bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicentre study of perfusion magnetic resonance imaging in paediatric brain tumours
Authors: Withey Stephanie , MacPherson Lesley , Oates Adam , Powell Stephen , Novak Jan , Abernethy Laurence , Pizer Barry , Grundy Richard , Bailey Simon , Mitra Dipayan , Arvanitis Theodoros , Auer Dorothee , Avula Shivaram , Peet Andrew 
Published: October 2019

Abstract
Studies in adults have shown that brain tumour perfusion correlates with grade. These studies are dominated by gliomas grade II to IV which are rare in children. The standard method, Dynamic Susceptibility Contrast MRI, provides estimates of relative cerebral blood volume (rCBV) but contrast agent leakage affects rCBV accuracy. The majority of perfusion studies have been conducted at single centres and variation in acquisition protocols makes the generalizability of results questionable. The aim of this study was to compare leakage-corrected rCBV with grade in paediatric brain tumours at multiple centres. Scans were analysed from 85 patients at 4 centres on 6 scanners prior to treatment. MRI protocols varied between centres. Histological diagnoses including grade were obtained. Whole-tumour median rCBV was significantly higher in the 45 high grade than the 40 low grade tumours (2.54 ± 1.63 ml/100ml vs 1.68 ± 1.36 ml/100ml, p=0.010). Low grade tumours, particularly pilocytic astrocytomas (grade I), displayed more contrast agent leakage consistent with their appearance on contrast enhanced images and required more leakage correction than high grade tumours. This finding differs from that in adults where contrast agent uptake is usually associated with higher grade. A cut-off of 1.70 ml/100ml for rCBV gave sensitivity and specificity of 76% and 65% respectively for discriminating grade. In summary, perfusion MRI can be used to help distinguish between low and high grade paediatric brain tumours. This finding is robust across multiple centres and acquisition protocols but correction should be made for leakage of contrast agent from the vessels.
Radiation-Induced Meningiomas: A perspective from the West of Scotland
Authors: Roberts Mari , McIlwraith Andrew , Owusu-Agyemang Kevin , Hamdan Alhafidz , Champeaux Charles , Houston Deborah , Grivas Athanasios 
Published: October 2019

Abstract

Introduction
Meningioma is the most common intracranial neoplasm to be induced by ionising radiation. Patients receiving childhood radiotherapy do not have routine surveillance to assess for this delayed complication. We aimed to examine our 30 year cohort of surgically treated meningioma in Glasgow.

Method
We retrospectively reviewed all patients who underwent surgery for meningioma and identified those who previously had childhood cranial irradiation. We then studied their demographics including gender and age at index cranial irradiation, latency period, histological grade and outcome.

Results
In total there were 982 patients with meningioma (WHO Grade 1 – 69%, Grade 2- 26%, and Grade 3- 1%). Of these, 22 patients had a radiation-induced meningioma. Eleven (50%) of these were WHO Grade 1. Median age at diagnosis of meningioma was 38 years old. Most cases were females (15; 68%, and most common indication for childhood irradiation was leukaemia (11; 50%), followed by pineal region tumours (4; 18%). Mean latency from irradiation to meningioma diagnosis was 25 years. Seven (32%) patients had multiple meningiomata; 5 (71.4%) of these had >2 lesions. Eight patients (36%) had recurrent meningiomata.

Conclusion
Patients receiving cranial radiation should be enrolled into a surveillance program guided by the reported latency period. A local registry of such patients would provide more information on protective and prognostic factors.
Non-viral delivery of therapeutic microRNAs to glioma cells using chitosan nanocomplexes
Authors: Boissinot Marjorie , Limam Sarra , Collado-González Maria , Gonzalez-Espinosa Yadira , Wurdak Heiko , Goycoolea Francisco M , Short Susan C 
Published: October 2019

Abstract

One of the biggest challenges when treating brain tumours is achieving efficient delivery of therapeutic agents to the brain and more specifically to the cancer cells. MicroRNA-1300 was identified in our group as a very promising therapeutic microRNA given its cytotoxic effect when introduced in both established as well as cancer-stem-like patient-derived glioblastoma cultures, while not affecting differentiated glioblastoma cells. We are now collaborating to assess the potential efficiency of the natural biopolymer chitosan to form nanocomplexes containing the mature form of microRNA-1300 for delivery.
Chitosan has been established as a highly attractive biocompatible polymer to deliver both in vitro and in vivo therapeutic nucleotides intracellularly. In previous studies, we have shown chitosan’s efficacy to form spherical nanocomplexes with microRNA and apply them to the downregulation of JAMA-A mRNA in MCF-7 breast cancer cells. Chitosan can also be chemically conjugated to introduce affinity towards a wide range of cellular targets (e.g. with aptamers).

