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The stochastic elasticity of variance model introduced by Kim et al. (Appl Stoch Models Bus Ind 30(6):753–765, 2014) is a useful model for forecasting extraordinary volatility behavior which would take place in a financial crisis and high volatility of a market could be linked to default risk of option contracts. So, it is natural to study the pricing of options with default risk under the stochastic elasticity of variance. Based on a framework with two separate scales that could minimize the number of necessary parameters for calibration but reflect the essential characteristics of the underlying asset and the firm value of the option writer, we obtain a closed form approximation formula for the option price via double Mellin transform with singular perturbation. Our formula is explicitly expressed as the Black–Scholes formula plus correction terms. The correction terms are given by the simple derivatives of the Black–Scholes solution so that the model calibration can be done very fast and effectively.

Tissue conductivity measurements made with electrical properties tomography (EPT) can be used to define temporal changes in tissue habitats on longitudinal multiparametric MRI. We aimed to demonstrate the added insights for identifying tumor habitats obtained by including EPT with diffusion- and perfusion-weighted MRI, and to evaluate the use of these tumor habitats for determining tumor treatment response in post-treatment glioblastoma. Tumor habitats were developed from EPT, diffusion-weighted, and perfusion-weighted MRI in 60 patients with glioblastoma who underwent concurrent chemoradiotherapy. Voxels from EPT, apparent diffusion coefficient (ADC), and cerebral blood volume (CBV) maps were clustered into habitats, and each habitat was serially examined to assess its temporal change. The usefulness of temporal changes in tumor habitats for diagnosing tumor progression and treatment-related change was investigated using logistic regression. The performance of significant predictors was measured using the area under the curve (AUC) from receiver-operating-characteristics analysis with 1000-fold bootstrapping. Five tumor habitats were identified, and of these, the hypervascular cellular habitat (odds ratio [OR] 5.45; 95% CI, 1.75–31.42; p = .02), hypovascular low conductivity habitat (OR 2.00; 95% CI, 1.45–3.05; p < .001), and hypovascular intermediate habitat (OR 1.57; 95% CI, 1.18–2.30; p = .006) were predictive of tumor progression. Low EPT and low CBV reflected a unique hypovascular low conductivity habitat that showed the highest diagnostic performance (AUC 0.86; 95% CI, 0.76–0.96). The combined habitats showed high performance (AUC 0.90; 95% CI, 0.82–0.98) in the differentiation of tumor progression from treatment-related change. EPT reveals low conductivity habitats that can improve the diagnosis of tumor progression in post-treatment glioblastoma. • Electrical properties tomography (EPT) demonstrated lower conductivity in tumor progression than in treatment-related change. • EPT allowed identification of a unique hypovascular low conductivity habitat when combined with cerebral blood volume mapping. • Tumor habitats with a hypovascular low conductivity habitat, hypervascular cellular habitat, and hypovascular intermediate habitat yielded high diagnostic performance for diagnosing tumor progression.

Although rats with melanin-pigmentated retinal pigment epithelial (RPE) cells are physiologically more appropriate models for human eye research than their albino counterparts, reliable models from the former strain are not available to study retinal degeneration. Here, we describe the development of a novel Pde6b-knockout Long–Evans (LE Pde6b KO) rat model that recapitulates key features of human retinitis pigmentosa (RP). After the generation of the Pde6b-knockout Sprague–Dawley rats with the CRISPR-Cpf1 system, the LE rat was back-crossed over 5 generations to develop the pigmented LE Pde6b KO strain. Interestingly, LE Pde6b KO displayed well-developed bone-spicule pigmentation; a hallmark of fundus in patients with RP which cannot be observed in non-pigmented albino rats. Moreover, the rat model showed progressive thinning of the retina, which was evident by intravital imaging with optical coherence tomography. Histologically, significant atrophy was observed in the outer nuclear layer. Functionally, LE Pde6b KO presented a marked decrease of amplitude level during electroretinogram testing, demonstrating significant loss of visual function. Therefore, these findings suggest that the LE Pde6b KO model robustly recapitulates the hallmark phenotype of RP. We believe that the LE Pde6b KO model may be used effectively for preclinical translational research to further study retinal degeneration.

ObjectiveA lack of understanding of the clinical course of neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS) often complicates the decision-making in terms of optimal timing and mode of treatment. We investigated the outcomes of stereotactic radiosurgery (SRS) in this population.MethodsWe retrospectively analyzed NF2 patients treated with Gamma-Knife SRS for VS in our tertiary referral center. A total of 41 treated lesions from 33 patients were collected with a follow-up period of 69.1 (45.0-104.8) months. We reviewed the treatment history, hearing function, and other treatment-related morbidities in individual cases. We also analyzed pre- and post-treatment tumor volumes via imaging studies. Longitudinal volumetric analyses were conducted for the tumor volume response of the 41 treated lesions following SRS. The growth pattern of 22 unirradiated lesions during an observation period of 83.4 (61.1-120.4) months was separately evaluated.ResultsMost treated lesions showed effective tumor control up to 85% at 60 months after SRS, whereas unirradiated lesions progressed with a relative volume increase of 14.0% (7.8-27.0) per year during the observation period. Twelve (29%) cases showed pseudoprogression with significant volume expansion in the early follow-up period, which practically reduced the rate of tumor control to 57% at 24 months. Among the patients with serviceable hearing, two (20%) cases lost the hearing function on the treated side during the early follow-up period within 24 months.ConclusionsProgressive NF2-associated VS can be adequately controlled by SRS but the short-term effects of this treatment are not highly advantageous in terms of preserving hearing function. SRS treatment candidates should therefore be carefully selected.

