bluuebunny/crossref_metadata_2025_split huggingface dataset:
IN VITRO MODELLING OF CROSSTALK BETWEEN PAEDIATRIC CEREBELLAR TUMOURS AND HEALTHY BRAIN TISSUE IN THE POST-SURGICAL MICROENVIRONMENT
Authors: Porter Harry , McCrorie Phoebe , Moloney Cara , Collier Pamela , Croxall Nicola , Onion David , Kotowska Anna , Scurr David , Diksin Mohammed , Grundy Richard , Rahman Ruman 
Published: September 2023

Abstract

AIMS
Atypical Teratoid Rhabdoid Tumours (ATRT) and Medulloblastoma are embryonal brain tumours arising in the cerebellum. Many in vitro models of paediatric brain tumours fail to recapitulate key pathophysiological characteristics. We aim to address this gap by developing a bespoke model incorporating cellular and acellular aspects of the TME.

METHOD
Cerebellar tissue from a healthy human autopsy donor brain was decellularized to form cerebellar ECM and incorporated into a “blank slate” hydrogel. Spheroid-forming multi-well plates were coated with the hydrogel and used to culture patient-derived Medulloblastoma and ATRT cells in co-culture with primary human cerebellar astrocytes.

RESULTS
Tissue decellularization and retention of ECM components was demonstrated using colorimetric assays and Orbitrap Secondary Ion Mass Spectrometry. Biocompatibility of the ECM hydrogel was shown in 2D and 3D culture conditions using the CellTiter-Glo® 3D cell viability assay. Furthermore, the size and morphology of spheroids grown on the hydrogel was characterised using a high-throughput imaging and analysis methodology. Cell lines were labelled to facilitate discrimination between tumour cells and astrocytes. Optical sections of co-culture spheroids generated using confocal microscopy showed cell-cell contact between tumour cells and astrocytes. Finally, co-culture spheroids were separated by fluorescence activated cell sorting to facilitate downstream analyses on individual cell types.

CONCLUSIONS
This work presents a highly characterised model of medulloblastoma and ATRT interactions with healthy brain tissue, mimicking the immediate post-surgical microenvironment. Future work will utilise transcriptomics to assess the tumour-astrocyte crosstalk modelled using this system.
DIFFERENTIAL CELL SURFACE PROTEOMICS OF FLOTILLIN-1, HMGB1 AND AMINOPEPTIDASE IN H3 MUTATED PAEDIATRIC HIGH-GRADE GLIOMA
Authors: Walugembe Chloe , Litchfield-Williams Matthew , Snary Anya , Layfield Robert , Haque Farhana 
Published: September 2023

Abstract

AIMS
High-grade gliomas (HGG) are the deadliest central nervous system tumour in children. Despite this, treatment options remain elusive, leaving children with a dismal prognosis. Histone H3.3 mutations, K27M and G34V/R have been identified as the two most common recurrent somatic mutations in paediatric HGG (pHGG). These mutations are present in 50% of pHGG compared to only 1% in adults.
Our previous research on cell membrane protein analyses have identified different signature of unique and common cell membrane proteins in H3-G34R/V mutated pHGG, in comparison to H3 wild type tumour. Among these we have identified flotillin-1, HMGB1 and aminopeptidase N. Flotillin-1 promotes numerous malignancies, High mobility group box 1(HMGB1) functions as an oncogene and aminopeptidase N is a cell surface metallo- protease involved in tumour progression. We have now verified the expression and localization of these cell surface proteins in H3 mutated and wildtype tumour, in order to target them for developing novel therapeutics.

METHOD
Cell membrane proteomics were further verified though mass-spectrometric data analyses. Expression and localization of flotillin-1, HMGB1 and Aminopeptidase in H3.3 mutated pHGG cell lines in comparison to H3 wildtype glioma were analysed, using different protein expression assays including immunofluorescence microscopy and western blot assays.

RESULTS
Experimental analyses showed differential protein expression and localization of Flotillin-1, HMGB1 and Aminopeptidase and verified the mass-spectrometric proteomic data in H3-G34V pHGG, in comparison to wild- type pHGG.

