bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical and Oncological Score to Estimate the Survival Benefit of Resection and Chemoradiotherapy in Elderly (≥70 Years) Glioblastoma Patients: A Preliminary Analysis Authors
Authors: Zorman Mark , Webb Philip , Nixon Mickaela , Sravanam Sanskrithi , Honeyman Susan , Nandhabalan Meera , Apostolopoulos Vasileios , Stacey Richard , Hobbs Claire , Plaha Puneet
Published: October 2022

AIMS

Elderly patients with glioblastoma are perceived to face a poor prognosis with perceptions surrounding older age and a relative lack of randomized data contributing. This study aimed to evaluate survival prognosticators in elderly glioblastoma patients to more accurately guide their treatment.

METHOD

The records of 169 elderly (≥70 years) patients with a new diagnosis of glioblastoma who had undergone neurosurgical intervention were retrospectively examined for patient sex, age, performance status, comorbidities, MGMT promoter methylation, surgical intervention and chemoradiation regime. The adjusted survival impact of these factors was determined using Cox proportional hazards model and used to devise a two-stage scoring system to estimate patient survival at the stage of surgical (Elderly Glioblastoma Surgical Score, EGSS) and oncological management (Elderly Glioblastoma Oncological Score, EGOS).

RESULTS

The median overall survival (mOS) of the cohort was 28.8 weeks. Gross-total and subtotal resection were associated with improved survival compared to biopsy alone (respective mOS 65.3 and 28.1 vs 15.7 weeks, p<0.001). Hypofractionated radiotherapy (40Gy in 15 fractions) with Temozolomide was non-inferior to the Stupp protocol, p=0.72. Exploratory subgroup analysis revealed a significant benefit of Temozolomide-based approaches in MGMT-methylated patients as well as a trend towards improved survival in MGMT-unmethylated patients. Our EGSS and EGOS scores successfully estimated survival in this retrospective cohort with 65% and 73% accuracy.

CONCLUSION

Where appropriate and safe, elderly glioblastoma patients may benefit from surgical resection and combined chemoradiotherapy with Temozolomide. The proposed EGSS and EGOS scores take into account important prognostic factors to help guide which patients should receive such treatment.
Awake Craniotomy Is Well-tolerated in the Elderly: Our Early Experience
Authors: Khan Rosina , Okoh Magnus , Ogbu Ikenna , Chan Huan , Albanese Erminia
Published: October 2022

AIMS

Awake craniotomy for brain tumour resection aims to increase the extent of resection while minimising neurological deficit. The major concerns for patients during awake craniotomies include peri-operative discomfort/pain and anxiety for some patients. Older patients are generally not offered aggressive operative options due to longer lengths of hospital stay (LOS), expected higher rates of peri-operative morbidity/mortality, and poorer survival. However, increased extent of glioma resection is associated with greater overall and progression-free survival. Furthermore, previous studies have shown that awake craniotomies are well tolerated in elderly patients. This study aims to evaluate our experience in awake craniotomies for glioma resection in patients over 65 years old.

METHOD

Seventeen elderly patients who had undergone awake craniotomies at University Hospitals of North Midlands between 2015 and 2021 were included. Outcome measures included LOS, post-operative morbidity/mortality, and the difference between pre- and post-operative Hospital Anxiety and Depression scores (HADS).

RESULTS

There was an 11% operative mortality rate in our cohort. The average LOS was 5.7 days. The median pre- and post-operative score at 6 months was 1 indicating that there is no difference post-operatively. There was a positive net difference between pre- and post-operative anxiety/depression scores in our cohort.

CONCLUSION

Awake craniotomies are generally well tolerated among the elderly patients with unchanged post-operative performance status and improved HADS scores. These findings suggest that awake craniotomies should be offered to elderly patients if deemed appropriate.
Transcriptome-wide Mendelian Randomisation Using Expression, Protein and Splicing Quantitative Trait Loci to Identify Novel Drug Targets Associated With Risk of Gliomagenesis
Authors: Thornton Zak , Robinson Jamie , Kurian Kathreena
Published: October 2022

AIMS

To use two-sample Mendelian Randomisation to prioritise novel genes for drug targeting in glioma risk using expression, protein and splicing quantitative trait loci (eQTLs, pQTLs and sQTLs, respectively).

METHOD

We used genetic variants from GWAS to compare the effects of eQTLs, pQTLs and sQTLs on genetic liability to glioma risk (n=12,496). eQTL data was retrieved from the MetaBrain study of five different brain tissues (n=108 to 2,970). pQTL data was retrieved from the BrainQTL study of dorsolateral prefrontal cortex tissue (n = 330), and sQTL data was retrieved from Genotype-Tissue Expression (GTEx) Project (v8) of 13 brain tissues (n=114 to 209). SNPs which were trans-QTLs (>1 Mb) due to risk of horizontal pleiotropy, and greater than GWAS significance (P > 5 × 10-8) were excluded. Instruments were constructed using independent SNPs (r2 < 0.001). Results underwent relevant sensitivity analysis; colocalisation and Steiger filtering.

RESULTS

We found 123 MR associations for 28 genes with genetically predicted altered expression, protein or splicing levels affected risk of glioma. These included genes recurrently associated with glioma risk such as TERT, RTEL1, CDKN2A/B and EGFR, and novel putative genes; BTN3A2, GALNT6, GMPPB and FAIM. Following sensitivity analyses, we found that 58 MR associations for 25 genes had robust evidence.

