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Background: Chiasmatic cavernous hemangioma (CCH) is a rare disease. Most cases are treated with surgical resection through approaches such as pterional and orbitozygomatic craniotomy. However, with advancements in surgical technique and heightened patient demand for improved postoperative quality of life, there have been reports in recent years exploring more minimally invasive surgical approaches, such as the subfrontal trans-eyebrow keyhole and endoscopic endonasal transsphenoidal approach. In this article, the cases of CCH in the reported literature are reviewed, the indications and techniques of minimally invasive surgery for the removal of CCH through the subfrontal trans-eyebrow keyhole approach are discussed, and the effects of different surgical approaches are analyzed., Methods: We reviewed the literature on surgical cases of intracranial cavernous hemangiomas (with chiasma as the center) involving the visual pathway published from 2000 to 2023 in PubMed and other relevant databases; ultimately, 55 cases from 37 articles were retrieved, to which we added an additional case, making the total number of cases examined 56. We analyzed the patient's medical records, including pathological symptoms, relationship with the chiasma location, surgical approach, and prognosis., Results: The analysis of the data of 56 cases indicated that most patients experienced a decrease in visual acuity (64.3%) and visual-field defects (58.9%). Gradual changes in pituitary function were also observed (43.8%). The surgical approach is determined by the location of the lesion. Over the past 5 years, although the pterional (46.4%) approach has remained the most common, the proportion of subfrontal (12.5%) approaches has gradually increased. In the case we report, we found that the lesion in the patient involved the anterior chiasma and the right medial optic nerve. The patient presented with acute visual deterioration, suggesting the possibility of hemorrhage in the hemangioma. We attempted the right-sided subfrontal trans-eyebrow keyhole approach and achieved complete resection of the cavernous hemangioma. Postoperatively, the patient showed improvement in visual acuity and visual field, with obvious recovery observed at the 3-month follow-up., Conclusions: According to our results, the subfrontal trans-eyebrow keyhole approach for the resection of CCH is mainly suitable for cases in which the lesions are located above and anterior to the optic chiasm, the medial or superior aspect of the intracranial segment of the optic nerve is involved, and there is no invasion into the optic nerve canal. Compared with the traditional surgical approach, the minimally invasive subfrontal trans-eyebrow keyhole approach has demonstrated better clinical outcomes in the resection of CCH. However, according to the specific conditions of different patients, it is still necessary to comprehensively consider the choice of surgical approach. This study provides a valuable reference for further exploration of the treatment of CCH., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The escalating volume of decoration and renovation waste (D&RW) amid the rapid urbanization in China has posed significant challenges for the effective recycling of this waste stream, primarily due to the difficulty of accurately assessing its precise composition. To enhance the recycling of high-value materials from D&RW, a comprehensive understanding of its composition and quality is crucial before sorting. In this study, we propose a hybrid method that combines instance segmentation deep learning (DL) models with morphological machine learning (ML) models to automate the classification and evaluation of D&RW. A meticulously labeled dataset comprising 53,000 individual grains is curated for classification and instance segmentation. Subsequently, the ML model predicts the equivalent thickness of a grain according to the grain morphological data vector. The D&RW grains are then evaluated for weight based on the model outputs. The proposed method exhibits remarkable accuracy, as indicated by a relative low error of 2.8% in total weight evaluation between the model's predictions and manual sorting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

T helper cells, particularly T follicular helper (T FH ) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from T FH cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in T FH -deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of T FH cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals., (© 2024. The Author(s).)

Tissue-resident memory T (TRM) cells infiltrating solid tumors could influence tumor progression and the response to immune therapies. However, the proportion and prognostic value of TRM cells in the bone marrow (BM) of patients with acute myeloid leukemia (AML) are unclear. In this study, we used flow cytometry to assay the phenotype of 49 BM samples from patients newly diagnosed with AML (ND-AML). We found that the BM CD8 + effector memory (TEM) cells highly expressed CD69 (CD8 + TRM-like T cells), and their percentage was significantly increased in patients with ND-AML compared with that in healthy individuals (HI). The high percentage of CD8 + TRM-like subset was associated with poor overall survival in our ND-AML cohort. The Kaplan-Meier Plotter database verified a significantly reduced survival rate among patients with high expression of CD8 + TRM-like T cell characteristic genes ( CD8A , CD69 , and TOX ), especially the M4 and M5 subtypes. Phenotypic analysis revealed that the BM CD8 + TRM-like subpopulation exhibited exhausted T cell characteristics, but its high expression of CD27 and CD28 and low expression of CD57 suggested its high proliferative potential. The single-cell proteogenomic dataset confirmed the existence of TRM-like CD8 + T cells in the BM of patients with AML and verified the high expression of immune checkpoints and costimulatory molecules. In conclusion, we found that the accumulation of BM CD8 + TRM-like cells could be an immune-related survival prediction marker for patients with AML., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the Chinese Medical Association (CMA) and Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College (IHCAMS).)

