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Introduction Circular RNAs (circRNAs) play critical roles in tumorigenesis, but their clinical efficacy in esophageal squamous cell carcinoma (ESCC) still retains controversial. This meta‐analysis aims at evaluating the associations between circRNA expressions and clinicopathologic features as well as the diagnostic and prognostic values of circRNAs in ESCC. Materials & Methods PubMed, EMBASE, and other online databases were systematically searched to collect studies on circRNAs and clinicopathological features, diagnostic, and/or prognostic assessments of ESCC. The quality of included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) and Newcastle‐Ottawa Scale (NOS) scales. The included studies were quantitatively weighted and merged, and diagnostic indicators, hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated. P values were merged by Fisher᾽s method. Sources of heterogeneity were traced using subgroup, sensitivity, and meta‐regression analyses. Results As a result, 12 studies were included, representing 769 ESCC patients. The meta‐analysis showed that abnormal expressions of circRNAs were associated to TNM stage as well as lymph node and distant metastases in ESCC cases. CircRNA was used to distinguish ESCC patients from healthy controls, and the merged sensitivity, specificity, and the area under the curve (AUC) of ESCC were 0.78 (95% CI: 0.74–0.81), 0.79 (95% CI: 0.75–0.83), and 0.86, respectively. The survival analysis showed that upregulated oncogenic circRNA levels in ESCC tissues was associated with the shorter overall survival (OS) of the patients (univariate analysis: HR = 2.25, 95% CI: 1.71–2.95, p = 0.000, I 2 = 0.0%; multivariate analysis: HR = 2.50, 95% CI: 1.61–3.89, p = 0.000, I 2 = 0.0%), while the OS of ESCC patients presenting overexpressions of tumor‐suppressive circRNAs was significantly ameliorated (HR = 0.29, 95% CI: 0.20–0.42, p = 0.000, I 2 = 0.0%). The subgroup analyses based on circRNA biofunctions, sample size, and reference gene also revealed robust results. Conclusion CircRNAs can be used as promising molecular biomarkers for the early diagnosis and prognosis monitoring of ESCC., CircRNAs have been highlighted as novel biomarkers for the management of esophageal squamous cell carcinoma (ESCC), but the findings remain controversial. The present meta‐analysis sought to evaluate the clinicopathologic, diagnostic and prognostic significance of circRNA expression in ESCC.

Background: Excess prostate tissue is trimmed near the prostate capsula boundary during transurethral plasma kinetic enucleation of prostate (PKEP) and transurethral bipolar plasmakinetic resection of prostate (PKRP) surgeries. If a large portion of the tissue is removed, a prostate capsula perforation can potentially occur. As such, real-time accurate prostate capsula (PC) detection is critical for the prevention of these perforations. Objective: This study investigated the potential for using image denoising, image dimension reduction and feature fusion to improve real-time prostate capsula detection with two objectives. First, this paper mainly studied feature selection and input dimension reduction. Secondly, image denoising was evaluated, as it is of paramount importance to transient stability assessment based on neural networks. Methods: Two new feature fusion techniques, maxpooling bilinear interpolation single-shot multibox detector (PBSSD) and bilinear interpolation single shot multibox detector (BSSD) were proposed. Before original images were sent to the neural network, they were processed by principal component analysis (PCA) and adaptive median filter (AMF) for dimension reduction and image denoising. Results: The results showed that the application of PCA and AMF with PBSSD increased the mean average precision (mAP) for prostate capsula images by 8.55% and reached 80.15%, compared with single shot multibox detector (SSD) alone. Application of PCA with BSSD increased the mAP for prostate capsula images by 4.6% compared with SSD alone. Conclusion: Compared with other methods, ours were proven to be more accurate for real-time prostate capsula detection. The improved mAP results suggest that the proposed approaches are powerful tools for improving SSD networks.

The purpose of this study was to explore the effects of brisk walking on blood pressure (BP) in Chinese Han occupational populations to identify the appropriate volume of exercise needed for BP management. Eight‐hundred and two office staff with sedentary lifestyles were recruited to receive a prescription pedometer‐assisted brisk walking intervention for 3 months. To evaluate exercise intervention efficiency using statistical methods, the effective steps was divided as follows: 4000‐ 12 000 (Level 4) steps/day. The data of 688 participants who completed the study were analyzed. After intervention, Systolic BP (SBP) and Diastolic BP (DBP) at Levels 1–3 were significantly decreased (p

This study investigated the potential for using principal component analysis (PCA) to improve real-time forest fire detection with popular algorithms, such as YOLOv3 and SSD. Before YOLOv3/SSD training, the authors utilised PCA to extract features. Results showed that PCA with YOLOv3 increased the mean average precision (mAP) by 7.3%. PCA with SSD increased the mAP by 4.6%. These results suggest that PCA to be a robust tool for improving different objective detection networks.

This study investigated the potential for using Principal Component Analysis (PCA) and Adaptive Median Filter (AMF) to improve real-time prostate capsula detection with the traditional Region-based Fully Convolutional Network (R-FCN), Faster Region-based Convolutional Neural Network (Faster R-CNN), You Only Look Once-Version 3 (YOLOv3) and Single Shot Multibox Detector (SSD) algorithms. The processing steps included data augmentation (rotation, vertical flip, and horizontal flip) to increase the size of the dataset from 149 to 596 images, PCA-based feature extraction, AMF-based image denoising and a training phase incorporating the sample image set. The data were then used to test a series of combined methods that were applied to the detection of prostate capsula (PC). The results showed that application of PCA and AMF to Faster R-CNN increased the mean average precision (mAP) for the PC images by 9.4%. The application of PCA and AMF to R-FCN, YOLOv3 and SSD increased the mAP by 7.22%, 7.14% and 3.29% for the same dataset, respectively. This study represents the first application of PCA and AMF to traditional object detection algorithms, such as R-FCN, Faster R-CNN, YOLOv3, or SSD, and the improved mAP results suggest that this approach is a robust tool for improving multiple network architectures.

Background and Aim: The standard of care for patients with gliomas should follow established guidelines. In real-world management, however, the management sometimes deviates from these guidelines. We organized a discussion of real-world clinical cases and summarized different considerations from Chinese and European specialists.Case Presentation: A multidisciplinary team comprising experts from Europe and China discussed two patients with glioma treated at Sun Yat-sen University Cancer Center and Liaoning Cancer Hospital and Institute, China. Patient 1 was a 43-year-old man with a recurrent oligodendroglioma in the left frontal lobe diagnosed based on histology alone. He had undergone a biopsy and was diagnosed with an oligodendroglioma 3 years previously. He underwent chemoradiotherapy followed by 12 cycles of chemotherapy with temozolomide (TMZ), and complete remission was achieved. However, the tumor recurred within a short period of time and was resected by a second surgery. The pathologic diagnosis of the recurrent tumor was a glioblastoma because 1p/19q was intact when detected by sequencing. Pathologic consultation from another hospital still considered an anaplastic oligodendroglioma based on the positive result of 1p19q loss of heterozygosity (LOH) determined by fluorescence in situ hybridization. Patient 2 was a 50-year-old man with a left temporal glioblastoma. He underwent tumor resection but no radiotherapy. After seven cycles of TMZ (5/28-day regimen), his symptoms deteriorated, and his treatment was changed to a TMZ dose-dense regimen (7 days on/7 days off) and bevacizumab (7.5 mg/kg every 2 weeks), plus tumor-treating field therapy. Consultation Results: The pathological diagnosis based on biopsy for Patient 1 was an oligodendroglioma (World Health Organization Grade II), whereas the result of the second surgical sample was glioblastoma or anaplastic oligodendroglioma (questionable). Although the accuracy of fluorescence in situ hybridization for the detection of 1p/19q LOH requires improvement, 1p/19q LOH is typically not reconstituted in oligodendroglioma. More likely, it was due to sampling; a positive observation field may be missed with consequent negative results, and both oligodendroglioma (with 1p/19q co-deletion and isocitrate dehydrogenase mutation) and astrocytoma (without 1p/19q co-deletion) may exist. With respect to further treatment for cases such as Patient 1, both Chinese and European experts agree that procarbazine + lomustine chemotherapy is appropriate, while re-irradiation is suggested only if the tumor recurs outside the original radiotherapy field or within the radiotherapy field in the future. Considering the medical history, the rapid tumor regrowth without postoperative radiotherapy in Patient 2 was not surprising. After application of a rescue treatment regimen, the general condition of the patient improved, which may have resulted from the bevacizumab. A consensus was reached between the Chinese and European experts regarding subsequent treatment of Patient 2. Continuation of TMZ and bevacizumab was suggested until further deterioration. Whether tumor-treating field therapy should play a role in this patient could not be evaluated. However, some other molecular targeted agents (e.g. vascular endothelial growth factor receptor tyrosine kinase inhibitors such as regorafenib or apatinib) after bevacizumab failure, the effectiveness of these drugs remains unclear. Conclusion: In clinical practice, although we should follow established guidelines, the final treatment regimen requires informed consent from the patient. Thus, some real-world cases may deviate from the established guidelines. When patients reach end-stage disease with a marked decrease in their performance status and no standard treatment options, active antitumor treatment might be more likely to be attempted in China, while symptomatic treatment is more frequently performed in Europe. Although treatment philosophies for patients with glioma are slightly different between Eastern and Western medical experts, any treatment strategies should satisfy these patients.

