Predicting prostate cancer in men with PSA levels of 4-10 ng/mL: MRI-based radiomics can help junior radiologists improve the diagnostic performance.

To develop MRI-based radiomics model for predicting prostate cancer (PCa) in men with prostate-specific antigen (PSA) levels of 4-10 ng/mL, to compare the performance of radiomics model and PI-RADS v2.1, and to further verify the predictive ability of radiomics model for lesions with different PI-RADS v2.1 score. 171 patients with PSA levels of 4-10 ng/mL were divided into training (n = 119) and testing (n = 52) groups. PI-RADS v2.1 score was assessed by two radiologists. All volumes of interest were segmented on T2-weighted imaging, diffusion weighted imaging, and apparent diffusion coefficient sequences, from which quantitative radiomics features were extracted. Multivariate logistic regression analysis was performed to establish radiomics model for predicting PCa. The diagnostic performance was assessed using receiver operating characteristic curve analysis. The radiomics model exhibited the best performance in predicting PCa, which was better than the performance of PI-RADS v2.1 scoring by the junior radiologist in the training group [area under the curve (AUC): 0.932 vs 0.803], testing group (AUC: 0.922 vs 0.797), and the entire cohort (AUC: 0.927 vs 0.801) (P < 0.05). The radiomics model performed well for lesions with PI-RADS v2.1 score of 3 (AUC = 0.854, sensitivity = 84.62%, specificity = 84.34%) and PI-RADS v2.1 score of 4-5 (AUC = 0.967, sensitivity = 98.11%, specificity = 86.36%) assigned by junior radiologist. The radiomics model quantitatively outperformed PI-RADS v2.1 for noninvasive prediction of PCa in men with PSA levels of 4-10 ng/mL. The model can help improve the diagnostic performance of junior radiologists and facilitate better decision-making by urologists for management of lesions with different PI-RADS v2.1 score.

Magnetic resonance imaging-radiomics evaluation of response to chemotherapy for synchronous liver metastasis of colorectal cancer.

BACKGROUND: Synchronous liver metastasis (SLM) is an indicator of poor prognosis for colorectal cancer (CRC). Nearly 50% of CRC patients develop hepatic metastasis, with 15%-25% of them presenting with SLM. The evaluation of SLM in CRC is crucial for precise and personalized treatment. It is beneficial to detect its response to chemotherapy and choose an optimal treatment method. AIM: To construct prediction models based on magnetic resonance imaging (MRI)-radiomics and clinical parameters to evaluate the chemotherapy response in SLM of CRC. METHODS: A total of 102 CRC patients with 223 SLM lesions were identified and divided into disease response (DR) and disease non-response (non-DR) to chemotherapy. After standardizing the MRI images, the volume of interest was delineated and radiomics features were calculated. The MRI-radiomics logistic model was constructed after methods of variance/Mann-Whitney U test, correlation analysis, and least absolute shrinkage and selection operator in feature selecting. The radiomics score was calculated. The receiver operating characteristics curves by the DeLong test were analyzed with MedCalc software to compare the validity of all models. Additionally, the area under curves (AUCs) of DWI, T2WI, and portal phase of contrast-enhanced sequences radiomics model (Ra-DWI, Ra-T2WI, and Ra-portal phase of contrast-enhanced sequences) were calculated. The radiomics-clinical nomogram was generated by combining radiomics features and clinical characteristics of CA19-9 and clinical N staging. RESULTS: The AUCs of the MRI-radiomics model were 0.733 and 0.753 for the training (156 lesions with 68 non-DR and 88 DR) and the validation (67 lesions with 29 non-DR and 38 DR) set, respectively. Additionally, the AUCs of the training and the validation set of Ra-DWI were higher than those of Ra-T2WI and Ra-portal phase of contrast-enhanced sequences (training set: 0.652 vs 0.628 and 0.633, validation set: 0.661 vs 0.575 and 0.543). After chemotherapy, the top four of twelve delta-radiomics features of Ra-DWI in the DR group belonged to gray-level run-length matrices radiomics parameters. The radiomics-clinical nomogram containing radiomics score, CA19-9, and clinical N staging was built. This radiomics-clinical nomogram can effectively discriminate the patients with DR from non-DR with a higher AUC of 0.809 (95% confidence interval: 0.751-0.858). CONCLUSION: MRI-radiomics is conducive to predict chemotherapeutic response in SLM patients of CRC. The radiomics-clinical nomogram, involving radiomics score, CA19-9, and clinical N staging is more effective in predicting chemotherapeutic response.