CONCLUSION

We identified four novel associations not previously found in GWAS; BTN3A2 (6p22.2), FAIM (3q22.3), GALNT6 (12q13.13) and GMPPB (3p21.31) are implicated in glioma risk and are also not located on a known glioma risk locus. Further analysis is required to identify the suitability of these genes for drug targeting in glioma.
Early Post-treatment Pseudo-continuous Arterial Spin Labelling Stratifies 12 Month Survival in Gliomas
Authors: Maguire Alice , Obasi Emeka , Markus Julia , Gupta Meetakshi , Kosmin Michael , Sokolska Magdalena , Hyare Harpreet
Published: October 2022

AIMS

Arterial spin labelling (ASL) is a non-invasive perfusion technique that uses endogenous contrast and is proving to be of value in paediatric neuro-oncology. ASL derived rCBV has been shown to correlate with Dynamic Susceptibility Contrast (DSC) -derived CBV and could be an alternative perfusion technique when DSC is not possible. The aim of the study was to investigate whether early post-treatment tumour ASL can stratify patient survival at 12 months.

METHOD

180 consecutive patients diagnosed with glioblastoma and undergoing treatment between 2017-2021 were imaged with an extended MRI protocol that included pseudo-continuous ASL (pCASL). Patients that were imaged with pCASL within 1-3 months of completing radiotherapy were identified retrospectively. Scanner generated Perfusion weighted images were inspected and regions of interest encompassing the tumour were generated and compared with a control region in the contra-lateral grey matter. Overall survival data was collated and a comparison of tumour ASL was assessed with t-test statistics between patients surviving < and >12 months.

RESULTS

43 patients were identified (23 male, median age 58 years, diagnoses: IDHwt-GBM 17, IDHmut-Astrocytoma 13, IDHmut 1p19q co-deleted Oligodendroglioma 13). Tumour ASL was 3.22 (± 2.1) in patients that survived less than 12 months compared to 1.64 (± 1.9) in patients that survived greater than 12 months, p=0.02).

CONCLUSION

Early post-treatment ASL can stratify patient survival at 12 months and show promise as an alternative to DSC perfusion in the prognostication of patients being treated for glioma.
The Role of miRNAs in Gliomas in Response to Hypoxia
Authors: Smith Louise , Chakraborty Sajib , Lourdusamy Anbarasu , McIntyre Alan , Smith Stuart
Published: October 2022

AIMS

Identifying significant miRNAs that are either under or overexpressed in hypoxia compared to normoxia in glioma cells. Further exploring the effect and role of hypoxia on miR-92a-3p and miR-149-5p in gliomas in apoptotic and cellular senescence pathways.

METHOD

A range of glioma cells were used for screening, including primary cell lines: GIN28 and GIN31; low-grade cell lines: LGG19 and LGG24; a paediatric cell line: SF188 and a commercially available glioblastoma cell line U87. These cells were cultured at both 1% (hypoxia) and 20% (normoxia) oxygen levels. Screening of miRNAs was achieved by quantitative polymerase chain reaction (qPCR) using miRNA specific primers. Knockdowns/in were achieved by transfecting with miR-92a-3p and miR-149-5p mimics and inhibitors. Caspase-glo assay was used to assess the effect of hypoxia on apoptosis.

RESULTS

A range of miRNAs were differentially expressed in hypoxia in a range of glioma cell lines. miRNA 92a-3p and miR-149-5p were found to be downregulated and upregulated respectively in primary gliomablastoma cells in hypoxia compared to normoxia. These particular miRNAs are also found to have multiple targets in apoptosis and cellular senescence.

CONCLUSION

The screening of 90 miRNAs among the different categories of gliomas highlighted multiple miRNAs that were significant in hypoxia compared to normoxia. Using primary cell lines have identified hypoxia-affected miRNAs in glioblastomas. This discovery will increase our knowledge and understanding of the hypoxia effect on miRNAs which may aid and direct targeted therapy to conquer hypoxia in glioblastomas.
Multifocal and Multicentric Glioblastomas: A 10 Year Single Centre Experience
Authors: Maye Helen , Mavrovounis Georgios , Roncaroli Federico , McBain Catherine , Bailey Matthew , D’Urso Pietro , Coope David , Leach John , Leggate James , Karabatsou Tina
Published: October 2022

AIMS

The aims of this study are to share our experience of a large series of multifocal/multicentric glioblastomas (mGBM) and analyse the clinical, histological/molecular and neuroimaging characteristics as well as the outcomes of the patients in order to inform and contribute to future patient care.

METHOD

We conducted a retrospective single centre study of all multifocal/multicentric glioblastomas treated at our institution over a 10 year period. Data was collected from electronic patient records including patient demographics, clinical presentation, diagnostic imaging, treatment plans and histopathology/molecular findings. Time to recurrence/progression and overall survival was assessed.

RESULTS

1158 glioblastomas were treated surgically over this time period of which 121 multifocal/multicentric tumours were identified (10.4%). The median age at diagnosis was 63 years with a slight male predominance (54.5%). Half of all patients (61/121) presented with focal neurological deficits. 69% of patients underwent a craniotomy for diagnosis/debulking of the larger enhancing component of the tumour whilst 31% underwent only a biopsy. The median time to recurrence/progression was 154 days. Median length of survival was 269 days. Those who underwent craniotomy had significantly prolonged survival compared to biopsy alone 301 vs 198 days (p= 0.027) as did those who had a near total resection 401 vs 269 for subtotal resection (P=0.006) and those < 60 years (p=< 0.001). 88% of patients were IDH1 wildtype. Radiotherapy and chemotherapy confer a significant survival advantage when compared with no further treatment (p<0.001).

