bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of invasive fungal infections in lung transplant recipients in Western Australia
Authors: Chang Andrew , Musk Michael , Lavender Melanie , Wrobel Jeremy , Yaw Meow‐Chong , Lawrence Sharon , Chirayath Shiji , Boan Peter 
Published: March 2019

AbstractBackgroundInvasive fungal infections (IFI) are common after lung transplantation with reported incidence of 8.1% to 16% at 12 months post‐transplant, and 3‐month all‐cause mortality after IFI of 21.7%.MethodsWe performed a retrospective study of IFI and fungal colonization in lung transplants (LTs) from November 2004 to February 2017.Results137 LTs were followed for a median 4.1 years (IQR 2.1‐6.2 years). In addition to nebulized amphotericin for the transplant admission to all LTs, systemic mold‐active azole was given to 80/130 (61.5%) LTs in the first 6 months post‐transplant, 57/121 (47.1%) in the period 6‐12 months after transplant, and 93/124 (75%) in the period more than 12 months post‐transplant. Mold airways colonization was found in 81 (59.1%) LTs before and 110 (80.3%) LTs after transplantation. There were 13 IFIs for an overall incidence of 2.1 per 100 person‐years, occurring at a median 583 days (IQR 182‐1110 days) post‐transplant, a cumulative incidence of 3.8% at 1 year, 7.6% at 3 years and 10.1% at 5 years post‐transplant. All‐cause 3‐month mortality after IFI was 7.7%. Aspergillus species followed by Scedosporium apiospermum and Cryptococcus species were the commonest fungi causing IFI.ConclusionsIn our cohort the rate of IFI was comparatively low, likely because of comprehensive early antifungal use and preemptive therapy at any time after transplant. Prospective studies of fungal colonization late after LT are required to determine the risks and benefits of watchful waiting compared to preemptive therapy.
Membraneless organelles: P granules in Caenorhabditis elegans
Authors: Marnik Elisabeth A. , Updike Dustin L. 
Published: March 2019

AbstractMembraneless organelles are distinct compartments within a cell that are not enclosed by a traditional lipid membrane and instead form through a process called liquid‐liquid phase separation. Examples of these non‐membrane‐bound organelles include nucleoli, stress granules, P bodies, pericentriolar material and germ granules. Many recent studies have used Caenorhabditis elegans germ granules, known as P granules, to expand our understanding of the formation of these unique cellular compartments. From this work, we know that proteins with intrinsically disordered regions (IDRs) play a critical role in the process of phase separation. IDR phase separation is further tuned through their interactions with RNA and through protein modifications such as phosphorylation and methylation. These findings from C elegans, combined with work done in other model organisms, continue to provide insight into the formation of membraneless organelles and the important role they play in compartmentalizing cellular processes.
Thromboelastographic platelet mapping in dogs with complicated Babesia rossi infection
Authors: van Rooyen Liesl J. , Hooijberg Emma H. , Schoeman Johan P. , Goddard Amelia 
Published: March 2019

