bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fishing for Justice: England's Inshore Fisheries’ Social Movements and Fixed Quota Allocation
Authors: Anbleyth-Evans Jeremy W. , Williams Chris 
Published: February 2020

English inshore fishers have long campaigned through the New Under 10m Fishermen's Association to have a fair share of the UK's fishing opportunities and to be involved in inshore fisheries management. They argue that their allocation of ∼2% of the UK Share of Total Allowable Catch species is unjust, with the inshore fleet contributing 78% of the workforce. Their concern, beyond quota shares, is that Local Ecological Knowledge / real time information from fishing grounds does not feature as information in the determination of the Marine Management Organisation's Fixed Quota Allocation pool. This is thought to be top down, inflexible and having limited potential for adaptive co-management. At the same time, this entails increased distrust for the Common Fisheries Policy, often through conflated ideas about who is to blame for the allocation of national quota within the UK. Once the overall Total Allowable Catch levels have been agreed on, every December at an EU wide level, fishing opportunities are given out by the member state. Many fishers and the wider public are surprised it is the member state's responsibility to assign access between fleets. Indeed, it is the Fixed Quota Allocation system which has left only 2% of the UK share of TAC species with inshore fishers, a decision which would benefit from a public enquiry. Leasing enough UK, Fixed Quota allocation Units is a barrier to entry for young fishers, as lease costs are high and inshore fisheries are mixed. An ageing knowledge base, with few new recruits to continue practising it, means the intergenerational transmission of fisher LEK is more at risk. Alongside this, the associated cultural value created by fisheries communities is under threat as a result of the inequality in terms of access to fishing opportunities. The newly recognised Coastal Producer Organisation could manage the 2% of the UK share of Total Allowable Catch, alongside promised ‘uplifts’ and any increases which may occur as a result of leaving the ‘relative stability’ system of EU Total Allowable Catch share. The Coastal Producer Organisation will listen to fishers and manage quota adaptively without permanently gifting fishing rights. Catchapp can be a way for members to integrate their fisher LEK to form the basis for real time updates to changes on fishing grounds. This can support determination in a scientifically robust manner improving on the previous monthly pool allocations for the seasonal mixed inshore fishery. This is an urgent requirement to improve buy in, compliance, confidence in science and foster adaptive co-management.
Exome Sequencing Identifies Glycosylation Defects As a Probable Cause of Immune Thrombotic Thrombocytopenic Purpura
Authors: Massicano Felipe , Staley Elizabeth M. , Halkidis Konstantine , Kocher Nicole K. , Williams Lance A. , Marques Marisa B. , Guillory Bryan K. , Cao Wenjing , Basu Malay K. , Zheng X. Long 
Published: February 2020

Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal syndrome, resulting primarily from autoantibodies against ADAMTS13. However, the mechanism underlying the autoantibody formation and the contribution of other genomic alterations to the pathogenesis of iTTP are largely unknown.
Methods: Whole exome sequencing (WES) and bioinformatic analyses were performed to determine the genetic variations in 40 patients with iTTP who had ADAMTS13 activity &lt;10 IU/dL and a positive inhibitor or an elevated anti-ADAMTS13 IgG in concordance with clinical presentations of severe thrombocytopenia and microangiopathic hemolytic anemia with various degrees of organ injury. WES was also performed at the same time in fifteen age-, gender-, and ethnicity- matched individuals who did not have a history of iTTP or other hematological disorders as controls.
Results: WES identified variants or mutations in the genes involving in glycosylation, including O-linked glycosylation, to be the major pathway affected in patients with iTTP. We propose that the altered glycosylation may be responsible for the development of autoantibodies against ADAMTS13 which impair the proteolytic cleavage of von Willebrand factor, accelerate the clearance of ADAMTS13 from circulation, and result in severe thrombocytopenia platelets in patients with iTTP. We also identified defects in ankyrin repeat containing protein ANKRD36C, a protein with hitherto unknown function, as the most statistically significant genomic alterations associated with iTTP (p &lt; 10-5). Moreover, candidate gene analysis revealed that various genes involving in hemostasis, complement activation, platelet function and signaling pathway, and inflammation were all affected in patients with iTTP, which may contribute to the onset, progress, severity, and long-term outcome of iTTP. Finally, we also identified two patient subgroups where the disease mechanism might be different.
Conclusion: Our findings provide novel insight into the pathogenic mechanism underlying ADAMTS13 autoantibody production and the potential contribution of other genetic abnormalities in modifying the iTTP clinical presentations in the individuals with severe deficiency of plasma ADAMTS13 activity.