Scheduling periodic real-time traffic in wireless networks is challenging due to the unreliable wireless channels. We first formulate the scheduling problem as a restless multi-armed bandit (RMAB) problem. Then, we theoretically prove the indexability of the scheduling problem. Based on the indexability, we further derive the closed-form Whittle’s index. It motivates us to propose a simple index-based scheduling algorithm which schedules users with higher indices. Simulation results have demonstrated that the derived scheduling algorithm outperforms the earliest deadline first (EDF) and myopic algorithms in terms of the total discounted reward.

Purpose Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. Materials and Methods Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP- 14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. Results Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. Conclusion R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

Real-time device to device (D2D) communications are important for applications of intelligent transportation, Internet of Things, etc. Most recently, researchers have focused on improving the throughput of the D2D communications underlaying cellular networks, while they have ignored the real-time requirements of packet transmissions. In this paper, we investigate the resource allocation problems for real-time D2D communications aiming to maximize the total utility of packets meeting their deadlines. First, we adopt the Markov Decision Process (MDP) to model the problem. Based on this model, we propose an optimal offline channel and slot allocation algorithm. Considering the high time complexity of the optimal offline algorithm, we then propose an online joint packet admission control, channel, and slot assignment algorithm. The online algorithm is $O(\log _2(\mu))$ -competitive, where $\mu$ is related to the deadlines of packets. We have proved the optimality of the online algorithm in terms of the competitive ratio among all of the online algorithms. Additionally, we have proposed a method to reduce the pessimism of the online algorithm. Simulation results show that the optimal offline algorithm achieves better performance than the online algorithm. The online algorithm outperforms the well-known real-time task scheduling algorithm EDF in terms of the total utility.

Background Differential diagnosis of tumour recurrence (TuR) from treatment effects (TrE), mostly induced by radiotherapy and chemotherapy, is still difficult by using conventional computed tomography (CT) or magnetic resonance (MR) imaging. We have investigated the diagnostic performance of PET/CT with 3 tracers, 13N-NH3, 18F-FDOPA, and 18F-FDG, to identify TuR and TrE in glioma patients following treatment. Methods Forty-three patients with MR-suspected recurrent glioma were included. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the lesion and the lesion-to-normal grey-matter cortex uptake (L/G) ratio were obtained from each tracer PET/CT. TuR or TrE was determined by histopathology or clinical MR follow-up for at least 6 months. Results In this cohort, 34 patients were confirmed to have TuR, and 9 patients met the diagnostic standard of TrE. The SUVmax and SUVmean of 13N-NH3 and 18F-FDOPA PET/CT at TuR lesions were significantly higher compared with normal brain tissue (13N-NH3 0.696 ± 0.558, 0.625 ± 0.507 vs 0.486 ± 0.413; 18F-FDOPA 0.455 ± 0.518, 0.415 ± 0.477 vs 0.194 ± 0.203; both P 18F-FDG (6.918 ± 3.190, 6.016 ± 2.807 vs 6.356 ± 3.104, P = 0.290 and 0.493). L/G ratios of 13N-NH3 and 18F-FDOPA were significantly higher in TuR than in TrE group (13N-NH3, 1.573 ± 0.099 vs 1.025 ± 0.128, P = 0.008; 18F-FDOPA, 2.729 ± 0.131 vs 1.514 ± 0.141, P 13N-NH3; 84.6%, 100% and 0.938, for 18F-FDOPA; and 80.8%, 100%, and 0.952, for the combination, respectively. Conclusion Our results suggest that although multiple tracer PET/CT may improve differential diagnosis efficacy, for glioma TuR from TrE, 18F-FDOPA PET-CT is the most reliable. The combination of 18F-FDOPA and 13N-NH3 does not increase the diagnostic efficiency, while 18F-FDG is not worthy for differential diagnosis of glioma TuR and TrE.

OBJECTIVE This study was designed to retrospectively analyze the dynamic changes of peripheral blood lymphocyte subsets and prognosis among patients with intracranial germ cell tumors. METHODS A total of 150 intracranial germ cell tumors patients diagnosed between June 2011 till November 2019 were retrospectively investigated. Peripheral blood total T lymphocytes (CD3+) percentage, T helper/inducible lymphocytes(CD3+CD4+)percentage, T inhibitory/toxic lymphocytes (CD3+CD8+) percentage, B lymphocyte (CD19+) percentage, NK lymphocyte (CD3/CD16+CD56+) percentage, regulatory T cells (CD4+CD25+,CD8+CD25+), and T helper/toxic lymphocyte ratio (CD4+/CD8+ ratio) were quantified by flow cytometry analysis. Clinical information was extracted from the database in Sun Yat-sen University Cancer Center and survival data was confirmed through outpatient visits and telephone follow-up. RESULTS T lymphocytes population was increased after anti-tumor treatment, with significant difference of total T lymphocytes (CD3+), inhibitory/toxic T cells (CD3+CD8+) and regulatory T cells (CD4+CD25+ and CD8+CD25+), (p=0.008, p=0.000, p=0.008 and p=0.001 respectively), while B lymphocytes(CD19+) decreased after chemotherapy(p=0.003). The dynamic levels of T lymphocyte and B lymphocyte subpopulation after chemotherapy did not present significant differences between gender, age, and locations of tumors (p >0.05), except CD4+CD25+ T cells in younger children (age< 16 years older) increased significantly than the elder (age >16), p=0.04. Patients with increased CD19+ B cells presented significant suboptimal outcomes compared with the no increased (p=0.024). Similarly, increased CD3+ T cells, CD3+CD8+ T cells, CD4+CD25+ T cells reduced the risk of death (p=0.006, p=0.019, p=0.042 respectively). Multivariate Cox Regression analysis showed: increased CD19+ B cells, p=0.04, HR=1.688, 95%CI=1.025-2.779. CONCLUSION After anti-tumor treatment, cell-mediated immunity activated, enhanced, and dominated in anti-tumor response. An increased level of CD19+ subsets was an independent predictor for inferior overall survival. Systemic circulating T cells immunity played an important role and mediating antitumor responses may pave the road for new immunity strategies.

BackgroundProteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy.MethodsThe genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS.ResultsThe CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-β were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy.ConclusionThis study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.

Background: Medulloblastoma (MB) is one of the most malignant neuroepithelial tumors in the central nervous system. This study aimed to establish an effective prognostic nomogram and risk grouping system for predicting overall survival (OS) of patients with MB.Materials and Methods: The nomogram was constructed based on data from the database of Surveillance, Epidemiology, and End Results (SEER). This database consisted of 2,824 patients with medulloblastoma and was used as the training cohort. The data of another additional 161 patients treated at the Sun Yat-sen University Cancer Center (SYSUCC) were used as the external validation cohort. Cox regression analysis was used to select independent prognostic factors. Concordance index (C-index) and calibration curve were used to predict the prognostic effect of the nomogram for overall survival.Results: In the training cohort, Cox regression analyses showed that the prognostic factors included histopathology, surgery, radiotherapy, chemotherapy, tumor size, dissemination, and age at diagnosis. The internal and external validated C-indexes were 0.681 and 0.644, respectively. Calibration curves showed that the nomogram was able to predict 1-, 3-, and 5-year OS for patients with MB precisely. Using the training cohort, a risk grouping system was built, which could perfectly classify patients into four risk nomogroups with a 5-year survival rate of 83.9%, 76.5%, 64.5%, and 46.8%, respectively.Conclusion: We built and validated a nomogram and risk grouping system that can provide individual prediction of OS and distinguish MB patients from different risk groups. This nomogram and risk grouping system could help clinicians making better treatment plan and prognostic assessment.

