bluuebunny/crossref_metadata_2025_split huggingface dataset:
The logistical management of tertiary urethral disease in the United Kingdom: Implications from an online audit of male reconstructive urethral surgery
Authors: Payne Stephen R , Fowler Sarah , Mundy Anthony R , Alhasso A. , Almallah Y. , Anderson P. , Andrich D. , Baird A. , Biers S. , Browning A. , Chapple C. , Cherian J. , Clarke L. , Conn I. , Dickerson D. , Doble A. , Dorkin T. , Duggan B. , Eardley I. , Garaffa G. , Greenwell T. , Hadway P. , Harding C. , Hilmy M. , Inman R. , Kayes O. , Kirchin V. , Krishnan R. , Kumar V. , Lemberger J. , Malone P. , Moore J. , Moore K. , Mundy A. , Noble J. , Nurse D. , Palmer M. , Payne S. , Pickard R. , Rai J. , Rees R. , Roux J. , Seipp C. , Shabbir M. , Saxby M. , Sharma D. , Sinclair A. , Summerton D. , Tatarov O. , Thiruchelvam N. , Venn S , Watkin N. , Zacherakis E. 
Published: January 2020

Objective: To determine those patient groupings, based on volume and risk, whose optimal urethral reconstructive management might be provided by a reorganisation of UK reconstructive surgeons. Methods: Between 2010 and 2017, ~689 men/year were enrolled onto an online audit platform collecting data about urethral reconstruction in the UK; this accrual was compared against hospital episode statistics (HES). The available workforce, and where this was based, was collected. Individual and institutional incumbent patient volumes, pathology, surgical complexity and outcomes from treatment were collated to stratify volume/risk groups. Results: More than 90% of all HES-recorded data were accrued, being provided by 50 surgeons at 39 operative sites. Most reconstructive surgery was provided at 10 centres performing >20 procedures/year. More than 50% of all interventions were of a high-volume low-risk type. Of activity, 32.3% was intermediate volume or moderate risk, and 12.5% of men presented for lower-volume or higher-risk procedures. Conclusion: Correlation of detailed volume/outcome data allows the definition of patient populations presenting for urethral reconstruction. Stratification of each group’s management, to optimise the surgical outcome, may be applied to a hierarchical service delivery model based on the complexity of the patient’s presenting urethral pathology. Level of evidence: Level IV
Does routine histology alter management post circumcision?
Authors: Kerr Lynne , Hendry Jane , Crookshanks Aaron , Taylor Joby 
Published: January 2020

Objective: Circumcision is a commonly performed urological procedure, histology is often requested with unexpected malignancy cited as the reason. This paper aims to determine if routine histology following circumcision alters the clinical management of patients. Patients and methods: The clinical records of 508 consecutive adult patients circumcised at a district general hospital between 1/1/12 and 31/12/16 were retrospectively reviewed. Two groups were available for comparison, those with histological diagnosis (359 patients) and those with a clinical diagnosis only (149 patients). The following data were collected: indication for circumcision; preoperative clinical and histological diagnosis; patient follow-up (mean 40 months). Results: A total of 508 patients were reviewed. Histology was requested for 359 specimens (70.7%). Six cases of squamous cell carcinoma were correctly identified clinically and there were no cases of unexpected malignancy. The clinical diagnosis of lichen sclerosus was correct in 92% of cases; 39 patients were re-referred following discharge, only one required further management of a urethral stricture. Conclusion: The results of our study show there is no difference in the outcomes or re-referral rates of patients who have routine histology requested following circumcision compared with those who do not. Clinical diagnosis is consistently accurate. There is a minimal number of patients referred back to the service, even with lichen sclerosus, and histology does not affect the rate of this. We conclude that routine histology does not alter patient management following circumcision and is not required unless a clinical suspicion of malignancy exists. This study represents the largest cohort of circumcision patients and includes the longest period of follow-up to add to the current body of literature. Levels of evidence: 2b retrospective consecutive cohort study with follow up.
Shadow Education in Europe: Growing Prevalence, Underlying Forces, and Policy Implications
Authors: Bray Mark 
Published: January 2020