Methods
We have optimised of the composition and characterised the biophysical properties of chitosan-microRNA nanocomplexes of varying (+/-) charge ratios using both a control nontargeting microRNA coupled to a fluorochrome (CS-miRdy547, efficiency of cell entry) and mature microRNA-1300 (CS-mi1300, efficient release and biological effect). We have tested the nanocomplexes in 2D monolayers and 3D spheroid cultures on established U251 as well as two patient-derived cultures. Reverse transfection was used as positive control.

Results
The control nanoparticles of CS-miRdy547 are taken up by the patient-derived cultures in 2D and 3D. Analysis is ongoing using the CS-miR-1300 nanoparticles.
NPI-0052 and gamma-radiation induce a synergistic apoptotic effect in the most aggressive medulloblastoma subgroup
Authors: Frisira Eleni , Rashid Fatima , Michod David , Victoria Niklison Chirou Maria 
Published: October 2019

Abstract
Group 3 medulloblastoma (MB) is the most aggressive and least characterised of all MB subgroups. These tumours are highly metastatic and patients undergo aggressive treatments leaving survivors with severe side effects. The standard of care for these patients consists of surgical resection followed by gamma-radiation and chemotherapy. Whilst this conventional therapy is successful in the majority of cases, however, many survivors are left with lifelong severe neurocognitive and physical sequelae.
Interestingly, the proteasome plays a vital role in the pathogenesis of different tumours, therefore proteasome inhibition can be used as a new strategy for treating MB. NPI-0052 is a proteasome inhibitor that can penetrate the blood-brain barrier with a good safety profile, making it an appealing treatment for brain tumors.
In the present study, we evaluate the anticancer activity of NPI-0052 in a range of MB patient derived MB cells and cell lines. Our preclinical work demonstrated that NPI-0052 can inhibit proteasome activity and activate apoptosis in MB cells. We also show that the p53-family plays a substantial role in NPI-0052’s mechanism of action. Moreover, we observe that NPI-0052 has a synergistic apoptotic effect with gamma-radiation, a component of the current MB therapy, in both cells and tumour organoids. Our work underscores the use of NPI-0052 as a novel therapy for reducing the doses of gamma-radiation in G3-MB patients.
HiSpots®: A novel ex vivo patient-derived 3D model of glioblastoma.
Authors: Brown Jo , Zaben Malik , Siebzehnrubl Florian , P Gray William 
Published: October 2019

Abstract
There are limited chemotherapeutic options for glioblastoma, which contributes to its poor prognosis. Established cell lines have many phenotypic differences from their original tumours, and drugs showing success in animal models often fail to translate to humans. HiSpots® aim to provide a representative 3D in vitro model of glioblastoma using ex vivo human tumour samples, suitable for mechanistic studies.
HiSpots® are a high-density 3D cell culture technique. Cancer and microenvironment cells are mechanically and enzymatically isolated from fresh resected or biopsied tumours, seeded onto PTFE membranes and cultured on an air-liquid interface. Cultures were stained for beta-III tubulin (TUJ1), glial fibrillary acidic protein (GFAP), nestin, and ionized calcium binding adapter molecule 1 (IBA1) to identify tumour cells and microglia. Serum-containing and serum-free media were compared. HiSpots® were created at three densities: low, medium and high, for comparison.
Medium density HiSpots® best supported TUJ1+GFAP+Nestin+ tumour cells, and the density did not affect the proportion of microglia. Medium and high density HiSpots® formed multiple cell layers, creating structures up to 40μm thick with variable cell type distribution. Medium and high density HiSpots® and tumour cells were best supported in serum-free media.
Medium density HiSpots® cultured in serum-free media have been demonstrated as the best choice to support the heterogeneity of glioblastoma. These HiSpots® contain mostly tumour cells and microglia. HiSpots® therefore allow for the culture of human glioblastoma cells, including microenvironmental microglia. These HiSpot® models will be evaluated as a model for mechanistic studies in the future.
Combined extradural-interdural-intradural approach to a trigeminal nerve cystic haemangiopericytoma with intra-operative cranial nerve monitoring
Authors: Frantzias Joseph , Lavrador José , Pereira Noémia , Gullan Richard , Ashkan Keyoumars , Vergani Francesco , Bhangoo Ranjeev , Thomas Nick 
Published: October 2019