Ultrasound-guided percutaneous interventions have numerous advantages over traditional techniques. Accurate needle placement in the target anatomy is crucial for successful intervention, and reliable visual information is essential to achieve this. However, previous studies have revealed several challenges, such as the variability in needle echogenicity and the common misalignment of the ultrasound beam and the needle. Advanced techniques have been developed to optimize needle visualization, including hardware-based and image-processing-based methods. This paper proposes a novel strategy of integrating ultrasound-based deep learning approaches into an optical navigation system to enhance needle visualization and improve tip positioning accuracy. Both the tracking and detection algorithms are optimized utilizing optical tracking information. The information is introduced into the tracking network to define the search patch update strategy and form a trajectory reference to correct tracking results. In the detection network, the original image is processed according to the needle insertion position and current position given by the optical localization system to locate a coarse region, and the depth-score criterion is adopted to optimize detection results. Extensive experiments demonstrate that our approach achieves promising tip tracking and detection performance with tip localization errors of 1.11 ± 0.59 mm and 1.17 ± 0.70 mm, respectively. Moreover, we establish a paired dataset consisting of ultrasound images and their corresponding spatial tip coordinates acquired from the optical tracking system and conduct real puncture experiments to verify the effectiveness of the proposed methods. Our approach significantly improves needle visualization and provides physicians with visual guidance for posture adjustment.

The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Because of the rapid mutation and high airborne transmission of SARS-CoV-2, a universal vaccine preventing the infection in the upper respiratory tract is particularly urgent. Here, a mosaic receptor-binding domain (RBD) nanoparticle (NP) vaccine is developed, which induces more RBD-targeted type IV neutralizing antibodies (NAbs) and exhibits broad cross-protective activity against multiple SARS-CoV-2 sublineages including the newly-emerged BF.7, BQ.1, XBB. As several T-cell-reactive epitopes, which are highly conserved in sarbecoviruses, are displayed on the NP surface, it also provokes potent and cross-reactive cellular immune responses in the respiratory tissue. Through intranasal delivery, it elicits robust mucosal immune responses and full protection without any adjuvants. Therefore, this intranasal mosaic NP vaccine can be further developed as a pan-sarbecovirus vaccine to block the viral entrance from the upper respiratory tract., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objectives: To develop and validate a deep learning imaging signature (DLIS) for risk stratification in patients with multiforme (GBM), and to investigate the biological pathways and genetic alterations underlying the DLIS., Methods: The DLIS was developed from multi-parametric MRI based on a training set (n = 600) and validated on an internal validation set (n = 164), an external test set 1 (n = 100), an external test set 2 (n = 161), and a public TCIA set (n = 88). A co-profiling framework based on a radiogenomics analysis dataset (n = 127) using multiscale high-dimensional data, including imaging, transcriptome, and genome, was established to uncover the biological pathways and genetic alterations underpinning the DLIS., Results: The DLIS was associated with survival (log-rank p < 0.001) and was an independent predictor (p < 0.001). The integrated nomogram incorporating the DLIS achieved improved C indices than the clinicomolecular nomogram (net reclassification improvement 0.39, p < 0.001). DLIS significantly correlated with core pathways of GBM (apoptosis and cell cycle-related P53 and RB pathways, and cell proliferation-related RTK pathway), as well as key genetic alterations (del&#95;CDNK2A). The prognostic value of DLIS-correlated genes was externally confirmed on TCGA/CGGA sets (p < 0.01)., Conclusions: Our study offers a biologically interpretable deep learning predictor of survival outcomes in patients with GBM, which is crucial for better understanding GBM patient's prognosis and guiding individualized treatment., Key Points: • MRI-based deep learning imaging signature (DLIS) stratifies GBM into risk groups with distinct molecular characteristics. • DLIS is associated with P53, RB, and RTK pathways and del&#95;CDNK2A mutation. • The prognostic value of DLIS-correlated pathway genes is externally demonstrated., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: This study aimed to compare nutritional effectiveness and complication rate between early nasojejunal and nasogastric tube feeding in patients with an intracerebral hemorrhage., Methods: This was a retrospective study. Eighty patients with an intracerebral hemorrhage were divided into a nasojejunal and a nasogastric tube feeding group. Feeding tubes were placed within 6 h after admission, and enteral feeding began within 2 h after tube placement. The nutritional status and complication rate of the 2 groups were compared before and 2 and 4 weeks after beginning feeding., Results: Serum prealbumin, serum albumin, and hemoglobin levels were significantly higher in the nasojejunal tube feeding group than in the nasogastric tube feeding group at 2 and 4 weeks after beginning feeding (all, p < 0.05). The incidence of gastric retention, pulmonary aspiration, and pneumonia were lower in the early nasojejunal tube feeding group than in the early nasogastric tube feeding group (all, p < 0.05). There was no significant difference in the incidence of diarrhea between the 2 groups., Conclusion: Compared with early nasogastric feeding, early nasojejunal feeding provides better nutritional effectiveness and a lower incidence of gastric retention, pulmonary aspiration, and pneumonia in patients with an intracerebral hemorrhage., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To develop and validate a deep learning model for predicting overall survival from whole-brain MRI without tumor segmentation in patients with diffuse gliomas., Methods: In this multicenter retrospective study, two deep learning models were built for survival prediction from MRI, including a DeepRisk model built from whole-brain MRI, and an original ResNet model built from expert-segmented tumor images. Both models were developed using a training dataset (n = 935) and an internal tuning dataset (n = 156) and tested on two external test datasets (n = 194 and 150) and a TCIA dataset (n = 121). C-index, integrated Brier score (IBS), prediction error curves, and calibration curves were used to assess the model performance., Results: In total, 1556 patients were enrolled (age, 49.0 ± 13.1 years; 830 male). The DeepRisk score was an independent predictor and can stratify patients in each test dataset into three risk subgroups. The IBS and C-index for DeepRisk were 0.14 and 0.83 in external test dataset 1, 0.15 and 0.80 in external dataset 2, and 0.16 and 0.77 in TCIA dataset, respectively, which were comparable with those for original ResNet. The AUCs at 6, 12, 24, 26, and 48 months for DeepRisk ranged between 0.77 and 0.94. Combining DeepRisk score with clinicomolecular factors resulted in a nomogram with a better calibration and classification accuracy (net reclassification improvement 0.69, p < 0.001) than the clinical nomogram., Conclusions: DeepRisk that obviated the need of tumor segmentation can predict glioma survival from whole-brain MRI and offers incremental prognostic value., Key Points: • DeepRisk can predict overall survival directly from whole-brain MRI without tumor segmentation. • DeepRisk achieves comparable accuracy in survival prediction with deep learning model built using expert-segmented tumor images. • DeepRisk has independent and incremental prognostic value over existing clinical parameters and IDH mutation status., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Necroptosis is a recently discovered form of cell death that plays a vital role in the progression of cancer, the spread of metastases, and the immunologic response to tumors. Due to the dual role of necrotic apoptotic processes in tumor pathogenesis and the heterogeneity of gliomas, the function of necroptosis in the glioma microenvironment is still poorly understood. We characterized the expression of necroptosis-related genes (NRGs) within glioma samples at both the genetic and transcriptional levels, identifying three distinct subtypes. Additionally, we constructed a risk score, which is capable of accurately predicting patient prognosis, correlates with tumor mutation burden (TMB), tumor stem cell index (CSC), immune checkpoints, and predicts tumor drug sensitivity. To facilitate its application in the clinic, we developed a nomogram and demonstrated that it predicts the prognosis of glioma patients with good accuracy and reliability using multiple datasets. We examined the function of necroptosis in the tumor microenvironment (TME) and the prognosis of gliomas, which may be useful for guiding individualized treatment plans for gliomas targeting necroptosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ba, Su, Gao, Liao, Wu, Cao, Liang, Gong and Guo.)

