bluuebunny/crossref_metadata_2025 huggingface dataset:
PREDICTING GLIOBLASTOMA GENE EXPRESSION THERAPY RESPONSE WITH MACHINE LEARNING
Authors: Thomas Morgan , Theophanous Stelios , Whittle Isabelle , Finetti Martina , Pollock Steven , Ahmed Nazia , Tanner Georgette , Chakrabarty Aruna , Ismail Azzam , Bulpitt Andrew , Stead Lucy
Published: September 2023

AIMS

The rapid recurrence of therapy-resistant glioblastoma leaves patients with a dismal 2-year survival rate of just 16%, highlighting the need to develop treatments that combat or prevent glioblastoma recurrence. Recently, glioblastoma patients have been stratified by their gene expression response to therapy. Specifically, genes with JARID2 binding sites in their promoter (JBS-genes) either become up- or down-regulated on progression from the primary to the recurrent tumour. Importantly, these two responses appear to employ different mechanisms of therapy resistance. Using gene expression data from primary tumours, we aim to predict the direction of JBS- gene dysregulation. Ultimately, this prediction could guide treatment decisions that prevent the acquisition of therapy resistance in glioblastoma.

METHOD

We used gene expression data from 84 primary glioblastoma tumours that had been labelled as either ‘Up’ or ‘Down’ responders based on the direction of JBS-gene dysregulation in matched recurrent tumours. We converted the RNA-sequencing data from the primary tumours to single-sample pathway scores, which were used to train several binary classification machine learning models.

RESULTS

A ridge regression model achieved an accuracy of 73.9% in predicting the direction of JBS-gene dysregulation in an independent set of 23 primary glioblastoma tumours.

CONCLUSIONS

Our classifier performs better than random chance demonstrating that gene expression data is informative and molecular features influence this gene expression response to therapy. However, there remains scope for improvement. This suggests further studies may benefit from integrating multiple data types such as genomics, epigenomics, tumour architecture, or clinical variables.
GLIOBLASTOMA CELL INVASION IS TARGETABLE BY COMBINATION TREATMENT WITH MIGRASTATIC INHIBITORS
Authors: Prior Sally , Senior Jessica , Jaworska Kayley , Burns Eryn , Ahmed Zara , Butler Hayley , Brüning-Richardson Anke
Published: September 2023

AIMS

One of the hallmarks of cancer is cell migration and invasion, a striking feature of glioblastoma (GBM). The highly migratory potential of tumour cells enables recurrence of GBM tumours leading to poor survival and patient death. We recently characterised a panel of migrastatic inhibitors and reported on the ability of glioma cells to overcome drug activity by employing a mesenchymal to amoeboid migratory switch. Here we demonstrate that targeting different signalling pathways involved in cell migration induces synergistic drug activity of single inhibitors.

METHOD

The previously described inhibitors CCG-1423 and Rhosin Hydrochloride were used singly or in combination to target cell migration in established glioma cell lines. Characterisation of drug activity was achieved by 2D and 3D migration and invasion assays and cytoskeletal and morphological changes were assessed by immunofluorescence assays.

RESULTS

When used in single applications, the inhibitors did not have a significant effect on cell migration in 2D and 3D. However, combination treatments led to significantly reduced migration in both 2D and 3D with notable effects on the cytoskeleton as evidenced by changes in focal adhesion dynamics and in actin localisation. Cellular features also changed in response to combination treatment as noted by increase in cell size and adhesion to neighbouring cells.

CONCLUSIONS

The observed effects are in keeping with targeting two distinct signalling pathways driving cells to either adopt amoeboid or mesenchymal cell migration/invasion mechanisms. We propose that a ‘cocktail’ of migrastatic inhibitors should be included in future experimental designs for consideration as novel, complementary treatment strategies in GBM.
TUMOUR TREATING FIELDS (TTFIELDS) THERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA: A META-ANALYSIS AND SYSTEMATIC REVIEW OF REAL-WORLD SURVIVAL DATA
Authors: Ballo Matthew , Conlon Patrick , Lavy-Shahaf Gitit , Urman Noa , Kinzel Adrian , Vyamzal Josef , Rulseh Aaron
Published: September 2023

AIMS

Tumour Treating Fields (TTFields) are electric fields that disrupt processes required for cancer cell viability and tumour progression. TTFields therapy gained FDA approval and CE accreditation for newly diagnosed glioblastoma (ndGBM) following the EF-14 study (NCT00916409). We aimed to determine the real-world survival benefit of TTFields therapy.

METHOD

Survival data from clinical studies in TTFields therapy-treated patients with ndGBM were identified using a literature search and analysed. The Cochran Q test and Higgins I2 statistic were used to assess and quantify inter-study heterogeneity. Survival curves were pooled using a distribution-free random-effects method.

RESULTS

Among studies evaluating the clinical effcacy of TTFields therapy in ndGBM, six studies were identified which compared the addition of TTFields therapy to standard of care (SOC) vs SOC alone. The meta-analysis showed a significant improvement in OS for TTFields therapy-treated patients vs SOC alone (P < 0.001). The pooled effect was robust and independent of any individual study. In post-approval studies, the pooled median OS was 22.2 months (95% CI, 17.3–42.6) and 17.3 months (95% CI, 13.6–22.0) for TTFields therapy-treated patients and SOC, respectively. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields therapy use. Average device usage of ≥75% was associated with prolonged survival vs <75% usage (pooled HR: 0.63; 95% CI, 0.48–0.83; P = 0.001).

