bluuebunny/crossref_metadata_2025_split huggingface dataset:
WALLABY pilot survey: the Tully–Fisher relation in the NGC 4808, Vela, and NGC 5044 fields
Authors: Mould Jeremy , Jarrett T H , Courtois Hélène , Bosma Albert , Deg Nathan , Dupuy Alexandra , Staveley-Smith Lister , Taylor E N , English Jayanne , Rajohnson S H A , Kraan-Korteweg Renée , Forbes Duncan , Dénes Helga , Lee-Waddell Karen , Shen Austin , Wong O I , Holwerda Benne , Koribalski Bärbel , Leahy Denis , Piña Pavel Mancera , Yu Niankun 
Published: June 2024

ABSTRACT
The Tully–Fisher Relation (TFR) is a well-known empirical relationship between the luminosity of a spiral galaxy and its circular velocity, allowing us to estimate redshift independent distances. Here we use high signal-to-noise H i 21-cm integrated spectra from the second pilot data release (PDR2, 180 deg2) of the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY). In order to prepare for the full WALLABY survey, we have investigated the TFR in phase 2 of the pilot survey with a further three fields. The data were obtained with wide-field Phased Array Feeds on the Australian Square Kilometre Array Pathfinder (ASKAP) and have an angular resolution of 30 arcsec and a velocity resolution of $\sim$4 km s−1. Galaxy luminosities have been measured from the Wide-field Infrared Survey Explorer, and optical galaxy inclinations from the Dark Energy Camera Legacy Survey. We present TFRs for wavelengths from 0.8 to 3.4 μm. We examine sources of galaxy inclination data and investigate magnitudes from the DECam Local Volume Exploration Survey and DENIS catalogues and the 4HS target catalogue based on the VISTA Hemisphere Survey. We consider the baryonic TFR. These are all of interest for TFR using the full WALLABY survey of 200 000 galaxies. We demonstrate that WALLABY TFR distances can take their place among state-of-the-art studies of the local velocity field.
African, Black, and Western Conceptions of Human Dignity
Authors: Molefe Motsamai 
Published: June 2024

Abstract
The article highlights the potential that African and Black Philosophy can contribute towards the debates on human dignity. It facilitates a three-way philosophical conversation among the Western, African, and Black conceptions of human dignity. It is motivated by the skepticism in the African and Black approaches to ethics that reject the view that some ontological capacity can ground intrinsic value, or human dignity. The article distinguishes the merit-based (the African and Black Philosophy) from the capacity-based approaches (the Western philosophy) to human dignity. In light of the comparisons among the three theories of human dignity, the article identifies three important lessons for moral-political philosophy. First, the Western conception of human dignity needs to explain and justify grounding of value on a descriptive feature. Secondly, the Black conception of dignity is a version of virtue-based account of it, which places a prime on resistance and struggle against domination. Finally, the capacity-based approach seems to have moral-theoretic advantages in dealing with issues in bioethics, environmental ethics, and political philosophy, which the African and Black conceptions of human dignity seems not to have.
ATRT-02. RECAPITULATING THE POST-SURGICAL BRAIN MICROENVIRONMENT OF ATYPICAL TERATOID RHABDOID TUMOURS TO IDENTIFY MEMBRANE PROTEIN CANDIDATES FOR TARGETED THERAPY
Authors: Mistry Shaylen M , Porter Harry , McCorie Phoebe , Snary Anya , Bailey Hannah , Layfield Robert , Rahman Ruman 
Published: June 2024

Abstract

BACKGROUND
Atypical Teratoid Rhabdoid Tumours – (AT/RT) are rare and aggressive tumours primarily arising in the hind brain of children under three, conferring median survival of &lt;12 months. Surgery remains the only standard treatment; however tumours recur from post-surgical residual disease. The utilisation of PolyEthylene Glycol Diacrylate – (PEGDA) hydrogel and decellularised human brain cerebellum extracellular matrix aim to recapitulate AT/RT post-surgery brain microenvironments, where we hypothesise AT/RT plasma membrane proteins represent viable molecular therapy targets.

METHODS
AT/RT and astrocyte membrane protein cellular fractions were extracted and analysed using liquid chromatography-mass spectrometry. Proteomic analyses was integrated to identify differentially expressed AT/RT and astrocyte membrane proteins.

