Objective
To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa).
Methods
This IRB-approved ...study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis.
Results
For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 95% CI 0.923–0.976) than PI-RADS (Az: 0.878 0.834–0.914, p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 0.945–0.988 vs. 0.940 0.905–0.965, p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 0.960–0.995) and PCa versus TZ (Az: 0.968 0.940–0.985).
Conclusion
Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa.
Key Points
•
Machine
-
based analysis of MR radiomics outperformed in TZ cancer against PI
-
RADS
.
•
Adding MR radiomics significantly improved the performance of PI
-
RADS
.
•
DKI
-
derived Dapp and Kapp were two strong markers for the diagnosis of PCa
.
Background
Vesical Imaging‐Reporting and Data System (VI‐RADS) is a pathway for the standardized imaging and reporting of bladder cancer staging using multiparametric (mp) MRI.
Purpose
To investigate ...additional role of morphological (MOR) measurements to VI‐RADS for the detection of muscle‐invasive bladder cancer (MIBC) with mpMRI.
Study Type
Retrospective.
Population
A total of 198 patients (72 MIBC and 126 NMIBC) underwent bladder mpMRI was included.
Field Strength/Sequence
3.0 T/T2‐weighted imaging with fast‐spin‐echo sequence, spin‐echo‐planar diffusion‐weighted imaging and dynamic contrast‐enhanced imaging with fast 3D gradient‐echo sequence.
Assessment
VI‐RADS score and MOR measurement including tumor location, number, stalk, cauliflower‐like surface, type of tumor growth, tumor‐muscle contact margin (TCM), tumor‐longitudinal length (TLL), and tumor cellularity index (TCI) were analyzed by three uroradiologists (3‐year, 8‐year, and 15‐year experience of bladder MRI, respectively) who were blinded to histopathology.
Statistical Tests
Significant MOR measurements associated with MIBC were tested by univariable and multivariable logistic regression (LR) analysis with odds ratio (OR). Area under receiver operating characteristic curve (AUC) with DeLong's test and decision curve analysis (DCA) were used to compared the performance of unadjusted vs. adjusted VI‐RADS. A P‐value <0.05 was considered statistically significant.
Results
TCM (OR 9.98; 95% confidence interval CI 4.77–20.8), TCI (OR 5.72; 95% CI 2.37–13.8), and TLL (OR 3.35; 95% CI 1.40–8.03) were independently associated with MIBC at multivariable LR analysis. VI‐RADS adjusted by three MORs achieved significantly higher AUC (reader 1 0.908 vs. 0.798; reader 2 0.906 vs. 0.855; reader 3 0.907 vs. 0.831) and better clinical benefits than unadjusted VI‐RADS at DCA. Specially in VI‐RADS‐defined equivocal lesions, MOR‐based adjustment resulted in 55.5% (25/45), 70.4% (38/54), and 46.4% (26/56) improvement in accuracy for discriminating MIBC in three readers, respectively.
Data Conclusion
MOR measurements improved the performance of VI‐RADS in detecting MIBC with mpMRI, especially for equivocal lesions.
Level of Evidence
3
Technical Efficacy
Stage 2
Insulin resistance plays a key role in the development and progression of type 2 diabetes mellitus (T2DM). Recent studies found that insulin resistance was associated with the dysfunction of KH‐type ...splicing regulatory protein (KSRP) expression and AKT pathway, and that oxymatrine possesses an antidiabetic effect. The aim of the present study was to investigate whether the protection of oxymatrine against T2DM was associated with the modulation of the KSRP expression and AKT pathway. Sprague‐Dawley rats were fed a high‐fat diet and injected with streptozotocin intraperitoneally to induce T2DM, which led to an increase in blood glucose levels and insulin resistance, and a decrease in insulin sensitivity and glycogen synthesis concomitant with KSRP downregulation, PTEN upregulation, and AKT phosphorylation deficiency. The administration of oxymatrine decreased blood glucose levels and insulin resistance, increased insulin sensitivity, and improved glycogen synthesis in the liver of T2DM rats, through a reversal in the expression of KSRP, PTEN, and AKT. On the basis of these observations, we concluded that oxymatrine can protect T2DM rats from insulin resistance through the regulation of the KSRP, PETN, and AKT expression in the liver.