Abstract

Objectives
Haemangiopericytoma of the trigemimal nerve is extremely rare, with only two previous cases described to our knowledge. We present the surgical approach to this tumour, and describe a previously poorly reported method of monitoring the function of the branches of the trigeminal nerve: mapping of the sensory roots through transcranial somatosensory cortex sensory evoked potentials (SSEPs), motor evoked potentials (MEP) for the motor root and blink reflex.

Design
Case and technical reports

Subjects
32 year-old male patient presenting with headaches and vomiting, found to have a mixed cystic-solid tumour of the left middle skull base region, in close relation with the foramen ovale and Meckel’s cave.

Methods
The radiological features of the tumour, technical aspects of the technical approach and neurophysiologic monitoring will be described.

Results
A pterional craniotomy with fronto-temporal extradural-interdural-intradural approach, and the tumour was debulked with MEP, SSEP and blink reflex monitoring of the branches of the trigeminal nerve. Complete tumour removal was achieved with no post-operative cranial nerve deficits.
The histopathology revealed a cystic haemangiopericytoma.

Conclusions
Haemangiopericytoma is a rare entity. MEP and SSEP monitoring of the trigeminal nerve can be used to achieve complete and safe removal of the tumour.
A profile of arginine methyltransferase receptors in two immortal glioblastoma cell lines: the precursor to a novel target?
Authors: Deepak Srihari , Sabrina Samuel Miss , Greenman John , Achawal Shailendra , Beltran-Alvarez Pedro 
Published: October 2019

Abstract

Background
Glioblastoma is a deadly disease with a median survival of 15 months after treatment. While maximal safe surgical resection and adjuvant chemoradiotherapy continues to be the mainstay of treatment, glioblastoma demostrates a remarkably heterogeneous molecular profile, and there is a drive to discover further chemotherapeutic targets that can effectively augment current multimodal therapy.

Introduction
Post-translational modification of proteins plays a key role in maintenance of regulatory cell networks, and protein arginine methyltransferases (PRMT) are one of the enzymes involved in symmetric and asymmetric methylation of various proteins. We aim to demonstrate the entire range of PRMT proteins expressed in two different glioblastoma cell lines (U87MG and U251) in order to elucidate a consistency in expression of these proteins across cell lines.

Methods
Cells from 2 different glioblastoma cell lines (U87MG and U251) were cultured and lysed using standard aseptic techniques. Protein profiling was done using SDS-PAGE electrophoresis with a molecular weight marker as the reference and all primary antibodies to various PRMTs (1–10) and respective secondary antibodies. Membranes were visualised with a chemiluminescent protocol. Experiments were repeated in order to reduce bias.

Conclusion
It was clearly seen that in both cell lines there is a strong tendency for PRMT5 expression and relative under-expresssion of PRMT 9/10. In addition, however, there are varying expressions of other PRMTs as well. We aim to further explore this to improve the strength of this correlation.
The clinical and economic burden of systemic sclerosis related interstitial lung disease
Authors: Morrisroe Kathleen , Stevens Wendy , Sahhar Joanne , Ngian Gene-Siew , Ferdowsi Nava , Hansen Dylan , Patel Shreeya , Hill Catherine L , Roddy Janet , Walker Jennifer , Proudman Susanna , Nikpour Mandana 
Published: October 2019

Abstract

Objective
To quantify the burden of interstitial lung disease (ILD) in SSc.

Methods
Clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with healthcare databases for the period 2008–2015. ILD was defined by characteristic fibrotic changes on high-resolution CT (HRCT) lung, while severity was defined by the extent lung involvement on HRCT (mild &lt;10%, moderate 10–30%, severe &gt;30%). Determinants of healthcare cost were estimated using logistic regression.

