bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Scoping Review of Graduate Nurses’ Education and Use of QSEN Competencies
Authors: Ferro Allison L , Yoder Linda H 
Published: November 2023

ABSTRACT

Introduction
The QSEN Institute developed the quality and safety education for nurses (QSEN) competencies for both undergraduate and graduate-prepared nurses to support their development of the knowledge, skills, and attitudes needed to deliver safe, quality care. The purpose of this scoping review was to (1) determine the extent of evidence about the current use of QSEN competencies in graduate nursing curricula and (2) determine the application of the QSEN competencies among graduate-prepared nurses in clinical practice.

Materials and Methods
Arksey and O’Malley’s methodological framework for scoping reviews was used to explore the literature about the use of the QSEN competencies in graduate nursing education and practice available in PubMed, Cumulative Index to Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online, and Web of Science. Quality was assessed using Melnyk, Gallagher-Ford, and Fineout-Overholt’s critical appraisal tools.

Results
In total, 423 articles were reviewed, 10 of which met inclusion criteria; five described quality improvement projects, two addressed curricular design, and three were program evaluations. Only one article described the use of QSEN competencies in practice. Overall, the amount of literature was scant and of low quality. All the articles described the use of QSEN competencies in graduate education except one, which also described them in practice in a graduate nurse residency program.

Conclusions
Although the QSEN competencies were adopted for use in graduate curricula and practice settings, there is a wide variation in the actual use and application with limited reporting of outcomes. The graduate QSEN competencies can be leveraged to equip nurses with the knowledge, skills, and attitudes to address quality and safety challenges in any nursing environment including the operational environment in deployed and austere settings. This review provides recommendations to address gaps in research, graduate nursing education, and clinical practice.
ANGI-06. BIOLOGY OF GLIOBLASTOMA INVASION: A SINGLE-CELL LEVEL ANALYSIS OF TUMOR CORE VS. INFILTRATING EDGE
Authors: Pai Balagopal , Chang Wan Sze , Zaslavsky Elena , Tsankova Nadejda 
Published: November 2023

Abstract
Glioblastoma (GBM) is a highly proliferative and diffusely infiltrating tumor, consisting of a necrotic core showing extensive microvascular proliferation and an infiltrating edge that extends beyond the surgical resection margin. The aggressiveness of GBM can be attributed to the existence of glioma stem-like cell populations (GSC) at this infiltrating edge. Although many studies have characterized GSC biology in culture, their contributions to invasion in vivo, and in the context of their microenvironment, remains poorly understood. In this study, we used macro-dissected biopsies of the tumor core and the infiltrative edge from six genetically-distinct glioblastoma tumors, to generate a spatiotemporal map of tumor invasion at a single-cell level. Unbiased clustering of ~40,000 nuclei and integrated analysis identified various cell types composing the tumor microenvironment, with predominance of tumor cells at the core and non-neoplastic cells at the edge, as expected. Inferred copy number alterations based on gene expression confirmed tumor cell identity in the core and the edge datasets. Differential expression analysis of core vs. edge tumor clusters revealed distinct transcriptomic signatures including several genes previously implicated in GBM invasion, such as EGFR, matrix metalloproteinases, and MAPK signaling pathway members. Several genes from this newly defined “GBM invasion signature” were further validated in a PDX invasion model, in which the transcriptome within the tumor core and infiltrative edge were similarly sequenced and analyzed at the single cell level. We are currently employing 10X-visium combined with immunohistochemistry to spatially deconvolute and corroborate the defined GBM invasion/infiltration signature at the tissue level in tumor biopsies. Overall, our study aims to provide high resolution map of glioma tumor invasion that can prioritize new and unique targetable pathways.
BIOM-20. NEAT1 EXPRESSION IS ASSOCIATED WITH GLIOBLASTOMA PATIENT RESPONSE TO IMMUNE CHECKPOINT INHIBITORS
Authors: Toker Joseph , Iorgulescu J Bryan , Ling Alexander , Villa Genaro , Parida Laxmi , Getz Gad , Wu Catherine , Reardon David , Antonio Chiocca E , Mineo Marco 
Published: November 2023

