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Abstract Objective This study aimed to evaluate the effectiveness and safety of everolimus in treating seizures associated with focal cortical dysplasia type 2 (FCD 2). Methods A prospective, crossover, placebo‐controlled clinical trial (ClinicalTrials.gov: NCT03198949) enrolled patients aged 4–40 years with pathologically confirmed FCD 2 and a history of ≥3 seizures per month for two out of the 3 months prior to screening. The trial included a 4‐week baseline phase, two 12‐week core phases, and a 29‐week extension phase. Patients received everolimus or placebo in a blinded manner during core phase I, with crossover to the alternate treatment in core phase II. Everolimus dosage started at 4.5 mg/m2/day, targeting a serum level of 5–15 ng/mL. The primary outcome was the proportion of patients achieving ≥50% seizure reduction from baseline in the last month of each core phase. Safety profiles were compared between groups. Results Between May 11, 2017, and June 19, 2020, 21 patients completed the core phases. There was no significant difference in the primary outcome between everolimus and placebo groups (24% vs. 19%, p = 0.66). The patients showed varied responses. Three patients with a pathogenic variant in the MTOR gene or no genetic abnormalities achieved seizure freedom with everolimus in the last month of the core phase, while none of the patients with variants in other genes did. Adverse events, such as mucositis or skin ulceration, were more common with everolimus (19/21 vs. 7/21, p

Abstract The olive flounder, Paralichthys olivaceus, also known as the Korean halibut, is an economically important flatfish in East Asian countries. Here, we provided four fully phased genome assemblies of two different olive flounder individuals using high-fidelity long-read sequencing and their parental short-read sequencing data. We obtained 42–44 Gb of ~15-kb and ~Q30 high-fidelity long reads, and their assembly quality values were ~53. We annotated ~30 K genes, ~170-Mb repetitive sequences, and ~3 M 5-methylcytosine positions for each genome assembly, and established a graph-based draft pan-genome of the olive flounder. We identified 5 M single-nucleotide variants and 100 K structural variants with their genotype information, where ~13% of the variants were possibly fixed in the two Korean individuals. Based on our chromosome-level genome assembly, we also explored chromosome evolution in the Pleuronectiformes family, as reported earlier. Our high-quality genomic resources will contribute to future genomic selection for accelerating the breeding process of the olive flounder.

Abstract Background Whole-genome sequencing (WGS) analyses have found higher genetic burden in autistic females compared to males, supporting higher liability threshold in females. However, genomic evidence of sex differences has been limited to European ancestry to date and little is known about how genetic variation leads to autism-related traits within families across sex. Methods To address this gap, we present WGS data of Korean autism families (n = 2255) and a Korean general population sample (n = 2500), the largest WGS data of East Asian ancestry. We analyzed sex differences in genetic burden and compared with cohorts of European ancestry (n = 15,839). Further, with extensively collected family-wise Korean autism phenotype data (n = 3730), we investigated sex differences in phenotypic scores and gene-phenotype associations within family. Results We observed robust female enrichment of de novo protein-truncating variants in autistic individuals across cohorts. However, sex differences in polygenic burden varied across cohorts and we found that the differential proportion of comorbid intellectual disability and severe autism symptoms mainly drove these variations. In siblings, males of autistic females exhibited the most severe social communication deficits. Female siblings exhibited lower phenotypic severity despite the higher polygenic burden than male siblings. Mothers also showed higher tolerance for polygenic burden than fathers, supporting higher liability threshold in females. Conclusions Our findings indicate that genetic liability in autism is both sex- and phenotype-dependent, expanding the current understanding of autism’s genetic complexity. Our work further suggests that family-based assessments of sex differences can help unravel underlying sex-differential liability in autism.

