bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual, situational, and cultural correlates of acquiescent responding: Towards a unified conceptual framework
Authors: Lechner Clemens M. , Partsch Melanie V. , Danner Daniel , Rammstedt Beatrice
Published: March 2019

Acquiescence (‘yea‐saying’) can seriously harm the validity of self‐report questionnaire data. Towards a better understanding of why some individuals and groups acquiesce more strongly than others do, we developed a unified conceptual framework of acquiescent responding. Our framework posits that acquiescent responding is a joint function of respondent characteristics (e.g. age, education, values), situational/survey characteristics (e.g., interview privacy, respondents’ interest), and cultural characteristics (e.g., social norms, economic development). The framework posits two putative mechanisms through which these characteristics may relate to acquiescence: cognitive processing capacities and deferential communication styles. Multilevel analyses using data from 60 heterogeneous countries from the World Values Survey (N = 90,347) support our framework's proposition that acquiescence is a joint function of respondent, situational, and cultural characteristics. Acquiescence was higher among respondents who were older (over 55 years old), less educated, who valued deference (i.e., conformity and tradition), and, unexpectedly, were male. Interview privacy corresponded to lower acquiescence, but this association was small and vanished after including respondent characteristics. Unexpectedly, acquiescence was higher in interviewees who showed a stronger interest in the interview. Finally, acquiescence was considerably higher in countries with stronger social norms of deference. We discuss implications of these findings for the validity of research based on self‐report data and delineate how our framework can guide future inquiries into acquiescent responding.
The circadian rhythm of corticosteroid‐binding globulin has little impact on cortisol exposure after hydrocortisone dosing
Authors: Melin Johanna , Hartung Niklas , Parra‐Guillen Zinnia P. , Whitaker Martin J. , Ross Richard J. , Kloft Charlotte
Published: March 2019

Context

Optimization of hydrocortisone replacement therapy is important to prevent under‐ and over dosing. Hydrocortisone pharmacokinetics is complex as circulating cortisol is protein bound mainly to corticosteroid‐binding globulin (CBG) that has a circadian rhythm.

Objective

A detailed analysis of the CBG circadian rhythm and its impact on cortisol exposure after hydrocortisone administration.

Design and Methods

CBG was measured over 24 hours in 14 healthy individuals and, employing a modelling and simulation approach using a semi‐mechanistic hydrocortisone pharmacokinetic model, we evaluated the impact on cortisol exposure (area under concentration‐time curve and maximum concentration of total cortisol) of hydrocortisone administration at different clock times and of the changing CBG concentrations.

Results

The circadian rhythm of CBG was well described with two cosine terms added to the baseline of CBG: baseline CBG was 21.8 µg/mL and interindividual variability 11.9%; the amplitude for the 24 and 12 hours cosine functions were relatively small (24 hours: 5.53%, 12 hours: 2.87%) and highest and lowest CBG were measured at 18:00 and 02:00, respectively. In simulations, the lowest cortisol exposure was observed after administration of hydrocortisone at 23:00‐02:00, whereas the highest was observed at 15:00‐18:00. The differences between the highest and lowest exposure were minor (≤12.2%), also regarding the free cortisol concentration and free fraction (≤11.7%).

Conclusions

Corticosteroid‐binding globulin has a circadian rhythm but the difference in cortisol exposure is ≤12.2% between times of highest and lowest CBG concentrations; therefore, hydrocortisone dose adjustment based on time of dosing to adjust for the CBG concentrations is unlikely to be of clinical benefit.
MARCH MADNESS: NCAA TOURNAMENT PARTICIPATION AND COLLEGE ALCOHOL USE
Authors: White Dustin R. , Cowan Benjamin W. , Wooten Jadrian J.
Published: March 2019

While athletic success may improve the visibility of a university to prospective students and thereby benefit the school, it may also increase risky behavior in the current student body. Using the Harvard School of Public Health College Alcohol Study, we find that a school's participation in the NCAA Basketball Tournament is associated with a 47% increase in binge drinking by male students at that school. Additionally, we find evidence that drunk driving increases by 5% among all students during the tournament. (JEL I12, I23, Z28)
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

Aim

The 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 methods

This 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).