Purpose: Metastatic nasopharyngeal carcinoma (mNPC) remains incurable. This prospective study aimed to investigate whether adding cetuximab to cisplatin-based induction therapy could improve efficacy and survival for chemotherapy-naive mNPC patients. Patients and Methods: Eligible chemotherapy-naive mNPC patients were enrolled, including those initially diagnosed with mNPC (IM) and those with first-relapse metastases after radiotherapy (RM). Patients all received induction chemotherapy (IC) including docetaxel and cisplatin plus cetuximab. Those who obtained objective remission after IC would continue to receive radiotherapy concurrent with cetuximab and cisplatin, and further capecitabine as maintenance. Contemporaneous patients who received conventional therapy served as controls. Results: Forty-three patients were enrolled, including 17 IM and 26 RM patients. Thirty-nine (90.7%) patients had WHO III subtype. The overall response and complete response (CR) rates were, respectively, 79.1 and 34.9% after induction therapy and 76.7 and 46.5% after chemoradiotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) rates reached 34.9 and 30%, respectively. Subgroup analysis showed that compared with RM patients, IM patients had a higher 5-year OS (58.8 vs. 19.2%) and PFS (52.9 vs. 19.2%). The IM group had a higher CR rate of induction treatment than the RM group (52.9 vs. 23.1%). No treatment-related death was observed. Twelve patients (27.9%) remained alive with disease-free survival times from 60+ to 135+ months. Control patients showed a substantially lower survival rate (5-year OS, 10.9%) and few long-term survivors. Conclusions: This regimen resulted in significantly improved efficacy and survival, which indicates a potentially curative role for chemotherapy-naive mNPC, especially in newly diagnosed patients. A phase III clinical trial (NCT02633176) is ongoing for confirmation.

OBJECTIVES: To observe the improvement effect and its mechanism of chlorogenic acid (CGA) on the glucose tolerance and its curve characteristics in high fat diet-induced obesity (DIO) rats. METHODS: Eight of 56 male SD rats were randomly selected as the normal diet group (CON), and the rest were fed with high-fat diet. After 4 weeks, 24 DIO rats were screened and then randomly divided into high fat diet group (HFD group), 50% CGA group and 98% CGA group. The CGA groups received intragastric administrations of 50% CGA and 98% CGA (80 mg/kg/d) once a day for 8 weeks, respectively, while the CON and HFD groups received a carrier solution PBS. Body weight was measured weekly and OGTT was performed every 4 weeks. Fasting insulin and insulin release were measured, HOMA-IR was calculated. Histopathological examination by hematoxylin and eosin staining method were evaluated in the pancreatic tissues. Non-targeted metabolomics analysis of rat serum was performed using UHPLC-Q-Orbitrap MS. RESULTS: Before the intervention of CGA, blood glucose levels at 120 min after glucose loading (P

Glioma, especially glioblastoma (GBM), is the most aggressive malignant brain tumor and its standard therapy is often ineffective because of temozolomide (TMZ) resistance. Reversal of the TMZ resistance might improve the prognosis of glioma patients. We previously found that interferon-α (IFN-α) and anti-epileptic drug levetiracetam (LEV) could sensitize glioma to TMZ, respectively. In this study, we further investigated the efficiency of combining of LEV and IFN-α for improving the efficacy of TMZ. We evaluated whether LEV and IFN-α could increase TMZ efficacy using colony formation assay and cell viability assay with MGMT-positive and MGMT-negative glioma cell lines in vitro. Subcutaneous xenografts and orthotopic xenografts mice models were used in vivo to observe the tumor growth and mice survival upon treatments with TMZ, TMZ + IFN-α, TMZ + LEV, or TMZ + LEV + IFN-α. The expression levels of MGMT, markers of pro-apoptotic and anti-apoptotic in tumor samples were analyzed by Western blotting. The combinational use of IFN-α, LEV, and TMZ showed the best anti-tumor activity in MGMT-positive cell lines (U138, GSC-1, U118, and T98 G). TMZ + LEV + IFN-α further obviously increased TMZ + LEV or TMZ + IFN-α efficiency in MGMT-positive cell lines, while not in negative cell lines (SKMG-4, U87, U373, and U251) in vitro, which were also observed in subcutaneous mice models (U138, GSC-1 compared to SKMG-4, U87) and orthotopic models (GSC-1) in vivo. Strikingly, the combination of LEV and IFN-α together with TMZ significantly prolonged the survival of mice with orthotopic GSC-1 glioma. Furthermore, we confirmed that the combination of LEV and IFN-α enhanced the inhibition of MGMT and the activation of apoptosis in U138 tumor on the basis of TMZ treatment. The combination use of LEV and IFN-α could be an optimal method to overcome TMZ resistance through obvious MGMT inhibition in MGMT-positive glioma.

Network slicing in 5G is expected to essentially change the way in which network operators deploy and manage vertical services with different performance requirements. Efficient and secure slice provisioning algorithms are important since network slices share the limited resources of the physical network. In this article, we first analyze the security issues in network slicing and formulate an Integer Linear Programming (ILP) model for secure 5G core network slice provisioning. Then, we propose a heuristic 5G core network slice provisioning algorithm called VIKOR-CNSP based on VIKOR, which is a multi-criteria decision making (MCDM) method. In the slice node provisioning stage, the node importance is ranked with the VIKOR approach by considering the node resource and topology attributes. The slice nodes are then provisioned according to the ranking results. In the slice link provisioning stage, the k shortest path algorithm is implemented to obtain the candidate physical paths for the slice link, and a strategy for selecting a candidate physical path is proposed to increase the slice acceptance ratio. The strategy first calculates the path factor Pf which is the product of the maximum link bandwidth utilization of the candidate physical path and its hop-count, and then chooses the candidate physical path with the smallest Pf to host the slice link. Extensive simulations show that the proposed algorithm can achieve the highest slice acceptance ratio and the largest provisioning revenue-to-cost ratio, satisfying the security constraints of 5G core network slice requests.

Background and Aim: Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) gene, which confers a limited response to standard-of-care treatment with temozolomide (TMZ), resulting in a lower survival. Dianhydrogalactitol (VAL-083) is a novel bi-functional DNA-targeting agent that induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated repair of the O6 guanine alkylator TMZ. A Phase 2 study has been initiated for VAL-083 in newly diagnosed MGMT unmethylated GBM. Subjects and Methods: The study has two parts: part 1 is a dose–escalation and induction format to enroll up to ten patients in which they received VAL-083 at 20, 30, or 40 mg/m2 per day for 3 days every 21 days concurrently with standard radiation treatment and VAL-083 for up to eight additional cycles. Part 2 comprises an expansion phase to enroll up to twenty additional patients. This study was performed with approval by the Institutional Review Board of Sun Yat-sen University Cancer Center (B2016-058-01) on January 13, 2017, and registered with the ClinicalTrials.gov (NCT03050736) on February 13, 2017. Results: After completion of dose escalation, VAL-083, 30 mg/m2 per day, in combination with radiation therapy, was generally safe and well tolerated. At the cutoff date, 23 patients had been enrolled, 14 of whom had been treated in the expansion phase. Consistent with prior studies, myelosuppression was the most common adverse event. Pharmacokinetic assessment indicated that the levels of VAL-083 were as high in the cerebrospinal fluid as in plasma, 2 h postinfusion. Of the 22 patients who had reached their four precycle magnetic resonance imaging assessments, 12 were assessed with disease progression, with a median progression-free survival of 9.9 (95% confidence interval 7.3–12.0) months for all the patients studied. Conclusion: These preliminary data support VAL-083 as a potentially valuable treatment option for newly diagnosed GBM.

Background and Aim: Guidelines recommend adjuvant treatment for patients with high-grade gliomas and low-grade gliomas with high risk of progression. In clinical practice, however, treatments may not conform to these suggested guidelines. In this study, we reviewed the treatments and outcomes in patients with gliomas at Sun Yat-Sen University Cancer Center (SYSUCC), China. Materials and Methods: Medical records and radiologic images of 1215 glioma patients who underwent surgery at the center from 2000 to 2017 were retrospectively reviewed, and their clinicopathological characteristics, treatment method, and overall survival (OS) were analyzed. The study was approved by the Ethics Committee of SYSUCC on February 20, 2019 (approval No. GZR2019-219). Results: A total of 1001 patients diagnosed with glioma (initially World Health Organization 2007 criteria, then 2016 criteria) were enrolled, including 90 patients with Grade I, 307 Grade II, 239 Grade III, and 365 Grade IV gliomas. A total of 331 of 604 patients with high-grade glioma (54.8%) and 159 of 397 with low-grade glioma (40.1%) received postsurgical radiotherapy, and 285 patients with high-grade tumors (47.1%) and 80 with low-grade tumors (20.2%) received adjuvant chemotherapy. The median OS was 17.5 months for Grade IV and 43.1 months for Grade III gliomas. The median OS of patients with low-grade glioma was not reached. The 5-year survival rates of patients with Grades I, II, III, and IV gliomas were 94.7%, 73.7%, 45.7%, and 18.6%, respectively. Multivariate analysis identified onset age, preoperative seizure, tumor location, pathological subtype, resection extent, and postsurgical treatment as independent predictors of OS in patients with high-grade gliomas. Patients with high-grade glioma who received postsurgical treatment had better survival than those without adjuvant therapy (Grade III: 52.6 vs. 20.3 months, P = 0.012; Grade IV: 22.6 vs. 12.1 months, P < 0.001). Among patients with diffuse low-grade gliomas, age, performance status, preoperative seizure, Ki-67 index, tumor subtype, and resection extent were associated with clinical outcomes. Conclusion: Glioma patients are not always treated according to guidelines. Although standard care may lead to favorable prognoses, individualized treatments may be more acceptable and result in better outcomes and should thus be considered in routine clinical practice.