The SARS-CoV-2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first-generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS-CoV-2 variants as the major target. Here, receptor binding domain (RBD)-conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single-dose and a prime-boost strategy, these RBD-conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS-CoV-2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross-protective NAbs against almost all the notable SARS-CoV-2 variants including the Omicron variant in rhesus macaques by the third re-boost with trivalent vaccines is found. These results suggest that RBD-based monovalent or multivalent nanoparticle vaccines provide a promising second-generation vaccine strategy for SARS-CoV-2 variants., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: T cell dysregulation is a common event in leukemia. Recent findings have indicated that aberrant expression of immune checkpoint proteins may be associated with disease relapse and progression in acute myeloid leukemia (AML). TOX, a transcription factor in the HMG-box protein superfamily, was found to be a potential target for immunotherapy not only in solid tumors but also in hematological malignancies. However, little is known about TOX expression and co-expression with immune checkpoint proteins or the exhausted phenotype in the T cell subsets in AML. Thus, in this study, we analyzed TOX expression and co-expression with PD-1, Tim-3, and CD244 in T cells., Methods: TOX expression and co-expression with PD-1, Tim-3, and CD244 in CD3+, CD4+, regulatory T (Treg), and CD8+ T cells were analyzed by multi-color fluorescent flow cytometry in peripheral blood (PB) and bone marrow (BM) samples from patients with de novo AML and AML in complete remission (CR) and healthy individuals (HIs)., Results: A significantly increased percentage of TOX+CD3+, CD4+, and CD8+ T cells was found in PB from patients with de novo AML in comparison with HIs. Double-positive TOX+CD244+, TOX+PD-1+, and TOX+Tim-3+ T cells markedly increased in the CD3+, CD4+, and CD8+ T cell populations in de novo AML patients compared with HIs, and similar trends were demonstrated for TOX+Tim-3+CD3+/CD4+/CD8+ T cells in de novo AML compared with AML-CR patients. In addition, the number of TOX+, TOX+PD-1+, and TOX+Tim-3+Treg cells significantly increased in de novo AML patients compared with HIs, and TOX+PD-1+Treg cells were higher in de novo AML compared with AML-CR patients. Moreover, TOX positively correlated with Tim-3 expression in CD8+ and Treg cells, and a positive correlation between the expression of TOX+ CD4+ and CD244+CD4+ T cells was found. Furthermore, an increased percentage of TOX+Tim-3+ T cells in BM was also found in de novo AML patients compared with HIs., Conclusions: Increased TOX concurrent with PD-1, Tim-3, and CD244 in T cells may contribute to T cell exhaustion and impair their function in AML. Such exhausted T cells may be partially revised when AML patients achieve CR after chemotherapy. TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in AML., (© 2021 International Clinical Cytometry Society.)

Aim: To characterize immune suppression in lymphoma, thymocyte selection-associated high mobility group box protein (TOX) expression and co-expression with programmed cell death receptor-1 (PD-1), T cell immunoglobulin mucin-domain-containing-3 (Tim-3), and CD244 in CD3+, CD4+, CD8+, and regulatory T (Treg) cells from patients with lymphomas were analyzed., Methods: TOX expression and co-expression with PD-1, Tim-3, and CD244 in CD3+, CD4+, Treg, and CD8+ T cells were analyzed by multi-color fluorescent flow cytometry using peripheral blood (PB) from 13 newly diagnosed, untreated lymphoma patients, and 11 healthy individuals., Results: An increased percentage of TOX+ CD3+, CD4+, and CD8+ T cells was found in PB from patients with B cell non-Hodgkin's lymphoma (B-NHL) in comparison with healthy controls. Moreover, TOX+PD-1+ and TOX+Tim-3+ double-positive T cells increased among the CD3+, CD4+, and CD8+T cell populations in the B-NHL group. There was apparent heterogeneity in TOX expression and co-expression with PD-1, Tim-3, and CD244 in CD3+, CD4+, and CD8+ T cells in different lymphoma patients. In addition, the percentage of CD4+CD25+FoxP3+ T cells (Treg) among the CD3+ and CD4+ T cells significantly increased, and the number of TOX+ and TOX+PD-1+ Treg cells also significantly increased in the B-NHL group., Conclusions: Higher expression of TOX concurrent with PD-1, Tim-3, and CD244 in T cells from patients with B-NHL may contribute to T cell exhaustion and impair their special anti-tumor T cell activity. TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in hematological malignancies., (© 2021 John Wiley & Sons Australia, Ltd.)