Purpose: Private supplementary tutoring, widely known as shadow education, has long been visible in East Asia, and now has spread to other parts of the world including Europe. This article maps the phenomenon, showing variations within Europe and analyzing its growth, underlying forces, and policy implications. Design/Approach/Methods: The article assembles a regional picture from available national sources. It focuses on the 28 members of the European Union. Findings: Within Europe, four subregions may be identified. Most prominent for the longest duration has been Southern Europe, pushed by political forces and cultural factors. In Eastern Europe, shadow education became prominent following the collapse of the Soviet Union and accompanying economic and social structures during which teachers and others had to earn extra incomes. In Western Europe, the advent of marketization alongside government schooling has fueled the growth of shadow education. Only in Northern Europe does shadow education remain modest in scale, but it is growing there too. Originality/Value: The article identifies forces underlying the growth of shadow education in Europe and highlights policy implications. By contributing this regional perspective to the wider literature on shadow education, the article permits juxtaposition with patterns in East Asia and elsewhere.
An update on the molecular pathogenesis and potential therapeutic targeting of AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1
Authors: Al-Harbi Sayer , Aljurf Mahmoud , Mohty Mohamad , Almohareb Fahad , Ahmed Syed Osman Ali 
Published: January 2020

Abstract
Acute myeloid leukemia (AML) with t(8;21)(q22;q22.1);RUNX1-RUNX1T1, one of the core-binding factor leukemias, is one of the most common subtypes of AML with recurrent genetic abnormalities and is associated with a favorable outcome. The translocation leads to the formation of a pathological RUNX1-RUNX1T1 fusion that leads to the disruption of the normal function of the core-binding factor, namely, its role in hematopoietic differentiation and maturation. The consequences of this alteration include the recruitment of repressors of transcription, thus blocking the expression of genes involved in hematopoiesis, and impaired apoptosis. A number of concurrent and cooperating mutations clearly play a role in modulating the proliferative potential of cells, including mutations in KIT, FLT3, and possibly JAK2. RUNX1-RUNX1T1 also appears to interact with microRNAs during leukemogenesis. Epigenetic factors also play a role, especially with the recruitment of histone deacetylases. A better understanding of the concurrent mutations, activated pathways, and epigenetic modulation of the cellular processes paves the way for exploring a number of approaches to achieve cure. Potential approaches include the development of small molecules targeting the RUNX1-RUNX1T1 protein, the use of tyrosine kinase inhibitors such as dasatinib and FLT3 inhibitors to target mutations that lead to a proliferative advantage of the leukemic cells, and experimentation with epigenetic therapies. In this review, we unravel some of the recently described molecular pathways and explore potential therapeutic strategies.
Supramaximal calcium signaling triggers procoagulant platelet formation
Authors: Abbasian Nima , Millington-Burgess Sarah L. , Chabra Shirom , Malcor Jean-Daniel , Harper Matthew T. 
Published: January 2020