Results

Among 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.

Conclusions

In 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

Background

Dissipative 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).

Methods

In 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.

Results

Left 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).

Conclusion

Vector 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.
Threshold protective effect of deuterated polyunsaturated fatty acids on peroxidation of lipid bilayers
Authors: Firsov Alexander M. , Fomich Maksim A. , Bekish Andrei V. , Sharko Olga L. , Kotova Elena A. , Saal Harry J. , Vidovic Dragoslav , Shmanai Vadim V. , Pratt Derek A. , Antonenko Yuri N. , Shchepinov Mikhail S.
Published: March 2019

Autoxidation of polyunsaturated fatty acids (PUFAs) damages lipid membranes and generates numerous toxic by‐products implicated in neurodegeneration, aging, and other pathologies. Abstraction of bis‐allylic hydrogen atoms is the rate‐limiting step of PUFA autoxidation, which is inhibited by replacing bis‐allylic hydrogens with deuterium atoms (D‐PUFAs). In cells, the presence of a relatively small fraction of D‐PUFAs among natural PUFAs is sufficient to effectively inhibit lipid peroxidation (LPO). Here, we investigate the effect of various D‐PUFAs on the stability of liposomes under oxidative stress conditions. The permeability of vesicle membranes to fluorescent dyes was measured as a proxy for bilayer integrity, and the formation of conjugated dienes was monitored as a proxy for LPO. Remarkably, both approaches reveal a similar threshold for the protective effect of D‐PUFAs in liposomes. We show that protection rendered by D‐PUFAs depends on the structure of the deuterated fatty acid. Our findings suggest that protection of PUFAs against autoxidation depends on the total level of deuterated bi‐sallylic (CD2) groups present in the lipid bilayer. However, the phospholipid containing 6,6,9,9,12,12,15,15,18,18‐d10‐docosahexaenoic acid exerts a stronger protective effect than should be expected from its deuteration level. These findings further support the application of D‐PUFAs as preventive/therapeutic agents in numerous pathologies that involve LPO.
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

Numerical 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

Aims

Post‐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 results

Clinical 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.

Conclusions

Although 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

Aims

Primary 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 results

We 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.

Conclusions

Overall, 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

Objective

Dandruff 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.

Methods

The 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.

Results

Ketomed® 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.

Conclusion

From 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

In 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

Within‐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

This 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

Piscirickettsia 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.
Clinical and psychological characteristics in gastroesophageal reflux disease patients overlapping with laryngopharyngeal reflux symptoms
Authors: Wong Ming‐Wun , Bair Ming‐Jong , Chang Wei‐Chuan , Hsu Ching‐Sheng , Hung Jui‐Sheng , Liu Tso‐Tsai , Yi Chih‐Hsun , Lei Wei‐Yi , Vaezi Michael F , Gyawali C Prakash , Chen Chien‐Lin
Published: March 2019

Background and Aim

Laryngopharyngeal reflux (LPR) defined as reflux of gastric content reaching above the upper esophageal sphincter is frequently found in patients with gastroesophageal reflux disease (GERD). This study aimed to investigate clinical and psychological differences between GERD patients with or without LPR symptoms.

Methods

This study enrolled 303 consecutive patients with proton pump inhibitor treatment‐naïve scheduled for upper endoscopy because of troublesome reflux symptoms and recognized as GERD by non‐dyspepsia reflux disease questionnaire score. Included GERD patients were further categorized into two study groups: with or without LPR by reflux symptoms index score. All participants were also evaluated with questionnaires for depression, anxiety, and sleep disturbances.