Abstract Low-level somatic mutations in the human brain are implicated in various neurological disorders. The contribution of low-level brain somatic mutations to autism spectrum disorder (ASD), however, remains poorly understood. Here, we performed high-depth exome sequencing with an average read depth of 559.3x in 181 cortical, cerebellar, and peripheral tissue samples to identify brain somatic single nucleotide variants (SNVs) in 24 ASD subjects and 31 controls. We detected ~2.4 brain somatic SNVs per exome per single brain region, with a variant allele frequency (VAF) as low as 0.3%. The mutational profiles, including the number, signature, and type, were not significantly different between the ASD patients and controls. Intriguingly, when considering genes with low-level brain somatic SNVs and ASD risk genes with damaging germline SNVs together, the merged set of genes carrying either somatic or germline SNVs in ASD patients was significantly involved in ASD-associated pathophysiology, including dendrite spine morphogenesis (p = 0.025), mental retardation (p = 0.012), and intrauterine growth retardation (p = 0.012). Additionally, the merged gene set showed ASD-associated spatiotemporal expression in the early and mid-fetal cortex, striatum, and thalamus (all p

Room temperature gas sensing is crucial for practical devices used in indoor environments. Among various materials, metal oxides are commonly used for gas sensing, but their strong insulating properties limit their effectiveness at room temperature. To address this issue, many studies have explored diverse methods such as nanoparticle decoration or conductive support, etc. Here, we report the emergence of gas-sensing functionality at room temperature with improved CO gas selectivity on SnO2 nanoparticles through sequential steps by using amorphous carbon (a-C) support and PtOx decoration. The SnO2 decorated on amorphous carbon shows enhanced gas adsorption compared to inactive gas sensing on SnO2 decorated carbon support. The higher Vo site of SnO2 on a-C induces gas adsorption sites, which are related to the higher sp2 bonding caused by the large density of C defects. The ambiguous gas selectivity of SnO2/a-C is tailored by PtOx decoration, which exhibits six values of sensing responses (Rg/Ra or Ra/Rg) under CO gas at room temperature with higher selectivity. Compared to PtOx/a-C, which shows no response, the enhanced CO gas sensing functionality is attributed to the CO adsorption site on PtOx-decorated SnO2 particles. This report not only demonstrates the applicability of CO gas sensing at room temperature but also suggests a strategy for using SnO2 and carbon compositions in gas sensing devices.

Brain tumours: antibody blocks blood vessel abnormality An antibody targeting key signalling pathways could prevent brain tumor vessels from being abnormal, thereby improving drug delivery into tumor tissues. Glioblastoma multiforme is considered one of the most deadly cancers and it invades brain tissue coupled with the loss of vascular integrity. This pathological vascular changes are closely associated with the hyperactivation of a signalling pathway called VEGFR2 and inactivation of another pathway, Tie2. Now, Injune Kim at the Korea Advanced Institute of Science and Technology, Weon Sup Lee at PharmAbcine Inc., both in Daejeon, South Korea, and co-workers have developed a Tie2-activating antibody that effectively stops vascular abnormalization in and around glioblastoma in the spontaneous mouse tumor model. As well as activating Tie2, the antibody suppresses the VEGFR2 pathway. The study therefore reveals a potential strategy for improving glioblastoma treatment through multiple vascular mechanisms.

Abstract Observations of comorbidity in heart diseases, including cardiac dysfunction (CD) are increasing, including and cognitive impairment, such as Alzheimer’s disease and dementia (AD/D). This comorbidity might be due to a pleiotropic effect of genetic variants shared between CD and AD/D. Here, we validated comorbidity of CD and AD/D based on diagnostic records from millions of patients in Korea and the University of California, San Francisco Medical Center (odds ratio 11.5 [8.5–15.5, 95% Confidence Interval (CI)]). By integrating a comprehensive human disease–SNP association database (VARIMED, VARiants Informing MEDicine) and whole-exome sequencing of 50 brains from individuals with and without Alzheimer's disease (AD), we identified missense variants in coding regions including APOB, a known risk factor for CD and AD/D, which potentially have a pleiotropic role in both diseases. Of the identified variants, site-directed mutation of ADIPOQ (268 G > A; Gly90Ser) in neurons produced abnormal aggregation of tau proteins (p = 0.02), suggesting a functional impact for AD/D. The association of CD and ADIPOQ variants was confirmed based on domain deletion in cardiac cells. Using the UK Biobank including data from over 500000 individuals, we examined a pleiotropic effect of the ADIPOQ variant by comparing CD- and AD/D-associated phenotypic evidence, including cardiac hypertrophy and cognitive degeneration. These results indicate that convergence of health care records and genetic evidences may help to dissect the molecular underpinnings of heart disease and associated cognitive impairment, and could potentially serve a prognostic function. Validation of disease–disease associations through health care records and genomic evidence can determine whether health conditions share risk factors based on pleiotropy.

