bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated analysis of the miRNA-mRNA network associated with LMP1 gene in nasopharyngeal carcinoma
Authors: Yang Yang , Liu Wen , Zhang Yan , Wu Shuo , Luo Bing
Published: April 2019

Epstein-Barr virus oncogenic latent membrane protein 1 (LMP1) has been known to play important roles in nasopharyngeal carcinoma (NPC). LMP1 gene also induced a variety of microRNAs (miRNAs) which bear pivotal roles in regulation of mRNAs expression. However, little was known about the global change of mRNAs and miRNAs induced by LMP1 gene in NPC. In our study, one NPC tissue microarray profile and two LMP1-associated microarray expression profiles data were downloaded from the Gene Expression Omnibus database. A protein-protein interaction network was constructed by using bioinformatics platform Gene-Cloud of Biotechnology Information (GCBI). 78 differentially expressed miRNAs and 3322 differentially expressed genes were identified in order to generate a macroscopic network between miRNAs and mRNAs associated with LMP1 gene. In addition, two significant models were generated to illustrate the expression tendency. Our study provided a way to reveal the interaction between miRNAs and mRNAs in LMP1 axis, bringing insights into the pathogenesis of NPC.
CNNcon: A Quantitative Imaging Tool for Lung CT Image Feature Analysis
Authors: Causey Jason , Qualls Jake , Moore Jason H. , Prior Fred , Huang Xiuzhen
Published: April 2019

Background

Lung CT scans are widely used for lung cancer screening and diagnosis. Current research focuses on quantitative analytics (radiomics) to improve screening and detection accuracy. However there are very limited numbers of portable software tools for automatic lung CT image analysis.

Results

Here we build a Docker container, CNNcon, as a quantitative imaging tool for analyzing lung CT image features. CNNcon is developed from our recently published algorithm for nodule analysis, based on convolutional neural networks (CNN). When provided with a list of the centroid coordinates of regions of interest (ROI) in a volumetric CT study containing potential lung nodules, CNNcon can automatically generate highly accurate malignancy prediction of each ROI. CNNcon can also generate a vector of image features of each ROI, to facilitate further analyses by combining image features and other clinical features. As a Docker container, CNNcon is portable to various computer systems, convenient to install, and easy to use. CNNcon was tested on different computer systems and generated identical results.

Conclusions

We anticipate that CNNcon will be a useful tool and broadly acceptable to the research community interested in quantitative image analysis.

Availability

CNNcon and document are publicly available and can be downloaded from the website: http://bioinformatics.astate.edu/CNN-Container/
Germline genomic patterns are associated with cancer risk, oncogenic pathways and clinical outcomes
Authors: Feng Xiaowen , Xu Xue , Li Derek , Cui Qinghua , Wang Edwin
Published: April 2019

Germline genetic polymorphism is prevalent and inheritable. So far mutations of a handful of genes have been associated with cancer risks. For example, women who harbor BRCA1/2 germline mutations have a 70% of cumulative breast cancer risk; individuals with congenital germline APC mutations have nearly 100% of cumulative colon cancer by the age of fifty. At present, gene-centered cancer predisposition knowledge explains only a small fraction of the inheritable cancer cases. Here we conducted a systematic analysis of the germline genomes of cancer patients (n=9,712) representing 22 common cancer types along with non-cancer individuals (n=16,670), and showed that seven germline genomic patterns, or significantly repeatedly occurring sequential mutation profiles, could be associated with both carcinogenesis processes and cancer clinical outcomes. One of the genomic patterns was significantly enriched in the germline genomes of patients who smoked than in those of non-smoker patients of 13 common cancer types, suggesting that the germline genomic pattern was likely to confer an elevated carcinogenesis sensitivity to tobacco smoke. Several patterns were also associated with somatic mutations of key oncogenic genes and somatic-mutational signatures which are associated with higher genome instability in tumors. Furthermore, subgroups defined by the germline genomic patterns were significantly associated with distinct oncogenic pathways, tumor histological subtypes and prognosis in 12 common cancer types, suggesting that germline genomic patterns enable to inform treatment and clinical outcomes. These results demonstrated that genetic cancer risk and clinical outcomes could be encoded in germline genomes in the form of not only mutated genes, but also specific germline genomic patterns, which provided a novel perspective for further investigation.
Personality maturation among emerging adults and future career success
Authors: Kalfon Hakhmigari Maor , Michaeli Yossi , J. Dickson Daniel , Scharf Miri , Shulman Shmuel
Published: April 2019

Purpose

The purpose of this paper is to examine the role of maturation processes – personality change and reflectivity as characterized by greater awareness to self and others – during emerging adulthood in predicting career success.

