bluuebunny/crossref_metadata_2025_split huggingface dataset:
QOLP-23. EVALUATION OF FINANCIAL TOXICITY (FT) IN PEOPLE WITH RARE CENTRAL NERVOUS SYSTEM (CNS) TUMORS USING AN INNOVATIVE WEB-BASED STUDY DESIGN
Authors: Timmer Michael , Vera Elizabeth , Acquaye Alvina , Chambers Claudia , Christ Alexa , Levine Jason , Wooley Joseph , Leeper Heather , Raygada Margarita , Scheurer Michael , Wall Kathleen , Gilbert Mark , Armstrong Terri , Penas-Prado Marta 
Published: November 2021

Abstract

BACKGROUND
Financial toxicity (FT) refers to the negative financial impact of cancer. Research exploring FT in patients with CNS tumors is limited to more common diagnoses or within single institutions. Total income, work interference and symptom burden are all key parameters when investigating FT in patients with rare CNS tumors.

METHODS
A web-based study of 210 participants’ responses to financial, clinical, symptom burden (MDASI-BT/MDASI-SP), depression and anxiety (PROMIS-Depression/Anxiety), work interference (SF-36) and general health status (EQ-5D-3L) is reported using descriptive statistics and tests of associations.

RESULTS
Patients were white (93%) employed (48%) females (72%), with median age of 47 (19-75). The most common diagnosis was ependymoma (80%). Original tumor location was the brain in 83 (40%) and spine in 115 (55%). Median time from tissue diagnosis was 48 months (0 – 402). Income was lower than the poverty level in 6% and lower than the median U.S. in 23%. A change in work due to their tumor was reported by 60%, with the majority stopping work (31%). One-third reported lack of access to health-care services and 10% required home care services. Difficulty walking was reported by 42% and difficulty in performing activities due to physical health by over 60%. Anxiety and depression scores aligned with the average for the U.S. population; however, 21% were taking antidepressants and 42% reported not being able to complete work or activities due to depression. Half of all patients reported moderate-severe pain, fatigue, and weakness with higher symptom burden and depression associated with change in work status (p &lt; 0.003).

CONCLUSION
Patients with rare CNS tumors report an impact of their tumor diagnosis on activities/work patterns, with an associated higher symptom burden. Future studies exploring financial impact in patients with rare CNS tumors and targeted programs to address these outcomes are needed.
RBIO-04. LACTATE DEHYDROGENASE A (LDHA) MEDIATES NOVEL CROSSTALK BETWEEN METABOLIC GLYCOLYSIS AND CHROMATIN REMODELING
Authors: Li Jie , Ning Jianfang , Koga Tomoyuki , Li Ming , Zhu Shan , Venteicher Andrew , Taha Birra , Akers Johnny , Chen Clark 
Published: November 2021

Abstract

INTRODUCTION
Lactate dehydrogenase A (LDHA) encodes an enzyme that catalyzes the inter-conversion between pyruvate and lactate in glycolysis. Here, we demonstrate that LDHA mediates a novel role in DNA repair independent of this metabolic function.

METHODS
siRNA screen, The Cancer Genome Atlas (TCGA) survival analysis, ionizing radiation (IR), g-H2AX, and chromatin assays, site-directed mutagenesis.

RESULTS
In an orthogonal siRNA-informatic screen to identify genes 1) when silenced caused IR sensitivity in patient-derived glioblastoma lines and 2) lowered expression is associated with improved survival in TCGA, LDHA surfaced as the top candidate. The survival association was validated by LDHA immunohistochemical staining in an independent collection of glioblastoma samples. In vitro and in vivo, silencing of LDHA sensitized glioblastoma lines to IR and enhanced radiation-induced g-H2AX accumulation. Such sensitization was not observed after treatment with an LDHA inhibitor, suggesting the metabolic function of LDHA is distinct from its role in DNA repair. Supporting this hypothesis, truncation mutations that suppressed the LDHA glycolysis function minimally affected its role in DNA repair. Mechanistically, cytoplasmic LDHA translocates into the nucleus in response to IR. This translocation was associated with subsequent chromatin transition into an open conformation and enhanced homologous recombination.

