 point), preoperative hemoglobin level (1 point), gravidity number (1 point), number of CS (1 point), and MRI T2 dark intraplacental bands (4 points), cervical canal length (3 points), placenta thickness on the uterine scar area (4 points), empty vascular shadow of the uterus (1 point), low signal discontinuity in the muscular layer of the posterior wall of the bladder (6 points) and attachment position of the placenta (1 point) were imputed. From the ROC analysis, a total score of 7 points was identified as the optimal cutoff value, allowing good differentiation of intraoperative massive bleeding in the derivation cohort (AUC, 0.863; 95% confidence interval [CI]: 0.811-0.916) and in the validation cohort (AUC, 0.933; 95% CI: 0.885-0.980). Data conclusion The scoring system for intraoperative massive hemorrhage consists of MRI and clinical indicators, and using a cutoff value of 7 points for a high risk of massive bleeding, the developed scoring system could accurately assess the risk of intraoperative massive hemorrhage in patients with placenta previa and accreta. This scoring system can potentially reduce the incidence of intraoperative massive bleeding by identifying patients at high risk. Level of evidence 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:947-958.

PURPOSE The purpose of this study was to compare the diagnostic value of Young's modulus (E) and shear modulus (G) in the differential diagnosis of benign and malignant breast masses using sound touch elastography (STE) and to explore the relationship between G and E in breast lesions. METHODS A total of 96 consecutive women with 110 pathologically confirmed breast masses were included. All masses were detected by conventional and STE ultrasound. Emean, Emax, Emin, ESD, Gmean, Gmax, Gmin, and GSD were determined and evaluated for evidence of significant differences between benign and malignant breast masses. Receiver operator characteristics were used to compare the diagnostic efficacy of E and G and to determine the G cutoff value that would aid in the differential diagnosis of breast cancer. RESULTS Emean, Emax, ESD, Gmean, Gmax, and GSD in cases of malignant breast masses were significantly higher than those in cases of benign masses (P < 0.05). There was no significant difference between Emin and Gmin (P = 0.565). In applying the Emean, Emax, ESD, Gmean, Gmax, and GSD to the receiver operator characteristics: (1) the area under the curve (AUC) of Gmean and Gmax is greater than the AUC of Emean and Emax, and the AUC of ESD is equal to the AUC of GSD. (2) The sensitivity and specificity were highest when the Gmean was 10.14 kPa. They were 84.1% and 80.3% respectively. (3) The sensitivity and specificity were highest when the Gmax was 52.20 kPa. They were 88.6% and 87.9% respectively. CONCLUSIONS These preliminary results of STE evaluation of breast masses suggest that the diagnostic value of G is greater than E. Furthermore, STE is a valuable tool in the differential diagnosis of breast lesions.

Aims Carotid intima-media thickness (CIMT) has been widely used to risk stratify and predict coronary artery disease (CAD) despite its significant limitations. To test whether radial artery intima thickness (RIT) is closely associated with atherosclerotic risk factors, and whether RIT has an independent and additive value for diagnosis of CAD. Methods and results One hundred and sixteen consecutive CAD patients and 79 age and gender-matched healthy controls were enrolled in this study. RIT, radial media thickness, radial intima-media thickness, and CIMT were measured with a high-resolution ultrasound biomicroscopy. Binary logistic regression was used to assess association between CAD and ultrasonic parameters, biochemical biomarkers or traditional risk factors. Receiver-operating characteristic curves were plotted to compare performances of several diagnostic models. RIT was positively associated with age, systolic blood pressure, statin administration, and hypertension. The independent value of RIT for differentiating CAD was similar to that of CIMT, but the add-on value of RIT to traditional risk factors for detecting CAD was superior to that of CIMT. Moreover, addition of RIT and CIMT to traditional risk factors increased AUC for detecting CAD from 0.724 to 0.867 significantly (P = 0.003). Conclusion RIT could detect CAD independently similarly to CIMT. The add-on value of RIT to traditional risk factors for detecting CAD was superior to CIMT and addition of RIT and CIMT to traditional risk factors markedly increased the power to diagnose CAD. Thus, RIT measured by ultrasound biomicroscopy provided a novel approach to non-invasive diagnosis of CAD.

