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Objective: To verify the association between CD44 and CD133 expression levels and the prognosis of patients with lower grade gliomas (LGGs) and constructing radiomic models to predict those two genes’ expression levels before surgery. Materials & methods: Genomic data of patients with LGG and the corresponding T2-weighted fluid-attenuated inversion recovery images were downloaded from The Cancer Genome Atlas and The Cancer Imaging Archive, which were utilized for prognosis analysis, radiomic feature extraction and model construction, respectively. Results & conclusion: CD44 and CD133 expression levels in LGG can significantly affect the prognosis of patients with LGG. Based on the T2-weighted fluid-attenuated inversion recovery images, the radiomic features can effectively predict the expression levels of CD44 and CD133 before surgery.

Determination of 1p/19q co-deletion status is important for the classification, prognostication, and personalized therapy in diffuse lower-grade gliomas (LGG). We developed and validated a deep learning imaging signature (DLIS) from preoperative magnetic resonance imaging (MRI) for predicting the 1p/19q status in patients with LGG. The DLIS was constructed on a training dataset (n = 330) and validated on both an internal validation dataset (n = 123) and a public TCIA dataset (n = 102). The receiver operating characteristic (ROC) analysis and precision recall curves (PRC) were used to measure the classification performance. The area under ROC curves (AUC) of the DLIS was 0.999 for training dataset, 0.986 for validation dataset, and 0.983 for testing dataset. The F1-score of the prediction model was 0.992 for training dataset, 0.940 for validation dataset, and 0.925 for testing dataset. Our data suggests that DLIS could be used to predict the 1p/19q status from preoperative imaging in patients with LGG. The imaging-based deep learning has the potential to be a noninvasive tool predictive of molecular markers in adult diffuse gliomas. The authors developed a deep learning model predictive of 1p/19q status from preoperative imaging in 555 lower-grade gliomas (LGG), and achieved an area under the curve (AUC) of 0.983 in the testing dataset. They reveal that developing deep learning imaging signatures could be a noninvasive tool for predicting molecular markers in LGG.

Objective: Lower grade gliomas (LGGs), classified as World Health Organization (WHO) grade II and grade III gliomas, comprise a heterogeneous group with a median survival time ranging from 4–13 years. Accurate prediction of the survival times of LGGs remains a major challenge in clinical practice. Methods: We reviewed the expression data of 865 LGG patients from 5 transcriptomics cohorts. The comparative profile of immune genes was analyzed for signature identification and validation. In-house RNAseq and microarray data from the Chinese Glioma Genome Atlas (CGGA) dataset were used as training and internal validation cohorts, respectively. The samples from The Cancer Genome Atlas (TCGA) and GSE16011 cohorts were used as external validation cohorts, and the real-time PCR of frozen LGG tissue samples (n = 36) were used for clinical validation. Results: A total of 2,214 immune genes were subjected to pairwise comparison to generate 2,449,791 immune-related gene pairs (IGPs). A total of 402 IGPs were identified with prognostic values for LGGs. The HOXA9-related and CRH-related scores facilitated identification of patients with different prognoses. An immune signature based on 10 IGPs was constructed to stratify patients into low and high risk groups, exhibiting different clinical outcomes. A nomogram, combining immune signature, 1p/19q status, and tumor grade, was able to predict the overall survival (OS) with c-indices of 0.85, 0.80, 0.80, 0.79, and 0.75 in the training, internal validation, external validation, and tissue sample cohorts, respectively. Conclusions: This study was the first to report a comparative profiling of immune genes in large LGG cohorts. A promising individualized immune signature was developed to estimate the survival time for LGG patients.

The purpose of this study was to investigate the predictive value of standard MR imaging features and apparent diffusion coefficient (ADC) values as specific markers for isocitrate dehydrogenase (IDH)-mutated lower grade gliomas (LGGs). Standard MR imaging features including location, T2-FLAIR mismatch sign, signal heterogeneity, margin, growth pattern, degree of enhancement and peritumoral edema, and ADC parameters of 74 LGGs were retrospectively assessed. The values of these imaging features in predicting IDH genotypes were further analyzed. Inter-rater agreement of T2-FLAIR mismatch sign reached the highest κ value. The specificity of T2-FLAIR mismatch sign to predict IDH-mutated LGGs was 100%. IDH-mutated LGGs also tended to manifest single-lobe invasion, distinct margin, less degree of contrast enhancement and peritumoral edema, and higher normalized minimum and mean ADC than IDH-wildtype LGGs (all P

Background Laser-assisted hatching (LAH) has been widely applied to facilitate blastocyst hatching in IVF-ET treatment, however, the effect of LAH on subsequent development and clinical outcomes of the lower grade cleavage stage embryos (LGCE) remains unknown. Our study aimed at evaluating the effect of LAH on blastocyst formation and the clinical pregnancy outcomes of LGCE embryos after transfer. Methods A total of 608 cycles of IVF/ICSI treatment from November 2017 to September 2019 were included in our study as follows: 296 in the LAH group and 312 in the N-LAH group. The total blastocyst rate, usable blastocyst rate, good-grade blastocyst rate and clinical pregnancy rate were statistically compared between the two groups. Results The total blastocyst rate (50.7% vs 40.2%, P P P = 0.002), usable blastocyst rate (B = 0.478, OR 95% CI = 1.331–1.955, P P > 0.05, respectively). Conclusions A higher proportion of total blastocysts and usable blastocysts can be obtained by LAH in LGCE, which may be beneficial to the outcome of the IVF/ICSI-ET cycle.

Introducción: El plasma rico en plaquetas (PRP) es un biomaterial con alta concentración de plaquetas y factores de crecimiento que favorecen la regeneración de tejidos tras su aplicación en intervenciones quirúrgicas como la exodoncia del tercer molar. Material y métodos: El estudio se realizó con 20 pacientes con necesidad de exodoncia del tercer molar inferior bilateral. Las exodoncias se realizaron en un mismo tiempo quirúrgico y en uno de ellos, escogido aleatoriamente, se aplicó el gel de PRP y el otro tomado como grupo control. La evaluación posoperatoria se llevó acabo posterior a los tres meses; los parámetros evaluados fueron: dolor posoperatorio, curación de herida y densidad ósea mediante tomografía computarizada Cone Beam. Resultados: El dolor posoperatorio durante el tercer día, primera y segunda semana presentó menor grado en los sitios de aplicación de PRP que el grupo control (p

A questionnaire regarding splenic embolization in trauma was submitted to an international sample of IR faculty members, to compare their practice to the available recommendations. A 21 multiple-choice questionnaire was sent to an international cohort of 96 IR faculty. Questions included the initial patient evaluation, embolization materials and techniques, post-procedure management, availability of an institutional protocol, and use of guidelines. For each question, there were from a minimum of 45 to a maximum of 52 responders: 94% require a CT with contrast prior to embolization, and 87% use the American Association for the Surgery of Trauma (AAST) scale to grade the splenic injuries. Embolization is performed across all values of the AAST scale. Of the patients with injuries of grade III or greater, embolization is primarily done for those patients who are hemodynamically stable. Unstable patients are embolized less frequently and primarily in cases in which the injuries are of a lower grade. Coils are the preferred material for proximal embolization (69%). Particles/Gelfoam is the preferred material for distal embolization (38%). In total, 63% administer intravenous antibiotics before the procedure and 15% administer intra-arterial antibiotics during the procedure. After embolization, follow-up imaging is recommended by 87%, antibiotics are administered regularly by 33%, clinical follow-up is recommended by 73%, and vaccination against encapsulated organisms is routinely recommended by 39%. There is significant variability among a heterogeneous cohort of respondents. Available recommendations may not be sufficiently addressing the practice of splenic embolization.