Abstract
Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite advances in therapeutic intervention, including maximal tumor resection, chemotherapy, and radiotherapy, GBM patient median survival remains approximately 20.9 months. A promising approach to overcome current therapeutic challenges is the use of inhibitors of immune checkpoints, such as PD-1/PD-L1, which have been demonstrated to be effective against many different solid cancers. Despite the strong interest in applying these strategies to GBM, clinical studies evaluating the efficacy of monoclonal antibodies against PD-1/PD-L1 have yielded disappointing results. However, an analysis of the data from these studies, considering clinical factors such as MGMT promoter methylation and the use of steroids, indicated that immune checkpoint inhibitor (ICI) therapy may benefit a subset of GBM patients. Moreover, additional clinical studies in GBM have demonstrated the importance of the timing of ICI treatment, although the markers associated with response remain unclear. Therefore, understanding the molecular basis of clinical response to PD-1/PD-L1 inhibitors is critical to identify GBM patients who can benefit from this type of therapy. By analyzing the transcriptomic profile of two different cohorts of GBM patients, we identify NEAT1 as a long noncoding RNA upregulated in GBM patients with longer survival upon anti-PD-1/PD-L1 treatment. Higher expression of NEAT1 was associated with upregulation of the interferon-gamma pathway and downregulation of cell-cycle-related genes. Single-cell RNA-sequencing analysis showed that higher NEAT1 expression in tumor cells correlated with the number of infiltrating macrophages and microglia. Among the GBM immune infiltrates, we found that macrophages and microglia had the highest NEAT1 median expression. Macrophage expression of NEAT1 was associated with enrichment in the TNF-alpha signaling pathway and the regulation of different inflammatory cytokines. Our findings suggest that NEAT1 is an important factor in shaping the tumor-immune microenvironment and a potential marker to predict GBM patient response to ICI.
BIOM-35. IDENTIFICATION AND VALIDATION OF POTENTIAL BIOMARKERS FOR DECITABINE-MEDIATED SENSITIZATION TO TEMOZOLOMIDE IN GLIOBLASTOMA
Authors: Hurtado Thenzing Silva , Inocencio Julio , Mead Andy , Fang Gang , Pai Balagopal , Tsankova Nadejda , Yong Raymund 
Published: November 2023

Abstract
Glioblastoma (GBM) is an aggressive form of brain cancer with limited treatment options and a poor prognosis. Our previous research demonstrated that the DNA hypomethylating agent decitabine (DAC) enhances the sensitivity to temozolomide (TMZ) of a subset of primary GBM cell lines derived from fresh surgical tissue specimens, and that this effect may be mediated by upregulation of DNA mismatch repair genes including MLH1. In this context, we aim to identify additional biomarkers for DAC-mediated sensitization to TMZ with potential clinical utility through in vitro and in vivo experiments. We performed single cell RNA sequencing on three DAC-sensitized and three DAC-desensitized cell lines and found 4 genes that exhibited significant differential expression: DCN, LUM, CRABP2 and NUPR1. We validated these findings using quantitative immunoblots, RT-qPCR and immunohistochemistry, finding that NUPR1 protein expression levels varied most significantly between DAC-sensitized and desensitized GBM tissues. Long-range direct methylation sequencing of non-amplified genomic DNA enriched using CRISPR/Cas9 demonstrated several CpG sites within the 4 genes that may be predictive of TMZ sensitization response after treatment with DAC. Finally, we performed mouse survival experiments using orthotopic patient-derived xenografts (PDXs) of the six GBM cell lines, with preliminary results showing that in selected PDX survival was significantly increased with combined DAC-TMZ versus TMZ monotherapy as predicted by in vitro assays. In conclusion, our study demonstrates that combining DAC with TMZ may be a potential treatment strategy for GBM in a subset of patients. There likely exist several biomarkers that can be used at the time of diagnosis, alone or in combination, to predict the response to epigenetic preconditioning using DAC for TMZ sensitization, which will be necessary for optimal patient selection in an early phase clinical trial. Further data and validation studies are necessary to strengthen these findings and to confirm their clinical relevance.
BIOM-46. STANDARDIZATION OF LIQUID BIOPSY FOR PEDIATRIC DIFFUSE MIDLINE GLIOMA USING DDPCR
Authors: Li Daphne , Bonner Erin , Huang Tina , Koschmann Carl , Nazarian Javad , Saratsis Amanda 
Published: November 2023

