bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Experiences of People With Glioma and Their Caregivers: Living With Uncertainty and Long Term Consequences (COBra Study)
Authors: Baddeley Elin , Retzer Ameeta , Sivell Stephanie , Seddon Kathy , Bulbeck Helen , Nelson Annmarie , Calvert Melanie , Grant Robin , Adams Richard , Watts Colin , Aiyegbusi Olalekan Lee , Rivera Samantha Cruz , Kearns Pamela , Dirven Linda , Byrne Anthony 
Published: October 2022

Abstract

AIMS
Glioma, the most common primary brain tumour, has variable survival rates. Existing evidence describes detriment to quality of life from persistent symptoms/side effects, functional loss and feelings of disconnection, particularly in glioblastoma; however, there remains limited focus on the experience of longer-term survivors.
This study aimed to ascertain the lived experience of people with glioma and their caregivers, part of a larger study identifying outcomes for a core outcome set for use in glioma trials (COBra study).

METHOD
Semi-structured interviews with UK glioma patients, or patient-caregiver dyads, analysed using Thematic Analysis.

RESULTS
Nineteen interviews were undertaken. Patients and caregivers described living with uncertainty long after diagnosis and treatment, including prognostic uncertainty and anxiety surrounding recurrence and worsening symptoms. Patients described an inability to plan long-term, struggling to return to normal activities, either due to progressive tumour symptoms, and/or treatment side effects. Long-term physical and psychological side effects were highly impactful; patients felt left alone to cope, with support following treatment dropping off rapidly. Patients/caregivers sought self-directed ways to cope, focusing on routine and achieving some normality. However, the physical and neurological effects of glioma and its treatment affected all aspects of daily life and social interactions, impacting on sense of wellbeing and quality of life.

CONCLUSION
People with glioma, and their caregivers, struggle with loss of normality and living with uncertainty long after diagnosis. They proactively engage in self-directed approaches towards mitigating these effects, but experience gaps in support after treatment finishes. Clinical follow up should target these aspects of assessment and intervention.
SYNGN: A Novel Patient-Specific Drug-Matching Strategy in Glioblastoma
Authors: Marino Silvia 
Published: October 2022

Abstract

AIMS
The alteration of the glioblastoma genome by epigenetic mechanisms that share functions with normal developmental processes, such as self-renewal and fate specification of neural stem cells (NSC), is a key piece of evidence that links brain cancer pathogenesis with dysregulated stem cell functions. A patient-specific comparison of glioblastoma cells with NSC, a putative cell of origin of at least a proportion of these tumours, is not feasible as patient-matched endogenous NSC are not surgically accessible and all epigenetic studies in glioblastoma have so far compared epigenetic changes of different tumours with each other or to comparators obtained from foetal brains or an unrelated donor. We reasoned that availability of matched GIC and NSC pairs would allow to identify crucial epigenetic differences on a patient-specific basis and would provide essential therapeutic contrast to define disease-and patient-intrinsic biomarkers of drug response that are less confounded by germline variation.

METHOD
We have harnessed state-of-the-art stem cell technologies and next-generation sequencing methods to compare the epigenetic and transcriptional profile of IDH-wildtype glioblastoma with that of patient-matched normal expanded potential stem cell-derived NSC (iNSC).

RESULTS
We demonstrate that integrated analysis of the transcriptome and DNA methylome of GIC/iNSC pairs identifies druggable target genes (PTGER4, ALDH3B1, NTRK2 and others) in a proportion of patients and we validate this patient-specific prediction of drug response at pre-clinical level in 3D synGLICO and in in vivo models.

CONCLUSION
We provide proof of principle that the SYNGN platform can identify patient-specific druggable targets in glioblastoma.
Identifying Enhancing Tumour Without Contrast-Enhanced Imaging
Authors: Ruﬄe James , Mohinta Samia , Gray Robert , Hyare Harpreet , Nachev Parashkev 
Published: October 2022

Abstract

AIMS
Brain tumours are heterogenous entities comprising multiple broad tissue sub-types when imaged with MRI. Delineating the enhancing tumour component is vital for neuro-oncological therapeutic planning, to-date only demonstrable with contrast-enhanced imaging. But not all patients can undergo this necessary contrast-enhanced acquisition, whether due to allergy, renal impairment, or scanning acquisition parameters. We therefore evaluated how well fully convolutional deep learning models identify a patient’s enhancing tumour when contrast-enhanced imaging was not available.