Design/methodology/approach

A sample of 205 of Israeli emerging adults was followed over a 12-year period. Participants completed measures of self-criticism at age 23 and 29, reflectivity at the age of 29 and subjective and objective career outcomes such as satisfaction with work and level of income at the age of 35. Hierarchical regressions determined the extent that decreases in self-criticism as well as greater reflectivity that predicted future career success.

Findings

The findings of this paper indicated that greater decreases in self-criticism were longitudinally associated with less frequent negative experiences at work and lesser tendency to have doubts about one’s career. Greater reflective capacity was longitudinally associated with a future higher income, greater career satisfaction and a stronger perception of one’s career as a means to implement inner interests.

Research limitations/implications

The results of this paper suggest that decreasing negative self-perception and enhancing awareness about self and others might facilitate a future career success.

Originality/value

This is among the first studies that demonstrate the role of personality maturation during emerging adulthood for future career success.
Organizational citizenship behaviors in the era of changing employment patterns
Authors: Lo Presti Alessandro , Manuti Amelia , Briscoe Jon P.
Published: April 2019

Purpose

The increasing flexibility and discontinuity of labor relations have been associated with the development of new forms of psychological contracts as well as the development of more self-directed and mobile career attitudes. The purpose of this paper is to examine the relationship between the forms of psychological contract and protean/boundaryless career attitudes on the one hand and organizational citizenship behaviors (OCB) on the other.

Design/methodology/approach

In total, 458 employees of three large Italian organizations were sampled through a self-report questionnaire. Zero-order correlations were carried out to examine the associations between study variables while dominance analysis, along with multiple linear regression, was used for evaluating their unique contribution with respect to OCB.

Findings

OCB were positively predicted by relational and balanced psychological contracts, protean career attitude and boundaryless mindset.

Practical implications

Organizations must pay particular attention to the content of the psychological contract and the career attitudes of their employees because they influence their willingness to carry out OCB.

Originality/value

The results add new evidence to the careers literature in terms of boundary conditions with regard to the effects of protean and boundaryless career attitudes as well as different forms of psychological contracts.
Comparative genome‐scale modelling of the pathogenic Flavobacteriaceae species Riemerella anatipestifer in China
Authors: Liu Jibin , Zeng Qiurui , Wang Mingshu , Cheng Anchun , Liu Mafeng , Zhu Dekang , Chen Shun , Jia Renyong , Zhao Xin‐Xin , Wu Ying , Yang Qiao , Zhang Shaqiu , Liu Yunya , Yu Yanling , Zhang Ling , Chen Xiaoyue
Published: April 2019

Riemerella anatipestifer (RA) is a gram‐negative bacterium that has a high potential to infect waterfowl. Although more and more genomes of RA have been generated comparaed to genomic analysis of RA still remains at the level of individual species. In this study, we analysed the pan‐genome of 27 RA virulent isolates to reveal the intraspecies genomic diversity from various aspects. The multi‐locus sequence typing (MLST) analysis suggests that the geographic origin of R. anatipestifer is Guangdong province, China. Results of pan‐genome analysis revealed an open pan‐genome for all 27 species with the sizes of 2967 genes. We identified 387 genes among 555 unique genes originated by horizontal gene transfer. Further studies showed 204 strain‐specific HGT genes were predicted as virulent proteins. Screening the 1113 core genes in RA through subtractive genomic approach, 70 putative vaccine targets out of 125 non‐cytoplasmic proteins have been predicted. Further analysis of these non A. platyrhynchos homologous proteins predicted that 56 essential proteins as drug target with more interaction partners were involved in unique metabolic pathways of RA. In conclusion, the present study indicated the essence and the diversity of RA and also provides useful information for identification of vaccine and drugs candidates in future.
Perception of Western governments’ hostility to Islam among European Muslims before and after ISIS: the important roles of residential segregation and education
Authors: Hekmatpour Peyman , Burns Thomas J.
Published: April 2019

Perception of Western governments’ hostility to Islam is one of the indicating features of Islamic fundamentalism and, in some cases, is serving as a pull to join extremist groups. In this paper, using data from two waves of a cross‐national survey, we investigate what affects European Muslims’ opinions about Western governments. We find that residential segregation is associated with perceived hostility of Western governments to Islam. Further, we find that Muslims living in segregated neighbourhoods and enclaves have a higher probability of believing that Western governments are hostile to Islam. National origins of Muslim immigrants have a significant impact, with people from African countries measuring less perceived hostility than others. We also find that education is associated with perceived hostility of Western governments to Islam in a non‐linear way. People with the highest and lowest levels of education tend to be less likely to believe that Western governments are hostile to Islam, relative to people with mid‐level education. This non‐linear effect is best explained by education’s differential effects on perceptions of key world events. During the time between 2011 – before ISIS’s announcement of its Caliphate in Iraq and Syria – and 2013, subsequent to that announcement, we see a sharp decrease in perception of Western governments’ hostility to Islam, particularly among more educated European Muslims. We make the case that this decrease can be attributed, in some ways, to the emergence of ISIS. We discuss our findings in terms of theoretical and policy implications.
A multi‐level model of commitment‐based human resource practices on team performance: the team cognition model
Authors: Liu Min‐Shi , Wang Mei‐Ling
Published: April 2019

