bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytology smears for DNA extraction: Practical approach for selecting the best slide
Authors: Gupta Neha , Brenkert Ryan , Lee Joong Won , Klein Melissa , Spitzer Silvia , Chau Karen , Das Kasturi 
Published: July 2018

AbstractBackgroundNext generation sequencing (NGS) to detect actionable genetic abnormalities is standard of care in advanced stage lung adenocarcinoma. Many studies have shown that the molecular results obtained from fine needle aspiration cytology material are comparable to those obtained from formalin‐fixed tissue samples. We undertook this study to validate DNA extraction from cytology material for molecular studies and to find any correlation between DNA yield, pattern of tumour cells and tumour fraction.MethodsDNA was extracted from 34 cytology slides of pulmonary adenocarcinoma cases with predetermined EGFR mutation status. Cytology slides were reviewed for pattern of tumour distribution and tumour fraction. NGS was performed on five slides with variable DNA and compared with original results.ResultsThere were 14 alcohol‐fixed and 20 air‐dried smears. The mean DNA yield was 1.74 μg and median of 0.4 μg (range, 0.02‐21 μg). Tumour fractions varied from 10% to 90%. No correlation was found between tumour fraction and DNA yield (P = 0.14). The mean DNA yield was high in slides with tumour throughout the slide (sheets or scattered clusters) as compared to rare scattered clusters and/or single cells. EGFR mutation was found in four of the five cases sent for NGS lung panel while one case revealed BRAF mutation.ConclusionsDNA with good quantity and quality can be extracted from the cytology slides for NGS irrespective of type of fixation. DNA yield has better correlation with distribution pattern of tumour cells on the slides rather than tumour fraction.
Effective tax rates and firm size in Ethiopia
Authors: Mascagni Giulia , Mengistu Andualem 
Published: July 2018

AbstractThe literature on Effective Tax Rates (ETRs) focuses on high‐ and middle‐income countries, but there is very little evidence on low‐income countries. This article addresses this gap with new evidence from Ethiopia. We investigate corporate ETRs in Ethiopia and whether the distributional effects they have in practice are in line with the corporate tax policy design. We calculate ETRs in line with the literature in this field, using profit tax at the numerator and gross profit at the denominator. We then analyse ETRs not only using panel data, focusing particularly on their relation to firm size, but also including other explanatory variables. Our main result is that, despite a proportional tax rate, small firms face a higher effective tax burden than larger firms, while middle‐sized firms face the lowest burden of all. We highlight that tax systems can have practical implications that differ largely from their policy design, due to compliance costs and imperfect enforcement. Measures to reduce compliance costs for small firms are particularly recommended.
α‐Synuclein concentration increases over time in plasma supernatant of single donor platelets
Authors: Stefaniuk Catherine M. , Hong Hong , Harding Clifford V. , Maitta Robert W. 
Published: July 2018

AbstractObjectivesIn platelets, α‐synuclein is important in calcium‐dependent granule release. Notably, cells release α‐synuclein in setting of cell damage or death. Therefore, we investigated α‐synuclein levels in plasma of single donor platelet (SDP) units during storage.MethodsAliquots were obtained from same SDP units for 7 days from day of donation. Additionally, randomly sampled SDP units at same storage time points were also assayed by enzyme‐linked immunosorbent assay.Resultsα‐Synuclein in SDP plasma increased continuously over time at each assayed time point. Significant increases were measured on day 3 (11.7 ± 9.6 ng/mL, P = 0.025), day 5 (15.3 ± 5.9 ng/mL, P = 0.002), and highest on day 7 (23.7 ± 5.6 ng/mL, P < 0.0001) compared to day 0 (1.1 ± 0.8 ng/mL). Similar significant results were obtained in randomly sampled SDP units at same corresponding time points. Flow cytometry showed that platelets had strong expression of α‐synuclein and lacked expression of other synucleins.ConclusionsIncreases of α‐synuclein during SDP storage is a steady and continuous process that increases with time. Our findings indicate that α‐synuclein may represent a biomarker of platelet biological state during storage. Further research will be needed to determine how α‐synuclein increases correlate with platelets’ function.
Aplastic anemia: Etiology, molecular pathogenesis, and emerging concepts
Authors: Shallis Rory M. , Ahmad Rami , Zeidan Amer M. 
Published: July 2018