Purpose This study presents the characteristics of patients with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) with SLC35A2 somatic variants in the brain who underwent epilepsy surgery and showed clinical improvement in seizures. Methods We collected 10 patients with SLC35A2 somatic mutations in the brain who underwent surgery to treat drug-resistant epilepsy at Severance Children’s Hospital from 2014 to 2019 and retrospectively reviewed their genetic profiles, neuropathologic results, clinical features, pre-operative evaluations, and post-operative outcomes. Results Six of the 10 patients with SCL35A2 somatic mutations in the brain had Lennox Gastaut syndrome (LGS) evolving from infantile spasms (IS), three had LGS, and one had IS. The median value of variant allele frequencies (VAFs) was 5.7% (1.7% to 5.8%; range, 1.4% to 22.9%). Nonsense mutations were the most common (50%), followed by missense mutations (40%) and a splicing site mutation (10%). Eight patients (80%) had good post-operative outcomes, with freedom from disabling seizures in five (Engel class I) and rare disabling seizures in three (Engel class II). Four of the eight patients who could be assessed for social quotient (SQ) after surgery showed SQ improvements by 12.2±6.4. Although all patients were finally diagnosed with MOGHE, seven (70%) were initially diagnosed with gliosis, two with mild malformation of cortical development, and one with no abnormality. Conclusion All patients with SCL35A2 brain somatic mutations, even with low VAFs, had refractory epilepsy such as LGS or IS, and were finally diagnosed with MOGHE. This report is the first in Korea to our knowledge.

Interferon regulatory factor (IRF) 3 and IRF7 are important innate immune-related genes that induce type I interferon (IFN). In this study, PmIRF3 and PmIRF7 were identified from red sea bream (Pagrus major) infected by red sea bream iridovirus (RSIV), and expression and functional analyses were performed. PmIRF3 and PmIRF7 consisted of 465 and 436 amino acids, respectively, and contained a well-conserved IRF domain, IRF3 domain, and serine-rich domain (SRD). PmIRF3 and PmIRF7 are ubiquitously expressed in the liver and gills in normal fish, and with a high expression being recorded in kidney and spleen during RSIV infection. In P. major fin cells (PMF cells), pAcGFP-PmIRF3 and pAcGFP-PmIRF7 were localized to the cytoplasm, and overexpression of PmIRF3 and PmIRF7 using the pcDNA3.1 vector induced type I IFN. In addition, in the experiment in vitro, PMF cells overexpressed with PmIRF3 or PmIRF7 exhibited antiviral activity against RSIV and significantly reduced viral genome copies and virus titer. Therefore, PmIRF3 and PmIRF7 may have antiviral activity through the induction of type I IFN against RSIV infection of red sea bream.

Lipid is one of the most important nutritional factors affecting growth and survival of larval fish. This study aims to determine optimum level of lipid in formulated microdiets for the 10-day old rockfish (Sebastes schlegeli) larvae. Five granulated microdiets (CL11, CL14, CL17, CL20, and CL23) containing various (11%, 14%, 17%, 20%, and 23%, respectively) levels of lipid were prepared, and their lipid levels were controlled by adding fish oil at the expense of dextrin. The effects of feeding rockfish larvae with these formulated microdiets were compared with two commercial microdiets (Belgium and Japan), and local crumble diet. At the end of the 29-day feeding trial, weight gain (%) and total length (mm) of larval fish fed the CL20 diet were significantly (P 0.05) affected by the experimental diets. Crude lipid content of the whole-body fish was relatively well reflected from lipid levels of the experimental diets. In conclusion, the greatest weight gain and longest total length were obtained in larval fish fed the CL20 diet among the experimentally formulated microdiets. The optimum lipid level in the experimentally formulated microdiet was estimated to be 17.3% for rockfish larvae based on the broken-line analysis.

