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Mixed-matrix membranes (MMMs) with excellent mechanical and separation performance are usually challenging to be fabricated due to the significant incompatibility between nanofillers and the polymer matrix. This work provides a facile technique to construct MMMs through covalently attaching metal-organic frameworks (MOFs) within the polymer matrix via ring-opening metathesis polymerization. Norbornene-modified UiO-66-NH 2 was successfully copolymerized into polynorbornene matrix in less than 10 min. Owing to strong covalent interaction among MOFs and polymers, exceptional toughening effects for MMMs through cavitation were observed. For MMMs with 20 wt % MOF loading, 520 times improvement in mechanical toughness was realized in comparison with neat polymers (52 vs 0.1 MJ/m 3 ), far exceeding most of the previous MMMs. Such MMMs exhibited excellent gas separation performance for H 2 /CO 2 and H 2 /N 2 with high H 2 permeability at 91-230 barrers and H 2 /N 2 and H 2 /CO 2 selectivity at >1000 and 6-7, respectively, surpassing the 2008 Robeson Upper Bound. As a proof for the scalable preparation of MMMs, a large and thin MMM (dimension: 98 × 165 cm; thickness: 3-5 μm) was also prepared in the factory for gas separation.

Background: Increasing evidence suggests that SALL4 plays oncogenic roles in cancer development and progression. We have previously shown that SALL4 is highly expressed in gastric cancer, and its upregulation is associated with lymph node metastasis and poor prognosis. The role of SALL4 in gastric cancer metastasis and the underlying mechanism remain unclear., Materials and Methods: The biological roles of SALL4 in gastric cancer cell mobility, migration, and invasion were investigated by wound healing, transwell migration assay, and Matrigel invasion assay. The effects of SALL4 on epithelial-mesenchymal transition (EMT) in gastric cancer cells were examined by quantitative real-time PCR and Western blot. The downstream target genes of SALL4 were identified by microarray. The regulation of TGF-β1 by SALL4 in gastric cancer cells was analyzed by luciferase reporter assay and chromatin immunoprecipitation assay., Results: SALL4 knockdown inhibited, while SALL4 overexpression promoted the motility, migration, and invasion abilities of gastric cancer cells in vitro. SALL4 knockdown also suppressed the peritoneal metastasis of gastric cancer cells in nude mice. SALL4 knockdown suppressed, while SALL4 overexpression induced the activation of TGF-β/SMAD signaling pathway and triggered EMT in gastric cancer cells. TGF-β1 was identified as a direct target gene of SALL4. The results of chromatin immunoprecipitation study and luciferase reporter assay further confirmed that SALL4 bound to the promoter of TGF-b1 gene and activated its expression. TGF-β1 knockdown reversed SALL4-mediated promotion of gastric cancer cell motility, migration, and invasion, indicating that TGF-β1 acts as a downstream effector of SALL4. Furthermore, the expression of TGF-β1 was found to be closely associated with that of SALL4 in gastric cancer tissues., Conclusion: SALL4 promotes the metastasis of gastric cancer, at least partly, by directly activating TGF-β1, suggesting that SALL4 may serve as a new target for gastric cancer therapy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Aims: To study the diagnostic performance of the ratio of Duke jeopardy score (DJS) to the minimal lumen diameter (MLD) at coronary computed tomographic angiography (CCTA) and machine learning based CT-FFR for differentiating functionally significant from insignificant lesions, with reference to fractional flow reserve (FFR)., Methods and Results: Patients who underwent both coronary CTA and FFR measurement at invasive coronary angiography (ICA) within 2 weeks were retrospectively included in our study. CT-FFR, DJS/MLD CT ratio, along with other parameters, including minimal luminal area (MLA), MLD, lesion length (LL), diameter stenosis, area stenosis, plaque burden, and remodeling index of lesions, were recorded. Lesions with FFR ≤0.8 were considered to be functionally significant. One hundred and twenty-nine patients with 166 lesions were ultimately included for analysis. The LL, diameter stenosis, area stenosis, plaque burden, DJS and DJS/MLD CT ratio were all significantly longer or larger in the group of FFR ≤ 0.8 (p < 0.001 for all), while smaller MLA, MLD and CT-FFR value were also noted (p < 0.001 for all). CT-FFR and DJS/MLD CT ratio showed the largest AUC among all single parameters (AUC = 0.85 and AUC = 0.83, respectively; p < 0.001 for both) for diagnosing functionally significant stenosis. Combining CT-FFR and DJS/MLD CT ratio provided incremental value for discrimination between flow-limiting and non-flow-limiting coronary lesions and yielded the best diagnostic performance (accuracy of 83.7%)., Conclusions: The combination of ML-based CT-FFR and DJS/MLD CT allows accurate non-invasive discrimination between flow-limiting and non-flow-limiting coronary lesions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To assess pre-procedural plaque characteristics as determined by coronary CT angiography (CCTA) and their associations with late revascularization in symptomatic post-procedural patients., Methods: Symptomatic patients with pre-procedural CCTA were prospectively enrolled and referred for invasive coronary angiography (ICA). Plaque characterization was performed on the basis of baseline CCTA data. Multivariate logistic regression analysis with a stepwise selection method was performed to identify independent predictors of late revascularization., Results: Seventy-eight patients with 134 lesions were included. Late revascularization was performed to treat 15 ISRs and 22 de novo lesions. Lesions with late revascularization showed higher prevalence rates of low-attenuation plaque (LAP) and positive remodelling (PR) (70.3% vs. 23.7% and 86.5% vs. 30.9%; both p < 0.001) at baseline CCTA. However, the incidence of spotty calcification or napkin-ring sign (NRS) was not significantly different between the subgroups. According to ROC curve analysis, PR and LAP showed the largest AUC values for diagnosing lesions with late revascularization (AUC = 0.78 and 0.73, both p < 0.001). In multivariate analysis, LAP and PR (odds ratio = 6.30 and 13.94; both p < 0.05) were revealed to be independent predictors for late revascularization., Conclusions: LAP and PR observed by baseline CCTA independently predict late revascularization caused by ISR or progression of de novo lesions., Key Points: • LAP and PR observed by baseline CT are predictors of late revascularization. • NRS and spotty calcification are not associated with late revascularization. • CT plaque characterization is useful in identifying lesions at high risk of late revascularization.