Theta burst stimulation for upper limb motor dysfunction in patients with stroke: A protocol of systematic review and meta-analysis.

BACKGROUND: Upper limb dysfunction is one of common sequelae of stroke which limits daily activities and decreases quality of life of patients, as well as increasing caregiving burden on families. Theta burst stimulation (TBS) is considered to be a beneficial therapy for post-stroke patients with upper limb motor dysfunction, but there is a lack of a high quality evidence. We aim to investigate the effectiveness and safety of TBS for upper limb motor dysfunction in patients with stroke. METHODS: The following databases will be searched: PubMed, EMBASE, The Cochrane Library, Web of Science, China Biology Medicine (CBM), China National Knowledge infrastructure (CNKI), Technology Periodical Database (VIP) and WanFang Data from the inception to October 2019. All relevant randomized controlled trials (RCTs) using TBS to treat poststroke patients with upper limb motor dysfunction will be included. The primary outcome is Upper Limb Fugl-Meyer Assessment (UL-FMA). Secondary outcomes will include Action Research Arm Test (ARAT), Box and Block Test (BBT), Wolf Motor Function Test (WMFT), Motor Assessment Scale (MAS), Nine Hole Peg Test (NHPT), Grip strength and other scales evaluating the upper limb motor function. Adverse effects will also be evaluated. Two reviewers will screen studies, extract data and assess the risk of bias of included studies independently. Data analysis will be conducted using Review Manager software (RevMan, version 5.3.5) and R software (version 3.6.1). RESULTS: Our SR will be conducted according to AMSTAR 2.0 and reported in compliance with PRISMA. The findings of this SR will be disseminated through peer-reviewed publications or conference presentations. CONCLUSION: Our study will provide evidence for the effectiveness and safety of theta burst stimulation for upper limb motor dysfunction in patients with stroke. ETHICS AND DISSEMINATION: This systematic review (SR) does not require formal ethical approval since no privacy health information will be included. The findings of this SR will be disseminated through peer-reviewed publications or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42019142462.

Alterations of brain local functional connectivity in amnestic mild cognitive impairment.

BACKGROUND: Resting-state functional magnetic resonance imaging studies using a regional homogeneity (ReHo) method have reported that amnestic mild cognitive impairment (aMCI) was associated with abnormalities in local functional connectivity. However, their results were not conclusive. METHODS: Seed-based d Mapping was used to conduct a coordinate-based meta-analysis to identify consistent ReHo alterations in aMCI. RESULTS: We identified 10 studies with 11 datasets suitable for inclusion, including 378 patients with aMCI and 435 healthy controls. This meta-analysis identified significant ReHo alterations in patients with aMCI relative to healthy controls, mainly within the default mode network (DMN) (bilateral posterior cingulate cortex [PCC], right angular gyrus, bilateral middle temporal gyri, and left parahippocampal gyrus/hippocampus), executive control network (right superior parietal lobule and dorsolateral prefrontal cortex), visual network (right lingual gyrus and left middle occipital gyrus), and sensorimotor network (right paracentral lobule/supplementary motor area, right postcentral gyrus and left posterior insula). Significant heterogeneity of ReHo alterations in the bilateral PCC, left parahippocampal gyrus/hippocampus, and right superior parietal lobule/angular gyrus was observed. Exploratory meta-regression analyses indicated that general cognitive function, gender distribution, age, and education level partially contributed to this heterogeneity. CONCLUSIONS: This study provides provisional evidence that aMCI is associated with abnormal ReHo within the DMN, executive control network, visual network, and sensorimotor network. These local functional connectivity alterations suggest coexistence of functional deficits and compensation in these networks. These findings contribute to the modeling of brain functional connectomes and to a better understanding of the neural substrates of aMCI. Confounding factors merit much attention and warrant future investigations.