Background The biologic meaning of prognostic radiomics phenotypes remains poorly understood, hampered in part by lack of multicenter reproducible evidence. Purpose To uncover the biologic meaning of individual prognostic radiomics phenotypes in glioblastomas using paired MRI and RNA sequencing data and to validate the reproducibility of the identified radiogenomics linkages externally. Materials and Methods This retrospective multicenter study included four data sets gathered between January 2015 and December 2016. From a radiomics analysis set, a 13-feature radiomics signature was built using preoperative MRI for overall survival prediction. Using a radiogenomics training set with both MRI and RNA sequencing, biologic pathways were enriched and correlated with each of the 13 radiomics phenotypes. Radiomics-correlated key genes were identified to derive a prognostic radiomics gene expression (RadGene) score. The reproducibility of identified pathways and genes was validated with an external test set and a public data set (The Cancer Genome Atlas [TCGA]). A log-rank test was performed to assess prognostic significance. Results A total of 435 patients (mean age, 55 years ± 15 [standard deviation]; 263 men) were enrolled. The radiomics signature was associated with overall survival (hazard ratio [HR], 3.68; 95% CI: 2.08, 6.52; P < .001) in the radiomics validation subset. Four types of prognostic radiomics phenotypes were correlated with distinct pathways: immune, proliferative, treatment responsive, and cellular functions (false-discovery rate < 0.10). Thirty radiomics-correlated genes were identified. The prognostic significance of the RadGene score was confirmed in an external test set (HR, 2.02; 95% CI: 1.19, 3.41; P = .01) and a TCGA test set (HR, 1.43; 95% CI: 1.001, 2.04; P = .048). The radiomics-associated pathways and key genes can be replicated in an external test set. Conclusion Individual radiomics phenotypes on MRI scans predictive of overall survival were driven by distinct key pathways involved in immune regulation, tumor proliferation, treatment responses, and cellular functions in glioblastoma, which could be reproduced externally. © RSNA, 2021 Online supplemental material is available for this article.

Thymocyte selection-associated HMG box (TOX) is a transcription factor that belongs to the high mobility group box (HMG-box) superfamily, which includes four subfamily members: TOX, TOX2, TOX3, and TOX4. TOX is related to the formation of multiple malignancies and contributes to CD8+ T cell exhaustion in solid tumors. However, little is known about the role of TOX genes in hematological malignancies. In this study, we explored the prognostic value of TOX genes from 40 patients with de novo acute myeloid leukemia (AML) by quantitative real-time PCR (qRT-PCR) in a training cohort and validated the results using transcriptome data from 167 de novo AML patients from the Cancer Genome Atlas (TCGA) database. In the training cohort, higher expression of TOX and TOX4 was detected in the AML samples, whereas lower TOX3 expression was found. Moreover, both the training and validation results indicated that higher TOX2 , TOX3 , and TOX4 expression of AML patients (3-year OS: 0% vs. 37%, P = 0.036; 3-year OS: 4% vs. 61%, P < 0.001; 3-year OS: 0% vs. 32%, P = 0.010) and the AML patients with highly co-expressed TOX , TOX2 , TOX4 genes (3-year OS: 0% vs. 25% vs. 75%, P = 0.001) were associated with poor overall survival (OS). Interestingly, TOX2 was positively correlated with CTLA-4 , PD-1 , TIGIT , and PDL-2 (r s = 0.43, P = 0.006; r s = 0.43, P = 0.006; r s = 0.56, P < 0.001; r s = 0.54, P < 0.001). In conclusion, higher expression of TOX genes was associated with poor OS for AML patients, which was related to the up-regulation of immune checkpoint genes. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TOX genes in novel targeted therapies for AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liang, Zhao, Chen, Huang, Deng, Zeng, Tan, Zha, Chen and Li.)

