tbuckley/cabot-search huggingface dataset:
EPID-25. SKULL BASE MENINGIOMAS ARE ASSOCIATED WITH OBESITY IN MALES
Authors: Maryam Shahin, Brittany Stedelin, Christian Lopez Ramos, Ali Rae, Jared Edwards, Jacob Bagley, Stephen Bowden, Carli Bullis, Matthew Wood, Justin Cetas, Seunggu Han
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The female predominance of meningiomas may reflect hormonal influences on meningioma development, with known presence of estrogen and progesterone receptors. Progestin-associated meningiomas demonstrate a shift in the mutational landscape and are more frequently located at the skull base. Obesity and increased adipocytes increase aromatase and affect male hormone synthesis, thus increases circulating estrogen. OBJECTIVE Report prevalence of obesity in a consecutive series of male patients presenting with meningioma and the interaction with obesity. METHODS A retrospective review (20012019) was performed of male patients diagnosed with meningioma. Body mass index (BMI) &amp;gt;30 kg/m2 was considered obese. Obese male meningioma patients were characterized and compared to nonobese male meningioma patients. RESULTS Of 239 male patients with meningioma, 97 (40.6%) were obese at the time of surgery with overall mean BMI (30.0 kg/m2). This is above the age-adjusted baseline prevalence of obesity for males in Oregon, which was 34.8% between 2015–2016. Mean age at diagnosis for obese males was 55.3 years and 57.0 years for nonobese males. Within the obese group, most lesions were located on the skull base (48.5% n=47) compared to 34.0% convexity (n=33), 15.4% falx (n=16) and 1.0% multiple (n=1). Tumors were WHO grade I (73.6%), grade II (25.6%) or grade III (1.2%). Of the men in our series, patients with skull base meningiomas were more likely to be obese (OR: 1.7, 95% CI: 1.01–2.9, p=0.0309). CONCLUSIONS There is likely a hormonal influence on the pathogenesis of meningioma, and many men diagnosed with this disease are obese. Of 239 male patients with meningioma in our series, 97 (40.6%) were obese which exceeds the 34% age-adjusted baseline prevalence of obesity for males in Oregon. Patients with skull base meningiomas were more likely to be obese, consistent with prior series and suggestive of a hormone-driven association with skull base meningioma.
Two sides of the same coin? A review of the similarities and differences between idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease
Authors: Scott Matson, Joyce Lee, Oliver Eickelberg
Journal: European Respiratory Journal (2020)

Rheumatoid arthritis associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF) are distinct diseases; however, they share several clinical, radiographic and genetic features. For instance, usual interstitial pneumonia (UIP), which is an ILD pattern required for a diagnosis of IPF, is also the most common ILD pattern in RA-ILD. The presence of UIP in RA-ILD is a poor prognostic sign with outcomes similar to those seen in IPF. The recent finding of a shared genetic susceptibility between IPF and RA-ILD has sparked additional interest in this relationship. This review outlines these similarities and differences in clinical presentation, appearance and outcomes in RA-ILD and IPF. In addition, this review highlights previous research in molecular biomarkers in both conditions, exploring areas of overlap and distinction. This focus on biomarkers in IPF and RA-ILD aims to highlight potential areas of discovery and clues to a potential shared pathobiology through investigation of novel molecular markers or the repurposing of biomarkers from one condition to the other. The drive to better understand RA-ILD by leveraging our knowledge of IPF is underscored by our divergent treatment paradigms for these conditions and the concern for potential harm. As a result of advancing our understanding of the links between IPF and RA-ILD, current strategies for diagnosis, screening and treatment of ILD may fundamentally change in the coming years. Until then, clinicians face difficult clinical questions regarding the co-management of the articular disease and the ILD in RA.
