E. Edmund Kim

Prognostic Value of Metabolic Tumor Volume and Total Lesion Glycolysis in Head and Neck Cancer: A Systematic Review and Meta-Analysis

We conducted a comprehensive systematic review of the literature on volumetric parameters and a meta-analysis of the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with head and neck cancer (HNC). Methods: A systematic search of MEDLINE and EMBASE was performed using the key words PET, head and neck, and volume. Inclusion criteria were 18F-FDG PET used as an initial imaging tool; studies limited to HNC; patients who had not undergone surgery, chemotherapy, or radiotherapy before PET scans; and studies reporting survival data. Event-free survival and overall survival were considered markers of outcome. The impact of MTV or TLG on survival was measured by the effect size hazard ratio (HR). Data from each study were analyzed using Review Manager. Results: Thirteen studies comprising 1,180 patients were included in this study. The combined HR for adverse events was 3.06 (2.33–4.01, P < 0.00001) with MTV and 3.10 (2.27–4.24, P < 0.00001) with TLG, meaning that tumors with high volumetric parameters were associated with progression or recurrence. Regarding overall survival, the pooled HR was 3.51 (2.62–4.72, P < 0.00001) with MTV and 3.14 (2.24–4.40, P < 0.00001) with TLG. There was no evidence of significant statistical heterogeneity at an I2 of 0%. Conclusion: MTV and TLG are prognostic predictors of outcome in patients with HNC. Despite clinically heterogeneous HNC and the various methods adopted between studies, we can confirm that patients with a high MTV or TLG have a higher risk of adverse events or death.

Effects of nicotine on APP secretion and Aβ- or CT105-induced toxicity

Several lines of evidence indicated that overexpression or aberrant processing of amyloid precursor protein (APP) is causally related to Alzheimers disease (AD). Amyloid precursor protein is principally cleaved within the amyloid beta protein domain to release a large soluble ectodomain (APPs), known to have a wide range of trophic functions. The central hypothesis guiding this review is that nicotine may play an important role in APP secretion and protection against toxicity induced by APP metabolic fragments (beta-amyloid [Abeta], carboxyl terminal [CT]). Findings from our experiments have shown that nicotine enhances the release of APPs, which has neurotrophic and neuroprotective activities in concentration-dependent (>50 micromol/L) and time-dependent (>2 hours) manners. In addition, pretreatment of nicotine (>10 micromol/L for 24 hours) partially prevented Abeta or CT(105)-induced cytotoxicity in primary cultured neuron cells, and the effects of nicotine-induced protection were inhibited by the pretreatment with a nicotine alpha-bungarotoxin. Nicotine (>10 micromol/L for 24 hours) partially inhibited CT(105)-induced cytotoxicity when PC12 cells was transfected with CT(105). From these results, we proposed that nicotine or nicotinic receptor agonist treatment might improve the cognitive functions not only by supplementation of cholinergic neurotransmission, but also by protecting Abeta- or CT(105)-induced neurotoxicity probably through the increased release of APPs and the activation of nicotinic receptors.

Segmentation-Based MR Attenuation Correction Including Bones Also Affects Quantitation in Brain Study: An Initial Result of 18F-FP-CIT PET/MR for Patients with Parkinsonism

Attenuation correction (AC) with an ultrashort echo time (UTE) sequence has recently been used in combination with segmentation for cortical bone identification for brain PET/MR studies. The purpose of this study was to evaluate the quantification of 18F-fluoropropyl-carbomethoxyiodophenylnortropane (18F-FP-CIT) binding in brain PET/MR, particularly focusing on effects of UTE-based AC including bone segmentation. Methods: Sixteen patients with initially suspected parkinsonism were prospectively enrolled. An emission scan was acquired 110 min after 18F-FP-CIT injection on a dedicated PET/MR scanner, immediately followed by another emission scan using a PET/CT scanner 120 min after the injection. A UTE-based attenuation map was used to classify the voxels into 3 tissues: bone, soft tissue, and air. All PET images were spatially normalized, and a specific-to-nonspecific dopamine transporter (DAT) binding ratio (BR) was calculated using statistical probabilistic anatomic mapping. The level of agreement was assessed with intraclass correlation coefficients (ICCs). Voxelwise comparison between PET images acquired from PET/MR and PET/CT was performed. We compared non–attenuation-corrected images to analyze UTE-based AC effects on DAT quantification. Results: BR in the putamen obtained from PET/MR and PET/CT showed low interequipment variability, whereas BR in the caudate nucleus showed significant variability (ICC = 0.967 and 0.682 for putamen and caudate nucleus, respectively). BR in the caudate nucleus was significantly underestimated by PET/MR, compared with PET/CT (mean difference of BR = 0.66, P < 0.0001). Voxelwise analysis revealed that PET/MR showed significantly low BR in the periventricular regions, which was caused by a misclassification of the ventricle as air on the attenuation map. We also compared non-AC images, revealing low interequipment variability even in the caudate nucleus (ICC = 0.937 and 0.832 for putamen and caudate nucleus, respectively). Conclusion: Our data demonstrate spatial bias of the DAT BR on 18F-FP-CIT PET/MR. Voxelwise analysis and comparison to non-AC images identified the misclassification of ventricle as air to be the cause of bias. To obtain reliable quantification for brain PET/MR studies including 18F-FP-CIT PET, alternative and more reliable segmentation strategies are required.