CONCLUSIONS
This new knowledge will help us utilise Flotillin-1, HMGB1 and Aminopeptidase N, as potential therapeutic targets for these unique H3 mutated children’s brain tumours.
ADULT HISTONE G34 MUTANT GLIOMAS - A SINGLE CENTRE EXPERIENCE OVER 10 YEARS
Authors: Obrocki Ruth , Merve Ashirwad , Rees Jeremy 
Published: September 2023

Abstract

AIMS
Histone G-34-mutant (H3 G34) gliomas are rare, aggressive infiltrating tumours of the cerebral hemispheres and are classified as WHO grade 4 paediatric type diffuse high-grade glioma. They most commonly affect children and adolescents.
We describe the clinicopathological characteristics of adult H3 G34-mutant gliomas seen at the National Hospital for Neurology and Neurosurgery over the last 10 years.

METHOD
We retrospectively analyzed clinic radiological data on all cases identified from the neuropathology database. Data were extracted on patient demographics, clinical and radiological features and outcome.

RESULTS
Six patients (2 male, 4 female) were identified, The median age of onset was 26 years (range 17-38 years). One patient presented with a Motor Neurone Disease type syndrome (progressive asymmetric spastic tetraparesis and bulbar symptoms), two with cognitive decline and three with symptoms of raised intracranial pressure. All tumours were supratentorial - 2 patients had mass lesions typical of a high-grade glioma, 1 patient had imaging features consistent with an intraventricular ependymoma. 3 patients had imaging findings that suggested a non-tumour diagnosis with extensive white matter disease more in keeping with an inflammatory demyelinating process or a leucodystrophy.
The median overall survival was 23 Months (range 10 - 68 months).

CONCLUSIONS
Adult Histone G34-mutant gliomas have a variable presentation and are associated with a prognosis similar to other high-grade gliomas. The diagnosis should be considered in the differential of patients presenting with a predominantly white matter disorder. Multi-centre studies are needed to better delineate the phenotype and prognostic features.
MATHEMATICAL MODELLING OF SURVIVAL IN LOW GRADE GLIOMAS AT MALIGNANT TRANSFORMATION
Authors: Tan Lily , Ruffle James , Rees Jeremy , Kosmin Michael , Nachev Parahkev , Hyare Harpreet 
Published: September 2023

Abstract

AIMS
Low grade gliomas (LGG) represent 14.6% of gliomas and may remain stable years after initial diagnosis. MRI features suggesting malignant transformation (MT) include enlargement of non-enhancing areas and increasing enhancement but have low specificity. We report the first stages of a deep learning model to predict survival using radiomic feature extraction at MT, clinical and molecular genetics.

METHOD
Retrospective analysis of all LGGs treated at our institution (2005 - 2020) with histology, molecular genetics and MRIs. 766 patients: 457 IDH mutant astrocytomas, 251 IDH mutant 1p19q co-deleted oligodendrogliomas and 58 other gliomas; 398 male, 368 female; mean age 51 years; range 16-89. MRIs underwent in-house tumour segmentation pipeline with radiomic feature extraction of whole tumour (wt), enhancing (enh), non-enhancing (ne) component and oedema components.

RESULTS
At MT, mean wt volume was 36404mm3 (SD 37213mm3) with mean 2D-diameter of 75.90mm (SD 27.23mm). Mean tissue compartmental volumes: enh 9539mm3 (SD 17578mm3), ne 26865mm3 (SD 33796mm3), and oedema 61067mm3 (SD 61535 mm3). 92 lesions contained no post-contrast enhancing tissue. Lesions were more commonly frontal or temporally based, with relative sparing of parietal and occipital lobes. No predilection for left or right hemisphere.

CONCLUSIONS
Majority of LGGs demonstrate contrast enhancing lesions at MT in a frontal or temporal spatial distribution with no hemispheric predilection. We plan to extract the MRI features at MT to build a survival model with clinical, treatment and molecular genetic data. Defining the radiological features at MT would enable prognostication and support clinical decision-making in this patient group.
INTEGRATIVE ANALYSIS OF DIFFERENTIALLY REGULATED PROTEINS IN MENINGIOMA
Authors: Shah Maryam , Banton Matthew , Adams Claire , De Assis Leandro , Sharma Vikram , Hanemann Oliver 
Published: September 2023

Abstract

AIMS
Meningiomas are common primary intracranial tumours that arise from meninges. loss of chromosome 22q is common genetic event observed in meningiomas. About 50% of meningiomas harbour mutations in NF2 gene that resides on chromosome 22. Moreover, frequent mutations have been observed in AKT1, KLF4, TRAF7, and SMO genes. Meningiomas are divided into different genomic subgroups that express unique proteomic profiles. This study aims to investigate genomic background of meningioma and to determine the impact of mutations on underlying protein expression to identify druggable targets.