Cerebral glucose metabolic prediction from amnestic mild cognitive impairment to Alzheimer's dementia: a meta-analysis.

Brain 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been utilized to monitor disease conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's dementia (AD). However, the conversion patterns of FDG-PET metabolism across studies are not conclusive. We conducted a voxel-wise meta-analysis using Seed-based d Mapping that included 10 baseline voxel-wise FDG-PET comparisons between 93 aMCI converters and 129 aMCI non-converters from nine longitudinal studies. The most robust and reliable metabolic alterations that predicted conversion from aMCI to AD were localized in the left posterior cingulate cortex (PCC)/precuneus. Furthermore, meta-regression analyses indicated that baseline mean age and severity of cognitive impairment, and follow-up duration were significant moderators for metabolic alterations in aMCI converters. Our study revealed hypometabolism in the left PCC/precuneus as an early feature in the development of AD. This finding has important implications in understanding the neural substrates for AD conversion and could serve as a potential imaging biomarker for early detection of AD as well as for tracking disease progression at the predementia stage.

Correction to: Alterations of brain local functional connectivity in amnestic mild cognitive impairment.

[This corrects the article DOI: 10.1186/s40035-018-0134-8.].

Aberrant pattern of regional cerebral blood flow in Alzheimer's disease: a voxel-wise meta-analysis of arterial spin labeling MR imaging studies.

Many studies have applied arterial spin labeling (ASL) to characterize cerebral perfusion patterns of Alzheimer's disease (AD). However, findings across studies are not conclusive. A quantitatively voxel-wise meta-analysis to pool the resting-state ASL studies that measure regional cerebral blood flow (rCBF) alterations in AD was conducted to identify the most consistent and replicable perfusion pattern using seed-based d mapping. The meta-analysis, including 17 ASL studies encompassing 327 AD patients and 357 healthy controls, demonstrated that decreased rCBF in AD patients relative to healthy controls were consistently identified in the bilateral posterior cingulate cortices (PCC)/precuneus, bilateral inferior parietal lobules (IPLs), and left dorsolateral prefrontal cortex. The meta-regression analysis showed that more severe cognitive impairment in the AD samples correlated with greater decreases of rCBF in the bilateral PCC and left IPL. This study characterizes an aberrant ASL-rCBF perfusion pattern of AD involving the posterior default mode network and executive network, which are implicated in its pathophysiology and hold promise for developing imaging biomarkers.

Gray matter atrophy in progressive supranuclear palsy: meta-analysis of voxel-based morphometry studies.

Voxel-based morphometry (VBM) studies have provided cumulative evidence of gray matter (GM) atrophy in patients with progressive supranuclear palsy (PSP) relative to healthy controls (HC). However, not all findings have been entirely concordant. Herein, we performed a quantitative meta-analysis study in order to consistently quantify GM anomalies in PSP. We conducted a systematic search for VBM studies of PSP patients and HC using PubMed and Embase databases from January 2000 to May 2012. Meta-analysis of these VBM studies was performed using a newly improved voxel-based meta-analytic technique, effect-size signed differential mapping. A total of 9 cross-sectional VBM studies that involved 143 PSP patients and 216 HC subjects met the inclusion criteria. Considerable regional GM volume decrease was detected in the thalamus, basal ganglia, midbrain, insular cortex, and frontal cortex. These findings remained largely unchanged following jackknife sensitivity analyses. The present meta-analysis provided evidence of PSP-specific GM atrophy. This finding might help contribute to our understanding of the neurobiological basis underlying PSP.

Gray matter atrophy in Parkinson's disease with dementia: evidence from meta-analysis of voxel-based morphometry studies.