Abstract P390: Associations of Sleep Quality With Body Mass Index and Obesity: The Health Needs Assessment Study of Macao Residents
Authors: Yao Jie Xie, Alice Yuen Loke, Daphne Cheung, Bernice O.C. Lam Nogueira, Karry Liu, Angela Leung, Olivia Fung, Alice Tsang, Cindy Leong, Joe Cheong, Florence Van, Alex Molasiotis
Journal: Circulation (2020)

Background: There were inconsistent results in the relationship between poor sleep quality and obesity among different population in previous studies. Our study evaluated the association between sleep quality and obesity in a representative adult population of Chinese subjects living in the Macao Special Administrative Region, China. Methods: This cross-sectional study was an analysis of 1426 participants aged 18 to 90 years from a community-based health needs assessment study titled “Healthy Living, Longer Lives”. Recruitment was conducted in seven districts of Macao from 2017 to 2018. Stratified sampling by age and gender strata was adopted. The Chinese version of Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep quality. Higher score of PSQI indicates worse sleep quality. Height, weight, and other covariates were collected by self-administered questionnaire. Obesity was defined as body mass index (BMI) ≥ 25 kg/m 2 according to the WHO standard. Results: Of all participants, 263 (18.4%) were obese and 285 (20.0%) were overweight. The average BMI and global score of PSQI were 22.9±3.0 kg/m 2 and 4.48±2.58 for men, 22.1±3.3 kg/m 2 and 5.05±2.92 for women, respectively. After adjustment of age, sex, income, marital status, education, smoking, and drinking, a significant negative relationship was found between sleep quality and BMI: higher PSQI global score was associated with higher BMI (β = 0.09, 95% CI: 0.03 - 0.15; P &lt; 0.01). Within the 7 domains of PSQI, higher sleep disturbance score (β = 0.63, 95% CI: 0.34 - 0.93) and daytime dysfunction score (β = 0.41, 95% CI: 0.13 - 0.68) predicted higher BMI (both P &lt; 0.01). The poor sleep status (global PSQI score &gt; 5) was associated with 39.2% greater odds of being obese (95% CI: 1.04-1.87; P &lt; 0.05). Conclusions: In a population of young to older adult Macao residents, we found an inverse linear association between sleep quality and BMI. People with sleep disturbance and daytime dysfunction were more likely to be fat. Poor sleep quality was strongly associated with greater obesity.
Evaluation of lockdown effect on SARS-CoV-2 dynamics through viral genome quantification in waste water, Greater Paris, France, 5 March to 23 April 2020
Authors: S Wurtzer, V Marechal, JM Mouchel, Y Maday, R Teyssou, E Richard, JL Almayrac, L Moulin
Journal: Eurosurveillance (2020)

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease (COVID-19). People infected with SARS-CoV-2 may exhibit no or mild non-specific symptoms; thus, they may contribute to silent circulation of the virus among humans. Since SARS-CoV-2 RNA can be detected in stool samples, monitoring SARS-CoV-2 RNA in waste water (WW) has been proposed as a complementary tool to investigate virus circulation in human populations.AimTo test if the quantification of SARS-CoV-2 genomes in WW correlates with the number of symptomatic or non-symptomatic carriers.MethodWe performed a time-course quantitative analysis of SARS-CoV-2 by RT-qPCR in raw WW samples collected from several major WW treatment plants in Greater Paris. The study period was 5 March to 23 April 2020, including the lockdown period in France (from 17 March).ResultsWe showed that the increase of genome units in raw WW accurately followed the increase of human COVID-19 cases observed at the regional level. Of note, the viral genome could be detected before the epidemic grew massively (around 8 March). Equally importantly, a marked decrease in the quantities of genome units was observed concomitantly with the reduction in the number of new COVID-19 cases, 29 days following the lockdown.ConclusionThis work suggests that a quantitative monitoring of SARS-CoV-2 genomes in WW could generate important additional information for improved monitoring of SARS-CoV-2 circulation at local or regional levels and emphasises the role of WW-based epidemiology.
Development and Validation of a Tool Integrating the 21-Gene Recurrence Score and Clinical-Pathological Features to Individualize Prognosis and Prediction of Chemotherapy Benefit in Early Breast Cancer
Authors: Joseph A. Sparano, Michael R. Crager, Gong Tang, Robert J. Gray, Salomon M. Stemmer, Steven Shak
Journal: Journal of Clinical Oncology (2020)

The 21-gene recurrence score (RS) is prognostic for distant recurrence (DR) and predictive for chemotherapy benefit in early breast cancer, whereas clinical-pathological factors are only prognostic. Integration of genomic and clinical features offers the potential to guide adjuvant chemotherapy use with greater precision.