In Vivo Visualization and Monitoring of Viable Neural Stem Cells Using Noninvasive Bioluminescence Imaging in the 6-Hydroxydopamine-Induced Mouse Model of Parkinson Disease

Transplantation of neural stem cells (NSCs) has been proposed as a treatment for Parkinson disease (PD). The aim of this study was to monitor the viability of transplanted NSCs expressing the enhanced luciferase gene in a mouse model of PD in vivo. The PD animal model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA). The behavioral test using apomorphine-induced rotation and positron emission tomography with [18F]N-(3-fluoropropyl)-2′-carbomethoxy-3′-(4-iodophenyl)nortropane ([18F]FP-CIT) were conducted. HB1.F3 cells transduced with an enhanced firefly luciferase retroviral vector (F3-effLuc cells) were transplanted into the right striatum. In vivo bioluminescence imaging was repeated for 2 weeks. Four weeks after transplantation, [18F]FP-CIT PET and the rotation test were repeated. All 6-OHDA-injected mice showed markedly decreased [18F]FP-CIT uptake in the right striatum. Transplanted F3-effLuc cells were visualized on the right side of the brain in all mice by bioluminescence imaging. The bioluminescence intensity of the transplanted F3-effLuc cells gradually decreased until it was undetectable by 10 days. The behavioral test showed that stem cell transplantation attenuated the motor symptoms of PD. No significant change was found in [18F]FP-CIT imaging after cell transplantation. We successfully established an in vivo bioluminescence imaging system for the detection of transplanted NSCs in a mouse model of PD. NSC transplantation induced behavioral improvement in PD model mice.

Internet literacy and digital natives’ civic engagement: Internet skill literacy or Internet information literacy?

ABSTRACT This study aims to show the role of Internet literacy in empowering digital natives’ civic engagement. Using a survey of 10th graders, we analyzed the effects of digital media use and Internet literacy on adolescents’ political and social interest, participation, and efficacy, controlling for their home and school environments. In doing so, we try to highlight the following points. First, we emphasize that there are two separate dimensions of Internet literacy: Internet skill literacy and Internet information literacy. Second, we adopt a broader concept of civic engagement reflecting the changing youth practices observed in the contemporary media environment. The study empirically found that Internet information literacy, not Internet skill literacy, is intricately related to adolescents’ civic engagement. It was also shown that adolescents’ Internet use contributed only to new and alternative forms of participation. Overall, the findings show that an adolescent who can critically understand and effectively evaluate online information is more likely to become an active civic participant than one who lacks such skills. The study concludes with a few policy suggestions.

A comparative study on the relationship between social networking site use and social capital among Australian and Korean youth

ABSTRACT Social network sites (SNS) have become increasingly pervasive in the daily lives of adolescents. This study explores the relationship between SNS use and perceived online social capital among adolescents using survey data from Australia and Korea. We conducted a face-to-face survey of adolescents (12–15-year-olds) in major cities in Australia (N = 401) and Korea (N = 644) in 2013. There was no significant difference in time spent on SNS between adolescents in the two countries; however, significant differences in the way adolescents use SNS were found. Australian adolescents tended to use SNS for group activities, whereas Koreans used it for social monitoring. There was a positive relationship between SNS use and online social capital in both countries. However, the types of social capital that were found to have a strong relationship to SNS use were different. Among Australian adolescents, SNS activities had a higher correlation with bonding social capital compared to bridging capital, whereas the result was contrasting among Korean adolescents. The impact of SNS use on online social capital differed between the two countries, showing that Australian adolescents reporting low SNS use gained online social capital if they used SNS more intensely. Finally, the impact of SNS use and culture on perceived online social capital was examined by conducting hierarchical multiple regressions. Interpersonal communication and group activities emerged as significant predictors of online social capital.

