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In this study, our objective was to assess the performance of two deep learning-based hippocampal segmentation methods, SynthSeg and TigerBx, which are readily available to the public. We contrasted their performance with that of two established techniques, FreeSurfer-Aseg and FSL-FIRST, using three-dimensional T1-weighted MRI scans (n = 1447) procured from public databases. Our evaluation focused on the accuracy and reproducibility of these tools in estimating hippocampal volume. The findings suggest that both SynthSeg and TigerBx are on a par with Aseg and FIRST in terms of segmentation accuracy and reproducibility, but offer a significant advantage in processing speed, generating results in less than 1 min compared with several minutes to hours for the latter tools. In terms of Alzheimer's disease classification based on the hippocampal atrophy rate, SynthSeg and TigerBx exhibited superior performance. In conclusion, we evaluated the capabilities of two deep learning-based segmentation techniques. The results underscore their potential value in clinical and research environments, particularly when investigating neurological conditions associated with hippocampal structures., (© 2024 John Wiley & Sons Ltd.)

The morphological and compositional complexities of keratinized components make feathers ingenious skin appendages adapted to diverse ecological needs. Frizzling feathers, characterized by their distinct curling phenotypes, offer a unique model to explore the intricate morphogenesis in developing a keratin-based bioarchitecture over a wide range of morphospace. Here, we investigated the heterogeneous allocation of α- and β-keratins in flight feather shafts of homozygous and heterozygous frizzle chickens by analyzing the medulla-cortex integrations using quantitative morphology characterizations across scales. Our results reveal the intriguing construction of the frizzling feather shaft through the modified medulla development, leading to a perturbed balance of the internal biomechanics and, therefore, introducing the inherent natural frizzling compared to those from wild-type chickens. We elucidate how the localized developmental suppression of the α-keratin in the medulla interferes with the growth of the hierarchical keratin organization by changing the internal stress in the frizzling feather shaft. This research not only offers insights into the morphogenetic origin of the inherent bending of frizzling feathers but also facilitates our in-depth understanding of the developmental strategies toward the diverse integuments adapted for ecological needs.

Objectives: Eravacycline, a new tetracycline derivative, exhibits broad-spectrum antimicrobial susceptibility. This study aimed to comprehensively investigate in vitro activities of eravacycline, tigecycline, and ertapenem against various Gram-positive, Gram-negative, and anaerobic bacteria., Methods: Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. The following bacterial species were collected: vancomycin-sensitive (VS) Enterococci species, vancomycin-resistant Enterococci species (VRE), Staphylococcus aureus, Streptococcus anginosus, Bacteroides species, Clostridioides difficile, Clostridium innocuum, Clostridium perfringens, Parabacteroides distasonis, and Stenotrophomonas maltophilia., Results: We found that eravacycline exhibited superior in vitro activity compared to tigecycline and ertapenem. Notably, it exhibited the lowest MIC 90 for several bacterial species, including VS E. faecalis (0.12 µg/mL), VS E. faecium (0.12 µg/mL), and others. Besides, VRE was susceptible to eravacycline (MIC 90 :0.12 µg/mL) and tigecycline (MIC 90 :0.12 µg/mL), but was all resistant to ertapenem (MIC 90 > 64 µg/mL). S. aureus was also susceptible to eravacycline (MIC 90 :0.5 µg/mL) as well as tigecycline (MIC 90 :1.0 µg/mL). Furthermore, S. anginosus showed higher susceptibility to eravacycline (MIC 90 :2.0 µg/mL) and tigecycline (MIC 90 :4.0 µg/mL), but lower to ertapenem (MIC 90 :32.0 µg/mL). Eravacycline and tigecycline also demonstrated good susceptibility to anaerobes, including Bacteroides species (susceptibility rate: 100%), P. distasonis (100%), C. difficile (94.1‒100%), C. innocuum (94.1‒96.1%), and C. perfringens (88.9‒96.3%). For S. maltophilia, both tigecycline and eravacycline showed an MIC 90 of 2 µg/mL. A moderate-to-strong correlation (rho = 0.608-0.804, P < 0.001) was noted between the MIC values of eravacycline and tigecycline against various bacterial species., Conclusions: Our study highlights the potential of eravacycline as an effective treatment option for multidrug-resistant bacterial infections., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The modified Look-Locker inversion recovery (MOLLI) sequence is commonly used for myocardial T1 mapping. However, it acquires images with different inversion times, which causes difficulty in motion correction for respiratory-induced misregistration to a given target image., Hypothesis: Using a generative adversarial network (GAN) to produce virtual MOLLI images with consistent heart positions can reduce respiratory-induced misregistration of MOLLI datasets., Study Type: Retrospective., Population: 1071 MOLLI datasets from 392 human participants., Field Strength/sequence: Modified Look-Locker inversion recovery sequence at 3 T., Assessment: A GAN model with a single inversion time image as input was trained to generate virtual MOLLI target (VMT) images at different inversion times which were subsequently used in an image registration algorithm. Four VMT models were investigated and the best performing model compared with the standard vendor-provided motion correction (MOCO) technique., Statistical Tests: The effectiveness of the motion correction technique was assessed using the fitting quality index (FQI), mutual information (MI), and Dice coefficients of motion-corrected images, plus subjective quality evaluation of T1 maps by three independent readers using Likert score. Wilcoxon signed-rank test with Bonferroni correction for multiple comparison. Significance levels were defined as P < 0.01 for highly significant differences and P < 0.05 for significant differences., Results: The best performing VMT model with iterative registration demonstrated significantly better performance (FQI 0.88 ± 0.03, MI 1.78 ± 0.20, Dice 0.84 ± 0.23, quality score 2.26 ± 0.95) compared to other approaches, including the vendor-provided MOCO method (FQI 0.86 ± 0.04, MI 1.69 ± 0.25, Dice 0.80 ± 0.27, quality score 2.16 ± 1.01)., Data Conclusion: Our GAN model generating VMT images improved motion correction, which may assist reliable T1 mapping in the presence of respiratory motion. Its robust performance, even with considerable respiratory-induced heart displacements, may be beneficial for patients with difficulties in breath-holding., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 1., (© 2024 International Society for Magnetic Resonance in Medicine.)

Abstract: During interventional procedures of endovascular abdominal aortic aneurysm repair (EVAR), the dosimeter was conventionally placed on chest facing toward the surgical table, instead of the main source of scatter radiation. Purpose of this study is to evaluate the underestimation of occupational radiation exposure. Phantom experiments were performed in a hybrid operating room equipped with an interventional angiography system. Electric personal dosimeters were placed at the level of eyes, chest, abdomen, and gonad of three positions, representing the principal operator (PO), assistant operator (AO), and sterile nurse (SN). Personal dose equivalent was measured with two different orientations of radiation detection, facing the table and facing the phantom, respectively. In addition to fluoroscopy, the dose produced by digital subtraction angiography was also measured to estimate the radiation exposure of routine EVAR. In this study, staff doses of 26 EVAR cases were also collected in our hospital to correlate the estimated dose. Our results show that the facing-phantom dose normalized by dose area product of patient is significantly higher than the facing-table dose when the latter is regularly seen in clinical practice. This underestimation could be even worse at a more distant position (e.g., AO and SN) as the incident angle of scatter radiation is larger. Besides, the estimated dose is highly correlated with the on-site measured dose (R 2 ~ 0.8) at chest and gonad of the PO., (Copyright © 2023 Health Physics Society.)