OBJECTIVES This study aimed to evaluate the clinical value of the elastographic Q-analysis score (EQS) in assisting real-time elastography- and transrectal US-guided prostate biopsy. METHODS A total of 125 patients with 301 lesions were enrolled in this study; all were confirmed by pathologic results. The patients underwent transrectal US and elastographic examinations before biopsy. Elastographic Q-analysis score analysis software was used for measuring the mean EQS of the elastic images. First, the suspicious regions on elastography underwent biopsy. Then 12-core systematic prostate biopsy was performed. An EQS curve was used to calculate the mean EQS, and a receiver operating characteristic curve was drawn to find the cutoff point for the EQS to predict prostate cancer. RESULTS Of the 301 lesions in this study, 125 were malignant, and 176 were benign. The mean EQS values of benign and malignant lesions ± SD were 1.47 ± 0.75 and 2.98 ± 1.06, respectively. The difference was statistically significant (P

Covariate analysis based on population pharmacokinetics (PPK) is used to identify clinically relevant factors. The likelihood ratio test (LRT) based on nonlinear mixed effect model fits is currently recommended for covariate identification, whereas individual empirical Bayesian estimates (EBEs) are considered unreliable due to the presence of shrinkage. The objectives of this research were to investigate the type I error for LRT and EBE approaches, to confirm the similarity of power between the LRT and EBE approaches from a previous report and to explore the influence of shrinkage on LRT and EBE inferences. Using an oral one-compartment PK model with a single covariate impacting on clearance, we conducted a wide range of simulations according to a two-way factorial design. The results revealed that the EBE-based regression not only provided almost identical power for detecting a covariate effect, but also controlled the false positive rate better than the LRT approach. Shrinkage of EBEs is likely not the root cause for decrease in power or inflated false positive rate although the size of the covariate effect tends to be underestimated at high shrinkage. In summary, contrary to the current recommendations, EBEs may be a better choice for statistical tests in PPK covariate analysis compared to LRT. We proposed a three-step covariate modeling approach for population PK analysis to utilize the advantages of EBEs while overcoming their shortcomings, which allows not only markedly reducing the run time for population PK analysis, but also providing more accurate covariate tests.

One of the most critical requirements of the infection of the human immunodeficiency virus type 1 (HIV-1) is the interaction of its surface envelope glycoprotein gp120 with the cellular receptor CD4, which initiates virus entry to cells. Therefore, envelope glycoprotein gp120 has been validated as a potential target to develop HIV-1 entry inhibitors. Here we report the evaluation of a novel non-natural amino acid, termed 882376, reported earlier as a precursor of a CD4-mimetic miniprotein, as HIV-1 entry inhibitor. 882376 showed HIV-1 inhibitory activity against a large panel of primary isolates of different subtype. Moreover, genotyping of 882376 resistant HIV-1 virus revealed three amino acid substitutions in the gp120 including one in the CD4 binding site suggesting that this molecule may bind to gp120 and prevent its binding to CD4. Additional neutralization experiments indicate that 882376 is not active against mutant pseudoviruses carrying the amino acid substitutions S375H and S375Y located in the 'Phe43 cavity' which is the major site of CD4 binding, suggesting that this compound may interfere with the interaction between gp120 and CD4. The unnatural amino acid, 882376, is expected to serve as a lead for further optimization to more potent HIV-1 entry inhibitors.

The aim of the study described here was to screen breast lesions using either or both shear modulus (G) and its 1-mm shell (S) in sound touch elastography through a retrospective study of 209 consecutive women with breast lesions. The ability of G and S data to differentiate between malignant and benign lesions was evaluated using the receiver operating characteristic (ROC) curve. The optimal cutoff point, sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR–) were calculated. Then, the parameters were pooled to determine the area under the summary receiver operating curve (AUSROC). The pooled sensitivity (PSen), pooled specificity (PSpe), pooled LR+ (PLR+), pooled LR– (PLR–) and diagnostic score (DS) were calculated. Pathologic examination results were used as the reference. In total, 209 patients with 155 benign and 54 malignant lesions were enrolled. For Gmax, Gmean and Gsd, the cutoff values were 35.15 kPa (p = 0.0001), 10.18 kPa (p = 0.0001) and 5.18 kPa (p = 0.0001), respectively. For Smax, Smean and Ssd, the cutoff values were 40.94 kPa (p = 0.001), 13.12 kPa (p = 0.0001) and 7.97 kPa (p = 0.0001), respectively. There were no significant differences in Gmin and Smin between benign and malignant lesions. For the pooled six parameters, the PSen, PSpe, PLR+, PLR–, DS and AUSROC were 86% (95% confidence interval: 82%–89%), 82% (80%–85%), 4.90 (4.24–5.68), 0.17 (0.13–0.22), 3.36 (3.00–3.72) and 91% (88–93%), respectively. The G and S parameters of sound touch elastography could provide valuable data for the evaluation of breast lesions. Additionally, use of multiple parameters or combined use of the six parameters may be more effective in the evaluation of breast lesions.

