bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Central Nervous System Lymphoma – Management and Outcome in the ‘haematology era’
Authors: Kumar Siddhant , Islim Abdurrahman , Ali Tamara , Smith Jeffery , Haylock Brian , Shenoy Aditya , Husband David , J Mills Samantha , Brodbelt Andrew , Chavredakis Emmanuel , Lawson David , Chapman Grace , Wickramaratne Nawani , Ridzuan-Allen Adam , Harrison Imogen , D Jenkinson Michael
Published: October 2019

Introduction

Primary CNS lymphoma (PCNSL) requires a biopsy for diagnosis but can be inconclusive when steroids are administered. Without treatment median survival is 1.5–3.3 months, improving to 10–20 months with oncological treatment. This study aimed to compare outcomes of PCNSL treated under haematology to those of clinical oncologists.

Methods

Retrospective casenote review of patients with PCNSL treated under oncologists (2006–2010) and haematologists (2011–2016).

Results

121 cases were identified (median age 63 years; range 19–84). Median WHO performance status (PS) was 1. 11.6% required repeat biopsy.

10 patients were managed palliatively due to poor PS.

67 cases were managed under haematology. Median symptom duration was 28 days (range 2–540). Median time from MRI to diagnosis was 18 days (range 6–232). 66 patients received chemotherapy, 1 received radiotherapy. Median overall survival (OS) was 8 months (95%CI: 0.7–15.3), 5-year OS was 22.4%.

44 cases were managed under oncology. Median symptom duration was 28 days (range 2–365). Median time from MRI to diagnosis was 16 days (range 6–309). 34 patients received radiotherapy first-line, 10 received chemotherapy. Median OS was 7 months (95%CI: 0–21.5), 5-year OS was 15.9%.

Multivariate analysis demonstrated PS (HR 2.02 (95%CI: 1.08–3.76)) and symptom duration (HR 0.63 (95%CI: 0.41–0.96)) to be significant prognostic indicators for OS.

Discussion

PCNSL carries poor prognosis and outcomes from the ‘haematology era’ are similar to those achieved by clinical oncologists. Delay in diagnosis leads to worse outcomes and highlights the ongoing need to streamline current clinical services to improve outcomes.
Using Neuro-oncology to teach GCSE students STEM-subjects
Authors: Shahabi Lillie , Shahabi Golnaz , Wilcox Emma , Campos Catarina , Shah Zahra , Holgate Daisy , Furssedonn Lilly , Al-Tai Dhuha , Jando Saavun , Ranny Aaron , Nagra Nirvan , Seksaria Eesha , Ferreira Diogo , Dadhania Seema , Soni Shivani , Wang James , Camp Sophie , Syed Nelofer , Williams Matt
Published: October 2019

Background

The profile of brain tumours in the wider community has recently been raised. In this project we explored whether we could link brain tumour awareness with STEM education for secondary school pupils. We aimed to inspire the next generation by bringing research into formal and informal learning contexts.

Method

We worked with a local school to co-design and co-create a set of blended learning sessions. Each session consisted of some “biological” teaching and a practical activity. These included using IDH, MGMT and 1p/19q as models of varying genetic disorder and a Jenga-based game to teach radiobiology. Sessions were delivered every 1–2 weeks using a multidisciplinary team. We assessed impact through informal weekly feedback, a structured feedback form and linkage to GCSE curriculum items. We assessed costs using a staff-free FEC model.

Results

We delivered a total of 12 hours over 10 sessions. Feedback was overwhelmingly positive from the students – “The project has been very enlightening and rewarding”. We were able to link 60% of taught material to GCSE curriculum items. We estimated costs (materials) at £260. Students presented their work at the Imperial Science Festival and an additional conference.