CONCLUSION
The novel LDHA function in DNA repair suggests intricate crosstalks between glycolytic metabolism and DNA repair, offering a new platform for glioblastoma therapeutic development.
SURG-04. THE CLINICAL COURSE AND ROLE OF SURGERY IN PEDIATRIC MALIGNANT PERIPHERAL NERVE SHEATH TUMORS: A DATABASE STUDY
Authors: Lu Victor , Wang Shelly , Daniels David , Spinner Robert , Levi Allan , Niazi Toba 
Published: November 2021

Abstract

BACKGROUND
Malignant peripheral nerve sheath tumors (MPNST) are rare tumors found throughout the body, with their clinical course in children still to be completely understood. Correspondingly, this study aimed to determine survival outcomes and specific clinical predictors of survival in this demographic from a large national database.

METHODS
All MPNST patients aged ≤18 year in the U.S. National Cancer Database (NCDB) between 2005-2016 were retrospectively reviewed. Data were summarized and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses.

RESULTS
A total of 251 pediatric MPNST cases were identified. Overall, mean age at diagnosis was 13.1 years (range, 1-18) with there being 132 (53%) females and 119 (47%) males. There were 84 (33%) MPNSTs located in extremities, 127 (51%) less than 1cm in size, and 22 (9%) have metastasis at diagnosis. In terms of treatment, surgery was pursued in 187 (74%) patients, chemotherapy in 116 (46%) patients, and radiation therapy in 129 (61%) patients. Five-year overall survival was estimated to be 52% (95% CI, 45-59%), and with median survival of 64 months (range, 36-136). Multivariate regression revealed older age (HR 1.10, P&lt; 0.01), with metastases at time of diagnosis (HR 2.14, P=0.01), and biopsy only (HR 2.98, P&lt; 0.01) all significantly and independently predicted shorter overall survival. Chemotherapy and radiation therapy were not statistically significant.

CONCLUSIONS
Pediatric MPNSTs are rare malignant entities, and only approximately half of patients will survive to five years. There remains a clear survival benefit in pursuing maximal safe resection in these patients. As such, judicious workup with meticulous surgical resection by an expert team should then be considered the standard of care for these tumors in children.
SURG-14. COMPARABLE SURVIVAL OUTCOMES BETWEEN THE ELDERLY AND THEIR YOUNGER COUNTERPARTS AFTER RESECTION OF BENIGN MENINGIOMAS
Authors: Ma Jun , Alattar Ali , Dhawan Sanjay , Jakola Asgeir , Bartek Jr Jiri , Chen Clark 
Published: November 2021

Abstract

OBJECTIVE
Using the Surveillance, Epidemiology and End Results (SEER) database, we characterized the patterns of surgical recommendations and outcomes after benign meningioma resection in the elderly population.

METHODS
27,839 adult meningioma patients were identified in SEER between 1973- 2015 and 6,967 patients were identified between 2016-18. Patients were stratified into four age groups:18-39, 40-59, 60-79, and &gt; 80 years old. The likelihood for recommendation to proceed with resection, extent of resection, and survival outcome were determined using logistic regression models.

RESULTS
In a multi-variate model that accounted for gender, race, marital status, tumor size, and tumor location, the likelihood of recommendation to proceed with benign meningiomas resection decreased with advancing age. Relative to patients age 40-59, the likelihood of recommendation for surgery were 1.130 (95%CI=0.925-1.380, P=0.230), 0.593 (95%CI=0.531-0.662, P&lt; 0.001), and 0.173 (95%CI=0.146-0.205, P&lt; 0.001) for patients age 18-39, 60-79, and &gt;= 80, respectively. A similar trend in the likelihood of gross total resection (GTR) was observed. Relative to patients age 40-59, the likelihood of gross total resection were 1.009 (95%CI=0.913-1.114, P=0.867), 0.903 (95%CI=0.849-0.961, P=0.001), and 0.580 (95%CI=0.512-0.657, P&lt; 0.001) for patients age 18-39, 60-79, and &gt;= 80, respectively. However, survival after meningioma resection did not vary significantly as a function of patient age. Relative to patients age 40-59, the hazard of death after GTR of meningioma resection were 1.324 (95%CI=0.795-2/203, P=0.280), 0.813 (95%CI=0.639-1.035, P=0.092), and 0.913 (95%CI=0.618-1.350, P=0.649) for patients age 60-79, and &gt;= 80, respectively. These results were validated using SEER data from 2016-2018.