BackgroundDogs with Babesia rossi infection display a normocoagulable thromboelastogram, despite being markedly thrombocytopenic, which is purportedly due to large‐scale platelet activation. Thromboelastographic platelet mapping (TEG‐PM) evaluates individual contributions of thrombin, fibrinogen, and platelets to clot formation, and may elucidate some of the pathomechanisms of thrombocytopenia‐associated hemostatic alterations.ObjectiveThis study investigated potential differences in TEG‐PM variables in dogs with complicated B rossi infection compared with healthy controls, and whether these variables correlated with platelet activation indices.MethodsThe maximum amplitude (MA) following thrombin generation (MAThrombin) was determined using kaolin‐activated TEG. The TEG‐PM variables included MA following the addition of platelet agonists arachidonic acid (MAAA) and adenosine diphosphate (MAADP), and MA due to fibrin alone (MAFibrin). In addition, platelet indices and fibrinogen concentrations were determined.ResultsThirteen dogs with complicated B rossi infection and five healthy controls were included. The median MAFibrin and fibrinogen concentrations were significantly higher (P < 0.01 for both) and median platelet count was significantly lower (P < 0.01) in the babesiosis group vs the control group. No significant differences were found for MAThrombin and MAAA/ADP. maximum amplitude due to fibrin alone was positively correlated with fibrinogen concentration (r = 0.735), mean platelet volume (r = 0.517), and mean platelet mass (r = 0.498), and negatively correlated with hematocrit (r = −0.685), platelet count (r = −0.476), and plateletcrit (r = −0.479) (P < 0.05 for all).ConclusionsThis study suggests that the presence of hyperfibrinogenemia offsets the severe thrombocytopenia associated with B rossi to result in normal thromboelastograms and lack of overt clinical bleeding.
<p class="Body">Predation, prey preference and reproduction of predatory mites Amblydromalus limonicus (Garman), Amblyseius herbicolus (Chant) and Neoseiulus cucumeris (Oudemans) (Mesostigmata: Phytoseiidae) on immature Sericothrips staphylinus Haliday (Thysanoptera: Thripidae), a biocontrol agent of gorse
Authors: Lam Wendy , Paynter Quentin , Zhang Zhi-Qiang 
Published: March 2019

Gorse, Ulex europaeus, is an invasive weed that has serious agricultural, economic and ecological impacts. Although various biological control agents have been released in New Zealand, these have showed no noticeable impact on gorse populations. One such agent, Sericothrips staphylinus, was introduced to New Zealand in 1990 and although laboratory impact studies indicated it was a highly promising gorse biological control agent, it has not been as effective as was hoped. We hypothesized this was due to predation by natural enemies. This study investigated the predation and oviposition rates of three phytoseiid mites (Amblydromalus limonicus, Amblyseius herbicolus, and Neoseiulus cucumeris) that have been found on gorse plants in New Zealand on three S. staphylinus stages (1st instar larvae, 2nd instar larvae, and prepupa) in both choice and non-choice conditions. In non-choice conditions, A. limonicus had the highest predation and oviposition rate across all three immature stages, and N. cucumeris had the lowest. Amblydromalus limonicus, A. herbicolus, and N. cucumeris all had their highest predation rate when consuming 1st instar larvae, and their lowest predation rate when consuming prepupa. In the choice experiment, all three predatory mite species consumed their highest proportion of 1st instar larvae, and their lowest proportion of prepupae. The oviposition rate of all three mite species in the choice experiment was similar to the oviposition rate when presented with 1st instar larvae only. The results from this study confirm that A. limonicus, A. herbicolus, and N. cucumeris can predate and reproduce on S. staphylinus 1st instar larvae, 2nd instar larvae, and prepupa. This indicates that predation may be the reason why S. staphylinus is an ineffective biocontrol agent in New Zealand.
Geographic Mapping of Escherichia coli Susceptibility To Develop a Novel Clinical Decision Support Tool
Authors: Legenza Laurel , Barnett Susanne , Lacy James P. , See Codie , Desotell Natalee , Eibergen Andrea , Piccirillo Jeffrey F. , Rose Warren E. 
Published: March 2019

Antimicrobial resistance (AMR) varies regionally. This study longitudinally maps
Escherichia coli
susceptibility leveraging Wisconsin antibiograms (
n
= 202) collected from 2009, 2013, and 2015 to inform the development of a novel clinical decision support tool.
Spatial and temporal trends in exhumation of the Eastern Himalaya and syntaxis as determined from a multitechnique detrital thermochronological study of the Bengal Fan
Authors: Najman Yani , Mark Chris , Barfod Dan N. , Carter Andy , Parrish Randy , Chew David , Gemignani Lorenzo 
Published: March 2019