AbstractAplastic anemia (AA) is rare disorder of bone marrow failure which if severe and not appropriately treated is highly fatal. AA is characterized by morphologic marrow features, namely hypocellularity, and resultant peripheral cytopenias. The molecular pathogenesis of AA is not fully understood, and a uniform process may not be the culprit across all cases. An antigen‐driven and likely autoimmune dysregulated T‐cell homeostasis is implicated in the hematopoietic stem cell injury which ultimately founds the pathologic features of the disease. Defective telomerase function and repair may also play a role in some cases as evidenced by recurring mutations in related telomerase complex genes such asTERTandTERC. In addition, recurring mutations inBCOR/BCORL, PIGA, DNMT3A,andASXL1as well as cytogenetic abnormalities, namely monosomy 7, trisomy 8, and uniparental disomy of the 6p arm seem to be intimately related to AA pathogenesis. The increased incidence of late clonal disease has also provided clues to accurately describe plausible predispositions to the development of AA. The emergence of newer genomic sequencing and other techniques is incrementally improving the understanding of the pathogenic mechanisms of AA, the detection of the disease, and ultimately offers the potential to improve patient outcomes. In this comprehensive review, we discuss the current understanding of the immunobiology, molecular pathogenesis, and future directions of such for AA.
Cholinergic modulation of spatial learning, memory and navigation
Authors: Solari Nicola , Hangya Balázs 
Published: July 2018

AbstractSpatial learning, including encoding and retrieval of spatial memories as well as holding spatial information in working memory generally serving navigation under a broad range of circumstances, relies on a network of structures. While central to this network are medial temporal lobe structures with a widely appreciated crucial function of the hippocampus, neocortical areas such as the posterior parietal cortex and the retrosplenial cortex also play essential roles. Since the hippocampus receives its main subcortical input from the medial septum of the basal forebrain (BF) cholinergic system, it is not surprising that the potential role of the septo‐hippocampal pathway in spatial navigation has been investigated in many studies. Much less is known of the involvement in spatial cognition of the parallel projection system linking the posterior BF with neocortical areas. Here we review the current state of the art of the division of labour within this complex ‘navigation system’, with special focus on how subcortical cholinergic inputs may regulate various aspects of spatial learning, memory and navigation.
Micro‐computed tomography assessment of root dentin around fluoride‐releasing restorations after demineralization/remineralization
Authors: Zan Khine W. , Nakamura Keiki , Hamba Hidenori , Sadr Alireza , Nikaido Toru , Tagami Junji 
Published: July 2018

Using micro‐computed tomography (micro‐CT), this study assessed the inhibitory effect of three different types of restorations on root‐caries formation under a cariogenic challenge. Bovine‐root dentin blocks with a cylindrical cavity were divided into three restoration groups: a fluoride‐free self‐etch adhesive and a resin composite (SE‐ES); a self‐etch adhesive and a resin composite with multi‐ion release (FL‐BF); and a glass ionomer cement (Fuji‐VII). After the restorative procedures, the specimens were stored in artificial saliva for 1 d, then subjected to a demineralization solution for 4 d and a remineralization solution for 28 d. Mineral density and mean mineral loss of dentin around the restorations were measured using micro‐CT. The mean mineral loss values of dentin around the restorations were highest among SE‐ES restorations and lowest among Fuji‐VII restorations. Fuji‐VII showed the highest mineral density and the lowest mineral loss after 28 d of remineralization. The observations made by scanning electron microscopy demonstrated that Fuji‐VII created the smallest outer lesion followed by FL‐BF and SE‐ES. Fuji‐VII has a larger inhibitory effect on root caries around the restorations and enhances remineralization more effectively than either FL‐BF or SE‐ES. Multi‐ion and fluoride release from the restorative materials may be beneficial for inhibition of root‐dentin caries around the restorations.
Structure‐based design and molecular profiling of Smac‐mimetics selective for cellular IAPs
Authors: Corti Alessandro , Milani Mario , Lecis Daniele , Seneci Pierfausto , de Rosa Matteo , Mastrangelo Eloise , Cossu Federica 
Published: July 2018

