Porous Carbon Interlayer Derived from Traditional Korean Paper for Li-S Batteries.

A carbonized interlayer effectively helps to improve the electrochemical performance of lithium-sulfur (Li-S) batteries. In this study, a simple and inexpensive carbon intermediate layer was fabricated using a traditional Korean paper called "hanji". This carbon interlayer has a fibrous porous structure, with a specific surface area of 91.82 m2 g-1 and a BJH adsorption average pore diameter of 26.63 nm. The prepared carbon interlayer was utilized as an intermediary layer in Li-S batteries to decrease the charge-transfer resistance and capture dissolved lithium polysulfides. The porous fiber-shaped carbon interlayer suppressed the migration of polysulfides produced during the electrochemical process. The carbon interlayer facilitates the adsorption of soluble lithium polysulfides, allowing for their re-utilization in subsequent cycles. Additionally, the carbon interlayer significantly reduces the polarization of the cell. This simple strategy results in a significant improvement in cycle performance. Consequently, the discharge capacity at 0.5 C after 150 cycles was confirmed to have improved by more than twofold, reaching 230 mAh g-1 for cells without the interlayer and 583 mAh g-1 for cells with the interlayer. This study demonstrates a simple method for improving the capacity of Li-S batteries by integrating a functional carbon interlayer.

Clinical impact of craniectomy on shunt-dependent hydrocephalus after intracerebral hemorrhage: A propensity score-matched analysis.

PURPOSE: A consensus on decompressive craniectomy for intracerebral hemorrhage (ICH) has not yet been established. We aimed to investigate the development of shunt-dependent hydrocephalus based on the method of ICH surgery, with a focus on craniectomy. METHODS: We retrospectively enrolled 458 patients with supratentorial ICH who underwent surgical hematoma evacuation between April 2005 and December 2021 at two independent stroke centers. Multivariate analyses were performed to characterize risk factors for postoperative shunt-dependent hydrocephalus. Propensity score matching (1:2) was undertaken to compensate for group-wise imbalances based on probable factors that were suspected to affect the development of hydrocephalus, and the clinical impact of craniectomy on shunt-dependent hydrocephalus was evaluated by the matched analysis. RESULTS: Overall, 43 of the 458 participants (9.4%) underwent shunt procedures as part of the management of hydrocephalus after ICH. Multivariate analysis revealed that intraventricular hemorrhage (IVH) and craniectomy were associated with shunt-dependent hydrocephalus after surgery for ICH. After propensity score matching, there were no statistically significant intergroup differences in participant age, sex, hypertension status, diabetes mellitus status, lesion location, ICH volume, IVH occurrence, or IVH severity. The craniectomy group had a significantly higher incidence of shunt-dependent hydrocephalus than the non-craniectomy group (28.9% vs. 4.3%, p < 0.001; OR 9.1, 95% CI 3.7-22.7), craniotomy group (23.2% vs. 4.3%, p < 0.001; OR 6.6, 95% CI 2.5-17.1), and catheterization group (20.0% vs. 4.0%, p = 0.012; OR 6.0, 95% CI 1.7-21.3). CONCLUSION: Decompressive craniectomy seems to increase shunt-dependent hydrocephalus among patients undergoing surgical ICH evacuation. The decision to perform a craniectomy for patients with ICH should be carefully individualized while considering the risk of hydrocephalus.

Integrated proteogenomic characterization of glioblastoma evolution.

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.

Inhibition of DNMT1 methyltransferase activity via glucose-regulated O-GlcNAcylation alters the epigenome.

The DNA methyltransferase activity of DNMT1 is vital for genomic maintenance of DNA methylation. We report here that DNMT1 function is regulated by O-GlcNAcylation, a protein modification that is sensitive to glucose levels, and that elevated O-GlcNAcylation of DNMT1 from high glucose environment leads to alterations to the epigenome. Using mass spectrometry and complementary alanine mutation experiments, we identified S878 as the major residue that is O-GlcNAcylated on human DNMT1. Functional studies in human and mouse cells further revealed that O-GlcNAcylation of DNMT1-S878 results in an inhibition of methyltransferase activity, resulting in a general loss of DNA methylation that preferentially occurs at partially methylated domains (PMDs). This loss of methylation corresponds with an increase in DNA damage and apoptosis. These results establish O-GlcNAcylation of DNMT1 as a mechanism through which the epigenome is regulated by glucose metabolism and implicates a role for glycosylation of DNMT1 in metabolic diseases characterized by hyperglycemia.