In recent years, many studies of competitive advantage have focused on how to efficiently develop team performance, such as by developing organizational interventions and team cognition structures that facilitate teamwork activities. This study focuses on the multi‐level effects of commitment‐based human resource (HR) practices, team cognition (awareness of expertise location and shared task understanding), teamwork processes, and team performance. A cross‐sectional study was conducted of 154 teams. This study has not only verified that organizational‐level commitment‐based HR practices rely on team‐level team cognition to influence team performance, but also verified that teamwork processes constitute an important mediating factor. In addition, commitment‐based HR practices give signals to team members expressing the team's values and the team's concern and support for members. This helps team members to understand the team's mission, goals, assessed strategies, which facilitates members’ co‐ordination and integration of the team's mission and activities.
Does More Storage Give California More Water?
Authors: Nover D.M. , Dogan M.S. , Ragatz R. , Booth L. , Medellín‐Azuara J. , Lund J.R. , Viers J.H.
Published: April 2019

Increasing reservoir storage is commonly proposed to mitigate increasing water demand and provide drought reserves, especially in semiarid regions such as California. This paper examines the value of expanding surface reservoir capacity in California using hydroeconomic modeling for historical conditions, a future warm‐dry climate, and California's recently adopted policy to end groundwater overdraft. Results show expanding surface storage capacity rarely provides sizable economic value in most of California. On average, expanding facilities north of California's Delta provides some benefit in 92% of 82 years modeled under historical conditions and in 61% of years modeled in a warm‐dry climate. South of California's Delta, expanding storage capacity provides no benefits in 14% of years modeled under historical conditions and 99% of years modeled with a warm‐dry climate. Results vary across facilities between and within regions. The limited benefit of surface storage capacity expansion to statewide water supply should be considered in planning California's water infrastructure.
Seventh World congress on controversies to consensus in diabetes, obesity, and hypertension
Authors: Kurian Martin J. , Rentzepis Peter J. , Carracher Ann M. , Close Kelly L.
Published: April 2019

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.
A population genetic assessment of taxonomic species: The case of Lake Malawi cichlid fishes
Authors: Pinho Catarina , Cardoso Vera , Hey Jody
Published: April 2019

Organisms sampled for population‐level research are typically assigned to species by morphological criteria. However, if those criteria are limited to one sex or life stage, or the organisms come from a complex of closely related forms, the species assignments may misdirect analyses. The impact of such sampling can be assessed from the correspondence of genetic clusters, identified only from patterns of genetic variation, to the species identified using only phenotypic criteria. We undertook this protocol with the rock‐dwelling mbuna cichlids of Lake Malawi, for which species within genera are usually identified using adult male coloration patterns. Given high local endemism of male colour patterns, and considerable allele sharing among species, there persists considerable taxonomic uncertainty in these fishes. Over 700 individuals from a single transect were photographed, genotyped and separately assigned: (a) to morphospecies using photographs; and (b) to genetic clusters using five widely used methods. Overall, the correspondence between clustering methods was strong for larger clusters, but methods varied widely in estimated number of clusters. The correspondence between morphospecies and genetic clusters was also strong for larger clusters, as well as some smaller clusters for some methods. These analyses generally affirm (a) adult male‐limited sampling and (b) the taxonomic status of Lake Malawi mbuna, as the species in our study largely appear to be well‐demarcated genetic entities. More generally, our analyses highlight the challenges for clustering methods when the number of populations is unknown, especially in cases of highly uneven sample sizes.
Long‐term safety of a weekly and monthly subcutaneous buprenorphine depot (CAM2038) in the treatment of adult out‐patients with opioid use disorder
Authors: Frost Michael , Bailey Genie L. , Lintzeris Nicholas , Strang John , Dunlop Adrian , Nunes Edward V. , Jansen Jakob Billeskov , Frey Lars Chemnitz , Weber Bernd , Haber Paul , Oosman Sonia , Kim Sonnie , Tiberg Fredrik
Published: April 2019

Aims

To assess the long‐term safety of subcutaneous buprenorphine (CAM2038) weekly and monthly depots.

Design

Phase 3, open‐label, observational, multi‐centre 48‐week trial (ClinicalTrials.gov NCT02672111).