Results

There were 132 (43.6%) GERD patients with LPR symptoms and 171 (56.4%) GERD patients without LPR symptoms. GERD patients with LPR symptoms had more depression (P < 0.001), sleep disturbance (P = 0.002), irritable bowel syndrome (P = 0.008), functional dyspepsia (P = 0.005), and reflux symptoms burden (P < 0.001) than those without LPR symptoms. Erosive esophagitis was more in patients without LPR symptoms (P = 0.03). GERD patients with LPR symptoms (28.8%) had more complex psychological distress than those without LPR symptoms (28.8% vs 14%, P < 0.001). Reflux symptoms burden, sleep disturbance, and erosive esophagitis were independently associated with GERD overlapping with LPR symptoms.

Conclusions

Gastroesophageal reflux disease patients with LPR symptoms appear to have more reflux symptoms, psychological distress, and functional gastrointestinal disturbance but less erosive esophagitis. This work suggests that therapeutic strategy with tailored multidimensional approach is promising for GERD patients overlapping with LPR symptoms.
ZNF133 is associated with infliximab responsiveness in patients with inflammatory bowel diseases
Authors: Jung Eun Suk , Choi Ko‐woon , Kim Seung Won , Hübenthal Matthias , Mucha Sören , Park Jihye , Park Zewon , Ellinghaus David , Schreiber Stefan , Franke Andre , Oh Woo Yong , Cheon Jae Hee
Published: March 2019

Background and Aim

Infliximab has been widely prescribed for treating inflammatory bowel disease (IBD). However, the response rates to infliximab differ among patients. Therefore, we aimed to identify the genetic and clinical markers that predict infliximab response.

Methods

A total of 139 Korean patients with IBD who received infliximab were classified according to infliximab response as follows: (i) primary response vs nonresponse and (ii) sustained response vs loss of response. We performed an association study using whole‐exome sequencing data to identify genetic variants associated with infliximab response. Candidate variants were validated in 77 German patients with IBD. Stepwise multivariate logistic regression was performed to identify predictors.

Results

We found five candidate variants that were associated with primary nonresponse to infliximab (P < 5 × 10−6). Of the five variants, rs2228273 in ZNF133 was validated in German (combined P = 6.49 × 10−7). We also identified the best genetic variant (rs9144, P = 4.60 × 10−6) associated with the loss of infliximab response. In multivariate regression analysis, rs2228273 (P = 2.10 × 10−5), concurrent azathioprine/6‐mercaptopurine use, and bodyweight at the first infliximab use (< 50 kg) were associated with primary nonresponse. In addition, the Crohn's disease activity index at the first infliximab use and rs9144 (P = 0.001) were independently associated with the loss of response in patients with Crohn's disease.

Conclusions

We identified clinical and genetic markers associated with infliximab response in IBD patients. Our findings could provide insights to maximize the efficacy of infliximab therapy in IBD patients.
Reply to: Major Clinical Trials Failed the Amyloid Hypothesis of Alzheimer's Disease
Authors: McDade Eric
Published: March 2019

This is a response to the article by Huang et al.
Reply to: Why Amyloid Is Still a Target for Alzheimer's Disease
Authors: Zhao Hai‐Lu , Huang Yan‐Mei
Published: March 2019

This is a response to the article by Eric McDade
Major Clinical Trials Failed the Amyloid Hypothesis of Alzheimer's Disease
Authors: Huang Yan‐Mei , Shen Jian , Zhao Hai‐Lu
Published: March 2019

See the response from Zhao et al.
Neuroprotective effects of an engineered commensal bacterium in the 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine Parkinson disease mouse model via producing glucagon‐like peptide‐1
Authors: Fang Xin , Tian Puyuan , Zhao Xiaoxiao , Jiang Chunling , Chen Tingtao
Published: March 2019