Background
The high level of expertise required for accurate interpretation of prostate MRI.
Purpose
To develop and test an artificial intelligence (AI) system for diagnosis of clinically significant ...prostate cancer (CsPC) with MRI.
Study Type
Retrospective.
Subjects
One thousand two hundred thirty patients from derivation cohort between Jan 2012 and Oct 2019, and 169 patients from a publicly available data (U‐Net: 423 for training/validation and 49 for test and TrumpeNet: 820 for training/validation and 579 for test).
Field Strength/Sequence
3.0T/scanners, T2‐weighted imaging (T2WI), diffusion‐weighted imaging, and apparent diffusion coefficient map.
Assessment
Close‐loop AI system was trained with an Unet for prostate segmentation and a TrumpetNet for CsPC detection. Performance of AI was tested in 410 internal and 169 external sets against 24 radiologists categorizing into junior, general and subspecialist group. Gleason score >6 was identified as CsPC at pathology.
Statistical Tests
Area under the receiver operating characteristic curve (AUC‐ROC); Delong test; Meta‐regression I2 analysis.
Results
In average, for internal test, AI had lower AUC‐ROC than subspecialists (0.85 vs. 0.92, P < 0.05), and was comparable to junior (0.84, P = 0.76) and general group (0.86, P = 0.35). For external test, both AI (0.86) and subspecialist (0.86) had higher AUC than junior (0.80, P < 0.05) and general reader (0.83, P < 0.05). In individual, it revealed moderate diagnostic heterogeneity in 24 readers (Mantel–Haenszel I2 = 56.8%, P < 0.01), and AI outperformed 54.2% (13/24) of readers in summary ROC analysis. In multivariate test, Gleason score, zonal location, PI‐RADS score and lesion size significantly impacted the accuracy of AI; while effect of data source, MR device and parameter settings on AI performance is insignificant (P > 0.05).
Data Conclusion
Our AI system can match and to some case exceed clinicians for the diagnosis of CsPC with prostate MRI.
Evidence Level
3
Technical Efficacy
Stage 2
Purpose
A balance between preserving urinary continence as well as sexual potency and achieving negative surgical margins is of clinical relevance while implementary difficulty. Accurate detection of ...extracapsular extension (ECE) of prostate cancer (PCa) is thus crucial for determining appropriate treatment options. We aimed to develop and validate an artificial intelligence (AI)–based tool for detecting ECE of PCa using multiparametric magnetic resonance imaging (mpMRI).
Methods
Eight hundred and forty nine consecutive PCa patients who underwent mpMRI and prostatectomy without previous radio- or hormonal therapy from two medical centers were retrospectively included. The AI tool was built on a ResNeXt network embedded with a spatial attention map of experts’ prior knowledge (PAGNet) from 596 training patients. Model validation was performed in 150 internal and 103 external patients. Performance comparison was made between AI, two experts using a criteria-based ECE grading system, and expert-AI interaction.
Results
An index PAGNet model using a single-slice image yielded the highest areas under the receiver operating characteristic curve (AUC) of 0.857 (95% confidence interval CI, 0.827–0.884), 0.807 (95% CI, 0.735–0.867), and 0.728 (95% CI, 0.631–0.811) in training, internal, and external validation data, respectively. The performance of two experts (AUC, 0.632 to 0.741 vs 0.715 to 0.857) was lower (paired comparison, all
p
values < 0.05) than that of AI assessment. When experts’ interpretations were adjusted by AI assessments, the performance of two experts was improved.
Conclusion
Our AI tool, showing improved accuracy, offers a promising alternative to human experts for ECE staging using mpMRI.
Taxonomic and phylogenetic studies on the brown-rot fungi,
Fomitopsis
and its related genera, are carried out. On the basis of morphological characters and phylogenetic evidence of DNA sequences of ...multiple loci including the internal transcribed spacer (ITS) regions, the large subunit nuclear ribosomal RNA gene (nLSU), the small subunit nuclear ribosomal RNA gene (nSSU), the small subunit mitochondrial rRNA gene sequences (mtSSU), the translation elongation factor 1-α gene (
tef1
) and the second subunit of RNA polymerase II (
rpb2
), six new genera,
Fragifomes
,
Niveoporofomes
,
Piptoporellus
,
Rhodofomitopsis
,
Rubellofomes
and
Ungulidaedalea
are established. Four new species,
Buglossoporus eucalypticola
,
Daedalea allantoidea
,
Piptoporellus hainanensis
and
P. triqueter
are descibed from China. Illustrated descriptions of the novel species are provided. Identification keys to
Fomitopsis
and its related genera, as well as keys to the species of each genus are provided.