METHOD
We constructed a suite of deep-learning models to segment brain tumours when contrast-enhanced imaging was missing. Specifically, we developed all possible combinations of other structural sequences being provided, including T1-weighted, T2-weighted and FLAIR. Models were trained and tested with five-fold cross-validation on the 2021 BraTS-RSNA glioma population of 1251 patients, with additional out-of-sample validation with neuroradiologist hand-labelled lesions from our own centre.

RESULTS
Models missing post-contrast imaging still achieved a Dice coefficient for the whole tumour of 0.942. Model performances for identifying enhancing-tumour – despite no contrast-enhanced imaging being provided to the model – ranged from Dice coefficients of 0.759 (single sequence model) to 0.790 (three sequence T1 + T2 + FLAIR model). Moreover, models lacking contrast-enhanced imaging still robustly quantified the volume of enhancing tumour (R2 range 0.953-0.976).

CONCLUSION
Models missing contrast-enhanced imaging still identify both whole lesions and enhancing tumour components, and accurately quantifying the enhancing volumetric burden. These models provide opportunity for lesion detection in patients or clinical situations in which contrast-enhanced imaging cannot be acquired, and challenge the current nosology of defining ‘enhancing tumour’.
Modulation of GABA Neurotransmitter Signalling Impacts Glioblastoma Spheroid Growth and Response to Standard Treatment
Authors: Barrow Rhiannon , Poulter James A , Finetti Martina A , Wilson Erica , Johnson Colin A , Stead Lucy 
Published: October 2022

Abstract

AIMS
We have identified two subtypes within glioblastoma (GBM), defined by whether a specific subset of genes is upregulated (Up responders) or downregulated (Down responders) in response the standard treatment. The biology of therapy-driven transcriptional reprogramming in the two subtypes suggests the differential involvement of GABA neurotransmitter signalling in the underlying treatment resistance mechanisms. Our aim was to address our hypothesis that modulating GABA signalling will impact treatment response in GBM, in different ways for different responder subtypes.

METHOD
We identified two cell lines representing the different responder subtypes: established GBM cell line A172 is an Up responder; GBM63 is a patient derived Down responder. We have grown these cells as spheroids and inspected the response to standard treatment (2 Gy radiation and 30 mM temozolomide), via growth and cell viability assays, versus untreated controls in the presence and absence of a GABAA receptor (GABAAR) modulators. We have performed RNAseq to investigate the pathways affected by inhibition and treatment.

RESULTS
In all cases, modulation of GABAAR activity significantly alters both growth and response to standard treatment. However, this is most commonly in different directions in the Up vs Down responders. Furthermore, the majority of genes that are differentially expressed through treatment and inhibition are dysregulated in different directions.

CONCLUSION
Modulation of GABA neurotransmitter signalling impacts GBM spheroid growth and response to standard treatment. Identifying the key pathways affected in different responder subtypes may indicate how this can be used in the development of more effective combination treatments for GBM.
Intravoxel Incoherent Motion (IVIM) Diffusion-Weighted Imaging to Assess Treatment Response of Choline Kinase Inhibition on GL261 Mouse Glioblastoma
Authors: Ahmed Nooradean , Alrashidi Tareq , Bhaduri Sourav , Mukherjee Soham , Poptani Harish 
Published: October 2022

Abstract

AIMS
To monitor changes in IVIM parameters in response to JAS239 treatment in preclinical glioblastoma models.

METHOD
C57BL/6 mice were injected intracranially with 5x105 GL261 glioblastoma cells and tumours were observed on T2 weighted MRI. Mice were imaged on day 0 (T0, baseline), day 3 (T3), 6 (T6) of treatment and post-treatment day 10 (T10). IVIM DWI was performed using a single-shot spin-echo echo planar sequence and processed using Matlab to acquire IVIM parameters of f, D, and D*.