Diffuse midline glioma (DMG) is one of fatal glioblastoma multiforme (GBM) with no proven medical therapies. Tumor treating fields (TTFields) is a new revolutionary therapy for GBM which prolongs the overall survival time obviously. However, we can observe more tumor growth phenomena (such as distant multiple metastases) than before. This report describes an adult patient who presented headache and dizziness, accompanied by left limb weakness, nausea, and vomiting following car accident trauma, following imaging examinations suggested thalamus GBM. He was treated with subtotal excision. Final pathology was diagnosed as DMG with H3F3A mutation, isocitrate dehydrogenase (IDH) wild type. Following concurrent chemoradiation therapy (CCRT) and adjuvant temozolomide (TMZ) chemotherapy + TTFields therapy were carried out. Supratentorial tumor has been exhibited a partial radiological response for nine months until TTFields was used irregularly or even discontinued in the later stage. Especially, subtentorial and spinal multiple metastasis occurred during this time. Both supratentorial and subtentorial tumors were treated with surgery, radiotherapy, chemotherapy, even targeted drugs, with the only difference being TTFields, but we could see different consequences for tumor growth. One conclusion might be drawn that TTFields can provide a longer survival time (14 vs. 8 months reported before) for DMG patients and improve survival benefits. However, we can observe that patients maybe die from subtentorial metastasis because TTFields could not cover the subtentorial tumors, which is the focal challenge at present. So further research on subtentorial tumors with TTFields is urgently needed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4395). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Phoenixin-14 has been reported to be implicated in the process of blood glucose metabolism, reproduction, lipid deposition and cardioprotection. However, the role of phoenixin-14 in vascular smooth muscle cells (VSMCs) remains unkown. In this study, we focused on the effects of phoenixin-14 on VSMCs under oxidized low-density lipoprotein (ox-LDL) treatment. The experimental results demonstrated that phoenixin-14 inhibited mRNA level and nuclear translocation of β-catenin. Functionally, phoenixin-14 inhibited cell proliferation and facilitated apoptosis of VSMCs under ox-LDL stimulation, and CTNNB1 overexpression reversed these effects. Mechanistically, KCNQ1OT1 interacted with miR-183-3p to upregulate CTNNB1 in VSMCs. Furthermore, CTNNB1 expression was negatively correlated with miR-183-3p but positively associated with KCNQ1OT1. Rescue assays indicated that KCNQ1OT1 overexpression or Lithium chloride (LiCl) treatment reversed the effects of phoenixin-14 on proliferation and apoptosis of ox-LDL-stimulated VSMCs. In summary, phoenixin-14 regulates proliferation and apoptosis of ox-LDL-treated VSMCs by regulating the KCNQ1OT1/miR-183-3p/CTNNB1 axis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

TOX (thymocyte selection-associated HMG BOX) is a member of a family of transcriptional factors that contain the highly conserved high mobility group box (HMG-box) region. Increasing studies have shown that TOX is involved in maintaining tumors and promoting T cell exhaustion. In this review, we summarized the biological functions of TOX and its contribution as related to lymphocytic malignancies. We also discussed the potential role of TOX as an immune biomarker and target in immunotherapy for hematological malignancies.

The mortality and disability rate of patients with ruptured anterior communicating artery (AComA) aneurysm after bleeding is high. Even with the most advanced treatment methods, the incidence of complications remains high. The purpose of the present study was to determine the efficacy of microsurgery via supraorbital eyebrow keyhole approach (SOEK) in clipping ruptured AComA aneurysms. Between September 2010 and October 2018, 543 patients with intracranial aneurysms were admitted to the Department of Neurosurgery of the Third Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China). Among them, 85 patients with ruptured AComA aneurysm and subarachnoid hemorrhage (SAH) underwent microsurgical clipping via the SOEK approach. In those patients, the clipping rate, complications and clinical efficacy of treatment were evaluated. The average age of the patients was 52.69±9.94 years (range, 28-78 years). The proportions of small, medium and large aneurysms were 83.5, 15.3 and 1.2%, respectively. Procedural complications occurred in 9 cases (10.5%). The occlusion rate of the aneurysms was 98.8%. The average follow-up period was 37.9 (±24.5) months. A total of 81.2% of the patients with SAH had a good clinical prognosisat 1 year (modified Rankin scale score, ≤2). In conclusion, for a skilled and experienced surgeon, SOEK was indicated to be a safe procedure for the treatment of ruptured AComA aneurysms; it provided sufficient intra-operative exposure and a high clipping rate., (Copyright: © Bhattarai et al.)