CONCLUSIONS

Data suggest a significant survival benefit when TTFields therapy is added to SOC for patients with ndGBM. Usage of ≥75% may be meaningful in the real-world setting.
THREE FRACTION STEREOTACTIC RADIOTHERAPY (SRT) FOR VESTIBULAR SCHWANOMMA: THE WESSEX EXPERIENCE
Authors: Main Sean , Ching Jeng , Kaylan Jasdeep , Shanmugasundaram Ramkumar , Sinclair Georges , Clarke Enrico
Published: September 2023

AIMS

Retrospective review of SRT for vestibular schwannoma. University Hospital Southampton treat tumour vol umes max 2.5cm in diameter without brainstem compression with 21Gy/3#. This reviews the experience of local control and toxicity profile in our centre and the impact of limiting dmax.

METHOD

Retrospective analysis of patients treated for radiologically diagnosed vestibular schwannoma from 2019 to present. Patient notes, audiograms, imaging and radiotherapy planning system were reviewed for data collection. No patients were removed from analysis due to missing data.

RESULTS

36 patients have been treated with three fraction SRT. Median age 68 (47-83). PTV volume from 1.03cm3 to 5.52cm3 (median 2.37cm3). All patients have radiologically stable disease to date, with 14 patients (38.9%) having objective tumour response on imaging. 9 patients had serviceable hearing at baseline and 1 remained serviceable at follow up. 7 (19.4%) patients experienced treatment-related toxicity. 6 patients reported facial nerve toxicity in which 4 (66.7%) this was self-limiting with full recovery. 2 patients had persistent facial nerve symptoms (House-Brackmann score 2, and 3 respectively). Those with dmax <26Gy (n=15) experienced this less with only 1 patient experiencing facial nerve toxicity (House-Brackmann score 2).

CONCLUSIONS

Three fraction SRT provides excellent local control with high levels of objective radiological response in tumours up to 4cm3, however, long term follow-up is required. This treatment has acceptable toxicity with most symptoms resolving spontaneously. Permanent facial nerve toxicity was seen in 2 (5.6%) of patients. By limiting dmax to <26Gy the rate of facial nerve toxicity is reduced significantly.
CIRCULATING PROGNOSTIC BIOMARKERS IN MENINGIOMA: S100A4 AND FIBULIN-2
Authors: Kingdon Sarah , Sofela Agbolahan , Adams Claire , Hanemann Oliver
Published: September 2023

AIMS

We aim to identify circulating prognostic biomarkers that accurately identify high risk meningioma whilst reducing the burden of invasive diagnostics. In our proteomic analysis, S100A4 and Fibulin-2 are significantly over expressed in grade 2 tumours compared to grade 1. They are both calcium-binding proteins with S100A4 involved in mesenchymal transition while Fibulin-2 helps scaffold the extracellular matrix. Elevated levels correlate with aggressive phenotypes in multiple cancers.

METHOD

Anonymised pre-operative meningioma blood samples were obtained from ‘The Plymouth Brain Tumour Biobank’ and ‘UK Brain Archive Information Network (BRAIN-UK)’. In total, 155 samples were analysed via Enzyme-Linked Immunosorbent Assay (ELISA) for serum S100A4 and plasma Fibulin-2. The Area Under the Receiver Operating Characteristic (ROC) curve (AUC) was used to examine the specificity and sensitivity of both markers.

RESULTS

Circulating levels of S100A4 were significantly (*p<0.05) higher in grade 2 meningiomas (mean 276.7 pg/mL (+/- 49.9 pg/mL) compared to grade 1 (mean 153.10 pg/mL +/- 20.68 pg/mL).

Serum S100A4 & plasma Fibulin-2 cut-off values of 344.8 pg/mL & 2500 pg/mL respectively have a 95% specificity for identifying patients with grade 2 tumours over grade 1.

To improve the diagnostic accuracy of grade 1 vs grade 2 samples, we combined S100A4 and Fibulin-2 concentrations to achieve an improved AUC of 0.682, *p<0.05.

CONCLUSIONS

Serum S100A4 is significantly higher in grade 2 compared to grade 1 meningiomas (95% sensitivity; cut off 344.8 pg/mL). Combining S100A4 and the previously published Fibulin-2 improves the accuracy of predicting grade 2 meningiomas.
RADIOLOGICAL SURVEILLANCE AFTER RESECTION OF LOW GRADE DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOUR AND GANGLIOGLIOMA: HOW OFTEN AND FOR HOW LONG?
Authors: Marples Theodore , Wang Difei , Saumtally Tasneem , Kalyal Nida , Bodi Istvan , Hasegawa Harutomo , Selway Richard
Published: September 2023

AIMS

Prolonged follow-up with imaging has costs both financial and psychological. We sought to review clinical and radiological follow-up for operated dysembryoplastic neuroepithelial tumour (DNET) and ganglioglioma in our unit.

METHOD

Retrospective review of patients diagnosed with WHO grade 1 DNET or ganglioglioma identified from our histopathology database over the last 20 years.

RESULTS

44 patients were identified (DNET n=23, ganglioglioma n=21). Mean age at first surgery was 27.2 and 22.3 respectively. The median length of follow-up was 3.45 (0.84-13.9) years for DNET, and 5.03 (0.4-12.6) years for ganglioglioma. The majority of the patients had epilepsy (39/44, 88.6%) prior to surgery. Patients with DNET had 0.58 postoperative scans per year, whilst those with ganglioglioma had 1.17 scans per year. 11 (47.8%) DNET and 9 (42.9%) ganglioglioma patients had residual tumour after first surgery. None of the DNET patients had radiological change during follow-up. 9 (43%) patients with ganglioglioma had radiological change noted at least once during follow-up. 3 (13%) patients with DNET and 4 (19%) with ganglioglioma had further surgery for ongoing seizures due to residual tumour, but not for radiological progression.