Summary: Despite the recognized importance of antitumor immunity, our understanding of brain tumor immunity is poor. Orthotopic injection models have been widely used for immunological analyses. However, these models have limitations in analysis of antitumor immunity because the approach involves drilling skulls and injecting tumor cells, which can induce adverse effects. We describe a protocol for the induction of spontaneous brain tumor model, isolation of single cells from brain tumor microenvironment, and analysis of the immune responses using scRNA-seq and flow cytometry.For complete details on the use and execution of this protocol, please refer to Park et al. (2021). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Most somatic mutations that arise during normal development are present at low levels in single or multiple tissues depending on the developmental stage and affected organs. However, the effect of human developmental stages or mutations of different organs on the features of somatic mutations is still unclear. Here, we performed a systemic and comprehensive analysis of low-level somatic mutations using deep whole-exome sequencing (average read depth ~500×) of 498 multiple organ tissues with matched controls from 190 individuals. Our results showed that early clone-forming mutations shared between multiple organs were lower in number but showed higher allele frequencies than late clone-forming mutations [0.54 vs. 5.83 variants per individual; 6.17% vs. 1.5% variant allele frequency (VAF)] along with less nonsynonymous mutations and lower functional impacts. Additionally, early and late clone-forming mutations had unique mutational signatures that were distinct from mutations that originated from tumors. Compared with early clone-forming mutations that showed a clock-like signature across all organs or tissues studied, late clone-forming mutations showed organ, tissue, and cell-type specificity in the mutation counts, VAFs, and mutational signatures. In particular, analysis of brain somatic mutations showed a bimodal occurrence and temporal-lobe-specific signature. These findings provide new insights into the features of somatic mosaicism that are dependent on developmental stage and brain regions.

Abstract Focal malformations of cortical development (MCD) are linked to somatic brain mutations occurring during neurodevelopment. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a newly recognized clinico-pathological entity associated with pediatric drug-resistant focal epilepsy, and amenable to neurosurgical treatment. MOGHE is histopathologically characterized by clusters of increased oligodendroglial cell densities, patchy zones of hypomyelination, and heterotopic neurons in the white matter. The molecular etiology of MOGHE remained unknown so far. We hypothesized a contribution of mosaic brain variants and performed deep targeted gene sequencing on 20 surgical MOGHE brain samples from a single-center cohort of pediatric patients. We identified somatic pathogenic SLC35A2 variants in 9/20 (45%) patients with mosaic rates ranging from 7 to 52%. SLC35A2 encodes a UDP-galactose transporter, previously implicated in other malformations of cortical development (MCD) and a rare type of congenital disorder of glycosylation. To further clarify the histological features of SLC35A2-brain tissues, we then collected 17 samples with pathogenic SLC35A2 variants from a multicenter cohort of MCD cases. Histopathological reassessment including anti-Olig2 staining confirmed a MOGHE diagnosis in all cases. Analysis by droplet digital PCR of pools of microdissected cells from one MOGHE tissue revealed a variant enrichment in clustered oligodendroglial cells and heterotopic neurons. Through an international consortium, we assembled an unprecedented series of 26 SLC35A2-MOGHE cases providing evidence that mosaic SLC35A2 variants, likely occurred in a neuroglial progenitor cell during brain development, are a genetic marker for MOGHE.

Abstract Background Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) belongs to a group of conditions called the PIK3CA-related overgrowth spectrum (PROS). The varying phenotypes and low frequencies of each somatic mosaic variant make confirmative diagnosis difficult. We present 12 patients who were diagnosed clinically and genetically with MCAP. Genomic DNA was extracted mainly from the skin of affected lesions, also from peripheral blood leukocytes and buccal epithelial cells, and target panel sequencing using high-depth next-generation sequencing technology was performed. Results Macrocephaly was present in 11/12 patients (92%). All patients had normal body asymmetry. Cutaneous vascular malformation was found in 10/12 patients (83%). Megalencephaly or hemimegalencephaly was noted in all 11 patients who underwent brain magnetic resonance imaging. Arnold–Chiari type I malformation was also seen in 10 patients. Every patient was identified as having pathogenic or likely pathogenic variants of the PIK3CA gene. The variant allele frequency (VAF) ranged from 6.3 to 35.3%, however, there was no direct correlation between VAF and the severity of associated anomalies. c.2740G > A (p.Gly914Arg) was most commonly found, in four patients (33%). No malignancies developed during follow-up periods. Conclusions This is the first and largest cohort of molecularly diagnosed patients with MCAP in Korea. Targeted therapy with a PI3K-specific inhibitor, alpelisib, has shown successful outcomes in patients with PROS in a pilot clinical study, so early diagnosis for genetic counseling and timely introduction of emerging treatments might be achieved in the future through optimal genetic testing.