Disclosures
Zheng: Alexion: Speakers Bureau; Ablynx/Sanofi: Consultancy, Speakers Bureau; Shire/Takeda: Research Funding; Clotsolution: Other: Co-Founder.
Eosinophils, basophils and type 2 immune microenvironments in COPD-affected lung tissue
Authors: Jogdand Prajakta , Siddhuraj Premkumar , Mori Michiko , Sanden Caroline , Jönsson Jimmie , Walls Andrew F. , Kearley Jennifer , Humbles Alison A. , Kolbeck Roland , Bjermer Leif , Newbold Paul , Erjefält Jonas S. 
Published: February 2020

Although elevated blood or sputum eosinophils are present in many patients with COPD, uncertainties remain regarding the anatomical distribution pattern of lung-infiltrating eosinophils. Basophils have remained virtually unexplored in COPD. This study mapped tissue-infiltrating eosinophils, basophils and eosinophil-promoting immune mechanisms in COPD-affected lungs.Surgical lung tissue and biopsies from major anatomical compartments were obtained from COPD patients with severity grades Global Initiative for Chronic Obstructive Lung Disease stages I–IV; never-smokers/smokers served as controls. Automated immunohistochemistry andin situhybridisation identified immune cells, the type 2 immunity marker GATA3 and eotaxins (CCL11, CCL24).Eosinophils and basophils were present in all anatomical compartments of COPD-affected lungs and increased significantly in very severe COPD. The eosinophilia was strikingly patchy, and focal eosinophil-rich microenvironments were spatially linked with GATA3+cells, including type 2 helper T-cell lymphocytes and type 2 innate lymphoid cells. A similarly localised and interleukin-33/ST2-dependent eosinophilia was demonstrated in influenza-infected mice. Both mice and patients displayed spatially confined eotaxin signatures with CCL11+fibroblasts and CCL24+macrophages.In addition to identifying tissue basophilia as a novel feature of advanced COPD, the identification of spatially confined eosinophil-rich type 2 microenvironments represents a novel type of heterogeneity in the immunopathology of COPD that is likely to have implications for personalised treatment.
Blood eosinophil count in the general population: typical values and potential confounders
Authors: Hartl Sylvia , Breyer Marie-Kathrin , Burghuber Otto C. , Ofenheimer Alina , Schrott Andrea , Urban Matthias H. , Agusti Alvar , Studnicka Michael , Wouters Emiel F.M. , Breyer-Kohansal Robab 
Published: February 2020

There is growing interest in blood eosinophil counts in the management of chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Despite this, typical blood eosinophil levels in the general population, and the impact of potential confounders on these levels have not been clearly defined.We measured blood eosinophil counts in a random sample of 11 042 subjects recruited from the general population in Austria. We then: 1) identified factors associated with high blood eosinophil counts (>75th percentile); and 2) excluded subjects with these factors to estimate median blood eosinophil counts in a “healthy” sub-population (n=3641).We found that: 1) in the entire cohort, age ≤18 years (OR 2.41), asthma (OR 2.05), current smoking (OR 1.72), positive skin prick test (OR 1.64), COPD (OR 1.56), metabolic syndrome (OR 1.41), male sex (OR 1.36) and obesity (OR 1.16) were significantly (p<0.05) associated with high blood eosinophil counts (binary multivariable logistic regression analysis), and had an additive effect; and 2) after excluding these factors, in those older than 18 years, blood eosinophil counts were higher in males than in females (median 120 (5%–95% CI: 30–330)versus100 (30–310) cells·µL−1, respectively) and did not change with age.Median blood eosinophil counts in adults are considerably lower than those currently regarded as normal, do not change with age beyond puberty, but are significantly influenced by a variety of factors which have an additive effect. These observations will contribute to the interpretation of blood eosinophil levels in clinical practice.
Adherence to inhaled corticosteroids and clinical outcomes in mepolizumab therapy for severe asthma
Authors: d'Ancona Gráinne , Kavanagh Joanne , Roxas Cris , Green Linda , Fernandes Mariana , Thomson Louise , Dhariwal Jaideep , Nanzer Alexandra M. , Jackson David J. , Kent Brian D. 
Published: February 2020