Integumentary organs exhibit diverse morphologies and functions. The complex mechanical property of the architecture is mainly contributed by the ingenious multiscale assembly of keratins. A cross-scale characterization on keratin integration in an integument system will help us understand the principles on how keratin-based bio-architecture are built and function in nature. In this study, we used feather as a model integument organ. We develop autofluorescence (AF) microscopy to study the characteristics of its keratin assemblies over a wide range of length scales. The AF intensity of each feather component, following the hierarchy from the rachis to barb to barbule, decreased with the physical dimension. By combining the analysis of AF signal and tensile testing, we can probe regional material density and the associated mechanical strength in a composite feather. We further demonstrated that the AF micro-images could resolve subtle variations in the defective keratin assembly in feathers from frizzled chicken variants with a mutation in α -keratin 75. The distinction between AF patterns and the morphological features of feather components across different length scales indicated a synergetic interplay between material integration and complex morphogenesis during feather development. The work shows AF microscopy can serve as an easy and non-invasive approach to study multiscale keratin organizations and the associated bio-mechanical properties in diverse integumentary organs. This approach will facilitate our learning of many bio-inspired designs in diverse animal integumentary organs/appendages., Competing Interests: Conflicts of interest There are no conflicts of interest to declare. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Traditionally, most centers would use microelectrode recording (MER) to refine targeting in deep brain stimulation (DBS) surgery. In recent years, intraoperative imaging (IMG) guided DBS has become an alternative way to verify lead placement. Currently, there is still controversy surrounding the necessity of MER or IMG for DBS. This meta-analysis aims to explore lead accuracy, clinical efficacy and safety between IMG and MER guided DBS for Parkinson's disease (PD)., Methods: PubMed, Embase, Web of Science, Cochrane Library were searched up to Mar, 2021 for studies reporting comparisons between IMG and MER guided DBS for PD. Subgroup analysis was conducted to assess effects of different IMG technology and DBS targeting site., Results: Six studies, comprising of 478 patients were included in our analysis. The mean difference between the two implantation techniques in stereotactic accuracy, lead passes per trajectory, improvement% of Unified Parkinson's Disease Rating Scale part III and levodopa equivalent daily dose were -0.45 (95% confidence interval, CI=-1.11 to 0.20), -0.18 (95% CI=-0.41 to 0.06), 3.40 (95% CI=-5.36 to 12.16), and 5.00 (95% CI=-1.40 to 11.39), respectively. No significant differences were observed in each adverse event and operation/procedure time between the two implantation techniques., Conclusions: Both IMG and MER guided DBS offered effective control of motor symptoms for PD. Besides, IMG guided is comparable to MER guided DBS, in terms of safety, accuracy and efficiency. It is recommended for each hospital to select DBS guidance technology based on available resources and equipment., (Copyright © 2022 Sociedad Española de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.)

The upregulation of the HER2 oncogene is associated with a variety of human cancers and is associated with poor prognosis. Baicalein is reported to have anti-tumor activity, but the molecular mechanism of this effect in HER2-positive cancer cells has not been studied. In this study, our data showed that baicalein can inhibit the proliferation and transformation potential of ovarian cancer cells overexpressing HER2. Baicalein treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level. Baicalein acted on ovarian cancer cells overexpressing HER2 to downregulate the PI3K/Akt signaling pathway downstream of HER2 and inhibit the expression or activity of downstream targets, such as VEGF and cyclin D1 and MMP2. Oral administration of baicalein supplemented with a pharmaceutical excipient significantly inhibited the growth of HER2-overexpressing ovarian SKOV-3 cancer xenografts in mice. These results suggest that downregulation of HER2 gene expression by baicalein at the transcriptional level contributes to inhibit the in vitro and in vivo proliferation and HER2-mediated malignant transformation of HER2-overexpressing ovarian cancer cells., (© 2023 Wiley Periodicals LLC.)

Ovarian cancer is a lethal gynecological cancer because drug resistance often results in treatment failure. The CHK2, a tumor suppressor, is considered to be an important molecular target in ovarian cancer due to its role in DNA repair. Dysfunctional CHK2 impairs DNA damage-induced checkpoints, reduces apoptosis, and confers resistance to chemotherapeutic drugs and radiation therapy in ovarian cancer cells. This provides a basis for finding new effective agents targeting CHK2 upregulation or activation to treat or prevent the progression of advanced ovarian cancer. Here, the results show that baicalein (5,6,7-trihydroxyflavone) treatment inhibits the growth of highly invasive ovarian cancer cells, and that baicalein-induced growth inhibition is mediated by the cell cycle arrest in the G 2 /M phase. Baicalein-induced G 2 /M phase arrest is associated with an increased reactive oxygen species (ROS) production, DNA damage, and CHK2 upregulation and activation. Thus, baicalein modulates the expression of DNA damage response proteins and G 2 /M phase regulatory molecules. Blockade of CHK2 activation by CHK2 inhibitors protects cells from baicalein-mediated G 2 /M cell cycle arrest. All the results suggest that baicalein has another novel growth inhibitory effect on highly invasive ovarian cancer cells, which is partly related to G 2 /M cell cycle arrest through the ROS-mediated DNA breakage damage and CHK2 activation. Collectively, our findings provide a molecular basis for the potential of baicalein as an adjuvant therapeutic agent in the treatment of metastatic ovarian cancer.

Objectives: We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19., Methods: HCW who had at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2 (30 μg), half-dose mRNA-1273 (50 μg), mRNA-1273 (100 μg), and MVC-COV1901 (15 μg). The primary outcomes were humoral and cellular immunogenicity and secondary outcomes assessed safety and reactogenicity at 28 days post-booster., Results: MVC-COV1901 Three hundred and forty HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. The fold-rise of anti-spike IgG geometric mean titer was 8.4 (95% CI 6.8-10.4) for MVC-COV1901, 32.2 (27.2-38.1) for BNT162b2, 47.6 (40.8-55.6) for half-dose mRNA-1273 and 63.2 (53.6-74.6) for mRNA-1273. The live virus microneutralization assays (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron BA.1 variant were 6.4 to 13.5 times lower than those against the wild type. All booster vaccines induced a comparable T cell response., Conclusions: Third dose booster not only increases neutralizing antibody titer but also enhances antibody breadth against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those who received primary series of ChAdOx1 nCov-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The number of periprosthetic fractures above a total knee arthroplasty continues to increase. These fractures are associated with a high risk of morbidity and mortality. Techniques for addressing these fractures include open reduction internal fixation (ORIF) and revision arthroplasty, including distal femoral replacement (DFR). The primary aim of this review is to compare mortality and reoperation rates between ORIF and DFR when used to treat periprosthetic distal femur fractures., Methods: A systematic review including MEDLINE, Embase and Cochrane Library databases was completed from inception to April 10, 2021. Studies including a comparator cohort were meta-analyzed., Results: Fourteen studies were identified for inclusion, of which, five had sufficient homogeneity for inclusion in a meta-analysis. 30-day and 2-year mortality was 4.1% and 14.6% in the DFR group. There was no statistically significant difference between ORIF and DFR (log Odds-Ratio (OR) = -0.14, 95 %CI: -0.77 to 0.50). The reoperation rate in the DFR group was 9.3% versus 14.8% for ORIF, with no difference between groups (log OR = 0.10, 95 %CI: -0.59 to 0.79). There was no difference in rates of deep infection (log OR = 0.22, 95 %CI: -0.83 to 1.28). Direct comparison of functional outcomes was not possible, though did not appear significant., Conclusion: DFR in the setting of periprosthetic distal femur fractures is equivalent to ORIF with respect to mortality and reoperation rate and thus a safe and reliable treatment strategy. DFR may be more reliable in complex fracture patterns where the ability to obtain adequate fixation is difficult., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Epithelial-mesenchymal transition (EMT) of airway lung epithelial cells is considered a major driver of fibrosis and airway remodeling. Arsenic exposure is well known to cause the malignant transformation of cells, including those in the lung. Accumulating studies have shown that arsenic exposure is associated with chronic pulmonary diseases. However, clinical treatment for arsenic-induced pulmonary damage has not been well investigated. Materials and Methods: The therapeutic effects of montelukast and its combination with fluticasone on sodium arsenite-induced EMT changes in normal human bronchial cells were investigated. The cell migration ability was evaluated by Transwell and wound healing assays. EMT marker expression was determined by immunoblotting. Furthermore, the role of reactive oxygen species (ROS) generation in arsenic-induced EMT and the effect of montelukast on this process were determined by ROS inhibitor treatment and ROS measurement, respectively. Results: Montelukast was effective at reducing arsenic-induced cell migration and mesenchymal protein (fibronectin, MMP-2, N-cadherin, β-catenin, and SMAD2/3) expression. Arsenic-induced ROS production was attenuated by pretreatment with montelukast. Treatment with the ROS inhibitor N-acetyl cysteine reduced arsenic-induced NF-kB phosphorylation and the mesenchymal protein expression, indicating that ROS production is critical for arsenic-induced EMT. In addition, combined treatment with montelukast and fluticasone reversed the inhibitory effects of montelukast on cell migration. The expression of fibronectin, MMP-2 induced by arsenic was further enhanced by the combination treatment compared with montelukast treatment only. Conclusion: This study demonstrated that montelukast is effective at reducing arsenic-induced EMT in human bronchial epithelial cells. Through the inhibition of arsenic-induced ROS generation and NF-kB activation, which is critical for arsenic-induced EMT, montelukast inhibited arsenic-induced cell migration and the expression of extracellular matrix proteins and several EMT-regulating transcription factors. The combination of fluticasone with montelukast reversed the inhibitory effect of montelukast on arsenic-induced EMT. This study provides therapeutic strategies and mechanisms for arsenic-induced pulmonary epithelial damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Chiou, Tsai, Chen, Lin, Chuang, Hung and Kuo.)

