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Glioma accounts for 80% of all malignant brain tumours and is the most common adult primary brain tumour. Age is an important factor affecting the development of cancer, as somatic mutations accumulate with age. Here, we aimed to analyse the significance of age-dependent non-silent somatic mutations in glioma prognosis. Histological tumour grade depends on age at diagnosis in patients with IDH1, TP53, ATRX, and EGFR mutations. Age of patients with wild-type IDH1 and EGFR increased with increase in tumour grade, while the age of patients with IDH1 or EGFR mutation remained constant. However, the age of patients with EGFR mutation was higher than that of patients with IDH1 mutation. The hierarchical clustering of patients was dominantly separated by IDH1 and EGFR mutations. Furthermore, patients with IDH1 mutation were dominantly separated by TP53 and ATRX double mutation and its double wild-type counterpart. The age of patients with ATRX and TP53 mutation was lower than that of patients with wild-type ATRX and TP53. Patients with the double mutation showed poorer prognosis than those with the double wild type genotype. Unlike IDH1 mutant, IDH1 wild-type showed upregulation of expression of epithelial mesenchymal transition associated genes.

Traumatic brain injury (TBI) occurs frequently, and acute TBI requiring surgical treatment is closely related to patient survival. Models for predicting the prognosis of patients with TBI do not consider various factors of patient status; therefore, it is difficult to predict the prognosis more accurately. In this study, we created a model that can predict the survival of patients with TBI by adding hematologic parameters along with existing non-hematologic parameters. The best-fitting model was created using the Akaike information criterion (AIC), and hematologic factors including preoperative hematocrit, preoperative C-reactive protein (CRP), postoperative white blood cell (WBC) count, and postoperative hemoglobin were selected to predict the prognosis. Among several prediction models, the model that included age, Glasgow Coma Scale, Injury Severity Score, preoperative hematocrit, preoperative CRP, postoperative WBC count, postoperative hemoglobin, and postoperative CRP showed the highest area under the curve and the lowest corrected AIC for a finite sample size. Our study showed a new prediction model for mortality in patients with TBI using non-hematologic and hematologic parameters. This prediction model could be useful for the management of patients with TBI.

Inflammation in tumor microenvironments is implicated in the pathogenesis of tumor development. In particular, inflammasomes, which modulate innate immune functions, are linked to tumor growth and anticancer responses. However, the role of the NLRC4 inflammasome in gliomas remains unclear. Here, we investigated whether the upregulation of the NLRC4 inflammasome is associated with the clinical prognosis of gliomas. We analyzed the protein expression and localization of NLRC4 in glioma tissues from 11 patients by immunohistochemistry. We examined the interaction between the expression of NLRC4 and clinical prognosis via a Kaplan-Meier survival analysis. The level of NLRC4 protein was increased in brain tissues, specifically, in astrocytes, from glioma patients. NLRC4 expression was associated with a poor prognosis in glioma patients, and the upregulation of NLRC4 in astrocytomas was associated with poor survival. Furthermore, hierarchical clustering of data from the Cancer Genome Atlas dataset showed that NLRC4 was highly expressed in gliomas relative to that in a normal healthy group. Our results suggest that the upregulation of the NLRC4 inflammasome contributes to a poor prognosis for gliomas and presents a potential therapeutic target and diagnostic marker.

(1) Background: The elevation of glucose metabolism is linked to high-grade gliomas such as glioblastoma multiforme (GBM). The high glycolytic phenotype is associated with cellular proliferation and resistance to treatment with chemotherapeutic agents in GBM. MicroRNA-542-3p (miR-542-3p) has been implicated in several tumors including gliomas. However, the role of miR-542-3p in glucose metabolism in human gliomas remains unclear, (2) Methods: We measured the levels of cellular proliferation in human glioma cells. We measured the glycolytic activity in miR-542-3p knockdown and over-expressed human glioma cells. We measured the levels of miR-542-3p and HK2 in glioma tissues from patients with low- and high-grade gliomas using imaging analysis, (3) Results: We show that knockdown of miR-542-3p significantly suppressed cellular proliferation in human glioma cells. Knockdown of miR-542-3p suppressed HK2-induced glycolytic activity in human glioma cells. Consistently, over-expression of miR-542-3p increased HK2-induced glycolytic activity in human glioma cells. The levels of miR-542-3p and HK2 were significantly elevated in glioma tissues of patients with high-grade gliomas relative to that in low-grade gliomas. The elevation of HK2 levels in patients with high-grade gliomas were positively correlated with the high levels of miR-542-3p in GBM and low-grade gliomas (LGG) based on the datasets from the Cancer Genome Atlas (TCGA) database. Moreover, the high levels of miR-542-3p were associated with poor survival rate in the TCGA database, (4) Conclusions: miR-542-3p contributes to the HK2-mediated high glycolytic phenotype in human glioma cells.