Voxel-based morphometry (VBM) studies have provided cumulative evidence of gray matter (GM) atrophy in patients with Parkinson's disease with dementia (PDD) relative to healthy controls (HC). However, not all the studies reported entirely consistent findings. A systematic search for VBM studies of PDD patients and HC subjects published in PubMed and Embase databases from January 2000 to June 2012 was conducted. Meta-analysis was performed by using a newly improved voxel-based meta-analytic technique, effect size signed differential mapping, to quantitatively explore the GM abnormalities between PDD patients and HC subjects. A total of 6 cross-sectional VBM studies involving 105 PDD patients and 131 HC subjects met the inclusion criteria. Considerable regional GM decrease was detected in the medial temporal lobe (MTL) and basal ganglia. The findings of the present study remained largely unchanged in the entire brain jackknife sensitivity analyses. Meta-regression showed dementia severity correlated with the left MTL. The present meta-analysis provided evidence of PDD-related GM atrophy, which suggested MTL and basal ganglia were implicated in PDD. This finding could give us further insight about the pathophysiological basis revealed by structure abnormalities in PDD.

Gray matter atrophy in behavioral variant frontotemporal dementia: a meta-analysis of voxel-based morphometry studies.

BACKGROUND: Structural neuroimaging studies on behavioral variant frontotemporal dementia (bvFTD) using the voxel-based morphometry (VBM) method reported not entirely consistent findings. METHODS: A systematic review of VBM studies of bvFTD patients and healthy controls (HC) published in PubMed and Embase databases from 2000 to June 2011 was conducted. Meta-analysis was performed using a newly improved voxel-based meta-analytic tool, namely, effect size signed differential mapping, to quantitatively explore the gray matter (GM) changes between bvFTD patients and HC subjects. RESULTS: 11 VBM studies involving 237 bvFTD patients and 297 HC subjects met the inclusion criteria. Considerable regional GM volume decrease was detected in the anterior medial frontal cortex (BA 9), extending to other frontal areas (BA 8, 10, 46, 24, 32), and other brain areas, such as the insula cortex, as well as the subcortical striatal regions in patients with bvFTD compared with HC subjects. The findings of the present study remain largely unchanged in the entire brain jackknife sensitivity analyses. CONCLUSIONS: The present meta-analysis provides evidence of GM changes in the frontal-striatal-limbic brain areas in patients with bvFTD. Furthermore, GM atrophy in the fron-toinsular cortex and anterior cingulate cortex may be important anatomical changes for the diagnosis of patients with bvFTD.

Kinetic study for a stress testing of l,l-ethylenedicysteine by ultra-performance liquid chromatography/tandem mass spectrometry analysis.

This study proposed a stress testing to study oxidative stability and estimate the potential shelf-life of l,l-ethylenedicysteine (l,l-EC) under normal storage temperature condition (20-25 degrees C). l,l-EC was detected as a function of time at four different temperatures by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS). The degradation of l,l-EC followed the first order kinetics, and the temperature-dependent kinetics was well described by the linear Arrhenius equation. The activation energy (E(a)) was calculated, and the shelf-life at 25 and 4 degrees C was predicted. The results are useful for the proper storage and quality evaluation of l,l-EC.

Rapid disruption of Bombyx mori nucleopolyhedrovirus orf60 by red recombination system / 生物工程学报

BmNPV bacmid constructed recently and Red recombinant system were used to rapidly disrupted Bombyx monri nucleopolyhedrovirus (BmNPV) orf60 in Escherichia coli (E. coli) BW25113. BmNPV bacmid isolated from E. coli BmDH10Bac was electroporated into E. coli BW25113, which harbors plasmid pKD46 encoding lamda Red recombinase,to produce E. coli BW25113-Bac, which could be used for gene deletion of BmNPV. A linear fragment was amplified by PCR from plasmid pKD3 (containing a chloramphenicol acetyltransferase gene cat) using a pair of primers with length of 63bp,which had 45 bp homologous to the orf60 gene and 18bp homologous to cat sequences. The linear fragment was electroporated into E. coli BW25113-Bac and homologous recombination occurred between the linear fragment and orf60 with the help of lamda Red recombinase. Three specific primer pairs were used to confirm the replacement of orf60 by cat gene. Western blot analysis showed that orf60 was not expressed in BmN cells infected with knockout bacmid.