Setting

Twenty‐six out‐patient sites (United States, United Kingdom, Hungary, Denmark, Sweden, Germany, Australia) between 14 December 2015 and 12 April 2017.

Participants

Two hundred and twenty‐eight adults with opioid use disorder; 227 received CAM2038 (37 initiated onto CAM2038 and 190 converted from sublingual buprenorphine).

Interventions

CAM2038 weekly (8, 16, 24 or 32 mg) or monthly (64, 96, 128 or 160 mg) with flexible dosing and individualized titration utilizing multiple CAM2038 weekly and monthly doses.

Measurements

Safety variables, urine toxicology samples and self‐reported illicit opioid use were collected at each visit. Participants were administered a patient satisfaction survey at months 6 and 12, completed by 162 of 227 (71.4%) participants.

Findings

The study treatment period was completed by 167 of 227 (73.6%) participants. At least one treatment‐emergent adverse event (TEAE) was reported by 143 of 227 (63.0%) participants, of whom 60 of 227 (26.4%) reported as being drug‐related. Most of the TEAEs, reported by 128 of 227 (56.4%) of participants, were mild or moderate in intensity. Injection‐site reactions were reported by 46 of 227 (20.3%) participants, with most [45 of 46 (97.8%)] reported as mild to moderate. Five participants (2.2%) discontinued the study drug due to a TEAE, two cases (0.9%) of which were injection‐site‐related. No serious adverse events were attributed to the study drug. Among those remaining in the study, the percentage of opioid‐negative urine tests combined with self‐reports was 63.0% (17 of 27) in new‐to‐treatment participants and 82.8% (111 of 134) for those converted from sublingual buprenorphine. Participants reported high levels of satisfaction with CAM2038.

Conclusions

Subcutaneous buprenorphine delivered weekly or monthly (CAM2038) was well tolerated, with a systemic safety profile consistent with the known profile of sublingual buprenorphine. CAM2038 weekly and monthly was associated with high retention rates and low levels of illicit opioid use throughout this study.
Riparian zone as a main determinant of the structure of lizard assemblages in upland Amazonian forests
Authors: Faria Ayra Souza , Menin Marcelo , Kaefer Igor Luis
Published: April 2019

The use of lizards as model organisms in ecological studies is based on their success in occupying a great diversity of habitats, and some species are closely tied to the environment, which is disadvantaged by the legislation of several countries concerning land use. Our aim was to relate lizard species distribution patterns in rainforest environments to variation in environmental gradients, and provide ecologically based metrics for establishing buffer zones around streams. Lizards were sampled three times in 41 standardised transects near Manaus, Brazil, only in dry season, with Time Limited Visual Search associated with raking through leaf litter. We recorded 20 species from 10 families and used non‐metric multidimensional scaling to reduce the dimensionality of quantitative and qualitative compositions of species. Multiple linear regression models indicated that the environmental gradients distance to nearest stream, extent of canopy openness, vegetation density and slope did not significantly influence assemblage species distribution, with an indication of effect of litter depth. By means of piecewise linear regression, the use of riparian zone was estimated at ~190 m from quantitative species composition and ~211 m from qualitative species composition. Five species occurred only in the riparian zone. Our results suggest that conservation of the entire riparian lizard assemblage in Amazonian rainforest is likely to require protection of at least a 211 m buffer on either side of streams.
What did we learn from multiple omics studies in asthma?
Authors: Ivanova Olga , Richards Levi B. , Vijverberg Susanne J. , Neerincx Anne H. , Sinha Anirban , Sterk Peter J. , Maitland‐van der Zee Anke H.
Published: April 2019

More than a decade has passed since the finalization of the Human Genome Project. Omics technologies made a huge leap from trendy and very expensive to routinely executed and relatively cheap assays. Simultaneously, we understood that omics is not a panacea for every problem in the area of human health and personalized medicine. Whilst in some areas of research omics showed immediate results, in other fields, including asthma, it only allowed us to identify the incredibly complicated molecular processes. Along with their possibilities, omics technologies also bring many issues connected to sample collection, analyses and interpretation. It is often impossible to separate the intrinsic imperfection of omics from asthma heterogeneity. Still, many insights and directions from applied omics were acquired—presumable phenotypic clusters of patients, plausible biomarkers and potential pathways involved. Omics technologies develop rapidly, bringing improvements also to asthma research. These improvements, together with our growing understanding of asthma subphenotypes and underlying cellular processes, will likely play a role in asthma management strategies.
Improved Methods for Estimating Abundance and Related Demographic Parameters From Mark-Resight Data
Authors: McClintock Brett T. , White Gary C. , Pryde Moira A.
Published: April 2019