CONCLUSION

Near total resection of the larger enhancing component and post-operative chemo/radiotherapy can offer prolonged survival in patients with mGBM.
A Retrospective Review of the Management of Lung Cancer Patients Referred into the Regional Neuro-Oncology Pathway in Merseyside, United Kingdom
Authors: Heseltine Jonathan , Corte Ana , Kennedy Oliver , Sharples Harry , Brodbelt Andrew , Mehta Shaveta
Published: October 2022

AIMS

Brain metastases (BMs) are common in lung cancer and carry adverse prognostic significance. Such occurrences should be reviewed through a regional specialist neuro-oncology MDT. Our aim is to highlight which aspects of the pathway could be contributing to delays in the treatment of lung cancer patients with BMs.

METHOD

All lung cancer patients discussed at the Neuro-Oncology MDT in 2020 were identified. Details of the patient journey through the pathway from diagnosis to death were obtained from the Orion System, regional PACS system, regional neuro-oncology MDT notes and electronic case notes from Clatterbridge.

RESULTS

Full datasets were available for 100 patients discussed at the Neuro-Oncology MDT. 49 of these were patients presenting with BMs and lung cancer synchronously. Only 5 out of 13 (38%) of synchronous patients recommended for SRS received this treatment. 7 of 13 patients received a suboptimal treatment (best supportive care or whole-brain radiotherapy). Length of time from neuro-oncology MDT discussion to receiving SRS in the synchronous cohort was 47 versus 20.3 days in the asynchronous group. A review of all 13 cases found that 4 of the 7 cases of CNS-specific deterioration were potentially preventable. Further analysis of these cases revealed common themes of lengthy delays in histological sampling (9), delayed referral or discussion in the appropriate MDT (8) and not jointly referring to neuro-oncology and respiratory oncology (7).

CONCLUSION

Lung cancer patients with synchronous BMs receive SRS after full staging and biopsy. There is potential evidence of suboptimal outcomes due to inflexible MDT systems and delays for histology.
A Comparative Proteomic Analysis of the Cell Membrane of Histone 3 Mutated Paediatric High-Grade Gliomas in order to Identify Potential Immunotherapeutic Targets
Authors: Haque Farhana
Published: October 2022

AIMS

Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. We hypothesized that the histone 3 mutant tumours will have distinct mutation specific surfactome or cell surface proteins. We analysed the cell surface proteomics of H3.3 G34V and G34R mutated high-grade glioma in comparison to the H3 wild-type Glioma, to explore whether these proteins have the potential to be used as immunotherapeutic targets.

METHOD

We have at first isolated the cell membrane fractions from a range of patient cells carrying histone 3 mutations (G34R, G34V) relative to wild type histone 3. A comparative quantitative liquid chromatographic mass- spectrometry analyses of these cell surface membrane fractions were performed to identify specific targetable factors.

RESULTS

The results of these were analysed with the focus in identifying proteins that can be targeted for tumour specific immune modulation or immunotherapeutic intervention.

CONCLUSION

Results of these analyses will be presented.
Allied Heath Professional Support in Adult Neuro-oncology; Before and During COVID
Authors: Melhuish Sara , Bulbeck Helen
Published: October 2022

AIMS

To understand the current levels of Allied Health Professional (AHP) provision within adult neuro-oncology in the UK, gain insight into perceived gaps and any impact of the COVID-19 pandemic on this provision, from the Health Care Professional’s (HCP) perspective.

METHOD

In collaboration with brainstrust (a brain tumour charity) and the author, a mixed-methods, on-line survey of HCPs working within adult neuro-oncology was designed, tested and distributed to HCPs registered on the charity’s HCP database. Quantitative data was analysed using simple descriptive statistics. Qualitative data was analysed using thematic analysis.

RESULTS

51 HCPs from multiple roles and teams across the UK responded. 66% (34) reported a service delivery gap, including a lack of specialist AHP support, with high geographical variability. During the COVID-19 pandemic, 60.8% (31) respondents identified a reduction in access to AHP support. 58.8% (30) respondents reported a change in appointment modality, with an increase in telephone and video appointments and a decrease in face-to-face appointments and home visits. This modality change was highlighted as a possible cause of reduced HCP awareness of symptom progression that was also reported.

CONCLUSION

There is paucity of data regarding AHP provision within adult neuro-oncology and the impact of the COVID-19 pandemic on this provision. This study highlights concerns regarding overall specialist AHP support which reduced further during the COVID-19 pandemic. The impact on patients is unknown and highlights a need for further research to inform development of national guidelines for specialist AHP provision and the use of telehealth for this complex patient group.
Outcome of Image-Guided Surgical Biopsy of Brain Lesions: A Single Centre Experience
Authors: Saleh ElGhamry Ahmed Mohammed Nabil , Simon Natalie , Eltayeb Mohamed , Surash Surash
Published: October 2022

AIMS

The aim of this study was to quantify the accuracy of surgical biopsy for brain lesions using different image-guidance techniques, in our tertiary neurosurgical centre.

METHOD

Retrospective data was collected from electronic and paper patient notes. Data collected included: age, sex, comorbidities, pre-operative functional images, surgeon grade, biopsy method, number of targets, number of samples, result from frozen section and fixed sample histopathology, complications, and length of stay. Methods of biopsy included: ultrasound-guided, frame-based biopsy and frameless Brainlab guided biopsy (free-hand, Varioguide and registration tool -guided).

