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Although the Li metal has been gaining attention as a promising anode material for the next-generation high-energy-density rechargeable batteries owing to its high theoretical specific capacity (3860 mAh g-1), its practical use remains challenging owing to inherent issues related to Li nucleation and growth. This paper reports the fabrication of a lithiophilic multichannel layer (LML) that enables the simultaneous control of Li nucleation and growth in Li-metal batteries. The LML, composed of lithiophilic ceramic composite nanoparticles (Ag-plated Al2O3 particles), is fabricated using the electroless plating method. This LML provides numerous channels for a uniform Li-ion diffusion on a nonwoven separator. Furthermore, the lithiophilic Ag on the Li metal anode surface facing the LML induces a low overpotential during Li nucleation, resulting in a dense Li deposition. The LML enables the LiNi0.8Co0.1Mn0.1O2|| Li cells to maintain a capacity higher than 75% after 100 cycles, even at high charge/discharge rates of 5.0 C at a cutoff voltage of 4.4 V, and achieve an ultrahigh energy density of 1164 Wh kg-1. These results demonstrate that the LML is a promising solution enabling the application of Li metal as an anode material in the next-generation Li-ion batteries.

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BACKGROUND: Hyperosmolar therapy has long been a cornerstone in managing increased intracranial pressure and improving outcomes in severe traumatic brain injury (TBI). This therapy hinges on elevating serum osmolality, creating an osmotic gradient that draws excess water from the brain's cellular and interstitial compartments and effectively reducing cerebral edema. Given this information, we hypothesized that the serum hyperosmolality prior to any treatment could significantly impact the clinical outcomes of patients with severe TBI, potentially mitigating secondary cerebral edema after trauma. METHODS: Data were extracted from the Korean Multi-center Traumatic Brain Injury data bank, encompassing 4628 patients with TBI admitted between January 2016 and December 2018. Of these, 507 patients diagnosed with severe TBI (Glasgow Coma Scale score < 9) were selected for comprehensive analysis across four data domains: clinical, laboratory, initial computed tomography scan, and treatment. Serum osmolality was assessed prior to treatment, and the hyperosmolar group was defined by a pretreatment serum osmolality exceeding 320 mOsm/L, whereas favorable outcomes were characterized by a modified Rankin Scale score of ≤ 3 at 6 months after trauma. Multivariate regression with receiver operating characteristic curve analysis and propensity score matching were used to dissect the data set. RESULTS: Multivariate analysis showed serum osmolality is significantly associated with clinical outcome in patients with severe TBI (p < 0.001). The optimal cutoff value for predicting favorable outcome was 331 mOsm/L, with a sensitivity of 38.9% and a specificity of 87.7%. Notably, the propensity score matching analysis comparing patients with pretreatment serum hyperosmolality with those without indicated a markedly improved functional outcome in the former group (32.5% vs 18.8%, p = 0.025). CONCLUSIONS: The present study has uncovered a significant correlation between the pretreatment serum osmolality and the clinical outcomes of patients with severe TBI. These findings offer a novel perspective, indicating that a serum hyperosmolality prior to any treatment might potentially have a neuroprotective effect in patients with severe TBI.

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Background: Cerebral aneurysm coil embolization is often performed under general anesthesia to prevent patient movement and sudden high blood pressure. However, the optimal anesthetic agent remains uncertain. This study aimed to determine whether maintaining anesthesia with remimazolam in patients undergoing coil embolization could avoid hypotension or hypertension compared to sevoflurane. Methods: Thirty-three adult patients participated in this single-blinded, randomized controlled trial. Patients in Group R were induced and maintained with remimazolam, whereas those in Group S received propofol and sevoflurane. Results: The use of remimazolam significantly reduced the incidence of intraoperative hypotension events (33.3% vs. 80.0%; p = 0.010) but did not change the incidence of hypertension events (66.7% vs. 73.3%; p = 0.690). Patients in Group R maintained a significantly higher range of maximal (100.2 ± 16.6 vs. 88.1 ± 13.5 mmHg; p = 0.037) and minimal (69.4 ± 6.6 vs. 63.4 ± 4.8 mmHg; p = 0.008) mean arterial blood pressure than those in Group S during the intervention. Conclusions: This is the first study to demonstrate the feasibility of maintaining general anesthesia with remimazolam in patients undergoing cerebral aneurysm coil embolization. The findings suggest that remimazolam may maintains better hemodynamic stability, reducing the incidence of hypotensive events without compromising patient safety.

