bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre‐specified analysis of the Chinese population from the BERSON clinical trial
Authors: Chen Yundai , Yuan Zuyi , Lu Juming , Eliaschewitz Freddy G. , Lorenzatti Alberto J. , Monsalvo Maria Laura , Wang Nan , Hamer Andrew W. , Ge Junbo 
Published: March 2019

AimThe aim of this study was to evaluate the efficacy and safety of evolocumab with background atorvastatin in Chinese patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia.Materials and methodsThis is a pre‐specified analysis of patients in the BERSON study (ClinicalTrials.gov, NCT02662569) in China. Patients initiated background atorvastatin 20 mg/d, after which they were randomized 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or to placebo Q2W or QM. Co‐primary endpoints were percentage change in LDL cholesterol (LDL‐C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures and adverse events (AEs).ResultsAmong 453 patients randomized in China, 451 received at least one dose of study drug (evolocumab or placebo). Evolocumab significantly reduced LDL‐C compared with placebo at week 12 (Q2W, −85.0%; QM, −74.8%) and at the mean of weeks 10 and 12 (Q2W, −80.4%; QM, −81.0%) (adjusted P < 0.0001 for all) when administered with background atorvastatin. Non‐HDL‐C, ApoB100, total cholesterol, Lp(a), triglycerides, HDL‐C and VLDL‐C significantly improved with evolocumab vs placebo. No new safety findings were observed with evolocumab. The incidence of diabetes AEs was higher with evolocumab compared with placebo. There were no differences over time between evolocumab and placebo in measures of glycaemic control.ConclusionsIn patients in China with T2DM and hyperlipidaemia or mixed dyslipidaemia receiving background atorvastatin, evolocumab significantly reduced LDL‐C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.
Successful catheter ablation of atrial fibrillation improves but not reverses the abnormalities of left atrial mechanics and energy loss
Authors: Lin Mingjie , Hao Li , Cao Yuan , Zhao Yachao , Rong Bing , Han Wenqiang , Xie Fei , Zhong Jingquan 
Published: March 2019

BackgroundDissipative energy loss (EL), a new index to quantify the inefficient blood flow, has not been explored within left atrium (LA) in patients with atrial fibrillation (AF). We aimed to study the intra‐atrial flow and mechanics in patients with AF before and after successful catheter ablation by evaluating EL and LA global longitudinal strain (LAS).MethodsIn our study, there were 53 patients undergoing catheter ablation for AF at baseline (AF group) and 33 age‐ and sex‐matched controls. They were both assessed of LA EL using vector flow mapping (VFM) and of LAS using two‐dimensional tracking (2DTT) during systole (sys), early diastole (ed), and atrial contraction phase (ac). Out of 53 patients, 37 patients who sustained sinus rhythm and carried out the echocardiographic examination at 3 and 6 months follow‐up were evaluated of change in EL and LAS. The independent predictors of EL during three phases in AF group were performed using stepwise multivariate linear regression analyses.ResultsLeft atrium EL and LAS among all phases in AF group were significantly lower than controls (all P < 0.01). During follow‐up, LASsys and LASac both significantly improved at 3 and 6 months (both P < 0.01), and ELac significantly increased after 6 months (P < 0.05); ELsys, ELed and LASed were no significant change; EL and LAS among all phases were no normalized during follow‐up. The independent predictors of EL were: for ELsys, BSA (P = 0.004) and LASac (P = 0.025); for ELed, E (P = 0.001) and A (P = 0.014); for ELac, E/A (P < 0.001).ConclusionVector flow mapping and 2DTT revealed impaired intra‐atrial flow and mechanics. Successful catheter ablation for AF slightly improves but not reverses the aforementioned impairment, indicating the continuous LA dysfunction.
Fitness and microbial networks of the common wasp,Vespula vulgaris(Hymenoptera: Vespidae), in its native and introduced ranges
Authors: Gruber Monica A. M. , Quinn Oliver , Baty James W. , Dobelmann Jana , Haywood John , Wenseleers Tom , Lester Philip J. 
Published: March 2019