RESULTS

A percentage of 11.5% of cases (total = 52) were US-guided biopsy. Navigated frameless biopsies comprised 76.9% of all cases. In these cases, 42.3% of cases were guided by the registration tool, 23% used a fixed “Varioguide” instrument alignment tool and 11.5% were completed using the free-hand method. Overall accuracy of biopsy for all cases was 82.69%. Accuracy rates of different frameless methods were: 81.8% for Brainlab registration- guided biopsy, 66.7% for Brainlab Varioguide biopsy and 100% for Brainlab free-hand frameless biopsies. The percentage of complications was 5.8%.

CONCLUSION

In our centre, the accuracy of image-guided surgical biopsy for brain lesions was as high as 82.69% with a low complication rate of 5.8%. The Brain lab free-hand technique had the highest diagnostic yield and safety amongst all frameless stereotactic techniques.
Diagnostic Evolution of Synchronous Arteriovenous Malformation & Glioblastoma: A Case Report
Authors: Davis Jillian , Goldspring Rob , Scott Ian , Smith Stuart , Chattopadhyay Arpita
Published: October 2022

AIMS

We present the clinical course, radiology and histopathology of a case with synchronous pathology and aim to highlight learning points and diagnostic pitfalls.

METHOD

Case Notes, Radiology and Pathology were reviewed.

RESULTS

A 25 year old female with learning difficulties presented acutely with collapse. Initial CT-imaging demonstrated a right peritrigonal parenchymal haematoma with intraventricular extension. CT-Angiography revealed small vessels around the haematoma but no definite underlying vascular abnormality. Whilst the standard MRI sequences appeared to confirm the CT findings, the patient was unable to tolerate the planned MR angiogram or post-contrast sequences. Three months later, Digital Subtraction Angiography (DSA) revealed an “unusual” arteriovenous malformation (AVM) at the site of the previous haematoma. Over the following two months, the patient represented twice with acute headaches. CT imaging each time demonstrated further re-bleeds, with increasing oedema. Consequently, another DSA was performed for attempted embolisation but striking differences in the appearance of the AVM were now evident. Stereotactic radiosurgery was scheduled, but a planning CT-scan six weeks later revealed, for the first time, appearances suggestive of an underlying high-grade neoplasm. A biopsy was performed which showed a Glioblastoma (CNS WHO, 2021; Grade 4) alongside an arteriovenous malformation with well-developed arterial and venous structures. Despite optimal ICU management post-operatively, the patient deteriorated and sustained irreversible brain damage from which she did not recover.

CONCLUSION

Synchronous Glioblastoma and AVM is rare and can cause diagnostic and surgical challenges. These difficulties and the proposed angiogenic effects of tumour factors, as underlying aetiological agents of these synchronous lesions, is discussed.
The Management and Outcomes of Butterfly Gliomas at a U.K. Neurosurgical Unit
Authors: Sinha Siddharth , Avnon Adam , Perera Andrea , Lavrador Jose Pedro , Ashkan Keyoumars
Published: October 2022

AIMS

Butterfly glioblastomas (bGBM) are a rare subset of WHO grade IV tumours, that carry a poor prognosis with a median survival ranging between 3 to 6 months. Our study aims to add to the literature on how these tumours should be best managed when presenting to a neurosurgical unit.

METHOD

We performed a retrospective analysis from January 2009 to June 2021 of the electronic patient records of single large neurosurgical centre in London. We assessed patient demographics, initial clinical presentation, tumour characteristics (location, mutation, volumetric size), clinical management and overall survival (Kaplan-Meier estimator).

RESULTS

42 cases of bGBM were identified. These patients were managed with radiotherapy alone (n=3), with biopsy +/- adjuvant therapy (n=36) or attempted surgical resection (n=3). A further 38 cases of suspected bGBM were identified based on presentation and radiological imaging, however these patients were managed conservatively and did not undergo tissue diagnosis. No significant difference in survival was seen between conservative management compared to biopsy alone, with radiotherapy only or chemotherapy only (P=0.499) However, survival was significantly increased when patients received adjuvant chemoradiotherapy following biopsy or resection (P=0.04).

CONCLUSION

Butterfly glioblastoma has a devastating prognosis. Our study would suggest that unless a patient completes full adjuvant therapy with both chemotherapy and radiotherapy following biopsy or resection, they should be managed conservatively. This avoids unnecessary procedural interventions and can be deemed cost saving to the NHS. A larger prospective cohort study is recommended.
5-Aminolevulinic Acid (5-ALA) Use at The Walton Centre NHS Foundation Trust (WCFT)
Authors: Bennett Ruth , Akinsanya Elizabeth
Published: October 2022

AIMS

To audit the use of 5-ALA at WCFT to determine adherence to NICE guidance [NG99] and the Trust guideline.

METHOD

Data was retrospectively evaluated from 77 patients prescribed 5-ALA at WCFT Jan 2020 – Jan 2022.

RESULTS

Of the 77 patients, 61 (79%) patients had 5-ALA induced fluorescence documented intraoperatively which aided resection and 7 patients (9%) had no confirmed fluorescence. In patients with no fluorescence noted, the administration time to operation time was variable. The remaining 9 patients (12%) had no documentation on the presence or absence of fluorescence. Prior to surgery, 67 patients had an MDT outcome of likely high grade glioma. 66 patients had this confirmed with histology post-surgical resection. The remaining patients had various MDT diagnosis documented including oligoastrocytoma, oligodendroglioma and lesion. 87% of patients had the correct dose of 20mg/kg prescribed. 14 patients (18%) did not have liver function tests (LFT) checked during admission as per Trust policy. Of those checked, 29 patients (37%) had new derangement of LFT.