Eyes absent 4 (EYA4) participates in an important role in various cancers. Patients with low EYA4 expression have significantly favorable prognosis compared with those with high EYA4 expression. However, the expression and role of EYA4 in lower grade glioma (LGG) has not been fully elucidated.The R2 and UCSC Xena browser based on data from 284 cases in GSE16011 from Gene Expression Omnibus datasets and 530 cases of patients with LGG in The Cancer Genome Atlas database were extracted for bioinformatic analyses. The EYA4 expression in different subtypes of LGG was detected. Kaplan-Meier survival curves were generated to explore the association between EYA4 expression and overall survival (OS) in both datasets.Patients with LGG with lower EYA4 expression had significantly longer 5- and 10-year OS in 2 datasets (P0.001). By matching histological subtypes and gene expression profiles of patients with LGG, oligoastrocytoma and oligodendroglioma groups had lower EYA4 expression and longer OS compared with the astrocytoma group (P0.05). Patients with IDH1 mutations and 1p19q co-deletion had longer 5- and 10-year OS (P0.001), and EYA4 expression was significantly downregulated in these patients (P0.001).This study suggests that EYA4 can be used as a prognostic marker and provide a potential therapeutic target in patients with LGG with IDH1 mutation and 1p19q co-deletion.

Background While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. Objective To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. Methods IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. Results A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). Conclusion Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

Several studies have examined the prognostic significance of IDH1/2 mutation, 1p/19q codeletion and MGMT promoter methylation in lower-grade gliomas but most of these used the 2007 fourth edition of the WHO classification. We evaluate prognostic significance of these indicators in the 2016 WHO updated fourth edition of CNS tumor classification. A total of 180 intracranial glioma patients diagnosed according WHO 2016 edition between December 2016 and December 2018 Jinling Hospital (Nanjing, China) were reviewed retrospectively. We performed survival analysis on 109 patients with complete molecular pathology and follow-up data. Histologically, 52 were diagnosed as astrocytoma (WHO grade II and III), 17 as oligodendrogliomas (WHO grade II and III) and 40 as GBMs. At last follow-up, 50.5% patients had experienced tumor progression and 34.9% had died. Among grade II and III cases 36.2% experienced tumor progression and 27.5% died. In univariate Kaplan–Meier analysis, multifocal tumor, EGFR mutation or amplification, PIK3CA mutation and IDHwt/TERTpwt group were associated with shorter PFS (p p = 0.003, p = 0.005, p p = 0.010, p = 0.020, p = 0.018, p p = 0.04), MGMTp methylation (HR = 0.095, p = 0.003) and chemoradiotherapy (HR = 0.006, p = 0.002) were independent prognostic factors for OS. Beyond histological classification as well as IDH1/2 mutation, 1p/19q codeletion status, we could incorporate IDH1/2mt combined with TERTpmt, EGFR mutation or amplification and PIK3CA mutation into the diagnostic criteria for DLGGs to supplement WHO 2016 pathological criteria.

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that can progress into invasive ductal carcinoma (IDC). Studies suggest DCIS is often overtreated since a considerable part of DCIS lesions may never progress into IDC. Lower grade lesions have a lower progression speed and risk, possibly allowing treatment de-escalation. However, studies show significant inter-observer variation in DCIS grading. Automated image analysis may provide an objective solution to address high subjectivity of DCIS grading by pathologists. In this study, we developed and evaluated a deep learning-based DCIS grading system. The system was developed using the consensus DCIS grade of three expert observers on a dataset of 1186 DCIS lesions from 59 patients. The inter-observer agreement, measured by quadratic weighted Cohen’s kappa, was used to evaluate the system and compare its performance to that of expert observers. We present an analysis of the lesion-level and patient-level inter-observer agreement on an independent test set of 1001 lesions from 50 patients. The deep learning system (dl) achieved on average slightly higher inter-observer agreement to the three observers (o1, o2 and o3) (κo1,dl = 0.81, κo2,dl = 0.53 and κo3,dl = 0.40) than the observers amongst each other (κo1,o2 = 0.58, κo1,o3 = 0.50 and κo2,o3 = 0.42) at the lesion-level. At the patient-level, the deep learning system achieved similar agreement to the observers (κo1,dl = 0.77, κo2,dl = 0.75 and κo3,dl = 0.70) as the observers amongst each other (κo1,o2 = 0.77, κo1,o3 = 0.75 and κo2,o3 = 0.72). The deep learning system better reflected the grading spectrum of DCIS than two of the observers. In conclusion, we developed a deep learning-based DCIS grading system that achieved a performance similar to expert observers. To the best of our knowledge, this is the first automated system for the grading of DCIS that could assist pathologists by providing robust and reproducible second opinions on DCIS grade., The authors developed a deep-learning-based ductal carcinoma in situ (DCIS) grading system that achieved performance similar to expert observers. To the best of our knowledge, this is the first automated system for the grading of DCIS that could assist pathologists by providing robust and reproducible second opinions on DCIS grade.

A system of fifteen variables (7 morphological and 8 variables for assessing postural status) was applied to a sample of 284 male and female students from the first to the third grade of primary school, with the aim of determining the differences between boys and girls. The results showed that there were statistically significant differences between the examined samples in the following morphological variables: in the first class (body weight and skin fold of the triceps), in the second class (body height, body weight, skin fold of the triceps and skin fold of the biceps) and in third grade (body height, skin fold of triceps, skin fold of back, skin fold of biceps, and skin fold of lower leg). Statistically significant differences in the variables for assessing postural status exist in the following variables: in the first grade (head posture, shoulder posture, shoulder posture, chest shape and leg shape), in the second grade (shoulder posture, chest shape, and spinal deviation in frontal plane) and in the third grade (deviation of the spinal column in the frontal plane, holding the anterior abdominal wall and the shape of the legs). Based on the obtained results, it can be concluded that in the younger school-age in morphology there is a significant sexual dimorphism and with it in connection with the change of postural status.

BACKGROUND AND PURPOSE: Isocitrate dehydrogenase (IDH) wild-type lower-grade gliomas (histologic grades II and III) with epidermal growth factor receptor (EGFR) amplification or telomerase reverse transcriptase (TERT) promoter mutation are reported to behave similar to glioblastoma. We aimed to evaluate whether MR imaging features could identify a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma. MATERIALS AND METHODS: In this multi-institutional retrospective study, pathologically confirmed IDH wild-type lower-grade gliomas from 2 tertiary institutions and The Cancer Genome Atlas constituted the training set (institution 1 and The Cancer Genome Atlas, 64 patients) and the independent test set (institution 2, 57 patients). Preoperative MRIs were analyzed using the Visually AcceSAble Rembrandt Images and radiomics. The molecular glioblastoma status was determined on the basis of the presence of EGFR amplification and TERT promoter mutation. Molecular glioblastoma was present in 73.4% and 56.1% in the training and test sets, respectively. Models using clinical, Visually AcceSAble Rembrandt Images, and radiomic features were built to predict the molecular glioblastoma status in the training set; then they were validated in the test set. RESULTS: In the test set, a model using both Visually AcceSAble Rembrandt Images and radiomic features showed superior predictive performance (area under the curve = 0.854) than that with only clinical features or Visually AcceSAble Rembrandt Images (areas under the curve = 0.514 and 0.648, respectively; P CONCLUSIONS: MR imaging features integrated with machine learning classifiers may predict a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma.