RESULTS
PEGDA and decellularised brain tissue were biocompatible for AT/RT-astrocyte co-cultured spheroid growth. AT/RT and astrocyte KEGG Pathway analysis revealed more specific oncology-based pathway expression in membrane protein than total protein, thus reinforcing membrane proteins as suitable therapeutic targets. Between the top 20 expressed membrane proteins, only ATP1A1 was shared exclusively between all AT/RT cells and astrocytes, suggesting a potential functional role. Membrane proteins showing shared expression when normalised against each AT/RT cell line included ATP1A1, HSPD1, GNA13 and SLC3A2, indicating biological similarities between AT/RT subtypes. Membrane proteins expressed similarly in AT/RT-MYC subtypes include ATP1A1, SLC7A5 and EEF1A1. ATP1A1 network analyses of AT/RT and astrocyte membrane protein pathways displayed strong interactions with ATP1B1, SLC7A5 and SLC3A2, therefore likely to map common expressed shared pathways.

CONCLUSIONS
AT/RT membrane protein pathways offer novel therapeutic targets directly amenable for drug repurposing. Future work prioritises proteomic analysis utilising 3D AT/RT spheroids and cerebellum brain tissue to maximise accurately recapitulating AT/RT post-surgical microenvironments.
ATRT-08. ATYPICAL TERATOID RHABDOID TUMOR IN AN ADULT PATIENT WITH DOWN SYNDROME
Authors: Judd Dallin , Almefty Kaith K , Vern-Gross Tamara Z , Hoffman Lindsey M , Tiwari Nishant , Vaughn Jennifer A , Mangum Ross 
Published: June 2024

Abstract

BACKGROUND
Atypical teratoid/rhabdoid tumor (ATRT) is a malignant, highly aggressive embryonal tumor of the central nervous system. Long-term survival remains dismal despite aggressive multimodal therapy, including a maximal safe surgical resection and intensive systemic chemotherapy +/- radiation therapy. While these tumors typically present in infancy or early childhood, there are scattered case reports of adult-onset ATRT. Making prognostic conclusions or therapeutic decisions for this older patient population remains challenging due to the paucity of these reports.

CASE REPORT
A 25-year-old female with Down syndrome presented with nausea, vomiting, dysphagia, and facial droop and was found to have an avidly enhancing, left cerebellopontine angle mass. There was initial clinical suspicion for leukemic chloroma given the patient’s Down syndrome status and known association with higher rates of hematologic malignancy concurrent with a dramatic scarcity of solid tumors in the Down syndrome population. However, histology demonstrated sheets of high-grade rhabdoid cells with loss of INI1 expression, pathognomonic for ATRT. Further sequencing defined a frameshift mutation in SMARCB1 (p.C298), and methylation profiling matched with high confidence to the MYC subclass of ATRT. The patient was treated with subtotal surgical resection and focal proton radiation, followed by chemotherapy on a modified regimen based on the Children’s Oncology Group protocol, ACNS0333. Systemic methotrexate and all consolidative high-dose chemotherapy with stem cell rescue were omitted due to concern for heightened risk of treatment-related toxicity. The patient remains alive and clinically asymptomatic 19 months from diagnosis.

CONCLUSION
This report represents the first known case of ATRT in an adult patient with Down syndrome, offering unique mechanistic insight into the tumorigenesis of ATRT. Adult ATRT is a rare entity without standardized treatment or established prognostic understanding. Further studies are needed to define an appropriate risk-adapted therapeutic approach for this patient population.
ATRT-14. TARGETING ATYPICAL TERATOID RHABDOID TUMORS USING A NOVEL BI-FUNCTIONAL COREST INHIBITOR
Authors: Geethadevi Anupa , Collard Marianne , Findlay Tyler , Fisher Robert , Vaidya Nikhil , Deng Yiming , Eberhart Charles , Cole Philip , Alani Rhoda , Rubens Jeffrey , Raabe Eric 
Published: June 2024

Abstract

BACKGROUND
Atypical teratoid/rhabdoid tumors (ATRT) are deadly infantile brain tumors driven by a loss-of-function mutation of SMARCB1, a critical component of the SWI-SNF chromatin remodeling complex. However, residual SWI-SNF activity inhibits EZH2 at all loci except where CoREST colocalizes with these complexes, specifically contributing to ATRT pathogenesis. This results in hypermethylation and subsequent repression of genes coding for neuronal differentiation and tumor suppressors, accounting for ATRTs’ stem-like state, aggressive growth, and therapy resistance. We functionally inhibited the CoREST complex in ATRT cells by targeting its core enzymes LSD1 and HDAC1/2 using a bi-functional inhibitor, corin.