Effect of Bevacizumab Treatment in Cerebral Radiation Necrosis : Investigation of Response Predictors in a Single-Center Experience.

OBJECTIVE: Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect. METHODS: Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect. RESULTS: Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response. CONCLUSION: The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.

Safety and Efficacy of Low-dose Prasugrel in the Endovascular Treatment of Unruptured Aneurysms in the Elders (≥ 75 Years).

PURPOSE: The effectiveness and safety of low-dose prasugrel (PSG) premedication for endovascular treatment of unruptured intracranial aneurysms (UIAs) have been widely reported. In this study, we evaluated the clinical outcomes of elders patients (≥ 75 years) treated with PSG. METHODS: A total of 200 patients with 209 UIAs who were administered PSG as premedication (20 mg loading and 5 mg maintenance with 100 mg aspirin) between March 2018 and December 2021 were retrospectively enrolled. Among them, 39 patients were aged 75 years or over (elders group), and 161 patients were aged under 75 years (control group). Patients' clinical data were collected, and outcomes were compared between the two groups. RESULTS: Of the 200 patients with PSG, 9 cases (4.5%) had overall complications (7 ischemic, 2 hemorrhagic). In the comparison between the elders group and the control group, no significant differences were observed in the overall complication rates (elders group vs. control group; 2.6% vs. 5.0%, P = 1.00). Moreover, the rates of poor clinical outcome were comparable (2.6% vs. 1.2%, P = 0.48). The subgroup analysis of patients with stent-assisted procedures revealed no significant differences in complication rates (0% vs. 1.6%, P = 1.00) or poor clinical outcomes (0% vs. 0%, P = 1.00) during maintenance with aspirin 100 mg or PSG 5 mg. CONCLUSION: The complication rates in the elders treated with low-dose PSG premedication were similar to those in the control. Low-dose PSG premedication could be prescribed without any additional risk for the endovascular treatment of UIAs in elders patients.

Effect of Bevacizumab Treatment in Cerebral Radiation Necrosis : Investigation of Response Predictors in a Single-Center Experience

Objective@#: Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect. @*Methods@#: Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect. @*Results@#: Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response. @*Conclusion@#: The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.

Clinical Impact of Hydroxyapatite on the Outcome of Skull Base Reconstruction for Intraoperative High-Flow CSF Leak: A Propensity Score Matching Analysis.

Background: Despite recent advances in skull base reconstructive techniques, including the multilayer technique during the last decade, complete reconstruction of grade 3 intraoperative high-flow cerebrospinal fluid (CSF) leak remains challenging. This study was designed to investigate the role of injectable hydroxyapatite (HXA) used in the multilayer technique on the clinical outcome of skull base reconstruction for intraoperative high-flow CSF leak. Materials and Methods: This study enrolled 187 patients who experienced intraoperative high-flow CSF leak after endoscopic endonasal surgery for anterior skull base or suprasellar pathologies between January 2014 and July 2021. All skull base defects were reconstructed using the conventional multilayer technique including a vascularized naso-septal flap (NSF, n = 141) and the combined use of HXA with the conventional multilayer technique (HXA group, n = 46). We retrospectively evaluated the efficacy of the HXA group by 1:2 propensity score matching analysis. Results: Overall, 17 of 187 patients (9.1%) showed postoperative CSF leaks, resulting in second reconstruction surgery. There were no statistical differences in patient age, sex, body mass index, tumor location, tumor type, and degree of resection, except for the follow-up period between the two groups. The HXA group showed a significantly lower incidence of postoperative CSF leak than the control group (0% vs. 12.1%, p < 0.05). Postoperative lumbar drain (LD) was performed in 8.7% of the HXA group compared to 46.1% of the control group (p < 0.01). CSF leak-related infection rates showed a decreasing tendency in the HXA group compared to the control group (0 vs. 7.1%, p = 0.06). A total of 46 patients in the HXA group were well matched with the control group (92 patients) at a 1:2 ratio. In the propensity score-matched control group, there were higher rates of postoperative CSF leaks than in the HXA group. Conclusion: The use of HXA combined with the conventional multilayer technique completely reduced postoperative CSF leaks in this study. This technique resulted in reduced CSF leakage, even without postoperative LD, and decreased infection rates. Further randomized comparative studies are required to confirm our findings.

