Neutrophil extracellular traps promote ΔNp63+ basal cell hyperplasia in chronic rhinosinusitis.

BACKGROUND: Neutrophil extracellular traps (NETs) are observed in chronic rhinosinusitis (CRS), although their role remains unclear. OBJECTIVES: This study aimed to investigate the influence of NETs on the CRS epithelium. METHODS: Forty-five sinonasal biopsy specimens were immunofluorescence-stained to identify NETs and p63+ basal stem cells. Investigators treated human nasal epithelial cells with NETs and studied them with immunofluorescence staining, Western blotting, and quantitative real-time PCR. NET inhibitors were administered to a murine neutrophilic nasal polyp model. RESULTS: NETs existed in tissues in patients with CRS with nasal polyps, especially in noneosinophilic nasal polyp tissues. p63+ basal cell expression had a positive correlation with the release of NETs. NETs induced the expansion of Ki-67+p63+ cells. We found that ΔNp63, an isoform of p63, was mainly expressed in the nasal epithelium and controlled by NETs. Treatment with deoxyribonuclease (DNase) I or Sivelestat (NET inhibitors) prevented the overexpression of ΔNp63+ epithelial stem cells and reduced polyp formation. CONCLUSIONS: These results reveal that NETs are implicated in CRS pathogenesis via basal cell hyperplasia. This study suggests a novel possibility of treating CRS by targeting NETs.

Biofunctional Inorganic Layered Double Hydroxide Nanohybrid Enhances Immunotherapeutic Effect on Atopic Dermatitis Treatment.

Atopic dermatitis (AD) is a widespread, recurrent, and chronic inflammatory skin condition that imposes a major burden on patients. Conventional treatments, such as corticosteroids, are associated with various side effects, underscoring the need for innovative therapeutic approaches. In this study, the possibility of using indole-3-acetic acid-loaded layered double hydroxides (IAA-LDHs) is evaluated as a novel treatment for AD. IAA is an auxin-class plant hormone with antioxidant and anti-inflammatory effects. Following the synthesis of IAA-LDH nanohybrids, their ability to induce M2-like macrophage polarization in macrophages obtained from mouse bone marrow is assessed. The antioxidant activity of IAA-LDH is quantified by assessing the decrease in intracellular reactive oxygen species levels. The anti-inflammatory and anti-atopic characteristics of IAA-LDH are evaluated in a mouse model of AD by examining the cutaneous tissues, immunological organs, and cells. The findings suggest that IAA-LDH has great therapeutic potential as a candidate for AD treatment based on its in vitro and in vivo modulation of AD immunology, enhancement of macrophage polarization, and antioxidant activity. This inorganic drug delivery technology represents a promising new avenue for the development of safe and effective AD treatments.

House dust mite-induced Akt-ERK1/2-C/EBP beta pathway triggers CCL20-mediated inflammation and epithelial-mesenchymal transition for airway remodeling.

House dust mite (HDM) allergens cause inflammatory responses and chronic allergic diseases such as bronchial asthma and atopic dermatitis. Here, we investigate the mechanism by which HDM induces C-C chemokine ligand 20 (CCL20) expression to promote chronic inflammation and airway remodeling in an HDM-induced bronchial asthma mouse model. We showed that HDM increased CCL20 levels via the Akt-ERK1/2-C/EBPß pathway. To investigate the role of CCL20 in chronic airway inflammation and remodeling, we made a mouse model of CCL20-induced bronchial asthma. Treatment of anti-CCL20Ab in this mouse model showed the reduced airway hyper-responsiveness and inflammatory cell infiltration into peribronchial region by neutralizing CCL20. In addition, CCL20 induced the Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation through NLRP3 deubiquitination and transcriptional upregulation in BEAS-2B cells. As expected, anti-CCL20Ab markedly suppressed NLRP3 activation induced by CCL20. Moreover, HDM-induced CCL20 leads to epithelial-mesenchymal transition in the lung epithelium which appears to be an important regulator of airway remodeling in allergic asthma. We also found that anti-CCL20Ab attenuates airway inflammation and remodeling in an HDM-induced mouse model of bronchial asthma. Taken together, our results suggest that HDM-induced CCL20 is required for chronic inflammation that contributes airway remodeling in a mouse model of asthma.

Afebrile benign convulsions with or without a reversible splenial lesion in two pediatric patients with COVID-19.