Aims: To investigate the quantitative baseline CT plaque characterization of unrevascularized non-culprit intermediate coronary stenosis and its association with lesion volume progression and long-term prognosis., Methods: Patients with baseline coronary CT angiography (CCTA) and invasive coronary angiography (ICA) and at least one unrevascularized non-culprit intermediate coronary stenosis were prospectively enrolled for this study. All patients were followed up by a second CCTA at 1-year to 1.5-year interval. High-risk plaque features as well as other quantitative plaque measurements were recorded., Results: 140 patients with 165 unrevascularized non-culprit intermediate lesions were selected. Lesion volume progression was identified in 18 lesions (10.9%, 18/165) at follow-up CCTA and 15 patients experienced major adverse cardiac events (MACE) during a mean follow-up period of 51.5 months. Low attenuation plaque (LAP) was more frequently present in the lesion-progression subgroup and MACE subgroup (lesion-progression VS. non-lesion progression: 55.6% VS. 8.8% and MACE VS. MACE free: 40% VS. 12.8%, both p < 0.05), while other parameters showed no significant differences. Based on stepwise multivariable logistic regression analysis, LAP was an independent predictor (OR = 16.74, 95%CI = 5.02 to 55.84, p < 0.001) for lesion volume progression and MACE (OR = 4.25, 95%CI = 1.03 to 17.53, p = 0.046)., Conclusions: The presence of LAP of unrevascularized non-culprit intermediate stenosis is associated with lesion volume progression and an independent predictor for MACE occurrence., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To investigate the diagnostic performance of low dose stent imaging in patients with large (≥ 3 mm) and small (< 3 mm) calibre stents by third-generation dual-source CT., Methods: Symptomatic patients suspected of having in-stent restenosis (ISR) were prospectively enrolled. Coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) were performed within 1 month for correlation. Binary ISR was defined as an in-stent neointimal proliferation with diameter stenosis ≥ 50%. The radiation dose and image quality of CCTA were also assessed., Results: Sixty-nine patients with 140 stents were ultimately included for analysis. The mean total radiation dose of CCTA was 1.3 ± 0.72 mSv in all patients and 0.95 ± 0.17 mSv in patients with high pitch acquisition. The overall diagnostic accuracy of CCTA stent imaging of patient-based, lesion-based and stent-based analysis was 95.7%, 94.1% and 94.3%, respectively. Further, the diagnostic accuracy of CCTA in the small calibre stent group (diameter < 3 mm) was slightly lower than that of the large calibre stent group (diameter ≥ 3 mm) (88.5% versus 98.7%, p = 0.01)., Conclusions: Third-generation dual-source CT enables accurate diagnosis of coronary ISR of both large and small calibre stents. Low radiation dose could be achieved with preserved image quality., Key Points: • Third-generation DSCT enables accurate diagnosis of coronary ISR of all size stents. • Low radiation dose could be achieved with preserved image quality. • The diagnostic accuracy of CCTA of small calibre stents was 88.5%.

In this study, we established a rapid and efficient HPLC method to determine the accumulation of Huperzine A and Huperzine B in the fermentation broth of endophytic fungus Colletotrichum gloesporioides from Huperzia serrate. The chloroform extracts of fermentation broth were dissolved in methanol and filtered before injection for HPLC analysis. The analysis was performed on an Agilent Eclipse plus-C18 column (250 mm×4.6 mm, 5 μm) by isocratic elution. The mobile phase was 0.015 mol/L ammonium acetate-methanol (70:30, V/V), the flow rate was 1 mL/min and the detection wavelength was set at 308 nm. Huperzine A and Huperzine B could be well separated within 25 min. Good linearity of Huperzine A was found in the range of 1.50-48.00 μg/mL (r=0.999 5), and that of huperzine B was in 0.25-7.50 μg/mL (r=0.999 7). The average recoveries of Huperzine A and Huperzine B were 106.83% and 108.06%, respectively (RSD=3.34%, 3.60%). The results demonstrate that this method can detect the content of huperzine A and huperzine B in fermentation broth simply, rapidly, accurately and in good reproducibility. Under the optimized conditions, the accumulated content of huperzine A and huperzine B were measured from the sixth to the fifteenth day. Huperzine A and Huperzine B reached the highest (12.417 0 μg/mL and 4.660 3 μg/mL, respectively) at the fourteenth and eighth days. The analysis methodology could contribute to the future study of huperzine A and huperzine B biosynthesis in C. gloeosporioides, consequently facilitate the development of new drug resources.

Objectives: To study the diagnostic performance of the ratio between the Duke jeopardy score (DJS) and the minimal lumen diameter (MLD) (DJS/MLD CT ratio) as assessed by coronary computed tomographic angiography (CTA) for differentiating functionally significant from non-significant coronary artery stenoses, with reference to invasive fractional flow reserve (FFR)., Methods: Patients who underwent both coronary CTA and FFR measurement during invasive coronary angiography (ICA) within 2 weeks were retrospectively included in the study. Invasive FFR measurement was performed in patients with intermediate to severe coronary stenoseis. DJS/MLD CT ratio and anatomical parameters were recorded. Lesions with FFR ≤0.80 were considered to be functionally significant., Results: One hundred and sixty-one patients with 175 lesions were included into the analysis. Diameter stenosis in CT, area stenosis, plaque burden, lesion length (LL), ICA-based stenosis degree, DJS, LL/MLD 4 ratio, DJS/MLA ratio as well as DJS/MLD ratio were all significantly different between hemodynamically significant and non-significant lesions (p<0.05 for all). ROC curve analysis determined the optimal cut-off value for DJS/MLD CT ratio to be 1.96 (area under curve = 0.863, 95 % confidence interval = 0.803-0.910), yielding a high diagnostic accuracy (86.9%, 152/175)., Conclusions: In coronary artery stenoses detected by coronary CTA, the DJS/MLD ratio is able to predict hemodynamic relevance., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the morphological changes of coronary chronic total occlusion (CTO) as determined by coronary computed tomography angiography (CCTA) follow-up using semi-automated quantitative analysis., Materials and Methods: Thirty patients with 31 CTO lesions confirmed by invasive coronary angiography and baseline/follow-up CCTA were retrospectively included. CTOs were quantitatively analyzed by a semi-automated coronary plaque analysis software (Coronary Plaque Analysis, version 2.0, Siemens) after manually determining the lesion border. Recanalized lumen was defined as the linear-like enhanced opacity traversing the non-opacified occluded segment. Other parameters, such as total occlusion length, total occlusion volume, volume with low attenuation component (< 30 Hounsfield unit [HU]), volume with middle to high attenuation component (30-190 HU) as well as the calcification volume, were also recorded., Results: Recanalized lumen was found within 48.4% (15/31) occlusions on the follow-up CCTA, compared to 45.2% (14/31) occlusions on the baseline CCTA. Eleven of 14 lesions (78.6%) with CT-visible recanalized lumen within CTOs had a shorter occlusion length on follow-up compared to only 3 of 17 lesions (17.6%) without CT-visible recanalized lumen (odds ratio, 17.1, p < 0.001). The percentage of low attenuation component of occlusions was smaller on follow-up CCTA compared to baseline value (18.1 ± 20.1% vs. 22.6 ± 19.6%, p = 0.033)., Conclusion: Coronary computed tomography angiography enables non-invasive characterization of natural progression of untreated CTO lesions. Recanalized lumen within CTOs observed at baseline CCTA was associated with shortening of occlusion length on follow-up. Compared to their earlier stage, occlusions of later stage were presented with higher density of non-calcified components.

A novel series of benzodihydrofuran derivatives was developed as potent MEK inhibitors through scaffold hopping based on known clinical compounds. Further SAR exploration and optimization led to another benzofuran series with good oral bioavailability in rats. One of the compounds EBI-1051 (28d) demonstrated excellent in vivo efficacy in colo-205 tumor xenograft models in mouse and is suitable for pre-clinical development studies for the treatment of melanoma and MEK associated cancers. Compared to AZD6244, EBI-1051 showed superior potency in some cancer cell lines such as colon-205, A549 and MDA-MB-231., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A novel series of benzofuran derived EZH2 inhibitors were discovered through a scaffold hopping approach based on the clinical compound of EPZ-6438. Further rational structure-activity relationship exploration and optimization led to the discovery of more potent EZH2 inhibitors with oral bioavailability in mice and rats. A lead compound EBI-2511 (compound 34 ) demonstrated excellent in vivo efficacy in Pfeiffer tumor Xenograft models in mouse and is under preclinical development for the treatment of cancers associated with EZH2 mutations., Competing Interests: The authors declare no competing financial interest.