CONCLUSION

The use of 5-ALA has aided surgical resection, enabling greater resection in the majority of patients prescribed for at WCFT. It has been used in accordance with NICE for HGG resections in 87% of cases. Some improvement could be made in ensuring the correct dose is prescribed and the appropriate monitoring (LFT) is carried out post procedure. Theatre documentation could be improved so future audit can more easily identify extent of resection and extent of fluorescence.
A Longitudinal Study to Evaluate Biomarkers in Brain Tumour Patients
Authors: Whiteside Ellen
Published: October 2022

AIMS

To monitor brain tumour patient blood for predictive and prognostic biomarkers, in a prospective longitudinal study. Continuing the research of Dr. Abel the results may be used to predict tumour recurrence and progression from low- to high-grade. The results may be useful in the clinical management of malignant glioma patients.

METHOD

A patented panel of biomarkers will be investigated using FFPE tissue and blood components from adult brain tumour patients in the North West region. Biomarker expression will be analysed in different molecular sub-types of glioma, grouped by IDH and methylation status. An evaluation will be conducted to determine if reference ranges can be created to distinguish between high-and low-grade tumours. Spectroscopic analysis of blood samples will be tested to determine if cancerous and non-cancerous can be differentiated from each other. There will be testing of selected miRNA’s for up and down regulation patterns. Sample Intervals: Initial diagnosis, 24 hours post-surgery, pre-therapy, post-radiotherapy, after adjuvant therapy, at 3 then 6 monthly post therapy, at recurrence or suspected recurrence and at intervals during further therapy and follow up.

RESULTS

There are no results to report at this point in the study time line. Testing to start in April 2022.

CONCLUSION

The potential impact of research would work towards lower patient risk and less invasive procedures. If used as a screening tool could allow high NHS savings. There could be an impact on patient experience and survival if recurrence could be detected [NICE guideline NG99] recommendation for research.
Palliative Carboplatin Chemotherapy in Previously Treated High-Grade Glioma: Real-World Efficacy and Safety
Authors: Gupta Meetakshi , Mulholland Paul , Wilson Elena , Fersht Naomi , Kosmin Michael
Published: October 2022

AIMS

Effective third-line chemotherapy options for patients after temozolomide (TMZ) and nitrosourea-based chemotherapy for high-grade glioma (HGG) are not well defined. The use of carboplatin is limited due to uncertainly around its effectiveness and tolerability.

METHOD

Patients with HGG treated with single-agent carboplatin chemotherapy between 2005-2021 were identified from our institutional database. Patient and treatment-related details were acquired from electronic hospital records. SPSS Statistics for Windows, (Version 23.0, IBM Corp.) was used for data analysis.

RESULTS

A total of 16 HGG patients were identified. This included 9 glioblastoma (GBM) and 3 anaplastic astrocytomas (AA). These 12 patients were used for further analysis. The median age was 48 (22-73) years. All patients initially received a flat dose of 450 mg intravenous carboplatin every 3-4 weeks. All had previously received high dose RT (54-60 Gy), and temozolomide and lomustine-based chemotherapy. Carboplatin was used as 3rd or 4th line treatment. The median number of cycles given was 3 (range: 1-12). Five had rapid decline in performance status after 1-3 cycles. Five patients required dose/ cycle length adjustment due to grade 1 or 2 haematological toxicity. Other than cumulative fatigue, no other >/= grade 2 toxicities were reported. None required inpatient management for treatment toxicities. Median progression-free survival on carboplatin was 3 months (range 1-11 months) and overall survival was 8 months (range 1–26 months).

CONCLUSION

Carboplatin is a viable treatment option for HGG with acceptable toxicity rates. However, careful patient selection remains key to attaining maximum benefit.
The Evaluation of Novel Targets for CAR T Therapy in Glioblastoma
Authors: Alker Riza , Abel Peter , Griffiths David , Akhavan David
Published: October 2022

AIMS

The basis of this research revolves around the issue of limited expression of targetable tumour-specific antigens, heterogeneity, and mutation, which impede the development and success of CAR T therapy for glioblastoma. The research will identify an off-tumour cell target involved in tumour angiogenesis. The principal aim is to generate an off-tumour targeted CAR T and test their efficacy and safety in cell culture and animal models.

METHOD

Analyse the prevalence and distribution of the target molecules via immunohistochemistry (IHC). Confirm IHC results via mRNA extraction. Analyse the target molecule’s serum concentrations via the Luminex instrument. Generate the off-tumour targeted CAR T using lentivirus. Assess tumour burden and progression via a bioluminescent imaging system. Assess toxicity in vitro against human pericytes and in vivo by monitoring mouse weight and submitting histologic tissue for sectioning.

RESULTS

Utilise a scoring system to analyse the staining and correspond this to the serum concentrations to identify a blood-borne treatment response biomarker. If murine toxicity is observed, the CAR T construct will be affinity matured to selectively target molecules expressed at a cancerous level. A tandem bi-specific CAR T cells may also be created to mitigate immune escape and enhance anti-tumour efficacy.