Over the past decade, there has been much methodological development for the estimation of abundance and related demographic parameters using mark-resight data. Often viewed as a less-invasive and less-expensive alternative to conventional mark recapture, mark-resight methods jointly model marked individual encounters and counts of unmarked individuals, and recent extensions accommodate common challenges associated with imperfect detection. When these challenges include both individual detection heterogeneity and an unknown marked sample size, we demonstrate several deficiencies associated with the most widely used mark-resight models currently implemented in the popular capture-recapture freeware Program MARK. We propose a composite likelihood solution based on a zero-inflated Poisson log-normal model and find the performance of this new estimator to be superior in terms of bias and confidence interval coverage. Under Pollock's robust design, we also extend the models to accommodate individual-level random effects across sampling occasions as a potentially more realistic alternative to models that assume independence. As a motivating example, we revisit a previous analysis of mark-resight data for the New Zealand Robin (Petroica australis) and compare inferences from the proposed estimators. For the all-too-common situation where encounter rates are low, individual detection heterogeneity is non-negligible, and the number of marked individuals is unknown, we recommend practitioners use the zero-inflated Poisson log-normal mark-resight estimator as now implemented in Program MARK.
Assessing the instructional quality of private tutoring and its effects on student outcomes: Analyses from the German National Educational Panel Study
Authors: Guill Karin , Lüdtke Oliver , Köller Olaf
Published: April 2019

Background

A considerable proportion of secondary school students gets additional support from private tutoring lessons. Empirical findings on the effectiveness of private tutoring are inconclusive. The instructional quality of the tutoring lessons might influence their effectiveness.

Aims

We analysed (1) whether students privately tutored in the subjects German or mathematics outperformed their non‐tutored counterparts; (2) whether the instructional quality of the tutoring lessons can be described with the three dimensions, structure, challenge, and support; and (3) the effects of these quality dimensions on the students’ academic achievement and their global satisfaction with their school and family situation.

Sample

We used data from the German National Educational Panel Study (NEPS). From a total sample of N = 11,358 10th‐grade secondary school students, subsamples provided information about tutoring quality in mathematics (nM = 1,714), German (nG = 148), and English (nE = 490).

Methods

The model of three correlated dimensions of tutoring quality was evaluated with confirmatory factor analyses, and the effects on student outcomes were tested in a structural equation modelling framework.

Results

Analyses revealed neither global effects of private tutoring nor effects of its instructional quality on students’ grades in mathematics or German. However, the support dimension was positively related to students’ satisfaction with their school situation.

Conclusions

Private tutoring cannot be recommended as a generally effective strategy to improve academic achievement in school, but might be helpful to relieve the stress level induced by insufficient achievement in school.
Value of supranormal function on 99mTc‐mercaptoacetyltriglycine renal scan in paediatric patients with obstructive hydronephrosis
Authors: Martín‐Solé Oriol , Soria‐Gondek Andrea , Pérez‐Bertólez Sonia , Paredes Pilar , Tarrado Xavier , García‐Aparicio Luis
Published: April 2019

Objectives

To study related factors and clinical significance of supranormal function in paediatric patients with pelvi‐ureteric junction obstruction, and to predict which factors cause renal function overestimation.

Patients and Methods

Patients who underwent pyeloplasty from 2012 to 2017 were prospectively collected. Variables were compared between patients with and without supranormal function on 99mTc‐mercaptoacetyltriglycine renal scan (supranormal defined as differential renal function [DRF] ≥55%). Univariate, multivariate logistic and linear regressions analyses were performed.

Results

Of 100 patients, 18 were excluded because of comorbidities. Nine patients (11.5%) showed preoperative supranormal function. The preoperative anteroposterior pelvic diameter (APD; 24 mm vs 35 mm, P = 0.026) and the ratio between preoperative pelvic and kidney volumes (0.2 vs 0.6, P = 0.003) were higher in supranormal kidneys. For each unit increase in the preoperative ratio between pelvic and kidney volumes, the risk of supranormal function rose 3.23‐times (95% confidence interval [CI] 1.051–9.955). A preoperative APD ≥30 mm was a reliable predictor of supranormal function (area under the curve 0.804, 95% CI 0.707–0.902), with 88.9% sensitivity. Patients with either preoperative supranormal function or preoperative APD ≥30 mm had a greater reduction in renal function after pyeloplasty.