Results
SSc-ILD patients utilized more healthcare resources, including hospitalization, emergency department presentation and ambulatory care services, than those without ILD with a total cost per patient of AUD$48 368 (26 230–93 615) vs AUD$33 657 (15 144–66 905), P&lt;0.001) between 2008–2015. Healthcare utilization was associated with an annual median (25th–75th) excess cost per SSc-ILD patient compared with those without ILD of AUD$1192 (807–1212), P&lt;0.001. Increasing ILD severity was associated with significantly more healthcare utilization and costs with an annual excess cost per patient with severe ILD compared with mild ILD of AUD$2321 (645–1846), P&lt;0.001. ILD severity and the presence of coexistent PAH were the main determinants of overall healthcare cost above median for this SSc-ILD cohort (OR 5.1, P&lt;0.001, and OR 2.6, P=0.01, respectively). Furthermore, SSc-ILD patients reported worse physical HRQoL compared with those without ILD [34.3 (10.5) vs 39.1 (10.8), P&lt;0.001], with a progressive decline with increasing ILD severity (P=0.002).

Conclusion
SSc-ILD places a large burden on the healthcare system and the patient through poor HRQoL in addition to incremental healthcare resource utilization and associated direct cost.
Diet formulation method influences the response to increasing net energy in finishing pigs1
Authors: Marçal Danilo A , Kiefer Charles , Tokach Mike D , Dritz Steve S , Woodworth Jason C , Goodband Robert D , Cemin Henrique S , Derouchey Joel M 
Published: October 2019

Abstract
An experiment was conducted to compare the effects of increasing dietary net energy (NE) in finishing pig diets while either maintaining a standardized ileal digestible lysine:NE ratio (SID Lys:NE) or maintaining SID Lys as a constant percentage of the diet across increasing energy densities. A total of 150 pigs (Line 600 × 241; DNA, Columbus, NE; initially 35.7 kg) were used in a 91-d study. Pigs were blocked by sex and weight and randomly assigned to 1 of 5 treatments with 2 pigs per pen and 15 pens per treatment. Treatments included a low-energy control diet that was corn-soybean meal-based with added soybean hulls, and a 2 × 2 factorial arrangement of treatments with main effects of increasing dietary NE (medium or high by adding choice white grease) and formulation method (with a SID Lys:NE ratio or maintaining the same percentage SID Lys). Linear and quadratic contrasts were made using the control diet and the medium- and high-energy diets within each formulation method. Pigs and feeders were weighed approximately every 30 d to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F). At the end of the experiment, pigs were sent to a commercial processing facility for carcass data collection. From days 0 to 34 and 34 to 61, ADG and SID Lys intake increased as NE increased (linear, P &lt; 0.05) in pigs fed diets with a Lys:NE ratio, but not for those fed the same percentage Lys. As NE increased, NE intake and G:F increased (P &lt; 0.01) in pigs fed diets with either formulation method. From days 61 to 91, increasing NE had no effect (P &gt; 0.10) on ADG. There was no change in G:F in pigs fed diets with the same percentage Lys (P &gt; 0.10), but G:F decreased then increased (quadratic, P &lt; 0.01) in response to increasing NE in pigs fed diets with a SID Lys:NE ratio. Overall, increasing dietary NE increased (linear, P &lt; 0.001) daily NE intake and G:F (linear, P &lt; 0.018) with either formulation method. However, SID Lys intake, ADG, and hot carcass weight only increased (linear, P &lt; 0.01) when a SID Lys:NE ratio was maintained. Increasing NE without maintaining a constant SID Lys:NE ratio increased backfat depth (quadratic, P = 0.01), whereas it did not in pigs fed diets with a SID Lys:NE ratio. In conclusion, increasing dietary energy density increased NE intake and G:F regardless of formulation method. However, a SID Lys:NE ratio must be maintained to achieve increased ADG and minimize fat deposition.
Microtubule tyrosination/detyrosination specifies a mitotic error code
Authors: Ferreira Luísa T. , Orr Bernardo , Rajendraprasad Girish , Pereira António J. , Lemos Carolina , Lima Joana T. , Boldú Clàudia Guasch , Ferreira Jorge G. , Barisic Marin , Maiato Helder 
Published: October 2019