Comparison of Postoperative Complications between Simultaneous and Staged Surgery in Cranioplasty and Ventriculoperitoneal Shunt Placement after Decompressive Craniectomy.

OBJECTIVE: Cranioplasty (CP) and ventriculoperitoneal shunt (VPS) are required procedures following decompressive craniectomy (DC) for craniofacial protection and to prevent hydrocephalus. This study assessed the safety and efficacy of simultaneous operation with CP and VPS after DC, and determined the preoperative risk factors for postoperative complications. METHODS: Between January 2009 and December 2019, 81 patients underwent CP and VPS in simultaneous or staged operations following DC. Cumulative medical records and radiologic data were analyzed using univariate analysis to identify factors predisposing patients to complications after CP and VPS. RESULTS: CP and VPS were performed as simultaneous or staged operations in 18 (22.2%) and 63 (77.8%) patients, respectively. The overall postoperative complication rate was 16.0% (13/81). Patients who underwent simultaneous CP and VPS were significantly more likely to experience complications when compared with patients who underwent staged operations (33.3% vs. 9.6%, p<0.01). Univariate analysis revealed that simultaneous CP and VPS surgery was the only significant predictor of postoperative complications (p=0.031). CONCLUSION: This study provided detailed data on surgical timing and complications for CP and VPS after DC. We showed that simultaneous procedures were a significant risk factor for postoperative complications.

Early Diagnostic Ability of Human Complement Factor B in Pancreatic Cancer Is Partly Linked to Its Potential Tumor-Promoting Role.

Although plasma complement factor B (CFB, NX_P00751), both alone and in combination with CA19-9 (i.e., the ComB-CAN), previously exhibited a reliable diagnostic ability for pancreatic cancer (PC), its detectability of the early stages and the cancer detection mechanism remained elusive. We first evaluated the diagnostic accuracy of ComB-CAN using plasma samples from healthy donors (HDs), patients with chronic pancreatitis (CP), and patients with different PC stages (I/II vs III/IV). An analysis of the area under the curve (AUC) by PanelComposer using logistic regression revealed that ComB-CAN has a superior diagnostic ability for early-stage PC (97.1.% [95% confidence interval (CI): (97.1-97.2)]) compared with CFB (94.3% [95% CI: 94.2-94.4]) or CA19-9 alone (34.3% [95% CI: 34.1-34.4]). In the comparisons of all stages of patients with PC vs CP and HDs, the AUC values of ComB-CAN, CFB, and CA19-9 were 0.983 (95% CI: 0.983-0.983), 0.950 (95% CI: 0.950-0.951), and 0.873 (95% CI: 0.873-0.874), respectively. We then investigated the molecular mechanism underlying the detection of early-stage PC by using stable cell lines of CFB knockdown and CFB overexpression. A global transcriptomic analysis coupled to cell invasion assays of both CFB-modulated cell lines suggested that CFB plays a tumor-promoting role in PC, which likely initiates the PI3K-AKT cancer signaling pathway. Thus our study establishes ComB-CAN as a reliable early diagnostic marker for PC that can be clinically applied for early PC screening in the general public.

Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP downregulates stemness phenotype and mesenchymal trans-differentiation after irradiation in glioblastoma multiforme.