Discussion

We have co-developed and piloted an innovative multi-disciplinary toolkit to use neuro-oncology as a way of teaching STEM subjects, though a pupil-centred approach. We are now seeking to pilot the materials with other neuroscience centres/ universities to support secondary schools and neuroscience centres/ universities in working collectively to create structured, strategic, and sustainable mechanisms for engagement.
Characterisation of the anti-migratory activity of the 6-bromoindirubin-3’oxime (BIO) derivative VTIND42 in patient-derived GBM subpopulations
Authors: Peat Samuel , Bruning-Richardson Anke , Meijer Laurent , Lawler Sean , Thiéry Valérie , Morton Ruth
Published: October 2019

Introduction

Targeting the infiltrative nature of GBMs with anti-migratory drugs as combination treatment for prevention of tumour recurrence is an attractive disease management option. One such class of drugs are the GSK-3 inhibitors 6-bromoindirubin-3′-oximes (BIO). BIO has been proposed for use in combination therapy, however, the administration of indirubins remains problematic due to low solubility causing low bioavailability. We describe the characterisation of a BIO derivative, VTIND42, identified from a screen of 450 compounds with improved solubility.

Method

The compounds were initially screened on the following criteria, selective anti-migratory effect with enhanced potency over the lead compound BIO. Effect on cell migration in two cell subpopulations (core obtained, edge obtained) from the patient derived GBM40 was assessed by 3D migration/invasion assays and for cytoskeletal rearrangements by immunofluorescence.

Results

VTIND42 (1 µM) showed the best performance overall in terms of specificity and efficacy in comparison to BIO with a pronounced effect on GBM40 edge cell populations. Anti-migratory effects over 72 hours in GBM40 edge (24h, 10.74% p=0.04; 48h, 6.52% p=0.06, 72h, 4.26% p=0.06) in comparison to the control were observed; BIO (5 µM) significantly reduced migration over 72 hours (24h, 12.79% p<0.001; 48h 5.43% p<0.001; 72h 4.26% p<0.001). Immunofluorescence assays revealed cytoskeletal rearrangements; cells treated with VTIND42 showed an increased ratio of cells with stress fibres to cortical fibres and elongated cells.

Discussion

VTIND42 displayed increased efficacy in comparison to BIO, further investigations will determine its potential as a bioavailable anti-migratory drug for glioblastoma treatment potentially improving disease outcome in patients.
Cholesterol protects glioblastoma cells against premature mitosis
Authors: Gomez-roman Natividad , Jackson Mark , Chalmers Anthony J
Published: October 2019

Glioblastoma is the most common malignant primary tumour with a dismal prognosis. So far, no inhibitors targeting frequently altered pathways in GBM have improved patient survival. Premature entry to mitosis by small molecules that promote cancer cells to bypass the cell-cycle checkpoints have shown potent anti-tumour activity in vitro in a variety of cancers including GBM. We have reproduced these cytotoxic effects in our patient-derived GBM cell lines with the small molecule ME-344 and the Wee1-specific inhibitor AZ1775 both by by clonogenic survival and cell viability assays (EC50 values ranging from 0.003–0.02 μM and 0.2–0.4 μM, respectively). ME-344 and AZ1775 triggered profound morphological and cell cycle effects including mitotic induction, arrest and mitotic catastrophe. Bioinformatic analysis of global mRNA expression of our GBM cell lines stratified by ME-344 sensitivity showed a correlation between high ABCA1 and low cholesterol pathway gene expression with high sensitivity, and vice-versa. Cholesterol is a main component of membranes and is critical for cell growth and mitosis progression. GBM cells rely on cholesterol for survival. Due to the unique metabolic environment of the brain where a nearly unlimited supply of cholesterol is provided by astrocytes, targeting cellular activities regulated by cholesterol might lose their anti-tumour activity. Here we report that cholesterol confers cytoprotection to AZ1775 and ME344 in all GBM cell lines tested. These results suggest that cholesterol can override premature mitotic anti-tumour activity, indicating that mitotic induction and cholesterol inhibition might be a better therapeutic strategy for GBM than either treatment alone.
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