Inhibitor of Apoptosis Proteins (IAPs) is highly conserved negative regulators of apoptosis overexpressed in many cancer cells. Based on their endogenous antagonist, Smac/DIABLO, mimic compounds (Smac‐mimetics, SMs) have been developed to inhibit IAPs prosurvival activity, showing promising effects in advanced phases of clinical trials. Since different IAP homologs play distinctive roles in cancer cell survival and immunomodulation, SM‐induced apoptosis proceeds through diverse mechanisms. After binding to their BIR3 domain, SMs have been shown to rapidly induce auto‐ubiquitylation and degradation of cellular IAPs (cIAPs), thus leading to cell death mainly by activation of the noncanonical NF‐κB pathway. For this reason, we started the BIR3‐driven design of compounds selective for cIAP1 and with reduced affinity for X‐linked IAP (XIAP), in order to focus SMs antitumor activity on cIAPs degradation. In this work, we describe the crystal structures of the BIR3 domains of cIAP1 and XIAP, each in complex with a cIAP1‐selective SM (SM130 and SM114, respectively). The two SMs displayed 23‐ and 32‐fold higher affinity for cIAP1‐BIR3 over XIAP‐BIR3 in molecular displacement experiments based on fluorescence polarization. In vitro cell‐based assays confirmed that both selective SMs triggered apoptosis in cancer cells with different efficiencies by inducing caspases‐3, ‐8, and ‐9‐independent cIAP1 degradation. The design of cIAPs‐selective compounds represents an innovative approach in the field of anticancer drugs development, being useful to elucidate different prosurvival mechanisms and to reduce the adverse effects of pan‐IAPs compounds in cancer therapy.DatabaseStructural data are available in the Protein Data Bank database under the accession codes 6EXW (cIAP1‐BIR3/SM130 complex) and 6EY2 (XIAP‐BIR3/SM114 complex).
Multimodel ensembles improve predictions of crop–environment–management interactions
Authors: Wallach Daniel , Martre Pierre , Liu Bing , Asseng Senthold , Ewert Frank , Thorburn Peter J. , van Ittersum Martin , Aggarwal Pramod K. , Ahmed Mukhtar , Basso Bruno , Biernath Christian , Cammarano Davide , Challinor Andrew J. , De Sanctis Giacomo , Dumont Benjamin , Eyshi Rezaei Ehsan , Fereres Elias , Fitzgerald Glenn J. , Gao Y. , Garcia‐Vila Margarita , Gayler Sebastian , Girousse Christine , Hoogenboom Gerrit , Horan Heidi , Izaurralde Roberto C. , Jones Curtis D. , Kassie Belay T. , Kersebaum Kurt C. , Klein Christian , Koehler Ann‐Kristin , Maiorano Andrea , Minoli Sara , Müller Christoph , Naresh Kumar Soora , Nendel Claas , O'Leary Garry J. , Palosuo Taru , Priesack Eckart , Ripoche Dominique , Rötter Reimund P. , Semenov Mikhail A. , Stöckle Claudio , Stratonovitch Pierre , Streck Thilo , Supit Iwan , Tao Fulu , Wolf Joost , Zhang Zhao 
Published: July 2018

AbstractA recent innovation in assessment of climate change impact on agricultural production has been to use crop multimodel ensembles (MMEs). These studies usually find large variability between individual models but that the ensemble mean (e‐mean) and median (e‐median) often seem to predict quite well. However, few studies have specifically been concerned with the predictive quality of those ensemble predictors. We ask what is the predictive quality of e‐mean and e‐median, and how does that depend on the ensemble characteristics. Our empirical results are based on five MME studies applied to wheat, using different data sets but the same 25 crop models. We show that the ensemble predictors have quite high skill and are better than most and sometimes all individual models for most groups of environments and most response variables. Mean squared error of e‐mean decreases monotonically with the size of the ensemble if models are added at random, but has a minimum at usually 2–6 models if best‐fit models are added first. Our theoretical results describe the ensemble using four parameters: average bias, model effect variance, environment effect variance, and interaction variance. We show analytically that mean squared error of prediction (MSEP) of e‐mean will always be smaller than MSEP averaged over models and will be less than MSEP of the best model if squared bias is less than the interaction variance. If models are added to the ensemble at random, MSEP of e‐mean will decrease as the inverse of ensemble size, with a minimum equal to squared bias plus interaction variance. This minimum value is not necessarily small, and so it is important to evaluate the predictive quality of e‐mean for each target population of environments. These results provide new information on the advantages of ensemble predictors, but also show their limitations.
Mapping influenza activity in emergency departments in France using Bayesian model‐based geostatistics
Authors: Paireau Juliette , Pelat Camille , Caserio‐Schönemann Céline , Pontais Isabelle , Le Strat Yann , Lévy‐Bruhl Daniel , Cauchemez Simon 
Published: July 2018