Background Isocitrate dehydrogenase (IDH)-mutant lower-grade gliomas (LGGs) are further classified into two classes: with and without 1p/19q codeletion. IDH-mutant and 1p/19q codeleted LGGs have better prognosis compared with IDH-mutant and 1p/19q non-codeleted LGGs. Purpose To evaluate conventional magnetic resonance imaging (cMRI), diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) for predicting 1p/19q codeletion status of IDH-mutant LGGs. Material and Methods We retrospectively reviewed cMRI, DWI, SWI, and DSC-PWI in 142 cases of IDH mutant LGGs with known 1p/19q codeletion status. Features of cMRI, relative ADC (rADC), intratumoral susceptibility signals (ITSSs), and the value of relative cerebral blood volume (rCBV) were compared between IDH-mutant LGGs with and without 1p/19q codeletion. Receiver operating characteristic curve and logistic regression were used to determine diagnostic performances. Results IDH-mutant and 1p/19q non-codeleted LGGs tended to present with the T2/FLAIR mismatch sign and distinct borders ( P max were significantly different between the 1p/19q codeleted and 1p/19q non-codeleted groups ( P Conclusion 1p/19q codeletion status of IDH-mutant LGGs can be stratified using cMRI and advanced MRI techniques, including DWI, SWI, and DSC-PWI. A combination of cMRI, rADC, ITSSs, and rCBVmax may improve the diagnostic performance for predicting 1p/19q codeletion status.

Immunotherapy is an effective treatment for many cancer types. However, YTHDF2 effects on the prognosis of different tumors and correlation with tumor immune infiltration are unclear. Here, we analyzed The Cancer Genome Atlas and Gene Expression Omnibus data obtained through various web-based platforms. The analyses showed that YTHDF2 expression and associated prognoses may depend on cancer type. High YTHDF2 expression was associated with poor overall survival in lower-grade glioma (LGG). In addition, YTHDF2 expression positively correlated with expression of several immune cell markers, including PD-1, TIM-3, and CTLA-4, as well as tumor-associated macrophage gene markers, and isocitrate dehydrogenase 1 in LGG. These findings suggest that YTHDF2 is a potential prognostic biomarker that correlates with LGG tumor-infiltrating immune cells.

Purpose Incidentally discovered diffusely infiltrating lower-grade gliomas (incidental LGGs, iLGGs) are defined as gliomas occasionally found in patients without tumor-related symptoms. At present, very few in-depth research studies on incidental LGGs were reported. We aimed to find out the inherent difference between iLGGs and LGGs with tumor-related symptoms. Patients and methods We enrolled 2486 all-grade gliomas and screened 1594 lower-grade gliomas for further analysis. Medical records were retrospectively reviewed for iLGGs. Clinical and mRNA sequencing data were collected for in-depth analysis. Results We found that with increasing grade, the proportion of incidental glioma patients decreased obviously. In 1594 patients who underwent craniotomy for LGG, 80 (5%) patients were discovered incidentally. Grade II patients (88%) and patients bearing 1p/19q co-deletion in their tumors (23%) were more likely to be diagnosed as iLGGs. Regular radiological screening (48%) and trauma (24%) were the main complaint for brain imaging for iLGGs. Kaplan-Meier survival analysis indicated that iLGGs patients lived a significantly longer survival and Cox regression analysis revealed that iLGGs were an independent indicator of better prognosis. Subsequent gene set enrichment analysis and differential expression analysis based on the gene expression profile revealed that mitochondrial aerobic respiration process was enriched in iLGGs. Moreover, we found that iLGGs tended to generate energy by unique mitochondrial aerobic respiration. Conclusion These results provided a primitive exploration of iLGGs, which may potentially assist clinical neurosurgeons with personalized management of iLGGs.

Tumour microenvironment of brain lower grade glioma (LGG) consists of non‐tumour cells including stromal cells and immune cells mainly. These non‐tumour cells dilute the purity of LGG and play pivotal roles in tumour growth and development, thereby affecting patient prognosis. Tumour purity is also associated with molecular subtypes of LGG. In this study, we discovered the most relevant module to purity by weighted gene co‐expression network analysis (WGCNA) and afterwards performed consensus network analysis and survival analysis to filter 61 significant genes related to both purity and prognosis. In turn, we built a simplified model based on the calculation of purity score, and consensus measurement of purity estimation (CPE), with a satisfactory predictive performance by random forest regression. HLA‐E, MSN, GNG‐5, MYL12A, ITGB4, PDPN, AGTRAP, S100A4, PLSCR1, VAMP5 were selected as the most relevant genes correlating to both purity and prognosis. The risk score model based on the 10 genes could moderately predict patients’ overall survival. These 10 genes, respectively, were positively correlated positively to immunosuppressive cells like macrophage M2, but negatively correlated to patient prognosis, which may explain partially the poor prognosis with low‐purity group.

The purpose of this study was to examine how to conduct the dietary education of elementary school students more efficiently by adding dietary education content into the total school curriculum. To investigate dietary education delivered within school curriculum, the changes in dietary education in the area of practical education, from the first curriculum to the 2015 revised curriculum, are education on the production and supply of food, education on nutrition and health, and etiquette. It was conducted according to the flow of social change in the order of education, experience education on health and food making, and so on. Also, when compared to other countries, the curriculum and the time of education were presented in the domain of one curriculum rather than in a separate cirriculum. In 2018, the KFDA was divided into elementary, lower grade, middle grade, and high grades to provide education on health, etiquette, safety, and the environment in the 7th unit into education, and in 2019, eat less salty and less sweet, the education plan is divided into practice from thinking openness to practice, and it is understood that nutrition, food, especially food safety, proper eating habits, and cooking are the main educational content topics. The analysis framework results showed that using the food education materials produced by the governmental departments provided a more practical and diverse education.

The importance of genomic information in intrinsic brain tumors is highlighted in the World Health Organization (WHO) 2016 classification of gliomas, which now incorporates both phenotype and genotype data to assign a diagnosis. By using genetic markers to both categorize tumors and advise patients on prognosis, this classification system has minimized the risk of tissue sampling error, improved diagnostic accuracy, and reduced inter-rater variability. In the neurosurgical community, it is critical to understand the role genetics plays in tumor biology, what certain mutations mean for the patient's prognosis and adjuvant treatment, and how to interpret the results of sequencing data that are generated following tumor resection. In this review, we examine the critical role of genetics for diagnosis and prognosis and highlight the importance of tumor genetics for neurosurgeons caring for patients with diffuse lower grade gliomas.

The most recent cIMPACT-NOW update highlighted the homozygous deletion of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene as a clinically important molecular alteration in IDH-mutant glioma. Correspondingly, we systematically reviewed the contemporary literature to affirm the contemporary stance of the literature on the prognostic significance of this alteration in this setting based on the current World Health Organization (WHO) Grade classification. A systematic search of seven electronic databases from inception to February 2020 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria to include lower-grade glioma (LGG, WHO Grade II/III) and glioblastoma (GBM, WHO Grade IV) separately. Progression free survival (PFS) and overall survival (OS) from Kaplan–Meier and multivariable analyses were outcomes of interest. Nine institutional studies describing 2193 IDH-mutant gliomas satisfied criteria for evaluation, with 1756 (80%) LGG and 437 (20%) GBM. When reported, the proportion of CDKN2A homozygous deleted gliomas ranged from 9 to 43%, with a median incidence of 22%. For LGG, Kaplan–Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in three studies (median values, 31 versus 91 months), and shorter OS in five studies (median values, 61 versus 154 months). For GBM, Kaplan–Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in two studies (median values, 16 versus 30 months), and shorter OS in four studies (median values, 38 versus 86 months). By multivariable analyses, CDKN2A homozygous deletion was a predictor of significantly shorter PFS and OS in both LGG and GBM across all included studies. The CDKN2A homozygous deletion is an important prognostic factor for survival outcomes of IDH-mutant glioma patients across multiple histologic WHO grades with specific molecular features likely dependent on IDH-mutant status. Greater understanding of how identifying this deletion can assist in the stratification of management for these tumors to optimize clinical course is required.