BIOM-02. IDENTIFYING MGMT ALTERATIONS AS BIOMARKERS OF SURVIVAL IN LUNG ADENOCARCINOMA WITH BRAIN METASTASES
Authors: Yasin Mamatjan, Jeffrey Zuccato, Fabio Moraes, Michael Cabanero, Wumairehan Shali, Jessica Weiss, Ming Tsao, Kenneth Aldape, Frances Shepherd, Gelareh Zadeh
Journal: Neuro-Oncology (2020)

Abstract EGFR-mutant lung adenocarcinomas (EGFRm-LUAD) have a higher risk of developing brain metastases (BM) compared to non-EGFR-mutant tumors. BM development has significant prognostic impact and leads to poorer patient survival. MGMT promoter methylation is known to determine response to therapy in other cancer types including intracranial gliomas but has not been investigated in EGFRm-LUAD BM. This work aims to assess whether MGMT promoter methylation predicts patient survival or BM development in EGFRm-LUAD patients. A large cohort of 90 primary EGFRm-LUAD tumors, of which 33 (37%) developed BM, were profiled using the Illumina Infinium MethylationEPIC Bead chip. Using the previously reported MGMT-STP27 approach that uses two CpG sites to predict MGMT methylation status, Cox modeling was performed to assess whether MGMT methylation status correlates with overall survival independent of other clinical factors. MGMT methylation significantly predicted poorer survival in EGFRm-LUAD patients that developed BM (p=0.0003) and did not develop BM (p=0.003). A multivariate cox analysis, adjusting for cancer stage and smoking status as potential confounders, showed that MGMT methylation (HR=6.2, 95%CI:2.2–17.4, p=0.0005) and BM development (HR=2.6, 95%CI:1.3–5.3, p=0.007) were both independently predictive of worse overall survival in EGFRm-LUAD patients. This finding of poorer survival in MGMT methylated EGFRm-LUAD is validated in an independent LUAD patient cohort. Total mutation burden, calculated by the number of mutations per megabase of DNA, was substantially higher in MGMT methylated tumours with an interquartile range (IQR) of 58 (30–71) compared to MGMT unmethylated tumours with the IQR of 5.5 (4.3–6.1) resulting p-value of 0.01 for this comparison. Overall, this work shows that MGMT promoter methylation status is an important prognostic biomarker in LUAD patients. MGMT promoter methylation status in EGFRm–LUAD patients with BM may be used to guide patient treatment with potentially a greater extent of treatment for high-risk patients.
An unbiased approach to defining bona fide cancer neoepitopes that elicit immune-mediated cancer rejection
Authors: Cory A. Brennick, Mariam M. George, Marmar M. Moussa, Adam T. Hagymasi, Sahar Al Seesi, Tatiana V. Shcheglova, Ryan P. Englander, Grant L.J. Keller, Jeremy L. Balsbaugh, Brian M. Baker, Andrea Schietinger, Ion I. Mandoiu, Pramod K. Srivastava
Journal: Journal of Clinical Investigation (2020)

Identification of neoepitopes that are effective in cancer therapy is a major challenge in creating cancer vaccines. Here, using an entirely unbiased approach, we queried all possible neoepitopes in a mouse cancer model and asked which of those are effective in mediating tumor rejection and, independently, in eliciting a measurable CD8 response. This analysis uncovered a large trove of effective anticancer neoepitopes that have strikingly different properties from conventional epitopes and suggested an algorithm to predict them. It also revealed that our current methods of prediction discard the overwhelming majority of true anticancer neoepitopes. These results from a single mouse model were validated in another antigenically distinct mouse cancer model and are consistent with data reported in human studies. Structural modeling showed how the MHC I-presented neoepitopes had an altered conformation, higher stability, or increased exposure to T cell receptors as compared with the unmutated counterparts. T cells elicited by the active neoepitopes identified here demonstrated a stem-like early dysfunctional phenotype associated with effective responses against viruses and tumors of transgenic mice. These abundant anticancer neoepitopes, which have not been tested in human studies thus far, can be exploited for generation of personalized human cancer vaccines.
NCOG-64. INCIDENCE OF EARLY OCULAR COMPLICATIONS AFTER PROTON RADIATION FOR CHILDHOOD BRAIN TUMORS
Authors: Abhishek Bavle, Michael Confer, Hilarie Simpson, Theresa Gavula, Naina Gross, Maria Lim, Rene McNall-Knapp, Janine Collinge
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVES To determine the incidence, timing and risk factors of ocular complications after proton radiation (RT) in childhood brain tumor patients, to better inform screening for these complications. METHODS We performed a single-institution retrospective review of children treated with proton RT for brain tumors, with ophthalmology data available. Data abstracted included demographics, radiation details and ocular complications (cataract, dry eyes, retinal changes). RESULTS We treated 81 children with brain tumors, with protons, from 2010-18. Forty three patients with ophthalmology data available, were included in the study, with a median age of 8.3 years (y) (0.8 – 20.6y) (13 craniospinal irradiation/CSI, 27 involved-field radiation/IFRT, 3 whole ventricle). Median follow-up from end of radiation to last eye exam was 2.1y (0.2 – 7.2y). The incidence of ocular complications was 21% (9/43 patients) overall, and 62% (8/13) after CSI. Bilateral cataracts were detected at a median of 3.2y post-radiation, with incidence of 14% (6/43) overall and 38% (5/13) after CSI. Three patients underwent lens replacement. Dry eyes developed in 23% (3/13) of patients during or soon after CSI (0.04 and 0.7y post-RT). One patient with craniopharyngioma developed retinal scarring and cataracts, 2.2y and 3.5y, after IFRT. The median radiation dose to the lenses, for patients with cataract, was 26.02 Gy RBE (4 patients: 19.41 – 31.54). For 3 patients with dry eyes, the median dose (Gy RBE) was 27.93 (11.98 – 28.71) to lenses, 36.96 (25.12 – 47.49) to lacrimal glands and 30.78 (25.08 – 36.49) to corneas (mean doses to bilateral ocular structures). CONCLUSIONS Children are at risk for cataract and dry eyes after cranial protons, especially CSI, and need ophthalmology follow-up. Larger studies are needed to validate these findings and identify risk-mitigation strategies, with longer follow-up to determine the incidence of ocular complications, and functional outcomes, after cranial proton radiation.