CONCLUSION
This analysis provide evidence that surgeons exert caution in surgical resection of benign meningioma in the elderly, with decreased likelihood for recommending surgery in this population. In patients selected for and underwent gross resection, survival outcome in the elderly was comparable to their younger counterparts, suggesting safety of procedure in appropriately selected elderly.
TAMI-05. FATTY ACID SYNTHESIS IS REQUIRED FOR HER2+ BREAST CANCER BRAIN METASTASIS
Authors: Ferraro Gino , Ali Ahmed , Luengo Alba , Deik Amy , Abbott Keene , Bezwada Divya , Blanc Landry , Prideaux Brendan , Jin Xin , Posada Jessica , Amoozgar Zohreh , Ferreira Raphael , Chen Ivy , Naxerova Kamila , Ng Christopher , Westermark Anna , Davidson Shawn , Fukumura Dai , Dartois Véronique , Clish Clary , Heiden Matthew Vander , Jain Rakesh 
Published: November 2021

Abstract
Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2-positive breast cancer and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, resulting in site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase reduces human epidermal growth factor receptor 2-positive breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.
TAMI-13. MODULATION OF REDUCTIVE CARBOXYLATION FLUX OF GLUTAMINE IN GLIOBLASTOMA CELLS BY USING OSCILLATING MAGNETIC FIELD
Authors: Pichumani Kumar , Ijare Omkar , Hambarde Shashank , Sharpe Martyn , John Blessy , Baskin David , Helekar Santosh 
Published: November 2021

Abstract
Increased cell proliferation in glioblastoma (GBM) leads to hypoxia in the tumor microenvironment. This is a major concern in GBM patients as it promotes tumor invasion. Glutaminolysis is a hallmark of cancer cells and under hypoxic conditions glutamine metabolism proceeds through reductive carboxylation pathway. Recently, we have shown that oscillating magnetic field (OMF) produces oncolytic effects which can influence cellular metabolism. Here, we have explored the effect of OMF on glutamine metabolism in GBM cells. Patient-derived GBM cells were grown in high glucose (25 mM) DMEM supplemented with 20% fetal bovine serum (FBS), 2.0 mM glutamine and 1.0 mM pyruvate at 37 °C under humidified air and 5% CO2. Cells were divided into 2 groups (Test and Sham; n = 4 each group). When reached confluency (~2.0×106 cells/mL), cells in both groups were treated with 4.0 mM of [U-13C]glutamine in DMEM (supplemented with 20% FBS, and 1.0 mM pyruvate). The “Test” group was subjected to OMF for 3 hours, and the “Sham” group was treated similar to the “Test” group but with non-magnetic rods of the same dimensions as the magnets in the Test group. After 3 h, cells were harvested in 50% methanol analyzed by GC-MS. The 13C-isotopomer analysis showed that glutamine metabolism in GBM cells proceeds through reduction carboxylation, confirmed by the higher levels of M+5 citrate (15.42 ± 1.28 % ) than M+4 citrate (2.05 ± 0.28 %). When GBM cells were treated with OMF, a statistically significant decrease in the citrate M+5 was observed, compared to the “Sham” treated group (15.42 ± 1.28 % vs. 8.89 ± 1.30 %; p = 0.0003). This decrease in M+5 citrate upon OMF treatment clearly indicates that the OMF decreases the reductive carboxylation flux of glutamine in GBM cells which would have therapeutic value in treating GBM patients.
TAMI-28. IDENTIFICATION OF A NEUROLIGIN-3 BINDING PARTNER IN HIGH-GRADE GLIOMAS AND NORMAL PROGENITORS
Authors: Gillespie Shawn , Kim Yoon Seok , Geraghty Anna , Quezada Michael , Reed James , Woo Pamelyn , Monje Michelle 
Published: November 2021

