Flow chart showing the process of studies retrieved.

<p>Flow chart showing the process of studies retrieved.</p

The heterogeneity analysis of diagnostic effects.

<p>PLR: positive likelihood ratio. NLR: negative likelihood ratio. DOR: diagonistics odd ratio. Estimate [95% CI]: the pooled effect measure with the corresponding 95% confidence interval. Log(Estimate) [95% CI]: logarithmic transformation of the pooled effect measure with the corresponding 95% confidence interval. df: degrees of freedom. Q and P-value were the Q value and p value of Cochran’s Q test.</p><p>The heterogeneity analysis of diagnostic effects.</p

Characteristics of all included studies.

<p>Characteristics of all included studies.</p

Evaluation of the Diagnostic Performance of Magnetic Resonance Spectroscopy in Brain Tumors: A Systematic Review and Meta-Analysis

<div><p>Object</p><p>The aim of this study was to determine the suitability of magnetic resonance spectroscopy (MRS) for screening brain tumors, based on a systematic review and meta-analysis of published data on the diagnostic performance of MRS.</p><p>Methods</p><p>The PubMed and PHMC databases were systematically searched for relevant studies up to December 2013. The sensitivities and specificities of MRS in individual studies were calculated and the pooled diagnostic accuracies, with 95% confidence intervals (CI), were assessed under a fixed-effects model.</p><p>Results</p><p>Twenty-four studies were included, comprising a total of 1013 participants. Overall, no heterogeneity of diagnostic effects was observed between studies. The pooled sensitivity and specificity of MRS were 80.05% (95% CI = 75.97%–83.59%) and 78.46% (95% CI: 73.40%–82.78%), respectively. The area under the summary receiver operating characteristic curve was 0.78. Stratified meta analysis showed higher sensitivity and specificity in child than adult. CSI had higher sensitivity and SV had higher specificity. Higher sensitivity and specificity were obtained in short TE value.</p><p>Conclusion</p><p>Although the qualities of the studies included in the meta-analysis were moderate, current evidence suggests that MRS may be a valuable adjunct to magnetic resonance imaging for diagnosing brain tumors, but requires selection of suitable technique and TE value.</p></div

Meta-regression of potential risk of bias of methodological characteristics affecting the diagnostic sensitivity of MRS.

<p>Meta-regression of potential risk of bias of methodological characteristics affecting the diagnostic sensitivity of MRS.</p

Forest plot of estimate of diagnostic accuracy of SV and CSI stratified meta-analysis.

<p>Forest plot of estimate of diagnostic accuracy of SV and CSI stratified meta-analysis.</p

SROC curve of diagnostic performance of stratified meta-analysis.

<p>(A) Adult and child. (B) SV and CSI. (C) LTE and STE.</p

Forest plot of estimate of diagnostic accuracy of adult and child stratified meta-analysis.

<p>Forest plot of estimate of diagnostic accuracy of adult and child stratified meta-analysis.</p

Forest plot of estimate of diagnostic accuracy of MRS.

<p>(A) Forest plot of estimate of sensitivity and specificity of MRS. (B) Forest plot estimate of PLR, NLR and DOR of MRS. (C) SROC curve of diagnostic performance of MRS from all studies. Solid line represents the ROC curve, and dotted line represented 95% confidence ellipse. Hollow triangle represented observed data from each study and solid rhombus represented the summary estimate.</p

3‑((<i>R</i>)‑4-(((<i>R</i>)‑6-(2-Bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholin-2-yl)propanoic Acid (HEC72702), a Novel Hepatitis B Virus Capsid Inhibitor Based on Clinical Candidate GLS4

The inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. On the basis of the preclinical properties and clinical results of GLS4, we carried out further investigation to seek a better candidate compound with appropriate anti-HBV potency, reduced hERG activity, decreased CYP enzyme induction, and improved pharmacokinetic (PK) properties. To this end, we have successfully found that morpholine carboxyl analogues with comparable anti-HBV activities to that of GLS4 showed decreased hERG activities, but they displayed strong CYP3A4 induction in a concentration-dependent manner, except for morpholine propionic acid analogues. After several rounds of modification, compound <b>58</b> (HEC72702), which had an (<i>R</i>)-morpholine-2-propionic acid at the C6 position of its dihydropyrimidine core ring, was found to display no induction of the CYP1A2, CYP3A4, or CYP2B6 enzyme at the high concentration of 10 μM. In particular, it demonstrated a good systemic exposure and high oral bioavailability and achieved a viral-load reduction greater than 2 log in a hydrodynamic-injected (HDI) HBV mouse model and has now been selected for further development