CONCLUSION

The search for an off-tumour cell target for CAR T therapy in glioblastoma has not yet been completed. The discovery and validation of the novel molecule as a biomarker of treatment response would be a unique finding.
Discriminatory Ability of Gas Chromatography–Ion Mobility Spectrometry to Identify Patients Hospitalized With COVID-19 and Predict Prognosis
Authors: Nazareth Joshua , Pan Daniel , Kim Jee Whang , Leach Jack , Brosnan James G , Ahmed Adam , Brodrick Emma , Bird Paul , Wicaksono Alfian , Daulton Emma , Tang Julian W , Williams Caroline , Haldar Pranabashis , Covington James A , Pareek Manish , Sahota Amandip
Published: October 2022

Background

Rapid diagnostic and prognostic tests for coronavirus disease (COVID-19) are urgently required. We aimed to evaluate the diagnostic and prognostic ability of breath analysis using gas chromatography–ion mobility spectrometry (GC-IMS) in hospitalized patients with COVID-19.

Methods

Between February and May 2021, we took 1 breath sample for analysis using GC-IMS from participants who were admitted to the hospital for COVID-19, participants who were admitted to the hospital for other respiratory infections, and symptom-free controls, at the University Hospitals of Leicester NHS Trust, United Kingdom. Demographic, clinical, and radiological data, including requirement for continuous positive airway pressure (CPAP) ventilation as a marker for severe disease in the COVID-19 group, were collected.

Results

A total of 113 participants were recruited into the study. Seventy-two (64%) were diagnosed with COVID-19, 20 (18%) were diagnosed with another respiratory infection, and 21 (19%) were healthy controls. Differentiation between participants with COVID-19 and those with other respiratory tract infections with GC-IMS was highly accurate (sensitivity/specificity, 0.80/0.88; area under the receiver operating characteristics curve [AUROC], 0.85; 95% CI, 0.74–0.96). GC-IMS was also moderately accurate at identifying those who subsequently required CPAP (sensitivity/specificity, 0.62/0.80; AUROC, 0.70; 95% CI, 0.53–0.87).

Conclusions

GC-IMS shows promise as both a diagnostic tool and a predictor of prognosis in hospitalized patients with COVID-19 and should be assessed further in larger studies.
Brief Report: Prognostic relevance of 3q amplification in squamous cell carcinoma of the lung
Authors: Rous Fawzi Abu , Li Pin , Carskadon Shannon , Singh Sunny RK , Chacko Rebecca , Abushukair Hassan , Gadgeel Shirish , Palanisamy Nallasivam
Published: October 2022

Introduction

Amplification of 3q is the most common genetic alteration identified in squamous cell carcinoma of the lung (LUSC) with the most frequent amplified region being 3q26-3q28.

Methods

In this analysis, we aim to describe the prognostic relevance of 3q by focusing on a minimal common region (MCR) of amplification within 3q constituted by 25 genes. We analyzed 511 cases of LUSC from The Cancer Genome Atlas (TCGA) and included 476 in the final analysis.

Results

We identified a 25-gene MCR that was amplified in 221 (44.3%) cases and was associated with better disease specific-survival (DSS) (NR versus 9.25 years; 95% CI [5.24-NR]; log-rank p=0.011) and a progression-free interval (PFI) of 8 years (95% CI [5.1-NR]) versus 4.9 years (95% [3.5-NR]) (Log-rank p=0.020). Multivariable analysis revealed MCR amplification was associated with improved DSS and PFI.

Conclusion

Amplification of the 25-gene MCR within 3q was present in 44% of this cohort mainly composed of Caucasian patients with early-stage LUSC. This analysis is a strong indicator of the prognostic relevance of the 25-gene MCR within 3q. We are further evaluating its prognostic relevance in a racially diverse patient population with advanced LUSC.
Meta-analysis of GWAS for sea lice load in Atlantic salmon
Authors: Cáceres P. , Lopéz P. , Garcia B. , Cichero D. , Ødegård J. , Moen T. , Yáñez J.M.
Published: October 2022

Sea lice (Caligus rogercresseyi) is an ectoparasite that causes major production losses in the salmon aquaculture industry of the southern hemisphere. Atlantic salmon (Salmo salar) is an important salmonid for the aquaculture industry and a species which is highly susceptible to sea lice infestation. Genetic variation for resistance to sea lice, defined as parasite load, has been found in Atlantic salmon. In addition, sea lice load has been shown to be a polygenic trait, controlled by several quantitative trait loci (QTL) which have small to medium effect, making them difficult to map with sufficient statistical power when sample sizes are limited. The use of medium density single nucleotide polymorphisms (SNP) can also adversely affect the success of identifying genetic variants significantly associated to sea lice load. In order to improve the ability to detect QTL significantly associated to sea lice load, we combined genotype imputation from medium- to high SNP-density and performed genome-wide association studies (GWAS) across different populations of Atlantic salmon. The imputation of genotypes of 6,144 fish challenged against sea lice from four year-classes was performed to increase density from 70K SNPs to 600K SNPs. A meta-GWAS was then carried out for three different traits: lice count, lice density and log-lice density. Using this approach, we detected a genomic region highly associated to sea lice load on Atlantic salmon chromosomes (ssa) 3 and 12 pronounced peaks and several other regions surpassing the significance threshold across almost all other chromosomes. We also identified important genes within the QTL regions, many of these genes are involved in tissue reparation, such as Mucin-16-like isoform X2 and Filamentous growth regulator 23-like isoform X1. The QTL region on ssa03 also contained cytoskeletal-modifying and immune response related genes such as Coronin 1A and Claudin. Our results confirm the highly polygenic architecture of sea lice load, but they also show that high experimental power can lead to the identification of candidate genes and thus to increased insight into the biology of sea lice resistance in Altantic salmon.
Oligodendrocyte precursor cells stop sensory axons regenerating into the spinal cord
Authors: Kim Hyukmin , Skuba Andy , Xia Jingsheng , Han Sung Baek , Zhai Jinbin , Hu Huijuan , Kang Shin H. , Son Young-Jin
Published: October 2022