METHOD
Total 96 meningioma samples were sequenced using Illumina TruSight Oncology 500 panel. The raw sequence data was analyzed using TSO500 App. The variant data was annotated using Cancer Genome Interpreter and ANNOVAR. Clinical enrichment analysis was performed to investigate common pathways. Genomic data was correlated with LC-MS based proteomic data to determine variants effect on downstream processes.

RESULTS
Results showed an average of 1083 total and 7 driver mutations per sample. NF2 gene was found among highly mutated genes in tumour samples. Almost all NF2 mutations were frameshift, splice site and nonsense mutations, previously reported to be associated with high rate of multiple and recurring meningiomas. Additionally, driver mutations were identified in known meningioma genes including AKT1, KLF4, and TRAF7 along with previously unpublished mutations in ERBB2, MET, ARID5B, etc. The results correlate with tumour location, grade, and histopathological subtype.

CONCLUSIONS
The study identified common as well as unique driver mutations in meningioma samples. After functional validation, novel driver mutations could further enhance personalized treatment for meningioma patients.
TITLE THE TEENAGE AND YOUNG ADULT (TYA) POPULATION (16-24YO) BENEfiT FROM HAVING SPECIALIST NURSE INPUT
Authors: Hedges Sarah , La Jessica , Robinson Charlotte , Hurwitz Victoria , Kostick Ellie , Suarez Aeron , Harding Nicola , Fukuthi Renata , Brazil Lucy , Cikurel Katia , Al-Salihi Omar , Swampillai Angela , Chia Kazumi , Manik Vishal , Bhangoo Ranjeev , Ashkan Keyoumars , Lavrador Jose Pedro , Vergani Francesco , Gullan Richard , Zebian Bassel , Bleil Cristina 
Published: September 2023

Abstract

AIMS
The aim of this review is to analyse the need for a specialist nurse role for the TYA patients. Having a new dedicated TYA developmental role implemented can help by identifying areas for improvement from the wider team to ensure optimal support for patient group.

METHOD
Clinic attendance over a 1-year period has been measured. Looking specifically at patients who did not attend (DNA) appointments in a monthly TYA joint surgical and oncology clinic. We have evidence engaging this age group with the creation of a nurse led weekly telephone clinic for TYA patients and have looked at the trajectory of attendees throughout the year.

RESULTS
To date, nurse led clinic has had 107 individual bookings between August 2022 and February 2023. This is a devoted telephone clinic to provide holistic care.

CONCLUSIONS
There were 107 nurse lead telephone clinic appointments that were booked and attended by this patient group over 6-month period. This was protected time for which the nurse specialist was able to explore patients individual care needs in a holistic way. Figures for holistic needs assessment (eHNA) are yet to be collated; but the TYA group are now routinely offered eHNA to ensure a holistic care approach and support to this vulnerable patient group.
AN AUDIT OF STEROID-INDUCED DIABETES IN PRIMARY BRAIN TUMOUR PATIENTS
Authors: Bog Ji Yun , Lorimer Cressida , Brock Juliet , Chandy Edward 
Published: September 2023

Abstract

AIMS
Dexamethasone is an effective and commonly used treatment in patients with gliomas. However, it can also cause several metabolic side effects, including steroid-induced diabetes mellitus (SIDM), of which prevalence is estimated at 11-56%. We aimed to assess prevalence of SIDM in our local brain tumour population and audited adherence to recently published national guidance for monitoring and management of SIDM.

METHOD
Retrospective data review of all new primary malignant brain tumour patients seen in clinic over 12 months to assess local prevalence. Patients’ notes audited for 2 months pre- and post-adoption within the department of national guidelines focussing on how to screen and monitor for diabetes when initiating high dose steroids.

RESULTS
71 new patients seen over 12 months. 66 patients with high grade and 5 with low grade gliomas. 82% were on steroids at first oncological visit. 14% known diabetic or pre-diabetic. 7% subsequently developed SIDM.
19 patient notes audited over 2 months prior to intervention (Group 1) and 11 post intervention (Group 2). All patients were taking dexamethasone. 40% of Group 1 and 36% of Group 2 had neither HbA1c nor lab glucose checked at baseline. 1 patient in Group 1 developed SIDM.