RESULTS
Percentage changes in values with respect to baseline from saline treated control mice were compared to JAS239 treated animals with respect to baseline. Treated mice showed a slight increase in ADC and pseudo-diffusion on day 3 and day 6, with an increase in the perfusion fraction on day 6. However, no statistically significant difference between the two groups with respect to all 3 parameters (P&gt;0.05). Analysis of the change in parameters post treatment (T10) also showed no statistically (P&gt;0.05) significant difference between the mice treated with JAS239 and the control group treated with saline.

CONCLUSION
In this study of the IVIM based parameters, we observed no significant differences in these parameters which indicates that JAS329 may be ineffective in the treatment of GL261 tumours. There was no significant change in the diffusion and perfusion related parameters in the tumour region. IVIM parameters may be useful in studying the tumour microenvironment, however, these may not be sensitive in detecting tumour resistance to ChoK inhibitor therapies.
Development of Novel LAT1 Targeting Small Molecules for Boron Neutron Capture Therapy (BNCT) and Potential Application for Treating Glioblastoma
Authors: Morrison Kendall 
Published: October 2022

Abstract

AIMS
to make molecules that deliver more Boron than BPA for boron neutron capture therapy BNCT

METHOD
Boronated compounds were designed based on known LAT-1 substrates, synthesized using boronation techniques and purified using preparative HPLC. The compounds were formulated to achieve high concentrations when compared to BPA-fructose (BPA-F). Boronated compounds were tested for boron uptake and retention in multiple cell lines expressing either LAT1 and/or PEPT1. Compounds were further tested in multiple human xenograft models representing the cancer indication currently treatable by BNCT as well as in one syngeneic colon tumor model that may have high PEPT1 expression. Intracellular and intra tumor boron concentration were measured by ICP OES. We also synthesized 2 dipeptides and tested them in BNCT experiments with our collaborators at Kyoto University in Japan. They were tested in a CT26 mouse syngeneic model using neutrons from KURR1.

RESULTS
We synthesized multiple boronated compounds with better solubility than BPA (100 mg/ml v 30mg/ml in fructose). They were readily taken up in multiple cell lines and one of these compounds had longer retention than others. In competition experiments we were able to show that this compound was a superior substrate for LAT1. We also showed better BNCT results with our molecules compared to BPA.

CONCLUSION
BPA works for BNCT but it has limitations such as poor solubility. We made several new boronated compounds with better solubility than BPA and showed that we could deliver 2-3 x more boron in vitro and in vivo and better BNCT outcomes at KURR1.
The Value of Diffusion Tractography for Awake Surgery
Authors: Roach Joy , Voets Natalie , Pretorius Pieter , Birch Martin , Apostolopoulos Vasileios , Stacey Richard , Plaha Puneet 
Published: October 2022

Abstract

AIMS
Despite evidence of correspondence with intraoperative stimulation, there remains limited data on MRI diffusion tractography (DT)’s sensitivity to predict morbidity after brain tumour resection. Our aims were: (1) evaluate DT against subcortical stimulation mapping and performance changes during and following awake surgery; (2) evaluate the use of early post-operative DT to predict recovery from post-surgical deficits.

METHOD
We performed a retrospective review our first 100 awake neurosurgery procedures using DTneuronavigation. Intra-operative stimulation and performance outcomes were assessed to classify DT predictions for sensitivity and specificity calculations.

RESULTS
Between 2014 and 2019 a total of 91 adult brain tumour patients (mean age 49.2 years) underwent 100 awake surgeries with subcortical stimulation. The sensitivity and specificity of pre-operative DT predictions were 92.2% and 69.2%, varying among tracts. Post-operative deficits occurred after 41 procedures (39%), but were prolonged (&gt;3 months) in only 4 patients (4%). Post-operative DT was available in 51 patients and confirmed surgical preservation of tracts. Post-operative DT anticipated complete recovery in a patient with supplementary motor area syndrome, and indicated infarct-related damage to corticospinal fibers associated with delayed, partial recovery in a second patient.