Diffuse midline glioma (DMG) which occurs in midline structures and characterized by harboring K27M mutation in genes encoding the histone 3 protein is classified as World Health Organization (WHO) grade IV regardless of histological findings and has a poor prognosis. Nevertheless, because of its relatively rare incidence compared with other high-grade gliomas, a comprehensive description encompassing clinical features and genomic profiles of DMG is still lacking.In this study, we analyzed data of 24 patients who were diagnosed as DMG which was confirmed by surgical specimens in both pediatric and adult patients. We described the clinical outcomes of patients with DMG and their genomic profiles through a retrospective analysis of 24 patients with DMG.The clinical characteristics of the 24 patients with DMG were analyzed. Ten patients (41%) underwent tumor resection and 14 patients (59%) underwent tumor biopsy. The median overall survival was 10.4 months (95% confidence interval [CI], 8.4 to 12.5) and progression free survival was 3.9 months (95% CI, 2.6 to 5.2). Fifteen patients (62%) were accompanied by hydrocephalus. None of the patient, tumor, or treatment factors had any significant associated with survival. In both immunohistochemistry staining (n=24) and targeted next generation sequencing (n=15), TP53 mutation was the most common genetic mutation (25% and 46%, respectively) found in the patients except alterations in histone 3 protein.Although surgical treatment of patient with DMG does not affect the overall survival prognosis, it can help improve the patient's accompanying neurological symptoms in some limited cases. Hydrocephalus is often accompanied with DMG and treatment for hydrocephalus is often also required. Multidisciplinary therapeutic approach is needed.

Anaplastic meningioma is very rare and is generally known to have a poor prognosis. However, due to its rarity, the relationship between clinical prognosis and prognostic factors is not clear. We analyzed the prognostic factors influencing survival outcomes of patients with anaplastic meningioma. Moreover, we analyzed on the progression pattern and the response to treatment about anaplastic meningioma.Retrospective review of 48 patients with diagnosis of World Health Organization (WHO) grade 3 meningioma was performed. According to diagnosis type, primary anaplastic meningioma was included in 28 cases and secondary anaplastic meningioma in 20 cases. Gross total resection was performed in 36 patients (75.0%), and 32 patients (66.7%) received adjuvant radiotherapy after tumor resection with confirmed WHO grade 3 meningioma. Kaplan-Meier survival curve and Cox proportional hazards modeling were used for outcome analysis.The median progression-free survival (PFS) and overall survival (OS) were 13.9 months (95% confidence interval [CI], 8.8 to 19.1) and 56.9 months (95% CI, 24.1 to 89.7), respectively. Adjuvant radiotherapy was a robust prognostic factor for PFS and OS. Extent of resection and diagnosis type which appeared to be significant prognostic factors in univariate analysis were failed to prove statistical significance in multivariate analysis.Adjuvant radiotherapy is an essential treatment arm in patients with anaplastic meningiomas. Stereotactic radiosurgery seems to play an important role as a salvage treatment. But chemotherapy seems to have limited efficacy. Because of the disseminated nature of the disease, further investigations to improve survival outcome are needed.

Recently, semantic segmentation based on deep neural network (DNN) has attracted attention as it exhibits high accuracy, and many studies have been conducted on this. However, DNN-based segmentation studies focused mainly on improving accuracy, thus greatly increasing the computational demand and memory footprint of the segmentation network. For this reason, the segmentation network requires a lot of hardware resources and power consumption, and it is difficult to be applied to an environment where they are limited, such as an embedded system. In this paper, we propose a binarized encoder-decoder network ( BEDN ) and a binarized deconvolution engine ( BiDE ) accelerating the network to realize low-power, real-time semantic segmentation. BiDE implements a binarized segmentation network with custom hardware, greatly reducing the hardware resource usage and greatly increasing the throughput of network implementation. The deconvolution used for upsampling in a segmentation network includes zero padding. In order to enable deconvolution in a binarized segmentation network that cannot express zero, we introduce zero-aware binarized deconvolution which skips padded zero activations and zero-aware batch normalization embedded binary activation considering zero-skipped convolution. The BEDN , which is a binarized segmentation network proposed to be accelerated on BiDE , has acceptable accuracy while greatly reducing the computational and memory demands of the segmentation network through full-binarization and simple structure. BEDN has a network size of 0.21 MB, and its maximum memory usage is 1.38 MB. BiDE was implemented on Xilinx ZU7EV field-programmable gate array (FPGA) to operate at 187.5 MHz. BiDE accelerated the proposed BEDN within CamVid11 images of $480\times {360}$ size at 25.89 frames per second (FPS) achieving a performance of 1.682 Tera operations per second (TOPS) and 824 Giga operations per second per watt (GOPS/W).