Background/aim Understanding of the molecular events associated with progression and survival differences in patients with lower-grade gliomas (LGGs) is still unclear. The comparison of findings across studies using different datasets and methods is essential for a new molecular-based classification system. The aim of the study was to identify biomarkers for prognostic classification of patients with LGGs, and furthermore to lay a foundation for future development of targeted therapies for LGGs. Patients and methods Using information-theoretic and statistical approaches, we analyzed mRNA expression data for 18,413 genes from LGG samples in order to identify candidate biomarkers for survival. The candidate genes were then evaluated for their potential as prognostic biomarkers using multivariable Cox regression analyses that adjusted for the effects of age and grade. Results WEE1, EMP3, E2F7, CD58 and NSUN7 genes were identified as candidate biomarkers of LGGs and their high expression was associated with significantly shorter survival. The hazard ratios for mortality were 5.02 (95% CI=3.40-7.40) for WEE1, 5.45 (95% CI=3.63-8.18) for EMP3, 4.49 (95% CI=3.03-6.66) for E2F7, 4.77 (95% CI=3.22-7.06) for CD58 and 4.38 (95% CI=2.97-6.47) for NSUN7. In addition, the expression pattern of these genes, associated with shorter survival in LGGs, was also observed in glioblastoma multiforme. Conclusion Identification of genes associated with poor outcomes will provide insights into novel biological mechanisms that may lead to improvement in progression and survival for patients with LGGs.

BACKGROUND AND PURPOSE: Despite the improved prognostic relevance of the 2016 WHO molecular-based classification of lower-grade gliomas, variability in clinical outcome persists within existing molecular subtypes. Our aim was to determine prognostically significant metrics on preoperative MR imaging for lower-grade gliomas within currently defined molecular categories. MATERIALS AND METHODS: We undertook a retrospective analysis of 306 patients with lower-grade gliomas accrued from an institutional data base and The Cancer Genome Atlas. Two neuroradiologists in consensus analyzed preoperative MRIs of each lower-grade glioma to determine the following: tumor size, tumor location, number of involved lobes, corpus callosum involvement, hydrocephalus, midline shift, eloquent cortex involvement, ependymal extension, margins, contrast enhancement, and necrosis. Adjusted hazard ratios determined the association between MR imaging metrics and overall survival per molecular subtype, after adjustment for patient age, patient sex, World Health Organization grade, and surgical resection status. RESULTS: For isocitrate dehydrogenase (IDH) wild-type lower-grade gliomas, tumor size (hazard ratio, 3.82; 95% CI, 1.94–7.75; P

Objectives: FOSL1 is overexpressed in multiple cancers including malignant glioma and contributes to different cellular processes. However, little attention has been paid to the lower grade glioma ...

Objective: To analyze the prognostic effects of age in different tumor types and determine the prognostic significance of age related genes in patients with lower grade glioma (LGG). Methods: The relationships between age and tumor overall survival were determined by Kaplan-Meier survival analysis using The Cancer Genome Atlas (TCGA) dataset. The age related genes were identified using TCGA RNA-seq data. Univariate and multivariate cox regression were used to determine the prognostic significance of age related genes. The results derived from TCGA dataset were further validated using Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) datasets. Results: Age at initial pathologic diagnosis was most associated with the overall survival of LGG patients than other types of tumor patients. Age related genes EMP3, IGFBP2, TIMP1 and SERPINE1 were highly expressed in old LGG patients. The hypo-methylations of EMP3 and SERPINE1 were contributing to the high expressions of EMP3 and SERPINE1 in old LGG patients. Also, EMP3, IGFBP2, TIMP1 and SERPINE1 were highly expressed in LGG tumor tissues, compared with normal brain tissues. Moreover, high expressions of IGFBP2, EMP3, TIMP1 and SERPINE1 were associated with the worse prognosis of LGG patients. Furthermore, we demonstrated that EMP3 and SERPINE1 were connected with each other and the combination of EMP3 and SERPINE1 had better prognostic effects in glioma patients. Conclusions: Age related genes IGFBP2, EMP3, TIMP1 and SERPINE1 have significant prognostic effects in LGG patients.

Background. Glioma is the most common and lethal tumor in the central nervous system (CNS). More than 70% of WHO grade II/III gliomas were found to harbor isocitrate dehydrogenase (IDH) mutations which generated targetable metabolic vulnerabilities. Focusing on the metabolic vulnerabilities, some targeted therapies, such as NAMPT, have shown significant effects in preclinical and clinical trials. Methods. We explored the TCGA as well as CGGA database and analyzed the RNA-seq data of lower grade gliomas (LGG) with the method of weighted correlation network analysis (WGCNA). Differential expressed genes were screened, and coexpression relationships were grouped together by performing average linkage hierarchical clustering on the topological overlap. Clinical data were used to conduct Kaplan–Meier analysis. Results. In this study, we identified ACAA2 as a prognostic factor in IDH mutation lower grade glioma with the method of weighted correlation network analysis (WGCNA). The difference of ACAA2 gene expressions between the IDH wild-type (IDH-WT) group and the IDH mutant (IDH-MUT) group suggested that there may be different potential targeted therapies based on the fatty acid metabolic vulnerabilities, which promoted the personalized treatment for LGG patients.

Diffuse low-grade and intermediate-grade gliomas, also known as lower-grade gliomas (LGGs), are a class of central nervous system tumors. Overall survival varies greatly between patients, highlighting the importance of evaluating exact outcomes to facilitate individualized clinical management. We aimed to identify an mRNA-based prognostic signature to predict the survival of patients with LGGs. A total of 874 LGGs from two public datasets were included. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most prognostic mRNAs and build a risk score. A nomogram incorporating the risk score and clinical factors was established for individualized survival prediction. The performance of the nomogram was assessed in the training set (329 patients), internal validation set (140 patients), and external validation set (405 patients). 21 most prognostic mRNAs remained following the LASSO Cox regression. The 21-mRNA signature successfully stratified patients into high- and low-risk groups (P

Creating in vitro models of lower grade glioma represents a major challenge in neuro-oncology research. There are few such models that are tractable and widely used, which has hindered understanding of the biology of these tumors. Recently, substantial progress has been made in generating patient-derived in vitro organoid models of high grade glioma, but modeling lower grade disease remains difficult. Based on our experience creating neurosphere cultures of lower grade astrocytomas from genetically engineered mice, we hypothesized that modifying patient-derived organoid generation protocols to incorporate physiological oxygen levels would allow establishment and propagation of lower grade glioma organoids. In this study, we show that this approach supports efficient organoid model generation from primary glioma specimens across all histological subtypes and tumor grades (WHO Grade I-IV, n = 20). These organoid models retain key characteristics of their respective parental tumors, including IDH mutations and other genetic alterations, metabolite profiles, intratumoral heterogeneity, cellular composition, and cytoarchitectural features. Importantly, lower grade glioma organoids can be cultured for months and reanimated after biobanking. Our high success rate ( >90%) in establishing organoid models from primary lower grade glioma tissue samples further highlighted opportunities for treatment response assessments. To perform longitudinal measurements of therapy-induced changes in glioma organoid viability, we designed a novel, non-invasive imaging assay (termed rapid apex imaging) to determine real-time treatment response in low and high grade gliomas. We evaluated longitudinal responses of glioblastoma and IDH1 R132H-positive Grade II astrocytoma organoids to temozolomide and olaparib with and without radiation treatment. We quantified topological changes in organoid structure by building a bioinformatics tool to translate imaging data into a cellularity metric as a biomarker of organoid response. Our work unveils an effective new method to create in vitro, personalized models of lower grade glioma that supports elucidation of treatment sensitivity profiles.