Abstract

BACKGROUND
Diffuse midline glioma (DMG) is a highly morbid pediatric brain tumor. Up to 80% of DMGs harbor mutations in histone H3-encoding genes, associated with poor prognosis. We previously showed the feasibility of detecting H3 mutations in circulating tumor DNA (ctDNA) in the liquid biome of children diagnosed with DMG. However, detection of low levels of ctDNA is highly dependent on platform sensitivity and sample type. To address this, we optimized ctDNA detection sensitivity and specificity across two commonly used digital droplet PCR (ddPCR) platforms (RainDance and BioRad), and validated methods for detecting H3F3A c.83A &gt;T (H3.3K27M) mutations in DMG CSF, plasma, and primary tumor specimens across three different institutions.

METHODS
DNA was extracted from H3.3K27M mutant and H3 wildtype (H3WT) specimens, including H3.3K27M tumor tissue (n = 4), CSF (n = 6), plasma (n = 4), and human primary pediatric glioma cells (H3.3K27M, n = 2; H3WT, n = 1). ctDNA detection was enhanced via PCR pre-amplification and use of distinct custom primers and fluorescent LNA probes for c.83 A &gt;T H3F3A mutation detection. Mutation allelic frequency (MAF) was determined and validated through parallel analysis of matched H3.3K27M tissue specimens (n = 3).

RESULTS
We determined technical nuances between ddPCR instruments, and optimized sample preparation and sequencing protocols for H3.3K27M mutation detection and quantification. We observed 100% sensitivity and specificity for mutation detection in matched DMG tissue and CSF across assays, platforms and institutions.

CONCLUSION
ctDNA is reliably and reproducibly detected in the liquid biome using ddPCR, representing a clinically feasible, reproducible, and minimally invasive approach for DMG diagnosis, molecular subtyping and therapeutic monitoring.
BIOM-63. PROTEOMIC BASED PROFILING OF CSF FOR CNSL MANAGEMENT
Authors: Aastha Aastha , Wilding Hannah , Khan Shahbaz , Mikolajewicz Nicholas , Ignatchenko Vladimir , De Macedo Filho Leonardo Jose Monteiro , Bhanja Debarati , Heebner Madison , Glantz Michael , Mansouri Alireza , Kislinger Thomas 
Published: November 2023

Abstract
Central nervous system lymphoma (CNSL) is a rare subtype of non-Hodgkin lymphoma, primarily affecting the brain and spinal cord. CNSL exhibits a dismal prognosis, as reflected by a low 5-year survival rate of 30%, with the current standard of care. The advent of multi-agent intrathecal chemotherapy (MAITC) in conjunction with systemic therapy has demonstrated encouraging outcomes, enhancing both progression-free survival and overall survival in patients with CNSL. Given the potential morbidity associated with MAITC, identification of minimally-invasive biomarkers for guiding patient management are necessary. Leveraging the longitudinal, large volume of Cerebrospinal fluid (CSF) afforded through our MAITC program, the objective of this study is to identify CSF-based proteomic biomarkers that can serve as reliable indicators of MAITC treatment response and CNSL management. Patient-matched CSF samples from the Penn State Health Neuroscience biorepository were banked at pre- and post-therapeutic endpoint in 22 primary and 36 secondary CNSL patients. The samples were profiled using high-throughput fluid sample protocol coupled with mass-spectrometry that only requires 30 μl of CSF. More than 1000 unique proteins were detected using shotgun proteomics, and 797 proteins were present in 70% of the analyzed samples, which were used for downstream analysis. We were able to effectively discriminate between primary and secondary CNSL based on protein abundance. Furthermore, the findings suggest significant changes in the cellular processes related to glycoprotein metabolism and redox signalling in response to the treatment, indicating a potential impact on protein modification and the cellular response to oxidative stress. Our comprehensive, pathway-level analysis uncovered significant molecular alterations, shedding light on their potential prognostic significance in the context of CNS lymphoma. Future work is underway to identify biomarker signatures that would predict optimal response to MAITC therapy, exhibiting potential to improve clinical decision making.
BIOM-64. A PROGNOSTIC SCORING SYSTEM FOR IMMUNODEFICIENCY-ASSOCIATED PRIMARY CNS LYMPHOMAS: AN INTERNATIONAL MULTI-CENTER STUDY
Authors: Karschnia Philipp , Traub Benjamin-Leon , Doubrovinskaia Sofia , Richter Benjamin , Seidel Sabine , Kuschel Luis , Hinz Felix , Rejeski Kai , Winter Sebastian F , Müller Katharina , Quach Stefanie , Herold-Mende Christel , Kessler Tobias , Sahm Felix , Schlegel Uwe , Platten Michael , Dietrich Jorg , von Baumgarten Louisa , Baehring Joachim , Wick Wolfgang , Kaulen Leon 
Published: November 2023