CONCLUSIONS

Radiological change following tumour resection did not occur for DNET whereas it was more common for gangliogliomas. A reduction in postoperative imaging in our practice could be considered for operated low grade DNET and ganglioglioma, given that for all patients the indication for reoperation was seizures rather than tumour progression.
AUTOMATED VASARI FEATURE SET REPORTING FOR GLIOMAS IS EffCIENT AND EFFECTIVE
Authors: Lee Faith , Ruffle James , Mohinta Samia , Kopanitsa Valeria , Nachev Parashkev , Hyare Harpreet
Published: September 2023

AIMS

The quantitative evaluation of gliomas using the VASARI MRI feature sets aims to facilitate consistent radiological reporting of gliomas but rarely done in clinical practice due to user variability in addition to technical and time constraints. We questioned whether deep-learning driven systems for automated VASARI feature derivation might resolve these issues, with comparison to neuroradiologist ground truths.

METHOD

VASARI imaging features were derived for 125 gliomas, both manually and using the automated model. Tumour segmentation models were constructed using 1251 patients from RSNA-BRATS with nnU-Net, and a processing pipeline developed within Python. The following features were compared: tumour location (F1); side of lesion (F2); proportion enhancing (F5); proportion non-enhancing (nCET) (F6); multifocal (F9); proportion edema (F14); ependymal extension (F19) and deep white matter (WM) invasion (F21).

RESULTS

The out-of-sample Dice performance for the tumour segmentation model was 0.945. Automated VASARI feature sets could be derived at a rate of under 0.5 seconds per patient. There was high concordance between manual and automatic segmentation in determining side of lesion (F2, 91.2%), ependymal extension (F19, 86.4%), anatomical tumour location (F1, 77.6%), deep WM invasion (F21, 65.6%) and proportion of enhancing tumour (F5, 54.4%; r=0.377, p<0.001). Automated segmentation overestimated proportions of edema (F14, 92.8%) and nCET (F6, 86.4%).

CONCLUSIONS

Automated VASARI feature set generation provides quick and accurate predictions however, proportions of oedema and non-contrast tumour were frequently over-estimated. Future empirical work will focus on optimization and further systematic evaluation of this automated pipeline for more accurate quantitative radiology reporting and corresponding clinical decision-making.
NON-ENHANCING/MINIMALLY ENHANCING GLIOMAS: CAN WE IDENTIFY LOW GRADE GLIOMAS?
Authors: Saady Yuta J , Mair Richard , Joannides Alexis , Santarius Thomas , Matys Tomasz , Price Stephen J
Published: September 2023

AIMS

Gliomas are traditionally separated into low-grade (LGG) and high-grade (HGG). As LGG are slower growing and with pressures on operating capacity, there is an argument that surgery for these patients can wait. Pre- operatively, contrast enhancement on imaging is usually taken as the method of differentiating grade, with the belief that the absence of enhancement indicates LGG. We therefore assessed patients with minimal/non- enhancing tumours and compared factors at diagnosis with final histological outcome.

METHOD

We identified a cohort of patients over a 19-month period with a first presentation to the neurosurgical oncology clinic with minimal/patchy/scattered foci of enhancement (ME) or no areas of contrast enhancement (NE) on imaging, collecting factors at diagnosis and histological outcome using electronic patient records.

RESULTS

Of 60 patients identified, 53.3% were HGG, 35.0% LGG and 11.7% non-glioma. In NE tumours HGG and LGG rates were equal (43.3%), whereas in ME tumours HGG comprised 63.3% versus 26.7% LGG. HGG patients were older on average than LGG (median age 53 years versus 33 years) and more prevalent in males (62.95%) compared to females (45.45%). HGG formed the majority of patients presenting with seizure only (60%), neurological deterioration only (50%) or ≥2 symptoms (57.6%), whereas LGG was higher in presentations with headache only (66.7%) or none of the symptoms (66.7%).

CONCLUSIONS

It is not possible to differentiate between ‘high-grade’ and ‘low-grade’ gliomas based on imaging findings alone. Age is clearly a differentiating factor, but symptoms do not appear to be. We are working to develop methods to better differentiate these tumours pre-operatively.
SURVIVAL OUTCOMES AFTER WHOLE BRAIN RADIOTHERAPY
Authors: Ho Andrew , Kazmi Farasat , Hendry Hannah , Gkogkou Pinelopi
Published: September 2023

AIMS

Cerebral metastases from extra-cranial primary cancer carries a poor prognosis. For patients in whom surgical resection or SRS are not suitable, local control rates are poor. There is considerable debate surrounding the value of whole brain radiotherapy in this patient cohort in terms of local control, survival and functional status. We aimed to measure survival in patients receiving whole brain radiotherapy at the Norfolk and Norwich University Hospital.

METHOD

All patients who completed a course of whole brain radiotherapy at our centre between April 2018 and December 2022 were retrospectively analysed. Patients who were receiving prophylactic cranial irradiation of small cell lung cancer were excluded. Baseline demographics, oncologist declared ECOG performance status at referral for treatment, radiotherapy dose and survival were recorded.