The importance of maximal resection in the treatment of glioblastoma (GBM) has been reported in many studies, but maximal resection of thalamic GBM is rarely attempted due to high rate of morbidity and mortality. The purpose of this study was to investigate the role of surgical resection in adult thalamic glioblastoma (GBM) treatment and to identify the surgical technique of maximal safety resection. In case of suspected thalamic GBM, surgical resection is the treatment of choice in our hospital. Biopsy was considered when there was ventricle wall enhancement or multiple enhancement lesion in a distant location. Navigation magnetic resonance imaging, diffuse tensor tractography imaging, tailed bullets, and intraoperative computed tomography and neurophysiologic monitoring (transcranial motor evoked potential and direct subcortical stimulation) were used in all surgical resection cases. The surgical approach was selected on the basis of the location of the tumor epicenter and the adjacent corticospinal tract. Among the 42 patients, 19 and 23 patients underwent surgical resection and biopsy, respectively, according to treatment strategy criteria. As a result, the surgical resection group exhibited a good response with overall survival (OS) (median: 676 days, p < 0.001) and progression-free survival (PFS) (median: 328 days, p < 0.001) compared with each biopsy groups (doctor selecting biopsy group, median OS: 240 days and median PFS: 134 days; patient selecting biopsy group, median OS: 212 days and median PFS: 118 days). The surgical resection groups displayed a better prognosis compared to that of the biopsy groups for both the O6-methylguanine-DNA methyltransferase unmethylated (log-rank p = 0.0035) or methylated groups (log-rank p = 0.021). Surgical resection was significantly associated with better prognosis (hazard ratio: 0.214, p = 0.006). In case of thalamic GBM without ventricle wall-enhancing lesion or multiple lesions, maximal surgical resection above 80% showed good clinical outcomes with prolonged the overall survival compared to biopsy. It is helpful to use adjuvant surgical techniques of checking intraoperative changes and select the appropriate surgical approach for reducing the surgical morbidity.

Oligodendroglioma (OD) is a subtype of glioma occurring in the central nervous system. The 1p/19q codeletion is a prognostic marker of OD with an isocitrate dehydrogenase (IDH) mutation and is associated with a clinically favorable overall survival (OS), however, the exact underlying mechanism remains unclear. Long non-coding RNAs (lncRNAs) have recently been suggested to regulate carcinogenesis and prognosis in cancer patients. Here, we performed in silico analyses using low-grade gliomas from datasets obtained from The Cancer Genome Atlas to investigate the effects of ceRNA with 1p/19q codeletion on ODs. Thus, we selected modules of differentially expressed genes that were closely related to 1p/19q codeletion traits using weighted gene co-expression network analysis and constructed 16 coding RNA&ndash, miRNA&ndash, lncRNA networks. The ceRNA network participated in ion channel activity, insulin secretion, and collagen network and extracellular matrix (ECM) changes. In conclusion, ceRNAs with a 1p/19q codeletion can create different tumor microenvironments via potassium ion channels and ECM composition changes, furthermore, differences in OS may occur. Moreover, if extrapolated to gliomas, our results can provide insights into the consequences of identical gene expression, indicating the possibility of tracking different biological processes in different subtypes of glioma.

Glioblastoma multiforme (GBM) is an aggressive malignancy classified by the World Health Organization as a grade IV glioma. Despite the availability of aggressive standard therapies, most patients experience recurrence, for which there are currently no effective treatments. We aimed to conduct a phase I/IIa clinical trial to investigate the safety and efficacy of adoptive, ex-vivo-expanded, and activated natural killer cells and T lymphocytes from peripheral blood mononuclear cells of patients with recurrent GBM. This study was a single-arm, open-label, investigator-initiated trial on 14 patients recruited between 2013 and 2017. The immune cells were administered via intravenous injection 24 times at 2-week intervals after surgical resection or biopsy. The safety and clinical efficacy of this therapy was examined by assessing adverse events and comparing 2-year overall survival (OS). Transcriptomic analysis of tumor tissues was performed using NanoString to identify the mechanism of therapeutic efficacy. No grade 4 or 5 severe adverse events were observed. The most common treatment-related adverse events were grade 1 or 2 in severity. The most severe adverse event was grade 3 fever. Median OS was 22.5 months, and the median progression-free survival was 10 months. Five patients were alive for over 2 years and showed durable response with enhanced immune reaction transcriptomic signatures without clinical decline until the last follow-up after completion of the therapy. In conclusion, autologous adoptive immune-cell therapy was safe and showed durable response in patients with enhanced immune reaction signatures. This therapy may be effective for recurrent GBM patients with high immune response in their tumor microenvironments. Trial registration: The Korea Clinical Research Information Service database: KCT0003815, Registered 18 April 2019, retrospectively registered.