1. Variation in microbial communities between populations is increasingly hypothesised to affect animal fitness and performance, including for invasive species. Pathogenic species may be lost during the introduction process, enhancing invader fitness and abundance.2. This study assessed fitness, immune gene expression, and microbial network complexity of invasive common wasps,Vespula vulgaris. Microbial networks were assayed using 16S and 18S sequencing and gene expression arrays in the native (Belgium) and introduced range (New Zealand). The immune gene expression of the waspDown syndrome cell adhesion molecule(Dscam) gene homologue was examined.Dscamexpression can be induced by viruses, Gram‐positive and Gram‐negative bacteria, and parasites.3. Individual nest fitness was higher in the native range of Belgium than in the introduced New Zealand range. Microbial communities of wasps in the introduced range were more diverse with more complex networks, although some microorganisms were range‐specific. Microbial networks in the introduced range showed higher clustering coefficients, number of connected paths, network centralisation, number of neighbours and network density.4. Larvae, workers, virgin and foundress queens had higher expression ofDscamin the New Zealand samples. These immune gene expression patterns were associated with higher pathogen pressure and lower relative fitness.5. Epidemiological theory predicts that a high density of pathogen and microbial hosts should result in a high rate of disease infection, prevalence, and highly connected microbial networks. The results of this study support these predictions. Wasps displayed lower relative fitness and more highly connected microbial networks in New Zealand than in Belgium.
SKA1 induces de novo MTX‐resistance in osteosarcoma through inhibiting FPGS transcription
Authors: Yu Wenxi , Min Daliu , Lin Feng , Zheng Shuier , Tang Lina , He Aina , Hu Haiyan , Shen Zan 
Published: March 2019

De novo methotrexate (MTX)‐resistance, whose underlying mechanism remains largely unknown, usually leads to very poor prognosis in patients with osteosarcoma (OS). In this study, we established the de novo MTX‐resistant OS cell line SF‐86 and identified the candidate gene spindle and kinetochore associated complex subunit 1 (SKA1) as potentially related to de novo MTX‐resistance. Analysis of a cohort of 95 OS patients demonstrated that SKA1 overexpression significantly correlated with de novo MTX‐resistance and poor 5‐year survival. Mechanistically, SKA1 overexpression lead to a downregulation of folylpoly‐γ‐glutamate synthetase (FPGS), a key enzyme that converts MTX into its active form, MTX‐PG. We further demonstrated that SKA1 interacts with DNA‐directed RNA polymerase II subunit RPB3. ChIP analysis revealed that RPB3 binds the promoter region of the FPGS gene and triggers FPGS transcription upon MTX treatment in SW1353, a MTX‐sensitive OS cell line lacking endogenous SKA1 expression. On the contrary, this process is blocked in SF‐86 cells due to the formation of an inhibitory SKA1‐RPB3 complex. Furthermore, downregulation of SKA1 levels restores MTX sensitivity in SF‐86. Collectively, our study has established the de novo MTX‐resistant cell line SF‐86 and identified SKA1 as a novel regulator of FPGS, playing a key role in the development of de novo MTX‐resistance in OS.
An Electron‐Balance Based Approach to Predict the Decreasing Denitrification Potential of an Aquifer
Authors: Loschko Matthias , Wöhling Thomas , Rudolph David L. , Cirpka Olaf A. 
Published: March 2019

AbstractNumerical models for reactive transport can be used to estimate the breakthrough of a contaminant in a pumping well or at other receptors. However, as natural aquifers are highly heterogeneous with unknown spatial details, reactive transport predictions on the aquifer scale require a stochastic framework for uncertainty analysis. The high computational demand of spatially explicit reactive‐transport models hampers such analysis, thus motivating the search for simplified estimation tools. We suggest performing an electron balance between the reactants in the infiltrating solution and in the aquifer matrix to obtain the hypothetical time of dissolved‐reactant breakthrough at a receptor if the reaction with the matrix was instantaneous. This time we denote as the advective breakthrough time for instantaneous reaction (τinst). It depends on the amount of the reaction partner present in the matrix, the mass flux of the dissolved reactant, and the stoichiometry. While the shape of the reactive‐species breakthrough curve depends on various kinetic parameters, the overall timing scales with τinst. We calculate the latter by particle tracking. The effort of computing τinst is so low that stochastic calculations become feasible. We apply the concept to a two‐dimensional test case of aerobic respiration and denitrification. A detailed spatially explicit reactive‐transport model includes microbial dynamics. Scaling the time of local breakthrough curves observed at individual points by τinst decreased the variability of electron‐donor breakthrough curves significantly. We conclude that the advective breakthrough time for instantaneous reaction is efficient in estimating the time over which an aquifer retains its degradation potential.
Clinical–pathological correlations in post‐transplant thrombotic microangiopathy
Authors: Broecker Verena , Bardsley Victoria , Torpey Nicholas , Perera Ranmith , Montero Rosa , Dorling Anthony , Bentall Andrew , Neil Desley , Willicombe Michelle , Berry Miriam , Roufosse Candice 
Published: March 2019