Background: Physical activity has proven to be effective in improving blood pressure (BP), but research on the beneficial exercise volume for BP control is limited. We assessed the intervention effects of walking on BP in the Chinese Han occupational population with a sedentary lifestyle to explore the appropriate exercise volume needed for BP control.Methods: A total of 802 subjects were recruited from enterprises and institutions for our study. This study was designed as an intervention study for a baseline control trial. All participants received a 3-month open and prescription pedometer-assisted self-monitoring walking intervention. Multiple linear regression models were used to assess the association between physical activity and changes in systolic (SBP) and diastolic (DBP) BP. We divided the effective step counts into five levels: 4000-12000 (level 5) steps/day for statistical analysis to evaluate the exercise intervention efficiency.Results: Data of 688 participants who completed the study were analyzed. After 3 months, SBP and DBP decreased by 1.9 and 2.0 mmHg, respectively (P < 0.05). Taking level 5 (>12000 steps/day) as reference, SBP can be better controlled at levels 1-4: level 1 had the best effect (-6.05 mmHg, P=0.007), followed by level 2 (-3.54 mmHg, P=0.006), showing a significant dose-effect relationship between exercise and SBP. Furthermore, the effective step count of 6000-Conclusions: Brisk walking can effectively control BP in the Chinese Han occupational population with a sedentary lifestyle. There was a significant dose-effect relationship between exercise and SBP with differences in sex and age. Trial registration: ChiCTR-OOh-16010229. Registered 5 January 2017 - Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=17362.

The aim of this randomized phase II study was to investigate the optimal timing of the administration of thrombopoietin to prevent cytarabine-induced thrombocytopenia. Fifty-two patients who were scheduled for high-dose cytarabine treatment were randomly assigned to receive either the standard prophylactic mode (starting thrombopoietin, 15,000 units/day on days 2-11) or the pre-chemo mode (starting thrombopoietin, 15,000 units/day on days -4, -2, and 2-9) during the first cycle of chemotherapy with a switch to the other mode in the second cycle. The thrombocytopenia rate in the standard mode and the pre-chemo mode were PLT 50 × 10

With the tremendous increment of traffic in the next generation mobile networks, device to device (D2D) communication is proposed to relieve the traffic burden of the base station and improve the overall network capacity. It supports direct communications between devices and could reuse the resources of cellular users (CUs). Despite the advantages, D2D communications bring great challenges in interference management. In this paper, we study the power control and channel allocation problems in three scenarios: (1) one CU and one D2D pair; (2) one CU and multiple D2D pairs; (3) multiple CUs and multiple D2D pairs. The goal is to coordinate the mutual interferences and maximize the overall network capacity. We derive sufficient conditions to guarantee the efficiency of D2D communications in scenarios with one CU and one D2D pair. We propose the bio-inspired PSO-P power control algorithm for the scenarios with one CU and multiple D2D pairs, and the PSO-CP algorithm for the scenarios with multiple CUs and multiple D2D pairs to jointly assign channels and powers. Simulation results show that the proposed algorithms are efficient in improving the overall network capacity.

VAL-083 is a novel bi-functional DNA targeting agent that induces inter-strand DNA cross-links at N7-guanine, leading to DNA double-strand breaks and cell death. In vitro and in vivo studies have demonstrated VAL-083 circumvents MGMT-mediated chemo-resistance and differentiates it from other therapies used in the treatment of GBM, including temozolomide (TMZ). VAL-083 also acts as a radiosensitizer against GBM cancer stem cells in vitro. A Phase 2 study was conducted to evaluate the safety and tolerability of VAL-083 when administered concurrently with radiation therapy (RT) in newly diagnosed MGMT unmethylated GBM. Stage 1 was a dose-escalation phase to confirm the dose of VAL-083 in this setting. Patients received VAL-083 at 20, 30, or 40 mg/m2/day x 3 days every 21 days in combination with standard radiation treatment (RT) (2 Gy/day, 5 days/week for 6 weeks). Stage 2 was an expansion phase to enroll up to 20 additional patients at the 30 mg/m2/day of VAL-083 with RT. A total of 29 patients were enrolled in the study and completed treatment, with 25 patients receiving 30 mg/m2/day VAL-083. The median number of cycles completed by all patients was 9 (range 2-13). Consistent with our prior experience, myelosuppression was the most common adverse event. Pharmacokinetics (Cmax and AUC) of VAL-083 were broadly linear with respect to dose, and drug half-life was 0.8 hrs. In a sub-group of patients, levels of VAL-083 in CSF were found to be at least as high as those in plasma. The median progression free survival (PFS) for all patients enrolled was 9.3 (95%CI: 6.4-12.0) months. Eighteen (18/29; 62.1%) patients have died, and median overall survival for all patients enrolled was 19.6 (95%CI: 14.0-22.4) months. These results support the potential benefit of VAL-083 as a treatment alternative against GBM tumors with MGMT-mediated resistance to TMZ. Clinicaltrials.gov: NCT03050736.

Background Brain metastases are the most common intracranial tumors in adults, with a very poor prognosis, and poses distinct clinical challenges. This study aimed to develop a more accurate prognostic nomogram for predicting overall survival (OS) of patients with Brain Metastases. Methods We conducted a retrospective analysis of 1062 patients with brain metastases at the Sun Yat-sen University Cancer Center (SYSUCC, Guangzhou, China) between January 2010 and January 2018, Among them, 331 patients underwent surgery to remove brain metastases. Kaplan–Meier analysis was performed to screen for potential clinical variables that could be used to establish the nomogram for predicting overall survival. Results We found that age,gender, whether to remove intracranial lesions, radiotherapy, ECOG were independent prognostic factors for predicting the overall survival with brain metastases,and surgical resection for brain metastatic lesions could significantly improve OS,but only in certain groups of patients with brain metastases can benefit from intracranial lesion resection, such as no extracranial metastasis. And patients with brain metastases whose primary tumor is lung adenocarcinoma or breast cancer are more likely to benefit from surgery in terms of overall survival time.A nomogram for predicting 1- and 2-year overall survival rates was constructed, which exhibited good accuracy in predicting overall survival. Conclusion Through statistical analysis, we have found the factors related to the surgical benefit of patients with brain metastases, and established a prognostic nonogram,This nomogram may be used to guide individual treatments and in selecting an appropriate patient population for clinical trials.

Purpose This study aimed to analyze the preferred locations of secondary brain tumors of breast carcinoma according to different biological characteristics. Method 161 Breast cancer brain metastasis (BCBM) patients diagnosed between January 2007 and February 2018 were retrospectively analyzed. MR images when brain metastases occurred were collected, registered, segmented. The frequency and p-value heatmaps were constructed to compare two biological phenotypes using two-tailed Fisher’s exact test. Age, treatments, the status of ER, PR, and HER2, luminal subtype, tumor marker levels in peripheral blood including CEA, CA19-9, and CA15-3 were statistically analyzed. Survival data were analyzed by Kaplan–Meier method, log-rank test, and multivariate logistic regression. Result The frequency heat map shows lesions of patients with BCBM are more inclined to the cerebellar hemisphere. Older patients(>49 years old, median age) mainly occur in the left frontal lobe, the right parietal lobe, and adjacent meninges comparing with white matter of the left parietal lobe, cerebellar vermis, and areas around the fourth ventricle among younger patients and the difference is significant. Patients with tumors located on the surface of the brain are more likely to undergo surgical treatment, however, conservative treatment was considered if metastases are located at the midline structure. ER and PR-positive and HER-2 enriched patients have more significance in metastases, at the left parieto-occipital junction area, frontal lobe, parietal lobe, cerebellar hemisphere, and adjacent meninges. Metastases with high levels of CEA are found significantly at areas around the central anterior gyrus. Lesions with an elevated level of CA19-9 and CA15-3 tend to be frontal, parietal, and occipital. Besides, HER-2 enriched in primary sites and a normal level of CA15-3 in peripheral blood were two independent protective factors in determining prognostic outcomes. Conclusion The preferred locations of BCBM could be clues of further study and helpful for clinical strategies.

Ependymomas are glial brain tumors accounting for approximately 2~3% of all primary tumors of the central nervous system (CNS), and 12% of all pediatric intracranial tumors. To better understand the evolution process of ependymomas, we studied the clinical, pathological and genetic development of a rare girl case with repeatedly recurrent ependymoma. This girl was diagnosed as ependymoma at age of 9 years old, and experienced 7 times tumor relapse and received 9 times surgeries but finally ceased at 19 years old with multiregional recurrences. The pathological characteristics, radiographic images and therapeutic strategies of the patient were all retrieved. Molecular markers confirmed the diagnosis of anaplastic ependymoma based on the updated WHO guideline for CNS tumors. Whole-genome sequencing (WGS) was performed to elucidate the landscape of mutation signatures and to identify potential driver mutations along the tumor progression. The seven tumor specimens showed a highly branched evolutionary pattern. There were six gene mutations found in 5 of the 7 specimens (PCDHA4, PCDHA8, SEC14L6, SETD2, RIOK2, and SLCO2A1) and three in 6 of 7 the samples (RYR1, SNX25, DSC2). Strikingly, there was one gene, ADGRL3, which was found to be consistently mutated in the entire disease progression process. Our findings therefore suggest that ADGRL3 might play roles in the disease progression of ependymoma patient.