The Antarctic toothfish, Dissostichus mawsoni, belongs to the Nototheniidae family and is distributed in sub-zero temperatures below S60° latitude in the Southern Ocean. Therefore, it is an attractive model species to study the stenothermal cold-adapted character state. In this study, we successfully generated highly contiguous genome sequences of D. mawsoni, which contained 1 062 scaffolds with a N50 length of 36.98 Mb and longest scaffold length of 46.82 Mb. Repetitive elements accounted for 40.87% of the genome. We also inferred 32 914 protein-coding genes using in silico gene prediction and transcriptome sequencing and detected splicing variants using Isoform-Sequencing (Iso-Seq), which will be invaluable resource for further exploration of the adaptation mechanisms of Antarctic toothfish. This new high-quality reference genome of D. mawsoni provides a fundamental resource for a deeper understanding of cold adaptation and conservation of species.

The Antarctic toothfish, Dissostichus mawsoni, belongs to the Nototheniidae family and is distributed in sub-zero temperatures below S60° latitude in the Southern Ocean. Therefore, it is an attractive model species to study the stenothermal cold-adapted character state. In this study, we successfully generated highly contiguous genome sequences of D. mawsoni, which contained 1 062 scaffolds with a N50 length of 36.98 Mb and longest scaffold length of 46.82 Mb. Repetitive elements accounted for 40.87% of the genome. We also inferred 32 914 protein-coding genes using in silico gene prediction and transcriptome sequencing and detected splicing variants using Isoform-Sequencing (Iso-Seq), which will be invaluable resource for further exploration of the adaptation mechanisms of Antarctic toothfish. This new high-quality reference genome of D. mawsoni provides a fundamental resource for a deeper understanding of cold adaptation and conservation of species.

α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are differentially regulated in the nucleus accumbens (NAcc) of the brain after cocaine exposure. However, these results are supported only by biochemical and electrophysiological methods, but have not been validated with immunohistochemistry. To overcome the restriction of antigen loss on the postsynaptic target molecules that occurs during perfusion-fixation, we adopted an immersion-fixation method that enabled us to immunohistochemically quantify the expression levels of the AMPA receptor GluA1 subunit in the NAcc. Interestingly, compared to saline exposure, cocaine significantly increased the immunofluorescence intensity of GluA1 in two sub-regions, the core and the shell, of the NAcc on withdrawal day 21 following cocaine exposure, which led to locomotor sensitization. Increases in GluA1 intensity were observed in both the extra-post synaptic density (PSD) and PSD areas in the two sub-regions of the NAcc. These results clearly indicate that AMPA receptor plasticity, as exemplified by GluA1, in the NAcc can be visually detected by immunohistochemistry and confocal imaging. These results expand our understanding of the molecular changes occurring in neuronal synapses by adding a new form of analysis to conventional biochemical and electrophysiological methods.

Rationale: Aberrant androgen receptor (AR) signaling via full-length AR (AR-FL) and constitutively active AR variant 7 (AR-V7) plays a key role in the development of castration-resistant prostate cancer (CRPC) and resistance to hormone therapies. Simultaneous targeting of AR-FL and AR-V7 may be a promising strategy to overcome resistance to hormone therapy. This study aimed to identify novel drug candidates co-targeting AR-FL and AR-V7 activities and elucidate their molecular mechanism of anti-CRPC activities. Methods: Using a CRPC cell-based reporter assay system, we screened a small library of antimalarial agents to explore the possibility of repositioning them for CRPC treatment and identified bruceantin (BCT) as a potent anti-CRPC drug candidate. A series of cell-based, molecular, biochemical, and in vivo approaches were performed to evaluate the therapeutic potential and molecular mechanism of BCT in CRPC. These approaches include reporter gene assays, cell proliferation, RNA-seq, qRT-PCR, mouse xenografts, co-immunoprecipitation, GST pull-down, immobilized BCT pull-down, molecular modeling, and bioinformatic analyses. Results: We identified BCT as a highly potent inhibitor co-targeting AR-FL and AR-V7 activity. BCT inhibits the transcriptional activity of AR-FL/AR-V7 and downregulates their target genes in CRPC cells. In addition, BCT efficiently suppresses tumor growth and metastasis of CRPC cells. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7 by directly binding to HSP90 and inhibits HSP90 chaperone function, leading to degradation of AR-FL/AR-V7 through the ubiquitin-proteasome system. Clinically, HSP90 expression is upregulated and correlated with AR/AR-V7 levels in CRPC. Conclusion: Our findings suggest that BCT could serve as a promising therapeutic candidate against CRPC and highlight the potential benefit of targeting AR-FL/AR-V7-HSP90 axis to overcome resistance caused by aberrant AR-FL/AR-V7 signaling.

Optogenetics is a powerful technique that allows target-specific spatiotemporal manipulation of neuronal activity for dissection of neural circuits and therapeutic interventions. Recent advances in wireless optogenetics technologies have enabled investigation of brain circuits in more natural conditions by releasing animals from tethered optical fibers. However, current wireless implants, which are largely based on battery-powered or battery-free designs, still limit the full potential of in vivo optogenetics in freely moving animals by requiring intermittent battery replacement or a special, bulky wireless power transfer system for continuous device operation, respectively. To address these limitations, here we present a wirelessly rechargeable, fully implantable, soft optoelectronic system that can be remotely and selectively controlled using a smartphone. Combining advantageous features of both battery-powered and battery-free designs, this device system enables seamless full implantation into animals, reliable ubiquitous operation, and intervention-free wireless charging, all of which are desired for chronic in vivo optogenetics. Successful demonstration of the unique capabilities of this device in freely behaving rats forecasts its broad and practical utilities in various neuroscience research and clinical applications., Although wireless optogenetic technologies enable brain circuit investigation in freely moving animals, existing devices have limited their full potential, requiring special power setups. Here, the authors report fully implantable optogenetic systems that allow intervention-free wireless charging and controls for operation in any environment.