Conclusion

Supranormal function is related to large hydronephrosis where geometrical features are modified. A preoperative APD ≥30 mm is a reliable predictive factor of supranormal function. Preoperative renal function is overestimated either in supranormal patients or severe hydronephrotic kidneys. DRF should be interpreted with caution in kidneys with large hydronephrosis with or without supranormal function. Surgical indication should not entirely rely upon DRF.
Modulating autophagy as a therapeutic strategy for the treatment of paediatric high‐grade glioma
Authors: Howarth Alison , Madureira Patricia A. , Lockwood George , Storer Lisa C. D. , Grundy Richard , Rahman Ruman , Pilkington Geoffrey J. , Hill Richard
Published: April 2019

Paediatric high‐grade gliomas (pHGG) represent a therapeutically challenging group of tumors. Despite decades of research, there has been minimal improvement in treatment and the clinical prognosis remains poor. Autophagy, a highly conserved process for recycling metabolic substrates is upregulated in pHGG, promoting tumor progression and evading cell death. There is significant crosstalk between autophagy and a plethora of critical cellular pathways, many of which are dysregulated in pHGG. The following article will discuss our current understanding of autophagy signaling in pHGG and the potential modulation of this network as a therapeutic target.
Three‐dimensional forward stratigraphic modelling of the sedimentary architecture of meandering‐river successions in evolving half‐graben rift basins
Authors: Yan Na , Colombera Luca , Mountney Nigel P.
Published: April 2019

The spatial organisation of meandering‐river deposits varies greatly within the sedimentary fills of rift basins, depending on how differential rates of fault propagation and subsidence interplay with autogenic processes to drive changes in fluvial channel‐belt position and rate of migration, avulsion frequency and mechanisms of meander‐bend cut off. This set of processes fundamentally influences stacking patterns of the accumulated successions. Quantitative predictions of the spatio‐temporal evolution and internal architecture of meandering fluvial deposits in such tectonically active settings remain limited. A numerical forward stratigraphic model—the Point‐Bar Sedimentary Architecture Numerical Deduction (PB‐SAND)—is applied to examine relationships between differential rates of subsidence and resultant fluvial channel‐belt migration, reach avulsion and channel‐deposit stacking in active, fault‐bounded half‐grabens. The model is used to reconstruct and predict the complex morphodynamics of fluvial meanders, their generated channel belts, and the associated lithofacies distributions that accumulate as heterogeneous fluvial successions in rift settings, constrained by data from seismic images and outcrop successions. The 3D modelling outputs are used to explore sedimentary heterogeneity at various spatio‐temporal scales. Results show how the connectivity of sand‐prone geobodies can be quantified as a function of subsidence rate, which itself decreases both along and away from the basin‐bounding fault. In particular, results highlight the spatial variability in the size and connectedness of sand‐prone geobodies that is seen in directions perpendicular and parallel to the basin axis, and that arises as a function of the interaction between spatial and temporal variations in rates of accommodation generation and fault‐influenced changes in river morphodynamics. The results have applied significance, for example, to both hydrocarbon exploration and assessment of groundwater aquifers. The expected greatest connectivity of fluvial sandbody in a half‐graben is primarily determined by the complex interplay between the frequency and rate of subsidence, the style of basin propagation, the rates of migration of channel belts, the frequency of avulsion and the proportion and spatial distribution of variably sand‐prone channel and bar deposits.
Repressive role of stabilized hypoxia inducible factor 1α expression on transforming growth factor β‐induced extracellular matrix production in lung cancer cells
Authors: Ando Akira , Hashimoto Naozumi , Sakamoto Koji , Omote Norihito , Miyazaki Shinichi , Nakahara Yoshio , Imaizumi Kazuyoshi , Kawabe Tsutomu , Hasegawa Yoshinori
Published: April 2019

Activation of transforming growth factor β (TGF‐β) combined with persistent hypoxia often affects the tumor microenvironment. Disruption of cadherin/catenin complexes induced by these stimulations yields aberrant extracellular matrix (ECM) production, characteristics of epithelial‐mesenchymal transition (EMT). Hypoxia‐inducible factors (HIF), the hallmark of the response to hypoxia, play differential roles during development of diseases. Recent studies show that localization of cadherin/catenin complexes at the cell membrane might be tightly regulated by protein phosphatase activity. We aimed to investigate the role of stabilized HIF‐1α expression by protein phosphatase activity on dissociation of the E‐cadherin/β‐catenin complex and aberrant ECM expression in lung cancer cells under stimulation by TGF‐β. By using lung cancer cells treated with HIF‐1α stabilizers or carrying doxycycline‐dependent HIF‐1α deletion or point mutants, we investigated the role of stabilized HIF‐1α expression on TGF‐β‐induced EMT in lung cancer cells. Furthermore, the underlying mechanisms were determined by inhibition of protein phosphatase activity. Persistent stimulation by TGF‐β and hypoxia induced EMT phenotypes in H358 cells in which stabilized HIF‐1α expression was inhibited. Stabilized HIF‐1α protein expression inhibited the TGF‐β‐stimulated appearance of EMT phenotypes across cell types and species, independent of de novo vascular endothelial growth factor A (VEGFA) expression. Inhibition of protein phosphatase 2A activity abrogated the HIF‐1α‐induced repression of the TGF‐β‐stimulated appearance of EMT phenotypes. This is the first study to show a direct role of stabilized HIF‐1α expression on inhibition of TGF‐β‐induced EMT phenotypes in lung cancer cells, in part, through protein phosphatase activity.
Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study
Authors: Mistraletti Giovanni , Paroni Rita , Umbrello Michele , Moro Salihovic Bedrana , Coppola Silvia , Froio Sara , Finati Elena , Gasco Paolo , Savoca Adriana , Manca Davide , Chiumello Davide , Reiter Russel J. , Iapichino Gaetano
Published: April 2019