BACKGROUND Glioma often recurs and the imaging evaluation whether the tumor has returned after glioma treatment is still challenging. PET/CT is one of the most important techniques to assess the post-treatment of glioma. However, differentiating tumor recurrence (TuR) from treatment effects (TrE) remains difficult. In this study, we aim to retrospectively compare the diagnostic performance of three PET tracers 13N-NH3, 18F-DOPA, and 18F-FDG on PET/CT in differentiating between TuR and TrE in post-treatment glioma patients. METHODS Forty-three patients with MRI-suspected recurrent glioma were included. The maximum and mean standardized uptake value (SUVmax and SUVmean) of the lesion and the lesion-to-normal Gray-matter cortex uptake (L/G) ratio were recorded and the reference standard was verified by surgical histopathology or more than 6 months of follow-up with clinical/radiological. The diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. RESULTS 34 patients were confirmed as glioma TuR and 9 patients met the standard of TrE. The median time interval from primary diagnosis surgery to PET/CT was 14.83 months (range, 4.10-62.77 months). The SUVmax of 13N-NH3 and 18F-DOPA PET/CT at the lesions was significantly higher than normal brain tissue (13N-NH3 0.696±0.095 vs 0.486±0.071, 18F-DOPA 0.455±0.079 vs 0.194±0.031, both P< 0.001), while 18F-FDG was not (6.918±0.525 vs 6.356±0.510, P=0.290). TuR showed significantly higher L/G ratios than TrE both in 13N-NH3 and 18F-DOPA PET/CT (13N-NH3, 1.573±0.099 vs 1.025±0.128, P=0.008; 18F-DOPA, 2.729±0.131 vs 1.514±0.141, P< 0.001). The sensitivity, specificity and the area under the curve (AUC) by ROC analysis were 57.7, 100% and 0.803 for 13N-NH3, and 84.6, 100% and 0.938 for 18F-DOPA respectively. CONCLUSIONS PET/CT is a powerful tool to distinguish glioma TuR from TrE, and 18F-DOPA PET/CT has remarkably better differential diagnosis efficacy than 13N-NH3 and 18F-FDG.

Background Differentiating glioma recurrence from treatment-related changes can be challenging on conventional imaging. We evaluated the efficacy of quantitative parameters measured by dual-energy spectral computed tomographic (CT) for this differentiation. Methods Twenty-eight patients were examined by dual-energy spectral CT. The effective and normalized atomic number (Zeff and Zeff-N, respectively); spectral Hounsfield unit curve (λHU) slope; and iodine and normalized iodine concentration (IC and ICN, respectively) in the post-treatment enhanced areas were calculated. Pathological results or clinicoradiologic follow-up of ≥2 months were used for final diagnosis. Nonparametric and t-tests were used to compare quantitative parameters between glioma recurrence and treatment-related changes. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and accuracy were calculated using receiver operating characteristic (ROC) curves. Predictive probabilities were used to generate ROC curves to determine the diagnostic value. Results Examination of pre-contrast λHU, Zeff, Zeff-N, IC, ICN, and venous phase ICN showed no significant differences in quantitative parameters (P > 0.05). Venous phase λHU, Zeff, Zeff-N, and IC in glioma recurrence were higher than in treatment-related changes (P 3, achieving 66.7, 91.7, 83.3, and 91.7% sensitivity; 100.0, 77.8, 88.9, and 77.8% specificity; 100.0, 73.3, 83.3, and 73.3% PPV; 81.8, 93.3, 88.9, and 93.3% NPV; and 86.7, 83.3, 86.7, and 83.3% accuracy, respectively. The respective areas under the curve (AUCs) were 0.912, 0.912, 0.931, and 0.910 in glioma recurrence and treatment-related changes. Conclusions Glioma recurrence could be potentially differentiated from treatment-related changes based on quantitative values measured by dual-energy spectral CT imaging.

Twist is a transcription factor involved in the process of epithelial to mesenchymal transition (EMT) of carcinoma cells, and the promotion of invasion of gliomas through the mesenchymal adjusting process. However, its clinical significance in human glioma has not yet to be understood. To delineate the clinical-pathological significance and prognostic value of Twist, the expression of Twist was evaluated by Immunohistochemistry for 187 glioma samples. We found that Twist demonstrated frequent nuclear expression in the glioma samples and its expression levels were associated with tumor grade (P

BACKGROUND: The present study explored the predictive value of systemic inflammatory indexes in diagnosing grade III gliomas of oligodendroglial origin. METHODS: A retrospective study of 154 patients with grade III gliomas was conducted. Systemic inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), albumin-to-gamma-glutamyl transferase ratio (AGR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, prognostic nutritional index, and fibrinogen-to-albumin ratio, were reviewed. The resulting predictive model was externally validated using a demographic-matched cohort of 49 grade III glioma patients. RESULTS: In the training set, gliomas of oligodendroglial origin tended to have a lower NLR (P=0.018) and a higher AGR (P=0.036) than those with tumors of astrocytic origin. Moreover, both NLR and AGR had predictive value for oligodendroglial tumors, when compared with astrocytic tumors. The best diagnostic value was obtained using NLR + AGR (AUC =64.9%, 95% CI: 55.5–74.3%, P=0.005). In the validation set, NLR + AGR satisfactorily predicted the presence of oligodendroglial tumors (AUC =66.5%, 95% CI: 50.6–82.4%, P

OBJECTIVE Brain metastases are the most common malignant tumors of the central nervous system. In patients with brain metastases with surgical indications, total surgical resection is the most effective treatment for prolonging patient survival and relieving neurological symptoms. In this study, the clinical data of 147 patients in a single group underwent microsurgery of brain metastases were retrospectively analyzed to investigate the therapeutic value of microsurgery in patients with brain metastases. METHODS From January 2000 to December 2017, patients who underwent microsurgical removal of brain metastases from the Department of Neurosurgery in Sun Yat-sen University Cancer Center were retrospectively analyzed. The clinical and pathological features and prognosis of the patients were collected and analyzed. The characteristics of brain metastases were analyzed through surgical recording and videos. RESULTS A total of 147 patients were enrolled, including 86 males and 61 females. The average age was 54.4 years, of which 125 were younger than 65 years old. 137 people with KPS ≥ 70. 95.9% (141 patients) had an RPA grade of I-II, of which 51 (34.7%) were RPA class I and 90 (61.2%) were RPA class II. 90.5% (133 patients) were single brain metastases. 71.5% (105 cases) of patients with metastases are located in the cerebral area. The distribution of primary lesions suggested that the lung cancer was the most, reaching 62.6%; followed by breast source (10.9%). The surgical video analysis suggest that most brain metastatic lesions have obvious supplying vessels, relatively clear boundaries with a pseudo-capsule structure. The 5-year OS of all patients reached 15% with a median survival of 42.3 months. CONCLUSION The brain metastases have clear blood supplying vessels and relatively clear boundaries that favors gross total resection. Surgical treatment is associated with better prognosis in patients with brain metastases.

Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated methylguanine DNA-methyltransferase (MGMT gene, which confers a limited response to standard of care treatment with temozolomide (TMZ) resulting in a lower survival. VAL-083 is a novel bi-functional DNA targeting agent that induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated repair of the O6 guanine alkylator TMZ. A Phase 2 study has been initiated for VAL-083 in newly diagnosed MGMT unmethylated GBM. The study has 2 stages: Stage 1 is a dose-escalation and induction format to confirm the recommended dose of VAL-083 when administered concurrently with radiation therapy (RT) based on safety and tolerability. The subjects received VAL-083 at 20, 30, or 40 mg/m2/day x 3 days every 21 days along with standard radiation treatment. Stage 2 comprises an expansion phase to enroll up to 30 patients. The dose escalation stage is complete and 30 mg/m2/day of VAL-083 in combination with RT was generally safe and well-tolerated. As of 17 May, 2019, 18 patients have been enrolled. Fifteen patients have completed their prospectively planned MRI scans and had their initial assessment for tumor progression. Of these 15 patients, seven were assessed as a complete response (CR), and eight patients as having stable disease (SD). Of the remaining three patients, one died prior to their post-cycle 3 MRI and two have not been on study long enough to reach their planned post-cycle 3 MRI. As of the data cutoff, 14 of the 18 patients were still alive. Consistent with our prior experience, myelosuppression was the most common adverse event. Three dose-limiting toxicities have been reported - one at the 40 mg/m2/day and two at the 30 mg/m2/day dose. Further enrollment, safety & study updates will be presented at the meeting. Clinicaltrials.gov identifier: NCT03050736.