IntroductionInhaled corticosteroids (ICS) achieve disease control in the majority of asthmatic patients, although adherence to prescribed ICS is often poor. Patients with severe eosinophilic asthma may require treatment with oral corticosteroids (OCS) and/or biologic agents such as mepolizumab. It is unknown if ICS adherence changes on, or alters clinical response to, biologic therapy.MethodsWe examined ICS adherence and clinical outcomes in OCS-dependent severe eosinophilic asthma patients who completed 1 year of mepolizumab therapy. The ICS medicines possession ratio (MPR) was calculated (the number of doses of ICS issued on prescription/expected number) for the year before and the year after biologic initiation. Good adherence was defined as MPR >0.75, intermediate 0.74–0.51 and poor <0.5. We examined outcomes after 12 months of biologic therapy, including OCS reduction and annualised exacerbation rate (AER), stratified by adherence to ICS on mepolizumab.ResultsOut of 109 patients commencing mepolizumab, 91 who had completed 12 months of treatment were included in the final analysis. While receiving mepolizumab, 68% had good ICS adherence, with 16 (18%) having poor ICS adherence. ICS use within the cohort remained similar before (MPR 0.81±0.32) and during mepolizumab treatment (0.82±0.32; p=0.78). Patients with good adherence had greater reductions in OCS dose (median (interquartile range) OCS reduction 100 (74–100)%versus60 (27–100)%; p=0.031) and exacerbations (AER change −2.1±3.1versus0.3±2.5; p=0.011) than those with poor adherence. Good ICS adherence predicted the likelihood of stopping maintenance OCS (adjusted OR 3.19, 95% CI 1.02–9.94; p=0.045).ConclusionICS nonadherence is common in severe eosinophilic asthma patients receiving mepolizumab, and is associated with a lesser reduction in OCS requirements and AER.
Antibacterial activities of the extracts, fractions and isolated compounds from Canarium patentinervium Miq. against bacterial clinical isolates
Authors: Mogana R. , Adhikari A. , Tzar M. N. , Ramliza R. , Wiart C. 
Published: February 2020

AbstractBackgroundCanarium patentinerviumleaves are used by the local indigenous people of Malaysia for wound healing. The current study is undertaken to screen the comprehensive antibacterial activity of the leaves and barks extracts, fractions and isolated compounds from this plant. Bioassay guided fractionation was also undertaken to deeply evaluate the antibacterial activity of the water fraction of the leaves extract. This is to provide preliminary scientific evidence to the ethnopharmacology usage of this plant by investigating antibacterial properties of the plant and its isolated constituents.MethodsBio-assay guided fractionation and subsequent isolation of compounds using open column chromatography. The antibacterial activity against gram positive and gram negative ATCC strain and resistant clinical strains were evaluated using microtiter broth dilution method to determine minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assay. The chemical structure of the isolated compounds from the water fraction of the ethanol extract of leaves was elucidated using Nuclear Magnetic Resonance (NMR).ResultsThe ethanol extract of the leaves and barks showed antimicrobial activity against all four ATCC and eight clinical isolates. The ethanol extract of the leaves and the corresponding water fraction had good activity against MRSAS. aureus.(MIC: 250 μg/ml) and had bactericidal effect on eight of the clinical strains (MSSA,MRSA, oxacillin-resistant CONS, oxacillin-sensitive CONS,Enterococcus faecalis,Klebsielaspecies, Kleb pneumoniaeESBL andCandida parapsilosis). Further phytochemical investigation of the water fraction of the crude ethanol extract of leaves afforded compound 7 (hyperin) and compound 8 (cynaroside) that had bactericidal activity against tested bacterial species (MIC 50 μg/ml and 100 μg/ml). The two compounds were isolated from this genus for the first time.ConclusionsThese results may provide a rational support for the traditional use ofCanarium patentinerviumMiq. in infections and wound healing, since the antimicrobial compounds isolated were also present in the leaves extract.
Hospitalisation and mortality in patients with comorbid COPD and heart failure: a systematic review and meta-analysis
Authors: Axson Eleanor L. , Ragutheeswaran Kishan , Sundaram Varun , Bloom Chloe I. , Bottle Alex , Cowie Martin R. , Quint Jennifer K. 
Published: February 2020