Abstract Background Noonan syndrome (NS) is a developmental disorder caused by mutations of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2). Although NS patients have diverse neurological manifestations, the mechanisms underlying the involvement of SHP2 mutations in neurological dysfunction remain elusive. Methods Induced pluripotent stem cells generated from dermal fibroblasts of three NS-patients (NS-iPSCs) differentiated to the neural cells by using two different culture systems, 2D- and 3D-cultured systems in vitro. Results Here we represent that SHP2 mutations cause aberrant neural development. The NS-iPSCs exhibited impaired development of EBs in which BMP and TGF-β signalings were activated. Defective early neuroectodermal development of NS-iPSCs recovered by inhibition of both signalings and further differentiated into NPCs. Intriguingly, neural cells developed from NS-NPCs exhibited abundancy of the glial cells, neurites of neuronal cells, and low electrophysiological property. Those aberrant phenotypes were also detected in NS-cerebral organoids. SHP2 inhibition in the NS-NPCs and NS-cerebral organoids ameliorated those anomalies such as biased glial differentiation and low neural activity. Conclusion Our findings demonstrate that SHP2 mutations contribute to precocious gliogenesis in NS-iPSCs during neural development in vitro.

To delineate a livestock manure-derived groundwater plume (LDGP) in agro-livestock farming areas with the extensive use of chemical fertilizers, multilevel monitoring wells (MLWs) were installed for depth-specific sampling of groundwater, and then hydrochemical, nitrate N-O isotopic and microbiological data of shallow groundwater collected from the MLWs were evaluated with the help of multivariate statistical tools. The LDGP was distinguished from the pervasive agricultural contamination based on δ15Nnitrate (10‰). Fecal coliforms and Escherichia coli were not observed in the LDGP, whereas bovine enterovirus type 2 was detected at a sample collected at a depth of 18 m below ground level (bgl) downgradient manure piles, indicating a potential virus risk. Among hydrochemical parameters, Ca2+, Mg2+, Na+, Cl- and SiO2(aq) were shown to be effective indicators to trace the LDGP. On the other hand, nitrate was not effective to discriminate the LDGP because of denitrification in deep parts (>6 m bgl) within the LDGP, although nitrate contamination was serious at shallow parts (≤6 m bgl; 62.4 to 119.1 mg/L, median 97.9 mg/L). Thus, an integrated hydrochemical index consisting of Ca2+, Mg2+, Na+, Cl- and SiO2(aq) was suggested based on the result of principal component analysis with isometric log-ratio transformed data to delineate the LDGP in shallow unconsolidated aquifers overlying silicate bedrocks, and a threshold of the index was determined to be 1.17. The application of the index to three other agro-livestock farming areas with prevalent agricultural contamination successfully distinguished the groundwater samples within the LDGP (11 of 40 samples) that showed the index values exceeding the threshold and a median δ15Nnitrate of 12.5 ‰. The study results show that the hydrochemical index can be used for the quick evaluation of a LDGP in agro-livestock farming areas given its cost efficiency and easily accessible analysis devices for water chemistry compared to isotopes, although the broad use of the index to determine LDGPs needs to be further verified by application to various geology and land uses. Livestock manures should be carefully managed to protect groundwater resources, including impermeable covers above or beneath the manure piles, given the potential risk of virus at deep parts and nitrate at shallow parts within the LDGP. The methodology to select hydrochemical indicators for distinguishing a LDGP and the combination of the indicators to develop an index suggested in this study will be useful to build new indices adapted to local conditions.

The role of brain somatic mutations in neurodegenerative diseases such as Alzheimer’s disease (AD) is not well understood. Here the authors carry out high-depth exome sequencing ~500× on brain tissue from patients with AD and controls, and identify mutations in a number of genes that are known to contribute to phosphorylation and aggregation of tau, including PIN1.