Radiation therapy is among the most essential treatment methods for glioblastoma multiforme (GBM). Radio-resistance and cancer stem cell properties can cause therapeutic resistance, cancer heterogeneity, and poor prognoses in association with GBM. Furthermore, the GBM subtype transition from proneural to the most malignant mesenchymal subtype after radiation therapy also accounts for high resistance to conventional treatments. Here, we demonstrate that the inhibition of macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) by 4-iodo-6-phenylpyrimidine (4-IPP), a dual inhibitor targeting MIF and DDT, downregulates stemness phenotype, intracellular signaling cascades, mesenchymal trans-differentiation, and induces apoptosis in proneural glioma stem cells (GSCs). In an analysis of The Cancer Genome Atlas, high MIF and DDT expression were associated with poor prognosis. GSC growth was effectively inhibited by 4-IPP in a time- and dose-dependent manner, and 4-IPP combined with radiation therapy led to significantly reduced proliferation compared with radiation therapy alone. The expression of stemness factors, such as Olig2 and SOX2, and the expression of pAKT, indicating PI3K signaling pathway activation, were decreased in association with both 4-IPP monotherapy and combination treatment. The expression of mesenchymal markers, TGM2 and NF-κB, and expression of pERK (indicating MAPK signaling pathway activation) increased in association with radiation therapy alone but not with 4-IPP monotherapy and combination therapy. In addition, the combination of 4-IPP and radiation therapy significantly induced apoptosis compared to the monotherapy of 4-IPP or radiation. In vivo results demonstrated a significant tumor-suppressing effect of 4-IPP when combined with radiation therapy. Collectively, our results showed that the targeted inhibition of MIF and DDT has the potential to strengthen current clinical strategies by enhancing the anticancer effects of radiation therapy.

Electrochemical Generation of Mesopores and Residual Oxygen for the Enhanced Activity of Silver Electrocatalysts.

The development of stable and efficient electrocatalysts is of key importance for the establishment of a sustainable society. The activity of a metal electrocatalyst is determined by its electrochemically active surface area and intrinsic activity, which can be increased using highly porous structures and heteroatomic doping, respectively. Herein, we propose a general strategy of generating mesopores and residual oxygen in metal electrocatalysts by reduction of metastable metal oxides using Ag2O3 electrodeposited onto carbon paper as a model system and demonstrating that the obtained multipurpose porous Ag electrocatalyst has high activity for the electroreduction of O2 and CO2. The presence of mesopores and residual oxygen is confirmed by electrochemical and spectroscopic techniques, and quantum mechanical simulations prove the importance of residual oxygen for electrocatalytic activity enhancement. Thus, the adopted strategy is concluded to allow the synthesis of highly active metal catalysts with controlled mesoporosity and residual oxygen content.

Clinical Pathway for Emergency Brain Surgery during COVID-19 Pandemic and Its Impact on Clinical Outcomes.

BACKGROUND: One of the challenges neurosurgeons are facing in the global public health crisis caused by the coronavirus disease 2019 (COVID-19) pandemic is to balance COVID-19 screening with timely surgery. We described a clinical pathway for patients who needed emergency brain surgery and determined whether differences in the surgery preparation process caused by COVID-19 screening affected clinical outcomes. METHODS: During the COVID-19 period, patients in need of emergency brain surgery in our institution were managed using a novel standardized pathway designed for COVID-19 screening. We conducted a retrospective review of patients who were hospitalized through the emergency room and underwent emergency brain surgery. A total of 32 patients who underwent emergency brain surgery from February 1 to June 30, 2020 were included in the COVID-19 group, and 65 patients who underwent surgery from February 1 to June 30, 2019 were included in the pre-COVID-19 group. The baseline characteristics, disease severity indicators, time intervals of emergency processes, and clinical outcomes of the two groups were compared. Subgroup analysis was performed between the immediate surgery group and the semi-elective surgery group during the COVID-19 period. RESULTS: There were no significant differences in baseline characteristics and severity indicators between the pre-COVID-19 group and COVID-19 group. The time interval to skin incision was significantly increased in the COVID-19 group (P = 0.027). However, there were no significant differences in the clinical outcomes between the two groups. In subgroup comparison, the time interval to skin incision was shorter in the immediate surgery group during the COVID-19 period compared with the pre-COVID-19 group (P = 0.040). The screening process did not significantly increase the time interval to classification and admission for immediate surgery. The time interval to surgery initiation was longer in the COVID-19 period due to the increased time interval in the semi-elective surgery group (P < 0.001). CONCLUSION: We proposed a clinical pathway for the preoperative screening of COVID-19 in patients requiring emergency brain surgery. No significant differences were observed in the clinical outcomes before and after the COVID-19 pandemic. The protocol we described showed acceptable results during this pandemic.

Growth profile assessment of young adults with tethered cord syndrome: a retrospective cohort analysis of Korean conscription data.