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A 65-year-old woman was diagnosed with an 8 cm large common bile duct stone and multiple stones in both intrahepatic ducts because of abnormal liver function tests. After a multidisciplinary approach, surgical removal was considered, and primary closure after laparoscopic removal of the common bile duct stone was performed. The patient recovered without complications and was discharged on the fourth postoperative day. Endoscopic removal of common bile duct stones is the standard treatment, but surgical removal through laparoscopic common bile duct exploration is also a safe and effective treatment method for such huge gallstones.

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Primary extraosseous intracranial Ewing sarcoma (ES) is an extremely rare disease, limited to the pediatric population, that primarily originates in the skull. Here, we present an unusual case of adult Ewing's sarcoma originating from the brain parenchyma. The 50-year-old male patient visited our hospital with severe headache lasting 3 weeks. MRI presented 6.1×6.2×5.2 cm sized heterogeneously enhanced mass containing peritumoral edema in the right frontal lobe. The patient underwent right frontal craniotomy, at which time the gray and red masses adhered to the surrounding brain parenchyma. The mass was completely resected using neuronavigation and electrophysiological monitoring. Histopathological examination revealed ES-compatible findings of small round cell tumor and CD-99 positive membranous immunostaining. Next generation sequencing revealed translocation and fusion of EWSR1 and FLI1, consistent with a confirmed diagnosis of ES. Consequently, the patient underwent postoperative radiotherapy. The present case revealed adult primary intracranial ES arising from the frontal lobe. Although its etiology remains poorly understood, intraparenchymal ES should be included in the differential diagnosis of parenchymal brain tumors.

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Potential synergism between Bruton's tyrosine kinase (BTK) inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab (R2A) in patients with aggressive relapsed/refractory aggressive (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint of this study is objective response rate (ORR), and the secondary endpoints are complete remission (CR) rate, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). A total of 66 patients are enrolled mostly with diffuse large B-cell lymphoma. The ORR is 54.5% and CR rate is 31.8% meeting the primary end point. The median DoR is 12.9 months, and 1-year PFS and OS rate is 33.1% and 67.5% respectively. Adverse events (AE) are manageable with the most frequent AE being neutropenia (31.8%). Patients with MYD88 mutations, subtypes known for NF-κB activation, and high BTK expression by immunohistochemistry respond well. Overall, these results show a significant efficacy of the R2A regimen in patients with aggressive R/R B-cell NHL, with exploratory biomarkers suggesting potential associations with response. (ClinicalTrials.gov 51 identifier: NCT04094142).

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HemoHIM G is a functional food ingredient composed of a triple herbal combination of Angelica sinensis, Ligusticum chuanxiong, and Paeonia lactiflora, to improve impaired immune function. Considering the pharmacological benefits of its constituent herbal components, HemoHIM G is anticipated to have various health benefits; however, its toxicity has not been thoroughly evaluated. Here, we conducted a comprehensive study to assess the safety of HemoHIM G in terms of acute oral toxicity, 13-week repeat-dose toxicity, and genotoxicity. In the oral acute toxicity study, Sprague-Dawley rats were orally administered a single dose of HemoHIM G at 5000 mg/kg/day, the limit dose for the acute study. No abnormal findings or adverse effects were observed in this study, as confirmed by gross pathology. A 13-week repeated-dose toxicity study was conducted with HemoHIM G at doses of 1250, 2500, and 5000 mg/kg/day to examine the subchronic toxicity in both male and female rats after 28 days of dose-range finding study. No test substance-related clinical signs or mortality was observed at any of the tested doses. Gross pathology, hematology, blood chemistry, and histopathology were within normal ranges, further supporting the safety of HemoHIM G. Therefore, the NOAEL of HemoHIM G was considered to be at 5000 mg/kg/day for both sexes of rats. Bacterial reverse mutation tests, a chromosome aberration test in human peripheral blood lymphocytes, and a mouse micronuclei test were conducted to identify the potential genotoxicity of HemoHIM G. HemoHIM G is non-mutagenic and non-clastogenic. Collectively, these findings provide valuable evidence for the safe use of HemoHIM G as a functional food ingredient.