Cavernous malformations (CMs) of cranial nerves (CN) III, IV, and VI are extremely rare, and limited studies have assessed functional outcomes after treatment. This systematic review investigated the clinical features of CMs in ocular motor CNs, including the treatment results, and compared different surgical methods for functional preservation of ocular motor CNs. ‘PubMed’, ‘SCOPUS’, ‘Web of Science’, and ‘Google Scholar’ databases were searched to identify case reports and studies published between January 1980 and December 2018. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-seven patients were identified (median age, 46 years; range, 3 months-71 years). CN III was involved in 17 patients (63.0%), CN IV in 8 (29.6%), and CN VI in 2 (7.4%). Treatments included gross total resection (GTR) and nerve transection in 6 patients (22.2%), GTR and nerve continuity preservation in 7 (25.9%), subtotal resection (STR) and nerve continuity preservation in 4 (14.8%), GTR and end-to-end anastomosis in 5 (18.5%), and conservative care in 3 (11.1%), while the treatment method for 2 (7.4%) patients has not been described in the literature. In 22 patients who underwent surgical treatment, functional changes included improvement in 9 patients (40.9%), no change in 10 (45.5%), and worsening symptoms in 3 (13.6%). Functional preservation was achieved in 12 (54.5%) of the 22 patients; the nerve continuity preservation method conferred a significant advantage for functional preservation compared with other surgical methods (p = 0.004). Functional preservation of ocular motor CNs can be achieved by nerve continuity preservation.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high infectivity in humans, attributed to the strong affinity of its spike (S) protein to human angiotensin-converting enzyme 2 (ACE2). Here, we analyzed the structural similarity of the S protein between SARS-CoV-2 and other SARS-related coronaviruses (CoVs). Methods We performed multiple alignment analysis of nine amino acid sequences of CoV S proteins from NCBI with MAFFT web-based software, followed by phylogeny analysis. Three-dimensional structure modeling was performed by SWISS-MODEL. We calculated the template modeling score between the S protein of SARS-CoV-2 and that of other SARS-related CoVs. Results The S1 domain of the unclassified CoV RaTG13 (the host of which is the intermediate horseshoe bat) was structurally very similar to that of SARS-CoV-2, implying that RaTG13 could be the origin of SARS-CoV-2. In addition, the folding property of the entire S protein was nearly the same between SARS-CoV-2 and RaTG13 after the PRRA amino acid insertion was removed from SARS-CoV-2. Conclusions RaTG13 could have a high binding affinity to ACE2, similar to SARS-CoV-2, and it is therefore highly likely to infect other animals. Therefore, massive research and monitoring of CoVs in animals is necessary to prevent future COVID-19-like disasters.

BACKGROUND The elevation of glucose metabolism is linked to high-grade gliomas such as glioblastoma multiforme (GBM). The high glycolytic phenotype is associated with cellular proliferation and resistance to treatment with chemotherapeutic agents in GBM. MicroRNA-542-3p (miR-542-3p) has been implicated in several tumors including gliomas. However, the role of miR-542-3p in glucose metabolism in human gliomas remains unclear. METHODS We measured the levels of cellular proliferation in human glioma cells. We measured the glycolytic activity in miR-542-3p knockdown and over-expressed human glioma cells. We measured the levels of miR-542-3p and HK2 in glioma tissues from patients with low- and high-grade gliomas using imaging analysis. RESULTS We show that knockdown of miR-542-3p significantly suppressed cellular proliferation in human glioma cells. Knockdown of miR-542-3p suppressed HK2-induced glycolytic activity in human glioma cells. Consistently, over-expression of miR-542-3p increased HK2-induced glycolytic activity in human glioma cells. The levels of miR-542-3p and HK2 were significantly elevated in glioma tissues of patients with high-grade gliomas relative to that in low-grade gliomas. The elevation of HK2 levels in patients with high-grade gliomas were positively correlated with the high levels of miR-542-3p in GBM and low-grade gliomas (LGG) based on the datasets from the Cancer Genome Atlas (TCGA) database. Moreover, the high levels of miR-542-3p were associated with poor survival rate in the TCGA database. CONCLUSIONS miR-542-3p contributes to the HK2-mediated high glycolytic phenotype in human glioma cells.