Abstract

BACKGROUND
Immunodeficiency-associated (ID-) primary CNS lymphomas (PCNSL) were introduced as a distinct entity in the 2021 World Health Organization classification of brain tumors. Given their rarity, larger clinical studies and prognostic models to guide management are lacking.

METHODS
PCNSL, newly diagnosed between 2004-2023 at six centers in the USA and in Germany, were retrospectively analyzed for concurrent immunodeficiency. Clinical, radiological, and pathological data were collected and assessed for prognostic significance using univariate and multivariate analyses.

RESULTS
Among 1112 patients with newly diagnosed PCNSL, 93 (8.4%) were identified as ID-PCNSL. Median age at diagnosis was 57 years and most tumors (66%) stained positive for Epstein-Barr virus (EBV). In addition to immune reconstitution, tumor-directed treatments were administered in 91/93 patients. These included chemotherapy (87%), radiation (25%), and autologous stem cell transplantation (14%). Outcome varied with a median overall survival (OS) of 46 months (range: 1-206 months). Age ≥ 60 years, Karnofsky performance status (KPS) &lt; 70, EBV positivity, and non-rituximab or -methotrexate-based chemotherapy were associated with shorter OS on multivariate analysis adjusting for clinical and demographic factors. A prognostic scoring system was designed based on the sum of treatment-unrelated (age, KPS, EBV) unfavorable factors. The resulting score was highly prognostic and stratified ID-PCNSL into four subgroups: median OS was not reached, 90, 26, and 1 months (p &lt; 0.0001) in cases with zero, one, two, or three unfavorable factors, respectively. Prognostic value was retained when limiting analysis to patients (n = 53), who had received HD-MTX and rituximab combination chemotherapy, with median OS of 98, 90, 46 and 4 months (p &lt; 0.0001).

CONCLUSIONS
EBV was associated with inferior outcome in ID-PNCSL, which may reflect peculiar genetic alterations. An easily-applicable prognostic score based on three variables (age, KPS, EBV) allowed ID-PCNSL stratification into four risk groups. Prospective validation and therapeutic relevance warrant further investigation.
BIOS-04. THE ROLE OF MACHINE LEARNING, PREDICTIVE MODELING, AND DEEP LEARNING IN ASSESSING METABOLIC BIOMARKERS TO IMPROVE PROGNOSTICATION IN GLIOBLASTOMA MULTIFORME
Authors: Kuo Cathleen , Brown Nolan , Gendreau Julian 
Published: November 2023