METHODS
We evaluated the efficacy of corin to target ATRT cells (BT37, CHLA05 and CHLA06) by measuring cell proliferation (BrdU immunofluorescence/IF), apoptosis (CC3 IF, cPARP Western blotting/WB, MUSE Annexin V), histone modifications (WB) and neuronal differentiation (WB, IF). Whole mRNA sequencing and ATAC-Seq were performed to see the global transcriptomic and chromatin changes driven by corin. Further, we examined the long-term survival advantage rendered by corin in an in-vivo orthotopic xenograft model of ATRT.

RESULTS
Corin reprogrammed the chromatin structure in ATRT cells in favor of pathways related to neuronal differentiation, cell differentiation, and axonal development while downregulating pathways related to proliferation and cell cycle (mRNA Seq, ATAC-Seq). Corin inhibited AT/RT cell growth and proliferation (p&lt;0.05), increased apoptosis (p&lt;0.05), increased H3K4me1 and H3K9Ac levels (p &lt; 0.001), and induced neuronal differentiation (IF: Beta-3-tubulin, MAP2, Synaptophysin). Intratumoral delivery of corin increased the median survival of mice bearing aggressive orthotopic CHLA06 tumors from 14 to 35 days compared to control (p=0.02, Log Rank test).

CONCLUSIONS
Targeting the CoREST complex with corin disrupts ATRT’s epigenetic abnormalities, reversing their stem-like state and slowing tumor growth, thus presenting a promising new strategy that may translate into the clinical setting to help improve ATRT’s dismal survival.
ATRT-17. INHIBITING THE MAP KINASE PATHWAY WITH MEK INHIBITOR MIRDAMETINIB SUPPRESSES CANCER GROWTH IN ATYPICAL TERATOID/RHABDOID TUMORS
Authors: Deng Yiming , Malebranche Kristen , Findlay Tyler , Geethadevi Anupa , Eberhart Charles , Rubens Jeffrey , Raabe Eric 
Published: June 2024

Abstract

BACKGROUND
Atypical teratoid/rhabdoid tumors (ATRT) are poor-prognosis infantile brain tumors. Our prior studies examining ATRT primary tissues have shown an increased expression of phospho-ERK, a downstream effector of MEK in the mitogen-activated protein kinase (MAPK) pathway. The elevated MAPK pathway potentially contributes to drug resistance, aggressive cancer growth, and poor treatment outcomes. Mirdametinib is a highly specific MEK1/2 inhibitor reported to have superior blood-brain-barrier penetration compared to other MEK inhibitors. We hypothesized that mirdametinib can suppress ATRT tumor growth and improve overall survival.

METHODS
Mirdametinib effects were assessed through western blot for MAPK markers. Western blot analysis, Muse flow cytometer assays, and immunofluorescence were used for proliferation and apoptosis. Mirdametinib impact on survival was determined in orthotopic xenograft models of ATRT.

RESULTS
Mirdametinib decreased MAPK pathway activity in five ATRT cell lines (western blot: phospho-ERK). Cell lines treated with mirdametinib exhibited lower rates of proliferation (western blot: phospho-Rb; BrdU immunofluorescence staining: CHLA05 p=0.015, CHLA06 p&lt;0.0001, BT37 p&lt;0.0001 compared to DMSO control by t-test). Mirdametinib induced apoptosis in ATRT cells (western blot: cPARP; Muse Annexin V Assay: CHLA04, CHLA05, CHLA06, and BT37, p&lt;0.0001, CHLA266, p&lt;0.01 compared to DMSO control by t-test; cleaved caspase-3 immunofluorescence staining: CHLA05, CHLA06, and BT37, p&lt;0.0001 compared to DMSO control by t-test). Daily oral delivery of mirdametinib treatment significantly extended the survival of mice bearing the very aggressive orthotopic CHLA06 tumors (17 to 24 days, log-rank test p=0.038 compared to vehicle control) and decreased the expression of phospho-ERK (western blot). Testing against additional ATRT orthotopic xenografts is currently underway.

CONCLUSIONS
Mirdametinib inhibits the MAPK pathway both in vitro and in vivo, suppressing proliferation and inducing apoptosis in ATRT. Our studies suggest that pharmacologically inhibiting the MAPK pathway with mirdametinib may be an effective strategy to target ATRT and help extend survival in this deadly disease.
BIOM-01. CARBONIC ANHYDRASE IX INTERPLAY WITH LOCAL AND SYSTEMIC IMMUNE RESPONSE IN PEDIATRIC BRAIN TUMORS
Authors: Kapitancuke Monika , Petroska Donatas , Petrosiute Agne , Luciunaite Asta , Grinceviciene Svitrigaile , Matulis Daumantas , Rocka Saulius , Rinkevicius Dainius , Raugalas Ramunas , Rascon Jelena 
Published: June 2024

Abstract

BACKGROUND
Brain tumors (BT) remain the leading cause of death among childhood cancers. There is an urgent need to identify novel targets in these patients. BT progression depends on the adaptive responses to hypoxia. Carbonic anhydrase IX (CAIX) helps cancer cells survive in a hypoxic environment and can be potentially as a therapeutic target. The role of CAIX in the interplay between the tumor and immune cells requires in-depth investigation to design effective therapies.