Maturation of metabolic connectivity of the adolescent rat brain

Neuroimaging has been used to examine developmental changes of the brain. While PET studies revealed maturation-related changes, maturation of metabolic connectivity of the brain is not yet understood. Here, we show that rat brain metabolism is reconfigured to achieve long-distance connections with higher energy efficiency during maturation. Metabolism increased in anterior cerebrum and decreased in thalamus and cerebellum during maturation. When functional covariance patterns of PET images were examined, metabolic networks including default mode network (DMN) were extracted. Connectivity increased between the anterior and posterior parts of DMN and sensory-motor cortices during maturation. Energy efficiency, a ratio of connectivity strength to metabolism of a region, increased in medial prefrontal and retrosplenial cortices. Our data revealed that metabolic networks mature to increase metabolic connections and establish its efficiency between large-scale spatial components from childhood to early adulthood. Neurodevelopmental diseases might be understood by abnormal reconfiguration of metabolic connectivity and efficiency. DOI: http://dx.doi.org/10.7554/eLife.11571.001

Gray matter correlates of dopaminergic degeneration in Parkinson's disease: A hybrid PET/MR study using (18) F-FP-CIT.

Dopaminergic degeneration is a hallmark of Parkinsons disease (PD), which causes various symptoms affected by corticostriatal circuits. So far, the relationship between cortical changes and dopamine loss in the striatum is unclear. Here, we evaluate the gray matter (GM) changes in accordance with striatal dopaminergic degeneration in PD using hybrid PET/MR. Sixteen patients with idiopathic PD underwent 18F‐FP‐CIT PET/MR. To measure dopaminergic degeneration in PD, binding ratio (BR) of dopamine transporter in striatum was evaluated by 18F‐FP‐CIT. Voxel‐based morphometry (VBM) was used to evaluate GM density. We obtained voxelwise correlation maps of GM density according to the striatal BR. Voxel‐by‐voxel correlation between BR maps and GM density maps was done to evaluate region‐specific correlation of striatal dopaminergic degeneration. There was a trend of positive correlation between striatal BR and GM density in the cerebellum, parahippocampal gyri, and frontal cortex. A trend of negative correlation between striatal BR and GM density in the medial occipital cortex was found. Voxel‐by‐voxel correlation revealed that the positive correlation was mainly dependent on anterior striatal BR, while posterior striatal BR mostly showed negative correlation with GM density in occipital and temporal cortices. Decreased GM density related to anterior striatal dopaminergic degeneration might demonstrate degeneration of dopaminergic nonmotor circuits. Furthermore, the negative correlation could be related to the motor circuits of posterior striatum. Our integrated PET/MR study suggests that the widespread structural progressive changes in PD could denote the cortical functional correlates of the degeneration of striatal dopaminergic circuits. Hum Brain Mapp 37:1710–1721, 2016.

Online Activities, Digital Media Literacy, and Networked Individualism of Korean Youth

Networked individualism enables Internet users to connect and socialize via their loose and transient multiple networks, whereas digital media literacy is a precondition of effective Internet use. In this study, an attempt has been made to find the link between networked individualism, digital media literacy, and young people’s perception of their social capital. A nationally representative face-to-face survey was conducted with Korean adolescents in 2013. Networked individualism was higher in adolescents who frequently engaged in online activities and who demonstrated greater digital media literacy. Belonging to multiple, diverse networks and having many connections was positively correlated to adolescents’ online social capital. Findings indicate that online activities and skills influence the ways adolescents connect to others and perceive of their social connectedness.

The Effectiveness of Recombinant Human Thyroid-Stimulating Hormone versus Thyroid Hormone Withdrawal Prior to Radioiodine Remnant Ablation in Thyroid Cancer: A Meta-Analysis of Randomized Controlled Trials

We evaluated the efficacy of recombinant human thyroid-stimulating hormone (rhTSH) versus thyroid hormone withdrawal (THW) prior to radioiodine remnant ablation (RRA) in thyroid cancer. A systematic search of MEDLINE, EMBASE, the Cochrane Library, and SCOPUS was performed. Randomized controlled trials that compared ablation success between rhTSH and THW at 6 to 12 months following RRA were included in this study. Six trials with a total of 1,660 patients were included. When ablation success was defined as a thyroglobulin (Tg) cutoff of 1 ng/mL (risk ratio, 0.99; 95% confidence interval, 0.96-1.03) or a Tg cutoff of 1 ng/mL plus imaging modality (RR 0.97; 0.90-1.05), the results of rhTSH and THW were similar. There were no significant differences when ablation success was defined as a Tg cutoff of 2 ng/mL (RR 1.03; 0.95-1.11) or a Tg cutoff of 2 ng/mL plus imaging modality (RR 1.02; 0.95-1.09). When a negative 131I-whole body scan was used solely as the definition of ablation success, the effects of rhTSH and THW were not significantly different (RR 0.97; 0.93-1.02). Therefore, ablation success rates are comparable when RRA is prepared by either rhTSH or THW.