PURPOSE: Tethered cord syndrome (TCS) is characterized by progressive spinal cord degeneration secondary to congenital spinal dysraphism. The associated accompanying physical inactivity and musculoskeletal deformities have raised interest in the growth profile of adult TCS patients. However, few previous studies have investigated the growth profile of adult TCS patients. METHODS: We retrospectively reviewed the demographic data and medical records of 20-year-old Korean conscription examinees who were registered between April 2004 and September 2019. In total, 151 examinees with a diagnosis of TCS were enrolled. The height, weight, and body mass index (BMI) of 300 randomly selected examinees were compared to the TCS group. Obesity was defined by the World Health Organization and Asian-Pacific criteria for BMI and compared between the groups. Growth profile differences according to tethering location and musculoskeletal deformities were analyzed in both groups. RESULTS: The mean height, weight, and BMI values of the TCS group were lower than those of the control group. The TCS group had a lower proportion of obese and overweight individuals, and a higher proportion of underweight individuals, according to both BMI criteria. The tethering level was not associated with the degree of obesity in the tethered group. The mean height, weight, and BMI were lower in the tethered group regardless of the existence of musculoskeletal deformity. CONCLUSION: Enrollees with a history of TCS were smaller than controls of the same age. Monitoring of health behaviors, including nutrition, diet, and exercise, is warranted for TCS patients.

Clinical Pathway for Emergency Brain Surgery during COVID-19 Pandemic and Its Impact on Clinical Outcomes

Background@#One of the challenges neurosurgeons are facing in the global public health crisis caused by the coronavirus disease 2019 (COVID-19) pandemic is to balance COVID-19 screening with timely surgery. We described a clinical pathway for patients who needed emergency brain surgery and determined whether differences in the surgery preparation process caused by COVID-19 screening affected clinical outcomes. @*Methods@#During the COVID-19 period, patients in need of emergency brain surgery in our institution were managed using a novel standardized pathway designed for COVID-19 screening. We conducted a retrospective review of patients who were hospitalized through the emergency room and underwent emergency brain surgery. A total of 32 patients who underwent emergency brain surgery from February 1 to June 30, 2020 were included in the COVID-19 group, and 65 patients who underwent surgery from February 1 to June 30, 2019 were included in the pre-COVID-19 group. The baseline characteristics, disease severity indicators, time intervals of emergency processes, and clinical outcomes of the two groups were compared. Subgroup analysis was performed between the immediate surgery group and the semi-elective surgery group during the COVID-19 period. @*Results@#There were no significant differences in baseline characteristics and severity indicators between the pre-COVID-19 group and COVID-19 group. The time interval to skin incision was significantly increased in the COVID-19 group (P = 0.027). However, there were no significant differences in the clinical outcomes between the two groups. In subgroup comparison, the time interval to skin incision was shorter in the immediate surgery group during the COVID-19 period compared with the pre-COVID-19 group (P = 0.040). The screening process did not significantly increase the time interval to classification and admission for immediate surgery.The time interval to surgery initiation was longer in the COVID-19 period due to the increased time interval in the semi-elective surgery group (P < 0.001). @*Conclusion@#We proposed a clinical pathway for the preoperative screening of COVID-19 in patients requiring emergency brain surgery. No significant differences were observed in the clinical outcomes before and after the COVID-19 pandemic. The protocol we described showed acceptable results during this pandemic.

Comparison of Postoperative Complications between Simultaneous and Staged Surgery in Cranioplasty and Ventriculoperitoneal Shunt Placement after Decompressive Craniectomy / 대한신경손상학회지

Objective@#Cranioplasty (CP) and ventriculoperitoneal shunt (VPS) are required procedures following decompressive craniectomy (DC) for craniofacial protection and to prevent hydrocephalus. This study assessed the safety and efficacy of simultaneous operation with CP and VPS after DC, and determined the preoperative risk factors for postoperative complications. @*Methods@#Between January 2009 and December 2019, 81 patients underwent CP and VPS in simultaneous or staged operations following DC. Cumulative medical records and radiologic data were analyzed using univariate analysis to identify factors predisposing patients to complications after CP and VPS. @*Results@#CP and VPS were performed as simultaneous or staged operations in 18 (22.2%) and 63 (77.8%) patients, respectively. The overall postoperative complication rate was 16.0% (13/81). Patients who underwent simultaneous CP and VPS were significantly more likely to experience complications when compared with patients who underwent staged operations (33.3% vs. 9.6%, p<0.01). Univariate analysis revealed that simultaneous CP and VPS surgery was the only significant predictor of postoperative complications (p=0.031). @*Conclusion@#This study provided detailed data on surgical timing and complications for CP and VPS after DC. We showed that simultaneous procedures were a significant risk factor for postoperative complications.

