bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticipatory prescribing in community end-of-life care in the UK and Ireland during the COVID-19 pandemic: online survey
Authors: Antunes Bárbara , Bowers Ben , Winterburn Isaac , Kelly Michael P , Brodrick Robert , Pollock Kristian , Majumder Megha , Spathis Anna , Lawrie Iain , George Rob , Ryan Richella , Barclay Stephen 
Published: June 2020

BackgroundAnticipatory prescribing (AP) of injectable medications in advance of clinical need is established practice in community end-of-life care. Changes to prescribing guidelines and practice have been reported during the COVID-19 pandemic.Aims and objectivesTo investigate UK and Ireland clinicians’ experiences concerning changes in AP during the COVID-19 pandemic and their recommendations for change.MethodsOnline survey of participants at previous AP national workshops, members of the Association for Palliative Medicine of Great Britain and Ireland and other professional organisations, with snowball sampling.ResultsTwo hundred and sixty-one replies were received between 9 and 19 April 2020 from clinicians in community, hospice and hospital settings across all areas of the UK and Ireland. Changes to AP local guidance and practice were reported: route of administration (47%), drugs prescribed (38%), total quantities prescribed (35%), doses and ranges (29%). Concerns over shortages of nurses and doctors to administer subcutaneous injections led 37% to consider drug administration by family or social caregivers, often by buccal, sublingual and transdermal routes. Clinical contact and patient assessment were more often remote via telephone or video (63%). Recommendations for regulatory changes to permit drug repurposing and easier community access were made.ConclusionsThe challenges of the COVID-19 pandemic for UK community palliative care has stimulated rapid innovation in AP. The extent to which these are implemented and their clinical efficacy need further examination.
Organisational changes and challenges for inflammatory bowel disease services in the UK during the COVID-19 pandemic
Authors: Kennedy Nicholas A , Hansen Richard , Younge Lisa , Mawdsley Joel , Beattie R Mark , Din Shahida , Lamb Christopher A , Smith Philip J , Selinger Christian , Limdi Jimmy , Iqbal Tariq H , Lobo Alan , Cooney Rachel , Brain Oliver , Gaya Daniel R , Murray Charles , Pollok Richard , Kent Alexandra , Raine Tim , Bhala Neeraj , Lindsay James O , Irving Peter M , Lees Charlie W , Sebastian Shaji 
Published: June 2020

ObjectiveTo determine the challenges in diagnosis, monitoring, support provision in the management of inflammatory bowel disease (IBD) patients and explore the adaptations of IBD services.MethodsInternet-based survey by invitation of IBD services across the UK from 8 to 14 April 2020.ResultsRespondents from 125 IBD services completed the survey. The number of whole-time equivalent gastroenterologists and IBD nurses providing elective outpatient care decreased significantly between baseline (median 4, IQR 4–7.5 and median 3, IQR 2–4) to the point of survey (median 2, IQR 1–4.8 and median 2, IQR 1–3) in the 6-week period following the onset of the COVID-19 pandemic (p<0.001 for both comparisons). Almost all (94%; 112/119) services reported an increase in IBD helpline activity. Face-to-face clinics were substituted for telephone consultation by 86% and video consultation by 11% of services. A variation in the provision of laboratory faecal calprotectin testing was noted with 27% of services reporting no access to faecal calprotectin, and a further 32% reduced access. There was also significant curtailment of IBD-specific endoscopy and elective surgery.ConclusionsIBD services in the UK have implemented several adaptive strategies in order to continue to provide safe and high-quality care for patients. National Health Service organisations will need to consider the impact of these changes in current service delivery models and staffing levels when planning exit strategies for post-pandemic IBD care. Careful planning to manage the increased workload and to maintain IBD services is essential to ensure patient safety.
Very early-life exposure to microbiota-induced TNF drives the maturation of
neonatal pre-cDC1
Authors: Köhler Arnaud , Delbauve Sandrine , Smout Justine , Torres David , Flamand Véronique 
Published: June 2020

Objective
Induction of immune protection against pathogens is particularly crucial during
the neonatal period dominated by anti-inflammatory and tolerance immunity. The
preclinical study was carried out to determine whether environmental factors such as
microbiota may influence early life immunity by impacting the development and the
functional maturation of precursors of type 1 conventional dendritic cells (pre-cDC1),
endowed with regulatory properties.