The strategy of Divide-and-Conquer (D&C) is one of the frequently used programming patterns to design efficient algorithms in computer science, which has been parallelized on shared memory systems and distributed memory systems. Tzeng and Owens specifically developed a generic paradigm for parallelizing D&C algorithms on modern Graphics Processing Units (GPUs). In this paper, by following the generic paradigm proposed by Tzeng and Owens, we provide a new and publicly available GPU implementation of the famous D&C algorithm, QuickHull, to give a sample and guide for parallelizing D&C algorithms on the GPU. The experimental results demonstrate the practicality of our sample GPU implementation. Our research objective in this paper is to present a sample GPU implementation of a classical D&C algorithm to help interested readers to develop their own efficient GPU implementations with fewer efforts.

Objectives: To assess the diagnostic performance of the calcification remodeling index (RI) as assessed by coronary computed tomography angiography (coronary CTA) to predict the presence of severe coronary stenosis in atherosclerotic coronary lesions with moderate to severe calcification., Methods: Patients who underwent coronary CTA and invasive coronary angiography (ICA) within one month and had moderately to severely calcified lesions as revealed by coronary CTA, were retrospectively included. The calcification RI was calculated as the ratio of the cross-sectional lumen area (with inclusion of calcium area) of the most severely calcified site to the proximal reference lumen area. Other parameters, such as the calcium volume, regional Agatston score, calcification length, involved calcium arc quadrants and CTA-assessed diameter stenosis, were also recorded. A multivariate model was used to identify the variables that predict the presence of severe coronary stenosis (diameter stenosis ≧ 70%) as determined by ICA., Results: 422 patients with 629 lesions were finally included in the study. Lesions with severe stenoses as determined by ICA tended to have larger calcium volumes, regional Agatston scores, CTA-assessed diameter stenoses, longer calcium length, more involved calcium arc quadrants and a significantly smaller calcification remodeling index. ROC curve analysis determined the best cutoff value of the calcification RI as 0.94 (AUC = 0.816, p < 0.001), which yielded highest diagnostic accuracy (83.3%, 524/629) to identify severe coronary stenosis. Among all parameters, calcification RI ≦0.94 is the strongest independent predictor (odds ratio: 17.5, p < 0.001) of severe coronary stenosis., Conclusions: With an optimalcut-off value of 0.94, calcification RI is the strongest independent predictor of severe coronary stenosis in calcified coronary atherosclerotic lesions., (Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the feasibility of calcification characterization by coronary computed tomography angiography (CCTA) to predict the use of rotational atherectomy (RA) for coronary intervention of lesions with moderate to severe calcification., Materials and Methods: Patients with calcified lesions treated by percutaneous coronary intervention (PCI) who underwent both CCTA and invasive coronary angiography were retrospectively included in this study. Calcification remodeling index was calculated as the ratio of the smallest vessel cross-sectional area of the lesion to the proximal reference luminal area. Other parameters such as calcium volume, regional Agatston score, calcification length, and involved calcium arc quadrant were also recorded., Results: A total of 223 patients with 241 calcified lesions were finally included. Lesions with RA tended to have larger calcium volume, higher regional Agatston score, more involved calcium arc quadrants, and significantly smaller calcification remodeling index than lesions without RA. Receiver operating characteristic curve analysis revealed that the best cutoff value of calcification remodeling index was 0.84 (area under curve = 0.847, p < 0.001). Calcification remodeling index ≤ 0.84 was the strongest independent predictor (odds ratio: 251.47, p < 0.001) for using RA., Conclusion: Calcification remodeling index was significantly correlated with the incidence of using RA to aid PCI. Calcification remodeling index ≤ 0.84 was the strongest independent predictor for using RA prior to stent implantation.

Objective: To study the predictive value of transluminal attenuation gradient (TAG) derived from diastolic phase of coronary computed tomography angiography (CCTA) for identifying systolic compression of myocardial bridge (MB)., Materials and Methods: Consecutive patients diagnosed with MB based on CCTA findings and without obstructive coronary artery disease were retrospectively enrolled. In total, 143 patients with 144 MBs were included in the study. Patients were classified into three groups: without systolic compression, with systolic compression < 50%, and with systolic compression ≥ 50%. TAG was defined as the linear regression coefficient between intraluminal attenuation in Hounsfield units (HU) and length from the vessel ostium. Other indices such as the length and depth of the MB were also recorded., Results: TAG was the lowest in MB patients with systolic compression ≥ 50% (-19.9 ± 8.7 HU/10 mm). Receiver operating characteristic curve analysis was performed to determine the optimal cutoff values for identifying systolic compression ≥ 50%. The result indicated an optimal cutoff value of TAG as -18.8 HU/10 mm (area under curve = 0.778, p < 0.001), which yielded higher sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy (54.1, 80.5, 72.8, and 75.0%, respectively). In addition, the TAG of MB with diastolic compression was significantly lower than the TAG of MB without diastolic compression (-21.4 ± 4.8 HU/10 mm vs. -12.7 ± 8 HU/10 mm, p < 0.001)., Conclusion: TAG was a better predictor of MB with systolic compression ≥ 50%, compared to the length or depth of the MB. The TAG of MB with persistent diastolic compression was significantly lower than the TAG without diastolic compression.

Objectives: To study the diagnostic value of transluminal attenuation gradient (TAG) measured by coronary computed tomography angiography (CCTA) for identifying relevant dynamic compression of myocardial bridge (MB)., Methods: Patients with confirmed MB who underwent both CCTA and ICA within one month were retrospectively included. TAG was defined as the linear regression coefficient between luminal attenuation and distance. The TAG of MB vessel, length and depth of MB were measured and correlated with the presence and degree of dynamic compression observed at ICA. Systolic compression ≧50 % was considered significant., Results: 302 patients with confirmed MB lesions were included. TAG was lowest (-17.4 ± 6.7 HU/10 mm) in patients with significant dynamic compression and highest in patients without MB compression (-9.5 ± 4.3 HU/10 mm, p < 0.001). Linear correlation revealed relation between the percentage of systolic compression and TAG (Pearson correlation, r = -0.52, p < 0.001) and no significant relation between the percentage of systolic compression and MB depth or length. ROC curve analysis determined the best cut-off value of TAG as -14.8HU/10 mm (area under curve = 0.813, 95 % confidence interval = 0.764-0.855, p < 0.001), which yielded high diagnostic accuracy (82.1 %, 248/302)., Conclusions: The degree of ICA-assessed systolic compression of MB significantly correlates with TAG but not MB depth or length., Key Points: • TAG is associated with the extent of dynamic compression of MB. • TAG is superior to depth and length for identifying dynamic compression. • Cut-off value of TAG as -14.8HU/10 mm yielded high predictive value.

