Analysis of Risk Factors Associated with Proximal Junctional Kyphosis Following Long Instrumented Fusion from L1 to Sacrum: Age Itself Does Not Independently Increase the Risk.

Background and Objectives: This study is a retrospective analysis aimed at understanding the incidence and risk factors of proximal junctional kyphosis (PJK) following long-instrumented spinal fusion from L1 to the sacrum in patients with mild to moderate sagittal imbalance. Materials and Methods: It recruited consecutive patients undergoing instrumented fusion from L1 to the sacrum for degenerative lumbar disease between June 2006 and November 2019 in a single institution. The patients' preoperative clinical data, muscle status at T12-L1 on magnetic resonance images, and sagittal spinopelvic parameters were analyzed. Univariate analysis was used to compare clinical and radiographic data between PJK and non-PJK patients. Logistic regression analysis was used to investigate the independent risk factors for PJK. Results: A total of 56 patients were included in this study. The mean age at surgery was 67.3 years and mean follow-up period was 37.3 months. In total, 10 were male and 46 were female. PJK developed in 23 (41.1%) out of 56; of these patients, 20 (87.0%) developed PJK within 1 year postoperatively. In the univariate analysis between PJK and non-PJK patients, the PJK group showed more frequent osteoporosis, lower body mass index, smaller cross-sectional area (CSA) and more fat infiltration (FI) in erector spinae muscle at T12-L1 and larger preoperative TLK and PT with statistical significance (p < 0.05). In the logistic regression analysis, severe (>50%) FI in erector spinae muscle (OR = 43.60, CI 4.10-463.06, R2N = 0.730, p = 0.002) and osteoporosis (OR = 20.49, CI 1.58-264.99, R2N = 0.730, p = 0.021) were statistically significant. Conclusions: Preexisting severe (>50%) fat infiltration in the erector spinae muscle and osteoporosis were independent risk factors associated with PJK following instrumented fusion from L1 to the sacrum, but age was not a risk factor.

Histone demethylase PHF2 activates CREB and promotes memory consolidation.

Long-term memory formation is attributed to experience-dependent gene expression. Dynamic changes in histone methylation are essential for the epigenetic regulation of memory consolidation-related genes. Here, we demonstrate that the plant homeodomain finger protein 2 (PHF2) histone demethylase is upregulated in the mouse hippocampus during the experience phase and plays an essential role in memory formation. PHF2 promotes the expression of memory-related genes by epigenetically reinforcing the TrkB-CREB signaling pathway. In behavioral tests, memory formation is enhanced by transgenic overexpression of PHF2 in mice, but is impaired by silencing PHF2 in the hippocampus. Electrophysiological studies reveal that PHF2 elevates field excitatory postsynaptic potential (fEPSP) and NMDA receptor-mediated evoked excitatory postsynaptic current (EPSC) in CA1 pyramidal neurons, suggesting that PHF2 promotes long-term potentiation. This study provides insight into the epigenetic regulation of learning and memory formation, which advances our knowledge to improve memory in patients with degenerative brain diseases.

Quantitative analysis in peritumoral volumes of brain metastases treated with stereotactic radiotherapy.

PURPOSE: The purpose of this study was to verify changes in diffusion tensor imaging (DTI) factors in patients with brain metastases treated with stereotactic radiotherapy (SRT). We also investigated the impact of SRT on peritumoral volumes though the use of DTI. METHODS: A total of 28 patients with brain metastases who had undergone SRT between March 2014 and December 2015 were enrolled. Magnetic resonance imaging with DTI factors, such as fractional anisotropy (FA) and apparent diffusion tensor (ADC) value, was performed 1 day before the procedure and 3 months after the procedure. DTI data from tumor lesions, edema volumes, and the volumes that received 12Gy were measured. RESULTS: Tumor volume (P=0.001) and ADC values in the volumes that received 12Gy (P=0.018) and the edema volumes (P=0.003) significantly decreased after the procedure. Decreases in tumor volume were only correlated with decreases in edema volumes (P<0.001). Decreases in edema volumes were correlated with increases in FA values and decreases in ADC values of the volumes that received 12Gy [P=0.019 (FA)/0.002 (ADC)] and the edema volumes [P=0.011 (FA)/0.002 (ADC)]. CONCLUSIONS: It was possible to quantify changes in peritumoral volumes in patients with brain metastases after SRT by using DTI. ADC values of peritumoral volumes decreased significantly after SRT. Therefore, it was confirmed through DTI that performing SRT on tumor lesions has a positive effect on the structure and function of peritumoral volumes.