Design
Pre-cDC1 phenotype and cytokine expression in the spleen of neonates from
antibiotic-treated mothers were established. The role of myeloid-derived tumour
necrosis factor (TNF) was tested in vitro and in vivo. RNA sequencing analysis on
neonatal sorted pre-cDC1 was performed. The early life protective
CD8+ T-cell response against Listeria
monocytogenes was monitored.

Results
We observed that first exposure to microbiota promotes TNF secretion by
monocytes and macrophages shortly after birth. We demonstrated that this
myeloid-derived inflammatory cytokine is crucial to induce the maturation of these
neonatal regulatory pre-cDC1. Myeloid TNF signalling acts on C1q and β-catenin pathway
and modifies the fatty acid metabolism in neonatal pre-cDC1. Furthermore, we showed
that during neonatal L. monocytogenes infection,
microbiota-associated myeloid TNF promotes the capacity of these pre-cDC1 to induce
protective CD8+ T-cell responses, by modulating their ability to
secrete interleukin-10 (IL-10) and IL-12p40.

Conclusion
Our findings emphasise the role of microbiota-derived TNF to kick-start the
differentiation and the functional maturation of the neonatal splenic pre-cDC1
compartment. They bring a better understanding of potential mechanisms underlying some
microbiota-linked immune dysfunction in early life.
Aneurysms of the communicating segment of the internal carotid artery with posterior communicating artery agenesis are associated with perforator infarction after embolization
Authors: Simonato Davide , Gargalas Sergios , Cox Pete J , Young Victoria , Corkill Rufus , Kuker Wilhelm , Fuschi Maurizio , Houdart Emmanuel , Labeyrie Marc-Antoine 
Published: June 2020

BackgroundWhile anatomic features associated with the risk of posterior communicating artery (PcoA) occlusion after embolization of aneurysms of the PcoA segment of the internal carotid artery (ICA) are well known, the link between perforator origin and perforator infarction has only been reported following neurosurgical clipping. The aim of this study was to determine the origin of anterior thalamic perforators and correlate it with risk of perforator infarction after embolization of PcoA segment aneurysms.MethodsOne-hundred-and-ninety consecutive patients treated for PcoA segment aneurysms between 2017 and 2019 were included. PcoA and anterior thalamic perforator origin anatomy was assessed with computed tomography (CT) angiography, digital subtracted angiography, and high-resolution three-dimensional rotational cone-beam CT angiography (CBCT-A) by two independent interventional neuroradiologists. The presence of perforator infarction after embolization was ascertained from the patient’s notes and follow-up imaging.ResultsCBCT-A was superior in demonstrating the origin of perforators (P<0.001). The prevalence of perforator origin was estimated at 86% (95% CI 81%–92%) for PcoA, 8% (95% CI 4%–13%) for aneurysm wall, and 5% (95% CI 2%–9%) for ICA. The aneurysm wall origin was exclusively associated with PcoA agenesis, as well as higher risk of perforator infarction after aneurysm coiling compared with other variants (OR=14, 95% CI 2–88, P=0.006).ConclusionsOur study suggests that anterior thalamic perforators may arise from aneurysm wall when there is no PcoA. Anatomic association between PcoA agenesis and perforator arising from ICA could underlie such findings, and careful consideration is essential before aneurysm repair to anticipate the risk of thalamic infarction in such cases.
First clinical multicenter experience with the new Scepter Mini microballoon catheter
Authors: Vollherbst Dominik F , Chapot René , Wallocha Marta , Saatci Isil , Cekirge Saruhan , Rouchaud Aymeric , Mounayer Charbel , Kocer Naci , Kizilkilic Osman , Sourour Nader A , Shotar Eimad , Psychogios Marios N , Brehm Alex , Bendszus Martin , Möhlenbruch Markus A 
Published: June 2020