BACKGROUND: Seizures in children with coronavirus disease 2019 (COVID-19) were markedly increased during the Omicron variant surge. Most seizures occurred with fever. New-onset afebrile seizures were rarely reported; therefore, their courses are not well-known. CASE PRESENTATION: Two patients (7 and 26 months of age, respectively) with COVID-19 showed recurrent afebrile seizures immediately after resolution of a fever lasting for 2-3 days. Bilateral convulsive seizures lasted for approximately 1 min/episode (6 of 7 total episodes) and occurred 3-4 times within 2-3 h. However, the patients were alert between seizures, which is in contrast to seizures occurring with encephalopathy or encephalitis. Only one episode required acute antiseizure medication. Brain magnetic resonance imaging showed a reversible splenial lesion in one patient. The serum uric acid level was slightly increased (7.8 mg/dL) in this patient. Electroencephalography findings were all normal. During the follow-up period, no seizures or developmental problems have been observed. CONCLUSIONS: COVID-19-associated, afebrile benign convulsions with or without a reversible splenial lesion are similar to 'benign convulsions with mild gastroenteritis'; therefore, continuation of antiseizure medication does not seem necessary.

Four-dimensional flow MR imaging for evaluating treatment response after transcatheter arterial chemoembolization in cirrhotic patients with hepatocellular carcinoma.

PURPOSE: To prospectively evaluate the potential of four-dimensional (4D) flow magnetic resonance imaging (MRI) in predicting treatment responses after transcatheter arterial chemoembolization (TACE) in cirrhotic patients with hepatocellular carcinoma (HCC). METHODS: A total of 195 patients were classified into four groups (A-D): A, cirrhotic patients without HCC (n = 30); B, cirrhotic patients with HCC before TACE (n = 75); C, cirrhotic patients with HCC showing an incomplete response following TACE (n = 56); and D, cirrhotic patients with HCC achieving a complete response (CR) following TACE (n = 34). The patients were subjected to routine laboratory tests and 4D flow MRI using a 3-T MRI system to measure the quantitative parameters of blood flow in the portal vein (PV), splenic vein (SV), and superior mesenteric vein. The data collected by 4D flow MRI were compared among the groups using one-way analysis of variance. A multivariate analysis was performed to verify the association of clinical characteristics and 4D flow parameters with CR after TACE treatment. RESULTS: The average through-plane velocity, peak velocity magnitude, average net flow, peak flow, and net forward volume in the PV and SV were significantly lower in groups B and C (P < 0.05) compared to those in group A. Moreover, average through-plane velocity and peak velocity magnitude in the PV in groups B and C were significantly lower than those in group D (P < 0.05). The multivariate analysis demonstrated that the average through-plane velocity and peak velocity magnitude in the PV were independently associated with CR in HCC patients after TACE (P < 0.05). CONCLUSION: The quantitative flow data obtained by 4D flow MRI may be useful for predicting CR after TACE in cirrhotic patients with HCC.

Automated segmentation of whole-body CT images for body composition analysis in pediatric patients using a deep neural network.

OBJECTIVES: To develop an automatic segmentation algorithm using a deep neural network with transfer learning applicable to whole-body PET-CT images in children. METHODS: For model development, we utilized transfer learning with a pre-trained model based on adult patients. We used CT images of 31 pediatric patients under 19 years of age (mean age, 9.6 years) who underwent PET-CT from institution #1 for transfer learning. Two radiologists manually labeled the skin, bone, muscle, abdominal visceral fat, subcutaneous fat, internal organs, and central nervous system in each CT slice and used these as references. For external validation, we collected 14 pediatric PET/CT scans from institution #2 (mean age, 9.1 years). The Dice similarity coefficients (DSCs), sensitivities, and precision were compared between the algorithms before and after transfer learning. In addition, we evaluated segmentation performance according to sex, age (≤ 8 vs. > 8 years), and body mass index (BMI, ≤ 20 vs. > 20 kg/m2). RESULTS: The algorithm after transfer learning showed better performance than the algorithm before transfer learning for all body compositions (p < 0.001). The average DSC, sensitivity, and precision of each algorithm before and after transfer learning were 98.23% and 99.28%, 98.16% and 99.28%, and 98.29% and 99.28%, respectively. The segmentation performance of the algorithm was generally not affected by age, sex, or BMI, except for precision in the body muscle compartment. CONCLUSION: The developed model with transfer learning enabled accurate and fully automated segmentation of multiple tissues on whole-body CT scans in children. KEY POINTS: • We utilized transfer learning with a pre-trained segmentation algorithm for adult to develop an algorithm for automated segmentation of pediatric whole-body CT. • This algorithm showed excellent performance and was not affected by sex, age, or body mass index, except for precision in body muscle.