NIMG-53. GLUTAMATE/GABA RATIO ON MRS IS ELEVATED IN PATIENTS WITH LOWER GRADE GLIOMAS AND SEIZURES
Authors: Roberta Rudà, Riccardo Pascuzzo, Francesca Mo, Alessia Pellerino, Peter B Barker, Alberto Bizzi, Riccardo Soffietti
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND There is lack of information on the role of excitatory and inhibitory neurotransmitters in the development of seizures in patients with lower grade gliomas. Increase of glutamate and downregulation of GABA have been suggested in preclinical models and human surgical samples to be associated with brain tumor-related epilepsy. MATERIAL AND METHODS We prospectively investigated with the use of magnetic resonance spectroscopy (MRS) the differences in the ratio of metabolites (glutamate/GABA, glutamate/creatine and GABA/creatine) in the peritumoral areas between patients with or without seizures in a series of lower grade gliomas. Tumors were classified according to WHO Classification of 2016 as follows:11 grade II IDH mutated and 1p/19q codeleted; 3 grade III IDH mutated and 1p/19q codeleted; 6 grade II IDH mutated and 1p/19q intact; 1 grade III IDH mutated and 1p/19q intact; 1 grade II IDH wild-type. Patients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors. RESULTS At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency). CONCLUSIONS The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).
IMMU-46. LINEAGE DEPLETED HEMATOPOIETIC STEM CELLS POTENTIATE IMMUNE CHECKPOINT RESPONSE TO ANTI-PD1 AND ANTI-CD276 IN MURINE GLIOMA
Authors: Trisha Larkin, Marjorie Cruz, Catherine Flores
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Glioblastoma multiforme (GBM) is a malignant brain tumor with rapid growth and infiltration, high treatment resistance, and dismal survival. Intratumoral heterogeneity and poor CNS penetration contribute to treatment resistance. Flores et al. demonstrated that hematopoietic stem cell transfer could reprogram gene expression within the tumor microenvironment, sensitizing glioma-bearing mice to treatment with immune checkpoint blockade. The objectives of this study are to expand on the role of HSCs in potentiating efficacy to immune checkpoint blockade with anti-PD1 and anti-CD276. METHODS KR158B murine glioma cells were implanted into the caudate nucleus of C57BL/6 mice. Hematopoietic stem cells were derived from naïve syngeneic mice and lineage depleted using the CliniMacs system. On Day 5, HSCs (105cells) were administered. Anti-CD276 and PD-1 monoclonal antibodies were administered every five days for a total of four dose administrations. Mice to allocated to no treatment, anti-CD276 only, or HSCs with or without PD1 and anti-CD276. Groups were followed for survival. Data was analyzed with GraphPad Prism. RESULTS The combination of lineage depleted HSCs + anti-CD276led to increased median survival when compared to the survival of mice treated with anti-CD276 monotherapy with the mice who received the combination surviving for a median of 62 days versus 36 days (p = 0.001, CI 0.204 to 1.655). The combination of HSCs + PD-1 therapy led to increased median survival of 60 days and long-term survivors, replicating prior findings from our group. Mice treated with HSC transfer, anti-B7-H3, and anti-PD-1 demonstrated a median survival of 76 days (p = 0.037). CONCLUSION We demonstrate a compounded survival effect when anti-B7-H3 and anti-PD1 were administered together with lineage depleted HSCs, suggesting an expanded avenue for overcoming treatment resistance. Future studies will be important to characterize the immune effects of combinatorial immune checkpoint administration with adjuvant HSC transfer.