The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins known to play roles in cell-shape determination as well as in signaling pathways. We have previously shown that amphetamine decreases phosphorylation levels of these proteins in the nucleus accumbens (NAcc), an important neuronal substrate mediating rewarding effects of drugs of abuse. In the present study, we further examined what molecular pathways may be involved in this process. By direct microinjection of LY294002, a PI3 kinase inhibitor, or of S9 peptide, a proposed GSK3β activator, into the NAcc core, we found that phosphorylation levels of ERM as well as of GSK3β in this site are simultaneously decreased. These results indicate that ERM proteins are under the regulation of Akt-GSK3β signaling pathway in the NAcc core. The present findings have a significant implication to a novel signal pathway possibly leading to structural plasticity in relation with drug addiction.

This study was conducted to determine the optimum operating conditions for the collecting device of agricultural by-product collector. A factorial experiment was performed using a test equipment with the collecting device. By targeting apple pruning branches, the collecting ratio for the branches was measured according to the rotational speed (100, 200, and 300 rpm), clearance from the soil surface (− 10, 0, and 10 mm), and forward-moving speed (0.6, 0.8, and 1.0 m/s) of the collecting device. The results were analyzed using mean collecting ratio of the triplicate experiment for each condition. Therefore, the total number of experiment is 81. Experimental results show that the collecting ratio was the highest when the collecting device was operated at 200 rpm rotational speed, 0 mm clearance from the soil surface, and 0.6 m/s moving speed. The conditions that ensured a ≥ 99% collecting ratio were 0.6 m/s and 0.8 m/s moving speed, 200 rpm rotational speed, and 0 mm clearance from the soil surface. Regarding the field capacity, the optimum operating conditions for the collecting device were determined as 0.8 m/s moving speed, 200 rpm rotational speed, and 0 mm clearance from the soil surface.

Many hedge funds and retail investors demand volatility and variance derivatives in order to manage their exposure to volatility and volatility-of-volatility risk associated with their trading positions. The Heston model is a standard popular stochastic volatility model for pricing volatility and variance derivatives. However, it may fail to capture some important empirical features of the relevant market data due to the fact that the elasticity of volatility of volatility of the underlying price takes a special value, i.e., 1/2, whereas it has a merit of analytical tractability. We exploit a multiscale stochastic extension of volatility of volatility to obtain a better agreement with the empirical data while taking analytical advantage of the original Heston dynamics as much as possible in the context of pricing discrete variance swaps. By using an asymptotic technique with two small parameters, we derive a quasi-closed form formula for the fair strike price of variance swap and find useful pricing properties with respect to the stochastic extension parameters.

Aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in maintaining cellular homeostasis in response to environmental stress. Under conditions of hypoxia or xenobiotic exposure, ARNT regulates the subset of genes involved in adaptive responses, by forming heterodimers with hypoxia-inducible transcription factors (HIF1α and HIF2α) or aryl hydrocarbon receptor (AhR). Here, we have shown that ARNT interacts with DDB1 and CUL4-associated factor 15 (DCAF15), and the aryl sulfonamides, indisulam and E7820, induce its proteasomal degradation through Cullin-RING finger ligase 4 containing DCAF15 (CRL4DCAF15) E3 ligase. Moreover, the two known neo-substrates of aryl sulfonamide, RNA-binding motif protein 39 (RBM39) and RNA-binding motif protein 23 (RBM23), are not required for ARNT degradation. In line with this finding, aryl sulfonamides inhibited the transcriptional activities of HIFs and AhR associated with ARNT. Our results collectively support novel regulatory roles of aryl sulfonamides in both hypoxic and xenobiotic responses.

Recent ground-breaking work shows that stochastic volatility models driven by fractional Brownian motion with short memory provide better calibration of the volatility surface and more robust estim...

OBJECTIVE. The existing literature lacks research into the benefits of initial screening imaging for patients with cerebellar hemangioblastoma. We aimed to evaluate the diagnostic yield of initial screening imaging using abdominal CT and whole-spine MRI in patients with cerebellar hemangioblastoma. MATERIALS AND METHODS. This retrospective study included 117 consecutive patients with histopathologically confirmed, newly diagnosed cerebellar hemangioblastomas at a single tertiary hospital between January 2006 and October 2018. Patients underwent contrast-enhanced abdominal CT, whole-spine MRI, or both to detect abdominal and spinal lesions of von Hippel-Lindau disease. Diagnostic yields and false referral rates for initial screening imaging were determined. RESULTS. After exclusion of six patients who forewent any initial imaging, 111 patients were included (53 men [mean age ± SD, 51 ± 13 years] and 58 women [mean age, 43 ± 16 years]). The diagnostic yield of abdominal CT was 3.8% (4 of 105; 95% CI, 1.1-9.3%), whereas the false referral rate was 1.0% (1 of 105; 95% CI, 0.0-5.2%). For whole-spine MRI, the corresponding values were 5.6% (4 of 71; 95% CI, 1.6-13.8%) and 2.8% (2 of 71; 95% CI, 0.3-9.8%), respectively. The respective diagnostic yields in patients with a single cerebellar hemangioblastoma were both 0% (0 of 98 and 66, respectively). CONCLUSION. For patients with a single cerebellar hemangioblastoma, screening examinations with abdominal CT and whole-spine MRI are unnecessary before the results of genetic testing are available.