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In this multi-center, assessor-blinded pilot study, the diagnostic efficacy of cCeLL-Ex vivo, a second-generation confocal laser endomicroscopy (CLE), was compared against the gold standard frozen section analysis for intraoperative brain tumor diagnosis. The study was conducted across three tertiary medical institutions in the Republic of Korea. Biopsy samples from newly diagnosed brain tumor patients were categorized based on location and divided for permanent section analysis, frozen section analysis, and cCeLL-Ex vivo imaging. Of the 74 samples from 55 patients, the majority were from the tumor core (74.3%). cCeLL-Ex vivo exhibited a relatively higher diagnostic accuracy (89.2%) than frozen section analysis (86.5%), with both methods showing a sensitivity of 92.2%. cCeLL-Ex vivo also demonstrated higher specificity (70% vs. 50%), positive predictive value (PPV) (95.2% vs. 92.2%), and negative predictive value (NPV) (58.3% vs. 50%). Furthermore, the time from sample preparation to diagnosis was notably shorter with cCeLL-Ex vivo (13 min 17 s) compared to frozen section analysis (28 min 28 s) (p-value < 0.005). These findings underscore cCeLL-Ex vivo's potential as a supplementary tool for intraoperative brain tumor diagnosis, with future studies anticipated to further validate its clinical utility.

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[This corrects the article DOI: 10.3389/fonc.2022.994054.].

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Activation of the innate immune system counteracts tumor-induced immunosuppression. Hence, small molecule-based toll-like receptor 7/8 agonists (TLR7/8a), which can modulate immunosuppression in the tumor microenvironment along with the activation of innate immunity, are emerging as essential components of cancer immunotherapy. However, the clinical application of synthetic TLR7/8a therapies is limited by systemic immune-associated toxicity and immune tolerance induced by uncontrolled stimulatory activities and repeated treatments. To address these limitations, a dynamic immunomodulation strategy incorporating masking and temporal recovery of the activity of TLR7/8a through prodrug-like TLR7/8a (pro-TLR7/8a) at the molecular level and a sustained and controlled release of active TLR7/8a from nanoliposome (pro-TLR7/8a) (NL(pro-TLR7/8)) in a macroscale depot are designed. Immunization with cationic NL(pro-TLR7/8) and anionic antigens triggers robust activation of innate immune cells as well as antigen-specific T cell responses, eliciting reprogramming of immunosuppressive cells into tumor-suppressive cells, with decreased systemic adverse effects and immune tolerance. Combination treatment with NL(pro-TLR7/8a) and immune checkpoint inhibitors (anti-CTLA-4 plus anti-PD-L1) or nanoliposomes (Doxorubicin) has synergistic effects on antitumor immunity in various tumor models. The concept of pro-TLR7/8a suggested herein may facilitate the advancement of small-molecule-based immunomodulators for clinical translation and safe and effective cancer immunotherapy.

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Primary extraosseous intracranial Ewing sarcoma (ES) is an extremely rare disease, limited to the pediatric population, that primarily originates in the skull. Here, we present an unusual case of adult Ewing’s sarcoma originating from the brain parenchyma. The 50-year-old male patient visited our hospital with severe headache lasting 3 weeks. MRI presented 6.1×6.2×5.2 cm sized heterogeneously enhanced mass containing peritumoral edema in the right frontal lobe. The patient underwent right frontal craniotomy, at which time the gray and red masses adhered to the surrounding brain parenchyma. The mass was completely resected using neuronavigation and electrophysiological monitoring. Histopathological examination revealed ES-compatible findings of small round cell tumor and CD-99 positive membranous immunostaining. Next generation sequencing revealed translocation and fusion of EWSR1 and FLI1, consistent with a confirmed diagnosis of ES. Consequently, the patient underwent postoperative radiotherapy. The present case revealed adult primary intracranial ES arising from the frontal lobe. Although its etiology remains poorly understood, intraparenchymal ES should be included in the differential diagnosis of parenchymal brain tumors.