AimsPost‐transplant thrombotic microangiopathy (TMA) is a rare and clinically challenging finding in renal transplant biopsies. In addition to recurrent atypical haemolytic uraemic syndrome, TMA in renal transplants is associated with various conditions, such as calcineurin inhibitor (CNI) treatment, antibody‐mediated rejection (ABMR), viral infections, sepsis, pregnancy, malignancies, and surgery. The therapeutic implications of this diagnosis are considerable. In order to better understand post‐transplant TMA and to identify histological or clinical differences between associated causes, we conducted a multicentre retrospective study.Methods and resultsClinical parameters and transplant renal biopsy findings from 81 patients with TMA were analysed. Biopsies from 38 patients were also analysed with electron microscopy. On the basis of clinical–pathological correlation, TMA was attributed to a main aetiology, whenever possible. TMA occurred at a median of 30 days post‐transplantation. Systemic features of TMA were present in only 18% of cases. Twenty‐two per cent of cases were attributed to CNI and 11% to ABMR. Although other potentially contributing factors were found in 56% of patients, in most cases (63%) no clearly attributable cause of TMA was identified. Histological differences between groups were minimal. The detection of ultrastructural features that are usually associated with ABMR may help to establish ABMR as the cause of TMA.ConclusionsAlthough CNI and ABMR appear to be the main contributors to post‐transplant TMA, the aetiology of most cases is probably multifactorial, and TMA cannot be unequivocally attributed to a single underlying aetiology. Morphological features of TMA are not discriminating, but electron microscopy may help to identify ABMR‐associated TMA.
Primary renal well‐differentiated neuroendocrine tumour (carcinoid): next‐generation sequencing study of 11 cases
Authors: Pivovarcikova Kristyna , Agaimy Abbas , Martinek Petr , Alaghehbandan Reza , Perez‐Montiel Delia , Alvarado‐Cabrero Isabel , Rogala Joanna , Kuroda Naoto , Rychly Boris , Gasparov Slavko , Michalova Kvetoslava , Michal Michal , Hora Milan , Pitra Tomas , Tuckova Inna , Laciok Simon , Mareckova Jana , Hes Ondrej 
Published: March 2019

AimsPrimary renal well‐differentiated neuroendocrine tumour (NET) (hereafter referred to as renal NET) is rare, with ~100 cases having been reported in the literature. There are also limited data on the molecular–genetic background of primary renal NETs.Methods and resultsWe analysed 11 renal NETs by using next‐generation sequencing (NGS) to identify characteristic genetic aberrations. All tumours were positive for synaptophysin, and also expressed insulinoma‐associated protein 1 (10/11), chromogranin‐A (8/11), and CD56 (3/11). Cytoplasmic positivity of CD99 was present in eight of 11 cases, and strong nuclear expression of α‐thalassaemia/mental retardation syndrome X‐linked (ATRX) was retained in all 11 cases. Molecular–genetic analysis of aberration ofVHLgave negative results in all cases. Loss of heterozygosity on chromosome 3p21 was found in three of nine analysable cases. NGS was successful in nine cases, showing a total of 56 variants being left after the updated filtering process, representing an average of five variants per sample. All analysable cases were negative forATRXandDAXX(death‐domain associated protein X) mutations. The most frequently mutated genes wereCDH1andTET2, with three mutations in two cases. Mutations inAKT3,ROS1,PIK3R2,BCRandMYCwere found in two cases. The remaining 41 genes were found to be mutated only in individual cases. In four cases, the mutations affected a subset of genes related to angiogenesis.ConclusionsOverall, the mutation profile of primary renal NETs is variable, and none of the studied genes or affected pathways seems to be specific for renal NET.
In vitro efficacy of antifungal agents alone and in shampoo formulation against dandruff‐associated Malassezia spp. and Staphylococcus spp.
Authors: Leong C. , Schmid B. , Buttafuoco A. , Glatz M. , Bosshard P. P. 
Published: March 2019