Background Brain invasion by meningioma is a stand-alone criterion for tumor atypia in the 2016 World Health Organization classification, but no imaging parameter has yet been shown to be sufficient for predicting it. The aim of this study was to develop and validate an MRI-based radiomics model from the brain-to-tumor interface to predict brain invasion by meningioma. Methods Preoperative T2-weighted and contrast-enhanced T1-weighted imaging data were obtained from 454 patients (88 patients with brain invasion) between 2012 and 2017. Feature selection was performed from 3222 radiomics features obtained in the 1 cm thickness tumor-to-brain interface region using least absolute shrinkage and selection operator. Peritumoral edema volume, age, sex, and selected radiomics features were used to construct a random forest classifier–based diagnostic model. The performance was evaluated using the areas under the curves (AUCs) of the receiver operating characteristic in an independent cohort of 150 patients (29 patients with brain invasion) between 2018 and 2019. Results Volume of peritumoral edema was an independent predictor of brain invasion (P < 0.001). The top 6 interface radiomics features plus the volume of peritumoral edema were selected for model construction. The combined model showed the highest performance for prediction of brain invasion in the training (AUC 0.97; 95% CI: 0.95–0.98) and validation sets (AUC 0.91; 95% CI: 0.84–0.98), and improved diagnostic performance over volume of peritumoral edema only (AUC 0.76; 95% CI: 0.66–0.86). Conclusion An imaging-based model combining interface radiomics and peritumoral edema can help to predict brain invasion by meningioma and improve the diagnostic performance of known clinical and imaging parameters.

The long-term plasticity of biological synapses was successfully emulated in an artificial synapse fabricated by combining low-surface defect van der Waals (vdW) and self-assembled (SA) materials. The synaptic operation could be achieved by facilitating hole trapping and releasing only via the amine (NH

Phosphorylation of the signaling component by protein kinase often leads to a kinase cascade or feedback loop. 3-Phosphoinositide- dependent kinase 1 (PDK1) signaling pathway diverges into various kinases including Akt and p70 S6 kinase (p70S6k). However, the PDK1 feedback mechanism remains elusive. Here, we demonstrated that UNC-51-like kinase (ULK1), an autophagy initiator kinase downstream of mechanistic target of rapamycin (mTOR), directly phosphorylated PDK1 on serine 389 at the linker region. Furthermore, our data showed that this phosphorylation affected the kinase activity of PDK1 toward downstream substrates. These results suggest a possible negative feedback loop between PDK1 and ULK1. [BMB Reports 2020; 53(7): 373-378].

As market observations say that many financial quantities are correlated in a time dependent, nonlinear or unpredictable way, in this study, we present an approach to price discretely sampled variance swaps based on the Heston model extended by incorporating deterministic or stochastic correlation between an underlying asset and its variance. We obtain a closed form exact formula for the fair delivery prices under the deterministic correlation model and an affine approximation formula under the stochastic correlation model. A comparison with Monte–Carlo simulations supports the validity of the pricing formulas. Based on the analytic results, we find that the fair delivery price increases as time to maturity or leverage effect increases or sampling frequency decreases. On the other hand, the impact scale of the correlation volatility is so imperceptible that the time dependent deterministic correlation model can still be a good proxy of the stochastic correlation environment in the case of variance swap pricing, while the approximation formula with the stochastic correlation is better than the exact formula with the deterministic correlation in computing sense.

Appropriate capturing the nature of financial market volatility is a significant factor for the pricing of volatility derivatives. A recent study by Gatheral, Jaisson and Rosenbaum [2018. “Volatili...

Background Amide proton transfer (APT) MRI has the potential to demonstrate antitumor effects by reflecting biologically active tumor portion, providing different information from diffusion-weighted imaging (DWI) or dynamic susceptibility contrast (DSC) imaging. Purpose To evaluate whether a change in APT signal intensity after antiangiogenic treatment is predictive of early treatment response in recurrent glioblastoma. Materials and Methods In this retrospective study, APT MRI, DWI, and DSC imaging were performed in patients with recurrent glioblastoma from July 2015 to April 2019, both before treatment and 4-6 weeks after initiation of bevacizumab (follow-up). Progression was based on pathologic confirmation or clinical-radiologic assessment, and progression patterns were defined as local enhancing or diffuse nonenhancing. Changes in mean and histogram parameters (fifth and 95th percentiles) of APT signal intensity, apparent diffusion coefficient, and normalized cerebral blood volume (CBV) between imaging time points were calculated. Predictors of 12-month progression and progression-free survival (PFS) were determined by using logistic regression and Cox proportional hazard modeling and according to progression type. Results A total of 54 patients were included (median age, 56 years [interquartile range, 49-64 years]; 24 men). Mean APT signal intensity change after bevacizumab treatment indicated a low 12-month progression rate (odds ratio [OR], 0.36; 95% confidence interval [CI]: 0.13, 0.90