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

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

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

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

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

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

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

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 <10%, moderate 10–30%, severe >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<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<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<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<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<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

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 < 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 < 0.01) in pigs fed diets with either formulation method. From days 61 to 91, increasing NE had no effect (P > 0.10) on ADG. There was no change in G:F in pigs fed diets with the same percentage Lys (P > 0.10), but G:F decreased then increased (quadratic, P < 0.01) in response to increasing NE in pigs fed diets with a SID Lys:NE ratio. Overall, increasing dietary NE increased (linear, P < 0.001) daily NE intake and G:F (linear, P < 0.018) with either formulation method. However, SID Lys intake, ADG, and hot carcass weight only increased (linear, P < 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

Incorrect 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.
The conceptualisation of a modified formative assessment model for non‐verbal students with autism and severe learning difficulties
Authors: Aidonopoulou‐Read Tereza
Published: October 2019

The popularity of formative assessment has increased since the publication of work by Black and Wiliam in 1998. Even though it is a useful teaching tool, in most cases it has only been possible to use it for students with high levels of cognitive and communicative ability. The aim of this article is to propose a modified, personalisable model of formative assessment for non‐verbal students with autism and severe learning difficulties. Five students with autism and severe learning difficulties participated in systematic video observations over a period of eight weeks, during which student behaviour and attainment were recorded. The behaviour checklist gave an accurate representation of the students' level of engagement and predicted attainment, but differences in passive learning objectives (those requiring passive co‐operation) and active ones (those requiring active contribution) were noted. The introduction of engaging resources improved engagement, but tangible rewards had a negative effect on attainment. Praise had a positive effect on engagement and attainment.
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

The 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

Sclerotic 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.
Identification of the sirohaem biosynthesis pathway in Staphylococcus aureus
Authors: Videira Marco A. M. , Lobo Susana A. L. , Sousa Filipa L. , Saraiva Lígia M.
Published: October 2019

Sirohaem is a modified tetrapyrrole and a key prosthetic group of several enzymes involved in nitrogen and sulfur metabolisms. This work shows that Staphylococcus aureus produces sirohaem through a pathway formed by three independent enzymes. Of the two putative sirohaem synthases encoded in the S. aureus genome and annotated as cysG, one is herein shown to be a uroporphyrinogen III methyltransferase that converts uroporphyrinogen III to precorrin‐2, and was renamed as UroM. The second cysG gene encodes a precorrin‐2 dehydrogenase that converts precorrin‐2 to sirohydrochlorin, and was designated as P2D. The last step was found to be performed by the gene nirR that, in fact, codes for a protein with sirohydrochlorin ferrochelatase activity, labelled as ShfC. Additionally, site‐directed mutagenesis studies of S. aureus ShfC revealed that residues H22 and H87, which are predicted by homology modelling to be located at the active site, control the ferrochelatase activity. Within bacteria, sirohaem synthesis may occur via one, two or three enzymes, and we propose to name the correspondent pathways as Types 1, 2 and 3, respectively. A phylogenetic analysis revealed that Type 1 is the most used pathway in Gammaproteobacteria and Streptomycetales, Type 2 predominates in Fibrobacteres and Vibrionales, and Type 3 predominates in Firmicutes of the Bacillales order. Altogether, we concluded that the current distribution of sirohaem pathways within bacteria, which changes at the genus or species level and within taxa, seems to be the result of evolutionary multiple fusion/fission events.
Label‐free superresolution effect of nonlinear reverse saturation absorption thin films through difference method
Authors: DING C. , WEI J.
Published: October 2019