AbstractObjectiveDandruff is a complex skin condition characterized by unpleasant itching and flaking of the scalp. It is primarily attributed to the over colonization of Malassezia yeasts such as Malassezia globosa and Malassezia restricta. Some studies also suggest the involvement of staphylococci bacteria in dandruff disease pathogenesis. We aimed to access the effectiveness of anti‐dandruff treatments by determining the efficacy of the active antifungal agents alone or in commercial shampoo formulations against Malassezia and Staphylococcus.MethodsThe minimum inhibitory concentrations of three anti‐dandruff shampoo antifungals (zinc pyrithione, ketoconazole and ciclopirox) and the witch hazel extract, hamamelitannin were tested against commensal Malassezia and Staphylococcus species using broth microdilution methods. In experiments simulating shampoo exposure and washing conditions on the scalp, we also tested the ability of the above agents in shampoo formulation (Head and Shoulders® (H&S), Ketomed®, Sebiprox®, Erol Healthcare Hair Shampoo® respectively) along with a generic over‐the‐shelf shampoo to inhibit microbial growth.ResultsKetomed® and H&S shampoo were the most effective treatments against Malassezia in in vitro assays and washing simulation experiments. Erol Healthcare Hair Shampoo® was less effective against Malassezia as it required a longer contact time to achieve growth inhibition for some species. Sebiprox® showed variable efficacy in washing and contact time experiments whereas the generic over‐the‐shelf shampoo was the least effective in inhibiting Malassezia and Staphylococcus growth.ConclusionFrom these findings, it is reasonable that patients with dandruff may benefit from applying specific antifungal shampoo although results may vary with microbial species, time of contact and shampoo formulation components.
Complement to “Optical and Judd‐Ofelt spectroscopic study of Er3+‐doped strontium gadolinium gallium garnet single‐crystal”
Authors: Xu Qing , Wang Yan , Wong Wing‐Han , Zhang Zi‐Bo , Zhang De‐Long 
Published: March 2019

AbstractIn the previous paper “Optical and Judd‐Ofelt spectroscopic study of Er3+‐doped strontium gadolinium gallium garnet single‐crystal” (J Am Ceram Soc. 2019;102:873–878), we have reported optical and Judd‐Ofelt spectroscopic properties of Er3+‐doped strontium gadolinium gallate (SrGdGa3O7) single‐crystal, and the Judd‐Ofelt study was performed on the basis of unpolarized absorption spectrum of the crystal. Present work reports the corrected unpolarized absorption spectrum and Er3+ concentration in the crystal, and hence corrected Judd‐Ofelt spectroscopic properties and cross‐section data. In addition, the polarization effect was considered in the Judd‐Ofelt analysis on the basis of polarization‐resolved absorption spectra. Effective Judd‐Ofelt parameters are presented and discussed in comparison with the results from the unpolarized spectrum, and consistent results have been obtained. This study also considers the effects of some other factors on the Judd‐Ofelt parameters. These include Er3+ concentration and selection of Er3+ absorption bands for the Judd‐Ofelt analysis.
Within‐host interactions shape virulence‐related traits of trematode genotypes
Authors: Klemme Ines , Karvonen Anssi 
Published: March 2019