RESULTS

88 patients received WBRT during this period. The median follow-up interval was 85 days. 12 patients received 30 Gy in 10 fractions, 59 received 20 Gy in 5 fractions and 17 received 12 Gy in 2 fractions. The median overall survival following completion of radiotherapy was 85 days. At 6 weeks after radiotherapy, 23.9% of patients had died. Univariate analysis with Cox proportional hazards model did not demonstrate a significant hazard ratio for age (<65 or ≥65), ECOG performance status or radiotherapy dose.

CONCLUSIONS

Survival following whole brain radiotherapy remains poor. In particular, almost a quarter of patients are not alive 6 weeks after treatment. This is particularly pertinent given the anticipated trajectory of acute toxicities from treatment.
ANTI-SEIZURE MEDICATION IN GLIOMA PATIENTS: GETTING IT RIGHT fiRST TIME
Authors: Brothwell Morag , Collins Jennifer , Dulley Louise
Published: September 2023

AIMS

Seizures affect between 60–90% patients with low grade glioma and between 40–60% patients with high grade glioma. There are no national guidelines for seizure management in glioma patients. This quality improvement project investigated the initiation of anti-seizure medication in glioma patients with new-onset seizures.

METHOD

A retrospective review was undertaken of new glioma patients’ electronic notes (2020-2022) seen in Oncology clinic at Colchester hospital.

RESULTS

Thirty-seven patients (twenty-five glioblastoma IDH-wt, two grade 3 astrocytoma IDH-mutant, one grade 2 astrocytoma IDH-mutant, three oligodendroglioma IDH-mutant, six radiological diagnoses of glioma) were included. Following neurosurgical discharge, twenty-three did not need anti-seizure medication, three had long standing anti-seizure medication which was not changed, one patient was advised to stop phenytoin medication after surgery, four patients were on levetiracetam 500mg twice daily and six patients were on levetiracetam 250mg twice daily, with no dose escalation plan in place. Three of these six patients were subsequently hospitalised with seizures, one of which interrupted chemoradiation. None of the four patients on 500mg BD were hospitalised with seizures.

CONCLUSIONS

This project highlights the need for local anti-seizure guidelines for new glioma patients, which should include consideration of personalised drug choice, dependent on seizure type and demographics. Patients should be escalated to the therapeutic levetiracetam dose to decrease the risk of morbidity from seizures. This supports the need for national guidelines on anti-seizure medication with neurology collaboration.
SHOULD CALCIUM SUPPLEMENTS BE PRESCRIBED PROPHYLACTICALLY FOR PATIENTS DIAGNOSED WITH A HIGH-GRADE GLIOMA (HGG) ON PROLONGED STEROID USE?
Authors: La Jessica , Hurwitz Victoria , Robinson Charlotte , Kostick Ellie , Suarez Aeron , Hedges Sarah , Harding Nicola , Fukuthi Renata , Brazil Lucy , Swampillai Angela , Al-Salihi Omar , Chia Kazumi , Manik Vishal , Bhangoo Ranjeev , Ashkan Keyoumars , Gullan Richard , Vergani Francesco , Lavrador Jose Pedro
Published: September 2023

AIMS

The case study review will evaluate whether patients on long term steroid would benefit from calcium supplements and if a protocol for a bone density scan should be in place in relation to how long patients have been on steroids for.

Duration of steroid use increases patients’ risk to steroid related toxicity when taken more than 3 weeks. These can include endocrine, skeletal and psychiatric side effects amongst many others. It is therefore important to assess how we can improve patients’ quality of life (QOL) with limited prognosis.

METHOD

In a single centre, patients diagnosed with a HGG will be reviewed if they were diagnosed with osteoporosis or spinal fractures between 2020- 2022, subsequent from prolonged steroid use.

RESULTS

All 7 patients identified had presented with severe lower back pain. 4 patients initially had bone density scans which prompted an MRI due to low minerals for patient age and osteoporosis, whilst the remaining 3 patients only had an MRI scan. All 7 patients had spinal fractures. The average dexamethasone use was 9 months unable to wean to stop.

CONCLUSIONS

Patients diagnosed with a HGG tumour sadly continue to have poor prognosis. For patients who have had limited debulking or biopsy only, this leaves them prone to require ongoing steroid use to help with side effects to improve QOL.

Though the figures are small, we can see patients who struggled to wean to stop dexamethasone since their intracranial surgery have had their QOL impacted due to steroid toxicities with no previous related comorbidities.
THE ROLE OF A GENOMICS CLINICAL NURSE SPECIALIST IN HELPING TO BUILD A PATHWAY FOR WHOLE GENOME SEQUENCING TO BE OFFERED TO NEURO-ONCOLOGY PATIENTS
Authors: Suarez Aeron , Hurwitz Victoria , La Jessica , Robinson Charlotte , Kostick Ellie , Hedges Sarah , Harding Nicola , Fukuthi Renata , Dias Ana , Alhaq Anwar , Clark Barnaby , Al-Sarraj Safa , Laxton Ross , Eggleton Kelly , Bhangoo Ranjeev , Ashkan Keyoumars , Gullan Richard , Vergani Francesco , Lavrador Jose Pedro , Bleil Cristina , Zebian Bassel , Brazil Lucy , Al-Salihi Omar , Swampillai Angela , Chia Kazumi , Manik Vishal
Published: September 2023

AIMS

Whole genome sequencing is currently being offered to paediatric, teenage and young adult neuro-oncology patients and this was being managed by a genomics practitioner who works cross-site. We found that some patients are being discharged from the hospital without 1 component of the test or the consent. Our aim is to create a solid pathway in which fresh tissue, blood sample and record of discussion are taken at a certain stage in their hospital admission.