Label‐free superresolution effect of nonlinear reverse saturation absorption (NRSA) thin films was investigated through difference method, where a subdiffraction‐limit spot signal was constructed by intensity subtraction of two spots obtained under different laser intensities. By using annealed InSb films as the NRSA thin films, we experimentally obtained the subdiffraction‐limit spot signal, and the optimal reduction ratio was approximately 52.5% of the original spot. Experimental results agreed well with theoretical simulations. The simulation results of a 9‐point array sample showed the capability to achieve nonfluorescence superresolution imaging using the NRSA effect.
A multicenter study of oral sarcomas in Brazil
Authors: de Carvalho Waldner Ricardo Souza , de Souza Lucas Lacerda , Pontes Flávia Sirotheau Corrêa , Uchôa Daniel Cavallero Colares , Corrêa Davi Lavareda , de Cáceres Cinthia Verónica Bardalez López , Lopes Márcio Ajudarte , Santos‐Silva Alan Roger , Vargas Pablo Agustin , de Andrade Bruno Augusto Benevenuto , Romañach Mário , Gomez Ricardo Santiago , Costa Sara Ferreira dos Santos , Batista Aline Carvalho , Mendonça Elismauro Francisco , Pinto Décio dos Santos , Gondak Rogério , da Cruz Perez Danyel Elias , Nonaka Cassiano , dos Santos Jean Nunes , Libório‐Kimura Tatiana Nayara , Câmara Jeconias , Ramôa Pires Fábio , de Souza Lélia Batista , Martins Manoela Domingues , de Almeida Oslei Paes , Fonseca Felipe Paiva , Pontes Hélder Antônio Rebelo
Published: October 2019

Objectives

The aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil.

Materials and methods

A cross‐sectional study was conducted on biopsies obtained from January 2007 to December 2016 at twelve Brazilian oral and maxillofacial pathology centres. Gender, age, evolution time, clinical aspects, tumour location, tumour size at diagnosis, radiographic aspects and histopathological diagnosis were evaluated. Data were analysed using descriptive statistical methods.

Results

From 176,537, a total of 200 (0.11%) oral sarcomas were reported, and the most prevalent were osteosarcomas (74 cases; 37%) and Kaposi's sarcomas (52 cases; 26%). Males were more affected than females at a mean age of 32.2 years old (range of 3–87 years). The most common symptoms were swelling¸ localised pain and bleeding at a mean evolution time of 5.14 months (range <1–156 months). The lesions were mostly observed in the mandible (90 cases; 45%), with a mean tumour size of 3.4 cm (range of 0.3–15 cm). Radiographically, the lesions presented a radiolucent aspect showing cortical bone destruction and ill‐defined limits.

Conclusions

Oral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas and Kaposi's sarcomas were the main sarcomas of the oral cavity in Brazil.
Which factors determine treatment choices in patients with advanced kidney failure? a protocol for a co-productive, mixed methods study
Authors: Roberts Gareth , Chess James A , Howells Teri , Mc Laughlin Leah , Williams Gail , Charles Joanna M , Dallimore D J , Edwards Rhiannon Tudor , Noyes Jane
Published: October 2019

Introduction

Kidney disease is common, affecting up to 1 in 10 of the adult population, and the numbers are expected to rise over the next decade. There are three main treatments that are available to patients with kidney disease: transplantation, dialysis and supportive care without dialysis. Dialysis can occur in a dialysis unit or in a person’s home, but unit-based dialysis remains the most common initial treatment for patients in Wales. This is a cause for concern as most studies suggest that it is associated with the lowest quality of life and the highest mortality, and is a more expensive treatment option.

This study aims to identify the factors that lead to patients choosing unit-based haemodialysis rather than home-based dialysis with a view to informing future changes in patient education and service commissioning in Wales. A secondary aim is to determine if the co-production of research leads to more sustainable services.

Methods and analysis

This mixed-method study taking place between October 2018 and September 2020 will use a sequential explanatory design whereby the descriptive quantitative cross-sectional analysis of linked health and administrative data sets inform qualitative data collection from patients, carers and health and care professionals. Qualitative findings will be used to interpret or explain quantitative descriptive results. Additional strands to the study include a review of materials and education provided to patients and an economic review of treatment modalities.