Dynamic light scattering analysis of SNARE-driven membrane fusion and the effects of SNARE-binding flavonoids.

Soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) proteins generate energy required for membrane fusion. They form a parallelly aligned four-helix bundle called the SNARE complex, whose formation is initiated from the N terminus and proceeds toward the membrane-proximal C terminus. Previously, we have shown that this zippering-like process can be controlled by several flavonoids that bind to the intermediate structures formed during the SNARE zippering. Here, our aim was to test whether the fluorescence resonance energy transfer signals that are observed during the inner leaflet mixing assay indeed represent the hemifused vesicles. We show that changes in vesicle size accompanying the merging of bilayers is a good measure of progression of the membrane fusion. Two merging vesicles with the same size D in diameter exhibited their hydrodynamic diameters 2D + d (d, intermembrane distance), 2D and 2D as membrane fusion progressed from vesicle docking to hemifusion and full fusion, respectively. A dynamic light scattering assay of membrane fusion suggested that myricetin stopped membrane fusion at the hemifusion state, whereas delphinidin and cyanidin prevented the docking of the vesicles. These results are consistent with our previous findings in fluorescence resonance energy transfer assays.

Ancient mitochondrial DNA analyses of ascaris eggs discovered in coprolites from joseon tomb.

Analysis of ancient DNA (aDNA) extracted from Ascaris is very important for understanding the phylogenetic lineage of the parasite species. When aDNAs obtained from a Joseon tomb (SN2-19-1) coprolite in which Ascaris eggs were identified were amplified with primers for cytochrome b (cyt b) and 18S small subunit ribosomal RNA (18S rRNA) gene, the outcome exhibited Ascaris specific amplicon bands. By cloning, sequencing, and analysis of the amplified DNA, we obtained information valuable for comprehending genetic lineage of Ascaris prevalent among pre-modern Joseon peoples.

Switchable beaming from a nanoslit with metallic gratings controlled by the phase difference between incident beams.

We propose a switching method for optical beaming generated from a metal slit surrounded by surface gratings. The principle of the method is based on the interference of diffracted surface plasmon polaritons from the gratings which are controlled by the relative phases of two oblique incident beams that are illuminated on the metal slit. By adjusting the relative position of the interference pattern of the incident beams with respect to the metal slit, beaming from the proposed structure can be switched from the on- to the off-mode by virtue of the change in the symmetry of the generated surface plasmon polaritons. An experimental demonstration of the method is presented in which an electrically controlled interferometric configuration is used.

Pediatric Eosinophilic Granuloma Associated With Delayed Epidural Hematoma Following on Seizure: A Case Report.

Eosinophilic granuloma (EG), a subtype of Langerhans cell histiocytosis (LCH), the monostotic form, is a rare condition characterized by a solitary bone lesion. It is even more unusual for this condition to be accompanied by an epidural hematoma (EDH). This case is unique in that it is the first to involve delayed EDH following a seizure. We describe a remarkable example of EG accompanied by an EDH and consider the rarity of this comorbidity. A 32-month-old boy developed a rapidly growing skull mass following a minor head injury. During surgical preparation for a biopsy, the patient experienced a single convulsion. Imaging following the seizure revealed an EDH in the vicinity of the mass. The mass was excised and confirmed to be an EG, but with positive margins. The patient underwent chemotherapy after systemic skeletal evaluation, in accordance with the LCH III protocol established by the Histiocytosis Society. EG is a rare neoplasm that typically presents as a painless growth on the skull that gradually enlarges over time. The correlation between EG and EDH is exceedingly uncommon, with only a few documented cases. This case study underscores the significance of considering EG in the differential diagnosis of an expanding cranium mass, even when associated with EDH. Prompt diagnosis and treatment can prevent serious complications and improve patient outcomes.

The Efficacy and Tolerability of Radiosurgery in Treating Benign Meningiomas: A Dose Comparison Study from a Single-Center Analysis.