Comprehensive diagnostic using histological and molecular characteristics began to be implemented in WHO 2016 but the relevance of oligodendroglial histological features to patients’ prognoses is still controversial. To elucidate the connection between oligodroglial histology and patient’s prognoses we analyzed 93 LrGGs resected for about 2 decades were reassessed for histological features based on WHO2007 with special interest to pure oligodendroglial diagnosis (namely, oligodendroglioma or anaplastic oligodendroglioma) and presence of classic for oligodendroglioma (CFO) features. Those histological features, patients’ OS, and tumor chromosomal/genetic characteristics were correlated each other in each of the 3 IDH-1p/19q based molecular groups. The reassessed morphology-based diagnosis was shown to be most strict for astrocytic, but loosened for oligodendroglial tumors as compared with the original institutional diagnoses and WHO2016. The pure oligodendroglial diagnosis by reassessment was associated with longer OS in IDHmut/codel group, but not in IDHmut/noncodel and IDH-wildtype groups. The presence of CFO was not associated with patients’ OS in any molecular groups. Gain of 8q was associated with the oligodendroglial diagnosis in IDHmut/noncodel group. Neither the oligodendroglial diagnosis nor CFO was predictive for the methylation status of the MGMT gene in any of the 3 molecular groups. NGS of the IDHmut/codel tumors suggested that mutations in the FUBP1 and CIC genes might be associated with poor prognosis. The oligodendroglial histological feature is not independently predictive for either patients’ prognosis or chemotherapeutic response in LrGGs, except the oligodendroglial diagnosis in IDHmut/codel tumors.

Background Lower-grade gliomas (LGGs) patients presented seizure-free have a worse survival than those presented with seizures. However, the current knowledge on its potential value in LGGs remains scarce. Purpose This study aimed to identify a novel gene signature associated with seizures-free for predicting poor prognosis for LGGs patients. Materials and Methods The RNA expression and clinical information of LGGs patients were downloaded from the Cancer Genome Atlas database. Differentially expressed genes (DEGs) were screened out between LGGs patients presented seizures-free and seizures. The novel gene signature was constructed by Lasso and multivariate regression analyses for predicting prognosis in LGGs. Its prognostic value was assessed and validated by Kaplan–Meier analyses and receiver operating characteristic (ROC) curves. Multivariate regression analysis was applied to identify the independent prognostic value of the gene signature. Furthermore, bioinformatics analysis was performed to elucidate the molecular mechanisms. Results A total of 253 DEGs were screened out between LGG patients presented with seizures and free of seizures. A 5-gene signature (HIST1H4F, HORMAD2, LILRA3, PRSS33, and TBX20 genes) was constructed from these 253 DEGs. Kaplan–Meier analyses and ROC curves assessed and validated the good performance of the 5-gene signature in differentiating and predicting prognosis of high- and low-risk patients. Multivariate regression analysis determined the independent prognostic value of the 5-gene signature. According to bioinformatics analysis, DEGs were mainly enriched in biological processes related to positive regulation of transcription from RNA polymerase II promoter, G-protein coupled receptor signaling pathway, and pathways of cytokine–cytokine receptor interaction, chemokine signaling pathway. Conclusion Our findings suggested that the 5-gene signature might serve as a potential prognostic biomarker and provide guidance for the personalized LGGs management., Graphical Abstract

Background: Tumor-infiltrating immune cells (TIICs), which play a pivotal role in the tumor microenvironment, are intimately related to tumor progression and clinical outcome. It remains unclear which factors influence tumor immune infiltration in lower-grade gliomas (LGGs). TEAD4 (TEA Domain Transcription Factor 4) is an essential member of the Hippo pathway that is involved in cancer progression, epithelial-mesenchymal transition, metastasis, and cancer stem cell function across multiple types of cancers. However, the prognostic value of TEAD4 and its association with TIICs in LGG have been hardly studied. Methods: LGG data were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). TEAD4 expression between different groups was compared by R and survival analysis was implemented by Kaplan–Meier curves. In Virto experiments were conducted to investigate the role of TEAD4 in glioma cells. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network were used to investigate the differential biological processes and signaling pathways. Multiple computational methods were employed to estimate the association between TEAD4 expression and tumor microenvironment in LGG. Correlations were analyzed by Spearman correlationResults: TEAD4 expression was up-regulated in higher-grade gliomas and correlated with a poorer clinical outcome. Glioma cell proliferation and migration were promoted by TEAD4 overexpression. GSEA and PPI network indicated that multiple immune-related pathways and hub genes were closely associated with TEAD4 expression in LGG specimens. TEAD4 expression was negatively associated with glioma purity. Multivariate Cox regression analysis indicated that TEAD4 expression and tumor purity were independent prognostic factors in LGG. TEAD4 expression was positively correlated with the infiltration of multiple immune cells, including plasma cells, CD8+ T cells, and macrophages M1 and M2. Correlation analysis showed that the TEAD4 level can predict the efficacy of immune checkpoint blockade therapy. Conclusions: TEAD4 is highly related to glioma malignancy grades and multiple immune cell infiltration, suggesting TEAD4 can serve as a new biomarker for anti-cancer therapies in LGG.

Background: Glutathione peroxidase-7 (GPX7), a newly discovered non-selenium-containing protein with glutathione peroxidase activity, is located near the endoplasmic reticulum. Various studies have reported the involvement of GPX7 in cancer disease progression. However, the expression patterns of GPX7 and its prognostic potential have not been evaluated from a pan-cancer perspective. Moreover, the relationship between GPX7 and prognosis in Brain Lower Grade Glioma (LGG) patients remains unclear.Methods: Expression levels of GPX7 were evaluated using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA2) were used to evaluate the effect of GPX7 on clinical prognosis in TCGA tumors. Correlations between GPX7 and cancer immune infiltrates were investigated using the Tumor Immune Estimation Resource (TIMER) site and Estimating the Proportions of Immune and Cancer cells (EPIC) algorithm. In addition, the GEPIA2 and STRING websites were used for enrichment analysis of GPX7-related genes. Finally, we constructed a prognostic Nomogram for LGG to verify the overall survival (OS) outcomes of patients.Results: GPX7 was found to be overexpressed in multiple tumors. Elevated expression levels of GPX7 were associated with poor prognosis regarding OS, disease-free survival (DFS) and progression-free survival (PFS) of LGG patients (OS Hazard ratio (HR) = 1.044, p < 0.0001; DFS HR = 1.035, p < 0.0001; PFS HR = 1.045, p < 0.0001). Concordance index (C-index) of the nomogram for LGG was 0.845 (95% CI, 0.825 to 0.865; p < 0.001). The nomogram exhibited a better predictability. In addition, GPX7 expression and the abundance of Cancer-associated fibroblasts (CAFs) were positively correlated in most cancer types. Enrichment analysis revealed that GPX7 may be involved in the glutathione derivative biosynthetic and glutathione metabolic biological processes.Conclusion: GPX7 was found to be upregulated in multiple tumors, which was correlated with poor prognosis in LGG. Therefore, GPX7 is a potential prognostic indicator for LGG. There is a strong correlation between GPX7 expression levels and glutathione metabolic pathways. GPX7 holds promise for the use of glutathione metabolism for guided therapy in cancer patients.