Objectives
To develop a machine learning (ML)‐assisted model to identify candidates for extended pelvic lymph node dissection (ePLND) in prostate cancer by integrating clinical, biopsy, and precisely ...defined magnetic resonance imaging (MRI) findings.
Patients and Methods
In all, 248 patients treated with radical prostatectomy and ePLND or PLND were included. ML‐assisted models were developed from 18 integrated features using logistic regression (LR), support vector machine (SVM), and random forests (RFs). The models were compared to the Memorial SloanKettering Cancer Center (MSKCC) nomogram using receiver operating characteristic‐derived area under the curve (AUC) calibration plots and decision curve analysis (DCA).
Results
A total of 59/248 (23.8%) lymph node invasions (LNIs) were identified at surgery. The predictive accuracy of the ML‐based models, with (+) or without (−) MRI‐reported LNI, yielded similar AUCs (RFs+/RFs−: 0.906/0.885; SVM+/SVM−: 0.891/0.868; LR+/LR−: 0.886/0.882) and were higher than the MSKCC nomogram (0.816; P < 0.001). The calibration of the MSKCC nomogram tended to underestimate LNI risk across the entire range of predicted probabilities compared to the ML‐assisted models. The DCA showed that the ML‐assisted models significantly improved risk prediction at a risk threshold of ≤80% compared to the MSKCC nomogram. If ePLNDs missed was controlled at <3%, both RFs+ and RFs− resulted in a higher positive predictive value (51.4%/49.6% vs 40.3%), similar negative predictive value (97.2%/97.8% vs 97.2%), and higher number of ePLNDs spared (56.9%/54.4% vs 43.9%) compared to the MSKCC nomogram.
Conclusions
Our ML‐based model, with a 5–15% cutoff, is superior to the MSKCC nomogram, sparing ≥50% of ePLNDs with a risk of missing <3% of LNIs.
Chronic brain hypoperfusion (CBH) is a common clinical feature of Alzheimer's disease and vascular dementia, but the underlying molecular mechanism is unclear. Our previous study reported that the ...down‐regulation of microRNA‐195 (miR‐195) promotes amyloidogenesis via regulation of amyloid precursor protein and β‐site amyloid precursor protein cleaving enzyme 1 (BACE1) expression at the post‐transcriptional level in CBH rats with bilateral common carotid artery occlusion (2VO). CBH owing to unilateral common carotid artery occlusion (UCCAO) increases tau phosphorylation levels at multiple phosphorylation sites in the brain, but the molecular mechanism is poorly understood. The purpose of this study was to investigate whether miR‐195 could both deregulate amyloid metabolism and indirectly deregulate tau phosphorylation in CBH. We observed that 2VO leads to tau hyperphosphorylation at Ser202/Thr205, Ser262, Thr231, and Ser422 and to the conversion from cyclin‐dependent kinase 5 (Cdk5)/p35 to Cdk5/p25 in rat hippocampi. Endogenous miR‐195 was knocked down using over‐expression of its antisense molecule (pre‐AMO‐miR‐195) via a lentivirus (lenti‐pre‐AMO‐miR‐195); this knockdown increased the tau phosphorylation at Ser202/Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over‐expression of miR‐195 using lenti‐pre‐miR‐195 decreased the tau phosphorylation and Cdk5/p25 activation. Further in vitro studies demonstrated that miR‐195 over‐expression prevented tau hyperphosphorylation and Cdk5/p35 activity, which were increased by miR‐195 inhibition. A dual luciferase reporter assay showed that miR‐195 bound to the Cdk5r1 gene, which encodes p35 protein, in the 3′UTR and inhibited p35 expression. We concluded that tau hyperphosphorylation involves the down‐regulation of miR‐195, which is mediated by Cdk5/p25 activation in 2VO rats. Our findings demonstrated that down‐regulation of miR‐195 led to increased vulnerability via the regulation of multiple targets.
