Lithiophilic Multichannel Layer to Simultaneously Control the Li-Ion Flux and Li Nucleation for Stable Lithium Metal Batteries.

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.

Primary Intracranial Ewing Sarcoma With an Unusual Presentation: A Case Report.

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.

Surgical Removal of a Huge Common Bile Duct Stone.

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.

A prospective multicenter assessor blinded pilot study using confocal laser endomicroscopy for intraoperative brain tumor diagnosis.

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.

Combination of acalabrutinib with lenalidomide and rituximab in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma: a single-arm phase II trial.

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).

Evaluation of acute, 28-day, 13-week repeated dose oral toxicity and genotoxicity of a herbal extract (HemoHIM G) from Angelica sinensis, Ligusticum chuanxiong, and Peaonia lactiflora.

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.

Corrigendum: Clinical feasibility of miniaturized Lissajous scanning confocal laser endomicroscopy for indocyanine green-enhanced brain tumor diagnosis.

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

Molecular Masking of Synthetic Immunomodulator Evokes Antitumor Immunity With Reduced Immune Tolerance and Systemic Toxicity by Temporal Activity Recovery and Sustained Stimulation.

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.

Recurrence of Rathke's Cleft Cyst Following Surgery and Histopathological Considerations for Recurrence: A Case Presentation.

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.

Role of human dural fibroblasts in the angiogenic responses of human endothelial cells: An in vitro dural model and the application of lab-on-a-chip for EDAS.

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.

The significance of decompressive craniectomy for older patients with traumatic brain injury: a propensity score matching analysis from large multi-center data.

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.

Modulation of Switching Characteristics in a Single VO2 Nanobeam with Interfacial Strain via the Interconnection of Multiple Nanoscale Channels.

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.

Hydration-induced rapid growth and regression after indirect revascularization of an anterior choroidal artery aneurysm associated with Moyamoya disease: A case report.

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.

Recurrence of Rathke’s Cleft Cyst Following Surgery and Histopathological Considerations for Recurrence: A Case Presentation

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.

Hydration-induced rapid growth and regression after indirect revascularization of an anterior choroidal artery aneurysm associated with Moyamoya disease: A case report

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.

Feasibility of rescue stenting technique in patients with acute ischemic stroke due to middle cerebral artery occlusion after failed thrombectomy: A single-center retrospective experience.

BACKGROUND: Despite remarkable advancements in intra-arterial mechanical thrombectomy (IAT), recanalization failure rates up to 24% have been reported. Recently, permanent stent placement (rescue stent, RS) during IAT has been suggested as an optional modality for better reperfusion and outcomes in these patients. However, previous studies were limited owing to non-standardized procedure protocols and small sample sizes. Here, we aimed to determine the efficacy and safety of RS in patients with acute ischemic stroke (AIS) with middle cerebral artery (MCA) occlusion. METHODS: Of the 243 patients in our IAT database (2015-2021), 183 were identified as having MCA occlusion alone. Among them, we extracted 53 patients in whom the IAT failed to show thrombolysis in cerebral ischemia (TICI) scores of 2A or worse. Intraoperatively, RS was deployed in 22 patients (RS group), whereas 31 patients (no-stent group) received IAT without stenting. The baseline characteristics and radiologic and clinical outcomes were reviewed. Comparisons between the groups and multivariate logistic analyses for recanalization and good functional outcomes (modified Rankin Scale 0-2) were performed. RESULTS: No baseline differences were noted (RS vs. no-stent); however, the recanalization outcomes (59.1% vs. 25.8%, p = 0.15) and proportion of good modified Rankin Scale scores (45.5% vs. 19.4%, p = 0.041) were better in the RS group. The parameters of symptomatic ICH (9.7% vs. 9.4%) and mortality (6.5% vs. 5.7%) showed no significant difference. In the multivariate analyses, 'hypertension' and 'RS deployment' were identified as significantly associated factors with recanalization and good prognosis. CONCLUSION: In select patients with MCA occlusion AIS after failed IAT, the RS technique can be an optional rescue treatment modality for acquiring better functional outcomes and delayed recanalization.

The relationship between air pollutant levels and aneurysmal subarachnoid hemorrhage.