Background: Susceptibility-weighted imaging (SWI) is sensitive to the accumulation of paramagnetic substances, such as hemorrhage and increased venous vasculature, both being frequently found in high-grade tumors. The purpose of this retrospective study is to differentiate high-grade and low-grade astrocytoma by objectively measuring quantitative intra-tumoral susceptibility signals (qITSS) on SWI., Methods: Precontrast SWI and 3D contrast-enhanced T1WI of 65 patients with astrocytoma were collected at 1.5 Tesla. All tumors were histologically confirmed and classified into two groups: high grade (WHO grade III and IV, n=50) and low grade (WHO grade II, n=15). After manual delineation of the tumor on T1WI, normalized contrast (NC) was calculated voxel by voxel within the tumor by using the concept of contrast to noise ratio. Thresholding on NC was applied to detect qITSS, and the volumetric percentage of qITSS can be obtained for each tumor. Two-sample t -test was applied to examine significant difference of qITSS percentage between high-grade and low-grade astrocytoma for different NC thresholds, ranging from 4 to 20. Receiver operating characteristic analysis was performed to evaluate the performance of differentiation., Results: P value was less than 0.01 for a large range of NC thresholds [4-20], reflecting significant difference of qITSS percentage between high-grade and low-grade astrocytoma. The area under the receiver operating characteristic curve was larger than 0.9 at NC thresholds from 8 to 16 and peaks at 0.949 with a NC threshold of 14. It was shown that astrocytoma grading by qITSS percentage is successful for a wide range of NC threshold, demonstrating robustness on threshold selection., Conclusions: Without relying on the selection of slice position and at the same time providing objective identification of hypointense signal in SWI, the qITSS percentage can be used to distinguish high-grade and low-grade astrocytoma reliably., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-58). Dr. HWC serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery, and Drs. TCC, YLC, WPS, HWC reported that they received grant supports from Ministry of Science and Technology (Taiwan) research grants (MOST 104-2221-E-110-039 and MOST 105-2221-E-110-054); Dr. DHL reported that he received grant support from Kaohsiung Veterans General Hospital (VGHKS107-160) in Taiwan. The other authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Acephate (Ac) is an organophosphate (OP) compound, which is able to inhibit the activity of acetylcholinesterase. Thus, the aim of this study was to optimize the detection of Ac using a thiolated acephate binding aptamer-citrate capped gold nanoparticle (TABA-Cit-AuNP) sensor that also incorporated an image processing technique. The effects of independent variables, such as the incubation period of TABA-Cit-AuNPs (3-24 h) for binding TABA to Cit-AuNPs, the concentration of phosphate buffer saline (PBS) (0.001-0.01 M), the concentration of thiolated acephate binding aptamer (TABA) (50-200 nM), and the concentration of magnesium sulphate (MgSO 4 ) (1-300 mM) were investigated. A quadratic model was developed using a central composite design (CCD) from response surface methodology (RSM) to predict the sensing response to Ac. The optimum conditions such as the concentration of PBS (0.01 M), the concentration of TABA (200 nM), the incubation period of TABA-Cit-AuNPs (3 h), and the concentration of MgSO 4 (1 mM) were used to produce a TABA-Cit-AuNPs sensor for the detection of Ac. Under optimal conditions, this sensor showed a detection ranging from 0.01 to 2.73 μM and a limit of detection (LOD) of 0.06 μM. Real sample analysis demonstrated this aptasensor as a good analytical method to detect Ac., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down-regulating the EGFR-ErbB2/PI3K/Akt signaling pathway. The berberine-mediated inhibition of MMP-2 and MMP-9 activity could be rescued by co-treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin-mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2., (© 2020 Wiley Periodicals LLC.)