Ethics and dissemination

The study will be conducted in accordance with the principles expressed in the Declaration of Helsinki. It has full approval from Health and Care Research Wales Research Ethics Committee #5. As a co-productive study involving patients, clinicians, third sector partners and academics, findings from this study will be shared on a continual basis. Study results will be published in peer-reviewed journals and presented at national and international conferences.
The Platonist Absurd Accumulation of Geometrical Objects: Metaphysics Μ.2
Authors: González-Varela José Edgar
Published: October 2019

In the first argument of Metaphysics Μ.2 against the Platonist introduction of separate mathematical objects, Aristotle purports to show that positing separate geometrical objects to explain geometrical facts generates an ‘absurd accumulation’ of geometrical objects. Interpretations of the argument have varied widely. I distinguish between two types of interpretation, corrective and non-corrective interpretations. Here I defend a new, and more systematic, non-corrective interpretation that takes the argument as a serious and very interesting challenge to the Platonist.
Engaging with the Bible in Visual Culture
Authors: Beaumont Sheona
Published: October 2019

Increasingly articulate contemporary art practices are engaging with biblical representation, revealing new relationships with religion through the availability of the word in image. Taking as exemplary the photographic publication of Adam Broomberg and Oliver Chanarin’s Holy Bible (2013), this essay considers the evidence for their hermeneutics between image and word that is characterized by open awareness of and expansive participation in the (rereading of the) Bible. Discussing this engagement, I explore imagistic readings of the Bible through the artists’ strategies of interpolation and repetition, as well as examining their chosen theme—catastrophe—for its revelatory power. Through the artists’ self-reflexive hermeneutics of indeterminacy, I argue that the discussion of the return of religion in art needs attuning to this kind of specific practitioner experience: a hermeneutical circle of imaginative, dialogical, and dynamic interpretative positions in which the notion of indeterminacy is persuasive for interpretative grist, historical accountability, and theological horizon.
Proclo commentatore del Timeo: esegesi procliana, esegesi a Proclo, e vettori materiali (Patmos Eileton 897)
Authors: Menchelli Mariella
Published: October 2019

Proclus’ Commentary on Plato’s Timaeus has been preserved in several manuscripts from the IX to the XVI centuries and in a paper scroll of the XI century, Patmos Eileton 897, containing two large parts of Book III (on the world’s body, on the recto, and on the world’s soul, on the verso of the scroll) and a large corpus of scholia vetera to it. This paper aims to examine the two main branches of the tradition of the Commentary and to give some observations on the exegetical apparatus to Proclus in the different forms of scholia figurata (and/or schemata), exegetical scholia, scholia to Proclus.
La terra di mezzo del commentario umanistico ai testi classici
Authors: Abbamonte Giancarlo
Published: October 2019

Scholars have lengthy debated on the originality of the humanistic commentary on the classical authors with respect to the medieval commentaries on the same authors. If the question can be regarded as still open for the works written in the first half of the 15th century, the birth of the printing determined a dramatic change in the contents and the form of the commentaries. From the point of view of the content the humanists are much more interested in the different readings transmitted by the manuscripts, whilst the printing allows both to have different layouts of the commentaries and to insert new tools as indexes and page numbers for consulting them. The present paper will present the new aspects of the printed commentaries and will try to explain the reasons which produced each change.
Intellectual Captivity
Authors: Bar-Itzhak Chen
Published: October 2019

This essay concerns the unequal distribution of epistemic capital in the academic field of World Literature and calls for an epistemic shift: a broadening of our theoretical canon and the epistemologies through which we read and interpret world literature. First, this epistemic inequality is discussed through a sociological examination of the “world republic of literary theory,” addressing the limits of circulation of literary epistemologies. The current situation, it is argued, creates an “intellectual captivity,” the ethical and political implications of which are demonstrated through a close reading of the acts of reading world literature performed by scholars at the center of the field. A few possible solutions are then suggested, drawing on recent developments in anthropology, allowing for a redistribution of epistemic capital within the discipline of World Literature: awareness of positionality, reflexivity as method, promotion of marginal scholarship, and a focus on “points of interaction.”
Secular Liturgies
Authors: Somerville-Wong Anastasia E.
Published: October 2019