Successful Management of Massive Congenital Hepatic Hemangioma and Systemic Hypertension With Sirolimus.

Congenital hepatic hemangioma (CHH) is a common benign vascular tumor of the liver, seen in infancy. The clinical manifestations vary from incidental findings to life-threatening complications. The authors present here a case of an infant with massive CHH who developed systemic hypertension because of compression of the right renal artery by the CHH and did not respond to other lines of treatment. After sirolimus therapy, the CHH size decreased and antihypertensive drugs were no longer necessary. In a critical situation, if the embolization and/or steroids do not seem to control the situation, then adding sirolimus may be considered as secondary therapy with good additive effects.

Clinical significance of respiratory virus coinfection in children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: The prevalence of refractory Mycoplasma pneumoniae (MP) pneumonia has been increasing. However, few studies have investigated the impact of respiratory virus coinfection in patients with MP pneumonia, and their results have been inconclusive. This study aimed to investigate the impact of respiratory virus coinfection in children hospitalized with MP pneumonia. METHODS: This study enrolled 145 children hospitalized with MP pneumonia between May 2019 and March 2020. The patients were divided into two groups: the respiratory virus coinfection and non-coinfection groups. All the children underwent polymerase chain reaction testing for respiratory virus infection. Information on clinical, laboratory, and radiologic findings were obtained retrospectively via medical chart reviews. RESULTS: Children in the respiratory virus coinfection group were younger than those in the non-coinfection group. Respiratory virus coinfection in children hospitalized with MP pneumonia was significantly associated with persistence of fever more than 6 days (adjusted odds ratio [aOR], 2.394; 95% confidence interval [95% CI], 1.172-4.892), severe pneumonia (aOR, 4.602; 95% CI, 1.154-18.353), and poor response to the stepwise approach for MP pneumonia (aOR, 4.354; 95% CI, 1.374-13.800). In addition, higher levels of liver enzymes and lactate dehydrogenase at admission were associated with respiratory virus coinfection in children with MP pneumonia. CONCLUSIONS: The results of this study suggest that respiratory virus coinfection in children hospitalized with MP pneumonia may be associated with refractory MP pneumonia.

Intravenous Tirofiban Infusion After Angioplasty and Stenting in Intracranial Atherosclerotic Stenosis-Related Stroke.

Background and Purpose: This study aimed to investigate the effectiveness and safety of intravenous infusion of tirofiban after emergent angioplasty with or without stenting in patients with intracranial atherosclerotic stenosis-related large-vessel occlusion stroke. Methods: We performed a retrospective case series study of 98 patients who underwent thrombectomy followed by angioplasty with or without stenting to treat intracranial atherosclerotic stenosis-related large-vessel occlusion. Patients were divided into 2 groups: those who received continuous intravenous infusion of tirofiban for 12 hours after procedure (intravenous tirofiban group, n=30) and those who did not receive postprocedural intravenous tirofiban (control group, n=68). The following treatment outcomes in the 2 groups were compared: early reocclusion of treated arteries on computed tomography angiography, parenchymal hematoma, symptomatic hemorrhage, and 90-day functional outcome. Results: Early reocclusion occurred in 18 patients (18.4%). The rate of early reocclusion was significantly lower in the intravenous tirofiban group than in the control group (3.3% versus 25%, P<0.001). The rates of parenchymal hematoma, symptomatic hemorrhage, 90-day good outcome, and mortality were not significantly different between the 2 groups. In multivariate logistic analysis, the only independent predictor of early reocclusion was no use of intravenous tirofiban (odds ratio, 9.212 [95% CI, 1.155-73.495], P=0.036). A good outcome (90-day modified Rankin Scale score of 0-2) was significantly less frequent in patients with early reocclusion than in those without it (16.7% versus 72.5%, P<0.001). Conclusions: The use of intravenous tirofiban for 12 hours was associated with decreased risk of early reocclusion of treated arteries, with no increased risk of hemorrhage after emergent angioplasty, with or without stenting, in patients with intracranial atherosclerotic stenosis-related large-vessel occlusion stroke. Early reocclusion was associated with a poor outcome in such cases.