To evaluate the value of ultrasonography in the diagnosis of anterior cruciate ligament injury (ACL injury) by conducting a systematic review and meta-analysis. A literature search was carried out in the Cochrane Library, Embase, Pubmed databases and included studies prior to April 2017. Based on inclusion and exclusion criteria, studies evaluating ultrasound to diagnose ACL injury were selected. MRI, arthroscopy and clinical-follow were considered the reference standards. The diagnostic accuracy of ultrasound was assessed using a combination of sensitivity, specificity, likelihood ratio (LR), post-test probability, diagnostic odds ratio (DOR) and by summarizing the area under the receiver operating characteristic (SROC) curve. A total of 4 studies involving 246 patients were eventually included in the analysis. In these four studies, the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, post-test probability and DOR were 90.0% (95% CI: 77-96), 97% (95% CI: 90-99), 31.08 (95% CI: 8.75-110.41), 0.11 (95% CI: 0.05-0.24), 89% (3%) and 288.81 (95% CI: 78.51-1062.48), respectively. The area under the SROC curve was 0.98 (95% CI: 0.97-0.99). Our meta-analysis showed that ultrasound can play an important role in the diagnosis of ACL injury. Because of its high sensitivity, high specificity and high diagnostic ability, ultrasound should be a part of the standard diagnostic work-up of an ACL injury.

Despite increasing use of the transradial approach (TRA) for coronary angiography, TRA failure and subsequent access site crossover remain a barrier to TRA adoption. The aim of this study was to elucidate patient and procedural characteristics associated with TRA to transfemoral approach (TFA) crossover and examine TRA to TFA crossover by operator experience over time. This retrospective analysis identified 1,600 patients who underwent coronary angiography with possible percutaneous coronary intervention through TRA by operators with varied TRA experience in an urban tertiary care center from October 2010 to August 2013. Univariate and multivariable logistic regression were used to identify independent predictors of access site crossover, from TRA to TFA, and strength of association is presented as odds ratio (OR, 95% confidence interval [CI]). Access site crossover was noted in 166 patients (10.4%). Multivariable predictors of access site crossover included age >75 years (OR 1.90, 95% CI 1.23 to 2.91, p = 0.004) and operator experience (OR 2.98, 95% CI 1.96 to 4.52, p, Link_to_subscribed_fulltext

Myocardial necrosis in the perioperative period of noncardiac surgery is associated with short-term mortality, but long-term outcomes have not been characterized. We investigated the association between perioperative troponin elevation and long-term mortality in a retrospective study of consecutive subjects who underwent hip, knee, and spine surgery. Perioperative myocardial necrosis and International Classification of Disease, Ninth Revision –coded myocardial infarction (MI) were recorded. Long-term survival was assessed using the Social Security Death Index database. Logistic regression models were used to identify independent predictors of long-term mortality. A total of 3,050 subjects underwent surgery. Mean age was 60.8 years, and 59% were women. Postoperative troponin was measured in 1,055 subjects (34.6%). Myocardial necrosis occurred in 179 cases (5.9%), and MI was coded in 20 (0.7%). Over 9,015 patient-years of follow-up, 111 deaths (3.6%) occurred. Long-term mortality was 16.8% in subjects with myocardial necrosis and 5.8% with a troponin in the normal range. Perioperative troponin elevation (hazard ratio 2.33, 95% confidence interval 1.33 to 4.10) and coded postoperative MI (adjusted hazard ratio 3.51, 95% confidence interval 1.44 to 8.53) were significantly associated with long-term mortality after multivariable adjustment. After excluding patients with coronary artery disease and renal dysfunction, myocardial necrosis remained associated with long-term mortality. In conclusion, postoperative myocardial necrosis is common after orthopedic surgery. Myocardial necrosis is independently associated with long-term mortality at 3 years and may be used to identify patients at higher risk for events who may benefit from aggressive management of cardiovascular risk factors.

Cleft lip and palate (CLP) is a common congenital defect usually diagnosed in the second trimester (Ghi et al. 2002; Maarse et al. 2010). It has been reported that CLP can be diagnosed in the first...

GII.4 noroviruses (NoVs) are a major cause of acute gastroenteritis in humans. A new variant of GII.4, the Sydney variant, has recently become more prevalent on a global scale. Intragenotype recombinations are widespread within the pandemic NoV GII.4 lineage, and are likely to be important forces driving the evolution and emergence of novel GII.4 viruses. In this study, we sought to examine the role that intergenotype recombination has played in the emergence of GII.4 Sydney 2012 variants. The results show that the GII.4 Sydney 2012 variants, Kawasaki194 and CA3477, were intergenotype recombination NoV strains with a GII.4 capsid and a GII.P16 polymerase gene. It has been reported for the first time that GII.4 new variant recombinants come from intergenotype recombination of GII.P16 and GII.4 strains in the complete genome.