Background: Glioma is the most lethal nervous system cancer. Recent studies have made great efforts to study the occurrence and development of glioma, but the molecular mechanisms are still unclear. This study was designed to reveal the molecular mechanisms of glioma based on protein-protein interaction network combined with machine learning methods. Key differentially expressed genes (DEGs) were screened and selected by using the protein-protein interaction (PPI) networks., Results: As a result, 19 genes between grade I and grade II, 21 genes between grade II and grade III, and 20 genes between grade III and grade IV. Then, five machine learning methods were employed to predict the gliomas stages based on the selected key genes. After comparison, Complement Naive Bayes classifier was employed to build the prediction model for grade II-III with accuracy 72.8%. And Random forest was employed to build the prediction model for grade I-II and grade III-VI with accuracy 97.1% and 83.2%, respectively. Finally, the selected genes were analyzed by PPI networks, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the results improve our understanding of the biological functions of select DEGs involved in glioma growth. We expect that the key genes expressed have a guiding significance for the occurrence of gliomas or, at the very least, that they are useful for tumor researchers., Conclusion: Machine learning combined with PPI networks, GO and KEGG analyses of selected DEGs improve our understanding of the biological functions involved in glioma growth., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Long-term survival and high-quality life of patients with gliomas depends on the extent of resection (EOR) and the protection of functional white matter fibers. The navigation system provides precise positioning for surgery based on preoperative magnetic resonance imaging (MRI) but the precision decreases when intraoperative brain drift occurs. Ultrasound (US) can support real-time imaging and correct brain shift. The real-time US-MRI multimodal fusion virtual navigation system (UMNS) is a new technique for glioma surgery. In order to obtain a maximum EOR and functional protection, this study aimed to explore the feasibility, efficiency, and safety of real-time UMNS for glioma surgery, and to evaluate the benefit of the new application by UMNS presetting markers between the tumor and functional white matter fiber surgery., Methods: A retrospective analysis included 45 patients who underwent glioma surgery, 19 patients with only intraoperative US, and 26 patients with UMNS. A preoperative plan was made by 3D-slicer software based on preoperative MRI. This was combined with a reconstruction of diffusion tensor imaging (DTI) that designed the important locations as "warning points" between functional white matter fibers and tumor. Following patient registration, markers were injected into preset "warning points" under image-guided UMNS in order to give us a warning during surgery in case of postoperative function deficits. The operating time, volumetric assessment in glioma resection, and postoperative complications were evaluated and used to compared those surgeries using intraoperative US (iUS) with those surgeries using intraoperate MRI (iMRI) navigation., Results: A total of 45 patients underwent glioma surgery. Gross total removal (GTR) of iUS alone was achieved in 6 of 19 cases, while this was achieved in 22 of 26 cases with UMNS alone, demonstrating an improvement in rate of GTR from 31.58% to 84.62%, respectively. This may be attributable to the superior US image quality provided by UMNS. In 13 of 26 cases, there was improved image quality (from poor/moderate to moderate/good) with the aid of UMNS. In addition, the consistency of EOR of postoperative MRI evaluated by UMNS (92.31%) was higher than when using iUS alone (42.11%). The whole process of intraoperative scanning time and marker injection did not lead to a significant delay of the operating time compared to using iUS alone, and has been reported to be shorter than with iMRI as well. Furthermore, the percentage of postoperative morbidity in the UMNS group was lower than that in the iUS group (motor deficit: 11.54% vs. 42.11%; aphasia: P =3.85% vs. 31.58%, respectively)., Conclusions: Real-time UMNS is an effective, timesaving technology that offers high quality intraoperative imaging. Injection markers between functional white matter fibers and tumor by UMNS can help to obtain a maximum EOR of glioma and functional protection postoperatively. The integration of iUS into the neuronavigation system offered quick and helpful intra-operative images., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Annals of Translational Medicine. All rights reserved.)

Purpose: Isocitrate dehydrogenase 1 (IDH1) has been proven as a prognostic and predictive marker in glioblastoma (GBM) patients. The purpose was to preoperatively predict IDH mutation status in GBM using multiregional radiomics features from multiparametric magnetic resonance imaging (MRI)., Methods: In this retrospective multicenter study, 225 patients were included. A total of 1614 multiregional features were extracted from enhancement area, non-enhancement area, necrosis, edema, tumor core, and whole tumor in multiparametric MRI. Three multiregional radiomics models were built from tumor core, whole tumor, and all regions using an all-relevant feature selection and a random forest classification for predicting IDH1. Four single-region models and a model combining all-region features with clinical factors (age, sex, and Karnofsky performance status) were also built. All models were built from a training cohort (118 patients) and tested on an independent validation cohort (107 patients)., Results: Among the four single-region radiomics models, the edema model achieved the best accuracy of 96% and the best F1-score of 0.75 while the non-enhancement model achieved the best area under the receiver operating characteristic curve (AUC) of 0.88 in the validation cohort. The overall performance of the tumor-core model (accuracy 0.96, AUC 0.86 and F1-score 0.75) and the whole-tumor model (accuracy 0.96, AUC 0.88 and F1-score 0.75) was slightly better than the single-regional models. The 8-feature all-region radiomics model achieved an improved overall performance of an accuracy 96%, an AUC 0.90, and an F1-score 0.78. Among all models, the model combining all-region imaging features with age achieved the best performance of an accuracy 97%, an AUC 0.96, and an F1-score 0.84., Conclusions: The radiomics model built with multiregional features from multiparametric MRI has the potential to preoperatively detect the IDH1 mutation status in GBM patients. The multiregional model built with all-region features performed better than the single-region models, while combining age with all-region features achieved the best performance., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To build a reliable radiomics model from multiregional and multiparametric magnetic resonance imaging (MRI) for pretreatment prediction of O 6 -methylguanine-DNA methyltransferase (MGMT) promotor methylation status in glioblastoma multiforme (GBM)., Methods: In this retrospective multicentre study, 1,705 multiregional radiomics features were automatically extracted from multiparametric MRI. A radiomics model with a minimal set of all-relevant features and a radiomics model with univariately-predictive and non-redundant features were built for MGMT methylation prediction from a primary cohort (133 patients) and tested on an independent validation cohort (60 patients). Predictive models combing clinical factors were built and evaluated. Both radiomics models were assessed on subgroups stratified by clinical factors., Results: The radiomics model with six all-relevant features allowed pretreatment prediction of MGMT methylation (AUC=0.88, accuracy=80 %), which significantly outperformed the model with eight univariately-predictive and non-redundant features (AUC=0.76, accuracy=70 %). Combing clinical factors with radiomics features did not benefit the prediction performance. The all-relevant model achieved significantly better performance in stratified analysis., Conclusions: Radiomics model built from multiregional and multiparameter MRI may serve as a potential imaging biomarker for pretreatment prediction of MGMT methylation in GBM. The all-relevant features have the potential of offering better predictive power than the univariately-predictive and non-redundant features., Key Points: • Multiregional and multiparametric MRI features reliably predicted MGMT methylation in multicentre cohorts. • All-relevant imaging features predicted MGMT methylation better than univariately-predictive and non-redundant features. • Combing clinical factors with radiomics features did not benefit the prediction performance.