High incidence of recurrency had been a significant threat among glioma patients. Moreover, the performance of traditional therapies among recurrent gliomas was far from satisfying. Advances in the tumor microenvironment (TME) and immune responses on the brain inspired immunotherapy researches. Nevertheless, verification of classic PD-1/PD-L1 inhibitors failed in phase III clinical trials. Additional gene targets were required for future studies among glioma patients. Immune cell infiltration (ICI) scores, defined based on multiple prognostic genes, were proved as the marker for the sensitivity of immunotherapies in many tumors. However, relevant results were not reported in gliomas. In the study, a retrospective cohort of 495 patients was classified into two ICI score subgroups. High ICI scores were closely related to high tumor mutation burden (TMB) values, indicating a high instability of genes. Furthermore, ICI scores were proved as reliable prognostic predictors. And a predictive model was built based on the ICI scores and multiple clinical features. The model showed its superiority through both internal validation and external validation. The ICI scores and the predictive model showed significant clinical values through decision curve analysis (DCA) since high ICI scores were related to high sensitivity for treatment. The prognostic immune-related gene list provided targets for immunotherapy researches.

Background: Lower-grade gliomas (LGG) are a diverse group of primary brain tumors with relatively poor overall survival in young adults. In this study, we aimed to establish novel method that are effectively predictive of prognosis of LGG patients. Methods: We detected and validated prognosis-associated genes using gene expression and c`Clinical data of LGG patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. We then established a novel prognostic 71-gene score and 17-gene nomograms and analyzed their relationship with overall survival (OS) and relapse-free survival (RFS) in LGG patients. We also performed Gene Set Enrichment Analysis to investigate the altered signalling pathways associated with the 71-gene score phenotype and hierarchical clustering analysis of 71 genes to detect subgroups of LGG patients with distinct clinical characteristics. Results: We identified 1489 genes significantly correlated with patients’ prognosis in LGG. The 71-gene score was predictive of favourable OS and RFS in LGG patients independently of clinicopathological characteristics. The wnt signalling pathway, glutathione metabolism, primary immunodeficiency, galactose metabolism were the potential pathways involved in the prognostication of the 71-gene score. Hierarchical clustering analysis of the 71 genes revealed three subgroups of LGG patients in the TCGA dataset. The cluster2 LGG tumours were associated with higher grade, more frequent radiation therapy, poorer OS and RFS than cluster1 and cluster3 tumours. The 71-gene nomogram incorporating the survival‐related clinical factors showed good prediction accuracies for overall survival, 3-year and 5‐year survival (area under curve [AUC] = 0.79, 0.67 and 0.75 respectively). Conclusions: The 71-gene nomogram may turn out to be a useful and robust method to remarkably ameliorate the prognostic prediction in LGG.

Lower grade gliomas (LGGs) are heterogenous diseases by clinical, histological and molecular criteria. Here, we developed a machine learning pipeline to extract cellular morphometric biomarkers from whole slide images of tissue histology; and identified and externally validated robust cellular morphometric subtypes of LGGs in multi-center cohorts. The subtypes have significantly independent predictive power for overall survival across all three independent cohorts. In the TCGA-LGG cohort, we found that patients within the poor-prognosis subtype responded poorly to primary therapy and follow-up treatment. Furthermore, LGGs within the poor-prognosis subtype were characterized by higher mutational burden, higher frequencies of copy number alterations, and higher level of tumor-infiltrating lymphocytes and immune checkpoint genes. Higher level of PD-1/PD-L1/CTLA-4 was confirmed by immunohistochemical staining. In addition, the subtypes learned from LGG demonstrates translational impact on Glioblastoma (GBM). Overall, we developed and validated a framework for the cellular morphometric subtype discovery in LGGs associated with specific molecular alterations, immune micro-environment, prognosis and treatment response.

Context.— Multifocal prostate cancer at radical prostatectomy (RP) may be graded with assessment of each individual tumor nodule (TN) or global grading of all TNs in aggregate. Objective.— To assess case-level grade variability between these 2 grading approaches. Design.— We reviewed 776 RPs with multifocal prostate cancer with 2 or more separate TNs of different Grade Groups (GGs). Two separate grades were assigned to each RP: one based on the TN with the highest grade and a global grade based on the Gleason pattern volumes for all TNs. We then compared the results of these 2 methods. Results.— The case-level grade changed by 1 or more GGs between the 2 grading methods in 35% (132 of 374) of GG3 through GG5 cases. Twelve percent (37 of 309) of GG2 cases with Gleason pattern 4 of more than 5% based on individual TN grading decreased their Gleason pattern 4 to less than 5% based on the global approach. Minor tertiary pattern 5 (Gleason pattern 5 Conclusions.— The global grading approach resulted in a lower grade in 35% of GG3 through GG5 cases compared with grading based on the highest-grade TN. Two significant risk factors for this discrepancy with a global grading approach occur when the highest-grade TN has a relatively small tumor volume and with a higher number of TNs per RP. The observed grade variability between the 2 grading schemes most likely limits the interchangeability of post-RP multi-institutional databases if those institutions use different grading approaches.

Fine needle aspiration cytology (FNAC) is a commonly performed procedure for parotid masses, although its accuracy in detecting malignancies widely varies through different series. We evaluated our single-center cohort of parotidectomies to highlight possible limitations of preoperative FNAC. Seven hundred and eighteen consecutive patients submitted to parotid surgery at San Raffaele Scientific Institute (Milan) were retrospectively evaluated (2002–2018). Five hundred and fifty four FNAC were analyzed. FNAC accuracy was assessed with and without inclusion of “inconclusive” results. The peculiar role of lower grade primary parotid cancers was investigated. FNAC reports were “diagnostic” in 502 cases (90.4%) and “inconclusive” in 52 (9.6%). Histopathology revealed 488 benign lesions (88.1%) and 66 malignancies (11.9%). FNAC sensitivity, specificity, PPV, NPV and accuracy in detecting malignancies were 59%, 99%, 89%, 95%, and 95%, respectively. Sensitivity fell to 48%, when “inconclusive” FNAC was computed. Within 66 parotid cancers, FNAC could discriminate malignancy in 32 cases (48.5%), provide proper grading in 21 (31.8%), and precise histopathological diagnosis in 15 (22.7%). Malignancy was more likely in patients with “inconclusive” FNAC than in those with “diagnostic” cytologies (23.1% vs 10.8%, p = 0.003). Low-intermediate-grade primary parotid cancers were associated to a higher rate of FNAC failure in comparison with high-grade ones (86.4% vs 19.0%; p

Background Gliomas are the most common primary malignant brain tumor. Diffuse low-grade and intermediate-grade gliomas, which together compose the lower-grade gliomas (LGGs; World Health Organization [WHO] grades II and III), present a therapeutic challenge to physicians due to the heterogeneity of their clinical behavior. Nomograms are useful tools for individualized estimation of survival. This study aimed to develop and independently validate a survival nomogram for patients with newly diagnosed LGG. Methods Data were obtained for newly diagnosed LGG patients from The Cancer Genome Atlas (TCGA) and the Ohio Brain Tumor Study (OBTS) with the following variables: tumor grade (II or III), age at diagnosis, sex, Karnofsky performance status (KPS), and molecular subtype (IDH mutant with 1p/19q codeletion [IDHmut-codel], IDH mutant without 1p/19q codeletion, and IDH wild-type). Survival was assessed using Cox proportional hazards regression, random survival forests, and recursive partitioning analysis, with adjustment for known prognostic factors. The models were developed using TCGA data and independently validated using the OBTS data. Models were internally validated using 10-fold cross-validation and externally validated with calibration curves. Results A final nomogram was validated for newly diagnosed LGG. Factors that increased the probability of survival included grade II tumor, younger age at diagnosis, having a high KPS, and the IDHmut-codel molecular subtype. Conclusions A nomogram that calculates individualized survival probabilities for patients with newly diagnosed LGG could be useful to health care providers for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free online software for implementing this nomogram is provided: https://hgittleman.shinyapps.io/LGG_Nomogram_H_Gittleman/. Key Points 1. A survival nomogram for lower-grade glioma patients has been developed and externally validated. 2. Free online software for implementing this nomogram is provided allowing for ease of use by practicing health care providers.