OBJECTIVE To compare a full-automated software to quantify 3D transthoracic echocardiography namely, 3DE-HM (three-dimensional echocardiography HeartModel, Philips Healthcare) with the traditional manual quantitative method (3DE-manual) for assessing volumes of left atrial and ventricular volumes, and left ventricular ejection fraction (LVEF). METHODS 3D full volume images acquired from 156 subjects were collected and divided into 3 groups, which include 70 normal control cases (Group A), 17 patients with left ventricular remodeling after acute myocardial infarction (AMI) (Group B), and 69 patients with left atrial remodeling secondary to hypertension (Group C). The 3DE-HM method was used to quantify left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial end-systolic volume (LAESV), and left ventricular ejection fraction (LVEF), respectively. The results were compared with those obtained with the 3DE-manual method for correlation and consistency analyses. The reproducibility of the 3DE-HM method was also evaluated. RESULTS There was a high correlation between LVEDV, LVESV, LAESV and LVEF values obtained with the 3DE-HM method and those obtained using the 3DE-manual method (r = 0.72 to 0.97). The correlation was strongest for Group B, patients with left ventricular remodeling post-AMI also demonstrated the greatest degree of morphologic changes. There was a significant difference in all parameters measured with the 3DE-HM method in different groups (P

Aim: To investigate the clinical utility of shear wave elastography (SWE) imaging in the identification of malignant and benign lesions of the liver lesions by conducting a meta-analysis. Material and methods: The Cochrane library, Embase and Pubmed were searched for relevant studies with publication data through February 2016. Studies evaluating the diagnostic accuracy of SWE in the identification of malignant and benign lesions of the liver using SWE technology were selected. The cytology, histology or clinical imaging was used as the reference standard. The pooled sensitivity, specificity, diagnostic odds ratio, likelihood ratio, and the area under hierarchical summary receiver operating characteristic curve (HSROC) were used to examine the diagnostic accuracy. Results: A total of 9 cohort studies involving 1046 liver lesions (malignant 679) from 968 patients were identified. All of the 9 studies were prospective studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of SWE in differentiating malignant and benign liver lesions were 82.2% (95% CI: 73.4–88.5), 80.2% (95% CI: 73.3–85.7), 4.159 (95% CI: 2.899–5.966), 0.222 (95% CI: 0.140–0.352), and 18.749 (95% CI: 8.746–40.195), respectively. The area under the HSROC curve was 87% (95% CI: 84–90). Conclusions: This meta-analysis indicates that SWE is useful in evaluating the stiffness of liver lesions and in differentiating between malignant and benign lesions. Due to the high sensitivity, specificity, and diagnostic odds ratio, SWE can be considered as a useful complement to conventional ultrasonography.

Human biomonitoring of exposure to environmental chemicals is important. Individual monitoring is not viable because of low individual exposure level or insufficient volume of materials and the prohibitive cost of taking measurements from many subjects. Pooling of samples is an efficient and cost-effective way to collect data. Estimation is, however, complicated as individual values within each pool are not observed but are only known up to their average or weighted average. The distribution of such averages is intractable when the individual measurements are lognormally distributed, which is a common assumption. We propose to replace the intractable distribution of the pool averages by a Gaussian likelihood to obtain parameter estimates. If the pool size is large, this method produces statistically efficient estimates, but regardless of pool size, the method yields consistent estimates as the number of pools increases. An empirical Bayes (EB) Gaussian likelihood approach, as well as its Bayesian analog, is developed to pool information from various demographic groups by using a mixed-effect formulation. We also discuss methods to estimate the underlying mean-variance relationship and to select a good model for the means, which can be incorporated into the proposed EB or Bayes framework. By borrowing strength across groups, the EB estimator is more efficient than the individual group-specific estimator. Simulation results show that the EB Gaussian likelihood estimates outperform a previous method proposed for the National Health and Nutrition Examination Surveys with much smaller bias and better coverage in interval estimation, especially after correction of bias.

Background— National and international guidelines recommend fasting lipid panel measurement for risk stratification of patients for prevention of cardiovascular events. However, the prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol (LDL-C) is uncertain. Methods and Results— Patients enrolled in the National Health and Nutrition Examination Survey III (NHANES-III), a nationally representative cross-sectional survey performed from 1988 to 1994, were stratified on the basis of fasting status (≥8 or P =0.73), and LDL-C by fasting status interaction term in the Cox proportional hazards model was not significant ( P interaction =0.11). Similar results were seen for the secondary outcome (fasting versus nonfasting C statistic=0.62 [95% confidence interval, 0.60–0.66] versus 0.62 [95% confidence interval, 0.60–0.66]; P =0.96; P interaction =0.34). Conclusions— Nonfasting LDL-C has prognostic value similar to that of fasting LDL-C. National and international agencies should consider reevaluating the recommendation that patients fast before obtaining a lipid panel.