METHOD

A poster was created to remind the theatre team that a fresh tumour tissue and EDTA blood sample are the required samples to proceed with whole genome sequencing. Consent training is being provided to all clinical nurse specialists who look after CNS tumours in order to secure the record of discussion at any point in their hospital appointment. After several shadowing and doing the consenting process with supervision, they are expected to be able to be independent in doing this.

RESULTS

The clinical nurse specialist team have consented 24 out of 37 paediatric, teenage and young adult neuro- oncology patients that were operated since July 2022. Almost all of them have had their bloods taken intra- operatively with some taken whilst still an in-patient.

CONCLUSIONS

Whole genome sequencing will soon be offered to all neuro-oncology patients and the entire team will need to be equipped in securing the record of discussion in order for this test to proceed and this will be led by the clinical nurse specialist team.
WHAT ROLE CAN A PERSONAL TRAINER PLAY IN IMPROVING QUALITY OF LIFE THROUGHOUT ONCOLOGY TREATMENT FOR PEOPLE WITH A BRAIN TUMOUR
Authors: Kostick Ellie , Hurwitz Victoria , La Jessica , Robinson Charlotte , Suarez Aeron , Hedges Sarah , Fukuthi Renata , Harding Nicola , Brazil Lucy , Swampillai Angela , Chia Kazumi , Manik Vishal , Africa Olivia , Clark Rebecca , Al-Salihi Omar
Published: September 2023

AIMS

Review of a single person case study to establish if a personal trainer (PT) could help build a personalised pro- gramme for people with brain tumours going through oncology treatment. The aim being to help manage resilience both physically and psychologically through treatment and improve quality of life.

METHOD

A young person who has completed radiotherapy and chemotherapy after surgical debulking of a brain tumour was contacted. He worked as a PT before diagnosis and continued throughout treatment. He gradually increased his exercise tolerance and tailored exercises to different days of the treatment cycle to match his needs. He managed his fatigue and gradually built his exercise tolerance up back to baseline and continue with treatment.

RESULTS

This patient created a ‘patient guide’ with suggested exercises from his unique perspective as a person who has been through treatment and as a PT.

CONCLUSIONS

This guide has not yet been trialled with the rest of the patient population. The hope is that this will be used to guide further research in this field and may lead to the implementation of a permeant PT member of staff to the oncology service. In his words ‘this is just an example of my journey and how I stumbled my way through the diffculty of a cancer diagnosis and subsequent treatment. If you can take something away and apply it to your own situation then that’s brilliant’, ‘each day is a testament to how well you’re doing’
A CASE ILLUSTRATION AND LITERATURE REVIEW OF THYROID CANCER METASTASIS TO THE PITUITARY FOSSA
Authors: Veljanoski Damjan , Sofela Agbolahan , Abdel-Fattah Abdel-Rahman , Shivane Aditya , Muquit Samiul
Published: September 2023

AIMS

To understand the clinico-radiological and histopathological features, treatment strategies and outcomes of patients with thyroid cancer metastasis to the pituitary fossa.

METHOD

A 71-year-old man presented with a few months’ history of headaches, blurred vision, diplopia and right sided ptosis.

MRI head revealed a 2.5cm pituitary fossa lesion distorting the optic chiasm with right sided cavernous sinus invasion. It also showed frontal, temporal and parieto-occipital lesions.

CT thorax, abdomen and pelvis found a retrosternal thyroid goitre.

An open biopsy of the occipital lobe lesion revealed a metastatic papillary adenocarcinoma from the thyroid gland. An ultrasound-guided fine needle aspiration of the goitre and abnormal level IV lymph nodes revealed Thy5. The patient subsequently underwent an endoscopic transsphenoidal resection of the pituitary tumour which was confirmed to be a carcinoma.

A date and language unrestricted literature search was performed across the MEDLINE, Embase (via Ovid) and Scopus databases using keywords relating metastasis, the pituitary & thyroid glands, and the brain. Citations reporting patients with thyroid metastasis to the pituitary fossa were included. A predetermined proforma was used to extract and store data from the included citations.

RESULTS

After de-duplication, 2,833 citations were screened for eligibility and 42 citations met the inclusion criteria.

CONCLUSIONS

We present a rare case illustration and literature review of patients with thyroid cancer metastasis to the pituitary fossa.
GLIOBLASTOMA: THE NEGLECTED CANCER IN THE TREATMENT REVOLUTION
Authors: Panks Christopher , Clemmow Richard
Published: September 2023

AIMS

A paper written from the perspective of people living with glioblastoma and their carers:

• Surveys the current treatment landscape in the UK

• Questions why standard of care has not significantly changed in two decades

• Argues for implementation of universal whole genome sequencing (WGS) for patients in line with a2018 government commitment that all patients in England with rare diseases should be offered WGS from2019

• Estimates how much WGS has been done

METHOD

OurBrainBank’s researcher gathered information from:

• Freedom of information requests

• Questions to health trusts and individual hospitals

• Interviews with patients and carers

• Interviews with clinicians, health administrators and researchers

• A literature review

RESULTS

The paper estimates that up to the end of 2022 fewer than 1% of glioblastoma patients in England diagnosed since January 2019, (the date originally suggested for implementation of the government commitment), have had WGS of their tumours. This figure rises to only 1.3% of GBM patients diagnosed since April 2021, the date when the WGS policy began to be rolled out.