PurposeWe investigated the efficacy of temozolomide during and after radiotherapy in Korean adults with anaplastic gliomas without 1p/19q co-deletion.Materials and MethodsThis was a randomized, open-label, phase 2 study and notably the first multicenter trial for Korean grade III glioma patients. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomized 1:1 to receive radiotherapy alone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy with concurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200 mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary end-point was 2-year progression-free survival (PFS). Seventy patients (83.3%) were available for the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status.ResultsThe two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overall survival (OS) did not reach to significant difference between the groups. In multivariable analysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.04 to 4.16). The IDH1 mutation was the only significant prognostic factor for PFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverse events over grade 3 were seen in 16 patients (40.0%) in the treatment group and were reversible.ConclusionConcurrent and adjuvant temozolomide in Korean adults with newly diagnosed non-co- deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimen needs further analysis with long-term follow-up at least more than 10 years.

Adsorptive separation of SF6/N2 mixtures is an important issue since SF6 is a significant greenhouse gas. Although separation performances should be evaluated under high pressure conditions to find an efficient adsorbent candidate for pressure swing adsorption (PSA) processes, no studies on metal–organic frameworks (MOFs) have focused on SF6/N2 separation at high pressures above 1 bar. In this study, we evaluated the potential of three hydrothermally stable adsorbents, including two MOFs (UiO-66 and UiO-67) and zeolite-13X, for SF6/N2 separation under normal PSA operation pressures (∼10 bar). Interestingly, UiO-67 with a high surface area and large pore size exhibited very high SF6/N2 selectivity (30∼37) at 10 bar as well as a significantly large SF6 working capacity (5.94 mmol g−1) between 10 bar and 1 bar. Moreover, UiO-67 showed facile regeneration at the ambient temperature as well as good cyclic adsorption and desorption behavior during 20 cycles. These results show that UiO-67 is a potential adsorbent for adsorptive SF6/N2 separation.

Purpose To assess the feasibility and safety of a novel 3D-printed biodegradable biliary stent using polycaprolactone (PCL) in an in vivo porcine model Materials and Methods In this animal study using domestic pigs, biodegradable radiopaque biliary stents made of polycaprolactone (PCL) and barium sulfate were produced using 3D printing and surgically inserted into the common bile duct (CBD) of pigs (stent group, n = 12). Another five pigs were allocated to the control group that only underwent resection and anastomosis of the CBD without stent insertion. To check the position and status of the stents and stent-related complications, follow-up computed tomography (CT) was performed every month. The pigs were sacrificed 1 or 3 months after surgery, and their excised CBD specimens were examined at both the macroscopic and microscopic levels. Results Three pigs (one in the stent group and two in the control group) died within one day after surgery and were excluded from further analysis; the remaining 11 in the stent group and 3 in the control group survived the scheduled follow-up period (1 month, 5 and 1; and 3 months, 6 and 2 in stent and control groups, respectively). In all pigs, no clinical symptoms or radiologic evidence of biliary complications was observed. In the stent group (n = 11), stent migration (n = 1 at 3 months; n = 2 at 1 month) and stent fracture (n = 3 at 2 months) were detected on CT scans. Macroscopic evaluation of the stent indicated no significant change at 1 month (n = 3) or fragmentation with discoloration at 3 months (n = 5). On microscopic examination of CBD specimens, the tissue inflammation score was significantly higher in the stent group than in the control group (mean ± standard deviation (SD), 5.63 ± 2.07 vs. 2.00 ± 1.73; P = 0.039) and thickness of fibrosis of the CBD wall was significantly higher than that of the control group (0.46 ± 0.12 mm vs. 0.21 ± 0.05mm; P = 0.012). Conclusion Despite mild bile duct inflammation and fibrosis, 3D-printed biodegradable biliary stents showed good feasibility and safety in porcine bile ducts, suggesting their potential for use in the prevention of postoperative biliary strictures.

Histone modification is a key epigenetic mechanism for regulation of chromatin dynamics and gene expression. Deleted in breast cancer 1 (DBC1) has been shown to act as a negative regulator of epigenetic modifiers and as a co-activator for nuclear receptors and other transcription factors. However, little is known about the role of DBC1 in the regulation of histone modifications and chromatin landscapes. Here, we analyzed genome-wide profiles of active enhancer and promoter marks in colorectal cancer cells and report DBC1 as a critical positive regulator of histone epigenetic writers KMT2D (H3K4 methyltransferase) and p300 (histone acetyltransferase). DBC1 is required for establishing the landscape of active enhancers, for genome-wide chromatin binding and enhancer recruitment of KMT2D and p300, and for gene activation involved in colorectal cancer progression. DBC1 interacts directly with KMT2D and p300, and enhances KMT2D-mediated histone H3K4 methylation (H3K4me1/2/3) and p300-mediated H3 acetylation. Importantly, DBC1 contributes to super-enhancer formation and function by facilitating the recruitment of KMT2D and p300 and by enhancing their functional interaction and cooperative cross-talk. Our results highlight the critical role of DBC1 as a key positive regulator of KMT2D and p300, and provide insights into regulatory mechanisms underlying the interplay between the enhancer epigenomic writers in enhancer activation.