Background: Face-lifting procedures are often performed to hide the effects of aging. Thread-lifting, a minimally invasive technique for the correction of facial aging, has become increasingly popular, and various materials for the procedure have been developed. Objective: This study compared tissue responses to two types of threading sutures placed under rat skin: polypropylene (PP) monofilament mesh suspension thread (a novel face-lifting material) and polydioxanone (PDO) barbed thread. Methods: Eight rats each were assigned to the PP monofilament mesh suspension, PDO barbed thread, and control groups. Tissue reactions were evaluated 28 days after subcutaneous loading of the materials. Results: Significant increases in tensile strength and the mean area occupied by collagen fibers were evident in skin loaded with PDO barbed thread and PP monofilament mesh suspension thread compared to control skin (p＜0.05). Compared to sites loaded with PDO barbed thread, those loaded with PP monofilament mesh suspension thread showed a significant increase in the number of collagen fibers and a lower grade of inflammation (p＜0.05). Conclusion: PP monofilament mesh suspension thread has skin-rejuvenating effects comparable to those of PDO barbed thread, but induces a less severe inflammatory response. This indicates that it is a safe and effective material for use in thread-lifting procedures on aging skin. (Ann Dermatol 31(6) 645∼653, 2019)

Presacral masses associated with anorectal malformations (ARM) are most frequently dermoid or teratomas. Sacrococcygeal teratoma (SCT), in isolation, is a different condition. There are limited data comparing the two. The aim of this study was to compare presacral masses associated with ARM and isolated SCTs. A retrospective review was performed from 1979 to 2018. Patients with presacral masses and associated ARM (n = 39) were identified and compared to patients with isolated SCTs (n = 32). Those with presacral mass and ARM had a lower proportion of immature and mixed teratomas by pathology and a longer time to mass resection. They had higher percentages of sacral anomalies (76% versus 9%), tethered cord (50% versus 6%), and other anomalies (51% versus 9%). For long-term bowel function, patients with presacral mass and ARM were more likely to be fecally incontinent and require enemas (59% versus 11%). Regarding isolated SCTs, 4% recurred with a time to recurrence of 7 months. Compared to patients with isolated SCT, patients with presacral mass and ARM had lower grade tumors. In addition, they had a higher proportion of sacral defects and other congenital defects, as well as worse bowel function outcomes.

Marjolin's tumor is a term used to describe a malignancy developing in the setting of a chronic wound, infection, or other tissue subject to chronic inflammatory changes. These malignancies usually present after many years of chronicity, and can range from lower grade basal cell carcinomas to high-grade sarcomas. We present the case of a squamous cell carcinoma that developed within a chronic periprosthetic infection of a total knee arthroplasty of 7 years duration. The intra-articular location, association with an orthopaedic implant, and brief latency period are all unique features of this case.

Incidence and treatment of blunt thoracic aortic injury (BTAI) has evolved, likely from improved imaging and emergence of endovascular techniques; however, multicenter data demonstrating this are lacking. We examined trends in incidence, management, and outcomes in BTAI.The American College of Surgeons National Trauma Databank (2003 to 2013) was used to identify adults with BTAI. Management was categorized as nonoperative repair, open aortic repair (OAR), or thoracic endovascular repair (TEVAR). Outcomes included demographics, management, and outcomes.There were 3,774 patients. Median age was 46.0 years (interquartile range [IQR] 29.3, 62.0 years), with 70.8% males, and median Injury Severity Score (ISS) of 34.0 (IQR 26.0, 45.0). The number of BTAIs diagnosed over the decade increased 196.8% (p0.001), median ISS decreased from 38 to 33 (p0.001), and significantly more patients were treated at a level I trauma center (p0.001). After FDA approval of TEVAR devices, there was a significant increase in endovascular repair overall (1.0% to 30.6%, p0.001) and in those treated operatively (0.0% to 94.9%, p0.001), with a marked decrease in OAR. Use of TEVAR was associated with significantly reduced median ICU LOS (9.0 vs 12.0 days, p = 0.048) and mortality (9.3% vs 16.6%; p = 0.015) compared with OAR. In modern BTAI care, TEVAR has nearly completely replaced OAR.The diagnosis of BTAI has increased, likely due to more sensitive imaging. Nearly 70% of patients get nonoperative care. Treatment with TEVAR improves outcomes relative to OAR. Part of the proportional increase in TEVAR use may represent overtreatment of lower grade BTAI amenable to medical management, and warrants further investigation.

The Steel Policy of India, 2017 aspires to achieve 300 million tonnes of steel-making capacity by 2030. This would translate into additional consumption of manganese and chrome ore other than iron ore as essential raw material for steel making. Similarly, ferro-alloys are one of the important inputs in the manufacture of alloys and special steel. The growth of the ferro-alloy industry is, thus, linked with the development of the iron and steel industry. With the abundant resources, there is huge potential of manganese ore and chromite and ferro-alloy industry in India. India has huge resources of manganese and chrome but the import of these minerals is increasing. Due to limited availability of high-grade manganese ore and chromite reserve in the country, lower grade ore has to be upgraded by beneficiation.

Surgery for lower grade glioma requires the use of brain mapping techniques to identify functional boundaries, which represent the limit of the resection. Two stimulation paradigms are currently available and their use should be tailored to the clinical context to extend tumor removal and decrease the odds of postoperative permanent deficits.

Objectives: The purpose of this study was to evaluate the relationship between exercise time and musculoskeletal problems and to determine the appropriate amount of exercise for children in both lower- and higher-grade levels of elementary and junior high schools. Materials and Methods: Mark-sheet-type questionnaires were distributed to and collected from all elementary and junior high schools in two cities. We collected 22,494 questionnaires in total. The relationship between exercise time and musculoskeletal problems was analyzed. The χ2 test and multivariate logistic regression analysis were used for statistical analyses. Results: The mean exercise time in school, in addition to physical education time, was 3.1 hours per week. In 56% of the children, the exercise time was less than 2 hours per week, and in 13% of the children, the exercise time was more than 10 hours per week. Although the rate of sports injury increased with an increase in exercise time, the duration of one-leg stand (a test of balance and muscle strength) also increased with an increase in exercise time. The cut-off values for sports injuries in boys/girls were 2.9/2.9 hours, 4.0/2.9 hours, and 7.5/4.2 hours in lower grade elementary school, higher grade elementary school, and junior high school, respectively. Conclusions: Although an appropriate amount of exercise improves one’s physical health and ability, excessive exercise leads to musculoskeletal problems. Approximately 7 hours/week of exercise is recommended for junior high school students. In elementary school, the exercise time should be carefully decided as the musculoskeletal system of the students is still immature.