While glucagon‐like peptide‐1 (GLP‐1) was reported to have a positive impact on Parkinson disease, it is extremely short half‐life greatly hindered its clinical use. In this study, the mouse strain MG1363‐pMG36e‐GLP‐1 was engineered to continuously express GLP‐1 to treat Parkinson disease in a 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP)‐treated Parkinson disease model. In our study, oral supplementation with MG1363‐pMG36e‐GLP‐1 significantly (p < 0.05) reduced MPTP‐induced locomotor impairments, increased tyrosine hydroxylase‐positive neurons, suppressed microglia and astrocyte activation, and down‐regulated expression of several inflammation‐related molecules. In addition, MG1363‐pMG36e‐GLP‐1 significantly (p < 0.01) reduced intestinal pathogen Enterobacteriaceae and markedly enhanced the number of probiotic Lactobacillus and Akkermansia. These data suggest that MG1363‐pMG36e‐GLP‐1 could be a novel therapeutic means for Parkinson disease.

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The effect of chemical and biological treatment on root and crown rot disease caused by Phytophthora cryptogea Pethybr. & Lafferty in Gerbera
Authors: Özkan Kahraman Çiğdem , Yıldız Figen
Published: March 2019

Phytophthora root and crown rot (Phytophthora cryptogea) on gerbera is difficult to manage because most gerbera cultivars are susceptible to P. cryptogea. This study was conducted in order to determine the in vivo (pot experiment) efficacy of some fungicides and biofungicides. In pot experiments, fungicides were applied 7 days after inoculation with P. cryptogea, while biofungicide was applied 7 days before inoculation. In this study, soil drenches of five fungicides were tested. “Ametoctradin+dimethomorph (100 ml/day),” “mandipropamid+difenoconazole (60 ml/day),” “propamocarb+fosetyl‐Al (200 ml/day),” “mancozeb+metalaxyl‐M (250 g/day)” and “azoxystrobin+difenoconazole (100 ml/day)” active substances were used. Similarly, one biofungicide Bacillus amyloliquefaciens syn. MBI 600 (50 g/100 L) was applied by soil drenching. Efficacy of treatments was assessed according to the percentage of the root system which was visibly rotten at the end of the experiment. Root and crown rot severity was rated on a scale of 0 = 0% root system necrotic, 1 = 1%‐25% necrotic, 2 = 26%‐50% necrotic, 3 = 51%‐75% necrotic and 4 = 76%‐100% necrotic from 12 to 21 days. In this experiment, “azoxystrobin 200 g/L + difenoconazole 125 g/L” exhibited the highest efficacy against P. cryptogea with a ratio of 43.75%. The other fungicides and biofungicides ametoctradin 300 g/L + dimethomorph 225 g/L, mandipropamid 250 g/L + difenoconazole 250 g/L, propamocarb 530 g/L + fosety‐Al 310 g/L, mancozeb 64%+metalaxyl‐M 4% and Bacillus amyloliquefaciens syn. MBI 600 11% were ineffective. Importance should be given to management strategies of P. cryptogea of and more experiments should be carried out for a better understanding of the use of registered fungicides and biofungicides.
Sequential application of bFGF and BMP‐2 facilitates osteogenic differentiation of human periodontal ligament stem cells
Authors: Kang Wenyan , Liang Qianyu , Du Lingqian , Shang Lingling , Wang Ting , Ge Shaohua
Published: March 2019

Background and Objectives

Basic fibroblast growth factor (bFGF) promotes cells proliferation and chemotaxis and maintains stemness while inhibits mineralized nodule formation. Bone morphogenetic protein 2 (BMP‐2) shows great potential in promoting bone formation. However, sequential application of these two growth factors on periodontal ligament stem cells (PDLSCs) has not been explored. In this study, we aimed to identify the optimal concentration and time of bFGF on PDLSCs proliferation, migration and then investigate the sequential delivery of bFGF and BMP‐2 on osteogenic differentiation of PDLSCs in vitro.