Abstract
High-grade gliomas, including diffuse intrinsic pontine glioma, are lethal cancers whose progression is strongly regulated by neuronal activity. One way in which gliomas detect neuronal activity is via interaction with the ectodomain of post-synaptic adhesion protein neuroligin-3 (NLGN3), which is shed from neurons and oligodendrocyte precursors (OPCs) by the ADAM10 sheddase in an activity dependent manner. NLGN3 signaling drives glioma growth, but the cognate binding partner of shed NLGN3 (sNLGN3) on glioma cells is unknown. Here, we employed a proximity labeling technique to identify chondroitin sulfate proteoglycan 4 (CSPG4) as a putative binding partner of sNLGN3 in gliomas. We then confirmed complexing between recombinant proteins with size exclusion chromatography and are determining kinetics and affinity by surface plasmon resonance. When looking for evidence of binding in cells, we were surprised to find that sNLGN3 triggers regulated intramembrane proteolysis (RIP) of CSPG4, leaving no trace of the interaction at the membrane. sNLGN3 binding first induces ADAM10-mediated cleavage and release of the CSPG4 ectodomain, followed by gamma secretase-mediated release of the intracellular domain and downstream signaling in OPCs and gliomas. Pre-treatment of glioma cells or OPCs with an ADAM10 inhibitor entirely blocks sNLGN3-induced CSPG4 shedding. Acute depletion of CSPG4 via CRISPR gene editing renders glioma cells insensitive to the growth-promoting effects of sNLGN3 in vitro. Furthermore, we find that tamoxifen-induced deletion of NLGN3 from murine OPCs reduces the total number of OPCs, suggesting that this signaling axis promotes maintenance of OPC stemness in an autocrine fashion. Indeed, gamma secretase inhibition accelerates OPC differentiation in vitro, pointing towards a fundamental role for sNLGN3-CSPG4 signaling in OPCs and high-grade gliomas. Altogether, our results form a critical missing link in understanding how glioma cells detect a key neuronal activity-regulated signal, suggest intriguing links to OPC biology and identify a therapeutic target to disrupt neuron-glioma interactions.
TAMI-56. TARGETING AMINO ACID METABOLIC VULNERABILITIES IN IDH-MUTANT AND IDH-WILDTYPE GLIOMAS
Authors: Ohba Shigeo , Hirayama Akiyoshi , Hitachi Keisuke , Yamaguchi Hisateru , Mukherjee Joydeep , Pieper Russell , Hirose Yuichi 
Published: November 2021

Abstract
IDH-wildtype glioma and IDH-mutant glioma have different genetical and metabolic background although their histological appearances are similar. The aim of the study is to reveal the difference in metabolites between IDH-wildtype glioma and IDH-mutant glioma, and to find the effective treatment targeting cancer metabolism according to the status of IDH in gliomas. Two artificial cell lines made from normal human astrocyte were used: NHAE6E7hTERTRas (IDH-wildtype) and NHAE6E7hTERTIDHmut (IDH-mutant). Capillary electrophoresis time-of-flight-mass spectrometry (CE-TOFMS) revealed that the amount of asparagine was lower in NHAE6E7hTERTRas cells compared with NHAE6E7hTERTIDHmut cells. L-asparaginase, which converts asparagine into aspartate, was more effective in the former cells than the latter cells. L-asparaginase induced autophagy and inhibition of autophagy by 3-MA suppressed L-asparaginase-induced antitumor effect. Adding asparagine into the culture medium rescued the antitumor effect of L-asparaginase. L-asparaginase increased the expression of asparagine synthetase (ASNS) and genetical or pharmacological inhibition of ASNS enhanced the antitumor effect of L-asparaginase. CE-TOFMS showed the lower amount of glutamine, glutamate and 2-oxoglutarate in NHAE6E7hTERTIDHmut cells than NHAE6E7hTERTRas cells. GLUD1 inhibitor inhibited proliferation by inducing higher ROS level and apoptosis in NHAE6E7hTERTIDHmut cells than NHAE6E7hTERTRas cells. ROS inhibitor, NAC suppressed GLUD1 inhibitor-induced ROS, apoptosis, and cytotoxicity in NHAE6E7hTERTIDHmut cells. Exogeneous dimethyl 2-oxoglutarate rescued the cytotoxicity induced by GLUD1 inhibitor. L-asparaginase and GLUD1 inhibitor will be new therapeutic option for IDH-wildtype glioma and IDH-mutant glioma, respectively.
BRMP-01. Awake cranial surgery with intraoperative language mapping for brain tumors. A single-center experience
Authors: Cervio Andrés , Giovannini Sebastían , Hasdeu Sonia , Pertierra Lucía , Diez Blanca 
Published: November 2021

Abstract

BACKGROUND
Maximal safe resection of brain tumors affecting language areas has been a matter of increasing interest worldwide in the last decades. Functional MRI, tractography, and awake cranial surgery are standard procedures in our department since 2006. The aim of this study was to describe our experience in a series of 58 patients who underwent awake cranial surgery with intraoperative language mapping.

METHODS
Retrospective study of 58 adult patients who underwent awake surgery for brain tumors between January 2006 and January 2021. Preoperative neuropsychological assessment served as inclusion criteria. Language was evaluated according to the BDAE (Boston diagnostic aphasia examination) and WAB (Western aphasia battery) and strength according to the MRC (Medical Research Council) motor scale in the preoperative, immediate postoperative, and 3-months follow up. Functional MRI and tractography depicting white-matter tracts, neuronavigation, cortical and subcortical stimulation were performed in all cases. Conscious sedation was the anesthetic technique (propofol, fentanyl, and NSAIDs). Minimum follow-up was 6 months.