Background: A pterional-orbital or subfrontal-orbital approach is recommended as a surgical treatment in cranio-orbital lesions. We describe a less invasive approach through an eyebrow incision combined supraorbital minicraniotomy and orbital osteotomy for treating some selected cranio-orbital lesions., Methods: Sixteen patients with different cranio-orbital lesions were treated using this less invasive approach. Postoperative outcomes were evaluated to shed light on specific parameters related to this approach., Results: The 16 patients with cranio-orbital lesions underwent 17 operations. A total resection was achieved in 11 lesions. All the patients were followed up for 3-54 months. Postoperative proptosis improved in all cases. Five cases of visual impairment were improved, but 4 patients with blindness did not recover. One patient with bitemporal hemianopia recovered. Three patients with ocular dyskinesia did not recover. Two patients had transient cranial nerve III palsy, and 2 patients had cranial nerve VI palsy. One had delayed hydrocephalus. One died 1 year later as a result of pulmonary metastases. One recurred and the patient underwent a second operation. All the patients had a modified Rankin Scale score ≤1 at 12 weeks follow-up., Conclusions: Some selected cranio-orbital lesions can be treated through a supraorbital eyebrow approach with orbital osteotomy. The presence of retro-ocular fat allows the orbital lesions to be classified as a lesion of the intraretro-ocular or extraretro-ocular fat. It is safe to resect the lesion of extraretro-ocular fat from the retro-ocular fat interface. However, the lesion with optic nerve and extraocular muscles involved should be removed from the intermuscular septae., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: MiR-135a is found to selectively induce apoptosis in glioma cell but not in normal neurons and glial cells. However, low transfection efficacy limits its application in vivo as other miRNAs. We prepared a new kind of nano-vector based on polyethylene glycol methyl ether (mPEG) and hyper-branched polyethylenimine (hy-PEI) in order to improve the miRNA delivery system into the glioma cells., Methods: The mPEG-g-PEI/miR-135a was constructed and detected by 1H NMR and FTIR analyses. Transmission electron microscope was utilized for its characteristics. Stability and release efficiency was assessed by electrophoresis. Biocompatibility was observed and analyzed through co-culture with astrocytes and malignant glioma cells (C6). Transfection rate was monitored by laser confocal microscopy and flow cytometry. The antitumor effect of mPEG-g-PEI/miR-135a to C6 was confirmed in vivo by MR scanning, pathology and survival curve. RT-PCR was used to assay transfection efficiency of mPEG-g-PEI/miR-135a in vitro and in vivo. And Western blotting was used to assess the expressions of the targeted proteins of miR-135a., Results: In this experiment, we found the optimal N/P ratio of mPEG-g-PEI/miR-135a was about 6 judged by Zeta potential, particle size and encapsulation ability. The stability of mPEG-g-PEI/miR-135a in serum and the release efficiency in acid(pH=5.0) of mPEG-g-PEI/miR-135a were simulated the environment in vivo and in tumor. The mPEG-g-PEI nano-vector was co-cultured with malignant glioma cell C6 and normal astrocytes in vitro and showed good biocompatibility evaluated by CCK8 assay. The cell experiments in vitro indicated that mPEG-g-PEI could significantly improve miR-135a transfection by enhancing uptake effect of both normal glial and glioma cells. Given the C6 implanted in situ model, we discovered that the mPEG-g-PEI/miR-135a could obviously increase the survival period and inhibit the growth of glioma confirmed by MRI and histochemistry. In addition, the transfection efficiency of mPEG-g-PEI was better than that of other transfection agents either in vitro or in vivo confirmed by RT-PCR. Moreover, the expressions of the targeted proteins of miR-135a were consistent with the in vitro results., Conclusion: These results suggest that mPEG-g-PEI is expected to provide a new effective intracellular miRNA delivery system with low toxicity for glioma therapy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

In fully-automatic radiomics model for predicting overall survival (OS) of glioblastoma multiforme (GBM) patients, the effect of image standardization parameters such as voxel size, quantization method and gray level on model reproducibility and prognostic performance are still unclear. In this study, 45792 multiregional radiomics features were automatically extracted from multi-modality MR images with different voxel sizes, quantization methods, and gray levels. The feature reproducibility and prognostic performance were assessed. Multiparametric and fixed-parameter radiomics signatures were constructed based on a training cohort (60 patients). In an independent validation cohort (32 patients), the multiparametric signature achieved better performance for OS prediction (C-Index = 0.705, 95% CI: 0.672, 0.738) and significant stratification of patients into high- and low-risk groups (P = 0.0040, HR = 3.29, 95% CI: 1.40, 7.70), which outperformed the fixed-parameter signatures and conventional factors such as age, Karnofsky Performance Score and tumor volume. This study demonstrated that voxel size, quantization method and gray level had influence on reproducibility and prognosis of radiomics features for GBM OS prediction. An automatic method to determine the optimal parameter settings was provided. It indicated that multiparametric radiomics signature had the potential of offering better prognostic performance than fixed-parameter signatures.