CONCLUSIONS
Diabetes mellitus in cancer patients increases risk of infections, cardiovascular comorbidities, and can reduce effcacy of treatment, leading to preventable admissions and decreased survival rates. Prevalence of SIDM in our local population is comparable to published data. Adoption of published guidance improved baseline monitoring but needs to be embedded within acute oncology pathways across the Trust.
THE KYNURENINE PATHWAY AND ITS ROLE IN GLIOBLASTOMA CELL MIGRATION
Authors: Sirnikova Diana , Reynisson Johannes , Brüning-Richardson Anke , Kirby Catherine 
Published: September 2023

Abstract

AIMS
The kynurenine (Kyn) pathway plays an important role in the pathogenesis of many cancers including glioblastomas (GBMs). The enzymes, indoleamine-2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (TDO2), regulate the first and rate-limiting step resulting in the formation of N-formyl-kynurenine, which is then readily converted into Kyn by kynurenine formaldehyde. Cancers expressing the IDO1 and TDO2 enzymes can produce immunosuppressive tryptophan metabolites that compromise the host immune system leading to poor patient prognosis. The inhibitors TD12, TD18 and TD34 were recently developed due to the lack of TDO2 and IDO1/TDO2 inhibitors, of which TD34 can block both IDO1 and TDO2 activity. Here, we investigated the ability of these novel inhibitors to also target cell migration in GBM as part of our ongoing research interest in this area.

METHOD
Two established brain tumour cell lines, U87 and U251 and one patient-derived cell line, E55, were used to determine IC50 values and anti-migratory concentrations by MTT for application in 2D and 3D migration/invasion assays.

RESULTS
Cell migration in all cell lines was significantly reduced in the presence of the TD12, TD18 and TD34 inhibitors. E55 appeared to be 100-fold more sensitive to drug activity; immunofluorescence analysis indicates changes in the actin cytoskeleton and cell adhesion

CONCLUSIONS
Initial results suggest that TDO2 and the IDO1 enzymes play also a role in cell migration in GBM and provide further evidence for the involvement of the Kyn pathway in the pathology of GBMs. This also supports the application of inhibitors targeting TDO2 and IDO1 as novel complementary treatment options in GBM.
Thermal annealing promoted room temperature phosphorescence: motion models and internal mechanism
Authors: Gao Yan , Lu Jie , Liao Qiuyan , Li Shuhui , Li Qianqian , Li Zhen 
Published: September 2023

ABSTRACT
Thermal annealing has been proven to be an efficient method to optimize the device performance of organic and polymeric opto-electronic materials. However, no detailed information of aggregate structures was obtained for a deeper understanding of what happens during thermal annealing. Herein, through modulation of molecular configurations by tunable linkage positions, and the amplified amplitudes of molecular motions by incorporation of additional methylene units, accurate changes of aggregated structures upon thermal annealing have been achieved, accompanying with the ‘turn-on’ room temperature phosphorescence (RTP) response by about 4800- and 177-fold increase of lifetimes. The stretching and swing motion models have been proposed, which afforded an efficient way to investigate the science of dynamic aggregation in depth.
Immune-Related Adverse Event Likelihood Score Identifies “Pure” IRAEs Strongly Associated With Outcome in a Phase I-II Trial Population
Authors: Mazzarella Luca , Giugliano Federica , Nicolo Eleonora , Esposito Angela , Crimini Edoardo , Tini Giulia , Uliano Jacopo , Corti Chiara , D’Amico Paolo , Aliaga Pamela Trillo , Valenza Carmine , Repetto Matteo , Antonarelli Gabriele , Ascione Liliana , Vivanet Grazia , Berton Giachetti Pierpaolo , Minchella Ida , Belli Carmen , Locatelli Marzia , Criscitiello Carmen , Curigliano Giuseppe 
Published: September 2023

Abstract

Background
Immune-related adverse events (IRAE) pose a significant diagnostic and therapeutic challenge in patients treated with immune-oncology (IO) drugs. IRAEs have been suggested to correlate with better outcome, but studies are conflicting. Estimating the true incidence of IRAEs is particularly difficult in the early phase I/II trial setting. A key issue is the lack of IRAE diagnostic criteria, necessary to discriminate “pure” IRAEs from other treatment-related adverse events not sustained by an autoimmune process.