Primary sensory axons stop regenerating as they re-enter the spinal cord, resulting in incurable sensory loss. What arrests them has remained unclear. We previously showed that axons stop by forming synaptic contacts with unknown non-neuronal cells. Here, we identified these cells in adult mice as oligodendrocyte precursor cells (OPCs). We also found that only a few axons stop regenerating by forming dystrophic endings, exclusively at the CNS:PNS borderline where OPCs are absent. Most axons stop in contacts with a dense network of OPC processes. Live imaging, immuno-EM and OPC-DRG co-culture additionally suggest that axons are rapidly immobilized by forming synapses with OPCs. Genetic OPC ablation enables many axons to continue regenerating deep into the spinal cord. We propose that sensory axons stop regenerating by encountering OPCs that induce presynaptic differentiation. Our findings identify OPCs as a major regenerative barrier that prevents intraspinal restoration of sensory circuits following spinal root injury.
Asynchronous haltere input drives specific wing and head movements inDrosophila
Authors: Rauscher Michael J , Fox Jessica L
Published: October 2022

Halteres are multifunctional mechanosensory organs unique to the true flies (Diptera). A set of reduced hindwings, the halteres beat at the same frequency as the lift-generating forewings and sense inertial forces via mechanosensory campaniform sensilla. Though it is well-established that haltere ablation makes stable flight impossible, the specific role of wing-synchronous input has not been established. Using small iron filings attached to the halteres of tethered flies and an alternating electromagnetic field, we experimentally decoupled the wings and halteres of flyingDrosophilaand observed the resulting changes in wingbeat amplitude and head orientation. We find that asynchronous haltere input results in fast saccades in the wing but not the head. We also find that wing and gaze optomotor responses are disrupted differently by asynchronous input. These effects of wing-asynchronous haltere input show that specific sensory information is necessary for maintaining wing amplitude stability and adaptive gaze control.
DeepBIO is an automated and interpretable deep-learning platform for biological sequence prediction, functional annotation, and visualization analysis
Authors: Wang Ruheng , Jiang Yi , Jin Junru , Yin Chenglin , Yu Haoqing , Wang Fengsheng , Feng Jiuxin , Su Ran , Nakai Kenta , Zou Quan , Wei Leyi
Published: October 2022

Here, we present DeepBIO, the first-of-its-kind automated and interpretable deep-learning platform for high-throughput biological sequence functional analysis. DeepBIO is a one-stop-shop web service that enables researchers to develop new deep-learning architectures to answer any biological question. Specifically, given any biological sequence data, DeepBIO supports a total of 42 state-of-the-art deep-learning algorithms for model training, comparison, optimization, and evaluation in a fully automated pipeline. DeepBIO provides a comprehensive result visualization analysis for predictive models covering several aspects, such as model interpretability, feature analysis, functional sequential region discovery,etc. Additionally, DeepBIO supports 9 base-level functional annotation tasks using deep-learning architectures, with comprehensive interpretations and graphical visualizations to validate the reliability of annotated sites. Empowered by high-performance computers, DeepBIO allows ultra-fast prediction with up to million-scale sequence data in a few hours, demonstrating its usability in real application scenarios. Case study results show that DeepBIO provides an accurate, robust, and interpretable prediction, demonstrating the power of deep learning in biological sequence functional analysis. Overall, we expect DeepBIO to ensure the reproducibility of deep-learning biological sequence analysis, lessen the programming and hardware burden for biologists, and provide meaningful functional insights at both sequence-level and base-level from biological sequences alone. DeepBIO is publicly available athttp://inner.wei-group.net/DeepBIO.
A high quality chromosome-level genome assembly for the golden mussel (Limnoperna fortunei)
Authors: R. N. Ferreira João Gabriel , Americo Juliana A. , do Amaral Danielle L. A. S. , Sendim Fábio , da Cunha Yasmin R. ,   The Darwin Tree of Life Project Consortium, Uliano-Silva Marcela , Rebelo Mauro de F.
Published: October 2022

The golden mussel (Limnoperna fortunei) is a highly adaptive species that causes environmental and socioeconomic losses in invaded areas. Reference genomes have proven to be a valuable resource for studying the biology of invasive species. While the current golden mussel genome has been useful for identifying new genes, its high fragmentation hinders some applications. In this Data Note, we provide the first chromosome-level reference genome for the golden mussel. The genome was built using Hi-C, PacBio HiFi and 10X sequencing data. The final assembly contains 99.4% of its total length assembled to the 15 chromosomes of the species and a scaffold N50 of 97.05 Mb. Approximately 47% of the genome was annotated as repetitive sequences. A total of 34 862 protein-coding genes were predicted, of which 84.7% were functionally annotated. This new high quality genome is expected to support both basic and applied research on this invasive species.