Human cortical organoids, three-dimensional neuronal cell cultures derived from human induced pluripotent stem cells, have recently emerged as promising models of human brain development and dysfunction. Transplantation of human brain organoids into the mouse brain has been shown to be a successful in vivo model providing vascularization for long term chronic experiments. However, chronic functional connectivity and responses evoked by external sensory stimuli has yet to be demonstrated, due to limitations of chronic recording technologies. Here, we develop an experimental paradigm based on transparent graphene microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human organoids transplanted in the mouse cortex. The transparency of graphene microelectrodes permits visual and optical inspection of the transplanted organoid and the surrounding cortex throughout the chronic experiments where local field potentials and multi-unit activity (MUA) are recorded during spontaneous activity and visual stimuli. These experiments reveal that visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in the power of the gamma and MUA bands as well as phase locking of MUA events to slow oscillations evoked by visual stimuli suggest functional connectivity established between the human and mouse tissue. Optical imaging through the transparent microelectrodes shows vascularization of the organoids. Postmortem histological analysis exhibits morphological integration and synaptic connectivity with surrounding mouse cortex as well as migration of organoid cells into the surrounding cortex. This novel combination of stem cell and neural recording technologies could serve as a unique platform for comprehensive evaluation of organoids as models of brain development and dysfunction and as personalized neural prosthetics to restore lost, degenerated, or damaged brain regions.

We evaluated the efficacy of sublingual immunotherapy for children aged 5-17 years with atopic dermatitis who were allergic to house dust mites.This open-label, controlled, randomised trial from June 2015 to February 2018 comprised 60 subjects from a specialist allergy centre in South Korea. Half received sublingual immunotherapy for 12 months and the other half formed the control group. The subjects were evaluated using specialist scores and specific immunoglobulin and skin prick tests.Sublingual immunotherapy significantly decreased the mean Scoring Atopic Dermatitis measurements in the sublingual group from baseline (30.2 ± 10.7) to 3 months (20.7 ± 8.5) and the effects persisted at 12 months (21.5 ± 12.4). However, the control group only showed a significant difference between baseline (30.4 ± 11.9) and 12 months (24.3 ± 10.2). The levels of Dermatophagoides farina-specific immunoglobulin G4 significantly increased in the treatment group from baseline (0.6 ± 0.5) to 12 months (1.0 ± 0.7), with no significant changes in the control group. New sensitisations to two or more allergens between baseline and 12 months were significantly lower in the sublingual group (21.4%) than controls (54.2%).Sublingual immunotherapy improved disease severity and prevented new sensitisations in children with atopic dermatitis who were allergic to dust mites.

Meso- and macrozooplankton play crucial roles in the trophic web and the biological carbon pump in the ocean by transferring energy from lower to higher trophic levels and vertically exporting carbon from the surface to the deep ocean and seabed. In this study, zooplankton community structures in the Ross Sea, Antarctica, were analyzed using metabarcoding methods. Both regular barcode (RB) (using a PacBio Sequel system) and mini barcode (MB) (using the Illumina MiSeq platform) methods were utilized. As the result of a combination of the two bioinformatic pipelines used in the RB, 55 reliable haplotypes were obtained from the pooled zooplankton net samples, whereas 183 amplicon sequence variants (ASVs) were isolated from the MB metabarcoding analyses of 14 individual stations. Among these, 39 (70.9%) and 125 (90.6%) showed higher than 99% sequence identity to the database, indicating that there were sufficient reference sequences to employ metabarcoding analysis—except for several taxa, including small-sized copepods, cnidarians, and pneumodermatids. A high degree of shared taxa showed that both metabarcoding analyses were feasible for use in the analysis of zooplankton assemblages in the Ross Sea. However, RB would be more useful for the construction of a reference database due to its relatively high cost, whereas MB would be more economic for ecological surveys due to its relatively low cost (albeit, only if reference sequences were well documented using RB). Zooplankton assemblages were highly diverse in each sample site, presumably due to the narrow covered volumes of the vertical net-towed samples from polynyas in the Ross Sea. As metabarcoding data accumulate, we will gain better insights into zooplankton communities and their ecological implications in the Ross Sea.

Anti-angiogenic therapy may not benefit all patients with recurrent glioblastomas, and imaging biomarker predicting treatment response to anti-angiogenic therapy is currently limited. We aimed to develop and validate vascular habitats based on perfusion and vessel size to predict time to progression (TTP) in patients with recurrent glioblastomas treated with bevacizumab.Sixty-nine patients with recurrent glioblastomas treated with bevacizumab who underwent pretreatment MRI with dynamic susceptibility contrast imaging and vessel architectural imaging were enrolled. Vascular habitats were constructed using vessel size index (VSI) and relative cerebral blood volume (rCBV). Associations with vascular habitats and TTP were analyzed using Cox proportional hazard regression analysis. In a prospectively enrolled validation cohort consisting of 15 patients ( ClinicalTrials.gov identifier; NCT04143425), stratification of TTP was demonstrated by the Kaplan-Meier method (log-rank test) using vascular habitats.Three vascular habitats consisting of high, intermediate, and low angiogenic habitats were identified with rCBV and VSI. Both high angiogenic and intermediate angiogenic habitats were significantly associated with a shorter TTP (hazard ratio [HR], 2.78 and 1.82, respectively; largest p = .003) and so was rCBV (HR, 2.15; p = .02). Concordance probability index of vascular habitat combining high and intermediate angiogenic habitats was 0.74. Vascular habitats stratified patients as good or poor responder in a prospective cohort (p = .059).Perfusion- and vessel size-derived vascular habitats predicted TTP in recurrent glioblastomas treated with anti-angiogenic therapy and aided patient stratification in a prospective validation cohort.ClinicalTrials.gov identifier: NCT04143425 KEY POINTS: • High and intermediate angiogenic habitats predicted TTP in recurrent glioblastomas treated with anti-angiogenic therapy. • Vascular habitats combining high and intermediate angiogenic habitats aided patient stratification for anti-angiogenic therapy in recurrent glioblastomas.