This paper, by the founder of the UK based Secular Liturgies Network and Forum, explores the concept and purpose of secular liturgy, and the potential for liturgical events in modern secular societies. It examines the practice of writing secular liturgy, discusses potential contributions from atheists, agnostics, humanists and religious progressives, and considers the new pastoral roles that may evolve alongside a secular liturgies movement. The author argues that secular liturgies and liturgical events have the potential to enrich secular culture, nurture community, facilitate healthy social interaction, advance ethical thought, promote creative writing and other arts, and galvanise people in their efforts towards sustainability and the creation of cultures and environments of health.
Detection and Countermeasure of Packet Misrouting in Wireless Adhoc Networks
Authors: Muruganandam D. , Manickam J. Martin Leo
Published: October 2019

A MANET is an infrastructure-less type network, which consists of number of mobile nodes connected through wireless network interfaces. The Communication among nodes is made successfully when the nodes dynamically set up route among one another. The open nature and infrastructureless
type of such networks causes the attacker's interest to penetrate through the network and decrease the network performance. Thus Security becomes a major concern for protected communication between mobile nodes. Packet misrouting stops the packet from reaching the destination by a malicious
intermediate node. But the malicious node makes the intuition to its neighbors that it has done the genuine packet forwarding action. Moreover the malicious node makes the neighbours to suspect the normal node as malicious one. The proposed work ensures the detection of malicious nodes and
avoids suspecting the trustworthy.
Diaminomaleonitrile Based Hybrid Receptor for Selective Colorimetric Sensing of Dihydrogen Phosphate and Fluoride Ions
Authors: Swami Suman , Aruna  , Agarwala Arunava , Shrivastava Rahul
Published: October 2019

A diaminomaleonitrile based hybrid receptor (A1) derived from 2-hydroxy-1-naphthaldehyde and substituted pyrazole derivative (1a) was successfully synthesized and characterized. The hybrid receptor (A1) showed instant colorimetric change to deep orange from light
yellow with bathochromic shifts upon interaction with both fluoride and dihydrogen phosphate ions. Further, UV-Visible studies revealed that receptor (A1) selectively senses fluoride and dihydrogen phosphate ions in comparison to PF–6, HSO –4,
ClO–4, Cl–, Br– and I– ions. Also, receptor (A1) act as 'turn off' fluorescent switch for both fluoride and dihydrogen phosphate ions. Moreover, synthesized sensor (A1) can sense fluoride and dihydrogen
phosphate ions in detection range of 10 –6–10–7 M.
Researches on Er3+ Doped NaY(WO4)2 Crystal for Fluorescence Temperature Sensor
Authors: Qin Yueting , Hao Liyu , Yang Tie , Ming Chengguo
Published: October 2019

To research and develop fluorescence temperature sensor, Er3+-doped NaY(WO4)2 crystal had been prepared. Under 808 nm excitation, the sample's fluorescent spectra were measured. Strong green up-conversion emissions at 525 nm and 550 nm were observed.
Their intensity ratio is variable with the increase of the sample's temperature. The maximal sensitivity of Er3+ doped NaY(WO4)2 crystal was about 0.0058/K. Our researches are helpful for exploiting temperature sen- sor based on fluorescence intensity ratio.
Releasing the brakes on BTK-targeting miRNA
Authors: Blunt Matthew D. , Steele Andrew J.
Published: October 2019

In this issue of Blood, Bottoni et al demonstrate that histone deacetylase (HDAC) inhibition promotes the upregulation of microRNAs (miRNAs or miRs) which target Bruton tyrosine kinase (BTK), subsequently suppressing prosurvival signaling in chronic lymphocytic leukemia (CLL) samples, and highlight a rationale for HDAC inhibitors in combination with ibrutinib to treat patients.1