Impact of adolescent complex regional pain syndrome on the psychopathology of young men ahead of military service: a retrospective cohort analysis of Korean conscription data.

BACKGROUND: The relationship between physical and psychopathological features in complex regional pain syndrome (CRPS) has been a subject of constant interest, but no data are available in adolescents. Therefore, we aimed to identify the factors associated with psychopathology in adolescents with CRPS ahead of military service. METHODS: We retrospectively reviewed all conscription examinees who had completed a Military Personality Inventory (MPI) during a period between February 2013 and December 2016. A total of 63 persons with a history of CRPS (19-years of age for all) were enrolled. Basic demographic and pain-related data were analyzed to examine their association with MPI results. The mean FGR score as well as the 8 subdomain scores were compared between those with pain duration at < 15 months (n = 30) versus ≥15 months (n = 33). Binary MPI results (normal-abnormal) were also compared between the two groups. RESULTS: In multivariate analysis, abnormal MPI was associated with pain duration, with an odds ratio (OR) at 1.05 for every 1-month increase (95% confidence interval (CI) 1.02-1.08; P = 0.002). Subjects with pain duration at ≥15 months have lower faking good response score (P < 0.001 vs. those with pain duration at < 15 months), and higher abnormal MPI result rate, faking bad response, inconsistency, anxiety, depression, somatization, paranoid, personality disorder cluster A, and personality disorder cluster B scores (P < 0.05). Pain duration was significantly associated with the MPI variables. CONCLUSIONS: Pain duration is associated with psychopathology in adolescents with CRPS. Psychopathologic features increased as the disease duration increased. A comprehensive understanding of time-dependent psychopathological factors could support the planning of multimodal approaches for managing adolescent CRPS.

Potential Regulatory Role of Human-Carboxylesterase-1 Glycosylation in Liver Cancer Cell Growth.

We previously reported that human carboxylesterase 1 (CES1), a serine esterase containing a unique N-linked glycosyl group at Asn79 (N79 CES1), is a candidate serological marker of hepatocellular carcinoma (HCC). CES1 is normally present at low-to-undetectable levels in normal human plasma, HCC tumors, and major liver cancer cell lines. To investigate the potential mechanism underlying the suppression of CES1 expression in liver cancer cells, we took advantage of the low detectability of this marker in tumors by overexpressing CES1 in multiple HCC cell lines, including stable Hep3B cells. We found that the population of CES1-overexpressing (OE) cells decreased and that their doubling time was longer compared with mock control liver cancer cells. Using interactive transcriptome, proteome, and subsequent Gene Ontology enrichment analysis of CES1-OE cells, we found substantial decreases in the expression levels of genes involved in cell cycle regulation and proliferation. This antiproliferative function of the N79 glycan of CES1 was further supported by quantitative real-time polymerase chain reaction, flow cytometry, and an apoptosis protein array assay. An analysis of the levels of key signaling target proteins via Western blotting suggested that CES1 overexpression exerted an antiproliferative effect via the PKD1/PKCµ signaling pathway. Similar results were also seen in another HCC cell line (PLC/RFP/5) after transient transfection with CES1 but not in similarly treated non-HCC cell lines (e.g., HeLa and Tera-1 cells), suggesting that CES1 likely exerts a liver cell-type-specific suppressive effect. Given that the N-linked glycosyl group at Asn79 (N79 glycan) of CES1 is known to influence CES1 enzyme activity, we hypothesized that the post-translational modification of CES1 at N79 may be linked to its antiproliferative activity. To investigate the regulatory effect of the N79 glycan on cellular growth, we mutated the single N-glycosylation site in CES1 from Asn to Gln (CES1-N79Q) via site-directed mutagenesis. Fluorescence 2-D difference gel electrophoresis protein expression analysis of cell lysates revealed an increase in cell growth and a decrease in doubling time in cells carrying the N79Q mutation. Thus our results suggest that CES1 exerts an antiproliferative effect in liver cancer cells and that the single N-linked glycosylation at Asn79 plays a potential regulatory role. These functions may underlie the undetectability of CES1 in human HCC tumors and liver cancer cell lines. Mass spectrometry data are available via ProteomeXchange under the identifier PXD021573.