Nitration of protein phosphatase 2A increases via Epac1/PLCε/CaMKII/HDAC5/iNOS cascade in human endometrial stromal cell decidualization.

Decidualization of the endometrial stroma is an essential differentiation process for embryo implantation and maintenance of pregnancy. We previously reported that protein phosphatase 2A (PP2A) acts as a key mediator during cAMP-induced decidualization of human endometrial stromal cells (hESCs). However, the mechanism underlying its activation has remained obscure in hESCs. In the present study, we aimed to reveal the mechanism that induces the nitration of PP2A catalytic subunit (PP2Ac) during cAMP-induced decidualization of hESCs. First, cAMP-induced PP2Ac nitration was significantly repressed using L-NAME, an inhibitor of nitric oxide synthase (NOS). Among several NOS isoforms, only inducible NOS (iNOS) was highly expressed in hESCs, indicating that iNOS directly induces the nitration of PP2Ac. Second, cAMP-induced iNOS expression and PP2Ac nitration were decreased by treatment with TSA, an inhibitor of histone deacetylase 5 (HDAC5). cAMP-induced phosphorylation of CaMKII and HDAC5 was suppressed by treatment with U73122 (an inhibitor of phospholipase C) or transfection of PLCε siRNA. Finally, small G protein Rap1 and its guanine nucleotide exchange factor Epac1 were found to be involved in cAMP-induced PP2A activation. Taken together, our results suggest that PP2Ac nitration during cAMP-induced decidualization of hESCs is induced through the Epac1-Rap1-PLCε-CaMKII-HDAC5-iNOS signaling pathway.

Bcl-2 Overexpression Induces Neurite Outgrowth via the Bmp4/Tbx3/NeuroD1 Cascade in H19-7 Cells.

Bcl-2 is overexpressed in the nervous system during neural development and plays an important role in modulating cell survival. In addition to its anti-apoptotic function, it has been suggested previously that Bcl-2 might act as a mediator of neuronal differentiation. However, the mechanism by which Bcl-2 might influence neurogenesis is not sufficiently understood. In this study, we aimed to determine the non-apoptotic functions of Bcl-2 during neuronal differentiation. First, we used microarrays to analyze the whole-genome expression patterns of rat neural stem cells overexpressing Bcl-2 and found that Bcl-2 overexpression induced the expression of various neurogenic genes. Moreover, Bcl-2 overexpression increased the neurite length as well as expression of Bmp4, Tbx3, and proneural basic helix-loop-helix genes, such as NeuroD1, NeuroD2, and Mash1, in H19-7 rat hippocampal precursor cells. To determine the hierarchy of these molecules, we selectively depleted Bmp4, Tbx3, and NeuroD1 in Bcl-2-overexpressing cells. Bmp4 depletion suppressed the upregulation of Tbx3 and NeuroD1 as well as neurite outgrowth, which was induced by Bcl-2 overexpression. Although Tbx3 knockdown repressed Bcl-2-mediated neurite elaboration and downregulated NeuroD1 expression, it did not affect Bcl-2-induced Bmp4 expression. While the depletion of NeuroD1 had no effect on the expression of Bcl-2, Bmp4, or Tbx3, Bcl-2-mediated neurite outgrowth was suppressed. Taken together, these results demonstrate that Bcl-2 regulates neurite outgrowth through the Bmp4/Tbx3/NeuroD1 cascade in H19-7 cells, indicating that Bcl-2 may have a direct role in neuronal development in addition to its well-known anti-apoptotic function in response to environmental insults.

Impact of isolated basal ganglia infarction at pretreatment DWI on outcomes after endovascular thrombectomy in acute anterior circulation stroke.