Species taxonomy

Eukaryota; Opisthokonta; Metazoa; Eumetazoa; Bilateria; Protostomia; Spiralia; Lophotrochozoa; Mollusca; Bivalvia; Autobranchia; Pteriomorphia; Mytilida; Mytiloidea; Mytilidae; Arcuatulinae; Limnoperna; Limnoperna fortunei (Dunker, 1857) (NCBI Taxonomy ID: 356393)
Brain-wide associations between white matter and age highlight the role of fornix microstructure in brain ageing
Authors: Korbmacher Max , de Lange Ann Marie , van der Meer Dennis , Beck Dani , Eikefjord Eli , Lundervold Arvid , Andreassen Ole A. , Westlye Lars T. , Maximov Ivan I.
Published: October 2022

Unveiling the details of white matter (WM) maturation throughout ageing is a fundamental question for understanding the ageing brain. In an extensive comparison of brain age predictions and age- associations of WM features from different diffusion approaches, we analysed UK Biobank diffusion Magnetic Resonance Imaging (dMRI) data across midlife and older age (N= 35,749, 44.6 to 82.8 years of age). Conventional and advanced dMRI approaches were consistent in predicting brain age. WM-age associations indicate a steady microstructure degeneration with increasing age from midlife to older ages. Brain age was estimated best when combining diffusion approaches, showing different aspects of WM contributing to brain age. Fornix was found as the central region for brain age predictions across diffusion approaches in complement to forceps minor as another important region. These regions exhibited a general pattern of positive associations with age for intra axonal water fractions, axial, radial diffusivities and negative relationships with age for mean diffusivities, fractional anisotropy, kurtosis. We encourage the application of multiple dMRI approaches for detailed insights into WM, and the further investigation of fornix and forceps as potential biomarkers of brain age and ageing.
ROCA: An Ontology to Describe and analyse Tool Use and Tool Making
Authors: Mercuriali Pierre R. , Corbato Carlos Hernandez , Langejans Geeske H.J.
Published: October 2022

To contribute to current discussions on the complexity of extinct and modern non-human and human primate tasks, we explore if ontologies are helpful as a means of representing tool tasks. We thus hope to help illuminate how primates approach tool tasks internally, such as breaking open a nutshell between a wooden anvil and a stone hammer to access its nutritious contents or fishing for termites with a leaf midrib. Ontologies are widely used in domains such as linguistics, medicine, archaeology, and cultural heritage, to help experts organize, reason on, and discover new knowledge in their field. We build a novel ontology, ROCA (from ‘roca’ - - rock, in Spanish) with which we can describe instances of tool use in a formal and uniform manner, including well-known primate ethograms and chaînes opératoires. We will see that representing tool use and tool making with an ontology provides auniform, unified, acentric, dynamic, and human-readable way to handle knowledge obtained from literature and to perform knowledge discovery. We build a representative corpus of 75 articles and books on primate and hominin tool use and tool making. We then extract and give semantic structure such as taxonomical relationships to relevant vocabulary, both manually and automatically, using NLP text mining techniques. We then show how the ontology can be used to discover new knowledge related to tool use and tool making.
βIII-Tubulin is a Brake on Extrinsic Cell-Death in Pancreatic Cancer
Authors: Kokkinos John , Sharbeen George , Ignacio Rosa Mistica C. , Pandzic Elvis , Youkhana Janet , Boyer Cyrille , Haghighi Koroush S. , Gunawarman Matthew , Goldstein David , Gebski Val , Pajic Marina , Pitiyarachchi Omali , Davis Meagan E. , Schulstad Grace , Arkell Oliver S.M. , Kopecky Chantal , Gonzales-Aloy Estrella , Erkan Mert , Morton Jennifer P. , Kavallaris Maria , Gunning Peter W. , Hardeman Edna C. , Johns Amber , Gill Anthony J. , Whan Renee M. , Mawson Amanda ,   Australian Pancreatic Cancer Genome Initiative, McCarroll Joshua A. , Phillips Phoebe A.
Published: October 2022

The microtubule protein, βIII-tubulin, has been implicated as a prognostic, pro-survival, and chemoresistance factor in some of the most lethal malignancies including pancreatic ductal adenocarcinoma (PDAC). However, precise survival mechanisms controlled by βIII-tubulin in cancer cells are unknown. Here, we report an unexpected role of βIII-tubulin as a brake on extrinsic caspase 8-dependent apoptosis in PDAC. We show that βIII-tubulin knockdown frees death-receptor DR5 to increase its membrane diffusion, clustering, and activation of cell-death. We demonstrate that βIII-ubulin silencing increases sensitivity of PDAC cells to chemotherapeutic and microenvironment-derived extrinsic cell-death signals including TRAIL, TNFα, and FasL. Finally, nanoparticle delivery of βIII-tubulin siRNA to mouse orthotopic PDAC tumours in vivo and human patient-derived PDAC tumour explants ex vivo increases extrinsic apoptosis and reduces tumour progression. Thus, silencing of βIII-tubulin represents an innovative strategy to unleash a suicide signal in PDAC cells and render them sensitive to microenvironment and chemotherapy-derived death signals.
Consistent, linear phenological shifts across a century of observations in South Korea
Authors: Pearse William D. , Stemkovski Michael , Lee Benjamin R. , Primack Richard B. , Lee Sangdon
Published: October 2022

The Korea Meteorological Agency (KMA) has monitored flowering dates over the past 100 years for seven economically important woody plant species. This unique dataset is perfect for understanding whether historical patterns of phenological plasticity are breaking down in the face of recent and rapid climate change. Here we show that a scientist armed only 50 years into this study would have been able to predict the phenological shifts of the last 50 years with a high degree of accuracy. This is despite record-breaking warm temperatures and unprecedented early flowering, suggesting consistency in phenological shifts over time.