METHODS
Fresh BT, blood, and intraoperative cerebrospinal fluid (iCSF) samples were collected prospectively from pediatric patients, who underwent brain tumor surgery at Vilnius University Hospital Santaros Klinikos from March 2022 to December 2023. All tumor types were included. Immunohistochemistry (IHC) and flow cytometry (FC) were performed to analyze the expression of CAIX and selected immunological markers in the fresh tumor, iCSF and peripheral blood mononuclear cells (PBMCs). Soluble CAIX content in serum and iCSF was assessed by ELISA. In addition, a retrospective analysis of previously diagnosed pediatric glioma specimens was performed by IHC.

RESULTS
Twelve patients with heterogeneous BT types have been enrolled prospectively and 17 patients with glioma were reviewed retrospectively. Glioma accounted for 72% (21/29) of all samples. IHC showed that 57% of gliomas were positive for CAIX as well as a moderate correlation between the CAIX score and the expression of CD44, CD206, and CCR2 markers. PD-1/PD-L1 expression was negligible. In the prospective cohort, 83% (10/12) of BT tissue was positive for CAIX by IHC and FC. Soluble CAIX was detectable in 40% of iCSF samples, but not in serum. We found a correlation trend of CAIX expression in the fresh tumor cells and iCSF with increased CCR2 expression on CD45+ PBMCs.

CONCLUSIONS
This interim analysis showed a correlation between CAIX tumor expression and immune biomarkers, prompting further investigation by enrolling more patients.
BIOM-05. THE GUT-MICROBIOTA COMPOSITION IN PEDIATRIC BRAIN TUMORS: AN EMERGING CRUCIAL PLAYER
Authors: Dossena Chiara , Bergamaschi Luca , Rossignoli Federico , Licata Armando G , Oriani Matilde , Marra Manuela , Carollo Maria , Massimino Maura , De Cecco Loris 
Published: June 2024

Abstract

BACKGROUND
Central nervous system (CNS) tumors represent the main cause of cancer-related deaths in children diagnosed at 0–14 years. It has been demonstrated that the bidirectional interaction between gut microbiota and brain, called microbiota-gut-brain axis, has a key role in pathophysiological processes, mediating proliferation of brain tumor cells. The aim of this study was to determine whether the gut microbiota composition of pediatric patients affected by CNS tumors has peculiarities.

METHODS
We included 42 pediatric patients from the clinical study NET-2019-12371188 that were divided in two groups: i) 12 affected by SNC tumors (group 1); ii) 30 affected by other tumor types (group 2), non related to CNS. From their stool samples, microbial DNA was extracted, 16S DNA libraries were generated and sequenced on IONS5xl (ThermoFisher). From the resulting operational taxonomic unit (OTU) tables, the composition of gut-microbiota was analyzed.

RESULTS
To determine the richness of gut microbiota in terms of different taxa, alpha diversity analysis was performed. We applied the number of observed features as data matrix and it was lower in group 1 compared to group 2 (p-value= 0.003); on the other side, the homogeneity of taxonomic groups was determined by Pielou’s evenness index, that was higher in group 1 (p-value=0.018), compared to group 2. Beta-diversity measured with unweighted UniFrac metrics revealed that the taxonomic and phylogenetics composition of gut microbiota is different between group 1 and 2 (p-value= 0.03). Finally, linear discriminant analysis effect size (LEfSe) revealed an increase of genus from RF32 order in group 1, while in group 2 genus Blautia ad genus from Coriobacteriaceaea family increased.

CONCLUSIONS
In conclusion, gut microbiota has a peculiar composition in pediatric patients affected by CNS tumors.
CP-14. VOLUMETRIC ANALYSIS OF PAEDIATRIC CRANIOPHARYNGIOMAS: CLINICAL-RADIOLOGICAL CORRELATION STUDY
Authors: Yamaki Vitor Nagai , Sidpra Jai , Peres Bruno Santanna , Massey Flavia , Quianga Catuto Domingos Alexandre , da Borsatto Guilherme Jose Costa , Telles Joao Paulo Mota , Silva Inês Nobrega , Martinez-Barbera Juan Pedro , Biswas Asthik , Mankad Kshitij , Gan Hoong-Wei , Marcus Hani J , Jeelani Noor ul Owase , Hargrave Darren R , Matushita Hamilton , Marie Suely Kazue Nagahashi , Aquilina Kristian 
Published: June 2024

Abstract

BACKGROUND
Craniopharyngioma are heterogeneous hypothalamopituitary tumours with solid and cystic components which have a distinct natural history. Neuroimaging follow-up and the definition of progressive disease is challenging due to unpredictable growth of the inflammatory cystic component.