Materials and Methods

Periodontal ligament stem cells were isolated by limiting dilution method. Dose‐dependent additive effects of bFGF and BMP‐2 on PDLSCs were detected. Cell counting assay, cell migration assay, alkaline phosphatase (ALP) activity assay, Alizarin red staining, quantitative real‐time polymerase chain reaction (qRT‐PCR), and western blot analysis were used to determine different application modalities of bFGF and BMP‐2 on proliferation, migration, and osteogenic differentiation of PDLSCs.

Results

50 ng/mL bFGF significantly promoted PDLSCs proliferation and chemotaxis while time‐dependently inhibited BMP‐2 induced ALP activity. Sequential application of 25 ng/mL bFGF for first 3 days and followed with 50 ng/mL BMP‐2 for another 9, 18, and 25 days significantly promoted PDLSCs osteogenic differentiation. Compared with bFGF and BMP‐2 simultaneous group, sequential application of bFGF and BMP‐2 group significantly enhanced ALP activity, osteogenesis‐related genes and proteins expression and mineral deposition.

Conclusion

Sequential application of bFGF and BMP‐2 synergistically promoted osteogenic differentiation of PDLSCs, and this sequential application modality of growth factors would provide a new strategy for periodontal regeneration.
Experimental models to unravel the molecular pathogenesis, cell of origin and stem cell properties of cholangiocarcinoma
Authors: Vicent Silvestre , Lieshout Ruby , Saborowski Anna , Verstegen Monique M. A. , Raggi Chiara , Recalcati Stefania , Invernizzi Pietro , van der Laan Luc J. W. , Alvaro Domenico , Calvisi Diego F. , Cardinale Vincenzo
Published: March 2019

Human cholangiocarcinoma (CCA) is an aggressive tumour entity arising from the biliary tree, whose molecular pathogenesis remains largely undeciphered. Over the last decade, the advent of high‐throughput and cell‐based techniques has significantly increased our knowledge on the molecular mechanisms underlying this disease while, at the same time, unravelling CCA complexity. In particular, it becomes clear that CCA displays pronounced inter‐ and intratumoural heterogeneity, which is presumably the consequence of the interplay between distinct tissues and cells of origin, the underlying diseases, and the associated molecular alterations. To better characterize these events and to design novel and more effective therapeutic strategies, a number of CCA experimental and preclinical models have been developed and are currently generated. This review summarizes the current knowledge and understanding of these models, critically underlining their translational usefulness and limitations. Furthermore, this review aims to provide a comprehensive overview on cells of origin, cancers stem cells and their dynamic interplay within CCA tissue.
Drift happens: Molecular genetic diversity and differentiation among populations of jewelweed (Impatiens capensis Meerb.) reflect fragmentation of floodplain forests
Authors: Toczydlowski Rachel H. , Waller Donald M.
Published: March 2019

Landscape features often shape patterns of gene flow and genetic differentiation in plant species. Populations that are small and isolated enough also become subject to genetic drift. We examined patterns of gene flow and differentiation among 12 floodplain populations of the selfing annual jewelweed (Impatiens capensis Meerb.) nested within four river systems and two major watersheds in Wisconsin, USA. Floodplain forests and marshes provide a model system for assessing the effects of habitat fragmentation within agricultural/urban landscapes and for testing whether rivers act to genetically connect dispersed populations. We generated a panel of 12,856 single nucleotide polymorphisms and assessed genetic diversity, differentiation, gene flow, and drift. Clustering methods revealed strong population genetic structure with limited admixture and highly differentiated populations (mean multilocus FST = 0.32, FST’ = 0.33). No signals of isolation by geographic distance or environment emerged, but alleles may flow along rivers given that genetic differentiation increased with river distance. Differentiation also increased in populations with fewer private alleles (R2 = 0.51) and higher local inbreeding (R2 = 0.22). Populations varied greatly in levels of local inbreeding (FIS = 0.2–0.9) and FIS increased in more isolated populations. These results suggest that genetic drift dominates other forces in structuring these Impatiens populations. In rapidly changing environments, species must migrate or genetically adapt. Habitat fragmentation limits both processes, potentially compromising the ability of species to persist in fragmented landscapes.
Nonproteinaceous effectors: the terra incognita of plant–fungal interactions
Authors: Collemare Jérôme , O'Connell Richard , Lebrun Marc‐Henri
Published: March 2019