We propose a novel class of multimodal image features based on the joint intensity matrix (JIM) to model fine-grained texture signatures in the radiomic analysis of lower grade glioma (LGG) tumors. Experiments use expanded JIM features to predict the genetic status and the survival outcome of LGG patients with preoperative T1-weighted, T1-weighted post-contrast, fluid attenuation inversion recovery (FLAIR), and T2-weighted MR images from The Cancer Imaging Archive ($\text{n}=107$ ). Texture features were extracted from regions of interest labeled by a radiation oncologist and summarized by 19 parameters. These parameters are then used to contrast mutant and wild gene type groups (i.e., IDH1, ATRX, TP53, and 1p/19q codeletion) via the Wilcoxon test, and to compare short and long survival patient groups with the Kaplan-Meier estimator. Random forest (RF) classification is employed to predict gene status (i.e., mutation or wild) and survival outcome (i.e., short or long survival), as well as to identify highly group-informative features. A subset of JIM features show statistically significant relationships with LGG gene status (i.e., in IDH1 and ATRX, with corrected p

Background and objectives: Recurrent malignancies had become a significant problem for the treatment of gliomas. Though immunotherapy was regarded as a possible solution, verification of immune-checkpoint inhibitors in multiple clinical cases failed. We aimed to explore target genes for immunotherapy and evaluate the genes through new scoring criteria.Methods: We firstly classified the patients through k-means clustering in immune cell level and gene level. Differential prognostic genes were weighted through principal component analysis (PCA) and Boruta algorithm. The comprehensive scoring of each component was defined as the ICI score. We further analyzed the relationship between ICI score and various clinical factors and prognosis. Moreover, a nomogram based on the ICI scores was built and validated through both internal and external validation.Results: The study cohort finally enrolled 495 patients. We identified a list of differential genes of which the expression level was closely related to prognosis. ICI scores were calculated for each case according to the expression level of prognostic genes. The cases in high ICI score group showed significantly lower survival probabilities (log-rank test; pConclusions: The differential genes were listed for further studies. ICI score had been confirmed to be closely related to prognosis and even genome instability. And the nomogram model based on ICI scores showed the feasibility in clinical practice in both internal and external validation.

Background Hypoxia-related long non-coding RNAs (lncRNAs) have been proven to play a role in multiple cancers and can serve as prognostic markers. Lower-grade gliomas (LGGs) are characterized by large heterogeneity. Methods This study aimed to construct a hypoxia-related lncRNA signature for predicting the prognosis of LGG patients. Transcriptome and clinical data of LGG patients were obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). LGG cohort in TCGA was chosen as training set and LGG cohorts in CGGA served as validation sets. A prognostic signature consisting of fourteen hypoxia-related lncRNAs was constructed using univariate and LASSO Cox regression. A risk score formula involving the fourteen lncRNAs was developed to calculate the risk score and patients were classified into high- and low-risk groups based on cutoff. Kaplan-Meier survival analysis was used to compare the survival between two groups. Cox regression analysis was used to determine whether risk score was an independent prognostic factor. A nomogram was then constructed based on independent prognostic factors and assessed by C-index and calibration plot. Gene set enrichment analysis and immune cell infiltration analysis were performed to uncover further mechanisms of this lncRNA signature. Results LGG patients with high risk had poorer prognosis than those with low risk in both training and validation sets. Recipient operating characteristic curves showed good performance of the prognostic signature. Univariate and multivariate Cox regression confirmed that the established lncRNA signature was an independent prognostic factor. C-index and calibration plots showed good predictive performance of nomogram. Gene set enrichment analysis showed that genes in the high-risk group were enriched in apoptosis, cell adhesion, pathways in cancer, hypoxia etc. Immune cells were higher in high-risk group. Conclusion The present study showed the value of the 14-lncRNA signature in predicting survival of LGGs and these 14 lncRNAs could be further investigated to reveal more mechanisms involved in gliomas.

INTRODUCTION Lower grade gliomas encompass grade 2 and 3 tumors. However, this term is more generalized and does not include the spectrum of radiological and tumor morphological patterns seen. Here we have established two distinct patterns of radiographic appearance seen within lower grade gliomas: ILGG and DLGG. Imaging plays a vital role in diagnosis, surveillance, characterization, and monitoring of intracranial tumors. Of particular importance is the differentiation of tumor features to reliably predict malignancy, tumor grade, possible molecular or genetic features, disease progression and recurrence, potential for malignant transformation, and postoperative outcomes. Our study will look at these radiographic characteristics of diffuse and infiltrating lower grade gliomas and discuss their predictive value. Understanding the distinct nature of these varieties of LGG will help us in surgical decision-making, prognostication, biopsy target and precision medicine. METHODS Pre-operative and post-operative MRI images of Grade 2 and 3 tumors were identified and analyzed in order to extract radiographic data, and correlated with patient demographics, clinical outcomes, extent of surgical resection, and molecular genetic analysis. RESULTS Out of 35 patients evaluated, 22 (62.9%) were labeled ILGGs and 13 (37.1%) were deemed DLGGs according to the pre-defined criteria. T2 habitat was higher in ILGG (mean = 2162) than DLGG (mean = 1482) as well as size, in cm (6.02 vs. 4.92). ADC habitat, lesion ADC, and percentage of the lesion that showed contrast-enhancement were similar. T2-FLAIR mismatch was significantly higher in ILGG (p = 0.02). Post-operative KPS scores were significantly higher in the DLGG group (p = 0.03). CONCLUSION T2-FLAIR mismatch can be a significant classifier for lower-grade gliomas. Our study shows there are differences in tumor morphology of diffuse and infiltrative lower-grade gliomas which can be correlated to outcomes after surgery. *Indicates corresponding author.

(1) Background: The 2016 WHO classification of Tumors of the Central Nervous System brought an escalating research interest in lower-grade gliomas (LGGs). This study aims to establish individualized prognostic nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with LGGs;(2) Methods: We searched the Surveillance, Epidemiology, and End Results (SEER) database for adult patients diagnosed with LGGs from 1998 to 2016. The patient data set selected from SEER was randomly divided into training and validation data sets at a ratio of 7:3. The significant prognostic factors were identified by using multivariate regression models in the training dataset. Then OS and CSS nomograms were developed and internally validated;(3) Results: After the inclusion and exclusion criteria set, a total of 12,630 patients were enrolled in our research. The prognosticators for OS contained age, sex, race, marital status, surgery, radiotherapy, chemotherapy, tumor size/site, laterality, WHO grade, while only chemotherapy among the 11 indicators mentioned above was not related to CSS. The c-indexes of OS and CSS of the validation cohort were 0.749 and 0.761, respectively. The calibration curve plots showed that the predicted probability of 3-, 5-, and 8-years survival rates corresponded well with the actual observed OS and CSS rates;(4) Conclusion: The present study using the SEER database constructed and internally validated prognostic nomograms to predict the OS and CSS of patients with LGGs. The nomograms showed perfect predictive abilities and may be useful clinical tools for decision aids and better supporting patient counselling.

BackgroundPediatric lower-grade gliomas (pLGGs) are a rare intracranial tumor that lacks a prognostic prediction model for clinical application. The present study aimed to construct a novel nomogram to predict overall survival for pLGGs.MethodsBased on data from the Surveillance, Epidemiology, and End Results (SEER) database, 746 pediatrics diagnosed with cerebral hemispheres lower-grade gliomas from 1998 to 2016 were enrolled for the research. All patients were randomly divided into training and validation datasets at a ratio of 7:3. The Cox and stepwise regression analysis was used to screen the independent prognosticators for developing the nomogram. The discriminating abilities and calibration of the nomogram were assessed by concordance index (C-index), receiver operating characteristic curves (ROCs), area under the ROCs (AUCs), and calibration curves. The accuracy and net benefits of the nomogram were evaluated by comparing it to the traditional prediction method by the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and the decision curve analysis (DCA). Finally, we employed risk stratifications for pLGGs. ResultsFive independent predicted indicators were associated with OS rates. The constructed nomogram showed reliable discrimination by the C-indexes of the novel nomogram for OS, which were 0.830 and 0.871, much higher than that in the traditional prediction method (0.749 and 0.728, respectively). The plotted calibration curves showed good consistency between the prediction survival rates and actual observed survival rates in both the training and validation dataset. IDI, NRI, and DCA showed the nomogram had a comparable clinical application to the traditional prediction method. Kaplan-Meier survival curves showed a significant difference among the three risk classifications.ConclusionIn conclusion, we developed a novel prognostic nomogram with improved accuracy, better clinical utility, and a more precise prediction of OS rates for hemisphere pLGGs than the traditional prediction method.