This retrospective study aimed to evaluate the impact of radiation dose on the outcomes of stereotactic radiosurgery (SRS) for benign meningiomas and determine an optimal dosing strategy for balancing tumor control and treatment-related toxicity. Clinical data of 147 patients with 164 lesions treated between 2014 and 2022 were reviewed. Primary outcomes included progression-free survival (PFS), local control rate (LCR), and radiation-induced toxicity, with secondary outcomes focusing on LCR and radiation-induced peritumoral edema (PTE) in two dose groups (≥14 Gy and <14 Gy). The results revealed a median follow-up duration of 47 months, with 1-year, 2-year, and 5-year PFS rates of 99.3%, 96.7%, and 93.8%, respectively, and an overall LCR of 95.1%. Radiation-induced toxicity was observed in 24.5% of patients, primarily presenting mild symptoms. Notably, no significant difference in LCR was found between the two dose groups (p = 0.628), while Group 2 (<14 Gy) exhibited significantly lower PTE (p = 0.039). This study concludes that SRS with a radiation dose < 14 Gy demonstrates comparable tumor control with reduced toxicity, advocating consideration of such dosing to achieve a balance between therapeutic efficacy and safety.

Neddylation of insulin receptor substrate acts as a bona fide regulator of insulin signaling and its implications for cancer cell migration.

Irregularities in insulin signaling have significantly increased the risk of various cancers, yet the precise underlying mechanisms remain unclear. Within our study, we observed that inhibiting neddylation enhances cancer cell migration across different cancer types by activating both insulin receptor substrates 1 and 2 (IRS1 and IRS2), along with the PI3K/AKT signaling pathway. Notably, in the context of high-grade serous carcinoma (HGSC) patients, whether they had type 2 diabetes mellitus or not, IRS1 and IRS2 displayed a parallel relationship with each other while exhibiting an inverse relationship with NEDD8. We also identified C-CBL as an E3 ligase responsible for neddylating IRS1 and IRS2, with clinical evidence further confirming a reciprocal relationship between C-CBL and pAKT, thereby reinforcing the tumor suppressive role of C-CBL. Altogether, these findings suggest that neddylation genuinely participates in IRS1 and IRS2-dependent insulin signaling, effectively suppressing cancer cell migration. Thus, caution is advised when considering neddylation inhibitors as a treatment option for cancer patients, particularly those presenting with insulin signaling dysregulations linked to conditions like obesity-related type 2 diabetes or hyperinsulinemia.

Tunable subwavelength hot spot of dipole nanostructure based on VO2 phase transition.

We propose a novel approach to generate and tune a hot spot in a dipole nanostructure of vanadium dioxide (VO2) laid on a gold (Au) substrate. By inducing a phase transition of the VO2, the spatial and spectral distributions of the hot spot generated in the feed gap of the dipole can be tuned. Our numerical simulation based on a finite-element method shows a strong intensity enhancement difference and tunability near the wavelength of 678 nm, where the hot spot shows 172-fold intensity enhancement when VO2 is in the semiconductor phase. The physical mechanisms of forming the hot spots at the two-different phases are discussed. Based on our analysis, the effects of geometric parameters in our dipole structure are investigated with an aim of enhancing the intensity and the tunability. We hope that the proposed nanostructure opens up a practical approach for the tunable near-field nano-photonic devices.

Pediatric Traumatic Brain Injury : The Epidemiology in Korea.

Traumatic brain injury (TBI) is one of the leading causes of death in the pediatric population in Korea. In addition, it can cause disability in children and adolescents, with physical and mental consequences. This causes a substantial burden on the health care system and occurs globally and not just in Korea. We searched and reviewed current data on the epidemiologic characteristics of pediatric TBI in Korea. Our review provides the recent epidemiological trend mainly focusing on incidence and mortality along with worldwide reported data. This review will be helpful to understand the global epidemiology of pediatric TBI and its differences between countries.

The Effect of Neddylation Blockade on Slug-Dependent Cancer Cell Migration Is Regulated by p53 Mutation Status.

The tumor suppressor protein p53 is frequently inactivated in human malignancies, in which it is associated with cancer aggressiveness and metastasis. Because p53 is heavily involved in epithelial-mesenchymal transition (EMT), a primary step in cell migration, p53 regulation is important for preventing cancer metastasis. p53 function can be modulated by diverse post-translational modifications including neddylation, a reversible process that conjugates NEDD8 to target proteins and inhibits the transcriptional activity of p53. However, the role of p53 in cancer migration by neddylation has not been fully elucidated. In this study, we reported that neddylation blockade induces cell migration depending on p53 status, specifically via the EMT-promoting transcription factor Slug. In cancer cell lines expressing wild type p53, neddylation blockade increased the transcriptional activity of p53 and expression of its downstream genes p21 and MDM2, eventually promoting proteasomal degradation of Slug. In the absence of p53, neddylation blockade increased cell migration by activating the PI3K/Akt/mTOR/Slug signaling axis. Because mutant p53 was transcriptionally inactivated but maintained the ability to bind to Slug, neddylation blockade did not affect the migration of cells expressing mutant p53. Our findings highlight how the p53 expression status influences neddylation-mediated cell migration in multiple cancer cell lines via Slug.