Molecular plant–fungal interaction studies have mainly focused on small secreted protein effectors. However, accumulating evidence shows that numerous fungal secondary metabolites are produced at all stages of plant colonization, especially during early asymptomatic/biotrophic phases. The discovery of fungal small RNAs targeting plant transcripts has expanded the fungal repertoire of nonproteinaceous effectors even further. The challenge now is to develop specific functional methods to fully understand the biological roles of these effectors. Studies on fungal extracellular vesicles are also needed because they could be the universal carriers of all kinds of fungal effectors. With this review, we aim to stimulate the nonproteinaceous effector research field to move from descriptive to functional studies, which should bring a paradigm shift in plant–fungal interactions.
Shared services in Brazilian local government: Urban development in small counties
Authors: Consciência Silvestre Hugo , Cunha Marques Rui , Dollery Brian , Moraes Correia Aldenisio
Published: March 2019

In this article we break new ground by investigating cooperative agreements in urban development services, which include urban development, housing and sanitation for small local governments in Brazil (i.e., those with fewer than 20,000 residents in 2013–15). We find that public expenditure on urban development can be explained by both horizontal (intermunicipal cooperation) and vertical (public–public partnerships) cooperation. Regarding the impact of public sector cooperation on public expenditure, our results show that housing and sanitation services are less costly under intermunicipal cooperation. By contrast, urban development services are less costly when local authorities do not cooperate with other public entities. For public–public partnerships (with the state or federal government) cooperation leads to an increase in public funding, which implies that cooperative agreements might not lead to lower public expenditure. The findings in this article provide useful empirical insights into the administrative reorganization of Brazilian local government.
The role of HD‐Zip class I transcription factors in plant response to abiotic stresses
Authors: Gong Shaohua , Ding Yanfei , Hu Shanshan , Ding Lihong , Chen Zhixiang , Zhu Cheng
Published: March 2019

Abiotic stresses usually affect plant growth and development, indirectly or directly causing crop production reduction and even plant death. To survive, plants utilize different mechanisms to adapt themselves to continuously changing surrounding environmental stresses. Homeodomain‐leucine zipper (HD‐Zip) transcription factors are unique to the plant kingdom and divided into four different subfamilies (HD‐Zip I∼IV). Many HD‐Zip I members have been shown to play critical roles in the regulation of plant developmental processes, signaling networks and responses to environmental stresses. This review focuses on the role of HD‐Zip I transcription factors in plant responses to various abiotic stresses, including abscisic acid‐mediated stress, drought and cold stress, oxidative stress, helping to identify the potential regulatory mechanisms that alleviate abiotic stress in plants.
Achieving dialysis safety: The critical role of higher‐functioning teams
Authors: Wong Leslie P.
Published: March 2019

The potential for harm from errors and adverse events in dialysis is significant. Achieving a culture of safety in dialysis to reduce the potential harm to patients has been challenging. Recently, improving dialysis safety has been highlighted by Nephrologists Transforming Dialysis Safety (NTDS), a national initiative to eliminate dialysis infections. Other aspects of dialysis safety are important, though less measurable. Approaching dialysis safety from a systematic thinking view helps us to understand the need for leadership and high‐functioning teams to deliver safe, reliable care in dialysis facilities. Resilience in healthcare is embodied by strong teamwork—interdependent professionals working together with clarity of goals and communication. This paper reframes the role of dialysis facility medical directors as leaders of these high‐functioning teams. Alignment between nephrologists and dialysis management is necessary for these teams to function. This will require nephrologists to embrace their leadership roles as medical directors and for dialysis facility management to provide adequate operational support. The accountability for dialysis safety is shared between the nephrologists and dialysis organizations; coleadership is required for safety culture and high‐functioning dialysis teams to develop.