PURPOSE: Acute infarction confined to the basal ganglia (BG) is occasionally observed on baseline imaging before endovascular thrombectomy. This study aimed to investigate the impact of isolated BG infarction revealed on pretreatment DWI in a large cohort of patients with acute anterior circulation stroke who underwent thrombectomy. METHODS: We retrospectively analyzed clinical and DWI data from 328 patients who underwent thrombectomy for emergent occlusions of the intracranial internal carotid artery or the middle cerebral artery. Characteristics and treatment outcomes were compared between patients with isolated BG infarction and those with non-isolated BG infarction. Binary logistic regression analyses were performed to identify independent predictors of good outcome (90-day mRS 0-2). RESULTS: Isolated BG infarction was found in 57 patients (17.4%). Patients with isolated BG infarction had a higher incidence of underlying severe intracranial atherosclerotic stenosis (21.1% vs. 10.7%, P = 0.032) than those with non-isolated BG infarction. Successful reperfusion occurred more frequently in patients with isolated BG infarction than those with non-isolated BG infarction (93% vs. 79%, odds ratio 3.529, 95% confidence interval 1.226-10.161, P = 0.014). On multivariate logistic regression analysis, independent predictors of good outcome were age, DWI-ASPECTS, and admission NIHSS score. There was no significant difference in the rate of good outcome between the two groups (54.4% vs. 42.8%, P = 0.110). CONCLUSION: Isolated BG infarction on pretreatment DWI may predict successful reperfusion after endovascular thrombectomy in patients with acute anterior circulation stroke. In addition, our study suggested a novel finding that isolated BG infarction was more frequently associated with underlying severe ICAS than non-isolated BG infarction.

Validation of a liquid chromatography-triple quadrupole mass spectrometric method for the determination of 5-nitro-5'-hydroxy-indirubin-3'-oxime (AGM-130) in human plasma and its application to microdose clinical trial.

A liquid chromatography-triple quadrupole mass spectrometric (LC-MS/MS) method was developed and validated for the determination of 5-nitro-5'-hydroxy-indirubin-3'-oxime (AGM-130) in human plasma to support a microdose clinical trial. The method consisted of a liquid-liquid extraction for sample preparation and LC-MS/MS analysis in the positive ion mode using TurboIonSpray(TM) for analysis. d3 -AGM-130 was used as the internal standard. A linear regression (weighted 1/concentration) was used to fit calibration curves over the concentration range of 10-2000 pg/mL for AGM-130. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 96.6% with a precision (coefficient of variation, CV) of 4.4%. For quality control samples at 30, 160 and 1600 pg/mL, the between run CV was ≤5.0 %. Between-run accuracy ranged from 98.1 to 101.0%. AGM-130 was stable in 50% acetonitrile for 168 h at 4°C and 6 h at room temperature. AGM-130 was also stable in human plasma at room temperature for 6 h and through three freeze-thaw cycles. The variability of selected samples for the incurred sample reanalysis was ≤12.7% when compared with the original sample concentrations. This validated LC-MS/MS method for determination of AGM-130 was used to support a phase 0 microdose clinical trial.

Predictors of Good Outcome After Stent-Retriever Thrombectomy in Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Factors related to prognosis after a modern mechanical thrombectomy in patients with acute basilar artery occlusion remain unclear. This study investigated the prognostic factors for patients with acute basilar artery occlusion who underwent a stent-retriever thrombectomy. METHODS: We analyzed clinical and pretreatment diffusion-weighted imaging (DWI) data in 50 consecutive patients with acute basilar artery occlusion treated with stent-retriever thrombectomy. A good outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The association between clinical and DWI parameters and functional outcome was evaluated with logistic regression analysis. RESULTS: In a univariate analysis, the following variables were significantly associated with outcome: age, hypertension, baseline National Institutes of Health Stroke Scale, posterior circulation Acute Stroke Prognosis Early CT Score on a pretreatment DWI, posterior circulation Acute Stroke Prognosis Early CT Score of ≥7 (versus <7), thalamic infarction, and bilateral thalamic infarction. In a multivariate model, only a low initial National Institutes of Health Stroke Scale score (odds ratio, 0.82; 95% confidence interval, 0.709-0.949; P=0.008) and high DWI posterior circulation Acute Stroke Prognosis Early CT Score (odds ratio, 1.854; 95% confidence interval 1.012-3.397; P=0.045) were significant independent predictors of good outcome. In a univariate analysis, bilateral thalamic infarction was associated with a poor outcome (odds ratio, 1.993; 95% confidence interval, 1.187-3.346; P=0.035) but not with a unilateral thalamic infarction (P=0.525). CONCLUSIONS: This study suggested that initial infarction severity and posterior circulation Acute Stroke Prognosis Early CT Score on a pretreatment DWI are independent predictors of clinical outcome after stent-retriever thrombectomy in patients with acute basilar artery occlusion.

Altered Sexual Response-Related Functional Connectivity and Morphometric Changes Influenced by Sex Hormones across Menopausal Status.