Rationale: Dieulafoy disease is characterized by the presence of dilated, tortuous arteries that project into the submucosa of the gastrointestinal tract and less frequently the bronchus., Patient Concerns: Dieulafoy disease of the trachea has not been previously described. A 60-year-old woman with recurrent episodes of massive hemoptysis., Diagnoses: Dieulafoy disease of the trachea., Interventions: Selective arterial embolization was undertaken., Outcomes: The intervention was successful and no fresh episode of acute hemoptysis was observed., Lessons: Apart from the bronchus, vascular anomaly may also be present in the trachea in Dieulafoy disease., Competing Interests: The authors report no conflicts of interest.

A novel series of pyrazolo[3,4-c]isoquinoline derivatives was discovered as B-Raf(V600E) inhibitors through scaffold hopping based on a literature lead PLX4720. Further SAR exploration and optimization led to the discovery of potent B-Raf(V600E) inhibitors with good oral bioavailability in rats and dogs. One of the compounds EBI-907 (13g) demonstrated excellent in vivo efficacy in B-Raf(V600E) dependent Colo-205 tumor xenograft models in mouse and is under preclinical studies for the treatment of melanoma and B-Raf(V600E) associated cancers., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The oncogenic mutation of BRAF(V600E) has been found in approximately 8% of all human cancers, including more than 60% of melanoma and 10% of colorectal cancers. The clinical proof of concept in treating BRAF(V600E)-driving melanoma patients with the BRAF inhibitors has been well established. We have sought to identify and develop novel BRAF(V600E) inhibitors with more favorable profiles. Our chemistry effort has led to the discovery of EBI-907 as a novel BRAF(V600E) inhibitor with potent anti-tumor activity in vitro and in vivo. In a LanthaScreen BRAF(V600E) kinase assay, EBI-907 showed an IC50 of 4.8 nM, which is >10 -fold more potent than Vemurafenib (IC50 = 58.5 nM). In addition, EBI-907 showed a broader kinase selectivity profile, with potent activity against a number of important oncogenic kinases including FGFR1-3, RET, c-Kit, and PDGFRb. Concomitant with such properties, EBI-907 exhibits potent and selective cytotoxicity against a broader range of BRAF(V600E)-dependent cell lines including certain colorectal cancer cell lines with innate resistance to Vemurafenib. In BRAF(V600E)-dependent human Colo-205 and A375 tumor xenograft mouse models, EBI-907 caused a marked tumor regression in a dose-dependent manner, with superior efficacy to Vemurafenib. Our results also showed that combination with EGFR or MEK inhibitor enhanced the potency of EBI-907 in cell lines with innate or acquired resistance to BRAF inhibition alone. Our findings present EBI-907 as a potent and promising BRAF inhibitor, which might be useful in broader indications.

Background: Surveys that describe the utilization of cardiac CT are available for the United States, Germany, and Taiwan, but not mainland China., Objectives: To analyze the clinical utilization of cardiac CT in mainland China., Methods: A 25-item questionnaire was created and 240 tertiary hospitals were randomly selected to participate. Survey data were collected and confirmed by email as well as phone interviews., Results: In total, 237 (99%) hospitals consented to this survey, but 85 were excluded because of lack of cardiac CT patient volume or advanced technology. Finally, 152 (64%) questionnaires were available for analysis. Median patient volume was 1,037 patients (range: 150-8,072) annually. The most common clinical indications for coronary CT angiography were exclusion of coronary artery disease in patients with low to intermediate pretest likelihood, asymptomatic individuals with cardiovascular risk factors, and follow-up after coronary bypass grafting. The median heart rate threshold for beta blocker administration was >70 beats/min; most centers (86%) used sublingual nitroglycerin. Prospectively ECG triggered acquisition was the predominant technique in 44% of hospitals. Most (59%) providers adjusted the tube current to the body mass, but few (16%) adjusted the contrast injection rate. Per case, the mean examination duration was 14.2 min; post-processing time 13.6 min; and reporting time 18.0 min., Conclusions: Cardiac CT is widely established in clinical practice in mainland China but there is a need for more uniform standards regarding performance and clinical utilization., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

To study the feasibility of evaluation of collateral channel (CC) classification in patients with coronary chronic total occlusion (CTO) by coronary computed tomography angiography (CTA) with reference to invasive coronary angiography (ICA) validation. We retrospectively included CTO-confirmed patients who underwent both coronary CTA and ICA within 1 month. Collaterals were classified by coronary CTA into three types: CC0, no continuous connection between donor and recipient vessel; CC1, continuous thread-like connection; CC2, continuous, small sidebranch-like connection. With comparison to ICA results, the diagnostic performance of CTA-based CC classification was further assessed. 118 patients with 132 ICA-confirmed CTO lesions were included. Compared to ICA-based evaluation, good overall diagnostic accuracy of CT-based CC classification was observed (78%, 103/132, κ = 0.674, p < 0.001). Coronary CTA was also revealed to be accurate in terms of assessment of collateral tortuosity (76.2%, 77/101) and identification of principal donor vessel (70.3%, 71/101). Impaired diagnostic performance was observed in sub-group of septal collaterals as the accuracy for evaluation of the above parameters was 60.6% (20/33), 72.7% (24/33) and 45.5% (15/33) respectively. Non-invasive evaluation of CC classification by coronary CTA correlates well with ICA findings. In addition, the septal collaterals are much less visible at coronary CTA than epicardial collaterals.