Purpose: To evaluate the effective doses received by donors and recipients, identify effective dose contributions, and make risk assessments., Materials and Methods: It was a retrospective study. 100 Donors and 100 recipients were enrolled with an operative day from March 2016 to August 2017. The dose was analyzed for all radiation-related examinations over a period of 2 years, 1 year before and 1 year after the LDLT procedure. The effective doses of plain X-rays, CT, fluoroscopy, and nuclear medicine per patient were simulated by a Monte Carlo software, evaluated by the dose-length product conversion factors, evaluated by the dose-area product conversion factors, and evaluated by the activity conversion factors, respectively. The risks of radiation-induced cancer were assessed on the basis of the ICRP risk model., Results: The median effective doses were 71 (range: 30-186) mSv for donors and 147 (32-423) mSv for recipients. The radiation examinations were mainly performed in the last three months of preoperative period to first month of postoperative period for recipients and donors. The HCC recipients received a higher effective dose, 195 (64-423) mSv, than those with other indications. The median radiation-induced cancer risk was 0.38 % in male and 0.48 % in female donors and was 0.50 % in male and 0.58 % in female recipients., Conclusion: Donors and recipients received a large effective dose, mainly from the CT scans. To reduce effective doses should be included in future challenges in some living donor liver transplants centers that often use CT examinations., Competing Interests: Declaration of Competing Interest This study was supported by a grant from Nuclear Technology Cooperative Research, Ministry of Science and Technology (MOST), Taiwan (MOST106−2623-E-040−001-NU). Hsien-Wen Chiang and Tou-Rong Chen report receipt of a grant from Nuclear Technology Cooperative Research, Ministry of Science and Technology, Taiwan. No other disclosures were reported. The MOST had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This paper proposes a UAV platform that autonomously detects, hunts, and takes down other small UAVs in GPS-denied environments. The platform detects, tracks, and follows another drone within its sensor range using a pre-trained machine learning model. We collect and generate a 58,647-image dataset and use it to train a Tiny YOLO detection algorithm. This algorithm combined with a simple visual-servoing approach was validated on a physical platform. Our platform was able to successfully track and follow a target drone at an estimated speed of 1.5 m/s. Performance was limited by the detection algorithm's 77% accuracy in cluttered environments and the frame rate of eight frames per second along with the field of view of the camera., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of this retrospective study was to investigate the differentiation of abscess and necrotic tumors, using susceptibility-weighted imaging (SWI) and apparent diffusion coefficients (ADC) either separated or combined., Methods: Imaging was performed on 26 patients with pyogenic brain abscesses, 31 patients with rim-enhancing glioblastomas, and 21 patients with rim-enhancing metastases. The degree of intralesional susceptibility signal (ILSS) was independently assessed by three observers. Average ADC in the lesion core was calculated. After receiver operating characteristic (ROC) analysis, the area under the ROC curve was compared using three different analytical models (ILSS, ADC, and ILSS-ADC combined) to differentiate abscess from the two rim-enhancing necrotic tumors., Results: The ILSS-ADC combined model had greater area under the ROC curves than ILSS or ADC used alone. In this study, the ILSS-ADC combined model showed 100% diagnostic accuracy differentiating abscesses from glioblastoma. The ADC model and the ILSS-ADC combined model performed equally well in distinguishing abscesses from metastases., Conclusion: It is concluded that SWI and ADC are complementary, and the combination of SWI and ADC may improve results compared with the use of only one model. Validation by an independent cohort is the next necessary step to broaden its applicability in routine clinical settings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to determine the reliability of a C1:C2 ratio in a cohort of patients with atlas fractures. Second, we aimed to consider the utility of the C1:C2 ratio with regard to diagnosis of transverse ligament (TL) injury., Design: This is a retrospective analysis., Methods: Patients with atlas fractures in the Waikato region between 2008 and 2010 were identified retrospectively through clinical coding and collated radiology trauma database., Main Outcome Measurements: The maximal width of C1 and C2 was measured using the first-taken trauma radiograph series. Combined overhang of lateral masses (△mm) and a C1:C2 ratio was then calculated. Final ratio and atlanto-dens interval (ADI) were measured at the last clinical follow-up., Results: A total of 24 patients with full radiographic records were included. Of these, five patients (21%) had TL injuries confirmed on computed tomography or magnetic resonance imaging. No patient with a ratio 1.15 had an intact TL, whereas a ratio of >1.10 captured 80% of TL injuries. The ratio ( P < 0.001) and delta values ( P < 0.001) were statistically significantly different between TL-injured and TL-intact cohorts. Two patients in the TL injury group demonstrated increased ADI on final follow-up with a ratio of >1.10., Conclusions: A C1:C2 ratio >1.10 on plain radiographs showed a sensitivity of 80% in detecting atlas fractures with associated TL injury. All patients with a ratio of ≥1.15 had TL rupture subsequently confirmed by an advanced modality. A ratio calculation on radiographs is a potentially useful method of describing atlas lateral mass displacement., Level of Evidence: Level III., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Craniovertebral Junction and Spine.)

Resting-state functional magnetic resonance imaging (MRI) has been used to investigate the brain activity related to autism spectrum disorder (ASD). In this study, we applied information from a large-scale dataset, the Autism Brain Imaging Data Exchange (ABIDE), to clinical applications. We recruited 21 patients with ASD and 23 individuals with neurotypical development (TD). We applied ASD biomarkers derived from ABIDE datasets and subsequently investigated the relationship between the MRI biomarkers and indicators from clinical screening questionnaires, the social responsiveness scale (SRS), and the Swanson, Nolan, and Pelham Questionnaire IV. The results indicated that the biomarkers generated from the default mode and executive control networks significantly differed between the participants with ASD and TD. In particular, the biomarkers derived from the default mode network were negatively correlated with the raw scores and model factors of the SRS. In summary, this study transferred the efforts of the global autism research community to clinical applications and identified connectivity-based biomarkers in ASD.

An exciplex could be formed by blending a selected hole-transporting material (HTM)/electron-transporting material (ETM) pair, and the corresponding energy band gap is roughly determined by the energy difference between the lowest unoccupied molecular orbital (LUMO) of the ETM and the highest occupied molecular orbital (HOMO) of the HTM. In this study, three HTM/ETM combinations are adopted to generate blue, green, and red exciplexes, allowing us to design precise device architectures for the fabrication of exciplex-based white OLEDs (WOLEDs) with daylight-like emissions. The CIE coordinates of this WOLED varied close to the Planckian locus as the biases increase, with a high color rendering index of about 96. This high performance suggests this exciplex-based WOLED can provide high-quality white-light illumination. Photoluminance and lifetime measurements of the exciplex behavior of the HTM/ETM combinations indicate that the HTM and ETM selected should possess higher triplet energy bandgaps than those of their corresponding exciplex to avoid energy loss., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: A variety of targeted drug therapies in clinical trials have been proven to be effective for the treatment of hepatocellular carcinoma (HCC). Our study aims to compare the short-term and long-term efficacies of different targeted drugs in advanced hepatocellular carcinoma (AHCC) treatment using a network meta-analysis approach., Methods: PubMed, Embase, Ovid, EBSCO, and Cochrane central register of controlled trials were searched for randomized controlled trials (RCTs) of different targeted therapies implemented to patients with AHCC. And the retrieval resulted in 7 targeted drugs, namely, sorafenib, ramucirumab, everolimus, brivanib, tivantinib, sunitinib, and sorafenib+erlotinib. Direct and indirect evidence were combined to evaluate stable disease (SD), progressive disease (PD), complete response (CR), partial response (PR), disease control rate (DCR), overall response ratio (ORR), overall survival (OS), and surface under the cumulative ranking curve (SUCRA) of patients with AHCC., Results: A total of 11 RCTs were incorporated into our analysis, including 6594 patients with AHCC, among which 1619 patients received placebo treatment and 4975 cases had targeted therapies. The results revealed that in comparison with placebo, sorafenib, and ramucirumab displayed better short-term efficacy in terms of PR and ORR, and brivanib was better in ORR. Regarding long-term efficacy, sorafenib and sorafenib+erlotinib treatments exhibited longer OS. The data of cluster analysis showed that ramucirumab or sorafenib+erlotinib presented relatively better short-term efficacy for the treatment of AHCC., Conclusion: This network meta-analysis shows that ramucirumab and sorafenib+erlotinib may be the better targeted drugs for AHCC patients, and sorafenib+erlotinib achieved a better long-term efficacy., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Mature galls induced by Daphnephila truncicola, D. taiwanensis, D. sueyenae, D. stenocalia, and D. ornithocephala on Machilus thunbergii in northern Taiwan were examined to verify the dictum that the morphology of galls is an expression of the extended phenotype of the respective gall-inducing insect. Based on their length-width ratio, the materials were grouped into either fleshy (those induced by D. taiwanensis and D. sueyenae) or slim galls (those induced by D. truncicola, D. stenocalia, and D. ornithocephala). Stem galls induced by D. truncicola showed an energy level of 0.0178 kJ/g. Among leaf galls, the greatest energy level was in the one induced by D. stenocalia (0.0193 kJ/g), followed by D. sueyenae (0.0192 kJ/g), D. taiwanensis (0.0189 kJ/g), and D. ornithocephala (0.0160 kJ/g). The numbers of reserve and nutritive cell layers in galls were greater in the stem galls induced by D. truncicola, similar to those in the fleshy leaf galls, than in the slim leaf galls. Based on the fungal taxa isolated from the larval chambers and considering the similarities and divergences among gall characteristics, the galls induced by D. truncicola and D. taiwanensis clustered into one, whereas those of D. sueyenae aligned with the 'D. stenocalia-D. ornithocephala' cluster. The present study verified that shapes, structure, nutritive tissues, energy levels, and multiple coexisting fungal taxa within galls reinforce that they are extended phenotypes of the respective gall-inducing Daphnephila species and they represent adaptive evolution of Daphnephila on M. thunbergii.