Our study retrospectively investigated differential patterns of the functional connectivity (FC) of core brain regions synchronous with morphometric changes associated with sexual dysfunction in menopausal women, and their correlations with sexual hormones. Twenty-three premenopausal women (mean age: 41.52 ± 7.38 years) and 21 menopausal women (mean age: 55.52 ± 2.80 years) underwent sex hormone level measurements with high-resolution T1 and functional magnetic resonance imaging (MRI) during rest, neutral, and sexual arousal conditions. Analysis of covariance adjusted for age was used to compare the FC and gray matter (GM) volume between the two groups. Menopausal women showed lower GM volumes in the superior frontal gyrus (SFG), superior temporal pole, parahippocampal gyrus (PHG), hippocampus (Hip), amygdala (Amg), and cerebellum (Cb) compared to premenopausal women (p < 0.05). In addition, compared to premenopausal women, menopausal women showed decreased FC of seed regions involved in the SFG, frontal eye fields, and Amg, as well as target regions involved in the PHG, Hip, inferior frontal gyrus, Cb, and vermis (p < 0.005). Furthermore, the FC between the right Amg and right Cb and between the left Amg and right Cb during sexual arousal in both groups was positively correlated with total estrogen and estradiol levels, respectively (p < 0.01). The GM volume values in the right Amg and right Cb were positively correlated with total estrogen and estradiol levels (p < 0.05). Our study demonstrated an association between menopause-related differential FC and GM volume variations and fluctuating sex hormones. Our findings highlight that overlapping brain regions with functional alterations and morphometric changes are closely linked with menopausal symptom-related decreases in sexual arousal and hormone levels.

Polymeric DNase-I nanozymes targeting neutrophil extracellular traps for the treatment of bowel inflammation.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a family of chronic disorders along the gastrointestinal tract. Because of its idiopathic nature, IBD does not have a fundamental cure; current available therapies for IBD are limited to prolonged doses of immunomodulatory agents. While these treatments may reduce inflammation, limited therapeutic efficacy, inconsistency across patients, and adverse side effects from aggressive medications remain as major drawbacks. Recently, excessive production and accumulation of neutrophil extracellular traps (NETs) also known as NETosis have been identified to exacerbate inflammatory responses and induce further tissue damage in IBD. Such discovery invited many researchers to investigate NETs as a potential therapeutic target. DNase-I is a natural agent that can effectively destroy NETs and, therefore, potentially reduce NETs-induced inflammations even without the use of aggressive drugs. However, low stability and rapid clearance of DNase-I remain as major limitations for further therapeutic applications. In this research, polymeric nanozymes were fabricated to increase the delivery and therapeutic efficacy of DNase-I. DNase-I was immobilized on the surface of polymeric nanoparticles to maintain its enzymatic properties while extending its activity in the colon. Delivery of DNase-I using this platform allowed enhanced stability and prolonged activity of DNase-I with minimal toxicity. When administered to animal models of IBD, DNase-I nanozymes successfully alleviated various pathophysiological symptoms of IBD. More importantly, DNase-I nanozyme administration successfully attenuated neutrophil infiltration and NETosis in the colon compared to free DNase-I or mesalamine.

Superior cerebellar artery occlusion remaining after thrombectomy for acute basilar artery occlusion.

To investigate the incidence and impact of superior cerebellar artery (SCA) occlusion remaining after thrombectomy for acute basilar artery occlusion (BAO). We retrospectively analyzed data from 116 patients who underwent thrombectomy for BAO. The patency of SCA was assessed on final angiograms. Clinical and radiologic data of the patients were retrieved from a prospectively collected database and analyzed. All patients underwent pretreatment and follow-up DWI to detect new infarctions in SCA territory. Ten patients (8.6%) had SCA occlusions on final angiograms. Of these, two patients had bilateral occlusions. A new infarction with a diameter ranged from 4 to 11 mm in corresponding SCA territory occurred in 5 of 10 patients. No patients with SCA occlusions experienced symptomatic cerebellar hemorrhage or malignant cerebellar infarction. Nine of 12 SCA occlusions showed spontaneous recanalization on follow-up CT angiography. Four of 10 patients showed 90-day favorable outcome (mRS 0-3) and 90-day mortality occurred in one patient. SCA occlusions remaining after thrombectomy for acute BAO had a benign clinical course. Most of these lesions recanalized spontaneously. Our study suggests that attempts to recanalize remnant SCA occlusion may be unnecessary after basilar artery thrombectomy.