Background and objectives

Critically ill patients present reduced endogenous melatonin blood levels, and they might benefit from its exogenous supplementation. The aim of this research was to evaluate the feasibility of different routes of administration and drug formulations of melatonin. The efficiency of absorption was assessed as well as the adequacy in achieving and maintaining the physiological nocturnal blood peak.

Methods

Twenty‐one high‐risk critically ill patients were randomly assigned to receive melatonin either: (a) per os, as a standard tablet (ST‐OS), (b) per os, as a suspension in solid lipid nanoparticles (SLN‐OS) or c) transdermal (TD), by applying a jellified melatonin microemulsion (μE) on the skin (μE‐TD). SLN‐OS and μE‐TD were lipid‐based colloidal systems. The endogenous melatonin blood values were observed for 24 hours; subsequently, melatonin 3 mg was administered and pharmacokinetics was studied for 24 hours further.

Results

In both groups that received ST‐OS and SLN‐OS, the median time‐to‐peak blood concentration was 0.5 hours; however, the area under the curve (AUC) after administration of SLN‐OS was significantly higher than after ST‐OS (157386 [65732‐193653] vs 44441 [22319‐90705] pg/mL*hours, P = 0.048). μE‐TD presented a delayed time‐to‐peak blood concentration (4 hours), a lower bioavailability (AUC: 3142 [1344‐14573] pg/mL*hours) and reached pharmacological peak concentration (388 [132‐1583] pg/mL).

Conclusions

SLN‐melatonin enterally administered offers favourable pharmacokinetics in critically ill patients, with higher bioavailability with respect to the standard formulation; μE‐TD provided effective pharmacological blood levels, with a time‐concentration profile more similar to the physiological melatonin pattern.
Changes of visualised Eustachian tube lengths by age and position: Radiologic study in sitting and supine positions using cone beam and conventional CT
Authors: Ha Seung Cheol , Baik Jin , Park Hyo Jung , Moon Hyun , Kang Byung Chul , Park Jun Woo , Kang Woo Seok , Park Hong Ju
Published: April 2019

Objectives

Patulous eustachian tube (ET) has been characterised by the visualisation of full‐length ET on computed tomography (CT) results. We wanted to investigate the changes of visualised ET lengths by age in supine and sitting positions.

Design

Retrospective study.

Setting

Tertiary care academic referral centre.

Participants

One hundred subjects who underwent cone beam CT (CBCT) in a sitting position and conventional CT in a supine position for non‐otitis‐related or dental complaints.

Main outcome measures

Visualised ET lengths from the nasopharyngeal orifice measured by different positions and ages.

Results

Subjects did not show visualisation of full‐length ET throughout the study. The visualised ET lengths (9.0 ± 2.5 mm) of the CBCT group were significantly larger than those (6.8 ± 2.3 mm) of the conventional CT group (P < 0.0001).Women showed longer visualised ET lengths than men in CBCT group (P < 0.001). The visualised ET lengths of the CBCT group were consistent or slightly increasing as a function of age (P = 0.06); however, the visualised ET lengths of the conventional CT group decreased as a function of age (P = 0.001). The slopes of regression lines of the two groups were significantly different.

Conclusions

When in the supine position, the ET lengths gradually shortened as the subjects got older, most likely due to venous engorgement and the collapse of surrounding tissues; this finding thus suggests that CT in a supine position is an inappropriate method to diagnose patulous ET. The visualised ET lengths by CBCT in a sitting position were consistent throughout the different ages of the subjects and may be used as a diagnostic test for patulous ET.
Correlations between computational fluid dynamics and clinical evaluation of nasal airway obstruction due to septal deviation: An observational study
Authors: Radulesco Thomas , Meister Lionel , Bouchet Gilles , Varoquaux Arthur , Giordano Jérôme , Mancini Julien , Dessi Patrick , Perrier Pierre , Michel Justin
Published: April 2019

Objectives

The primary objective of this study was to determine how computational fluid dynamics (CFD) could be correlated to clinical evaluation of nasal airway obstruction (NAO) in a population of patients with symptomatic septal deviation (SD). The secondary objective was to determine whether CFD could define which side was the more obstructed.