Methods
In patients treated with immune-oncology (IO) drugs in phases I-II trials at our institute, we identified high confidence (HC) or low confidence (LC) IRAEs by clinical consensus. We empirically developed an IRAE likelihood score (ILS) based on commonly available clinical data. Correlation with outcome was explored by multivariate Cox analysis. To mitigate immortal time-bias, analyses were conducted (1) at 2-month landmark and (2) modeling IRAEs as time-dependent covariate.

Results
Among 202 IO-treated patients, 29.2% developed &gt;1 treatment-related adverse events (TRAE). Based on ILS &gt;5, we classified patients in no IRAE (n = 143), HC IRAE (n = 24), or LC IRAE (n = 35). hazard ratios (HR) for HC were significantly lower than LC patients (HR for PFS ranging 0.24-0.44, for OS 0.18-0.23, all P &lt; .01).

Conclusion
ILS provides a simple system to identify bona fide IRAEs, pruning for other treatment-related events likely due to different pathophysiology. Applying stringent criteria leads to lower and more reliable estimates of IRAE incidence and identifies events with significant impact on survival.
Telomere length links with physiological phenotype and breeding patterns in a long-lived seabird
Authors: Guillen-Parra Mauricio , Velando Alberto , Barcenas-Flores Rocio , Nicolás-Toledo Leticia , Torres Roxana 
Published: September 2023

Abstract
Telomere length (TL) is known to covary with a suite of physiological traits involved in energy balances that may influence breeding success. Thus, TL may be an indicator of individual quality, influencing mate choice and breeding strategies. In the Brown Booby (Sula leucogaster), a long-lived seabird, we investigated in a total of 72 pairs whether TL may indicate the individual physiological phenotype by examining how it relates to mitochondrial DNA copy number (mtDNAcn) and corticosterone (CORT) levels. Then, we tested if TL is associated with mating patterns by looking for covariation with skin coloration (a condition-dependent sexual trait), whether there is assortative mating by TL, and if the degree of TL similarity between partners influences an individual’s likelihood of changing mates between reproductive seasons. Because environmental conditions can have important effects on the condition and reproductive strategies of individuals, the study was performed in 2 colonies with contrasting breeding conditions. We found that TL was positively related to mtDNAcn (but not CORT levels), suggesting that individuals with shorter telomeres may have a reduced mitochondrial density. TL was reflected in sexual coloration, but only in the colony with good breeding conditions. There was positive assortative mating by TL; however, the degree of assortative mating was unrelated to the probability of mate change, which greatly varied between the 2 colonies. Our results suggest that TL is associated with the physiological phenotype of individuals and their breeding patterns. Importantly, contrasting environmental conditions influenced the link between TL and sexual coloration and the propensity of individuals to change mate, highlighting the importance of environmental variation on mating patterns.
Gender Gaps in Political Ambition on Different Levels of Policy-Making
Authors: Devroe Robin , Coffé Hilde , Vandeleene Audrey , Wauters Bram 
Published: September 2023

Summary
Women consistently report lower levels of nascent political ambition than men. In this study, we investigate whether these gender differences occur to the same extent across local, national and European levels of policy-making. Using original data collected among a representative sample of young Flemish citizens aged between 18 and 35 (N = 1000), our descriptive results demonstrate a significant gender gap across all levels of policy-making, though the gap is slightly smaller at the local level. Stacked multivariate analyses confirm women’s lower levels of political ambition and show that the gender gap is significantly smaller at the local level compared with the European (but not the national) level, pointing to women’s lower levels of ambition for the European level.
Are Nonprobability Surveys Fit for Purpose?
Authors: Jerit Jennifer , Barabas Jason 
Published: September 2023

Abstract
Social scientists employ survey methods to explore the contours of human behavior. Today there are more opportunities to collect survey data than at any time in recent history. Yet sample quality varies dramatically due in part to the availability of nonprobability samples (NPSs) from commercial survey organizations. While these kinds of surveys have advantages in terms of cost and accessibility, the proprietary nature of the data can be problematic. In this synthesis, we describe situations in which researchers typically employ NPSs and consider whether these data are fit for purpose. Next, we discuss use cases that are not widespread but may be appropriate for these data. We conclude that potential utility of NPSs will remain out of reach unless scholars confront the tension between the operation of online survey organizations and the goals of transparent research.