Olive flounder (Paralichthys olivaceus) is a vital aquaculture species in East Asia. However, few studies that estimate the genetic parameters of this species have been conducted. We estimated the genetic parameters of growth traits and designed an optimum breeding programme for this species. Heritability, genetic and phenotypic correlations, and breeding values were estimated for growth traits: body weight (BW), total length (TL), and condition factor (CF). A linear mixed animal model using the restricted maximum likelihood (REML) algorithm was applied to the statistical analysis of 9 traits (BW, TL, and CF at 11, 18, and 22 months of age) for a total of 54,159 animals from 7 generations. Increases of 13%, 8%, and 6.5% in BW, TL, and CF at the harvest stage were observed, respectively, after 7 generations of selection. The heritabilities of all growth traits were moderate, ranging from 0.35 to 0.46. The phenotypic and genetic correlations between BW and TL were high and positive in all three stages (0.91 and 0.92, 0.91 and 0.93, and 0.88 and 0.91). The estimated breeding values of BW and TL increased over the generations; however, the estimated breeding value of CF fluctuated. The optimum progeny number within full-sib families for an accuracy of 0.632 is suggested to be between 10 and 25. Findings indicated that a considerable response to selection and single-trait selection based on BW would be effective in olive flounder.

An aggressive primary brain cancer, glioblastoma (GBM) is the most common cancer of the central nervous system in adults. However, an inability to identify its cell-of-origin has been a fundamental issue hindering further understanding of the nature and pathogenesis of GBM, as well as the development of novel therapeutic targets. Researchers have hypothesized that GBM arises from an accumulation of somatic mutations in neural stem cells (NSCs) and glial precursor cells that confer selective growth advantages, resulting in uncontrolled proliferation. In this review, we outline genomic perspectives on IDH-wildtype and IDH-mutant GBMs pathogenesis and the cell-of-origin harboring GBM driver mutations proposed by various GBM animal models. Additionally, we discuss the distinct neurodevelopmental programs observed in either IDH-wildtype or IDH-mutant GBMs. Further research into the cellular origin and lineage hierarchy of GBM will help with understanding the evolution of GBMs and with developing effective targets for treating GBM cancer cells.

Somatic mutations of low allele frequencies are often difficult to detect. Here, the authors develop RePlow, a computational method that leverages technical replication for detecting low-level somatic mutations using next-generation sequencing.

North Korea has shown more aggressive nuclear behavior during the Kim Jong Un era as has been evident in the rapid acceleration of its nuclear weapons development and its delivery system diversification, especially in 2016. This study seeks to determine why was there such an urgency in progressing its nuclear capability in the first few years following Kim Jong Un's ascent to power after the death of his father in 2011. It confines its research scope to Pyongyang's external motivations - its political and economic relations with the biggest regime backer, China - to conduct an academic investigation on whether Kim Jong Un's North Korea could still perceive China as a reliable patron. It concludes that the bilateral political and economic relations took a notable and simultaneous downturn, prompting it to focus on internal balancing, exemplifying the core principles of the IR theory of defensive realism. [ABSTRACT FROM AUTHOR]

Summary: The homeodomain is found in hundreds of transcription factors that play roles in fate determination via cell-autonomous regulation of gene expression. However, some homeodomain-containing proteins (HPs) are thought to be secreted and penetrate neighboring cells to affect the recipient cell fate. To determine whether this is a general characteristic of HPs, we carried out a large-scale validation for intercellular transfer of HPs. Our screening reveals that intercellular transfer is a general feature of HPs, but it occurs in a cell-context-sensitive manner. We also found the secretion is not solely a function of the homeodomain, but it is supported by external motifs containing hydrophobic residues. Thus, mutations of hydrophobic residues of HPs abrogate secretion and consequently interfere with HP function in recipient cells. Collectively, our study proposes that HP transfer is an intercellular communication method that couples the functions of interacting cells. : Lee et al. evaluate capabilities of homeodomain proteins (HPs) for transfer between cells. They find that intercellular transfer is a general but cell-context-sensitive property of HP. Intercellular HP transfer can be an unconventional way for the cells to communicate with neighboring cells that associate structurally and functionally. Keywords: homeodomain, cell-penetrating protein, protein secretion, intercellular protein transfer