Objectives: To investigate the feasibility of using susceptibility-weighted imaging (SWI) to discriminate abscesses and necrotic tumours., Methods: Twenty-one patients with pyogenic abscesses, 21 patients with rim-enhancing glioblastomas and 23 patients with rim-enhancing metastases underwent SWI. Intralesional susceptibility signal (ILSS) was analyzed employing both qualitative (QL) and semi-quantitative (SQ) methods. Logistic regression models and receiver operating characteristic analysis were used to demonstrate the discriminating power., Results: In QL analysis, ILSSs were seen in 12 of 21 abscesses, in 20 of 21 glioblastomas, and in 16 of 23 metastases. In SQ analysis, a low degree of ILSS (85.8 %) was in the majority of abscesses and a high degree of ILSS (76.2 %) was in the majority of glioblastomas. SQ model was significantly better than QL model in distinguishing abscesses from glioblastomas (P < .001). A derived ILSS cutoff grade of 1 or less was quantified as having a sensitivity of 85.7 %, specificity of 90.5 %, accuracy of 88.1 %, PPV of 90.0 %, and NPV of 86.4 % in distinguishing abscesses from glioblastomas., Conclusions: A high-grade ILSS may help distinguish glioblastomas from abscesses and necrotic metastatic brain tumours. The lack of ILSS or low-grade ILSS can be a more specific sign in the imaging diagnosis of abscesses., Key Points: • ILSS of SWI can contribute to differential diagnosis of rim-enhanced mass. • Low-grade ILSS can be a more specific sign in abscesses. • High-grade ILSS may help distinguish necrotic glioblastomas from abscesses. • ILSS spreads across the four ILSS categories in metastases.

Purpose: To achieve better spatial and temporal resolution of dynamic contrast-enhanced MR imaging, the concept of k-space data sharing, or view sharing, can be implemented for PROPELLER acquisition. As found in other view-sharing methods, the loss of high-resolution dynamics is possible for view-sharing PROPELLER (VS-Prop) due to the temporal smoothing effect. The degradation can be more severe when a narrow blade with less phase encoding steps is chosen in the acquisition for higher frame rate. In this study, an iterative algorithm termed pixel-based optimal blade selection (POBS) is proposed to allow spatially dependent selection of the rotating blades, to generate high-resolution dynamic images with minimal reconstruction artifacts., Methods: In the reconstruction of VS-Prop, the central k-space which dominates the image contrast is only provided by the target blade with the peripheral k-space contributed by a minimal number of consecutive rotating blades. To reduce the reconstruction artifacts, the set of neighboring blades exhibiting the closest image contrast with the target blade is picked by POBS algorithm. Numerical simulations and phantom experiments were conducted in this study to investigate the dynamic response and spatial profiles of images generated using our proposed method. In addition, dynamic contrast-enhanced cardiovascular imaging of healthy subjects was performed to demonstrate the feasibility and advantages., Results: The simulation results show that POBS VS-Prop can provide timely dynamic response to rapid signal change, especially for a small region of interest or with the use of narrow blades. The POBS algorithm also demonstrates its capability to capture nonsimultaneous signal changes over the entire FOV. In addition, both phantom and in vivo experiments show that the temporal smoothing effect can be avoided by means of POBS, leading to higher wash-in slope of contrast enhancement after the bolus injection., Conclusions: With the satisfactory reconstruction quality provided by the POBS algorithm, VS-Prop acquisition technique may find useful clinical applications in DCE MR imaging studies where both spatial and temporal resolutions play important roles.

This study aimed to automatically identify the cardiac rest period using a rapid free-breathing (FB) calibration scanning procedure, and to determine the optimal trigger delay for cardiac imaging. A standard deviation (SD) method was used to rapidly identify cardiac quiescent phases employing multiphase cine cardiac images. The accuracy of this method was investigated using 46 datasets acquired from 22 healthy volunteers. The possibility of using a low-resolution FB method to rapidly acquire cine images was also evaluated. The reproducibility and accuracy of the trigger delay obtained using the rapid calibration scanning process were assessed before its application to a real-time feedback system. The real-time trigger delay calibration system was then used to perform T1 -weighted, short-axis imaging at the end of the cardiac systolic period. Linear regression analysis of the trigger times obtained using the SD method and a reference method indicated that the SD algorithm accurately identified the cardiac rest period (linear regression: slope = 0.94-1, R(2)  = 0.68-0.84). Group analysis showed that the number of pixels in the left ventricular blood pool in images acquired at the end-systolic time calculated in real time was significantly lower than in those acquired 50 ms in advance or later (p < 0.01, paired t-test). The low-resolution FB imaging method was reproducible for the calibration scanning of an image in a vertical long-axis slice position (average SD of trigger times, 16-39 ms). Combined with rapid FB calibration scanning, the real-time feedback system accurately adjusted the trigger delay for T1 -weighted short-axis imaging. The real-time feedback method is rapid and reliable for trigger time calibration, and could facilitate cardiac imaging during routine examination., (Copyright © 2014 John Wiley & Sons, Ltd.)

Purpose: One of the technical advantages of functional magnetic resonance imaging (fMRI) is its precise localization of changes from neuronal activities. While current practice of fMRI acquisition at voxel size around 3 × 3 × 3 mm(3) achieves satisfactory results in studies of basic brain functions, higher spatial resolution is required in order to resolve finer cortical structures. This study investigated spatial resolution effects on brain fMRI experiments using balanced steady-state free precession (bSSFP) imaging with 0.37 mm(3) voxel volume at 3.0 T., Methods: In fMRI experiments, full and unilateral visual field 5 Hz flashing checkerboard stimulations were given to healthy subjects. The bSSFP imaging experiments were performed at three different frequency offsets to widen the coverage, with functional activations in the primary visual cortex analyzed using the general linear model. Variations of the spatial resolution were achieved by removing outer k-space data components., Results: Results show that a reduction in voxel volume from 3.44 × 3.44 × 2 mm(3) to 0.43 × 0.43 × 2 mm(3) has resulted in an increase of the functional activation signals from (7.7 ± 1.7)% to (20.9 ± 2.0)% at 3.0 T, despite of the threefold SNR decreases in the original images, leading to nearly invariant functional contrast-to-noise ratios (fCNR) even at high spatial resolution. Activation signals aligning nicely with gray matter sulci at high spatial resolution would, on the other hand, have possibly been mistaken as noise at low spatial resolution., Conclusions: It is concluded that the bSSFP sequence is a plausible technique for fMRI investigations at submillimeter voxel widths without compromising fCNR. The reduction of partial volume averaging with nonactivated brain tissues to retain fCNR is uniquely suitable for high spatial resolution applications such as the resolving of columnar organization in the brain.