Abstract
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in the United States, accounting for approximately 56.6% of all gliomas and 47.7% of all primary malignant CNS tumors. The prognosis of GBM is notably grim, with a 1-year relative survival rate of 41.4% and a 5-year survival rate of 5.8% following diagnosis. Recent efforts to identify potential therapeutic targets have utilized tumor omics data integrated with clinical information that leverages machine learning (ML) algorithms. However, there remains a paucity of studies assessing the value of these ML models as prognostic tools in GBM. A systematic search adhering to PRISMA guidelines was conducted to identify all studies describing the use of a ML algorithm involving GBM metabolic biomarkers and each algorithm's accuracy. Ten studies were included for final analysis. They were diagnostic (n = 3, 30%), prognostic (n = 6, 60%), or both (n = 1, 10%), respectively. Most studies analyzed data from multiple databases, while 50% (n = 5) included additional original samples. At least 2,536 data samples were run through a ML algorithm. 27 ML algorithms were recorded with a mean 2.8 algorithms per study. Algorithms were supervised (n = 22, 79%) or unsupervised (n = 6, 21%), and continuous (n = 21, 75%) or categorical (n = 7, 25%). The mean reported accuracy and AUC of ROC was 95.63% and 0.779, respectively. 106 metabolic markers were identified, but only EMP3 was reported in multiple studies. Many studies have identified potential biomarkers for GBM diagnosis and prognostication. These algorithms show promise; although, a consensus on even a handful of biomarkers has not been made. An integration of ML algorithms for biomarker detection combined with radiomics-based tumor imaging will be necessary to ascertain the greatest level of accuracy and precision.
CNSC-04. DIAGNOSIS AND TREATMENT OF PERIPHERAL AND CRANIAL NERVE TUMORS WITH EXPERT RECOMMENDATIONS: AN EUROPEAN NETWORK FOR RARE CANCERS (EURACAN) INITIATIVE
Authors: Pellerino Alessia , Verdijk Robert M , Nichelli Lucia , Andratschke Nicolaus H , Idbaih Ahmed , Goldbrunner Roland 
Published: November 2023

Abstract

BACKGROUND
The 2021 WHO classification of the CNS Tumors identifies as “Peripheral nerve sheath tumors” (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. Material and methods. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly.

RESULTS
Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively.

CONCLUSIONS
Given the heterogeneity and rarity of these tumors, there is a paucity of well-powered clinical trials, thus it is not possible to generate evidence-based treatment recommendations for non-surgical modalities. However, some clinical trials have been reported on targeted therapies in plexiform neurofibromas of NF1 patients or in heterogenous cohorts of soft-tissue tumors, including MPNSTs, with initial data of efficacy that need to be further investigated.
CNSC-18. DIFFERENTIAL EFFECTS OF NEUROTRANSMITTERS ON THE GROWTH OF GLIOBLASTOMA SUBTYPES
Authors: Irshad Khushboo , Singh Sanjay , Ahmad Khalil Ali , Aghoghovwia Ben , Alnassiry Sama , Lang Frederick , Pan Yuan 
Published: November 2023

Abstract
Glioblastomas are aggressive brain tumors associated with the worst patient prognosis. Neurons play critical roles in modulating the growth of glioblastoma. It has been demonstrated that glutamatergic neurons form bona fide synapses with glioblastoma tumor cells that are critical for tumor cell proliferation and migration. It is less clear whether the activity of other neuronal types influences glioblastoma pathophysiology, especially among the different glioblastoma molecular subtypes. Here, we examined the effects of neurotransmitters on the growth of glioblastoma cells characterized as the classical, proneural and mesenchymal subtypes. Patient-derived glioblastoma cell lines were exposed to varying concentrations of different neurotransmitters for 72 hours and assessed for cell viability using the CCK-8 assay. RESULTS: from the CCK8 assay indicate that acetylcholine and dopamine increase glioblastoma cell growth. Consistent with previous findings, we observed an increase in cell viability in all cell lines after being incubated with L-glutamate. The classical subtype has a stronger growth response to L-glutamate compared to the other two subtypes. Transcriptomic data from TCGA showed that the expression of GRIK4 (glutamate ionotropic receptor kainate type subunit 4) is the highest in the classical subtype. By comparing GRIK4 expression with patient survival in TCGA glioblastoma cases stratified by molecular subtypes, we found that high GRIK4 expression correlates with worse prognosis in the classical subtype, but not the proneural or mesenchymal patient groups. Our findings suggest that each glioblastoma subtype may differentially leverage neuromodulatory mechanisms to support their own growth. Ongoing studies are investigating the differential neuronal responses in glioblastoma subtypes using both pharmacological and genetic approaches.