CONCLUSION
Pre-operative DT provided very accurate predictions of the spatial location of tracts in relation to a tumour. As expected, however, the presence of a tract did not provide information on its functional status, resulting in variable DT specificity among individual tracts. While prolonged deficits were rare in our series, DT in the immediate post-operative period offered additional information to monitor neurological deficits and anticipate recovery potential.
Identification of an Inflammatory Biomarker Signature in Plasma-Derived Extracellular Vesicles of Glioblastoma Patients
Authors: Cilibrasi Chiara , Simon Thomas , Vintu Marian , Tolias Christos , Samuels Mark , Mazarakis Nektarios , Eravci Murat , Stewart Nicholas , Critchley Giles , Giamas Giorgios 
Published: October 2022

Abstract

AIMS
Description of effective biomarkers present in biofluids could prove invaluable in GBM diagnosis. Extracellular vesicles (EVs) are essential to intercellular crosstalk in the tumour bulk and circulating EVs have been described as a potential reservoir of GBM biomarkers. Therefore, EV-based liquid biopsies have been suggested as a promising tool for GBM

METHOD
Ethical approval was obtained for a prospective study of healthy donors and consenting GBM patients at the University Hospitals Sussex (Brighton). To identify GBM specific proteins, small EVs (sEVs) were isolated from plasma samples using differential ultracentrifugation and validated through Nanoparticles tracking analysis, transmission electron microscopy and detection of known sEVs markers such as CD9, CD63, CD81 and HSP70. sEVs content was characterised through mass spectrometry and bioinformatic tools.

RESULTS
Our data indicate the presence of a GBM inflammatory biomarker signature comprising members of the complement and regulators of inflammation and coagulation including VWF, FCGBP, C3, PROS1, and SERPINA1. Bioinformatic analysis highlighted that all potential markers exclusively identified in patient samples had already been linked with either GBM diagnosis, prognosis or associated signalling, suggesting that sEVs protein cargo could mirror the landscape of the original tumour and that selective circulating sEV-derived proteins might be used as hallmarks for GBM patients.

CONCLUSION
this study is a step forward in the development of a non-invasive liquid biopsy approach for the identification of valuable biomarkers that could significantly improve GBM diagnosis and, consequently, patients’ prognosis and quality of life.
Long Term Quality of Life Outcomes Following Surgical Resection Alone for Benign Paediatric Intracranial Tumours
Authors: Kumar Siddhant , Islim Abdurrahman , Moon Richard , Millward Christopher , Hennigan Dawn , Bakhsh Ali , Thorpe Antonia , Foster Mitchell , Pizer Barry , Mallucci Conor , Jenkinson Michael 
Published: October 2022

Abstract

AIMS
Survivors of paediatric intracranial malignancies are at increased risk of psychosocial, neuro-developmental and functional impairment, important measures of patients’ well-being. This study aimed to evaluate long-term quality of life outcomes (QOL) in patients with benign paediatric brain tumours treated curatively with surgical resection alone.

METHOD
Cross-sectional cohort study of benign paediatric intracranial tumours managed with surgery alone between 2000-2015. Validated QOL questionnaires were administered: SF-36, QLQ-BN20, QLQ-C30 and PedsQLTM.

RESULTS
Twenty-three patients participated (median age at surgery 13 years; range 1-18), twelve were male. The most common diagnosis was pilocytic astrocytoma (n=15). Median time from surgery to participation was 11 years (range 6-19). Fourteen patients achieved A-level qualifications and two obtained an undergraduate degree. Twelve patients were employed, eight were studying and three were unemployed or volunteering. Twelve patients were currently driving. QOL outcomes demonstrated significant limitation from social functioning (p=0.03) and cognitive functioning (p=0.023) compared to the general population norms. Patients also experienced increased loss of appetite (p=0.009) and symptoms of nausea and vomiting (p=0.031). Ten patients were under transitional teenager and young-adult (TYA) clinic follow-up. TYA patients achieved higher levels of education (p=0.014), were more likely to hold a driver’s license (p=0.041) and had improved physical functioning (p=0.005) compared to patients not transitioned through these services.