Benign meningioma manifesting with acute subdural hematoma and cerebral edema: a case report and review of the literature.

BACKGROUND: Spontaneous subdural hematoma rarely presents with a hypervascular or malignant tumor but even less frequently in a benign tumor like meningioma. We encountered a patient with acute subdural hematoma associated with benign meningioma. Here, we report this case along with a review of previous reports, especially focusing on their clinical features and possible bleeding mechanisms. CASE PRESENTATION: A 53-year-old Asian woman presented with severe headache and progressive neurologic deterioration due to cerebral edema. The patient was submitted to open surgery for evacuation of the subdural hematoma and concurrent tumor removal on the ipsilateral parietal convexity. A hypervascular, encapsulated mass was identified during surgery and completely removed including the adjacent dura mater (Simpson grade 0). The tumor was histologically confirmed as an angiomatous meningioma (World Health Organization grade I). Her clinical course was uneventful after surgery. CONCLUSIONS: Although meningiomas are commonly benign according to their histological traits, they can lead to spontaneous bleeding and cause neurologically unstable condition. Therefore, meningiomas need to be considered as a cause of spontaneous subdural hematoma if radiologically suspicious, which should be reflected by proper management for a positive outcome.

Magnetic resonance imaging performed on a hydrated mummy of medieval Korea.

Previous investigations have shown that magnetic resonance imaging (MRI) can be employed as an efficient non-invasive diagnostic tool in studies on Egyptian mummies. MRI, moreover, because it produces especially clear images of well-hydrated tissue, could be a particularly effective diagnostic option for mummies that still retain humidity within tissues or organs. Therefore, in the present study, we tested MRI on a 17th century mummy, one of the most perfectly preserved 'hydrated mummies' ever found in Korea, in order to determine the quality of images that could be obtained. We found that the diagnostic value of an MRI scan of the hydrated mummy was not inferior to that of a computed tomography scan. The T1- and T2-weighted magnetic resonance (MR) signals showed unique patterns not easily obtained by computed tomography, the resultant MR images revealing the organ specificities clearly. Overall, the quality of the MR images from the hydrated mummy was superb and the scientific value of MRI in the study of hydrated mummies should not be underestimated.

Neddylation blockade induces HIF-1α driven cancer cell migration via upregulation of ZEB1.

Neddylation is a process by which NEDD8 is covalently conjugated to target proteins by sequential enzymatic reaction. Its role in cancer cell migration has only been recently acknowledged. Previously in cancer cell migration, the epithelial to mesenchymal transition (EMT) process has been well-known to play an important role in both invasion and metastasis by promoting mesenchymal phenotype in epithelial cells. However, the role of neddylation in the EMT process and its mechanistic details are yet to be elucidated. We recently reported that neddylation plays a crucial role in cancer cell migration through the PI3K-Akt pathway. Here, we report that inhibiting neddylation activates the hypoxia-inducible factor 1α (HIF-1α) through the PI3K-Akt pathway, which eventually regulates the EMT-activator ZEB1 (zinc finger E-box binding homeobox 1) in various cancer cell lines. As induction of HIF-1α is known to deteriorate the state of cancer and EMT process is one of the hallmarks of metastasis in cancer, our findings uncover the role of neddylation between HIF-1α and ZEB1.

Pituitary Blastoma in a 19-Year-Old Woman: A Case Report and Review of Literature.

BACKGROUND: Pituitary blastoma is a malignant neoplasm of the pituitary gland that was recognized by the World Health Organization in 2017. It is commonly diagnosed in children before 24 months of age. Here, we report the first case of a young adult patient who was diagnosed with pituitary blastoma with increased levels of growth hormone instead of adrenocorticotropic hormone and provide a review of the literature. CASE DESCRIPTION: A 19-year-old woman presented to our hospital with visual disturbance. She had a medical history of Wilms' tumor and multinodular goiter. The brain imaging showed a 3.2 × 2.5 × 1.8-cm solid sellar and suprasellar cystic mass that upwardly displaced the optic chiasm. She had an elevated level of growth hormone but a normal level of adrenocorticotropic hormone, cortisol, and prolactin. The mass was subtotally removed through the left pterional craniotomy. The pathologic examination suggested a pituitary blastoma. Thereafter, the patient was treated with chemotherapy and radiotherapy. At 4-year follow-up postsurgery, her overall well-being is good. CONCLUSIONS: Although in this case the patient was a young adult, pituitary blastoma should be taken into consideration when children have an enhanced sellar and suprasellar mass with peripherally located cysts.