Surgical counseling enables shared decision-making (SDM) by improving patients' understanding.To provide answers to frequently asked questions (FAQs) in minimally invasive lumbar spine surgery.Retrospective review of prospectively collected data.Patients who underwent primary tubular minimally invasive lumbar spine surgery in form of transforaminal lumbar interbody fusion (MI-TLIF), decompression alone, or microdiscectomy and had a minimum of 1-year follow-up.(1) Surgical (radiation exposure and intraoperative complications) (2)Immediate postoperative (length of stay [LOS] and complications) (3) Clinical outcomes (Visual Analog Scale- back and leg, VAS; Oswestry Disability Index, ODI; 12-Item Short Form Survey Physical Component Score, SF-12 PCS; Patient-Reported Outcomes Measurement Information System Physical Function, PROMIS PF; Global Rating Change, GRC; return to activities; complications/reoperations) METHODS: The outcome measures were analyzed to provide answers to ten FAQs that were compiled based on the authors' experience and a review of literature. Changes in VAS back, VAS leg, ODI, and SF-12 PCS from preoperative values to the early (6 months) and late (6 months) postoperative time points were analyzed with Wilcoxon Signed Rank Tests. % of patients achieving minimal clinically important difference (MCID) for these patient-reported outcome measures (PROMs) at the two time points was evaluated. Changes in PROs from preoperative values too early (6 months) and late (≥6 months) postoperative time points were analyzed within each of the three groups. Percentage of patients achieving MCID was also evaluated.Three hundred sixty-six patients (104 TLIF, 147 decompression, 115 microdiscectomy) were included. The following FAQs were answered: (1) Will my back pain improve? Most patients report improvement by50%. About 60% of TLIF, decompression, and microdiscectomy patients achieved MCID at ≥6 months. (2) Will my leg pain improve? Most patients report improvement by50%. 56% of TLIF, 67% of decompression, and 70% of microdiscectomy patients achieved MCID at ≥6 months. (3) Will my activity level improve? Most patients report significant improvement. Sixty-six percent of TLIF, 55% of decompression, and 75% of microdiscectomy patients achieved MCID for SF-12 PCS. (4) Is there a chance I will get worse? Six percent after TLIF, 14% after decompression, and 5% after microdiscectomy. (5) Will I receive a significant amount of radiation? The radiation exposure is likely to be acceptable and nearly insignificant in terms of radiation-related risks. (6) What is the likelihood that I will have a complication? 17.3% (15.4% minor, 1.9% major) for TLIF, 10% (9.3% minor and 0.7% major) for decompression, and 1.7% (all minor) for microdiscectomy (7) Will I need another surgery? Six percent after TLIF, 16.3% after decompression, 13% after microdiscectomy. (8) How long will I stay in the hospital? Most patients get discharged on postoperative day one after TLIF and on the same day after decompression and microdiscectomy. (9) When will I be able to return to work?80% of patients return to work (average: 25 days after TLIF, 14 days after decompression, 11 days after microdiscectomy). (10) Will I be able to drive again?90% of patients return to driving (average: 22 days after TLIF, 11 days after decompression, 14 days after microdiscectomy).These concise answers to the FAQs in minimally invasive lumbar spine surgery can be used by physicians as a reference to enable patient education.

Internal carotid artery (ICA) injury during transsphenoidal surgery is a rare but serious complication. We analyzed a series of ICA injuries that occurred during a transsphenoidal approach to suggest an optimal management strategy.Between January 2015 and May 2020, we enrolled 10 cases of ICA injury at our institution.Among the 10 patients enrolled, 5 had pituitary adenoma, 2 had craniopharyngioma, and 1 each had skull base chondrosarcoma, tuberculum sellae meningioma, and nasopharyngeal cancer; 4 were revision surgery cases. The cavernous segment of the ICA was the most commonly injured area. The most common reason for ICA injury was a drill injury at the sellar floor opening. A direct repair was performed using a clip in only 1 patient. In the others, bleeding control of the injured ICA was achieved by packing multiple cotton pads. After angiography, 6 patients underwent immediate endovascular sacrifice of the injured ICA. In 3 patients who showed poor collateral flow from the anterior communicating and posterior communicating arteries, revascularization surgery was performed before endovascular trapping. After 6 postoperative months, 6 patients showed favorable functional outcomes, and 4 patients showed poor functional outcomes.Prompt control of bleeding, endovascular management of injured ICA, and consideration of revascularization surgery based on collateral flow may prevent catastrophic neurological sequelae.