Analyzing heart rate variability (HRV) in preterm infants can help track maturational changes and subclinical signatures of disease. We conducted an observational study to characterize the effect of demographic and cardiorespiratory factors on three features of HRV using a linear mixed-effects model. HRV-features were tailored to capture the unique physiology of preterm infants, including the contribution of transient pathophysiological heart rate (HR) decelerations. Infants were analyzed during stable periods in the incubator and subsequent sessions of Kangaroo care (KC) – an intervention that increases comfort. In total, 957 periods in the incubator and during KC were analyzed from 66 preterm infants. Our primary finding was that gestational age (GA) and postmenstrual age (PMA) have the largest influence on HRV while the HR and breathing rate have a considerably smaller effect. Birth weight and gender do not affect HRV. We identified that with increasing GA and PMA, overall HRV decreased and increased respectively. Potentially these differences can be attributed to distinct trajectories of intra- and extrauterine development. With increasing GA, the propensity towards severe HR decelerations decreases, thereby reducing overall variability, while with increasing PMA, the ratio of decelerations and accelerations approaches unity, increasing overall HRV.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The majority of glioblastoma multiforme (GBM) patients have an unmethylated MGMT promoter status, leading to limited response to TMZ and decreased survival. Current standard-of-care includes surgery followed by chemoradiation and TMZ. An unmethylated promoter for O6-methylguanine DNA methyltransferase (MGMT) is a validated biomarker for TMZ-resistance and is strongly correlated with poor outcomes. VAL-083 is a novel bi-functional DNA targeting agent that induces inter-strand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated drug-resistance and has demonstrated cytotoxicity in MGMT-unmethylated GBM cell lines, cancer stem cells (CSCs) and in vivo models. Furthermore, VAL-083 acts as a radiosensitizer in GBM CSCs and non-CSCs. A Phase 2, open-label, biomarker-driven, study is being conducted to evaluate the tolerability and efficacy of VAL-083 in combination with radiation therapy (RT) in newly diagnosed MGMT-unmethylated GBM patients. A treatment regimen, consisting of a 6-week induction period of VAL-083 given IV at 20, 30, or 40 mg/m2/day x 3 days every 21 days and concurrent radiation (2 Gy daily, 5 days/week) followed by up to 24 weeks of maintenance therapy with single-agent VAL-083, is being evaluated. The study has 2 stages: Stage 1, dose-escalation, has identified a recommended dose of 30 mg/m2/day of VAL-083 in combination with RT as generally safe and well-tolerated. Stage 2, an expansion stage, has enrolled 20 additional patients at 30 mg/m2/day IV infusion on days 1, 2, and 3 of 21-day cycles. As of January 11, 2021, all 29 subjects in the study have been enrolled and completed the treatment stage of the study. Tumor response are assessed by MRI, according to RANO criteria. Efficacy endpoints include progression-free survival (PFS) and overall survival (OS). Additional endpoints include safety evaluations and pharmacokinetic assessments of plasma and CSF samples. The trial is continuing as planned and an update on primary results on safety and efficacy, and pharmacokinetics will be provided at the meeting. Clinicaltrials.gov identifier: NCT03050736. Citation Format: Zhong-ping Chen, Cheng-cheng Guo, Qun-ying Yang, Jia-wei Li, Shao-xiong Wu, John Langlands, Gregory Johnson, Claire Kwan, Sarath Kanekal, Richard Schwartz, Jeffrey Bacha, Anne Steino, Dennis Brown. Phase 2 clinical trial of dianhydrogalactitol (VAL-083) in patients with newly diagnosed MGMT-unmethylated GBM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT172.

e14019 Background: High-grade glioma (HGG) is the most common malignant brain tumor and lacks effective treatment regimen. Anlotinib is a multikinase inhibitor blocking angiogenesis and tumor cell proliferation simultaneously. This study was performed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide (TMZ) in the treatment of recurrent HGG. Methods: This is a single-center, retrospective study. Eligible patients (pts) were diagnosed with pathologically confirmed high grades (WHO III/IV) glioma and had recurrent or progressive disease on or after prior treatment. Other key eligibility criteria included Karnofsky Performance Status (KPS) ≥ 40, aged 16 ̃75 years and having at least one measurable lesion (RANO criteria). Pts were administrated with anlotinib once daily for 14 days every 3 weeks till disease progression, intolerable toxicities or death. The initial dose was 12mg for younger pts ( < 40 years old) with KPS ≥ 60 and 10 mg for others. Combination treatment was allowed if previous TMZ was effective and tolerable. TMZ was administered on dose-dense schedule (150mg/m2, QD, d1-d7 and d15-d21 every 28 days) or metronomic schedule (25-50mg/m2 QD). The primary endpoint was progression-free survival at 6 months (PFS6m) accessed according to RANO criteria. The second endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Results: Between August 2019 and June 2020, 23 pts with HGG (15 grade IV; 8 grade III; 12 males, 11 females) were enrolled. The median age and median KPS was 42 years and 60. 16 pts have multifocal or disseminated disease. 18 pts received ≥2 lines previous treatment. At the data cutoff date on September 2020, the median duration of treatment was 9 weeks (range: 3-33). The PFS6m was 39.1% and the median PFS was 4.2 months (95% CI: 2.8, 5.6). The median OS was not reached (95% CI: NE, NE) and the OS at 12 months (OS12m) was 54.8%. 8 pts observed tumor response and 9 pts had stable disease. The ORR and DCR were 34.8% and 73.9% respectively. The results of survival analysis for subgroups were summarized in table below. Grade 1 or 2 treatment-related adverse events (TRAEs) occurred in 65.2% pts. No ≥ grade 3 TRAE was found. All hematological TRAEs occurred in patients received combination regimen. No TRAE-induced treatment termination occurred. The lower incidence of TRAE may partly attributed to that most pts (18/23) received lower initial dose (10mg) of anlotinib and the relatively shorter treatment duration. Conclusions: This study showed treatment with anlotinib alone or in combination with TMZ had promising efficacy and favorable tolerability in patients with recurrent HGG.[Table: see text]

Network slicing for 5G provides Network-as-a-Service (NaaS) for different use cases, allowing network operators to build multiple virtual networks on a shared infrastructure. With network slicing, service providers can deploy their applications and services flexibly and quickly to accommodate diverse services' specific requirements. As an emerging technology with a number of advantages, network slicing has raised many issues for the industry and academia alike. Here, the authors discuss this technology's background and propose a framework. They also discuss remaining challenges and future research directions. This publication was made possible by the NPRP award (NPRP 8-634-1-131) from the Qatar National Research Fund (a member of The Qatar Foundation), Huawei Technologies, and the China Scholarship Council (201506270075). The statements made herein are solely the responsibility of the authors. Scopus

Satellite platform vibration induced by the onboard dynamic components and exterior perturbation deteriorates platform stability and causes attitude jitter, resulting in image distortion and geometric accuracy degradation. This paper presents an attitude jitter detection method based on images and dense ground controls, which requires neither high-performance attitude measurement devices nor specific sensor configuration like parallax observation. Attitude variations will result in image space discrepancies at control points, from which the attitude jitter can be retrieved. The method was validated by a case study with ZY-3 satellite, which is the first civilian high-resolution stereo mapping satellite in China. The experimental results show that an almost constant jitter frequency of about 0.65 Hz was detected, which was consistent with the direct attitude observations. The photogrammetric method is theoretically capable of detecting attitude jitter up to half of the image line scanning rate according to Shannon's sampling theorem, which is far beyond the detectable range by direct attitude observations at a frequency usually not higher than 4 Hz. Currently, the attitude jitter of the roll angle and the pitch angle can be effectively detected and accurately estimated for the nadir camera. The pitch angle jitter is also well estimable for the forward and the backward cameras. With approximation, the roll angle jitter for the two off-nadir cameras can also be estimated, though with some deviation caused by the influence of the yaw angle jitter.

Providing reliable transmission for real-time traffic in wireless cellular networks is a great challenge due to the unreliable wireless links. This paper concentrates on the resource allocation problem aiming to improve the real-time throughput. First, the resource allocation problem is formulated as a Markov Decision Process and thus the optimal resource allocation policy could be obtained by adopting the value iteration algorithm. Considering the high time complexity of the optimal algorithm, we further propose an approximate algorithm which decomposes the resource allocation problem into two subproblems, namely link scheduling problem and packet scheduling problem. By this method, the unreliable wireless links are only constrained in the link scheduling problem, and we can focus on the real-time requirement of traffic in packet scheduling problem. For the link scheduling problem, we propose the maxRel algorithm to maximize the long-term network reliability, and we theoretically prove that the maxRel algorithm is optimal in scenarios with dynamic link reliabilities. The Least Laxity First algorithm is adopted for the packet scheduling problem. Extensive simulation results show that the proposed approximate resource allocation algorithm makes remarkable improvement in terms of time complexity, packet loss rate and delay.