Objectives: To investigate the morphologic characteristics of early and late stages of chronic total coronary artery occlusions (CTO) in coronary computed tomography angiography (coronary CTA)., Methods: We retrospectively analyzed patients who underwent coronary CTA and invasive coronary angiography and had at least one CTO with known duration. The following parameters were obtained in coronary CTA: calcification of the occluded segment; stump morphology; lesion length; remodeling index; presence of intra-occlusion linear contrast enhancement; and density of non-calcified CTO components. CT parameters were compared between patients with early (duration ≤ 12 months) and late (duration > 12 months) stage CTO., Results: One-hundred and twelve patients with 124 chronically occluded coronary arteries were analyzed. Fifty nine patients had early stage CTOs (62 lesions) and 53 patients had late stage CTOs (62 lesions). Calcification was more severe in late-stage versus early CTOs (Agatston score: early stage, 27.4 ± 46.7 vs. late stage, 58.3 ± 112.4; p = 0.049). Remodeling index was lower in late-stage CTOs (early stage, 0.96 ± 0.2 vs. late stage, 0.88 ± 0.22; p = 0.034). In patients with late stage CTO, the presence of intra-occlusion linear enhancement was more likely (45.2% vs 14.5%, p < 0.001), and the density of non-calcified components was significantly higher (85.4 ± 27.2 HU vs. 65.7 ± 30.1 HU, p < 0.001). Stump morphology was not different between the two groups., Conclusions: Coronary CTA reveals differences between chronic total coronary occlusions of longer and shorter duration. A long duration is associated with focal calcification and negative remodeling, as well as intra-occlusion enhancement and a higher density of non-calcified components., (Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: The J-CTO score is based on invasive angiography, combines several parameters of chronic total coronary occlusions (CTO), and is well established to predict the likelihood of success of percutaneous recanalization. The purpose of this study was to evaluate and validate a J-CTOCT score derived from coronary computed tomography angiography (coronary CTA)., Methods: Between April 2011 and December 2014, 159 consecutive patients were retrospectively included. All had at least one CTO in invasive angiography, had coronary CTA performed at an interval of no more than one week from invasive angiography, and had an attempt at percutaneous coronary intervention (PCI) following coronary CTA In parallel to the angiographic J-CTO score, the J-CTOCT score was determined by awarding one point each for a blunt vessel stump, bending > 45°, occlusion length ≥ 20 mm, presence of calcium covering > 50% of any vessel cross-section within the occlusion, or a previously failed attempt at PCI. a. Both scores were compared regarding their ability to predict successful recanalization., Results: A total of 171 CTO lesions were analyzed. Intraobserver (k = 0.814, p < 0.001) and interobserver agreement (k = 0.771, p < 0.001) for calculation of the J-CTOCT score were close. The mean occlusion length measured by coronary CTA was significantly shorter than in invasive angiography (27.6 ± 14.8 mm vs. 37.2 ± 18.8 mm, p < 0.001). The J-CTOCT score (mean: 1.9 ± 1.4) correlated closely to the angiographic J-CTO score (mean: 1.8 ± 1.3, r = 0.856, p < 0.001), and in 122/171 lesions (71%), the scores were identical. Both J-CTOCT score (area under curve: 0.882, p < 0.001) and angiographic J-CTO score (area under curve: 0.868, p < 0.001) yielded similarly high predictive value for successful guidewire crossing within 30 min (p = 0.496)., Conclusions: While the length of coronary occlusions in coronary CTA is significantly shorter than in invasive angiography, a J-CTOCT score determined by coronary CTA closely correlates to the angiographic J-CTO score. ., (Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

The goal of this study was to evaluate the diagnostic accuracy of transmural perfusion gradient (TPG) and transmural perfusion gradient reserve (TPGR) with 3.0 T cardiac magnetic resonance (CMR) against invasively determined fractional flow reserve (FFR) to detect coronary artery stenosis. Quantitative analysis of myocardial perfusion with CMR to diagnosis coronary artery disease (CAD) has been widely accepted. However, traditional transmural myocardial perfusion analysis with CMR neglects that endocardium is more vulnerable to ischemia than epicardium. TPG and TPGR can take the inhomogenous perfusion impairment into account and be more sensitive and specific for diagnosis of CAD. In this study, 71 patients (57 men, age 60.1 ± 6.4 years) with known or suspected CAD referred for invasive angiography study underwent rest and adenosine-induced stress CMR perfusion imaging scan. FFR was attempted to be measured in all major epicardial coronary arteries. FFR ≤0.75 was regarded to indicate a hemodynamic significant coronary lesion. A TPG ≤0.85 predicted significant CAD with sensitivity and specificity of 74.55% and 83.65%, respectively. Sensitivity and specificity of TPGR ≤0.81 were 90.91% and 89.94%, respectively. Area under the receiver-operating curve to detect FFR ≤0.75 was 0.86 for TPG and 0.95 for TPGR. TPGR yielded significantly better sensitivity and specificity for diagnosis of CAD than traditional myocardial blood flow, myocardial perfusion reserve, and TPG (p < 0.0001). In conclusion, TPG and TPGR analyses with MRI are capable of detecting hemodynamic stenosis of coronary artery and superior to traditional myocardial perfusion analysis. Furthermore, TPGR appears to be superior to TPG in the diagnosis of coronary artery stenosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To study the imaging features of coronary competitive reverse flow and incidence of a "reverse attenuation gradient" in coronary CT angiography (CTA) with correlation to invasive coronary angiography (ICA)., Methods: Patients who had undergone coronary CTA and ICA within 2 weeks were retrospectively identified in our database and reviewed. All cases with ICA-confirmed competitive reverse flow or chronic total occlusions (CTOs) were included for further analysis. The "reverse attenuation gradient sign" was defined as a reverse intraluminal opacification gradient of vessels which showed higher opacification in more distal compared with proximal segments. ICA findings were recorded and served as the reference to identify the clinical implications of this sign., Results: In total, 134 patients (mean age, 68.1 ± 11.3 years; range, 38-90 years; 104 men) were included in our study. ICA revealed 11 cases of coronary competitive reverse flow and 123 cases of CTO. A reverse attenuation gradient sign was present in 9 of 11 patients (82%) with coronary competitive reverse flow and 72 of 123 (59%) chronically occluded coronary arteries. Myocardial bridges, distal collateral filling, as well as direct visualization of collateral connection were all more frequent in cases with coronary competitive reverse flow group compared with cases with a CTO., Conclusions: The reverse attenuation gradient sign distal to an upstream coronary severe stenosis indicates the presence of competitive collateral flow. Coronary CTA is able to correctly detect coronary competitive collateral flow and differentiate it from CTOs., (Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the incidence and diagnostic performance of reverse attenuation gradient (RAG) sign in patients with coronary stent occlusion., Methods: We retrospectively included patients with suspected restenosis who underwent both coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) within 2 weeks. Stent occlusion at CCTA was defined as (1) complete contrast filling defect of large calibre stents (at least 3 mm), or (2) presence of RAG sign in patients with small calibre stents (less than 3 mm) or (3) presence of RAG sign in patients with non-diagnostic image quality of stents. The diagnostic performance of RAG sign was further assessed by comparison to ICA results., Results: A total of 162 patients with 231 implanted stents were included. ICA confirmed stent occlusion in 59 patients (99 stents). RAG sign was present in 59.3% (35/59) of all stent occlusions. As shown by patient-based analysis, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of our diagnostic criteria for detection of stent occlusion were 79.7% (47/59), 100% (103/103), 100% (47/47) and 89.6% (103/115) respectively. Superior diagnostic performance was confirmed by receiver operating characteristic (ROC) analysis with an area under the curve of 0.898., Conclusions: RAG sign observed at CCTA in patients with coronary stenting represents reverse collateral flow distal to stents and is highly specific to indicate stent occlusion., Key Points: • RAG sign in patients with previous stents represents retrograde collateral flow. • RAG sign in patients with previous stents indicates stent occlusion. • RAG sign improves detection of stent occlusion in small calibre stents.