METHODS
This multicentre retrospective observational study aimed to describe the clinical-radiological correlation of craniopharyngiomas at two paediatric neurosurgery units (GOSH,UK and USP,Brazil). Craniopharyngiomas treated over a 20-year period were identified and standardized clinical outcomes recorded. Baseline MRIs were reviewed and volumetric T1-weighted images segmented by a board-certified paediatric neuroradiologist.

RESULTS
Of 123 patients, 92 baseline MRIs were available for image analysis (USP=32; GOSH=60). No differences between series were identified in either demography (mean age: USP=9.2±4.6; GOSH=8.2±4.1 years) or tumour characteristics, with tumours being predominantly cystic (USP=75%; GOSH=76%), localised to the sellar/suprasellar region (USP=84%; GOSH: 88%), and on pre-chiasmatic (USP=34%; GOSH=22%) or retro-chiasmatic (USP=59%; GOSH=67%) locations. Pre-chiasmatic tumours were associated with an increased prevalence of visual symptoms at presentation (p=0.006) and worse recovery of visual acuity at long-term follow-up (p=0.021). Regarding volumetric analysis, mean volumes were 16.6±25.1cm3 for the cystic component and 38.3±10cm3 for the solid component. Volumes of the solid and cystic components had no correlation with each other. Larger cystic tumour volumes were correlated with a greater prevalence of diabetes insipidus at presentation (p=0.06). Larger solid tumours were significantly related to younger ages (p=0.02) and had worse PFS in our series. In terms of long-term outcomes, high volume cystic tumours were related to worse hypothalamic outcomes. In multivariate analysis (n=92), Paris classification did not predict long-term outcomes.

CONCLUSIONS
Volumetric analysis of craniopharyngiomas showed significant correlation with the onset of diabetes insipidus and hypothalamic long-term outcomes. Larger cystic craniopharyngioma were more common in younger patients. The Paris classification did not predict long-term outcomes in multivariate analysis.
CP-16. PROTEOMIC ANALYSIS OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA REVEALS A COMPLEX NETWORK OF ECM REMODELING
Authors: Knox Aaron , Medlin Stephen , Chee Keanu , Staulcup Susan , Prince Eric W , Hankinson Todd C , Mitra Siddhartha 
Published: June 2024

Abstract

BACKGROUND
Adamantinomatous craniopharyngiomas (ACPs) are the most challenging pituitary tumors in children. Despite their histological classification as benign, ACPs exhibit an aggressive clinical demeanor, posing challenges in management and conferring a suboptimal quality of life. The anatomical intricacies of ACPs often preclude complete surgical excision. The greatest morbidity of ACP is associated with damage to the hypothalamus - iatrogenically or through direct invasion, which may be dependent upon extracellular matrix (ECM) remodeling. We endeavored to describe the ECM components of ACPs and the protein milieu that may alter the ECM.

METHODS
High throughput imaging mass cytometry (IMC) alongside conventional histological staining methods. IMC offers unparalleled resolution in detecting ECM constituents, which may play pivotal roles in tumor pathophysiology and could represent novel therapeutic targets. We also employed SomaScan, an innovative, high-throughput, aptamer-based protein quantification platform. SomaScan utilizes Slow Off-Rate Modified Aptamers (SOMAmer Reagents) for the measurement of a broad spectrum of proteins within various biological fluids, including plasma and cyst fluid.

RESULTS
We identified prominent collagen tracts within ACP, which are further interspersed with areas of increased fibrosis surrounding wet keratin, suggestive of focal inflammatory response to cyst fluid. SomaScan identified elevated levels of proteins implicated in neutrophil degranulation. Neutrophil degranulation plays a significant role in ECM remodeling, a process critical to tumor progression and invasion. The association of neutrophils with ECM remodeling in ACPs suggests a potential mechanism through which these tumors might facilitate their own growth and invasion. The elevated protein markers of neutrophil degranulation may also serve as potential biomarkers or therapeutic targets, offering a novel approach to managing these tumors.

CONCLUSIONS
By integrating the data from IMC and SomaScan, our findings reveal a complex interplay between ACPs and the immune system, particularly highlighting the role of neutrophils in the tumor microenvironment.