Identification of ALDH6A1 as a Potential Molecular Signature in Hepatocellular Carcinoma via Quantitative Profiling of the Mitochondrial Proteome.

Various liver diseases, including hepatocellular carcinoma (HCC), have been linked to mitochondrial dysfunction, reduction of reactive oxygen species (ROS), and elevation of nitric oxide (NO). In this study, we subjected the human liver mitochondrial proteome to extensive quantitative proteomic profiling analysis and molecular characterization to identify potential signatures indicative of cancer cell growth and progression. Sequential proteomic analysis identified 2452 mitochondrial proteins, of which 1464 and 2010 were classified as nontumor and tumor (HCC) mitochondrial proteins, respectively, with 1022 overlaps. Further metabolic mapping of the HCC mitochondrial proteins narrowed our biological characterization to four proteins, namely, ALDH4A1, LRPPRC, ATP5C1, and ALDH6A1. The latter protein, a mitochondrial methylmalonate semialdehyde dehydrogenase (ALDH6A1), was most strongly suppressed in HCC tumor regions (∼10-fold decrease) in contrast to LRPPRC (∼6-fold increase) and was predicted to be present in plasma. Accordingly, we selected ALDH6A1 for functional analysis and engineered Hep3B cells to overexpress this protein, called ALDH6A1-O/E cells. Since ALDH6A1 is predicted to be involved in mitochondrial respiration, we assessed changes in the levels of NO and ROS in the overexpressed cell lines. Surprisingly, in ALDH6A1-O/E cells, NO was decreased nearly 50% but ROS was increased at a similar level, while the former was restored by treatment with S-nitroso-N-acetyl-penicillamine. The lactate levels were also decreased relative to control cells. Propidium iodide and Rhodamine-123 staining suggested that the decrease in NO and increase in ROS in ALDH6A1-O/E cells could be caused by depolarization of the mitochondrial membrane potential (ΔΨ). Taken together, our results suggest that hepatic neoplastic transformation appears to suppress the expression of ALDH6A1, which is accompanied by a respective increase and decrease in NO and ROS in cancer cells. Given the close link between ALDH6A1 suppression and abnormal cancer cell growth, this protein may serve as a potential molecular signature or biomarker of hepatocarcinogenesis and treatment responses.

FusionPro, a Versatile Proteogenomic Tool for Identification of Novel Fusion Transcripts and Their Potential Translation Products in Cancer Cells.

Fusion proteoforms are translation products derived from gene fusion. Although very rare, the fusion proteoforms play important roles in biomedical science. For example, fusion proteoforms influence the development of tumors by serving as cancer markers or cell cycle regulators. Although numerous studies have reported bioinformatics tools that can predict fusion transcripts, few proteogenomic tools are available that can predict and identify proteoforms. In this study, we develop a versatile proteogenomic tool "FusionPro," which facilitates the identification of fusion transcripts and their potential translatable peptides. FusionPro provides an independent gene fusion prediction module and can build sequence databases for annotated fusion proteoforms. FusionPro shows greater sensitivity than the available fusion finders when analyzing simulated or real RNA sequencing data sets. We use FusionPro to identify 18 fusion junction peptides and three potential fusion-derived peptides by MS/MS-based analysis of leukemia cell lines (Jurkat and K562) and ovarian cancer tissues from the Clinical Proteomic Tumor Analysis Consortium. Among the identified fusion proteins, we molecularly validate two fusion junction isoforms and a translation product of FAM133B:CDK6. Moreover, sequence analysis suggests that the fusion protein participates in the cell cycle progression. In addition, our prediction results indicate that fusion transcripts often have multiple fusion junctions and that these fusion junctions tend to be distributed in a nonrandom pattern at both the chromosome and gene levels. Thus, FusionPro allows users to detect various types of fusion translation products using a transcriptome-informed approach and to gain a comprehensive understanding of the formation and biological roles of fusion proteoforms.