BackgroundBalloon-assisted techniques can improve the endovascular treatment of cerebrospinal vascular malformations. The aim of this study was to report the first clinical multicenter experience with the new Scepter Mini dual-lumen microballoon catheter.MethodsPatients with cerebral or spinal vascular malformations treated with the Scepter Mini at seven European neurovascular centers were retrospectively reviewed. Clinical data, angiographic features of the vascular malformations, procedural parameters including the type of application, navigability, technical failures, complications and embolization success were assessed.ResultsThe usage of 34 Scepter Mini microballoon catheters in 20 patients was analyzed. Most treated malformations (80.0%) were cerebral arteriovenous malformations. Four different applications were reported: embolization via Scepter Mini (n=23, 67.6%), balloon-occlusion with simultaneous embolization via a second microcatheter (n=3, 8.8%), diagnostic angiography with simultaneous balloon-inflation for flow arrest (n=4, 11.8%), and navigation support (n=4, 11.8%). The mean diameter of the blood vessels in which the Scepter Mini was inflated was 1.9±0.5 mm. The navigability of the Scepter Mini was rated as ‘easy’ or ‘very easy’ in 88.2% of cases. Complete occlusion of the malformation was achieved in 60.9% of cases. Technical failures occurred in 4/23 embolization procedures, and all were related to insufficient stability of the balloon within the vessel. No complications related to the Scepter Mini were observed, while unrelated complications occurred in three patients (15.0%).ConclusionsThe Scepter Mini is a promising new device for balloon-assisted embolization of cerebrospinal vascular malformations via small feeders. Beyond embolization, the Scepter Mini can also be used for other applications, such as superselective flow arrest and navigation support.
Endovascular sacrifice of the proximal posterior inferior cerebellar artery for treatment of ruptured intracranial aneurysms
Authors: Malcolm James G , Grossberg Jonathan A , Laxpati Nealen G , Alawieh Ali , Tong Frank C , Cawley C Michael , Howard Brian M 
Published: June 2020

BackgroundRuptured aneurysms of the intracranial vertebral artery (VA) or posterior inferior cerebellar artery (PICA) are challenging to treat as they are often dissecting aneurysms necessitating direct sacrifice of the diseased segment, which is thought to carry high morbidity due to brainstem and cerebellar stroke. However, relatively few studies evaluating outcomes following VA or proximal PICA sacrifice exist. We sought to determine the efficacy and outcomes of endovascular VA/PICA sacrifice.MethodsA retrospective series of ruptured VA/PICA aneurysms treated by endovascular sacrifice of the VA (including the PICA origin) or proximal PICA is reviewed. Collected data included demographic, radiologic, clinical, and disability information.ResultsTwenty-one patients were identified. Median age was 57 years (IQR 11); 15 were female. The Hunt and Hess grade was mostly 3 and 4 (18/21). Seven cases (33%) involved VA-V4 at the PICA take-off, and 14 cases (67%) involved the PICA exclusively. For VA pathology, V4 was sacrificed in all cases, while for PICA pathology, sacrificed segments included anterior medullary (4/14), lateral medullary (7/14), and tonsillomedullary (3/14) segments. Four patients went to hospice (19%). Twelve patients (57%) had evidence of stroke on follow-up imaging: cerebellar (8), medullary (1), and both (3). One patient required suboccipital decompression for brainstem compression. No aneurysm re-rupture occurred. Median discharge modified Rankin Scale score was 2.0 (IQR 2), which decreased to 1.0 (IQR 1) at median follow-up of 6.5 months (IQR 23).ConclusionsEndovascular sacrifice of V4 or PICA aneurysms may carry less morbidity than previously thought, and is a viable alternative for poor surgical candidates or those with good collateral perfusion.
Chapter 8 Palaeobiogeography of New Caledonia
Authors: Maurizot P. , Campbell H. J. 
Published: June 2020

