Probabilistic graphical modelling using Bayesian networks for predicting clinical outcome after posterior decompression in patients with degenerative cervical myelopathy.

BACKGROUND: Probabilistic graphical modelling (PGM) can be used to predict risk at the individual patient level and show multiple outcomes and exposures in a single model. OBJECTIVE: To develop PGM for the prediction of clinical outcome in patients with degenerative cervical myelopathy (DCM) after posterior decompression and to use PGM to identify causal predictors of the outcome. METHODS: We included data from 59 patients who had undergone cervical posterior decompression for DCM. The candidate predictive parameters were age, sex, body mass index, trauma history, symptom duration, preoperative and last Japanese Orthopaedic Association (JOA) scores, gait impairment, claudication, bladder dysfunction, Nurick grade, American Spinal Injury Association (ASIA) grade, smoking, diabetes mellitus, cardiopulmonary disorders, hypertension, stroke, Parkinson's disease, dementia, psychiatric disorders, arthritis, ossification of the posterior longitudinal ligament, cord signal change, postoperative kyphosis and the cord compression ratio. RESULTS: In regression analyses, preoperative JOA (PreJOA) score, presence of a psychiatric disorder, and ASIA grade were identified as significant factors associated with the last JOS score. Dementia, sex, PreJOA score and gait impairment were causal factors in the PGM. Sex, dementia and PreJOA score were direct causal factors related to the last follow-up JOA (LastJOA) score. Being female, having dementia, and having a low PreJOA score were significantly related to having a low LastJOA score. CONCLUSIONS: The causal predictors of surgical outcome for DCM were sex, dementia and PreJOA score. Therefore, PGM may be a useful personalized medicine tool for predicting the outcome of patients with DCM.

Sex, dementia and preoperative neurological status are causal factors contributing to the postoperative outcome of patients with degenerative cervical myelopathy.The Bayesian network (BN) structure may be useful for predicting the probability for clinical outcomes for each patient who undergoes posterior decompressive surgery.The BN structure may provide a useful model in the current era of personalized medicine.

Variability of response on prophylactic prasugrel for endovascular treatment of intracranial aneurysms: Clinical implications.

BACKGROUND AND PURPOSE: Prophylactic prasugrel for endovascular treatment of intracranial aneurysms has been introduced and increased, but HTPR (high on-treatment platelet reactivity) or LTPR (low on-treatment platelet reactivity) of prasugrel is not uncommon in clinical circumstances. To investigate the predisposing factors of HTPR and LTPR on prasugrel premedication in the neurointerventional field and to determine its clinical implications. MATERIALS AND METHODS: Between February 2016 and December 2020, 191 patients treated with coil embolization using prophylactic prasugrel in 234 intracranial aneurysms were the final candidates for this study. Patient and aneurysm characteristics, clinical status, and laboratory study values were carefully reviewed retrospectively. We performed risk factor analyses for HTPR and LTPR on prasugrel. RESULTS: Ultimately, 20 patients (10.5%) had HTPR, and 74 patients (38.7%) were categorized as having LTPR. In multivariable analyses, the factors related to HTPR were BMI (adjusted OR 1.21, 95% CI 1.04-1.41, p = 0.01), history of antithrombotics (adjusted OR 3.79, 95% CI 1.39-10.34, p = 0.01), and hematocrit (adjusted OR 0.91, 95% CI 0.84-0.99, p = 0.03). Low BMI was the only risk factor for LTPR (adjusted OR 0.84, 95% CI 0.76-0.94, p = 0.001). CONCLUSION: In the neurointerventional field, high BMI and prior use of antithrombotic agents were related to HTPR, and low BMI was associated with LTPR on prophylactic prasugrel. High hematocrit levels decreased the risk of HTPR. When preparing endovascular treatment for intracranial aneurysms, attention to patients with these clinical features is required to address the possibility of ischemic or bleeding complications.

Epigenetic modification of gene expression in cancer cells by terahertz demethylation.

Terahertz (THz) radiation can affect the degree of DNA methylation, the spectral characteristics of which exist in the terahertz region. DNA methylation is an epigenetic modification in which a methyl (CH3) group is attached to cytosine, a nucleobase in human DNA. Appropriately controlled DNA methylation leads to proper regulation of gene expression. However, abnormal gene expression that departs from controlled genetic transcription through aberrant DNA methylation may occur in cancer or other diseases. In this study, we demonstrate the modification of gene expression in cells by THz demethylation using resonant THz radiation. Using an enzyme-linked immunosorbent assay, we observed changes in the degree of global DNA methylation in the SK-MEL-3 melanoma cell line under irradiation with 1.6-THz radiation with limited spectral bandwidth. Resonant THz radiation demethylated living melanoma cells by 19%, with no significant occurrence of apurinic/apyrimidinic sites, and the demethylation ratio was linearly proportional to the power of THz radiation. THz demethylation downregulates FOS, JUN, and CXCL8 genes, which are involved in cancer and apoptosis pathways. Our results show that THz demethylation has the potential to be a gene expression modifier with promising applications in cancer treatment.