Objectives: To evaluate the incidence of coronary in-stent restenosis (ISR) and neointimal proliferation by coronary CT angiography (CCTA) at 1-year follow-up in asymptomatic patients., Methods: 234 patients (mean age: 67 ± 10.2 years, range 39-88 years, 180 males and 54 females) with 379 stents were prospectively enrolled in this study. Binary ISR was classified by CCTA into 4 types using Mehran classification. Neointimal proliferation was similarly classified into focal and diffuse types. All patients with CCTA-revealed ISR or neointimal proliferation underwent further invasive coronary angiography (ICA) for validation. Fisher's exact test was used for comparison., Results: ICA revealed patent stents with neointimal proliferation in 39 patients (16.7%, 39/234) and binary ISR in 23 patients (9.8%, 23/234). Lesion-based analysis showed 12 type I ISR lesions, 4 type II ISR lesions, 1 type III ISR lesion and 7 type IV ISR lesions. Among cases with neointimal proliferation, 27 lesions were classified as focal type whereas 13 lesions were classified as diffuse type. Patients with diabetes mellitus were associated with higher incidence of CCTA-revealed neointimal proliferation (21/77 vs. 18/157, p=0.002) as well as ISR (12/77 vs. 11/157, p=0.038), compared to patients without diabetes. CCTA was found to have good diagnostic performance for neointimal proliferation and ISR detection as well as classification, with an overall accuracy of 84.4% (54/64)., Conclusions: Silent ISR as well as neointimal proliferation is not uncommon findings in asymptomatic post-stenting patients at 1-year interval, as revealed by CCTA. Patients with diabetes are prone to have higher incidence of neointimal proliferation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The authors examine the popularity of boys' given names in Beijing before and after the onset of the Cultural Revolution to clarify how exogenous and endogenous factors interact to shape fashion. Whereas recent work in the sociology of culture emphasizes the importance of endogenous processes in explaining fashion, their analysis demonstrates two ways in which politics shaped cultural expression during the Cultural Revolution: by promoting forms of expression reflecting prevailing political ideology and by limiting individuals' willingness to act differently. As argued by Lieberson and developed further in this article, the second condition is important because endogenous fashion cycles require a critical mass of individuals who seek to differentiate themselves from common practice. Exogenous factors can influence the operation of the endogenous factors. The authors discuss the implications of their study for understanding the nature of conformity under authoritarian regimes and social conditions supporting individual expression.

Purpose: To assess the correlation between the filling pattern of distal coronary vessels in patients with chronic total occlusion (CTO) observed at coronary computed tomographic (CT) angiography and the extent of downstream myocardial infarction (MI)., Materials and Methods: All patients gave written informed consent, and the institutional review board approved the study protocol. A total of 97 patients (mean age, 68.5 years ± 11.5 [standard deviation]; age range, 38-87 years; 77 men, 20 women) with 106 CTOs were prospectively enrolled. Distal filling of the epicardial segment was semiquantitatively classified by using a four-point scale according to patterns at coronary CT angiography (0 = absence of distal filling; 1 = partial distal filling, with a length less than one-third of the segment; 2 = partial distal filling, with a length between one-third and two-thirds of the segment; 3 = complete or partial distal filling, with a length longer than two-thirds of the segment). A coronary CT angiography score of 3 was considered indicative of well-developed collaterals. Downstream MI transmurality and wall motion abnormality were verified semiquantitatively with cardiac magnetic resonance imaging. Mann-Whitney U test and t test were used for comparison., Results: Coronary CT angiography revealed three lesions with a score of 0, 21 with a score of 1, 35 with a score of 2, and 47 with a score of 3. The non-MI subgroup was associated with higher collateral grading at CT angiography, whereas the transmural MI subgroup was associated with lower collateral grading (P = .005). When compared with the poorly developed (score 0-2) collaterals group, the well-developed (score 3) collateral group correlated to a lower summed transmurality score (P < .001) and a lower summed regional wall motion abnormality score (P = .029)., Conclusion: The presence of well-developed distal collaterals as revealed by coronary CT angiography in patients with CTO lesions correlates with the lower frequency and extent of downstream MI.

Purpose: To study the diagnostic performance of the ratio of lesion length (LL) to the fourth power of minimal lumen diameter (MLD) (MLD(4)) at coronary computed tomographic (CT) angiography for differentiating between hemodynamically significant and nonsignificant lesions, with correlation with fractional flow reserve (FFR)., Materials and Methods: This retrospective study had institutional review board approval, and the need to obtain informed consent was waived. Sixty-one patients (mean age, 65.3 years ± 8.8 [standard deviation]; range, 43-82 years; 43 men and 18 women; P = .019 for age) who underwent both coronary CT angiography and FFR measurement at conventional coronary angiography within 2 weeks were retrospectively included in this study. LL/MLD(4) ratio, along with other parameters, including minimal luminal area (MLA), stenosis diameter, stenosis area, plaque burden, remodeling index, and Agatston score of lesions, were recorded. Lesions with FFRs of less than 0.8 were considered to be functionally significant. Univariate and multivariate statistical tests were performed to identify variables associated with hemodynamically significant lesions., Results: Sixty-one patients with 85 lesions were ultimately included for analysis. LL, stenosis diameter, stenosis area, and plaque burden were longer or larger in the group with FFRs of less than 0.8 (P < .001 for all), while smaller MLA and MLD were also noted (P < .001). Mean LL/MLD(4) ratio was significantly larger in the group with FFRs of less than 0.8 than in the group with FFRs of 0.8 or greater (9.7 ± 7.5 vs 3.1 ± 3.6, P < .001). Rest myocardial perfusion defect was recorded in five lesions with FFRs of less than 0.8 (P = .006). LL/MLD(4) ratio proved at multivariate analysis to be the only independent predictor of hemodynamically significant stenosis (odds ratio = 1.44; P = .043). When 3.86 was used as the cutoff value for LL/MLD(4) ratio, the sensitivity and specificity for diagnosing hemodynamically significant lesions were 82.9% (29 of 35) and 82% (41 of 50), respectively., Conclusion: The LL/MLD(4) ratio, as characterized by using coronary CT angiography, correlates inversely with FFR measurements and is associated with the hemodynamic status of coronary stenoses. Online supplemental material is available for this article., (© RSNA, 2013.)

Purpose: To study the clinical importance of the reverse attenuation gradient (RAG) sign in patients with occlusive coronary artery disease observed with coronary computed tomographic (CT) angiography., Materials and Methods: All patients provided written informed consent, and the institutional review board committee approved the study protocol. Eighty consecutive patients (mean age, 67.1 years ± 12.1 [standard deviation]; range, 35-87 years; 62 men [mean age, 65.8 years ± 12.5; range, 35-86 years] and 18 women [mean age, 71.7 years ± 9.3; range, 58-87 years]) were enrolled prospectively in this study. The RAG sign was defined as the reverse intraluminal opacification gradient of vessels distal to the occlusive lesions, which has lower attenuation in the proximal segment and gradually increased attenuation along the vessel. Other parameters, such as lesion length and bridging collateral vessels visible at coronary CT angiography, were recorded. Mann-Whitney Wilcoxon and Fisher exact tests were used for comparison., Results: There were 94 occlusive lesions. Invasive coronary angiography was used to confirm 49 chronic total occlusions (CTOs) and 45 subtotal occlusions (SOs). The CTO group had the RAG sign significantly more frequently than did the SO group (65% [32 of 49] vs 7% [three of 45]; P < .001). Similarly, significant difference of measurements of the attenuation gradient (5.1 HU/10 mm ± 13.4 vs -13.4 HU/10 mm ± 8.7; P < .001) and lesion length (23.6 mm ± 22.7 vs 6 mm ± 3; P < .001) was noted between the groups. Bridging collateral vessels were present in only four cases of CTO at coronary CT angiography. All segments with RAG at coronary CT angiography were shown by means of invasive coronary angiography to be supplied by retrograde collateral vessels. When a combination of all those parameters was used for diagnosis of CTO, sensitivity and specificity were 90% (44 of 49) and 93% (42 of 45), respectively., Conclusion: The RAG sign represents the retrograde collateral flow distal to an occlusive lesion. This sign is highly specific for CTO and helps to differentiate CTO from SO.