Abstract
Procoagulant platelets promote thrombin generation during thrombosis. Platelets become procoagulant in an all-or-nothing manner. We investigated how distinct Ca2+ signaling between platelet subpopulations commits some platelets to become procoagulant, using the high-affinity Ca2+ indicator Fluo-4, which may become saturated during platelet stimulation, or low-affinity Fluo-5N, which reports only very high cytosolic Ca2+ concentrations. All activated platelets had high Fluo-4 fluorescence. However, in Fluo-5N–loaded platelets, only the procoagulant platelets had high fluorescence, indicating very high cytosolic Ca2+. This finding indicates a novel, “supramaximal” Ca2+ signal in procoagulant platelets (ie, much higher than normally considered maximal). Supramaximal Ca2+ signaling and the percentage of procoagulant platelets were inhibited by cyclosporin A, a mitochondrial permeability transition pore blocker, and Ru360, an inhibitor of the mitochondrial Ca2+ uniporter, with no effect on Fluo-4 fluorescence. In contrast, Synta-66, an Orai1 blocker, reduced Fluo-4 fluorescence but did not directly inhibit generation of the supramaximal Ca2+ signal. Our findings show a distinct pattern of Ca2+ signaling in procoagulant platelets and provide a new framework to interpret the role of platelet signaling pathways in procoagulant platelets. This requires reassessment of the role of different Ca2+ channels and may provide new targets to prevent formation of procoagulant platelets and limit thrombosis.
Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin
Authors: Politikos Ioannis , Lavery Jessica A. , Hilden Patrick , Cho Christina , Borrill Taylor , Maloy Molly A. , Giralt Sergio A. , van den Brink Marcel R. M. , Perales Miguel-Angel , Barker Juliet N. 
Published: January 2020

Abstract
Quality of immune reconstitution after cord blood transplantation (CBT) without antithymocyte globulin (ATG) in adults is not established. We analyzed immune recovery in 106 engrafted adult CBT recipients (median age 50 years [range 22-70]) transplanted for hematologic malignancies with cyclosporine/mycophenolate mofetil immunoprophylaxis and no ATG. Patients were treated predominantly for acute leukemia (66%), and almost all (96%) underwent myeloablation. Recovery of CD4+ T cells was faster than CD8+ T cells with median CD4+ T-cell counts exceeding 200/mm3 at 4 months. Early post-CBT, effector memory (EM), and central memory cells were the most common CD4+ subsets, whereas effector and EM were the most common CD8+ T-cell subsets. Naive T-cell subsets increased gradually after 6 to 9 months post-CBT. A higher engrafting CB unit infused viable CD3+ cell dose was associated with improved CD4+ and CD4+CD45RA+ T-cell recovery. Cytomegalovirus reactivation by day 60 was associated with an expansion of total, EM, and effector CD8+ T cells, but lower CD4+ T-cell counts. Acute graft-versus-host disease (aGVHD) did not significantly compromise T-cell reconstitution. In serial landmark analyses, higher CD4+ T-cell counts and phytohemagglutinin responses were associated with reduced overall mortality. In contrast, CD8+ T-cell counts were not significant. Recovery of natural killer and B cells was prompt, reaching medians of 252/mm3 and 150/mm3 by 4 months, respectively, although B-cell recovery was delayed by aGVHD. Neither subset was significantly associated with mortality. ATG-free adult CBT is associated with robust thymus-independent CD4+ T-cell recovery, and CD4+ recovery reduced mortality risk.
Microglia P2X4R-BDNF signalling contributes to central sensitization in a recurrent nitroglycerin-induced chronic migraine model
Authors: Long Ting , He Wei , Pan Qi , Zhang Shanshan , Zhang Dunke , Qin Guangcheng , Chen Lixue , Zhou Jiying 
Published: January 2020