AbstractThe Bengal Fan provides a Neogene record of Eastern and Central Himalaya exhumation. We provide the first detrital thermochronological study (apatite and rutile U-Pb, mica Ar-Ar, zircon fission track) of sediment samples collected during International Ocean Discovery Program (IODP) Expedition 354 to the mid–Bengal Fan. Our data from rutile and zircon fission-track thermochronometry show a shift in lag times over the interval 5.59–3.47 Ma. The oldest sample with a lag time of <1 m.y. has a depositional age between 3.76 and 3.47 Ma, and these short lag times continue to be recorded upward in the core to the youngest sediments analyzed, deposited at <1 Ma. We interpret the earliest record of short lag times to represent the onset of extremely rapid exhumation of the Eastern Himalayan syntaxial massif, defined as the syntaxial region north of the Nam La Thrust. Below the interval characterized by short lag times, the youngest sample analyzed with long lag times (>6 m.y.) has a depositional age of 5.59–4.50 Ma, and the zircon and rutile populations then show a static peak until >12 Ma. This interval, from 5.59–4.50 Ma to >12 Ma, is most easily interpreted as recording passive erosion of the Greater Himalaya. However, single grains with lag times of <4 m.y., but with high analytical uncertainty, are recorded over this interval. For sediments older than 10 Ma, these grains were derived from the Greater Himalaya, which was exhuming rapidly until ca. 14 Ma. In sediments younger than 10 Ma, these grains could represent slower, yet still rapid, exhumation of the syntaxial antiform to the south of the massif. Lag times <1 m.y. are again recorded from 14.5 Ma to the base of the studied section at 17 Ma, reflecting a period of Greater Himalayan rapid exhumation. Mica 40Ar/39Ar and apatite U-Pb data are not sensitive to syntaxial exhumation: We ascribe this to the paucity of white mica in syntaxial lithologies, and to high levels of common Pb, resulting in U-Pb ages associated with unacceptably high uncertainties, respectively.
Falling admissions to hospital with febrile seizures in the UK
Authors: Mccrorie Kirsty , Thorburn Joshua , Symonds Joseph , Turner Stephen W 
Published: March 2019

ObjectivesThere was a reduction in febrile seizure admissions in Scotland after 2008. Our hypothesis was that a similar trend would be seen in other countries.MethodsWe obtained the number of febrile and non-febrile seizure admissions in England and Scotland 2000–2013 and the incidence of all seizure admissions 2000–2013 in European countries. We compared the incidence of admission for febrile seizure (Scotland and England) and all seizures (all countries) between 2000–2008 and 2009–2013.ResultsThe incidence of febrile seizure admissions per 1000 children in 2009–2013 was lower than 2000–2008 in Scotland (0.79 vs 1.08, p=0.001) and England (0.92 vs 1.20, p<0.001). The incidence of all seizure admissions (but not non-febrile seizures) was lower in 2009–2013 compared with 2000–2008 in Scotland (1.84 vs 2.20, p=0.010) and England (2.71 vs 2.91, p=0.001). Across 12 European countries (including the UK), there was no difference in all seizure admissions after 2008. We explored the possibility that the fall was related to the introduction of routine pneumococcal vaccination in 2006 but there were insufficient data.ConclusionA fall in admissions for febrile (but not afebrile) seizures after 2008 in Scotland and England explains a fall in all emergency admissions for seizure. A fall in all seizure admissions has not occurred in other European countries, and more research is required to understand the different outcomes in the UK and non-UK countries.
Five-year outcomes of retinal vein occlusion treated with vascular endothelial growth factor inhibitors
Authors: Spooner Kimberly , Fraser-Bell Samantha , Hong Thomas , Chang Andrew A 
Published: March 2019