AbstractBackgroundDiscrepancy exists amongst studies investigating the effect of comorbid heart failure (HF) on the morbidity and mortality of chronic obstructive pulmonary disease (COPD) patients.MethodsMEDLINE and Embase were searched using a pre-specified search strategy for studies comparing hospitalisation, rehospitalisation, and mortality of COPD patients with and without HF. Studies must have reported crude and/or adjusted rate ratios, risk ratios, odds ratios (OR), or hazard ratios (HR).ResultsTwenty-eight publications, reporting 55 effect estimates, were identified that compared COPD patients with HF with those without HF. One study reported on all-cause hospitalisation (1 rate ratio). Two studies reported on COPD-related hospitalisation (1 rate ratio, 2 OR). One study reported on COPD- or cardiovascular-related hospitalisation (4 HR). One study reported on 90-day all-cause rehospitalisation (1 risk ratio). One study reported on 3-year all-cause rehospitalisation (2 HR). Four studies reported on 30-day COPD-related rehospitalisation (1 risk ratio; 5 OR). Two studies reported on 1-year COPD-related rehospitalisation (1 risk ratio; 1 HR). One study reported on 3-year COPD-related rehospitalisation (2 HR). Eighteen studies reported on all-cause mortality (1 risk ratio; 4 OR; 24 HR). Five studies reported on all-cause inpatient mortality (1 risk ratio; 4 OR). Meta-analyses of hospitalisation and rehospitalisation were not possible due to insufficient data for all individual effect measures. Meta-analysis of studies requiring spirometry for the diagnosis of COPD found that risk of all-cause mortality was 1.61 (pooled HR; 95%CI: 1.38, 1.83) higher in patients with HF than in those without HF.ConclusionsIn this systematic review, we investigated the effect of HF comorbidity on hospitalisation and mortality of COPD patients. There is substantial evidence that HF comorbidity increases COPD-related rehospitalisation and all-cause mortality of COPD patients. The effect of HF comorbidity may differ depending on COPD phenotype, HF type, or HF severity and should be the topic of future research.
Taking the ‘I’ out of LLINs: using insecticides in vector control tools other than long-lasting nets to fight malaria
Authors: Paaijmans Krijn P. , Huijben Silvie 
Published: February 2020

AbstractLong-lasting insecticidal nets, or LLINs, have significantly reduced malaria morbidity and mortality over the past two decades. The net provides a physical barrier that decreases human-mosquito contact and the impregnated insecticide kills susceptible mosquito vectors upon contact and may repel them. However, the future of LLINs is threatened as resistance to pyrethroids is now widespread, the chemical arsenal for LLINs is very limited, time from discovery of next-generation insecticides to market is long, and persistent transmission is frequently caused by vector populations avoiding contact with LLINs. Here we ask the question whether, given these challenges, insecticides should be incorporated in nets at all. We argue that developing long-lasting nets without insecticide(s) can still reduce vector populations and provide both personal and community protection, if combined with other approaches or technologies. Taking the insecticide out of the equation (i) allows for a faster response to the current pyrethroid resistance crisis, (ii) avoids an LLIN-treadmill aimed at replacing failing bed nets due to insecticide resistance, and (iii) permits the utilization of our current and future insecticidal arsenal for other vector control tools to target persistent malaria transmission.
The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil
Authors: Ishak Ricardo , de Oliveira Guimarães Ishak Marluísa , Vallinoto Antonio Carlos R. 
Published: February 2020

AbstractHTLV-1 was the first described human retrovirus and was soon found to be associated with severe clinical diseases, including a devastating lymphoma/leukemia and other inflammatory diseases. Although HTLV-2 is not usually pathogenic, it is widely distributed among native Indian populations in Brazil, particularly in the Amazon region of the country. Presently, HTLV spreads mainly by the sexual route and from mother to child, and virus persistence is an active biological factor aiding its transmission. Recently, the use of illicit drugs has been shown to be an additional risk factor, showing the influence of new habits on the epidemiology of HTLV in the region. Despite the detection of the virus in several different populations in the Amazon region of Brazil for almost 30 years, the exact prevalence of HTLV-1/2 is not well defined. The original biases in sampling and the selection of epidemiologically unsuitable populations were commonly repeated in most prevalence studies, generating unreliable and conflicting figures that do not represent the actual prevalence of HTLV. The improvements in clinical and laboratory facilities have resulted in the description of several clinical manifestations that were previously unknown in the region. The extent of the spread of the virus must be defined in this region, which is the largest geographical area of the country. As prophylaxis advances toward the use of vaccines against HTLV-1, it is important to determine who is at risk of being infected and developing a disease to successfully implement preventive measures, particularly as proposals are made to eradicate the virus among humans.
A willow sex chromosome reveals convergent evolution of complex palindromic repeats
Authors: Zhou Ran , Macaya-Sanz David , Carlson Craig H. , Schmutz Jeremy , Jenkins Jerry W. , Kudrna David , Sharma Aditi , Sandor Laura , Shu Shengqiang , Barry Kerrie , Tuskan Gerald A. , Ma Tao , Liu Jianquan , Olson Matthew , Smart Lawrence B. , DiFazio Stephen P. 
Published: February 2020