Abstract
New Caledonia is known as a global biodiversity hotspot. Like most Pacific islands, its modern biota is characterized by high levels of endemism and is notably lacking in some functional groups of biota. This is the result of its distinctive palaeobiogeographical history, which can be described in terms of three major episodes relating to Gondwana, Zealandia and New Caledonia. The geological record, the fossil record and the modern biota of the archipelago are all reviewed here. The geological record shows that the main island, Grande Terre, was submerged between 75 and 60 Ma. There is a 9 myr interval without any geological record between 34 and 25 Ma, immediately after the obduction of the Peridotite Nappe. Grande Terre may or may not have been submerged during this 9 myr interval. The ages given by molecular biology, independent of any geological calibration points, form a continuous spectrum from 60 Ma up to the present day. The derived lineage ages from molecular phylogenies all post-date 60 Ma, supporting the idea of the continuous availability of terrestrial environments since 60 Ma. Of the three common scenarios for the origin of the New Caledonia biota, long-distance dispersal is the most plausible, rather than vicariance or dispersal over short distances.
Chemotherapy and CDK4/6 Inhibitors: Unexpected Bedfellows
Authors: Roberts Patrick J. , Kumarasamy Vishnu , Witkiewicz Agnieszka K. , Knudsen Erik S. 
Published: June 2020

AbstractCyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as important therapeutic targets. Pharmacologic inhibitors of these kinases function to inhibit cell-cycle progression and exert other important effects on the tumor and host environment. Because of their impact on the cell cycle, CDK4/6 inhibitors (CDK4/6i) have been hypothesized to antagonize the antitumor effects of cytotoxic chemotherapy in tumors that are CDK4/6 dependent. However, there are multiple preclinical studies that illustrate potent cooperation between CDK4/6i and chemotherapy. Furthermore, the combination of CDK4/6i and chemotherapy is being tested in clinical trials to both enhance antitumor efficacy and limit toxicity. Exploitation of the noncanonical effects of CDK4/6i could also provide an impetus for future studies in combination with chemotherapy. Thus, while seemingly mutually exclusive mechanisms are at play, the combination of CDK4/6 inhibition and chemotherapy could exemplify rational medicine.
Abstract A02: Detection of circulating cell-free DNA in renal cancer using renal cancer-specific DNA mutations and methylation changes
Authors: Adamowicz Martyna J. , Thomson John , Warlow Sophie J. , Patra Utsa , Thain Helen , de Proce Sophie Marion , Laird Alexander , Aitman Timothy J. 
Published: June 2020

Abstract
Renal cell cancer (RCC) is the most deadly of urologic malignancies. It is a very invasive and chemoresistant disease that is often treated by surgical resection as it also responds poorly to radiotherapy. Importantly, more than 30% of RCCs recur or metastasize following treatment and in the cases believed to be curable by nephrectomy, distant metastasis can develop even 10 years post-surgery. There is therefore a significant focus on tissue-based biomarkers from the primary kidney tumors to help predict which patients are likely to recur, though there are no biomarkers used in routine clinical practice. Over recent years, much research has aimed at the utilization of blood-based biomarkers, mainly circulating cell-free DNA (cfDNA), as a method of noninvasive disease diagnosis and monitoring. cfDNA is detected through the identification of tumor-specific cfDNA mutations, although cfDNA methylation may be a more specific biomarker as many CpG sites can be tested in parallel. We have collected tumor tissue and pre- and post-surgery blood samples from renal cancer patients and generated exome sequencing and EPIC array data of 20 tumors with matched blood samples to detect tumor-specific DNA mutations and methylation patterns. We have identified well-known driver mutations in renal cancer in VHL in 11 tumors at 0.12-0.51 variant allele fraction (VAF); PBRM1 in 8 tumors at 0.12-0.45 VAF; BAP-1 in 2 tumors at 0.45 and 0.3 VAF; and SETD2 at 0.39 VAF; KDM5C at 0.27 VAF, and CTNNA2 at 0.2 VAF in one out of 20 patients. We aim to validate these changes using droplet digital PCR (ddPCR) in tumor and circulating tumor DNA (ctDNA) pre- and post-surgery. We next plan to combine the result of the exome sequencing with EPIC array data as well in house-developed cfDNA profiles based on publicly available tissue and individual cell type DNA methylation data. This approach will allow us to select the best mutation and methylation diagnostic and prognostic markers to aid the monitoring of early disease and relapse as well as the treatment of renal cell cancer.
Citation Format: Martyna J. Adamowicz, John Thomson, Sophie J. Warlow, Utsa Patra, Helen Thain, Sophie Marion de Proce, Alexander Laird, Timothy J. Aitman. Detection of circulating cell-free DNA in renal cancer using renal cancer-specific DNA mutations and methylation changes [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A02.
Abstract A12: DNA methylation-based liquid biopsy detects primary and recurrent meningioma
Authors: Sabedot Thais S. , Malta Tathiane M. , Snyder James , Walbert Tobias , Lee Ian , Kalkanis Steven , Castro Ana Valeria , Noushmehr Houtan 
Published: June 2020