AbstractIncorrect kinetochore-microtubule attachments during mitosis can lead to chromosomal instability, a hallmark of human cancers. Mitotic error correction relies on the kinesin-13 MCAK, a microtubule depolymerase whose activity in vitro is suppressed by α-tubulin detyrosination - a post-translational modification enriched on long-lived microtubules. However, whether and how MCAK activity required for mitotic error correction is regulated by microtubule tyrosination/detyrosination remains unknown. Here we found that microtubule detyrosination accumulates on correct, more stable, kinetochore-microtubule attachments, whereas constitutively high microtubule detyrosination near kinetochores compromised efficient error correction. Rescue experiments suggest that mitotic errors due to excessive microtubule detyrosination result from suppression of MCAK activity, without globally affecting kinetochore microtubule half-life. Importantly, MCAK centromeric activity was required and sufficient to rescue mitotic errors due to excessive microtubule detyrosination. Thus, microtubules are not just passive elements during mitotic error correction, and their tyrosination/detyrosination works as a ‘mitotic error code’ that allows centromeric MCAK to discriminate correct and incorrect kinetochore-microtubule attachments, thereby promoting mitotic fidelity.
Droplet digital polymerase chain reaction for rapid broad‐spectrum detection of bloodstream infections
Authors: Wouters Yannick , Dalloyaux Daisy , Christenhusz Anke , Roelofs Hennie M. J. , Wertheim Heiman F. , Bleeker‐Rovers Chantal P. , te Morsche René H. , Wanten Geert J. A. 
Published: October 2019

SummaryThe droplet digital polymerase chain reaction (ddPCR) is a novel molecular technique that allows rapid quantification of rare target DNA sequences. Aim of this study was to explore the feasibility of the ddPCR technique to detect pathogen DNA in whole blood and to assess the diagnostic accuracy of ddPCR to detect bloodstream infections (BSIs), benchmarked against blood cultures. Broad‐range primers and probes were designed to detect bacterial 16S rRNA (and Gram stain for differentiation) and fungal 28S rRNA. To determine the detection limit of ddPCR, 10‐fold serial dilutions of E. coli and C. albicans were spiked in both PBS and whole blood. The diagnostic accuracy of ddPCR was tested in historically collected frozen blood samples from adult patients suspected of a BSI and compared with blood cultures. Analyses were independently performed by two research analysts. Outcomes included sensitivity and specificity of ddPCR. Within 4 h, blood samples were drawn, and DNA was isolated and analysed. The ddPCR detection limit was approximately 1–2 bacteria or fungi per ddPCR reaction. In total, 45 blood samples were collected from patients, of which 15 (33%) presented with positive blood cultures. The overall sensitivity of ddPCR was 80% (95% CI 52–96) and specificity 87% (95% CI 69–96). In conclusion, the ddPCR technique has considerable potential and is able to detect very low amounts of pathogen DNA in whole blood within 4 h. Currently, ddPCR has a reasonable sensitivity and specificity, but requires further optimization to make it more useful for clinical practice.
There is fat in this sclerosis: A case report of sclerotic lipoma and review of the literature
Authors: Xiang Yan , Moshiri Ata S. , Chan Edward F. , Dasgupta Trisha S. , Kozic Heidi , Elenitsas Rosalie , Nguyen Cuong V. 
Published: October 2019

AbstractSclerotic lipomas, a lipoma variant, are benign subcutaneous tumors, so‐named because of their resemblance to sclerotic fibromas. Previous literature has suggested that these tumors may show a predilection for middle‐aged adult males. We report an unusual case of a sclerotic lipoma diagnosed on the scalp of a 66‐year‐old female. The patient presented to the outpatient clinic with a 3‐ to 4‐year history of an enlarging and irritated 2.6‐cm nodule on the anterior crown of the scalp, clinically thought to be a pilar cyst. Histopathological examination from the excisional specimen revealed a well‐circumscribed dermal to subcutaneous tumor with ample sclerotic collagen bundles, an increased number of CD34 positive spindled cells, and prominent S‐100 positive mature adipocytes comprising greater than 50% of the tumor. We present this case given its atypical clinical and histopathological presentation, review the literature of sclerotic lipomas, and discuss the differential diagnosis to raise awareness of this rare entity.