Non-water suppression MRS (NWS MRS) has several advantages. First, the unsuppressed water signal can be used as internal calibration for metabolite quantification and as a reliable frequency/phase reference for retrospective motion correction. Second, it avoids the potential artifacts caused by incomplete water suppression (WS) and extra radiofrequency deposition from WS pulses. However, the frequency modulation (FM) sidebands originating from a large water signal will distort the spectrum. Among the methods proposed to solve the problems caused by FM sidebands, post-acquisition processing methods are superior in flexibility for general use compared with experimental methods. In this study, we propose two algorithms based on advanced matrix decomposition to remove the FM sidebands. These methods, the simultaneous diagonalization (QZ) algorithm and its subsequent variant, the simultaneously generalized Schur decomposition (SGSD) algorithm, were numerically evaluated using computer simulations. In addition, we quantitatively compared the performance of these methods and the modulus method in an in vitro experiment and in vivo NWS MRS against conventional WS data. Our results show that the proposed SGSD algorithm can reduce the FM sidebands to achieve superior estimation of concentration on three major metabolites. This method can be applied directly to spectra pre-acquired under various experimental conditions without modifying the acquisition sequences., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background and Purpose: The combination of phase demodulation and field mapping is a practical method to correct echo planar imaging (EPI) geometric distortion. However, since phase dispersion accumulates in each phase-encoding step, the calculation complexity of phase modulation is Ny-fold higher than conventional image reconstructions. Thus, correcting EPI images via phase demodulation is generally a time-consuming task., Methods: Parallel computing by employing general-purpose calculations on graphics processing units (GPU) can accelerate scientific computing if the algorithm is parallelized. This study proposes a method that incorporates the GPU-based technique into phase demodulation calculations to reduce computation time. The proposed parallel algorithm was applied to a PROPELLER-EPI diffusion tensor data set., Results: The GPU-based phase demodulation method reduced the EPI distortion correctly, and accelerated the computation. The total reconstruction time of the 16-slice PROPELLER-EPI diffusion tensor images with matrix size of 128 × 128 was reduced from 1,754 seconds to 101 seconds by utilizing the parallelized 4-GPU program., Conclusions: GPU computing is a promising method to accelerate EPI geometric correction. The resulting reduction in computation time of phase demodulation should accelerate postprocessing for studies performed with EPI, and should effectuate the PROPELLER-EPI technique for clinical practice., (Copyright © 2011 by the American Society of Neuroimaging.)

Objective: This study investigates the application of a modified reversed gradient algorithm to the Propeller-EPI imaging method (periodically rotated overlapping parallel lines with enhanced reconstruction based on echo-planar imaging readout) for corrections of geometric distortions due to the EPI readout., Materials and Methods: Propeller-EPI acquisition was executed with 360-degree rotational coverage of the k-space, from which the image pairs with opposite phase-encoding gradient polarities were extracted for reversed gradient geometric and intensity corrections. The spatial displacements obtained on a pixel-by-pixel basis were fitted using a two-dimensional polynomial followed by low-pass filtering to assure correction reliability in low-signal regions. Single-shot EPI images were obtained on a phantom, whereas high spatial resolution T2-weighted and diffusion tensor Propeller-EPI data were acquired in vivo from healthy subjects at 3.0 Tesla, to demonstrate the effectiveness of the proposed algorithm., Results: Phantom images show success of the smoothed displacement map concept in providing improvements of the geometric corrections at low-signal regions. Human brain images demonstrate prominently superior reconstruction quality of Propeller-EPI images with modified reversed gradient corrections as compared with those obtained without corrections, as evidenced from verification against the distortion-free fast spin-echo images at the same level., Conclusions: The modified reversed gradient method is an effective approach to obtain high-resolution Propeller-EPI images with substantially reduced artifacts.

A diffusion tensor imaging (DTI) study was conducted in 12 adolescents with attention deficit/hyperactivity disorder and 14 age- and IQ-matched healthy controls. Inter-subject comparison of fractional anisotropy (FA) of the whole brain between the groups was obtained using the tract-based spatial statistics method. Results revealed significantly lower FA in widespread white matter tracts in cases relative to controls. Also, the FA measure of identified regions was associated with cognitive performance., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: HER2, a receptor tyrosine kinase, was originally identified based on its role in cancer research. The protein has subsequently received attention for its role in nerve injury and neurodevelopment. We investigated the polymorphic association of HER2 variants at amino acid residues 655 and 1170 with Parkinson's disease (PD), a neurodegenerative disorder., Design and Methods: Polymerase chain reaction (PCR) was used to amplify DNA samples from PD patients and control subjects. The resulting PCR fragments, which spanned HER2 residues 655 and 1170, were analyzed by restriction fragment length polymorphism and/or direct nucleotide sequencing., Results: The genetic distribution at residue 655 in PD patients did not differ from that in controls. However, homozygosity for genes encoding Pro at residue 1170 (Pro/Pro) occurred at a significantly lower rate among PD subjects. In other words, Ala-allele carries higher frequency in PD, especially among female PD subjects., Conclusion: Different signals or potency of the kinase activities resulting from the Ala1170Pro allele of HER2 may be associated with vulnerability to stress on dopaminergic neurons in PD., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: To evaluate the relative effectiveness of different treatments of hepatocellular carcinoma (HCC) via the hepatic artery., Materials and Methods: The study sample group consisted of 418 patients who were randomly selected from 2008 to 2012 with a first diagnosis of HCC and treated with transcatheter arterial chemoembolization (TACE) or without (TAE) chemotherapy or transcatheter arterial infusion (TAI). We collected data including tumor size preoperative and one month thereafter to compare change in areas across the three groups, along with various laboratory indexes for comparison., Results: The overall average change of areas was 240.8 ± 72.1 mm2. In the three groups it was 265.0 ± 58.0 mm2 vs. 250.5 ± 51.9 mm2 vs. 123.7 ± 26.2 mm2. In groups TACE and TAE values were larger than in group TAI (p<0.01), but the difference between the two was not statistically significant (p= 0.191). Additionally, U/L change of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in groups TACE and TAE was greater than in the TAI cases (24.0 ± 13.5 vs. 20. 9± 12.1 vs. 5.47 ± 8.20 and 25.6 ± 13.5 vs.23.2 ± 12.28 vs.5.48 ± 14.3) on the preoperative day and two days thereafter (p<0.01). Between the two groups there was no significant cariation (p= 0.320 and p= 0.609). However, the AST and ALT recovered to normal levels one month later on therapy with liver protecting drugs., Conclusion: The groups TACE and TAE demonstrated more effective reduction of tumor size than group TAI. While lipiodol caused acute liver function damage, this proved reversible.

Ganoderma, also known as Lingzhi or Reishi, has been used for medicinal purposes in Asian countries for centuries. It is a medicinal fungus with a variety of biological properties including immunomodulatory and antitumor activities. In this study, we investigated the molecular mechanisms by which Ganoderma tsugae (GT), one of the most common species of Ganoderma, inhibits the proliferation of HER2-overexpressing cancer cells. Here, we show that a quality assured extract of GT (GTE) inhibited the growth of HER2-overexpressing cancer cells in vitro and in vivo and enhanced the growth-inhibitory effect of antitumor drugs (e.g., taxol and cisplatin) in these cells. We also demonstrate that GTE induced cell cycle arrest by interfering with the HER2/PI3K/Akt signaling pathway. Furthermore, GTE curtailed the expression of the HER2 protein by modulating the transcriptional activity of the HER2 gene and the stability/degradation of the HER2 protein. In conclusion, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of cancer cells that highly express HER2.