FINDINGS
The average age was 35 years (16–74). The anatomopathological findings were: low-grade glioma in 75,8% (n = 44), high-grade glioma in 15,6% (n = 9) and others in 8,6% (n = 5). No complications were registered during postoperative course. At the immediate postoperative evaluation 65% of patients presented with speech disturbances but at the 3-months follow up speech recovery was observed in all cases. Only 1 patient remained with moderate aphasia. mRS score at 3- months follow up was ≤ 1 in 96% of patients. Two patients had a persistent moderate hemiparesis.

CONCLUSION
Tumor resection in awake patients showed to be a safe procedure, and well tolerated by the patients. Preoperative planning of anatomical and functional aspects and intraoperative neurophysiological assessment are the cornerstones for pursuing maximal safe resection.
CNTM-03. Functional connectivity networks in patients with brain tumors and vascular lesions in the occipital cortex
Authors: Rosengarth Katharina , Hense Katharina , Plank Tina , Greenlee Mark , Wendl Christina , Proescholdt Martin , Schmidt Nils-Ole 
Published: November 2021

Abstract

OBJECTIVE
Space-occupying brain lesions as brain tumors in the occipital lobe have only been sparsely investigated so far, as this localization is extremely rare with only 1% of cases. It is still unclear how this affects the overall organization of the visual system. We investigated functional connectivity of functional networks associated with higher visual processing between patients with occipital space-occupying lesion in the occipital cortex and healthy controls.

METHODS
12 patients with brain tumors, 7 patients with vascular lesions in the occipital cortex and 19 healthy subjects matched for age and sex were included. During functional MRI patients and subjects performed a visual excentricity mapping task. Data analysis was done using CONN toolbox based on Matlab. See-to-ROI connectivities of 23 Regions of Interest (ROIs) implemented in the CONN toolbox which were assigned to the Default Mode, Visual, Salience, Dorsal Attention, and Frontoparietal network were assessed. For each subject, connectivity was calculated using Fischer transformed pairwise correlations. These correlations were first considered separately for each group in one-sample analyses and then compared between the groups.

RESULTS
Main results show, that compared to control subjects and vascular patients, tumor patients showed weaker intra-network connectivity of components of all networks except the default-network. Tumor patients showed even stronger between-network connectivity in the default-mode network compared to the other groups. Weaker connectivity was observed within the salience network in both patient groups compared to controls.

CONCLUSION
The results indicate that in the course of the disease, compensatory countermeasures take place in the brain against a brain tumor or a space-occupying brain lesion with the aim of maintaining the performance level and cognitive processes for as long as possible. However, more research is needed in this area to understand the mechanisms and effects of brain tumors and space-consuming brain lesions on surrounding tissue.
The Changing Epidemiology and Microbiology of Patients With Prostate Abscess: Increase in Staphylococcal Infection
Authors: McCormick David W , Kaplan Julika , Whigham Cliff , Coburn Michael , Greenberg Stephen B 
Published: November 2021

AbstractBackgroundProstatic abscesses are rare and have been most commonly associated with gram-negative bacteria; however, Staphylococcus aureus has emerged as a leading cause, particularly in persons who are immunocompromised.MethodsWe conducted a retrospective chart review of all patients discharged from Ben Taub Hospital with a diagnosis of prostatic abscess during January 2011–January 2019. Demographic, clinical, microbiologic, and radiographic data were abstracted from the patients’ charts and analyzed for comorbidities, causative organisms, clinical course, and outcomes.ResultsWe identified 32 patients with a prostatic abscess during the study period. S. aureus was the most common causative organism (18/32, 56%). Most patients (24/32, 75%) were admitted to a general medicine service, and the median length of stay was 9 days. Twenty-one patients (66%) were treated with a combination of surgical drainage and antibiotic therapy; 11 (34%) were treated with antibiotics alone. All patients treated with antibiotics alone had full clinical recovery. Two patients (6.3%) died, both of whom had septic shock secondary to disseminated S. aureus infection.ConclusionsProstatic abscesses are rare and can be difficult to diagnose, leading to significant morbidity and mortality. S. aureus is a frequent causative organism especially in persons with diabetes mellitus or other immunocompromising conditions. Hematogenous spread of S. aureus infection to the prostate appears common. Prostatic abscesses can serve as the nidus of disseminated S. aureus infection.