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A 65-year-old woman was diagnosed with an 8 cm large common bile duct stone and multiple stones in both intrahepatic ducts because of abnormal liver function tests. After a multidisciplinary approach, surgical removal was considered, and primary closure after laparoscopic removal of the common bile duct stone was performed. The patient recovered without complications and was discharged on the fourth postoperative day. Endoscopic removal of common bile duct stones is the standard treatment, but surgical removal through laparoscopic common bile duct exploration is also a safe and effective treatment method for such huge gallstones.

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Recurrence of Rathke's cleft cysts (RCC) following surgery is not uncommon. We present a 33-year-old male patient with chronic headache and visual disturbances whose MRI showed mostly cystic, suprasellar mass with peripheral enhancement. Endoscopic extended transsphenoidal approach and tumor resection was performed and RCC was pathologically confirmed postoperatively. Early recurrence was first suspected at 3 months following surgery, and his serial MRIs showed a recurred mass without associated clinical symptoms. Upon further histopathological study, extensive squamous metaplasia and high Ki-67 were seen. Also, in this study, we discuss important factors associated with cyst recurrence following surgery.

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Encephaloduroarteriosynangiosis (EDAS), an indirect anastomosis procedure, is widely accepted as a primary treatment for moyamoya disease (MMD) to improve collateral blood flow. During surgical intervention, dural fibroblasts (DuF) are thought to produce various proteins that create an angiogenic microenvironment. However, the biophysiological evidence supporting the angiogenic properties of this surgical technique has not been thoroughly elucidated. The purpose of these studies was to determine whether DuF releases pro-angiogenic factors and chemokines and promotes angiogenic properties in human endothelial cells (ECs) under IL-1ß-mediated wound conditions, which are expected to occur during the process of neo-vascularization within the dura mater. Furthermore, a microfluidic chemotaxis platform was implemented to investigate the angiogenic activity of ECs in response to a reconstituted dura model. Transcriptome sequencing revealed that IL-1ß stimulation on DuF induced a significant upregulation of various pro-angiogenic genes, including IL-6, IL-8, CCL-2, CCL-5, SMOC-1, and SCG-2 (p < 0.05). Moreover, compared to ECs cultured in naïve media or naïve DuF media, those exposed to IL-1ß-DuF conditioned media expressed higher mRNA and protein levels of these pro-angiogenic factors (p < 0.001). ECs co-cultured with IL-1ß-DuF also exhibited considerable migration on the microfluidic chemotaxis platform. Furthermore, the chemotactic effects on the ECs were reduced upon neutralization of IL-8 or inhibition of NF-κB signaling. Our findings demonstrate that IL-1ß-DuFs release factors that activate and enhance the angiogenic properties of ECs. These results suggest a potential interaction between DuF and ECs following EDAS for MMD, and these components could be targeted for the development of therapeutic biomarkers.

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The efficacy of decompressive craniectomy (DC) for traumatic brain injury (TBI) have been investigated in two recent randomized clinical trials (RCTs) and DC is recommended as an optional treatment for improving overall survival compared to medical treatment. However, the two RCTs enrolled extremely young adults, and the efficacy of DC in older adults remains questionable. Therefore, to identify the efficacy of DC in older adults, we compared patients who received medical care with those who underwent DC after propensity score matching (PSM). From the Korea Multi-center Traumatic Brain Injury Database, 443 patients identified as having intracranial hypertension and a necessity of DC were retrospectively enrolled. The patients were classified into the DC (n = 375) and non-DC (n = 68) groups according to operation records. The PSM was conducted to match the patients in the DC group with those receiving medical care (non-DC). After PSM, the newly matched group (DC, n = 126) was compared with patients without DC (non-DC, n = 63). The mean difference in the logit of the propensity scores (LPS) was 0.00391 and the mean age of enrolled patients were 65 years. The results of the comparative analyses after PSM showed that the 6-month mortality rate of the non-DC group was higher than that of the DC group (61.9% vs. 51.6%, p = 0.179). In terms of favorable outcomes (modified Rankin Scale [mRS] score < 4), the DC group showed a lower rate of favorable mRS scores (11.9% vs. 17.5%, p = 0.296) than the non-DC group.