BackgroundMaps of influenza activity are important tools to monitor influenza epidemics and inform policymakers. In France, the availability of a high‐quality data set from the Oscour® surveillance network, covering 92% of hospital emergency department (ED) visits, offers new opportunities for disease mapping. Traditional geostatistical mapping methods such as Kriging ignore underlying population sizes, are not suited to non‐Gaussian data and do not account for uncertainty in parameter estimates.ObjectiveOur objective was to create reliable weekly interpolated maps of influenza activity in the ED setting, to inform Santé publique France (the French national public health agency) and local healthcare authorities.MethodsWe used Oscour® data of ED visits covering the 2016‐2017 influenza season. We developed a Bayesian model‐based geostatistical approach, a class of generalized linear mixed models, with a multivariate normal random field as a spatially autocorrelated random effect. Using R‐INLA, we developed an algorithm to create maps of the proportion of influenza‐coded cases among all coded visits. We compared our results with maps obtained by Kriging.ResultsOver the study period, 45 565 (0.82%) visits were coded as influenza cases. Maps resulting from the model are presented for each week, displaying the posterior mean of the influenza proportion and its associated uncertainty. Our model performed better than Kriging.ConclusionsOur model allows producing smoothed maps where the random noise has been properly removed to reveal the spatial risk surface. The algorithm was incorporated into the national surveillance system to produce maps in real time and could be applied to other diseases.
A trait‐based approach reveals the importance of biotic filter for elevational herb richness pattern
Authors: Jiang Zihan , Ma Keming , Liu Hongyan , Tang Zhiyao 
Published: July 2018

AbstractAimTo evaluate how a biotic filter (overstorey cover [OC]) shapes an elevational herb richness pattern and to test whether intermediate elevations represent more suitable habitats for herb species due to the minimal biotic and moderate abiotic filtering that occured there.LocationDongling Mountain, China.TaxonHerbs.MethodsWe sampled herb richness along a 1,000‐m vertical transect (OC and elevation covary) and four horizontal transects (across the OC gradient with no change in elevation). Functional traits related to shade (leaf mass per area [LMA] and leaf stem ratio [LSR]) and freezing tolerance (leaf thickness [LT] and hair density [HD]) were collected based on vegetation sampling plots. We divided the richness data into below‐ and above‐timberline groups and then assessed the most important driver for each group. By estimating the variations in species richness and functional diversity along horizontal transects, we examined how these parameters responded to OC while controlling for associated differences in elevation.ResultsHerb richness showed a unimodal relationship with elevation, with a peak around the timberline. Below the timberline, herb richness was better predicted by OC and showed a positive relationship with the functional diversity of LMA and LSR. The frost period performed better in predicting herb richness above the timberline, and herb richness was positively related to the functional diversity of HD.Main conclusionsThe results support our hypothesis and highlight the importance of OC in shaping herb richness patterns. Below the timberline, OC acts as a filter, sorting species based on their ability to tolerate shade, whereas the frost period limits richness above the timberline and favours species that can tolerate low temperatures. Therefore, we suggest that biotic interactions, as well as environmental and geographical factors, should be considered the main drivers of elevational plant richness patterns.
Variants in Notch signalling pathway genes, PSEN1 and MAML2, predict overall survival in Chinese patients with epithelial ovarian cancer
Authors: Xu Yuan , Cheng Lei , Dai Hongji , Zhang Ruoxin , Wang Mengyun , Shi Tingyan , Sun Menghong , Cheng Xi , Wei Qingyi 
Published: July 2018