Glioblastoma multiforme (GBM) is an aggressive malignancy classified by the World Health Organization as a grade IV glioma. Despite the availability of aggressive standard therapies, most patients experience recurrence, for which there are currently no effective treatments. We aimed to conduct a phase I/IIa clinical trial to investigate the safety and efficacy of adoptive, ex-vivo-expanded, and activated natural killer cells and T lymphocytes from peripheral blood mononuclear cells of patients with recurrent GBM. This study was a single-arm, open-label, investigator-initiated trial on 14 patients recruited between 2013 and 2017. The immune cells were administered via intravenous injection 24 times at 2-week intervals after surgical resection or biopsy. The safety and clinical efficacy of this therapy was examined by assessing adverse events and comparing 2-year overall survival (OS). Transcriptomic analysis of tumor tissues was performed using NanoString to identify the mechanism of therapeutic efficacy. No grade 4 or 5 severe adverse events were observed. The most common treatment-related adverse events were grade 1 or 2 in severity. The most severe adverse event was grade 3 fever. Median OS was 22.5 months, and the median progression-free survival was 10 months. Five patients were alive for over 2 years and showed durable response with enhanced immune reaction transcriptomic signatures without clinical decline until the last follow-up after completion of the therapy. In conclusion, autologous adoptive immune-cell therapy was safe and showed durable response in patients with enhanced immune reaction signatures. This therapy may be effective for recurrent GBM patients with high immune response in their tumor microenvironments. Trial registration: The Korea Clinical Research Information Service database: KCT0003815, Registered 18 April 2019, retrospectively registered.

Development and maintenance of software plat-form APIs are challenging because new APIs are constantly added in new software platforms. Furthermore, software plat-form API development requires a lot of stakeholders to work together on tight release schedules. Application developers use platform's APIs to create their applications and therefore providing a well-defined and comprehensive set of platform APIs may be the most basic requirement for software platforms. To provide such APIs, API usability should be secured and API backward compatibility should be guaranteed in subsequent platform re-leases. In these circumstances, sharing lessons learned from multiple years of experience of platform API development, mainte-nance, and releases using an integrated API development process can benefit API researchers and practitioners who have similar needs to create or adopt API development process for their projects. In this paper we share an API development and mainte-nance process for multi-device Tizen software platform, which we call the Tizen API Change Request (ACR) process. The process has been used among various Tizen API stakeholders for several years of Tizen platform and SDK releases to keep API usability and compatibility high. We believe the process can be further applied to various software platforms and projects to systematically develop and maintain their APIs.

Background: High sodium and/or low mineral intake are known to be associated with elevated blood pressure. It has been reported that substituting low-sodium, mineral-rich salt for refined salt lowers blood pressure (BP). And solar salt is emerging as a low sodium high mineral salt for a healthy diet in Korea. Therefore, this double-blind, randomized, and placebo-controlled trial was conducted to explore changes in BP from substituting refined salt with solar salt among hypertensive elderly subjects. Methods: Forty-three hypertensive and institutionalized elderly individuals aged 65 years or older were enrolled. Thirty-eight subjects (88.4%) completed the study. Subjects were provided with either a solar saltor refined salt-based diet for eight weeks. Results: Systolic BP decreased significantly in the solar salt-based diet group after 2, 4, and 8 weeks when compared to the refined salt-based diet group. And, diastolic BP was lowered significantly in the solar salt-based diet group compared to that in the refined salt-based diet group after 8 weeks. In addition, urinary sodium/potassium, and angiotension converting enzyme activity decreased significantly in the solar salt-based diet group compared to the refined salt-based group. Urinary potassium excretion was significantly increased in the solar salt-based diet group. Conclusions: These results may provide clinical evidence that solar salt has beneficial effects on BP in elderly patients. And, people such as Koreans, who do not consume enough minerals, may experience a greater anti-hypotensive effect by using solar salt. However, further large-scale studies are necessary. Korean J Health Promot 2015;15(3):98-107