Location of Ulnar Nerve Branches to the Flexor Carpi Ulnaris during Surgery for Cubital Tunnel Syndrome.

OBJECTIVE: Cubital tunnel syndrome, the most common ulnar nerve entrapment neuropathy, is usually managed by simple decompression or anterior transposition. One of the concerns in transposition is damage to the nerve branches around the elbow. In this study, the location of ulnar nerve branches to the flexor carpi ulnaris (FCU) was assessed during operations for cubital tunnel syndrome to provide information to reduce operation-related complications. METHODS: A personal series (HJY) of cases operated for cubital tunnel syndrome was reviewed. Cases managed by transposition and location of branches to the FCU were selected for analysis. The function of the branches was confirmed by intraoperative nerve stimulation and the location of the branches was assessed by the distance from the center of medial epicondyle. RESULTS: There was a total of 61 cases of cubital tunnel syndrome, among which 31 were treated by transposition. Twenty-one cases with information on the location of branches were analyzed. The average number of ulnar nerve branches around the elbow was 1.8 (0 to 3), only one case showed no branches. Most of the cases had one branch to the medial head, and one other to the lateral head of the FCU. There were two cases having branches without FCU responses (one branch in one case, three branches in another). The location of the branches to the medial head was 16.3±8.6 mm distal to the medial epicondyle (16 branches; range, 0 to 35 mm), to the lateral head was 19.5±9.5 mm distal to the medial epicondyle (19 branches; range, -5 to 30 mm). Branches without FCU responses were found from 20 mm proximal to the medial condyle to 15 mm distal to the medial epicondyle (five branches). Most of the branches to the medial head were 15 to 20 mm (50% of cases), and most to the lateral head were 15 to 25 mm (58% of cases). There were no cases of discernable weakness of the FCU after operation. CONCLUSION: In most cases of cubital tunnel syndrome, there are ulnar nerve branches around the elbow. Although there might be some cases with branches without FCU responses, most branches are to the FCU, and are to be saved. The operator should be watchful for branches about 15 to 25 mm distal to the medial epicondyle, where most branches come out.

Numerical Model for Cerebrovascular Hemodynamics with Indocyanine Green Fluorescence Videoangiography.

OBJECTIVE: The use of indocyanine green videoangiography (ICG-VA) to assess blood flow in the brain during cerebrovascular surgery has been increasing. Clinical studies on ICG-VA have predominantly focused on qualitative analysis. However, quantitative analysis numerical modelling for time profiling enables a more accurate evaluation of blood flow kinetics. In this study, we established a multiple exponential modified Gaussian (multi-EMG) model for quantitative ICG-VA to understand accurately the status of cerebral hemodynamics. METHODS: We obtained clinical data of cerebral blood flow acquired the quantitative analysis ICG-VA during cerebrovascular surgery. Varied asymmetric peak functions were compared to find the most matching function form with clinical data by using a nonlinear regression algorithm. To verify the result of the nonlinear regression, the mode function was applied to various types of data. RESULTS: The proposed multi-EMG model is well fitted to the clinical data. Because the primary parameters-growth and decay rates, and peak center and heights-of the model are characteristics of model function, they provide accurate reference values for assessing cerebral hemodynamics in various conditions. In addition, the primary parameters can be estimated on the curves with partially missed data. The accuracy of the model estimation was verified by a repeated curve fitting method using manipulation of missing data. CONCLUSION: The multi-EMG model can possibly serve as a universal model for cerebral hemodynamics in a comparison with other asymmetric peak functions. According to the results, the model can be helpful for clinical research assessment of cerebrovascular hemodynamics in a clinical setting.

The complex of miRNA2861 and cell-penetrating, dimeric α-helical peptide accelerates the osteogenesis of mesenchymal stem cells.

BACKGROUND: The restoration of the functional ability of mesenchymal stem cells (MSCs) using epigenetic modification is very promising for patients with weak osteogenesis ability. This study focused on the acceleration of osteogenesis from MSCs using microRNA (miRNA)2861 and a cell-penetrating peptide (CPP), LK. METHODS: We performed MSCs penetration test of complex between the LK peptides and miRNA 2861. Three different experiments were performed to investigate the effects of miRNA 2861 on osteogenic differentiation in MSCs: 1) intensity of alizarin red staining, which reflects the status of mineralization by osteoblasts; 2) gene expression related to osteoblast differentiation; and 3) confirmation of corresponding protein translation for comparison with RNA expression levels. RESULTS: We found that cLK effectively delivered miRNA 2861 into the cytoplasm of human MSCs and accelerated osteogenic differentiation from MSCs, as well as mineralization. CONCLUSION: The complex of miRNA 2861 with LK may have a positive effect on the osteogenic differentiation from MSCs and mineralization. Therapies using miRNAs combined with LK may be good candidates for the augmentation of osteogenesis in patients.

Disorders of Secondary Neurulation: Suggestion of a New Classification According to Pathoembryogenesis.