Purpose: To demonstrate the presence of a multilayer appearance of the capsule on contrast-enhanced (CE) susceptibility-weighted imaging (SWI) in patients with pyogenic brain abscesses. Possible origins for the appearance and effects of postprocessing settings are discussed., Materials and Methods: Fourteen patients with pyogenic brain abscesses underwent post gadolinium-enhanced SWI at 1.5 T. All SWI images were postprocessed with various filter and mask settings to compare the image appearance. Computer simulations using a paramagnetic spherical shell model were performed to verify the clinical findings., Results: Pyogenic brain abscesses demonstrated a multilayer appearance with a darkened ring within the enhanced capsule on CE-SWI in all patients. The multilayer appearance was slice-orientation-dependent, decreased with larger widths of the high-pass filter, and increased with larger numbers of phase mask multiplication operations, consistently on both simulation results and the clinical images., Conclusion: CE-SWI shows the multilayer appearance of the capsule in pyogenic brain abscesses, which may arise from postprocessing procedures originally designed to enhance susceptibility contrast. Although SWI may provide additional information valuable in the diagnosis of pyogenic brain abscesses, image interpretation should be exercised with caution, particularly for CE-SWI., (Copyright © 2012 Wiley-Liss, Inc.)

Berberine (BBR) is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanisms by which BBR repressed the metastatic potential of breast cancer cells. BBR was found to downregulate the enzymatic activities and expression levels of matrix metalloproteinases 2 and 9 (MMP2 and MMP9, respectively). The BBR-mediated suppression of MMP2 and MMP9 involved the inhibition of the Akt/nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) signaling pathways. Furthermore, BBR repressed the expression of the Akt protein by modulating the mRNA expression level and protein degradation of Akt. In conclusion, this study suggests that BBR can reduce the metastatic potential of highly metastatic breast cancer cells and may be a useful adjuvant therapeutic agent in the treatment of breast cancer by targeting the Akt pathway.

Background and Purpose: SWI is a high-resolution 3D, fully velocity-compensated gradient-echo sequence that uses both magnitude and phase data. The purpose of this study was to investigate the phase behavior of the capsule of pyogenic brain abscesses with noncontrast SWI., Materials and Methods: Fourteen patients with pyogenic brain abscesses were studied at 1.5T. In all of the patients, SWI images were obtained and reviewed in addition to conventional MR images. Phase values within the abscess capsule were measured and compared with those from the abscess cavities and contralateral normal white matter using 1-way repeated measures ANOVA with post hoc Bonferroni analysis., Results: SWI phase images showed mild hypointesity in 6 patients, isointensity in 3 patients, and mixed iso- to mild hypointensity in 5 patients. The means of phase in the cavity, rim of abscesses, and contralateral normal white matter were -7.552 × 10(-3) ± 0.024, -0.105 ± 0.080, and +0.029 ± 0.011 radians, respectively. Post hoc comparisons showed significant differences between any pair of the 3 regions (abscess cavity, rim capsule, and normal white matter) in SWI (all Ps < .005)., Conclusions: SWI phase imaging shows evidence of paramagnetic substances in agreement with the presence of free radicals from phagocytosis. SWI may provide additional information valuable in the characterization of pyogenic brain abscesses.

Purpose: This study aimed to determine the genetic role of HER2, one of the epidermal growth factor receptor (EGFR) family, in schwannoma. The latter is a neogrowth of myelin-producing Schwann cells in peripheral nerves, inducible by N-nitrosoethylurea in animals with mutation in the neu gene (homologous gene of human HER2 protein)., Methods: In this study we obtained genomic DNA samples from tissue blocks of schwannoma, initially by xylene treatment and alcohol extraction, followed by use of the DNA extraction kit. Evaluation of this genetic polymorphism in our subjects was conducted by direct nucleotide sequencing or restriction enzyme analyses after PCR work., Results: There were thirty extracted DNA samples from tissue blocks of schwannoma, and all were Ile/Ile homozygotes after genotype analyses. Two individuals received the leukocyte DNA extraction after peripheral blood sampling, both showing Ile/Ile homozygosity. This study gave the impression of an association of the HER2 polymorphism at codon 655 with tumorigenesis of schwannoma. Although the majority of the Taiwanese showed Ile/Ile homozygosity (about 83%), the present study revealed a 100% carriage rate among the tissue blocks from our subjects with schwannoma., Conclusion: Ile/Ile homozygosity at codon 655 of HER2 in schwannoma may imply some role in tumorigenesis of Ile655Val allele of HER2 in this nerve tumor.

Overexpression of the HER2 oncogene contributes to tumor cell invasion, metastasis and angiogenesis and correlates with poor prognosis. Magnolol has been reported to exhibit anti-tumor activities. However, the molecular mechanism of action of magnolol has not been investigated in HER2-positive cancer cells. Therefore, we examined the anti-cancer effects of magnolol on HER2-overexpressing ovarian cancer cells. Magnolol treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF-κB activation. Treatment of HER2-overexpressing ovarian cancer cells with magnolol down-regulated the HER2 downstream PI3K/Akt signaling pathway, and suppressed the expression of downstream target genes, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2) and cyclin D1. Consistently, magnolol-mediated inhibition of MMP2 activity could be prevented by co-treatment with epidermal growth factor. Migration assays revealed that magnolol treatment markedly reduced the motility of HER2-overexpressing ovarian cancer cells. Furthermore, magnolol-induced apoptosis in HER2-overexpressing ovarian cancer cells was characterized by the up-regulation of cleaved poly(ADP-ribose) polymerase (PARP) and activated caspase 3. These findings suggest that magnolol may act against HER2 and its downstream PI3K/Akt/mTOR-signaling network, thus resulting in suppression of HER2-mediated transformation and metastatic potential in HER2-overexpressing ovarian cancers. These results provide a novel mechanism to explain the anti-cancer effect of magnolol., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Berberine (BBR) is a natural alkaloid with significant antitumor activities against many types of cancer cells. This study investigated the molecular mechanisms by which BBR suppresses the growth of HER2-overexpressing breast cancer cells. The results show that BBR induces G1-phase cell cycle arrest by interfering with the expression of cyclins D1 and E and that it induces cellular apoptosis through the induction of a mitochondria/caspase pathway. The data also indicate that BBR inhibits cellular growth and promotes apoptosis by down-regulating the HER2/PI3K/Akt signaling pathway. Furthermore, it is also shown that a combination of taxol and BBR significantly slows the growth rate of HER2-overexpressing breast cancer cells. In conclusion, this study suggests that BBR could be a useful adjuvant therapeutic agent in the treatment of HER2-overexpressing breast cancer.

Nonmelanoma skin carcinoma (NMSC) is the most frequent cancer in the USA with over 1.3 million new diagnoses a year; however due to an underappreciation of its associated mortality and growing incidence and its ability to be highly aggressive, the molecular mechanism is not well delineated. Whereas the molecular profiles of melanoma have been well characterized, those for cutaneous squamous cell carcinoma (cSCC) have trailed behind. This importance of the new staging paradigm is linked to the ability currently to better clinically cluster similar biologic behavior in order to risk-stratify lesions and patients. In this paper we discuss the trends in NMSC and the etiologies for the subset of NMSC with the most mortality, cutaneous SCC, as well as where the field stands in the discovery of a molecular profile. The molecular markers are highlighted to demonstrate the recent advances in cSCC.