BACKGROUND AND OBJECTIVE Primary intracranial germ cell tumors (PIGCTs) are a group of heterogeneous tumors. It is very difficult to treat those patients without pathological diagnosis. This study retrospectively analyzed the clinical data and outcomes of patients with clinically diagnosed (without histologically confirmed) PIGCTs in SunYat-sen University Cancer Center. METHODS Patients who were clinically diagnosed as PIGCTs without histological diagnosis through surgical resection or biopsy were included in this study. Patients were analyzed for clinical characteristics, treatment patterns, outcomes and adverse effects. RESULTS From May 2002 to July 2014, 74 patients clinically diagnosed with PIGCTs received chemotherapy and/or radiotherapy at the Sun Yat-sen University Cancer Center. The median age was 16.5 years old (4–45 years old, majority was teenagers). The most of tumors were found in male, and located in the pineal and suprasellar regions. When the patients were grouped into diagnostic chemotherapy group (57 cases), diagnostic radiotherapy group (5 cases) and gamma knife radiosurgery group (12 cases) based on their initial anti-tumor therapy. The 5-year survival rates were 84.3%, 75.0% and 75.0%, respectively. There was a trend that the chemotherapy group got a better survival. Patients were allocated to secretory tumor group (49 cases) and non-secretory tumor group (25 cases) based on their levels of tumor makers (α-FP and β-hCG). The 5- year survival rates were 80% and 77.8% (P value = 0.966), respectively. CONCLUSION Clinical diagnosed PIGCT (without histological confirmation) patients may obtain good responses when receiving comprehensive treatments of chemotherapy combined with radiotherapy.

Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated methylguanine DNA-methyltransferase (MGMT) promoter region, which confers a limited response to standard-of-care treatment with temozolomide (TMZ), resulting in shorter median survival when compared to patients with methylated MGMT promoter. VAL-083 is a novel bi-functional DNA targeting agent that induces inter-strand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated TMZ resistance in vitro and in vivo. A Phase 2 study has been initiated for VAL-083 in newly diagnosed MGMT unmethylated GBM. The study has 2 stages: Stage 1 is a dose-escalation safety and tolerability phase to confirm the phase 2 dose of VAL-083 when administered concurrently with radiation therapy (RT). Patients received VAL-083 at 20, 30, or 40 mg/m2/day x 3 days every 21 days along with standard radiation treatment (RT) (2 Gy/day, 5 days/week). The dose escalation stage is complete, and 30 mg/m2/day of VAL-083 in combination with RT was generally safe and well-tolerated. Stage 2 comprises an expansion phase to enroll up to 20 additional patients at the 30 mg/m2/day of VAL-083 in combination with RT. As of June 2, 2020, all patients have been enrolled, with a total of 29 patients in the study, and 25 patients receiving 30 mg/m2/day VAL-083. Of the 29 patients enrolled, 27 have completed their prospectively planned MRI scans and had their initial assessment for tumor response. Two additional patients died prior to their post-cycle 3 MRI. Consistent with our prior experience, myelosuppression was the most common adverse event. Three patients have experienced dose-limiting toxicities - one (1/3; 33%) at the 40 mg/m2/day and two (2/25; 8%) at the 30 mg/m2/day dose. Further safety and efficacy updates will be presented at the meeting. Clinicaltrials.gov identifier: NCT03050736.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Current standard-of-care includes surgery followed by chemoirradiation and temozolomide (TMZ). An unmethylated promoter for O6-methylguanine DNA methyltransferase (MGMT) is a validated biomarker for TMZ-resistance and is strongly correlated with poor outcomes. The majority of glioblastoma multiforme (GBM) patients have an unmethylated MGMT promoter status, leading to limited response to TMZ and decreased survival. Dianhydrogalactitol (VAL-083) is a novel bi-functional DNA targeting agent that induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated drug-resistance and has demonstrated cytotoxicity in MGMT-unmethylated GBM cell lines, cancer stem cells (CSCs) and in vivo models. Furthermore, VAL-083 acts as a radiosensitizer in GBM CSCs and non-CSCs. A Phase 2, open-label, biomarker-driven, study has been initiated to evaluate the tolerability and efficacy of VAL-083 in combination with radiation therapy (RT) in newly diagnosed MGMT-unmethylated GBM patients. A treatment regimen, consisting of a 6-week induction period of VAL-083 given IV at 20, 30, or 40 mg/m2/day x 3 days every 21 days and concurrent radiation (2 Gy daily, 5 days/week) followed by up to 24 weeks of maintenance therapy with single-agent VAL-083, is being evaluated. The study has 2 stages: Stage 1 is a dose-escalation and induction format to establish a recommended dose of VAL-083 when administered concurrently with RT based on safety and tolerability. The dose escalation stage has been completed and we identified a recommended dose of 30 mg/m2/day of VAL-083 in combination with RT as generally safe and well-tolerated. Stage 2 comprises an expansion stage to enroll up to 20 additional patients at 30 mg/m2/day IV infusion on days 1, 2, and 3 of 21-day cycles and is currently ongoing. Tumor response will be assessed by MRI, according to RANO criteria. Efficacy endpoints include progression-free survival (PFS) and overall survival (OS). Additional endpoints include safety evaluations and pharmacokinetic assessments of plasma and CSF samples. As of 21st January 2020, 19 subjects have initiated treatment in stage 2. The enrollment, safety data and primary results update will be provided at the meeting. Clinicaltrials.gov identifier: NCT03050736. Citation Format: Zhong-ping Chen, Cheng-cheng Guo, Qun-ying Yang, Jia-Wei Lei, Shao-xiong Wu, Gregory Johnson, John Langlands, Claire Kwan, Sarath Kanekal, Richard Schwartz, Jeffrey A. Bacha, Anne Steino, Dennis M. Brown. Phase 2 trial of dianhydrogalactitol (VAL-083) in patients with newly diagnosed MGMT-unmethylated glioblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT273.

Due to the variable overlap of multiple symptoms, accurate early diagnosis of NK/T-cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is difficult, making the prognosis extremely poor. Hemophagocytic syndrome (HPS) is now diagnosed primarily based on the hemophagocytic lymphohistiocytosis (HLH)-2004 diagnostic criteria, and platelet count is one of the baseline evaluations. However, in our study, the data showed that decreased platelets were not only a clinical feature of HPS but also the key cells that regulate inflammation by releasing α-granules containing upregulated platelet factor 4 (PF4) and downregulated platelet-derived growth factors (PDGFs). Furthermore, we found that angiopoietin-4 (ANG-4), which has significant differential expression, has been less reported, that may affect hematopoiesis and proinflammatory responses and can be used as diagnostic biomarkers together with PF4 and PDGFs.

This paper introduces a simulation method of random disturbance, which could more real simulate complex application environment of mutli-hop wireless network. We define two models on packet discard and error to represent the packet loss situation in wireless network lines. The paper states the design plan, architecture and implementation scheme that could produce the noise interference randomly by NS2 tool. The paper also illustrates a new simulation communication experiment of mutli-hop wireless network and analysis the influences of random disturbance to the network performance, including end to end delay and packet loss rate and throughput.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Current standard-of-care includes surgery followed by chemo-radiation and temozolomide. An unmethylated promoter for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance and is strongly correlated with poor outcomes. Unmethylated MGMT represents the majority of newly diagnosed GBM tumors. VAL-083 is a first-in-class bi-functional DNA-targeting agent that has shown activity against GBM in NCI-sponsored clinical trials both as single agent and in combination with radiotherapy. VAL-083 induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and cell-death. VAL-083s unique mechanism-of-action circumvents MGMT-mediated chemoresistance, and it has demonstrated cytotoxicity in MGMT-unmethylated GBM cell-lines, cancer stem cells (CSCs) and in vivo models. Furthermore, VAL-083 acts as a radiosensitizer in GBM CSCs and non-CSCs. We completed a dose-escalation trial of VAL-083 in recurrent GBM, and a generally well-tolerated dosing regimen was selected for further clinical development. The present trial is an ongoing open-label, biomarker-driven, Phase 1/2 study to evaluate the tolerability and efficacy of VAL-083 in combination with radiotherapy in newly diagnosed MGMT-unmethylated GBM patients. A treatment regimen, consisting of a 6-week induction period of VAL-083 and concurrent radiation (2 Gy daily, 5 days/week) followed by up to 24 weeks of maintenance therapy with single-agent VAL-083, is being evaluated. The study is being conducted in two parts: 1) a dose-escalation part (20, 30, and 40mg/m2/day IV infusion on days 1,2,3 of a 21-day cycle) in up to 10 patients; 2) an expansion part in up to 20 additional patients at the determined well-tolerated dose. Tumor response will be assessed by MRI, according to RANO criteria. Efficacy endpoints include progression-free survival (PFS) and overall survival (OS). Additional endpoints include safety evaluations and pharmacokinetic assessments of plasma and CSF samples. Enrollment and safety data update will be provided at the meeting. Clinicaltrials.gov identifier: NCT03050736.