BACKGROUND: The relationship between air pollutants, including fine particles (particulate matter [PM] < 10 µm and < 2.5 µm), and aneurysmal subarachnoid hemorrhage (SAH) has been inadequately studied, and the results remain inconclusive. In this study, we attempted to investigate the relationship between air pollutant levels and aneurysmal SAH. METHODS: Ninety-two patients diagnosed with aneurysmal SAH were retrospectively included in the study. Medical records were reviewed, and levels of pollutants, including those of sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and PM with an aerodynamic diameter < 10 and 2.5 µm (PM10 and PM2.5), were collected from the open-source Air Korea website for a period of 4 days. Independent t-tests were conducted to identify the difference in the pollutant levels between the data obtained on the day of aneurysm rupture (D-0) and the other 3 days (D-7, D-2, and D-1). RESULTS: A majority (40.2%) of the patients experienced aneurysm rupture during the fall season when the mean daily pollutant levels were 0.004 ± 0.001 (ppm, SO2), 0.517 ± 0.218 (ppm, CO), 0.02056 ± 0.012 (ppm, O3), 0.02628 ± 0.015 (ppm, NO2), 36.36957 ± 24.538 (µg/m3, PM10), and 19.75581 ± 13.494 (µg/m3, PM2.5), respectively. The level of NO2 was significantly higher on the day of aneurysm rupture (P = .035) than on the other days, while the levels of CO and O3 were nonsignificantly higher (P = .081, P = .055, respectively) on the day of aneurysm rupture than on the other days. There was no significant differences in the PM levels between the 4 days. CONCLUSION: A relationship between PM levels and aneurysm rupture was not identified. Only the levels of classic air pollutant (CO, O3, and NO2) were higher on the aneurysm rupture day than on the other days.

Complications According to the Handling of the Pterygoid Plate During Bimaxillary Surgery.

BACKGROUND: During bimaxillary surgery, manipulation of the pterygoid plate is required to facilitate movement of the maxilla. This study examined the complications that occurred after handling the pterygoid plate during a Le Fort I osteotomy. PATIENTS AND METHODS: This study compared and analyzed complications according to the pterygoid plate handling method in 80 patients who underwent bimaxillary surgery at Pusan National University Dental Hospital from December 2015 to July 2020. The pterygoid plate was fractured or removed intentionally only if it interfered with the maxilla. Otherwise, it was not treated. The complications during surgery and the follow-up period were investigated. RESULTS: Fourteen patients experienced complications, of which excessive bleeding, hearing problems, and nonunion were encountered in 10, 2, and 2 patients, respectively. Of the 10 patients with excessive bleeding patients, the pterygoid plate was manipulated in 8 patients, which was controlled during surgery. Two patients complained of hearing loss with ear congestion immediately after surgery; both patients improved spontaneously within 1 month. Two nonunion patients underwent plate refixation at least 6 months postoperatively, and normal healing was achieved afterward. CONCLUSIONS: Fracture and removal of the pterygoid plate during orthognathic surgery did not significantly affect the occurrence of complications during and after surgery.

Radiologic assessment of rupture risk in small (<5 mm) posterior communicating artery aneurysms.

ABSTRACT: Although previous studies have investigated the predictors of posterior communicating artery (PCoA) aneurysm rupture with clinical and radiologic parameters, the accessibility of "small PCoA aneurysms (<5 mm)" has rarely been reported. Here, we designed a study to identify the factors which are thought to be risky and prone to rupture in small PCoA aneurysms (<5 mm).A total of 114 patients diagnosed with PCoA aneurysm under 5 mm in size on digital subtraction angiography were retrospectively enrolled and divided into ruptured (n = 51) and unruptured (n = 63) groups. Clinical variables were reviewed, and 10 radiologic parameters were obtained, including maximum diameter, height, width, neck width, aspect ratio, dome-to-neck ratio, bleb formation, size ratio, presence of fetal-type PCoA, and inflow angle. Statistical analyses were conducted to compare the groups (ruptured vs unruptured) and identify the risk factors for rupture.High rupture rate of small PCoA aneurysm is noted (51/114, 44.7%). In the comparison analysis, parameters of size ratio (P = .045), aspect ratio (P = .001), and bleb formation (P = .015) were significantly different between the 2 groups. In the regression model, the aspect ratio (P = .045) and bleb formation (P = .004) were significantly associated with the rupture of aneurysm.In respect of small (<5 mm) PCoA aneurysms of our cohort, morphologic parameters of "bleb formation" and "a high aspect ratio" are present more often in ruptured aneurysms as compared to unruptured aneurysms.