Understanding the mechanisms of glioblastoma at the molecular and structural level is not only interesting for basic science but also valuable for biotechnological application, such as the clinical treatment. In the present study, bioinformatics analysis was performed to reveal and identify the key genes of glioblastoma multiforme (GBM). The results obtained in the present study signified the importance of some genes, such as COL3A1, FN1, and MMP9, for glioblastoma. Based on the selected genes, a prediction model was built, which achieved 94.4% prediction accuracy. These findings might provide more insights into the genetic basis of glioblastoma., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Background: Malignant glioma is the most lethal primary tumor of the central nervous system, with notable cell invasion causing significant recurrence. Suppression of glioma invasion is very important for improving clinical outcomes. Drugs that directly disrupt the cytoskeleton have been developed for this purpose; however, drug resistance and unsatisfactory selectivity have limited their clinical use. Previously, we reported that protein kinase A (PKA, also known as cyclic-AMP dependent protein kinase) activation induced the differentiation of glioma cells., Methods: We used several small molecular inhibitors and RNA interference, combined with wound healing assays, Matrigel transwell assay, and microscopic observation, to determine whether activation of the PKA pathway could inhibit the invasion of human glioma cells., Results: Activation of PKA decreased the invasion of glioma cells. The mechanism operated via transcriptional upregulation of microtubule-associated protein 2 (MAP2), which was activated by the PKA pathway and led to ossification of microtubule dynamics via polymerization of tubulin. This resulted in morphological changes and a reduction in glioma cell invasion. Furthermore, chromosome immunoprecipitation and quantitative real-time polymerase chain reaction showed that signal transducer and activator of transcription 3 (STAT3) is involved in the transcriptional upregulation of MAP2., Conclusion: Our findings suggested that PKA may represent a potential target for anti-invasion glioma therapy and that the downstream modulators (eg, STAT3/MAP2) partially mediate the effects of PKA., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Damping characterizes the energy dissipation capacity of materials and structures, and it is affected by several external factors such as vibrating frequency, stress history, temperature, and stress amplitude. This study investigates the relationship between the damping and the stress amplitude of environment-friendly recycled aggregate concrete (RAC). First, a function model of a member's loss factor and stress amplitude was derived based on Lazan's damping-stress function. Then, the influence of stress amplitude on the loss tangent of RAC was experimentally investigated. Finally, parameters used to determine the newly derived function were obtained by numerical fitting. It is shown that the member's loss factor is affected not only by the stress amplitude but also by factors such as the cross section shapes, boundary conditions, load types, and loading positions. The loss tangent of RAC increases with the stress amplitude, even at low stress amplitude. The damping energy exponent of RAC is not identically equal to 2.0, indicating that the damping is nonlinear. It is also found that the energy dissipation capacity of RAC is superior to that of natural aggregate concrete (NAC), and the energy dissipation capacity can be further improved by adding modified admixtures.

Purpose: Osteoplastic craniotomy in retrosigmoid approaches to the cerebellopontine angle region has been suggested as an alternative to traditional osteoclastic craniectomy. It is important both for prevention of postoperative complications and for cosmetic purposes. The authors investigated a safe and effective method of cranial reconstruction by repositioning a 1-step formed bone flap without bone window extension in lateral suboccipital craniotomy., Methods: Twenty-three cases of various cerebellopontine angle pathologies, managed at the Department of Neurosurgery of the Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to November 2011, had bone-flap repositioning at the original site after craniectomy during the same operative setting. All patients had preoperative three-dimensional computed tomography reconstruction of the skull. Anatomical markers were made in three-dimensional images, and individualized bone windows were designed. During operation, a 1-step formed bone flap was made according to the preoperative simulation scheme. After the intradural procedure was completed, the bone flap was repositioned and fixed in situ., Results: No complication was observed. No delayed postcraniectomy pain occurred to any patient. Postoperative computed tomography scan of the skull showed good healing and shaping of the suboccipital bone at the surgical region., Conclusions: The present report provides acceptable results both clinically and radiologically. More comparative studies are required to evaluate possible advantages of this technique over osteoclastic craniectomy.

In adult mammalian brain, microvessels may produce a special microenvironment and then influence the characteristics of neural stem cells (NSCs). This work aims to compare the effects of cerebral microvascular endothelial cells (CMECs) and vascular endothelial growth factor (VEGF) on the behaviors of NSCs. An in vitro model with co-cultured CMECs and NSCs was established by using transwell co-culture system. The expression of nestin and NF in the early stage of the co-culture, and NF in the later stage were explored by immunostaining. Results demonstrate that both CMECs and VEGF stimulate the proliferation of NSCs and inhibit the differentiation. After removing CMECs or VEGF from the co-culture system, a further culture in medium for the differentiation of NSCs was performed. The percentage of NF-positive cells in the CMECs co-culture group is the highest, suggesting the improved neuronal differentiation of NSCs by CMECs.

Fibrous mats via electrospinning have been widely applied in tissue engineering. In this work, nanofibers were prepared via electrospinning from polymer with different content of carboxyl groups. A natural material, collagen, was then immobilized onto the nanofiber surface by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)/N-Hydroxysuccinimide (NHS) activation process. It was found that the immobilization degree of collagen could be facilely modulated. The obtained collagen-modified nanofibers were used for neural stem cells culture, and unmodified nanofibers were used as a control. Results indicated that the modification of collagen could enhance the attachment and viability of the cultured neural stem cells.

In adult mammalian brain, vascular cells reside throughout life, close to central nervous system germinal zones, and neural stem cells (NSCs) mainly localize in the dentate gyrus of the hippocampus, subventricular zone, and olfactory bulb. Microvessels appear to produce a special microenvironment that may influence the characteristics of NSCs. To explore this potential correlation, an in vitro model with cocultured cerebral microvascular endothelial cells (CMECs) and NSCs was established in our study by using a transwell coculture system. The expression of nestin and NF in the early stage of coculture, and NF in the late stage, was detected by immunostaining. The results demonstrated that CMECs can stimulate self-renewal of NSCs and inhibit their differentiation, implying the potential of CMECs in promoting the neural differentiation of NSCs.