Abstract
Meningiomas are mostly benign CNS tumors; however, a subset of these tumors may become atypical or malignant. The standard of care to monitor patients after diagnosis requires serial MRI assessments, which have limited value in distinguishing malignant tumors from benign disease. Therefore, the discovery of noninvasive methodologies that reflect meningioma tumor burden and its dynamic evolution in real-time is highly desirable. Liquid biopsy (LB) could be used to fine-tune surveillance and treatment with minimal risk to patients. Evidence of circulating tumor cells and cell-free (cf) tumor DNA in the blood has been shown in several tumor types; however, limited progress has been made for brain tumors with known biomarkers, possibly due to the unlikelihood of capturing point mutations in circulating DNA fragments. On the other hand, DNA methylation signatures are maintained even in small DNA fragments, which suggests that DNA methylation is an attractive marker to be studied in liquid biopsy of brain cancers. In order to identify DNA methylation-based biomarkers, we used archival serum and matching tissue specimens from primary (n=10) and recurrent (n=4) meningiomas. From isolated cfDNA from meningiomas and epileptic patients (n=5) as a control, we generated epigenetic data using Illumina Human EPIC array. cfDNA fragment size distribution revealed peaks with 150~200bp on average. We identified 482 CpGs (FDR&lt;0.001) differentially methylated between primary meningiomas and controls, of which 294 (61%) show a DNA methylation profile similar to the epigenome of the matched tumor tissue. Overall, we observed that recurrent samples are hypermethylated (56%) compared to primary. From this pilot data, we were able to investigate the LB methylome of meningioma patients and identify potential markers to detect tumor cells in the serum of these patients, which could eventually allow clinicians to monitor impending disease progression and recurrence.
Citation Format: Thais S. Sabedot, Tathiane M. Malta, James Snyder, Tobias Walbert, Ian Lee, Steven Kalkanis, Ana Valeria Castro, Houtan Noushmehr. DNA methylation-based liquid biopsy detects primary and recurrent meningioma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A12.
Abstract A14: Detection of a biomarker for B-cell non-Hodgkin lymphomas or leukemias using circulating tumor DNA without the use of PCR or next-gen sequencing
Authors: Stewart Jessica A. , Bhagwat Ashok S. 
Published: June 2020

Abstract
There is a critical need for the development of cheap, safe, and accurate tools for cancer surveillance. Patients diagnosed with cancer require an accurate assessment of tumor burden through the course of their treatment, and the need for tumor surveillance is even more acute for many indolent B-cell malignancies such as follicular lymphoma and chronic lymphocytic leukemia. Over the past several years, we have developed an assay that quantifies a tumor biomarker for many different types of B-cell non-Hodgkin lymphomas or leukemias (B-NHLs). This biomarker, uracils in DNA, originates from the activity of a B-cell maturation enzyme, activation-induced deaminase (AID), which converts cytosines in DNA to uracil. AID is normally not expressed in circulating B cells or any other human tissue and hence this marker is not present in any other types of cells in the human body. We have developed an ELISA-like assay using chemicals with a fluorescence readout that can detect this biomarker in DNA with high sensitivity without PCR or NGS. We will present applications of this technology to genomic DNA from B-NHL tumors and circulating tumor DNA in blood plasma of such patients. Our data show we can detect the presence of this marker in DNA of patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia.
Citation Format: Jessica A. Stewart, Ashok S. Bhagwat. Detection of a biomarker for B-cell non-Hodgkin lymphomas or leukemias using circulating tumor DNA without the use of PCR or next-gen sequencing [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A14.