AbstractWithin‐host interactions between co‐infecting parasites can significantly influence the evolution of key parasite traits, such as virulence (pathogenicity of infection). The type of interaction is expected to predict the direction of selection, with antagonistic interactions favouring more virulent genotypes and synergistic interactions less virulent genotypes. Recently, it has been suggested that virulence can further be affected by the genetic identity of co‐infecting partners (G × G interactions), complicating predictions on disease dynamics. Here, we used a natural host–parasite system including a fish host and a trematode parasite to study the effects of G × G interactions on infection virulence. We exposed rainbow trout (Oncorhynchus mykiss) either to single genotypes or to mixtures of two genotypes of the eye fluke Diplostomum pseudospathaceum and estimated parasite infectivity (linearly related to pathogenicity of infection, measured as coverage of eye cataracts) and relative cataract coverage (controlled for infectivity). We found that both traits were associated with complex G × G interactions, including both increases and decreases from single infection to co‐infection, depending on the genotype combination. In particular, combinations where both genotypes had low average infectivity and relative cataract coverage in single infections benefited from co‐infection, while the pattern was opposite for genotypes with higher performance. Together, our results show that infection outcomes vary considerably between single and co‐infections and with the genetic identity of the co‐infecting parasites. This can result in variation in parasite fitness and consequently impact evolutionary dynamics of host–parasite interactions.
Mortality outbreak by perch rhabdovirus in European perch (Perca fluviatilis) farmed in Italy: Clinical presentation and phylogenetic analysis
Authors: Caruso Claudio , Gustinelli Andrea , Pastorino Paolo , Acutis Pier Luigi , Prato Riccardo , Masoero Loretta , Peletto Simone , Fioravanti Maria Letizia , Prearo Marino 
Published: March 2019

AbstractThis work reports a mortality outbreak, occurred in 2015 and affecting juveniles of European perch (Perca fluviatilis L.) farmed in Italy. Perch rhabdovirus (PRV) was detected by viral isolation and biomolecular investigations. Phylogenetic analysis clustered our isolate into genogroup B, which also includes PRV isolates from Perca fluviatilis identified in France (2004–2009); diagnostic investigations also revealed opportunistic bacteria (Aeromonas hydrophila) and parasites (Chilodonella piscicola). Since, occasionally, PRV has been reported in the natural environment, which is often a source of eggs and broodstock for farms, it could be possible that both similar France and Italian isolate were imported from a same place elsewhere and have a common origin. Improving biosecurity measures (batch control) and disinfection of egg strings with an iodine‐based solution helps prevent apparent vertical transmission of PRV.
Multilocus sequence typing detects new Piscirickettsia salmonis hybrid genogroup in Chilean fish farms: Evidence for genetic diversity and population structure
Authors: Isla Adolfo , Saldarriaga‐Córdoba Mónica , Fuentes Derie E. , Albornoz Romina , Haussmann Denise , Mancilla‐Schulz Jorge , Martínez Alexis , Figueroa Jaime , Avendaño‐Herrera Ruben , Yáñez Alejandro 
Published: March 2019

AbstractPiscirickettsia salmonisis the causative bacterial pathogen of piscirickettsiosis, a salmonid disease that causes notable mortalities in the worldwide aquaculture industry. Published research describes the phenotypic traits, virulence factors, pathogenicity and antibiotic‐resistance potential for various P. salmonisstrains. However, evolutionary and genetic information is scarce for P. salmonis. The present study used multilocus sequence typing (MLST) to gain insight into the population structure and evolution of P. salmonis. Forty‐two Chilean P. salmonisisolates, as well as the type strain LF‐89T, were recovered from diseased Salmo salar, Oncorhynchus kisutchand Oncorhynchus mykissfrom two Chilean Regions. MLST assessed the loci sequences of dnaK, efp, fumC, glyA, murG, rpoD and trpB. Bioinformatics analyses established the genetic diversity among P. salmonis isolates (H = 0.5810). A total of 23 sequence types (ST) were identified, 53.48% of which were represented by ST1, ST5 and ST2. Population structure analysis through polymorphism patterns showed few polymorphic sites (218 nucleotides from 4,010 bp), while dN/dS ratio analysis indicated purifying selection for dnaK, epf, fumC, murG, and rpoD but neutral selection for the trpB loci. The standardized index of association indicated strong linkage disequilibrium, suggesting clonal population structure. However, recombination events were detected in a group of seven isolates. Findings included genogroups homologous to the LF‐89T and EM‐90 strains, as well as a seven‐isolate hybrid genogroup recovered from both assessed regions (three O. mykiss and four S. salar isolates). The presented MLST scheme has comparative potential, with promising applications in studying distinct P. salmonis isolates (e.g., from different hosts, farms, geographical areas) and in understanding the epidemiology of this pathogen.