Purpose: To evaluate the presence of linear intrathrombus enhancement in coronary total occlusion (CTO) lesions observed at coronary computed tomographic (CT) angiography and its correlation with the outcome of percutaneous coronary intervention (PCI)., Materials and Methods: All patients gave written informed consent, and the study protocol was approved by the hospital ethics committee. Consecutive patients with CTO confirmed at initial conventional coronary angiography were prospectively chosen to undergo a coronary CT angiography examination prior to their staged PCI. Linear intrathrombus enhancement was defined as a linear area of enhanced opacity traversing the nonopacified occluded segment with attenuation higher than 120 HU. Angiographic features, including lesion length, linear intrathrombus enhancement length, and calcification score, were measured at coronary CT angiography. Univariate and multivariate statistical tests were performed to identify variables associated with successful PCI., Results: Eighty patients with 88 CTO lesions were included in this study. Fifty-one lesions were successfully recanalized at PCI. Lesion length was longer in the PCI failure group (P = .043). Linear intrathrombus enhancement was observed in 30 (59%) of the 51 lesions successfully treated with PCI. However, linear enhancement was found in seven (19%) of 37 patients with failed PCI (P < .001 as compared with patients with successful PCI). Tortuous course was revealed to be the only angiographic parameter associated with unfavorable PCI outcome (P = .008). The presence of linear intrathrombus enhancement proved at multivariate analysis to be the only independent predictor of PCI success (odds ratio: 4.926; 95% confidence interval: 1.646, 14.74; P = .004)., Conclusion: The presence of coronary CT angiography-visible linear intrathrombus enhancement within the occluded segment predicts better outcome of PCI in CTOs.

Objectives: To evaluate the diagnostic accuracy of Mehran's in-stent restenosis (ISR) classification by coronary computed angiography (CCTA), with reference to invasive coronary angiography (ICA)., Methods: Consecutive symptomatic patients, who had clinically suspected ISR and implanted stent diameter ≥ 3 mm, were prospectively enrolled in our study. Mehran's classification was employed by CCTA and ICA to classify ISR lesions into four subtypes: focal, diffuse intrastent, diffuse proliferative and total occlusion. CCTA and ICA measurement of lesion length was further compared., Results: Sixty-one patients with 101 implanted stents were included in our study. The overall sensitivity, specificity, PPV and NPV of CCTA diagnosis of binary ISR, as shown by patient-based analysis (n = 61), were 100 % (49/49), 75 % (8/12), 92.45 % (49/53) and 100 % (8/8) respectively. Mehran's classification of CCTA correlated well with ICA findings. The diagnostic accuracy of CCTA for class I, class II, class III and class IV lesions was 92.5 %, 91.67 %, 100 % and 100 % respectively. Lesion length was assessed to be significantly longer with CCTA than with ICA (11.03 ± 5.89 mm versus 8.56 ± 4.99 mm, P < 0.001)., Conclusions: Angiographic patterns of in-stent restenosis can be accurately classified by coronary computed angiography. The lesion length measured by CCTA is longer than that assessed by invasive coronary angiography.

Objectives: To study the diagnostic performance of computed tomography (CT) quantification of minimal lumen area (MLA) based on multiple factors (image quality, calcification and lesion locations), with reference to intravascular ultrasound (IVUS)., Methods: Consecutive clinically ordered patients were prospectively enrolled in our study. CT quantification of MLA was manually measured on cross-sectional view and further compared with IVUS findings. A significant lesion was defined as ≤6 mm2 MLA for the left main (LM) coronary artery and a ≤4 mm2 MLA for other epicardial vessels., Results: Non-calcified lesions had good correlation between CT and IVUS (r=0.96) and the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 85% (51/60), 93.94% (31/33), 96.23% (51/53) and 77.5% (31/40) respectively. Decreased correlation (r=0.814) lower specificity (23.81% (5/21)) and positive predictive value (60.98% (25/41)) were observed in calcified subgroup. Artifact-absent lesions demonstrated excellent correlation (r=0.967) and the sensitivity, specificity, PPV and NPV were 96% (48/50), 93.94% (31/33), 96% (48/50) and 93.94% (31/33) respectively. Impaired correlation (r=0.584) was noted in artifact-present lesions and the sensitivity, specificity, PPV and NPV were 80% (28/35), 23.81% (5/21), 63.64% (28/44) and 41.67% (5/12) respectively. Excellent correlation between CT and IVUS was noted in proximal epicardial vessels (r=0.908) and the sensitivity, specificity, PPV and NPV were 92.31% (36/39), 78.13% (25/32), 83.72% (36/43) and 89.29% (25/28) respectively. Middle right coronary artery lesions showed non-significant correlation (r=0.54, p=0.055)., Conclusions: CT quantification of MLA can only be accurately achieved in non-calcified lesions with absence of artifact. Diagnostic performance is impaired in calcified lesions., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

How the state of spindle microtubule capture at the kinetochore is translated into mitotic checkpoint signaling remains largely unknown. In this paper, we demonstrate that the kinetochore-associated mitotic kinase BubR1 phosphorylates itself in human cells and that this autophosphorylation is dependent on its binding partner, the kinetochore motor CENP-E. This CENP-E-dependent BubR1 autophosphorylation at unattached kinetochores is important for a full-strength mitotic checkpoint to prevent single chromosome loss. Replacing endogenous BubR1 with a nonphosphorylatable BubR1 mutant, as well as depletion of CENP-E, the BubR1 kinase activator, results in metaphase chromosome misalignment and a decrease of Aurora B-mediated Ndc80 phosphorylation at kinetochores. Furthermore, expressing a phosphomimetic BubR1 mutant substantially reduces the incidence of polar chromosomes in CENP-E-depleted cells. Thus, the state of CENP-E-dependent BubR1 autophosphorylation in response to spindle microtubule capture by CENP-E is important for kinetochore function in achieving accurate chromosome segregation.

The diagnostic performance of in-stent restenosis (ISR) by 64-slice multidetector CT coronary angiography (CTCA) has been reported to be influenced by multiple factors. We evaluated individual factors (stent diameter, material and strut thickness) and therefore determined the proper population for follow-up by using this modality. A total of 171 stents were evaluated in 83 consecutive patients with stents imaged with CTCA and conventional coronary angiography. The stent diameter ranged from 2.25 mm to 4.5 mm. 2 models of stainless steel (Taxus Liberte (Boston Scientific, US), 56 stents and Cypher Select (Cordis, US), 34 stents) and 2 models of cobalt alloy (Endeavor (Medtronic, US), 33 stents and Firebird2 (MicroPort, China), 48 stents) were included. By comparing to conventional coronary angiography, the image quality and diagnostic accuracy for ISR were evaluated. The image quality of Taxus, Endeavor and Firebird are markedly better than Cypher in large caliber group (≧3.0 mm) (P < 0.001). Except for Cypher, all other stents with diameter ≧3.0 mm showed excellent diagnostic accuracy (sensitivity 100%, specificity 94.4-96% whereas stents with diameter <3.0 mm had poor diagnostic accuracy (sensitivity 100%, specificity 33.3-70%). Cypher is the stent with thickest strut in our study, and showed reduced image quality and diagnostic accuracy in all stent size, due to large number of unassessable stents. Among 16 binary ISR, 12 lesions were correctly diagnosed by CTCA while the other 4 lesions were unassessable. The main reason for low specificity in small caliber group is the large number of unassessable stents. CTCA has high diagnostic accuracy to identify ISR in selected stents with a diameter of ≧3.0 mm.