PurposeReport 5-year outcomes of patients receiving anti-vascular endothelial growth factor (VEGF) for the treatment of macular oedema secondary to retinal vein occlusion (RVO.MethodsRetrospective review of eyes with RVO which initiated anti-VEGF treatment. Data including age, gender, visual acuity (VA) and injection numbers were obtained from medical records. Optical coherence tomography scans were graded for presence or absence of macular oedema and central foveal thickness (CFT). Macular perfusion was assessed on fundus fluorescein angiography by masked graders.Results68 eyes (31 branch RVO, BRVO; 35 central RVO, CRVO and 2 hemi-RVO) with 5 years of follow-up after initiation of anti-VEGF treatment. Mean change in VA at 5 years was + 9.6 ± 21.6 letters among CRVO eyes and + 14.2 ± 15.6 letters among eyes with BRVO (p=0.001). Vision of 20/40 or better was achieved in 65 % of treated eyes. The proportion of eyes with a three-line improvement of vision (15 letters) at 5 years was 22 %. Mean CFT decreased by 257.6 ± 249.8 µm in eyes with CRVO and 145.6 ± 143.3 µm in eyes with BRVO.ConclusionThe results confirm good long-term outcomes can be achieved with anti-VEGF therapy for RVO.
Importance of publishing research varies by doctors’ career stage, specialty and location of work
Authors: McGrail Matthew Richard , O’sullivan Belinda G , Bendotti Hollie R , Kondalsamy-Chennakesavan Srinivas 
Published: March 2019

AbstractPurposeTo investigate whether publishing research is an important aspect of medical careers, and how it varies by specialty and rural or metropolitan location.MethodsAnnual national panel survey (postal or online) of Australian doctors between 2008 and 2016, with aggregated participants including 11 263 junior doctors not enrolled in a specialty (‘pre-registrars’), 9745 junior doctors enrolled as specialist trainees, non-general practitioner (GP) (‘registrars’) and 35 983 qualified as specialist consultants, non-GP (‘consultants’). Main outcome was in agreement that ‘research publications are important to progress my training’ (junior doctors) or ‘research publications are important to my career’ (consultants).ResultsOverall, the highest proportion agreeing were registrars (65%) and pre-registrars (60%), compared with consultants (36%). After accounting for key covariates, rural location was significantly associated with lower importance of publishing research for pre-registrars (OR 0.69, 95% CI 0.61 to 0.78) and consultants (OR 0.69, 95% CI 0.63 to 0.76), but not for registrars. Compared with anaesthetics, research importance was significantly higher for pre-registrars pursuing surgery (OR 4.46, 95% CI 3.57 to 5.57) and obstetrics/gynaecology careers, for registrars enrolled in surgery (OR 2.97, 95% CI 2.34 to 3.75) and internal medicine training, and consultants of internal medicine (OR 1.84, 95% CI 1.63 to 2.08), pathology, radiology and paediatrics.ConclusionsThis study provides new quantitative evidence showing that the importance of publishing research is related to medical career stages, and is most important to junior doctors seeking and undertaking different specialty training options. Embedding research requirements more evenly into specialty college selection criteria may stimulate uptake of research. Expansion of rural training pathways should consider capacity building to support increased access to research opportunities in these locations.
Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54
Authors: Alten Rieke , Batko Bogdan , Hala Tomas , Kameda Hideto , Radominski Sebastiao C , Tseluyko Vira , Babic Goran , Cronenberger Carol , Hackley Sarah , Rehman Muhammad , von Richter Oliver , Zhang Min , Cohen Stanley 
Published: March 2019