CONCLUSIONS

The government’s 2018 commitment to the implementation of WGS as applied to glioblastoma patients in England has failed by almost 2 orders of magnitude.

The paper calls for this to be addressed through:

• Universal frozen tissue storage

• Universal genomic sequencing for all GBM patients where tissue is available

• Specific, reliable GBM information on NHS and other offcial websites

• Increased funding for translational research
SRRM4-mediated REST to REST4 dysregulation promotes tumor growth and neural adaptation in breast cancer leading to brain metastasis
Authors: Deshpande Krutika , Martirosian Vahan , Nakamura Brooke N , Das Diganta , Iyer Mukund , Reed Max , Shao Ling , Bamshad Daniella , Buckley Noel J , Neman Josh
Published: September 2023

Background

Effective control of brain metastasis remains an urgent clinical need due a limited understanding of the mechanisms driving it. Although the gain of neuro-adaptive attributes in breast-to-brain metastases (BBMs) has been described, the mechanisms that govern this neural acclimation and the resulting brain metastasis competency are poorly understood. Herein, we define the role of neural-specific splicing factor Serine/Arginine Repetitive Matrix Protein 4 (SRRM4) in regulating microenvironmental adaptation and brain metastasis colonization in breast cancer cells.

Methods

Utilizing pure neuronal cultures and brain-naive and patient-derived BM tumor cells, along with in vivo tumor modeling, we surveyed the early induction of mediators of neural acclimation in tumor cells.

Results

When SRRM4 is overexpressed in systemic breast cancer cells, there is enhanced BBM leading to poorer overall survival in vivo. Concomitantly, SRRM4 knockdown expression does not provide any advantage in central nervous system metastasis. In addition, reducing SRRM4 expression in breast cancer cells slows down proliferation and increases resistance to chemotherapy. Conversely, when SRRM4/REST4 levels are elevated, tumor cell growth is maintained even in nutrient-deprived conditions. In neuronal coculture, decreasing SRRM4 expression in breast cancer cells impairs their ability to adapt to the brain microenvironment, while increasing SRRM4/RE-1 Silencing Transcription Factor (REST4) levels leads to greater expression of neurotransmitter and synaptic signaling mediators and a significant colonization advantage.

Conclusions

Collectively, our findings identify SRRM4 as a regulator of brain metastasis colonization, and a potential therapeutic target in breast cancer.
How variable progenitor clones construct a largely invariant neocortex
Authors: Shen Zhongfu , Yang Jiajun , Zhang Qiangqiang , Wang Kuiyu , Lv Xiaohui , Hu Xiaolin , Ma Jian , Shi Song-Hai
Published: September 2023

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors (RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.
Neurogenesis in primates versus rodents and the value of non-human primate models
Authors: Zhang Runrui , Quan Hongxin , Wang Yinfeng , Luo Fucheng
Published: September 2023

Neurogenesis, the process of generating neurons from neural stem cells, occurs during both embryonic and adult stages, with each stage possessing distinct characteristics. Dysfunction in either stage can disrupt normal neural development, impair cognitive functions, and lead to various neurological disorders. Recent technological advancements in single-cell multiomics and gene-editing have facilitated investigations into primate neurogenesis. Here, we provide a comprehensive overview of neurogenesis across rodents, non-human primates, and humans, covering embryonic development to adulthood and focusing on the conservation and diversity among species. While non-human primates, especially monkeys, serve as valuable models with closer neural resemblance to humans, we highlight the potential impacts and limitations of non-human primate models on both physiological and pathological neurogenesis research.
ORCHID: A phase II study of Olaparib in Metastatic Renal Cell Carcinoma Patients HarborIng a BAP1 or Other DNA Repair Gene Mutations
Authors: Ged Georges , Rifkind Irina , Tony Lori , Daugherty Keegan , Michalik Amber , Wang Hao , Carducci Michael , Markowski Mark
Published: September 2023

Background

DNA damage repair genes alterations (DDRa) are frequent events in renal cell carcinoma (RCC), including BAP1 and other DDRa. Olaparib is a poly ADP ribose polymerase inhibitor (PARPi) that is FDA-approved for the treatment of several malignancies with DDRa. Preclinical models demonstrated synthetic lethality with PARPi in RCC cell lines including BAP1 mutant lines. Here we report an interim analysis of the ORCHID study investigating the clinical activity of single agent olaparib in patients (pts) with advanced RCC (aRCC) harboring BAP1 other select DDRa.

Methods

We conducted a single center, single arm, investigator-initiated Phase 2 trial of olaparib in pts with aRCC. Eligible pts harbored select DDRa and had prior therapy with immune checkpoint inhibitors (ICIs) and/or VEGF-TKI. Pts were treated with olaparib at an initial dose of 150mg twice which was increased to 300mg twice daily after one month if well tolerated. The primary endpoint is disease control rate (DCR) by RECIST v1.1 (including complete response (CR), partial response (PR), and stable disease (SD) >6 months). Secondary endpoints included objective response rate (ORR), progression free survival (PFS), and safety.

Results

Eleven pts were enrolled with a median age of 59 years (48-72) including 9 pts with clear cell RCC and 2 pts with unclassified RCC. Most pts had BAP1 mutations (Table). 36% of pts had history of brain metastasis. Median number of prior lines of therapies was 2 (1-6) and all pts received prior ICI. The study met the pre-specified Simon’s 2 stage design for the first stage with 22% DCR in the evaluable pts (2/9), including deep PR (>70% reduction in tumor volume) and SD of 10 months. Both pts harbored BAP1 mutations. An additional pt with BRCA1 mutation had 20% decrease in measurable disease. There were no treatment related adverse events resulting in study discontinuation.