Schematic diagram of miR‐195 mediated Aβ aggregation and tau hyperphosphorylation in chronic brain hypoperfusion (CBH). First, CBH results in the elevation of nuclear factor‐κB (NF‐κB), which binds with the promoter sequences of miR‐195 and negatively regulates the expression of miR‐195. Second, down‐regulated miR‐195 induces up‐regulation of APP and BACE1 and leads to an increase in Aβ levels. Third, some of the elevated Aβ then enter the intracellular space and activate calpain, which promotes the conversion of Cdk5/p35 to Cdk5/p25 and catalyzes the degradation of IκB; IκB is an inhibitor of NF‐κB, which activates NF‐κB. Cdk5/p25 directly phosphorylates Tau. Fourth, down‐regulated miR‐195 induces an up‐regulation of p35, which provides the active substrates of p25. Our findings demonstrated that the down‐regulation of miR‐195 plays a key role in the increased vulnerability to dementia via the regulation of multiple targets following CBH.
Schematic diagram of miR‐195 mediated Aβ aggregation and tau hyperphosphorylation in chronic brain hypoperfusion (CBH). First, CBH results in the elevation of nuclear factor‐κB (NF‐κB), which binds with the promoter sequences of miR‐195 and negatively regulates the expression of miR‐195. Second, down‐regulated miR‐195 induces up‐regulation of APP and BACE1 and leads to an increase in Aβ levels. Third, some of the elevated Aβ then enter the intracellular space and activate calpain, which promotes the conversion of Cdk5/p35 to Cdk5/p25 and catalyzes the degradation of IκB; IκB is an inhibitor of NF‐κB, which activates NF‐κB. Cdk5/p25 directly phosphorylates Tau. Fourth, down‐regulated miR‐195 induces an up‐regulation of p35, which provides the active substrates of p25. Our findings demonstrated that the down‐regulation of miR‐195 plays a key role in the increased vulnerability to dementia via the regulation of multiple targets following CBH.
is a common brown-rot fungal species found in northern hemisphere. It grows on many different gymnosperm and angiosperm trees. Recent studies show that it is a species complex; three species from ...North America and one species from Europe have been recognized in this complex. In the current study, six new species in the
complex were discovered from East Asia, based on morphological characters and phylogenetic analyses inferred from the sequence data of the internal transcribed spacer (ITS) regions, the second subunit of RNA polymerase II (RPB2), and the translation elongation factor 1-α gene (TEF). Detailed descriptions of the six new species are provided. Our results also indicates that species of the
complex from East Asia usually have limited distribution areas and host specialization.
Background/Aims: Ischemic stroke is still one of the leading debilitating diseases with high morbidity and mortality. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) play an important role ...in cerebral ischemia/reperfusion (I/R) injury. However, the mechanism underlying the regulation of ROS generation is still not fully elucidated. This study aims to explore the role of transforming growth beta (TGF-β) signals in ROS generation. Methods: Sprague–Dawley rats were subjected to I/R injury, and PC-12 cells were challenged by hypoxia/reoxygenation (H/R) and/or treated with activin receptor-like kinase (ALK5) inhibitor Sb505124 or siRNA against ALK5. Brain damage was evaluated using neurological scoring, triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, infarct volume measurement, TUNEL staining, and caspase-3 activity measurement. Expression of TGF-β and oxidative stress-related genes was analyzed by real-time polymerase chain reaction and Western blot; NOX activity and ROS level were measured using spectrophotometry and fluorescence microscopy, respectively. Results: I/R contributed to severe brain damage (impaired neurological function, brain infarction, tissue edema, apoptosis), TGF-β signaling activation (upregulation of ALK5, phosphorylation of SMAD2/3) and oxidative stress (upregulation of NOX2/4, rapid release of ROS oxidative burst). However, Sb505124 significantly reversed these alterations and protected rats against I/R injury. As in the animal results, H/R also contributed to TGF-β signaling activation and oxidative stress. Likewise, the inhibition of ALK5 or ALK5 knockdown significantly reversed these alterations in PC-12 cells. Other than ALK5 knockdown, ALK5 inhibition had no effect on the expression of ALK5 in PC-12 cells. Conclusions: Our studies demonstrated that TGF-β signaling activation is involved in the regulation of NOX2/NOX4 expression and exacerbates cerebral I/R injury.
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