AbstractBackgroundAccording to our previous study, microglia P2X4 receptors (P2X4Rs) play a pivotal role in the central sensitization of chronic migraine (CM). However, the molecular mechanism that underlies the crosstalk between microglia P2X4Rs and neurons of the trigeminal nucleus caudalis (TNC) is not fully understood. Therefore, the aim of this study is to examine the exact P2X4Rs signalling pathway in the development of central sensitization in a CM animal model.MethodsWe used an animal model with recurrent intermittent administration of nitroglycerin (NTG), which closely mimics CM. NTG-induced basal mechanical and thermal hypersensitivity were evaluated using a von Frey filament test and an increasing-temperature hot plate apparatus (IITC). We detected P2X4Rs, brain-derived neurotrophic factor (BDNF) and phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK) expression profiles in the TNC. We investigated the effects of a P2X4R inhibitor (5-BDBD) and an agonist (IVM) on NTG-induced hyperalgesia and neurochemical changes as well as on the expression of p-p38-MAPK and BDNF. We also detected the effects of a tropomyosin-related kinase B (TrkB) inhibitor (ANA-12) on the CM animal model in vivo. Then, we evaluated the effect of 5-BDBD and SB203580 (a p38-MAPK inhibitors) on the release and synthesis of BDNF in BV2 microglia cells treated with 50 μM adenosine triphosphate (ATP).ResultsChronic intermittent administration of NTG resulted in chronic mechanical and thermal hyperalgesia, accompanied by the upregulation of P2X4Rs and BDNF expression. 5-BDBD or ANA-12 prevented hyperalgesia induced by NTG, which was associated with a significant inhibition of the NTG-induced increase in phosphorylated extracellular regulated protein kinases (p-ERK) and calcitonin gene related peptide (CGRP) release in the TNC. Repeated administration of IVM produced sustained hyperalgesia and significantly increased the levels of p-ERK and CGRP release in the TNC. Activating P2X4Rs with ATP triggered BDNF release and increased BDNF synthesis in BV2 microglia, and these results were then reduced by 5-BDBD or SB203580.ConclusionsOur results indicated that the P2X4R contributes to the central sensitization of CM by releasing BDNF and promoting TNC neuronal hyper-excitability. Blocking microglia P2X4R-BDNF signalling may have an effect on the prevention of migraine chronification.
Forecasts of future scenarios for airport noise based on collection and processing of web data
Authors: Pretto Marco , Giannattasio Pietro , De Gennaro Michele , Zanon Alessandro , Kuehnelt Helmut 
Published: January 2020

Abstract
Purpose
This paper presents an analysis of short-term (2025) scenarios for noise emission from civil air traffic in airport areas.

Methods
Flight movements and noise levels at a given airport are predicted using a web-data-informed methodology based on the ECAC Doc.29 model. This methodology, developed by the authors in a previous work, relies on the collection and processing of air traffic web data to reconstruct flight events to be fed into the ECAC model. Three new elements have been included: i) topographic information from digital elevation models, ii) a fleet substitution algorithm to estimate the impact of newer aircraft, and iii) a generator of flight events to simulate the expected traffic increase.

Results
The effects of these elements are observed in 2025 scenarios for the airports of London Heathrow, Frankfurt and Vienna-Schwechat. The results quantify the noise reduction from new aircraft and its increment due to the air traffic growth forecast by EUROCONTROL.
A pipeline to create predictive functional networks: application to the tumor progression of hepatocellular carcinoma
Authors: Folschette Maxime , Legagneux Vincent , Poret Arnaud , Chebouba Lokmane , Guziolowski Carito , Théret Nathalie 
Published: January 2020

Abstract
Background
Integrating genome-wide gene expression patient profiles with regulatory knowledge is a challenging task because of the inherent heterogeneity, noise and incompleteness of biological data. From the computational side, several solvers for logic programs are able to perform extremely well in decision problems for combinatorial search domains. The challenge then is how to process the biological knowledge in order to feed these solvers to gain insights in a biological study. It requires formalizing the biological knowledge to give a precise interpretation of this information; currently, very few pathway databases offer this possibility.

Results
The presented work proposes an automatic pipeline to extract automatically regulatory knowledge from pathway databases and generate novel computational predictions related to the state of expression or activity of biological molecules. We applied it in the context of hepatocellular carcinoma (HCC) progression, and evaluate the precision and the stability of these computational predictions. Our working base is a graph of 3383 nodes and 13,771 edges extracted from the KEGG database, in which we integrate 209 differentially expressed genes between low and high aggressive HCC across 294 patients. Our computational model predicts the shifts of expression of 146 initially non-observed biological components. Our predictions were validated at 88% using a larger experimental dataset and cross-validation techniques. In particular, we focus on the protein complexes predictions and show for the first time that NFKB1/BCL-3 complexes are activated in aggressive HCC. In spite of the large dimension of the reconstructed models, our analyses over the computational predictions discover a well constrained region where KEGG regulatory knowledge constrains gene expression of several biomolecules. These regions can offer interesting windows to perturb experimentally such complex systems.