CONCLUSION
Childhood brain-tumour survivors are particularly vulnerable and at greater risk of developing psychological, neuro-cognitive, socialisation and physical development challenges. Early identification, comprehensive assessment and specialist TYA cancer healthcare input are vital to support these patients and improve their quality of life.
Gliocova: Predictors of Post-Operative Complications, 30 Day Mortality and Readmission After First Surgical Intervention in Brain Tumour Patients in England Between 2013-2018
Authors: Mauricaite Radvile , Le Calvez Kerlann , Brodbelt Andrew , Bottle Alex , Gregory Jonathan , Booth Thomas , Williams Matt 
Published: October 2022

Abstract

AIMS
The Gliocova dataset uses linked English national cancer data on all 51,775 adult primary brain tumour patients diagnosed between 2013-2018. Here we investigate patient safety and post-operative complications after first surgical intervention.

METHOD
We identified patients undergoing first surgical intervention (surgical debulking or biopsy) and used a modified Delphi approach to identify diagnosis codes indicating potential post-surgical complications. We calculated Elixhauer Comorbidity Index (ECI) weights based on our data and developed regression models to link patient characteristics and ECI with 30-day mortality, readmission and chance of complication.

RESULTS
29,258 out of 51,775 patients underwent a surgical intervention (28,173 surgical debulking; and 1,207 biopsy). 11,959 (40.9\%) patients had at least one comorbidity during first intervention admission. In hospital mortality was 0.99\% (N = 289), 30-day mortality was 2.3\% (N = 677) and 30-day readmission was 12.7\% (N = 3,725). 13,137 patients (44.9\%) had at least one complication code from our defined list, either during their first surgical intervention or during a 30-day readmission. Predictors of 30-day mortality, readmission, and risk of complications included age, ECI score, number of complications, type of intervention (biopsy vs surgical debulking), income quintile, and tumour type (i.e., Glioblastoma versus other types of brain tumours).

CONCLUSION
To our knowledge this is the first study in England to assess post-surgical complications in a large brain tumour patient cohort. Our further work will focus on variation in outcomes between different centres/ centre volumes/ regions and the cost of complications. More information: https://blogs.imperial.ac.uk/gliocova/about-gliocova/.
MR Electrical Properties Tomography (MREPT) at 9.4T to Assess Treatment Response of Choline Kinase Inhibition on GL261 Glioblastoma
Authors: Alrashidi Tareq , Nooradean Ahmed , Bhaduri Sourav , Mukherjee Soham , Poptani Harish 
Published: October 2022

Abstract

AIMS
To monitor changes in tissue-conductivity based MR parameter in response to JAS239 treatment in preclinical glioblastoma model.

METHOD
C57BL/6 mice were injected intracranially with 5x105 GL261 glioblastoma cells and tumours were observed on T2 weighted MRI. Mice were imaged on day 0 (baseline), day 3 , 6 of treatment and post-treatment day 10. For MREPT, multi-slice-multi-echo sequence was used. Laplacian algorithm was employed to obtain the phase-based MREPT image reconstruction.

RESULTS
Saline treated mice showed a greater increase in tumour volume compared to JAS239 treated animals with respect to baseline. Percentage changes in conductivity values with respect to baseline from saline treated mice were compared to JAS239 treated animals. JAS239 group showed a slight increase in mean conductivity on day 3 and 6 compared to saline group. There were no statistically (p&gt; 0.05) significant differences between the two groups. 4 days after treatment completion (Day10), the mean of conductivity values of JAS239 treated animals compared to saline treated animals showed no statistically (p&gt; 0.05) significant differences. These results may indicate that GL261 tumour model is treatment resistant. Our findings agree with a study conducted by Bhaduri et al, where tumours were treated with JAS239.

CONCLUSION
EPT technique provides unique data on tissue conductivity which can be used to improve the assessment of treatment response in glioblastoma. MREPT parameter might be insensitive to evaluate choline kinase inhibitor. For future work, this technique can be incorporated into multiparametric MRI to complement diffusion and perfusion-weighted imaging of assessing treatment response in glioblastoma.