ObjectiveTo investigate the efficacy, safety and immunogenicity of PF-06438179/GP1111 (PF-SZ-IFX) compared with European reference infliximab (Remicade®; ref-IFX) in patients with moderate-to-severe, active rheumatoid arthritis after continued long-term use of PF-SZ-IFX, and in patients who were switched from ref-IFX to PF-SZ-IFX.MethodsREFLECTIONS B537-02 was a double-blind, active-controlled, multinational study in which patients (N=650) were initially randomised to PF-SZ-IFX or ref-IFX for 30 weeks (treatment period [TP] 1). During weeks 30–54 (TP2), the PF-SZ-IFX group (n=280) continued treatment with PF-SZ-IFX (PF-SZ-IFX/PF-SZ-IFX) and patients in the ref-IFX group (n=286) were rerandomised (1:1) to continue ref-IFX (ref-IFX/ref-IFX) (n=143) or switch to PF-SZ-IFX (ref-IFX/PF-SZ-IFX) (n=143) for a further 24 weeks. Efficacy, safety, immunogenicity and pharmacokinetics were evaluated.ResultsDuring TP2, patients in all three treatment groups continued to maintain comparable treatment response. At week 54, the American College of Rheumatology (ACR20) response rates were 71.1% (PF-SZ-IFX/PF-SZ-IFX), 64.3% (ref-IFX/ref-IFX) and 70.6% (ref-IFX/PF-SZ-IFX). Observations for other endpoints, including ACR50/70, Disease Activity Score in 28 Joints Based on High-Sensitivity C Reactive Protein(DAS28-CRP) remission, and mean change in DAS28-CRP and Health Assessment Questionnaire-Disability Index, were also comparable. Treatment-emergent adverse events were reported in 36.8% (PF-SZ-IFX/PF-SZ-IFX), 33.6% (ref-IFX/ref-IFX) and 37.8% (ref-IFX/PF-SZ-IFX) of patients; there were no clinically meaningful differences in the safety profiles between groups. The percentage of patients who were antidrug antibody-positive was generally stable through the treatment period and comparable overall between the PF-SZ-IFX/PF-SZ-IFX (52.1%; neutralising: 80.8%), ref-IFX/ref-IFX (60.1%; neutralising: 84.9%) and ref-IFX/PF-SZ-IFX (58.0%; neutralising 78.3%) groups.ConclusionsThe similar efficacy, safety and immunogenicity of PF-SZ-IFX compared with ref-IFX were maintained for up to 54 weeks and were not affected by blinded treatment switch from ref-IFX to PF-SZ-IFX at week 30.Trial registration numberNCT02222493.
Determining finite strain: how far have we progressed?
Authors: McCarthy Dave , Meere Patrick , Mulchrone Kieran 
Published: March 2019

Abstract

One of the main aims in the field of structural geology is the identification and quantification of deformation or strain. This pursuit has occupied geologists since the 1800s, but has evolved dramatically since those early studies. The quantification of strain in sedimentary lithologies was initially restricted to lithologies of known initial shape, such as fossils or reduction spots. In 1967, Ramsay presented a series of methods and calculations, which allowed populations of clasts to be used as strain markers. These methods acted as a foundation for modern strain analysis, and have influenced thousands of studies. This review highlights the significance of Ramsay's contribution to modern strain analysis. We outline the advances in the field over the 50 years since publication of
Folding and Fracturing of Rocks
, review the existing limitations of strain analysis methods and look to future developments.
Apoptosis signal-regulating kinase 1 activation by Nox1-derived oxidants is required for TNFα receptor endocytosis
Authors: Choi Hyehun , Stark Ryan J. , Raja Benjamin S. , Dikalova Anna , Lamb Fred S. 
Published: March 2019