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We demonstrate the modulation of electrical switching properties through the interconnection of multiple nanoscale channels (∼600 nm) in a single VO2 nanobeam with a coexisting metal-insulator (M-I) domain configuration during phase transition. The Raman scattering characteristics of the synthesized VO2 nanobeams provide evidence that substrate-induced interfacial strain can be inhomogeneously distributed along the length of the nanobeam. Interestingly, the nanoscale VO2 devices with the same channel length and width exhibit distinct differences in hysteric current-voltage characteristics, which are explained by theoretical calculations of resistance change combined with Joule heating simulations of the nanoscale VO2 channels. The observed results can be attributed to the difference in the spatial distribution and fraction ratios of M-I domains due to interfacial strain in the nanoscale VO2 channels during the metal-insulator transition process. Moreover, we demonstrate the electrically activated resistive switching characteristics based on the hysteresis behaviors of the interconnected nanoscale channels, implying the possibility of manipulating multiple resistive states. Our results may offer insights into the nanoscale engineering of correlated phases in VO2 as the key materials of neuromorphic computing for which nonlinear conductance is essential.

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The prevalence of aneurysm formation in adults with Moyamoya disease (MMD) is higher than that in the general population. The treatment strategy is often individualized based on the patient's disease characteristics. A 22-year-old man was diagnosed with MMD after presenting a small thalamic intracerebral and subarachnoid hemorrhage in the quadrigeminal cistern. Cerebral angiography revealed a small aneurysm (2.42 mm) in the left anterior choroidal artery. Since the hemodynamics in the left hemisphere was compromised, an indirect bypass surgery was performed. The patient's condition deteriorated postoperatively because of poor perfusion of the internal carotid artery, and massive hydration was required. During neurocritical care, the aneurysm increased in size (5.33 mm). An observation strategy was adopted because of the distal aneurysmal location and the high risk involved. Subsequently, the patient recovered, and newly developed collateral flow appeared from the external carotid artery. Additionally, a dramatic size reduction of the aneurysm (1.51 mm) was noticed. Our case suggests that MMD-related dissecting aneurysms on a distal cerebral artery, which present a high risk of embolization, could be managed by indirectly reducing the hemodynamic burden. Massive hydration in such cases should be avoided or balanced to avoid the risk of rapid growth and aneurysm rupture.

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Recurrence of Rathke’s cleft cysts (RCC) following surgery is not uncommon. We present a 33-yearold male patient with chronic headache and visual disturbances whose MRI showed mostly cystic, suprasellar mass with peripheral enhancement. Endoscopic extended transsphenoidal approach and tumor resection was performed and RCC was pathologically confirmed postoperatively. Early recurrence was first suspected at 3 months following surgery, and his serial MRIs showed a recurred mass without associated clinical symptoms. Upon further histopathological study, extensive squamous metaplasia and high Ki-67 were seen. Also, in this study, we discuss important factors associated with cyst recurrence following surgery.

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The prevalence of aneurysm formation in adults with Moyamoya disease (MMD) is higher than that in the general population. The treatment strategy is often individualized based on the patient’s disease characteristics. A 22-year-old man was diagnosed with MMD after presenting a small thalamic intracerebral and subarachnoid hemorrhage in the quadrigeminal cistern. Cerebral angiography revealed a small aneurysm (2.42 mm) in the left anterior choroidal artery. Since the hemodynamics in the left hemisphere was compromised, an indirect bypass surgery was performed. The patient’s condition deteriorated postoperatively because of poor perfusion of the internal carotid artery, and massive hydration was required. During neurocritical care, the aneurysm increased in size (5.33 mm). An observation strategy was adopted because of the distal aneurysmal location and the high risk involved. Subsequently, the patient recovered, and newly developed collateral flow appeared from the external carotid artery. Additionally, a dramatic size reduction of the aneurysm (1.51 mm) was noticed. Our case suggests that MMD-related dissecting aneurysms on a distal cerebral artery, which present a high risk of embolization, could be managed by indirectly reducing the hemodynamic burden. Massive hydration in such cases should be avoided or balanced to avoid the risk of rapid growth and aneurysm rupture.