Recently, advanced knowledge on secondary neurulation and its application to the clinical experience have led to the deeper insight into the pathoembryogenesis of secondary neurulation with new classifications of the caudal spinal dysraphic entities. Here, we summarize the dynamic changes in the concepts of disordered secondary neurulation over the last two decades. In addition, we suggest our new pathoembryogenetic explanations for a few entities based on the literature and the data from our previous animal research. Disordered secondary neurulation at each phase may cause various corresponding lesions, such as (1) failed junction with the primary neural tube (junctional neural tube defect and segmental spinal dysgenesis), (2) dysgenesis or duplication of the caudal cell mass associated with disturbed activity of caudal mesenchymal tissue (caudal agenesis and caudal duplication syndrome), (3) abnormal continuity of medullary cord to the surrounding layers, namely, failed ingression of the primitive streak to the caudal cell mass (myelomeningocele), focal limited dorsal neurocutaneous nondisjunction (limited dorsal myeloschisis and congenital dermal sinus), and neuro-mesenchymal adhesion (lumbosacral lipomatous malformation), and (4) regression failure spectrum of the medullary cord (thickened filum and filar cyst, retained medullary cord and low-lying conus, terminal myelocele, and terminal myelocystocele). It seems that almost every anomalous entity of the primary neural tube may occur in the area of secondary neurulation. Furthermore, the close association of the caudal cell mass with the activity of caudal mesenchymal tissue involves a wider range of surrounding structures in secondary neurulation than in primary neurulation. Although the majority of the data are from animals and many theories are still conjectural, these changing concepts of normal and disordered secondary neurulation will provoke further advancements in our management strategies as well as in the pathoembryogenetic understanding of anomalous lesions in this area.

Half-Centennial History of Journal of Korean Neurosurgical Society : Midway from Domestic Journal to International Journal with Good Influence in Global Neurosurgery.

October 2022 marks the 50th anniversary of the founding of Journal of Korean Neurosurgical Society (JKNS). Staring as official journal of Korean Neurosurgical Society (KNS) in 1972, JKNS is a journal that is listed in the science citation index (SCI) and its impact factor has been steadily rising in recent years. The past history of JKNS was reviewed with a focus on important milestone, and the direction of future development is suggested.

Escherichia coli cell factories with altered chromosomal replication scenarios exhibit accelerated growth and rapid biomass production.

BACKGROUND: Generally, bacteria have a circular genome with a single replication origin for each replicon, whereas archaea and eukaryotes can have multiple replication origins in a single chromosome. In Escherichia coli, bidirectional DNA replication is initiated at the origin of replication (oriC) and arrested by the 10 termination sites (terA-J). RESULTS: We constructed E. coli derivatives with additional or ectopic replication origins, which demonstrate the relationship between DNA replication and cell physiology. The cultures of E. coli derivatives with multiple replication origins contained an increased fraction of replicating chromosomes and the cells varied in size. Without the original oriC, E. coli derivatives with double ectopic replication origins manifested impaired growth irrespective of growth conditions and enhanced cell size, and exhibited excessive and asynchronous replication initiation. The generation time of an E. coli strain with three replication origins decreased in a minimal medium supplemented with glucose as the sole carbon source. As well as cell growth, the introduction of additional replication origins promoted increased biomass production. CONCLUSIONS: Balanced cell growth and physiological stability of E. coli under rapid growth condition are affected by changes in the position and number of replication origins. Additionally, we show that, for the first time to our knowledge, the introduction of replication initiation sites to the chromosome promotes cell growth and increases protein production.

Radiographic Follow-up After Normal Ultrasound Screening of the Hip in Breech Infants.

BACKGROUND: Breech presentation is one of the most important risk factors for developmental dysplasia of the hip, and all breech infants should be screened. The necessity of further follow-up of developmental dysplasia of the hip after normal clinical and sonographic screening is a controversial subject. The purpose of this study to identify the incidence of delayed dysplasia in breech infants after normal ultrasound screening and the necessity of further clinical and radiologic follow-up in these patients. METHODS: We included the 292 breech babies (128 boys and 164 girls) who showed normal hip ultrasound screening results. To determine the incidence of delayed radiographic dysplasia, anteroposterior hip radiographs were taken between 12 and 24 months of age to measure the acetabular index (AI). RESULTS: The mean AI values were 22.8±3.4 in boys and 24.9±3.1 in girls. Applying the Tönnis criteria, 29 patients (9.9%) were considered to have delayed radiographic dysplasia (16 boys and 13 girls). No significant difference was found in any demographic variables between babies with and without delayed radiographic dysplasia. None of these 29 infants underwent any treatment for radiographic dysplasia. Applying Kuong's criteria to 292 infants, only 2 patients (0.7%) demonstrated radiographic dysplasia on the hip anteroposterior radiographs taken at 14 months. CONCLUSIONS: The incidence of radiographic dysplasia significantly varied depending on which criteria were applied. In order to find out more accurate incidence rates of delayed radiographic dysplasia, large-scale studies of the normative AI data for Korean infants are required. LEVEL OF EVIDENCE: Prognostic Level III.