HGG-07. CYCLIN-DEPENDENT KINASES AS TARGET STRUCTURES FOR CANCER THERAPY – A COMPARATIVE IN VITRO ANALYSIS ON PATIENT-DERIVED GLIOBLASTOMA CELL CULTURE MODELS
Authors: Christin Riess, Carl Friedrich Classen, Claudia Maletzki
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Current therapeutic approaches have limited clinical success for Glioblastoma patients, making novel strategies urgent. Cyclin-dependent kinases (CDK) are crucial in cell cycle, oncogenic transcription, DNA repair, and stem-cell renewal. Glioma cells frequently show genomic alterations in CDKs. Here, we evaluated the antitumoral activity of selective CDK inhibitors (CDKI) abemaciclib (CDK4/6), palbociclib (CDK4/6), and dinaciclib (CDK1/2/5/9) alone and in combination with chemo-/radiotherapy. MATERIALS/ METHODS Low passage glioblastoma cell lines (N=5) with different molecular characteristics were cultured in 2D and 3D (neurospheroids (NSPs), glioma stem-cells (GSCs). The impact of CDKI alone or in combination with TMZ and radiation (2Gy) was examined. Viability was measured using Calcein-AM and 3D-Glo assays; DNA double-strand breaks by γ-H2AX immunofluorescence. Functional analyses were performed from a 2D culture (72h treatment). RESULTS Dinaciclib significantly affected viability of GBM cell lines even shortly after low-dose treatment. CDK 4/6 inhibitors were less effective. Abemaciclib and dinaciclib acted radio-sensitizing. Dinaciclib combined with different substances (72h, dose: IC20), synergistically potentiated antitumoral effects. In a scratch assay, abemaciclib decelerated wound healing; dinaciclib even induced cell death. Microarray analysis revealed altered gene expression: Genes mediating cell adhesion, division, DNA-binding, apoptosis (Casp3,Casp8), senescence (ASF1A,CENPA,FBXO31), and autophagy (ATG4D,ATG2A,SOGA1) were upregulated. Chemotaxis-mediating (CXCL8,CCL20) and proto-oncogenes like JUNB and FOS were strongly down-regulated. Long-term treatment induced dinaciclib resistance in 1/5 cases, and none abemaciclib-treated cells. This was reversed when dinaciclib was combined with TMZ. CONCLUSION Our results demonstrate strong anti-GBM activity of dinaciclib and abemaciclib, with additive effects of chemotherapy and radiosensitization, encouraging to move forward this strategy.
An insight into the in vivo imaging potential of curcumin analogues as fluorescence probes
Authors: Yu Liu, Chuang Zhang, Hao Pan, Li Li, Yanjie Yu, Bingmi Liu
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Curcumin and its derivatives have good electrical and optical properties due to the highly symmetric structure of delocalized π electrons. Apart from that, curcumin and its derivatives can interact with numerous molecular targets, thereby exerting less side effects on human body. The fluorescence emission wavelength and fluorescence intensity of curcumin can be enhanced by modifying its π-conjugated system and ß-diketone structure. Some curcumin-based fluorescent probes have been utilized to detect soluble/insoluble amyloid-ß protein, intracranial reactive oxygen species, cysteine, cancer cells, etc. Based on the binding characteristics of curcumin-based fluorescent probes with various target molecules, the factors affecting the fluorescence intensity and emission wavelength of the probes are analyzed, in order to obtain a curcumin probe with higher sensitivity and selectivity. Such an approach will be greatly applicable to in vivo fluorescence imaging.
PATH-38. METASTATIC MENINGIOMA CAUSING CHRONIC RESPIRATORY FAILURE
Authors: Dhiren Wallace, Gerald Wallace, Nichols Fenwick, John Vender, Ambika Sood, Samantha Mattox, Suash Sharma
Journal: Neuro-Oncology (2020)

Abstract Meningiomas are the most common primary intracranial tumor accounting for almost 37% of all CNS tumors. Malignant meningiomas are uncommon, accounting for 0.5% of all meningiomas. Malignant meningioma that is metastatic outside the cranium/skull is even rarer, with only a few case reports. Metastases to the lung and abdomen have been reported and thought to travel via venous drainage. WHO Grading suggest that Grade III meningiomas have the greatest potential to metastasize extra-cranially. We present the case for the 47-year-old Senegalese American man with biopsy proven Grade II meningioma metastatic to his lungs with resultant hypercapnic respiratory failure.