Neddylation of sterol regulatory element-binding protein 1c is a potential therapeutic target for nonalcoholic fatty liver treatment.

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for progression of steatohepatitis, liver cirrhosis, and liver cancer. Although pathological condition of NAFLD, which arises from an excessive accumulation of triglyceride in the liver, is accompanied by elevated sterol regulatory element-binding protein 1c (SREBP1c) level, it is largely unknown which factors are involved in the modification of SREBP1c. In this study, we discovered that neddylation of SREBP1c competes with its ubiquitination and stabilizes SREBP1c protein level, and eventually promotes hepatic steatosis. We also demonstrated that human homolog of mouse double minute 2 (HDM2) acts as an E3 neddylation ligase of SREBP1c. Further, treatment with the neddylation inhibitor, MLN4924, attenuates high-fat diet-induced hepatic steatosis by reducing the levels of SREBP1c protein and hepatic triglyceride. Our results indicate that the blockade of SREBP1c neddylation could be a novel approach in the defense against NAFLD.

The Effect of Vitamin D Supplementation in Patients with Acute Traumatic Brain Injury.

OBJECTIVE: To investigate the acute and long-term effects of vitamin D supplementation on the recovery of patients with traumatic brain injury (TBI). METHODS: A retrospective study was conducted involving 345 patients with TBI who visited a single trauma center. Vitamin D serum levels were measured without supplementation at admission, 1 month, and 3 months post-TBI (control group) from August to December 2016. From January 2017, vitamin D supplementation was provided to patients with TBI with low vitamin D serum levels at admission (supplement group). The outcomes were investigated by assessing performance function (Extended Glasgow Outcome Scale) and cognitive function (Mini-Mental Status Examination, and Clinical Dementia Rating) at 1 week and 3 months post-TBI. RESULTS: The mean vitamin D serum level in patients with TBI at admission was 13.62 ± 9.01 ng/mL. The level significantly increased from 14.03 ± 8.68 ng/mL at admission to 37.42 ± 12.57 ng/mL at 3 months post TBI in the supplement group (P < 0.001). The cognitive outcomes (Mini-Mental Status Examination/Clinical Dementia Rating, P = 0.042/P = 0.044) and GOS-E score (total TBI, P = 0.003; mild-to-moderate TBI, P = 0.002) significantly improved from the first week to 3 months post TBI in the patients with vitamin D supplementation. CONCLUSIONS: Administration of vitamin D supplements in mild-to-moderate TBI patients with significant vitamin D deficiency during the acute phase of the injury may improve long-term performance and cognitive outcomes. Therefore, the treatment strategies should be individually planned for the patients with TBI based on their baseline vitamin D level.

A new definition for wide-necked cerebral aneurysms.

BACKGROUND: Endovascular management of wide-necked aneurysms often requires assisted-techniques with adjunctive devices. Wide-necked aneurysm can be defined with a dome-to-neck ratio or aspect ratio; however, clinical definitions of wide-necked aneurysms vary. This study aimed to determine the most useful definition of wide-necked aneurysm to predict the need for an adjunctive device. METHODS: Among 552 cases of aneurysms, 343 (62.1%) and 209 (37.9%) cases of unruptured and ruptured aneurysms, respectively, were treated in a single institution. For each aneurysm, the (1) dome-to-neck ratio, (2) aspect ratio, and (3) K-ratio (defined as [dome height+maximum dome width]/[2×maximum neck width]) were measured. We statistically analyzed patient data to determine which of the three ratios was most predictive of the need for adjunctive devices. RESULTS: Among 552 cases of aneurysms, 277 (50.2%) and 275 (49.8%) cases were treated with and without adjunctive techniques, respectively. The mean dome-to-neck ratio, aspect ratio, and K-ratio were 1.17±0.39, 1.58±0.61, and 1.37±0.47, respectively. The K-ratio was the strongest predictor of the use of adjunctive devices (P<0.001), and 1.3 was the most appropriate K-ratio cut-off value (sensitivity, 72.9%; specificity, 63.6%). CONCLUSIONS: K-ratio was the most useful predictor of the need for adjunctive devices in the treatment of endovascular aneurysms. These results suggest that the K-ratio may be used to define wide-necked aneurysms requiring complicated management via adjunctive devices.