Objectives: To investigate the polymorphism distribution of Val-9Ala and Ile+58Thr of the Mn-superoxide dismutase (Mn-SOD) gene among subjects with Parkinson's disease (PD) by analyses of genders and clinical severity., Design and Methods: We examined the DNA genotypes of Val-9Ala and Ile+58Thr from 295 PD subjects and 111 controls by nucleotide sequencing and BsaWI restriction., Results: Ala/Ala homozygosity was found in four PD subjects but not in the controls. All of the genotypes at codon +58 among the examined samples were Ile/Ile homozygotes. Although higher carrier rate of Ala allele among PD subjects than the controls, there were no differences by analyses of the genders and clinical severity., Conclusion: The higher Ala-allele carrier rate among PD subjects may suggest a possible higher amount of mitochondrial Mn-SOD rendering higher intracellular stress in PD. In this study the polymorphisms at codons -9 and+58 did not give informative association evidences with PD., (2010 The Canadian Society of Clinical Chemists. All rights reserved.)

Purpose: To report possible erroneous estimates of diffusion parameters in the twice-refocused spin-echo (TRSE) technique, proposed to eliminate eddy-current-induced geometric distortions in diffusion-weighted echo-planar imaging, when stimulated echo signals are inappropriately included., Materials and Methods: Eleven subjects were included for imaging experiments on two 1.5 Tesla systems using the TRSE sequence. Three versions, two with unbalanced crusher gradients inserted to dephase the stimulated echo from the b = 0 images and one with balanced crusher gradients, were implemented. The apparent diffusion coefficients (ADC) and fractional anisotropy (FA) were derived and compared., Results: The ADCs obtained with unbalanced crusher gradients were closer to values reported in the literature. Stimulated echo led to ADC over-estimations by 34.2%, 50.4%, 54.0%, 51.5%, 24.0%, and 41.9% in the genu of corpus callosum, splenium of corpus callosum, bilateral corona radiata, internal capsule, mediofrontal gyrus, and the cuneus, respectively (P < 0.01), with concomitant reduction in FA in highly anisotropic regions. Over-estimations of diffusion coefficients were found to be roughly equal along all directions., Conclusion: Formation of stimulated echo in the TRSE technique can lead to erroneous estimations of the diffusion parameters, even if no prominent morphological artifacts are seen.

BACKGROUND.: An activating point mutation of the BRAF oncogene results in a V600E amino acid missense mutation found in a majority of papillary thyroid carcinomas (PTC). METHODS.: In this study, 28 matched tumor and serum samples obtained from patients with both benign and malignant thyroid disorders were analyzed for BRAF mutation using a gap-ligase chain reaction technique. RESULTS.: The BRAF mutation was absent in tumor DNA samples obtained from patients with benign adenomas, follicular neoplasms or carcinoma, and thyroid lymphoma. In contrast, 5 of 14 PTC tumors were positive for the BRAF mutation. Moreover, 3 of 14 patients with PTC were positive for BRAF mutation in serum and tumor. Of these 3 patients, 2 had lymph node metastasis and 2 had PTC in background of the Hashimoto's thyroiditis. CONCLUSIONS.: The detection of free circulating mutant BRAF in patients with PTC is possible and future studies are warranted to determine its clinical significance., (Copyright 2009 Wiley Periodicals, Inc.)

We examined the anti-angiogenic effects of Ganoderma tsugae methanol extract (GTME) on human epidermoid carcinoma A-431 cells. Our data indicate that GTME inhibits the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in vitro and in vivo, and also inhibits the capillary tube formation of human umbilical vein endothelial cells (HUVECs). We also show that the suppression of VEGF expression by GTME can be restored by treatment with EGF. These results suggest that GTME inhibits VEGF expression via the suppression of EGFR expression, resulting in the downregulation of VEGF secretion from epidermoid carcinoma A-431 cells. These findings reveal a novel role for G. tsugae in inhibiting EGFR and VEGF expression, which are important for tumor angiogenesis and growth. Thus, GTME may provide a potential therapeutic approach for anti-tumor treatment.

HER2/neu oncogene-mediated malignancy is clearly associated with various human cancers. Therefore, HER2/neu targeting is an effective approach to cancer therapy. We have previously demonstrated that Epstein-Barr virus nuclear antigen-1 (EBNA1) can suppress HER2/neu oncogene expression, although EBNA1 itself has oncogenic potential. Here, we found that the N-terminal domain of EBNA1 alone, named EBNA1-NT, which contains the N-terminal region of amino acid residues 1-86 of EBNA1, is required and sufficient to suppress HER2/neu oncogene expression at the transcriptional level. Furthermore, in EBNA1-NT-transfected HER2/neu-overexpressing cells, we found EBNA1-NT could down-regulate the endogenous production of p185(HER2/neu), lower transformation ability, sensitize paclitaxel-induced apoptosis and decrease tumorigenic potential. These data suggest that EBNA1-NT may act as a repressor of the HER2/neu oncogene.

Polymorphism in prion protein (PrP) is related to different phenotypes of spongiform encephalopathies and some mental illnesses. The octarepeat region of PrP, encompassing the codon 51 through 91, is related to cellular anti-oxidation function and may play a role in genetic contribution of PrP polymorphism to neurodegeneration, such as Parkinson's disease (PD). We analyzed the genomic patterns of PrP gene from 528 subjects and found a predominance of Met/Met variant at codon 129 of PD subjects without significant difference (97.3%, and 96.5% in controls). But among PD subjects there were one with heterozygosity of silent nucleotide substitution (NS) on octarepeats (R1-2-3g-3-4/R1-2-2-3-4) and three with heterozygosity of single copy deletion (CD) on octarepeats (R1-2-3-4/R1-2-2-3-4). Consistent genomic DNA and cDNA sequences were found in a PD subject without any octarepeat changes and the one with NS, but R1-2-3g-3-4/R1-2-2-3-4 of cDNA pattern occurred in the one with genomic CD. This is the first report of the polymorphic PrP octarepeat change among those with parkinsonism. We proposed a hypothesis about an initial secondary hairpin structure of the template strand followed by the transcript "shift backward" due to the high homology of the sequences between R2 and R3 motifs while synthesizing RNA. This phenomenon may be a key step of neurodegeneration resulting from PrP polymorphism and require further studies.

Ethnopharmacological Relevance: Ganoderma, known as Lingzhi or Reishi, has been traditionally administered throughout Asia for centuries as a cancer treatment and for other medicinal purposes., Aim of the Study: To investigate the inhibitory activity and explore the molecular mechanisms of anti-tumor effect on colorectal cancer cells in vitro and in vivo as well as to test the side effects of Ganoderma tsugae., Materials and Methods: Methanol fraction was obtained from dried fruiting bodies of Ganoderma. TLC and HPLC were performed to differentiate and confirm the identification of different species as well as to quantify the bioactive molecules in methanol extracts of Ganoderma species. MTT and Trypan blue exclusion assay as well as tumorigenesis study were used to assess the anti-tumor effect in vitro and in vivo. Using flow cytometry and Western Blots, we examined further the molecular mechanisms of anti-tumor effect. Finally, biochemical and hematological profiles and pathological examinations were used to evaluate the safety., Results: The Ganoderma tsugae extracts inhibit colorectal cancer cell proliferation caused by accumulating cells in G(2)/M phase, and it may be through downregulation of cyclin A and B1 and upregulation of p21 and p27. Tumorigenesis study in nude mice revealed the extracts caused tumor shrinkage. Additionally, safety assay showed Ganoderma tsugae extracts caused no significant side effects in an animal model., Conclusions: This study provides molecular evidence that Ganoderma tsugae extracts exert anti-tumor effects both in vitro and in vivo on colorectal adenocarcinoma cells by inducing G(2)/M cell cycle arrest. More importantly, no significant physiological changes resulting from treatment with Ganoderma tsugae extracts were observed in the animal model. Therefore, these data provide new insights into the possible therapeutic use of Ganoderma tsugae for treating colorectal cancer.