Tumor necrosis factor-α (TNFα) is a proinflammatory cytokine that is closely linked to the development of cardiovascular disease. TNFα activates NADPH oxidase 1 (Nox1) and reactive oxygen species (ROS), including superoxide (O2·−), production extracellularly is required for subsequent signaling in vascular smooth muscle cells (VSMCs). Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that is activated by oxidation of associated thioredoxin. The role of ASK1 in Nox1-mediated signaling by TNFα is poorly defined. We hypothesized that ASK1 is required for TNFα receptor endocytosis and subsequent inflammatory TNFα signaling. We employed a knockdown strategy to explore the role of ASK1 in TNFα signaling in VSMCs. siRNA targeting ASK1 had no effect on TNFα-induced extracellular O2·− production. However, siASK1 inhibited receptor endocytosis as well as phosphorylation of two endocytosis-related proteins, dynamin1 and caveolin1. Intracellular O2·− production was subsequently reduced, as were other inflammatory signaling steps including NF-κB activation, IL-6 production, inducible nitric oxide synthase and VCAM expression, and VSMC proliferation. Prolonged exposure to TNFα (24 h) increased tumor necrosis factor receptor (TNFR) subtype 1 and 2 expression, and these effects were also attenuated by siASK1. ASK1 coimmunoprecipitated with both Nox1 and the leucine rich repeat containing 8A anion channel, two essential components of the TNFR1 signaling complex. Activation of ASK1 by autophosphorylation at Thr845 occurs following thioredoxin dissociation, and this requires the presence of Nox1. Thus, Nox1 is part of the multiprotein ASK1 signaling complex. In response to TNFα, ASK1 is activated by Nox1-derived oxidants, and this plays a critical role in translating these ROS into a physiologic response in VSMCs. NEW & NOTEWORTHY Apoptosis signal-regulating kinase 1 (ASK1) drives dynamin1 and caveolin1 phosphorylation and TNFα receptor endocytosis. ASK1 modulates TNFα-induced NF-κB activation, survival, and proliferation. ASK1 and NADPH oxidase 1 (Nox1) physically associate in a multiprotein signaling complex. Nox1 is required for TNFα-induced ASK1 activation.
Transient inhibition of neddylation at neonatal stage evokes reversible cardiomyopathy and predisposes the heart to isoproterenol-induced heart failure
Authors: Zou Jianqiu , Ma Wenxia , Littlejohn Rodney , Li Jie , Stansfield Brian K. , Kim Il-man , Liu Jinbao , Zhou Jiliang , Weintraub Neal L. , Su Huabo 
Published: March 2019

Alterations in perinatal conditions (such as preterm birth) is linked to adult health and disease, in particular, the cardiovascular system. Neddylation, a novel posttranslational modification through which the ubiquitin-like protein NEDD8 is conjugated to protein substrates, has emerged as an important mechanism regulating embryonic cardiac chamber maturation. However, the importance of neddylation in postpartum cardiac development has not been investigated. Here, we aimed to determine whether transient, postnatal inhibition of neddylation has immediate and prolonged impact on the structure and function of the neonatal and adult hearts. Sprague-Dawley pups were given three intraperitoneal injections of MLN4924 (MLN), a specific neddylation inhibitor, at postnatal days (P)1, 3, and 5. Cardiac structure and function were temporally assessed during aging and after 2 wk of isoproterenol (ISO) infusion in adulthood. MLN treatment resulted in modest reduction of neddylated proteins in neonatal hearts. The MLN-treated rats developed cardiac hypertrophy and dysfunction by P7, which was accompanied by significantly reduced cardiomyocyte proliferation. At 3 mo of age, cardiac contractile function was restored in MLN-treated rats, but MLN-treated hearts displayed hypertrophic phenotype. Whereas ISO infusion triggered compensatory cardiac hypertrophy without impairing cardiac contractility in the control rats, the MLN-treated rats displayed a similar degree of hypertrophy, which quickly progressed to decompensation with ventricular wall thinning, chamber dilatation, and reduced ejection fraction as well as exacerbated pathological cardiac remodeling. Our findings suggest that neddylation is required for postnatal cardiac development and that perturbation of neddylation during development predisposes adult hearts to cardiac failure under stress conditions. NEW & NOTEWORTHY Our study demonstrates that perinatal perturbation of neddylation induces cardiomyopathy, impairs postnatal cardiac development, and increases susceptibility to catecholamine-induced cardiac dysfunction. The results reveal a previously unappreciated role of neddylation in postnatal cardiac maturation and call for close monitoring for the potential cardiotoxicity of MLN4924 (pevonedistat) and other agents that modify neddylation, especially in pregnant women and preadolescents.