Primary CNS germ cell tumors (CNS-GCTs) are a group of heterogeneous tumors, and comparative higher incidence in Asian countries. Here we present our institutional experience for CNS-GCTs treatment. There are 209 CNS-GCTs cases treated at Sun Yat-sen University Cancer Center during last 15 years. The median age of patients was 16 years old (4-69 y-old). The tumors were classified as Germinoma and Nongerminoma germ cell tumors(NG-GCTs), and also secretory sub-type(AFP≥10 ng/dL and/or β-HCG)≥50 IU/L) or non-secretory sub-type(normal level of tumor marker). There were 60 cases received Ventricle-peritoneal shunt (V-P shunt) or endoscopic third ventricle colostomy due to obstructive hydrocephalus. Treatment modality including: comprehensive treatment 84cases (40.2%), ie chemotherapy plus radiation therapy (some cases with chemo-Radio-chemo Sandwich Therapy) with or without surgical intervention; Monotherapy, ie Chemotherapy only:37 (17.7%), Radiotherapy Only:13 (6.2%). Surgery for tumor removal or biopsy:55cases (25.4%), in which 4 cases were failed from initial diagnostic chemotherapy. There were also some patients(about 6%) received Gamma knife radiosurgery. The 5 years overall survival(OS) rate was better for those with comprehensive treatment, compared those with monotherapy cases: 86.5% vs 66.7%. The 5 ys OS rate according tumor markers was also different: Non Secretory Subtype:79.8%,HCG increased Subtype: 92.9%, AFP increased Subtype: 64.8%, and AFP+HCG coincreased Subtype: 75.0%. Conclusion from our institutional experience: Although smaller number of patients need surgical tumor removal, clinical diagnosed CNS-GCT (without histological confirmation) patients may obtain good responses when receiving comprehensive treatments of chemotherapy combined with radiotherapy.

OBJECTIVE Temozolomide (TMZ), is the first line chemotherapeutic drug for glioma. Previous studies have suggested that interferon (IFN) and levetiracetam (LEV) could respectively reverse the resistance of TMZ by down-regulating MGMT expression. This study, we aim to investigate the therapeutic effect of a cocktail chemotherapy regimen combining TMZ, LEV, IFN in vivo. METHODS Glioma cell lines U251 and SKMG-4 (MGMT protein expression positive), U138 and GSC-1(MGMT protein expression negative) were used for producing xenograft tumors. The xenograft tumors were established by subcutaneously injecting 1×106 glioma cells into female BALB/C nude mice and divided into 5 treatment groups: Control, TMZ, TMZ+IFN, TMZ+LEV, TMZ+LEV+IFN. The treatment with TMZ (50 mg/kg, i.p.), IFN (2×105 IU, s.c.), LEV (150 mg/kg, i.p.) once a day for five consecutive days and xenograft tumors were measured every two days. RESULTS We identified that U138, U251, SKMG-4 tumor growth among TMZ, TMZ+IFN, TMZ+LEV, TMZ+LEV+IFN were all significantly inhibited (P< 0.05), compared with the control. As for U251 and SKMG-4, tumor killing effect of all 4 treatment groups were not different (P > 0.05). In the treatment of mice bearing U138 glioma, the tumor weight of TMZ+LEV+IFN (0.2688±0.1169 g) group was the lowest and significantly lower than that of TMZ+LEV (0.6574±0.08174g, P=0.0261), TMZ+IFN(0.6108±0.07317 g, P=0.0381), and TMZ (0.9054±0.07154 g, P=0.0017) group. Glioma stem cells GSC-1 was highly resistant to TMZ, tumor volume of TMZ group was not different from control group (P >0.05). While compared with TMZ (1.993±0.1274 g) group, in TMZ+IFN (1.506±0.1223g, P=0.0203), TMZ+LEV (1.178±0.1807g, P=0.0042), and TMZ+LEV+IFN (1.049±0.2171 g, P=0.0038) groups, GSC-1 tumor growth were significantly inhibited(P< 0.05). CONCLUSION Our data demonstrate that both IFN and LEV can sensitize TMZ effect on glioma in vivo, even for MGMT(+) tumors, and TMZ-LEV-IFN cocktail regimen seems the best. Key words: glioma, TMZ, LEV, IFN

How to reduce interference among neighbor nodes in wireless mesh networks is still an important and key issue nowadays. In this paper, an optimized channel assignment algorithm (OCA) is proposed to solve this problem based on link throughput and node priority. The effects of the numbers of network interface cards and channels on the network throughput are analyzed and evaluated. When there are seven of the numbers of both network interface cards and channels, the efficiency of utilizing network interface card and channel reaches highest. Compared with centralized channel assignment algorithm (CCA), the proposed algorithm has less packet loss rate and more network throughput significantly.

As regular topology networks, grid networks are widely adopted in network deployment. Link congestion and routing path length are two critical factors that affect the delay and throughput of a network. In this paper, we study the routing problem in grid networks concerning these two factors. The main objective of our routing algorithms is to minimize the maximum link congestion. The shortest path minimum maximum (SPMM) link congestion and non-shortest path minimum maximum (NSPMM) link congestion routing problems are studied. The two problems are first formulated as integer optimization problems. Then, corresponding routing algorithms (SPMM and NSPMM routing algorithms) are proposed. For SPMM routing algorithm, the path length is optimal, while for NSPMM routing algorithm, the path is limited in a submesh. Thus, the path length can be bounded. At last, we compare the proposed routing algorithms under different scenarios with other popular routing algorithms (RowColumn, ZigZag, Greedy, Random routing algorithms). The performances are evaluated through different metrics including link congestion, path length, path congestion, path congestion to path length ratio, delay and throughput.

The bandgap, electrical, and optical properties of PtSe2 depend dramatically on the vertical stacking and fabrication method. Here, we study the nonlinear absorption properties of the PtSe2 films composed of both semiconducting and semimetallic phases in a single film. These PtSe2 films exhibit remarkable thickness-dependent saturable absorption for femtosecond pulses at 400 nm and 800 nm. The saturation intensities decrease with the increase in the film thickness due to the accompanied increase in the semimetallic component and are much smaller than the reported values of PtSe2 synthesized by thermally assisted conversion. The saturable absorption characteristics are confirmed by time-resolved spectroscopies. The nonlinear refractive indexes of these PtSe2 films should be smaller than 1 × 10–12 cm2/W. Our results imply that the optical nonlinearities of PtSe2 could be flexibly tuned by the synthesis method and thickness.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Current standard-of-care includes surgery followed by chemo-radiation and temozolomide. An unmethylated promoter for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance and is strongly correlated with poor outcomes. Unmethylated MGMT represents the majority of newly diagnosed GBM tumors. VAL-083 is a first-in-class bi-functional DNA-targeting agent that has shown activity against GBM in NCI-sponsored clinical trials both as single agent and in combination with radiotherapy. VAL-083 induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and cell-death. VAL-083’s unique mechanism-of-action circumvents MGMT-mediated chemoresistance, and it has demonstrated cytotoxicity in MGMT-unmethylated GBM cell-lines, cancer stem cells (CSCs) and in vivo models. Furthermore, VAL-083 acts as a radiosensitizer in GBM CSCs and non-CSCs. We completed a dose-escalation trial of VAL-083 in recurrent GBM, and a generally well-tolerated dosing regimen was selected for further clinical development. The present trial is an ongoing open-label, biomarker-driven, Phase I/II study to evaluate the tolerability and efficacy of VAL-083 in combination with radiotherapy in newly diagnosed MGMT-unmethylated GBM patients. A treatment regimen, consisting of a 6-week induction period of VAL-083 and concurrent radiation (2 Gy daily, 5 days/week) followed by up to 24 weeks of maintenance therapy with single-agent VAL-083, is being evaluated. The study is being conducted in two parts. The dose-confirmation part (20, 30, and 40 mg/m2/day IV infusion on days 1-3 of a 21-day cycle) has been completed, and the expansion part has been initiated in up to 20 additional patients at 30 mg/m2/day IV infusion on days 1-3 of a 21-day cycle. Tumor response will be assessed by MRI, according to RANO criteria. Efficacy endpoints include progression-free survival (PFS) and overall survival (OS). Additional endpoints include safety evaluations and pharmacokinetic assessments of plasma and CSF samples. Trial design, enrollment and safety data update will be provided at the meeting. Clinicaltrials.gov identifier: NCT03050736. Citation Format: Zhong-ping Chen, Chengcheng Guo, Jeffrey Bacha, John Langlands, Anne Steino, Claire Kwan, Sarath Kanekal, Richard Schwartz, Lorena Lopez, Dennis Brown. Phase I/II study of dianhydrogalactitol (VAL-083) with radiation therapy in patients with newly diagnosed, MGMT-unmethylated glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT116.