Conclusion
This new pipeline allows biologists to develop their own predictive models based on a list of genes. It facilitates the identification of new regulatory biomolecules using knowledge graphs and predictive computational methods. Our workflow is implemented in an automatic python pipeline which is publicly available at https://github.com/LokmaneChebouba/key-pipeand contains as testing data all the data used in this paper.
Robust estimation of heritability and predictive accuracy in plant breeding: evaluation using simulation and empirical data
Authors: Lourenço Vanda Milheiro , Ogutu Joseph Ochieng , Piepho Hans-Peter 
Published: January 2020

AbstractBackgroundGenomic prediction (GP) is used in animal and plant breeding to help identify the best genotypes for selection. One of the most important measures of the effectiveness and reliability of GP in plant breeding is predictive accuracy. An accurate estimate of this measure is thus central to GP. Moreover, regression models are the models of choice for analyzing field trial data in plant breeding. However, models that use the classical likelihood typically perform poorly, often resulting in biased parameter estimates, when their underlying assumptions are violated. This typically happens when data are contaminated with outliers. These biases often translate into inaccurate estimates of heritability and predictive accuracy, compromising the performance of GP. Since phenotypic data are susceptible to contamination, improving the methods for estimating heritability and predictive accuracy can enhance the performance of GP. Robust statistical methods provide an intuitively appealing and a theoretically well justified framework for overcoming some of the drawbacks of classical regression, most notably the departure from the normality assumption. We compare the performance of robust and classical approaches to two recently published methods for estimating heritability and predictive accuracy of GP using simulation of several plausible scenarios of random and block data contamination with outliers and commercial maize and rye breeding datasets.ResultsThe robust approach generally performed as good as or better than the classical approach in phenotypic data analysis and in estimating the predictive accuracy of heritability and genomic prediction under both the random and block contamination scenarios. Notably, it consistently outperformed the classical approach under the random contamination scenario. Analyses of the empirical maize and rye datasets further reinforce the stability and reliability of the robust approach in the presence of outliers or missing data.ConclusionsThe proposed robust approach enhances the predictive accuracy of heritability and genomic prediction by minimizing the deleterious effects of outliers for a broad range of simulation scenarios and empirical breeding datasets. Accordingly, plant breeders should seriously consider regularly using the robust alongside the classical approach and increasing the number of replicates to three or more, to further enhance the accuracy of the robust approach.
A modified Delphi study to identify the features of high quality measurement plans for healthcare improvement projects
Authors: Woodcock Thomas , Adeleke Yewande , Goeschel Christine , Pronovost Peter , Dixon-Woods Mary 
Published: January 2020

Abstract
Background
The design and execution of measurement in quality improvement (QI) initiatives is often poor. Better guidance on “what good looks like” might help to mitigate some of the problems. We report a consensus-building process that sought to identify which features are important to include in QI measurement plans.

Methods
We conducted a three-stage consensus-building approach: (1) identifying the list of features of measurement plans that were potential candidates for inclusion based on literature review and the study team’s experience; (2) a two-round modified Delphi exercise with a panel of experts to establish consensus on the importance of these features; and (3) a small in-person consensus group meeting to finalise the list of features.

Results
A list of 104 candidate questions was generated. A panel of 19 experts in the Delphi reviewed these questions and produced consensus on retaining 46 questions in the first round and on a further 22 in the second round. Thematic analysis of open text responses from the panellists suggested a number of areas of debate that were explicitly considered by the consensus group. The exercise yielded 74 questions (71% of 104) on which there was consensus in five categories of measurement relating to: design, data collection and management, analysis, action, and embedding.

Conclusions
This study offers a consensus-based view on the features of a good measurement plan for a QI project in healthcare. The results may be of use to QI teams, funders and evaluators, but are likely to require further development and testing to ensure feasibility and usefulness.