Conclusions

This is the first study investigating single agent PARPi in RCC with the interim trial analysis indicating promising activity of olaparib in aRCC pts with BAP1 mutations including one pt with deep PR. These results support further development of PARPi in this setting.
Public Support for Democracy in the United States Has Declined Generationally
Authors: Claassen Christopher , Magalhães Pedro C
Published: September 2023

Support for democracy in the United States, once thought to be solid, has now been shown to be somewhat shaky. One of the most concerning aspects of this declining attachment to democracy is a marked age gap, with younger Americans less supportive of democracy than their older compatriots. Using age-period-cohort analysis of 12 national surveys collected between 1995 and 2019, we show that this age gap is largely a function of a long-term generational decline in support for democracy, with little evidence of an independent life-cycle effect apparent. The combination of generational decline without a positive and counterbalancing life-cycle effect offers a sober prognosis of how support for democracy in the United States might look in the future.
Assessment of natural radioactivity, radon gas and soil characteristics along the Volta Lake in the Kpando municipality of Volta region, Ghana
Authors: Amable Anthony Selorm Kwesi , Otoo Francis , Buah-Bassuah Paul Kingsley , Twum Anthony Kwabena
Published: September 2023

Assessment of radionuclides, indoor radon (222RnI), radon exhalation (222Rnex), and soil characteristics in the coastal part of Kpando has been studied using HPGe, CR-39 and sieving techniques. Statistical analysis between radionuclides, radon levels and soil characteristics was done using Pearson’s correlation. The mean radionuclide concentration, radon levels and soil characteristics were obtained as 226Ra (23.1 ± 1.4 Bq per kg), 232Th (34.6 ± 2.9 Bq per kg), 40K (187.1 ± 13.7 Bq per kg), 222RnI (64.70 ± 2.7 Bq per m3), 222Rnex (7.9 ± 0.5 μBq per m2h), sandy (45.9 ± 3.9%), silt (40.7 ± 3.1%), clay (13.5 ± 0.8%), porosity (0.6 ± 0.1) and moisture (7.6 ± 0.8%). Radiological effects estimated were within recommended limits. The maximum positive and negative coefficients exist between 222Ra/222Rnex (1.0) and 222Rnex/MC (−0.9), respectively. Radon exhalation correlates better with soil characteristics. The statistical analysis indicated that soil characteristics have significant effects on radionuclides and radon levels in soils and dwellings.
Preclinical Evidence for the Use of Oral Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone Regenerative Therapy: A Systematic Review
Authors: Olaechea Allinson , Benabdellah Karim , Vergara-Buenaventura Andrea , Gómez-Melero Sara , Cafferata Emilio A , Meza-Mauricio Jonathan , Padial-Molina Miguel , Galindo-Moreno Pablo
Published: September 2023

The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a promising therapeutic tool within this field due to their crucial role in intercellular communication across various cell types and organisms. This systematic review aims to evaluate the therapeutic potential of oral mesenchymal stem cell (MSC)-derived EVs for bone regeneration, specifically focusing on findings from preclinical models. Sixteen articles meeting the inclusion criteria were selected following document analysis. The biological effects of oral MSC-derived EVs predominantly involve the upregulation of proteins associated with angiogenesis, and inflammation resolution, alongside the downregulation of proinflammatory cytokines. Moreover, these therapeutic agents have been found to contain a significant quantity of different molecules (proteins, lipids, DNA, microRNAs, etc) further contributing to their modulatory potential. The findings from this systematic review underscore that oral MSC-derived EVs, irrespective of their specific population, have the ability to enhance the osteogenic repair response in maxillary bone or periodontal defects. In summary, this systematic review highlights the promising potential of oral MSC-derived EVs for bone regeneration based on evidence from preclinical models. The comprehensive assessment of their biological effects and the presence of microRNAs underscores their therapeutic significance. These findings support the utilization of oral MSC-derived EVs in enhancing the osteogenic repair response in various maxillary bone or periodontal defects, providing insights into the mechanisms involved and potential therapeutic applications in the field of personalized medicine.
Developing a culturally tailored digital health intervention for insomnia in Black women
Authors: Zhou Eric S , Revette Anna , Ritterband Lee M , Bethea Traci N , Delp Lauren , Simmons Patricia D , Rosenberg Lynn
Published: September 2023

Insomnia disorder is highly prevalent among Black women. Cognitive-behavioral therapy for insomnia (CBT-I) is considered the optimal treatment, but very little efficacy research has been conducted in minority populations. Culturally tailoring intervention content may increase participant engagement and improve treatment outcomes. We culturally tailored an Internet-delivered CBT-I program (Sleep Healthy Using the Internet; SHUTi) for Black women. First, relevant stakeholders were identified. Semi-structured interviews were conducted after stakeholders completed each of the six SHUTi intervention sessions. Questions focused on improving program relatability and engagement for Black women. Key themes pertinent to peripheral, evidential, and sociocultural strategies for cultural adaptation were identified using thematic content analysis, and adaptation recommendations were developed. A total of 50 interviews, across 9 stakeholders, were conducted. Two overarching themes were identified: (i) there was limited visual African American representation, and (ii) there was a lack of diversity in the environments and lifestyles of the patient vignettes. Respondents provided peripheral, evidential, and sociocultural recommendations for program modifications, emphasizing the importance of race-concordant visual content and didactic content exploring the diverse cultural and social contexts in which insomnia occurs for Black women. As more diverse patients seek evidence-based insomnia treatment, digital health interventions must consider whether it is therapeutically important to address and tailor for cultural differences. Here, stakeholders made clear recommendations for taking cultural contexts into account to improve patient engagement with the program. Further research should work to understand the extent to which culturally tailored interventions are beneficial for health outcomes among minority populations.
Taxonomic inflation and a reconsideration of speciation in the Andes: the case of the high-elevation tree frogDendropsophus molitor(Anura: Hylidae)
Authors: Arias-Cárdenas Alexandra , Barrientos Lucas S , Pardo-Diaz Carolina , Paz Andrea , Crawford Andrew J , Salazar Camilo
Published: September 2023