Proper bipolar attachment of sister kinetochores to the mitotic spindle is critical for accurate chromosome segregation in mitosis. Here we show an essential role of the formin mDia3 in achieving metaphase chromosome alignment. This function is independent of mDia3 actin nucleation activity, but is attributable to EB1-binding by mDia3. Furthermore, the microtubule binding FH2 domain of mDia3 is phosphorylated by Aurora B kinase in vitro, and cells expressing the nonphosphorylatable mDia3 mutant cannot position chromosomes at the metaphase plate. Purified recombinant mDia3 phosphorylated by Aurora B exhibits reduced ability to bind microtubules and stabilize microtubules against cold-induced disassembly in vitro. Cells expressing the phosphomimetic mDia3 mutant do not form stable kinetochore microtubule fibers; despite they are able to congress chromosomes to the metaphase plate. These findings reveal a key role for mDia3 and its regulation by Aurora B phosphorylation in achieving proper stable kinetochore microtubule attachment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The COOH terminal of pthA encoding three nuclear localizing signals (NLS) was amplified by polymerase chain reaction (PCR) from the plasmid of Xanthomonas axonopodis pv. citri, the pathogen of citrus canker disease. Then the sense and antisense strands of the nls were cloned into pBI121 vector. pthA-nls driven by the CaMV35 s promoter was transferred into sweet orange via Agrobacterium -mediated transformation. Successful integration was confirmed by PCR and Southern blotting, and 12 sense-nls (nls (+)) and 9 antisense-nls (nls (-)) transgenic clones were obtained. The expression of nls fragment was analyzed by RT-PCR, Real time q-PCR and Western blotting, in which the specific NLS protein was detected only in nls (+) transgenic clones. In an in vitro assay, when pin-puncture inoculation was performed with 2.5 × 10(7) cfu/ml of bacterial solution, the nls (+) transgenic clones showed no typical lesion development, while typical symptoms were observed in the wild types and the nls (-) transgenic clones. In vivo assay results indicated that the nls (+) transgenic clones showed less disease incidence, in comparison with the wild types and the nls (-) transgenic clones, when pin-puncture inoculation was performed with 10(4)-10(5) cfu/ml. The minimum disease incidence was 23.3% for 'Sucarri' sweet orange and 33.3% for 'Bingtang' sweet orange. When 10(4)-10(7) cfu/ml of pathogen was spray inoculated, the nls (+) transgenic clones did not show any symptom, and even the concentration raised to 10(9) cfu/ml, the disease incidence was 20-80%, while the wild types and the nls (-) transgenic clones had 100% disease development with whatever concentration of inoculum. Two transgenic clones were confirmed to be resistant to citrus canker disease in the repeated inoculation. The results suggested that the transformation of nls sense strands may offer an effective way to acquire resistance to citrus canker disease.

The majority of colorectal tumors are aneuploid because of the underlying chromosome instability (CIN) phenotype, in which a defective mitotic checkpoint is implicated. Adenomatous polyposis coli (APC), a tumor suppressor gene that is commonly mutated in colon cancers, has been suggested in causing CIN; however, the molecular mechanism remains unresolved. In this study, we report an interaction of tumor-associated N-terminal APC fragments (N-APC) with Mad2, an essential mitotic checkpoint protein, providing a direct molecular support for linking APC mutations to the generation of CIN. N-APC interacts with Mad2 in Xenopus egg extracts, colon cancer cells, and in vitro with purified components. The interaction between N-APC and Mad2 decreases the soluble pool of Mad2, which is essential for Mad2 cycling and releasing from unattached kinetochores to produce a diffusible |P;wait anaphase|P' signal. Addition of such an N-APC mutant of egg extracts inactivates the mitotic checkpoint. Expressing a tumor-associated N-APC mutant in mammalian cells with an intact mitotic checkpoint produces premature anaphase onset with missegregated chromosomes.

Cardiac-specific deletion of the receptor IA of bone morphogenetic protein (BMP) (ALK3) by Cre recombinase driven under the [alpha]-MHC promoter is lethal in mid-gestation with defects in the interventricular septum [ventricular septum defect (VSD)]. Analysis of expression of the ALK3 downstream genes is important to identify the signaling pathway for interventricular septum development. The mRNA expression level of a control group was compared with that of a test group. ALK3 downstream genes were screened using polymerase chain reaction (PCR)-select cDNA subtraction and microarray. It was found that the mice with an ALK3 knockout gene produced a VSD. The expression of some genes such as platelet-activating factor acetylhydrolase (PAF) and Pax-8 was down-regulated in the test group. Pax-8 gene expression was down-regulated by 7.1 times in the test group and expressed specifically in the 11.5-d embryonic (E11.5) heart. Furthermore, the expression of the protein-tyrosine kinase of the focal adhesion kinase subfamily (PTK) and [beta] subtype protein 14-3-3 was up-regulated in the test group. PTK gene expression was up-regulated by 3.7 times in the test group. These data provided support that the ALK3 gene plays an important role during heart development. The PAF and Pax-8 genes could be important ALK3 downstream genes in the BMP signaling pathway during interventricular septum development. PTK and [beta] subtype protein 14-3-3 might be regulatory factors in this pathway.

The accurate segregation of chromosomes in mitosis requires the stable attachment of microtubules to kinetochores. The details of this complex and dynamic process are poorly understood. In this study, we report the interaction of a kinetochore-associated mitotic checkpoint kinase, BubR1, with two microtubule plus end-associated proteins, adenomatous polyposis coli (APC) and EB1, providing a potential link in stable kinetochore microtubule attachment. Using immunodepletion from and antibody addition to Xenopus laevis egg extracts, we show that BubR1 and its kinase activity are essential for positioning chromosomes at the metaphase plate. BubR1 associates with APC and EB1 in egg extracts, and the complex formation is necessary for metaphase chromosome alignment. Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules. These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.

Bioeffects after exposure to ultrasound are correlated to its duration. Although diagnostic ultrasound has been suggested to induce apoptosis, the underlying signal transduction pathway remains elusive. In this study, women in the first trimester of pregnancy were exposed to transvaginal diagnostic ultrasound with 5.0-MHz frequency for 0, 10, 20, or 30 min. The chorionic villi were obtained 4 h after exposure and activation of caspase-3 and cytochrome c release were analyzed by Western blotting. In contrast with the 0- and 10-min groups, cleavage products of active caspase-3 and cytochrome c release significantly increased in 20- and 30-min groups in a time-dependent manner. We show that long-duration exposure to transvaginal ultrasound activates effector caspase-3-mediated apoptotic cascade of chorionic villi in the first trimester of pregnancy. This occurs through the intrinsic death pathway involved in cytochrome c release. Our findings provide a molecular rationale for discriminant use of transvaginal ultrasound at the early stage of pregnancy.