Essential to development, primary cilia are microtubule-based cellular organelles that protrude from the surface of cells. Acting as cellular antenna, primary cilia play central roles in transducing or regulating several signaling pathways, including Sonic hedgehog (Shh) and Wnt signaling. Defects in primary cilia contribute to a group of syndromic disorders known as “ciliopathies” and can adversely affect development of the brain and other essential organs, including the kidneys, eyes, and liver. The molecular mechanisms of how defective primary cilia contribute to neurological defects, however, remain poorly understood. In this mini review, we summarize recent advances in understanding of the interactions between primary cilia and signaling pathways essential to cellular homeostasis and brain development.

Purpose We analyzed the spectrum and the significance of pediatric thyroid nodules depicted on sonography and evaluated the follow-up change according to the age group. Materials and Methods We retrospectively reviewed the sonographic features of 82 nodules in 69 patients (6.6%) among 1282 children less than 13 years of age without a palpable lesion, from January 2006 to January 2013. Patients were divided into three age groups; infants, preschoolers, and schoolers. Thyroid nodules were evaluated according to their sonographic characteristics (simple cyst, colloid cyst, solid mass, or intrathyroid thymus) and the changes detected at follow-up (disappearance, decrease in size, no change or increase in size) were reported. Results There was a significant difference in the nodule patterns among the age groups (p < 0.001). The nodules in infants included a simple cyst (n = 12), a solid mass (n = 12), or an intra-thyroid thymus (n = 9). The preschoolers had a simple cyst (n = 11), a colloid cyst (n = 5), a solid mass (n = 3) or an intra-thyroid thymus (n = 5). However, the schoolers had a simple cyst (n = 2), a colloid cyst (n = 18), and a solid mass (n = 5), but there was no case of intra-thyroid thymus. Follow-up of 38 cases revealed significant differences among the age groups (p = 0.018). The nodules in infants showed findings such as disappearance of nodules (n = 9) and no change (n = 10) on follow-up sonography. In preschoolers, the nodules had disappeared (n = 2), decreased in size (n = 1), and showed no change (n = 11). However, the nodules in schoolers were found to be decreased in size (n = 1), show no change (n = 2), and increased in size (n = 2). The proven pathologic finding was benign in four patients. Conclusion There were significant differences in the prevalence and the interval change of thyroid nodules among infants, preschoolers, and schoolers. A large series of intrathyroid thymus was seen in infants and preschoolers, and masses did not increase in size in these age groups. The frequency of a colloid cyst could be increased in schoolers, and masses were increased in size in this age group, but none of the patients showed a malignant finding on pathology.

An amendment to this paper has been published and can be accessed via the original article.

Study DesignA prospective sonographic study.PurposeTo verify the effectiveness of simultaneous application of two landmarks, Doppler image of the vertebral artery and shape of the transverse tubercle of the seventh cervical (C7) vertebra.Overview of LiteratureCounting upwards from the C7 vertebra which only has a posterior tubercle of the transverse process is a commonly used method for ultrasound-guided cervical nerve root block. However, each transverse process has a different shape.MethodsSonograms of 20 volunteers were examined. At first, we identified the C7 transverse process based on the presence of the vertebral artery without the anterior tubercle. The C5 and C6 transverse processes were identified based on the presence of anterior tubercle without the vertebral artery. Subsequently, we placed needles on the C5, C6, and C7 transverse processes and the location and direction of needles were confirmed by fluoroscopy.ResultsIn the 120 segments, 93.3% of needles were placed correctly as desired; 97.5% of needles were placed on the 5C transverse process; 97.5% of needles were placed on the C6 transverse process; and 85.0% of needles were placed on the C7 transverse process, respectively. Both sides showed the same accuracy of 93.3%.ConclusionsSimultaneous application of Doppler image of the vertebral artery and shape of the C7 transverse tubercle showed 93.3% accuracy in identifying the target cervical level. Therefore, Doppler image of the vertebral artery can be considered to be a useful landmark for ultrasound-guided cervical nerve root block.