Dendropsophus molitor is a hylid frog endemic to the Eastern Cordillera of the Colombian Andes, where it exhibits extensive geographic variation in size and colour pattern. Previous multivariate analyses of acoustic and genetic data suggested that northern and southern populations of D. molitor were distinct lineages, and consequently, the northern populations were described as Dendropsophus luddeckei. In this study, we conducted morphometric and genetic analyses of populations of D. molitor and D. luddeckei to test the validity of this recent taxonomic split. We sequenced the mitochondrial genes 12S, 16S, and COI, and the nuclear marker POMC, and also tested whether variation in the MC1R gene was associated with colour polymorphism in these frogs. Phylogenetic analyses recovered D. molitor and D. luddeckei as polyphyletic and species delimitation tests failed to recover them as separate lineages. Genetic differentiation between populations was mostly explained by high intra- and interpopulation variation in the absence of a north-south split, and we found no differences in morphometry between northern and southern populations. In addition, the coding region of MC1R is not associated with colour polymorphism. Thus, multiple lines of evidence suggest that D. luddeckei is not a valid species and D. molitor should be considered a single species. Our study highlights the danger of taxonomic inflation in the face of limited geographic sampling and a lack of clear diagnostic characters.
Prevalence of trichomoniasis infection among adults in Nigerian community settings
Authors: Obetta K. Chukwuemeka , Ogbonna Innocent Okonkwo , Oyigbo Dorida Nneka , Ugwu Oliver Onyemaechi , Ugwu Kenneth Okonkwo , Onah Beatrice N. , Ugwunnadi Chinasa Maryrose , Acha Joseph O. , Chuke Ngozi Uzoamaka , Nkemjika Ogechi , Okoye Onyinyechi Elizabeth
Published: September 2023

Background:

Trichomonas vaginalis (TV) is a sexually transmitted pathogen. The study was conducted to determine its prevalence among 300 adult patients in 4 public health facilities in the Nsukka District of Enugu State, Nigeria.

Method:

The researchers collected high vagina swabs and urine samples were collected from 150 men and 150 women, respectively. The specimens were scrutinized for color, odor of discharge and urine, and motile trichomoniasis.

Results:

The prevalence of the TV was 45.0% (135/300) with women showing the highest prevalence (63.7%). Among the patients attending the University of Nigeria, Nsukka Medical Center, the prevalence was the highest at 31.9%. TV infection was more common among older adults aged 38 to 47 years (39.3%), married adults (76.3%), and those with secondary education (68.9%). Urogenital analysis reported that males with pains during urination were 51.0% and males with penile tingling were 12.2%. The highest vaginal Hydrogen ion concentration level of 6.8 was observed in women aged 38 to 47 years. Additionally, the results reported that Vaginal candidiasis, Bacterial vaginosis, and Herpes simplex virus type 2 antibodies were not independently associated with TV infection. In the unadjusted analysis, the odds of TV infection were higher in men (8.1), while Chlamydia trachomatis infection was higher in women (8.8). Among the adults diagnosed with herpes simplex virus type 2 antibodies, the odds of TV infection were 3.9 for both men and women. Men with penile human papillomavirus infection had lower odds of TV infection (1.9), while women with vaginal human papillomavirus infection had higher odds of TV infection (2.2).

Conclusion:

The prevalence of TV infection is high among sexually active adults in the Nigerian community. It is therefore crucial to implement the increased public health actions such as regular and early diagnosis to reduce its prevalence.
Serum uric acid and triglycerides in clear cell renal cell carcinoma: A restrospective cross-sectional study
Authors: Yue Dong , Tian Jun
Published: September 2023

The available evidence on the relationship between serum uric acid and triglycerides in clear cell renal cell carcinoma (ccRCC) is limited. The objective of this study is to investigate whether there is an independent association between serum uric acid and triglycerides in ccRCC, while adjusting for other variables. This cross-sectional study involved 1018 participants with ccRCC, who were admitted to a hospital in China from December 1st, 2013 to January 1st, 2023. The main independent variable investigated was serum uric acid, which was measured at baseline. The dependent variable was triglycerides. Covariates considered in this study included age, sex, body mass index, smoking status, hypertension, diabetes, coronary disease, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol, Total cholesterol, Blood urea nitrogen, and Creatinine. The study included 1018 participants with an average age of 56.92 ± 10.88 years old, and approximately 68% of them were male. The fully-adjusted linear regression analysis indicated a positive association between serum uric acid levels (100μmol/L) and triglyceride levels (mmol/L) after adjusting for confounding factors (β = 0.13, 95% CI [0.07, 0.18]). Furthermore, a smooth curve was constructed between serum uric acid and triglycerides based on the fully-adjusted model. In patients with ccRCC, there was a positive association between serum uric acid and triglycerides.