Development and validation of deep learning-based automatic brain segmentation for East Asians: A comparison with Freesurfer.

Purpose: To develop and validate deep learning-based automatic brain segmentation for East Asians with comparison to data for healthy controls from Freesurfer based on a ground truth. Methods: A total of 30 healthy participants were enrolled and underwent T1-weighted magnetic resonance imaging (MRI) using a 3-tesla MRI system. Our Neuro I software was developed based on a three-dimensional convolutional neural networks (CNNs)-based, deep-learning algorithm, which was trained using data for 776 healthy Koreans with normal cognition. Dice coefficient (D) was calculated for each brain segment and compared with control data by paired t-test. The inter-method reliability was assessed by intraclass correlation coefficient (ICC) and effect size. Pearson correlation analysis was applied to assess the relationship between D values for each method and participant ages. Results: The D values obtained from Freesurfer (ver6.0) were significantly lower than those from Neuro I. The histogram of the Freesurfer results showed remarkable differences in the distribution of D values from Neuro I. Overall, D values obtained by Freesurfer and Neuro I showed positive correlations, but the slopes and intercepts were significantly different. It was showed the largest effect sizes ranged 1.07-3.22, and ICC also showed significantly poor to moderate correlations between the two methods (0.498 ≤ ICC ≤ 0.688). For Neuro I, D values resulted in reduced residuals when fitting data to a line of best fit, and indicated consistent values corresponding to each age, even in young and older adults. Conclusion: Freesurfer and Neuro I were not equivalent when compared to a ground truth, where Neuro I exhibited higher performance. We suggest that Neuro I is a useful alternative for the assessment of the brain volume.

Preoperative prediction of Ki-67 and p53 status in meningioma using a multiparametric MRI-based clinical-radiomic model.

Purpose: To investigate the utility of preoperative multiparametric magnetic resonance imaging (mpMRI)-based clinical-radiomic analysis combined with machine learning (ML) algorithms in predicting the expression of the Ki-67 proliferative index and p53 tumor suppressor protein in patients with meningioma. Methods: This multicenter retrospective study included 483 and 93 patients from two centers. The Ki-67 index was classified into high (Ki-67≥5%) and low (Ki-67<5%)-expressed groups, and the p53 index was classified into positive (p53≥5%) and negative (p53<5%)-expressed groups. Clinical and radiological features were analyzed using univariate and multivariate statistical analyses. Six ML models were performed with different types of classifiers to predict Ki-67 and p53 status. Results: In the multivariate analysis, larger tumor volumes (p<0.001), irregular tumor margin (p<0.001), and unclear tumor-brain interface (p<0.001) were independently associated with a high Ki-67 status, whereas the presence of both necrosis (p=0.003) and the dural tail sign (p=0.026) were independently associated with a positive p53 status. A relatively better performance was yielded from the model constructed by combined clinical and radiological features. The area under the curve (AUC) and accuracy of high Ki-67 were 0.820 and 0.867 in the internal test, and 0.666 and 0.773 in the external test, respectively. Regarding p53 positivity, the AUC and accuracy were 0.858 and 0.857 in the internal test, and 0.684 and 0.718 in the external test. Conclusion: The present study developed clinical-radiomic ML models to non-invasively predict Ki-67 and p53 expression in meningioma using mpMRI features, and provides a novel non-invasive strategy for assessing cell proliferation.

Advances and challenges of operational seasonal prediction in Pacific Island Countries.

Seasonal climate forecasts play a critical role in building a climate-resilient society in the Pacific Island Countries (PICs) that are highly exposed to high-impact climate events. To assist the PICs National Meteorological and Hydrological Services in generating reliable national climate outlooks, we developed a hybrid seasonal prediction system, the Pacific Island Countries Advanced Seasonal Outlook (PICASO), which has the strengths of both statistical and dynamical systems. PICASO is based on the APEC Climate Center Multi-Model Ensemble (APCC-MME), tailored to generate station-level rainfall forecasts for 49 stations in 13 countries by applying predictor optimization and the large-scale relationship-based Bayesian regression approaches. Overall, performance is improved and further stabilized temporally and spatially relative to not only APCC-MME but also other existing operational prediction systems in the Pacific. Gaps and challenges in operationalization of the PICASO system and its incorporation into operational climate services in the PICs are discussed.