AbstractBackgroundSex chromosomes have arisen independently in a wide variety of species, yet they share common characteristics, including the presence of suppressed recombination surrounding sex determination loci. Mammalian sex chromosomes contain multiple palindromic repeats across the non-recombining region that show sequence conservation through gene conversion and contain genes that are crucial for sexual reproduction. In plants, it is not clear if palindromic repeats play a role in maintaining sequence conservation in the absence of homologous recombination.ResultsHere we present the first evidence of large palindromic structures in a plant sex chromosome, based on a highly contiguous assembly of the W chromosome of the dioecious shrubSalix purpurea. The W chromosome has an expanded number of genes due to transpositions from autosomes. It also contains two consecutive palindromes that span a region of 200 kb, with conspicuous 20-kb stretches of highly conserved sequences among the four arms that show evidence of gene conversion. Four genes in the palindrome are homologous to genes in the sex determination regions of the closely related genusPopulus, which is located on a different chromosome. These genes show distinct, floral-biased expression patterns compared to paralogous copies on autosomes.ConclusionThe presence of palindromes in sex chromosomes of mammals and plants highlights the intrinsic importance of these features in adaptive evolution in the absence of recombination. Convergent evolution is driving both the independent establishment of sex chromosomes as well as their fine-scale sequence structure.
DNA methylation-driven EMT is a common mechanism of resistance to various therapeutic agents in cancer
Authors: Galle Eva , Thienpont Bernard , Cappuyns Sarah , Venken Tom , Busschaert Pieter , Van Haele Matthias , Van Cutsem Eric , Roskams Tania , van Pelt Jos , Verslype Chris , Dekervel Jeroen , Lambrechts Diether 
Published: February 2020

Abstract
Background
Overcoming therapeutic resistance is one of the major hurdles in cancer care. One mechanism contributing to therapeutic resistance is a process in which epithelial cells switch to a mesenchymal state (epithelial-to-mesenchymal transition or EMT). The precise mechanisms driving EMT-mediated therapeutic resistance have, however, not been elucidated.

Results
Here, we study ten cell line pairs, for which parental cell lines were made resistant to either a targeted or chemotherapy-based treatment. First, we show by miRNA-200 overexpression that treatment resistance is driven by EMT. Next, we demonstrate that DNA methylation changes occur within each cell line pair and show that exposure to 5-azacytidine or knock down of DNA methyltransferases (DNMTs), both of which globally demethylate cells, result in EMT reversal and increased therapeutic sensitivity. This suggests DNA methylation to causally underlie EMT and treatment resistance. We also observe significant overlap in methylation profiles between resistant lines, suggesting a common epigenetic mechanism to cause resistance to therapy. In line with this hypothesis, cross-resistance to other targeted and chemotherapies is observed, while importantly, this is lost upon demethylation of the cells. Finally, we clinically validate that DNA methylation changes drive EMT-mediated resistance to sorafenib in patients with advanced hepatocellular carcinoma (HCC). Specifically, we develop a capture-based protocol to interrogate DNA methylation in low amounts of circulating tumor DNA (ctDNA). By interrogating the methylation status in liquid biopsies, longitudinally collected during sorafenib treatment, we assess whether DNA methylation changes also drive EMT and therapy resistance in a clinical setting. Particularly, by monitoring methylation changes in EMT genes, we are able to predict tumor response and acquired resistance to sorafenib.

Conclusions
We propose methylation changes underlying EMT to constitute a common resistance mechanism to cancer therapies. This process can be reversed pharmacologically and monitored non-invasively in ctDNA to predict resistance to treatment.