AbstractTo identify genetic variants in Notch signalling pathway genes that may predict survival of Han Chinese patients with epithelial ovarian cancer (EOC), we analysed a total of 1273 single nucleotide polymorphisms (SNPs) within 75 Notch genes in 480 patients from a published EOC genomewide association study (GWAS). We found that PSEN1 rs165934 and MAML2 rs76032516 were associated with overall survival (OS) of patients by multivariate Cox proportional hazards regression analysis. Specifically, the PSEN1 rs165934 AA genotype was associated with a poorer survival (adjusted hazards ratio [adjHR] = 1.41, 95% CI = 1.07‐1.84, and P = .014), compared with the CC + CA genotype, while MAML2 rs76032516 AA + AC genotypes were associated with a poorer survival (adjHR = 1.58, 95% CI = 1.16‐2.14, P = .004), compared with the CC genotype. The combined analysis of these two SNPs revealed that the death risk increased as the number of unfavourable genotypes increased in a dose‐dependent manner (Ptrend < .001). Additionally, the expression quantitative trait loci analysis revealed that the SNP rs165932 in the rs165934 LD block (r2 = .946) was associated with expression levels of PSEN1, which might be responsible for the observed association with SNP rs165934. The associations of PSEN1 rs165934 and MAML2 rs76032516 of the Notch signalling pathway genes with OS in Chinese EOC patients are novel findings, which need to be validated in other large and independent studies.
The impact of school support on depression among adolescent orphans: a cluster‐randomized trial in Kenya
Authors: Green Eric P. , Cho Hyunsan , Gallis John , Puffer Eve S. 
Published: July 2018

BackgroundThe objective of this study was to determine if a school support intervention for adolescent orphans in Kenya had effects on mental health, a secondary outcome.MethodsIn this paper, we analyzed data from a 4‐year cluster‐randomized trial of a school support intervention (school uniforms, school fees, and nurse visits) conducted with orphaned adolescents in Siaya County, western Kenya, who were about to transition to secondary school. 26 primary schools were randomized (1:1) to intervention (410 students) or control (425 students) arms. The study was longitudinal with annual repeated measures collected over 4 years from 2011 to 2014. We administered five items from the 20‐item Center for Epidemiologic Studies Depression Scale Revised, a self‐reported depression screening instrument.ResultsThe intervention prevented depression severity scores from increasing over time among adolescents recruited from intervention schools. There was no evidence of treatment heterogeneity by gender or baseline depression status. The intervention effect on depression was partially mediated by higher levels of continuous school enrollment among the intervention group, but this mediated effect was small.ConclusionsSchool support for orphans may help to buffer against the onset or worsening of depression symptoms over time, promoting resilience among an important at‐risk population.
Differential predation alters pigmentation in threespine stickleback (Gasterosteus aculeatus)
Authors: Gygax Michelle , Rentsch Ana K. , Rudman Seth M. , Rennison Diana J. 
Published: July 2018

AbstractAnimal pigmentation plays a key role in many biological interactions, including courtship and predator avoidance. Sympatric benthic and limnetic ecotypes of threespine stickleback (Gasterosteus aculeatus) exhibit divergent pigment patterns. To test whether differential predation by cutthroat trout contributes to the differences in pigmentation seen between the ecotypes, we used a within‐generation selection experiment on F2 benthic–limnetic hybrids. After 10 months of differential selection, we compared the pigmentation of fish under trout predation to control fish not exposed to trout predation. We found that stickleback exhibited more lateral barring in ponds with trout predation. Ponds with trout were also less turbid, and a greater degree of barring was negatively correlated with the magnitude of turbidity across pond replicates. A more benthic diet, a proxy for habitat use, was also correlated with greater lateral barring and green dorsal pigmentation. These patterns suggest that differential exposure to cutthroat trout predation may explain the divergence in body pigmentation between benthic and limnetic ecotypes.
Costs of walking: differences in egg size and starvation resistance of females between strains of the red flour beetle (Tribolium castaneum) artificially selected for walking ability
Authors: Matsumura Kentarou , Miyatake Takahisa 
Published: July 2018

AbstractIn many animals, movement often affects fitness components such as foraging or migration. On the other hand, individuals with higher mobility also often have fitness costs. This trade‐off between movement and other traits may explain the maintenance of variation in moving ability in a population. However, few studies have focused on movement by walking, although many previous studies of insects have investigated the evolution of variations in mobility with wing polymorphism. In this study, we focused on the walking ability of the red flour beetle (Tribolium castaneum) and investigated whether females with higher than lower walking ability have fitness costs. The present results showed that females with genetically higher walking ability produced smaller eggs and had lower starvation resistance than females with lower walking ability. These results suggest that higher walking ability is costly for females, and this fitness cost may explain maintenance of variations of walking ability in a population.