Design

This was an observational study.

Settings

Few publications have attempted to correlate CFD with clinical evaluation of NAO. This correlation would permit validation and improved interpretation. This study was performed in a university research laboratory specialised in fluid mechanics.

Participants

We included patients referred for septal surgery at our centre. Age range was 19–58 years. Preoperative CT scans were performed. All patients with non‐structural causes of NAO such as rhinitis, sinusitis or tumoral/autoimmune processes (ie, not due to anatomic obstruction) were excluded.

Main outcome measurement

For each nasal fossa, we compared CFD data (total pressure, heat flux, wall shear stress, temperatures, velocity and nasal resistances) with both patient perception scores and rhinomanometry using the Spearman correlation test (rs). Perception scores were graded from 0/4 to 4/4 on each side, based on the patient interview. We also compared CFD‐derived nasal resistances with rhinomanometry‐derived nasal resistances.

Results

Twenty‐two patients complaining of NAO with SD were analysed, and 44 analyses were performed comparing each side with its CFD data. Regarding correlations with patient perception scores, the best values we found were heat flux measures (rs = 0.86). Both rhinomanometry and CFD‐calculated nasal resistances had strong correlations with subjective perception scores (rs = 0.75, P < 0.001 and rs = 0.6, P < 0.001, respectively). We found a statistically significant difference between RMM‐NR and CFD‐NR (P = 0.003). Heat flux analysis allowed us to distinguish the more obstructed side (MOS) and the less obstructed side (LOS) in 100% of patients.

Conclusion

This study aimed to enhance our ability to interpret CFD‐calculated data in the nasal airway. It highlights and confirms that heat flux measures are very closely correlated to patient perception in cases of SD. It also helps to distinguish the more obstructed side from the less obstructed side and could contribute to further CFD studies.
Circular RNA cMras inhibits lung adenocarcinoma progression via modulating miR‐567/PTPRG regulatory pathway
Authors: Yu Chengtao , Tian Fang , Liu Jun , Su Minhui , Wu Min , Zhu Xuejun , Qian Wang
Published: April 2019

Objectives

Circular RNA, a type of RNA formed by a covalently closed loop, possesses sophisticated abilities of gene regulation in tumorigenesis and metastasis. However, the role of circRNAs on lung adenocarcinoma (LUAD) remains largely unknown.

Materials and methods

The role of cMras was examined both in vitro and in vivo. cMras expression in LUAD tissues was determined by quantitative real‐time PCR (qRT‐PCR). Downstream targets of cMras were predicted by bioinformatics tools and confirmed by RNA immunoprecipitation assay and luciferase assay. qRT‐PCR and western blot assay were used to detect the expression of specific targets.

Results

Thirty‐six paired LUAD and healthy tissues were collected and cMras resulted significantly downregulated in cancerous tissues. Its expression was negatively associated with tumour stages. cMras overexpression suppressed LUAD growth and metastasis, while endogenous cMras silencing resulted in the opposite effects. Bioinformatics analysis and experimental evidence confirmed that cMras was a sponge of miRNA‐567 and released its direct target, PTPRG. cMras overexpression decreased miR‐567 expression and subsequently increased PTPRG expression, while increased miRNA‐567 expression blocked the effects induced by cMras. Moreover, PTPRG was downregulated in LUAD and patients with low PTPRG expression exhibited significantly poor prognosis. These results suggested that cMras/miR‐567/PTPRG regulatory pathway might be associated to LUAD tumorigenesis and development.

Conclusions

A novel circular RNA cMras and its functions were identified, discovering a cMras/miR‐567/PTPRG regulatory pathway in LUAD tumorigenesis and development.
Lymph node fine‐needle cytology in the era of personalised medicine. Is there a role?
Authors: Cozzolino Immacolata , Giudice Valentina , Mignogna Chiara , Selleri Carmine , Caputo Alessandro , Zeppa Pio
Published: April 2019

The 2016 World Health Organisation revised classification of lymphoma has sub‐classified well‐defined entities and added a number of provisional entities on the basis of new knowledge on genetic, epigenetics and phenotypical data; prognostic and predictive features are also part of this classification. New knowledge on well‐defined entities further enlightens the mechanisms of lymphomagenesis, which are more complex and multifactorial than once believed. Therapies are also more complex because traditional clinical trials have been integrated with new drugs and compounds with unique mechanisms of actions against distinct molecular targets. As lymphoma acquires additional genetic and phenotypic features over the time, pathological assessment is also necessary. Histological evaluation and tissue collection by surgical biopsies are necessary for phenotypical and molecular purposes; however, these are demanding procedures for both the patient and the health care system. At the same time, the choice of the best treatment for a specific entity, in different phases and different patients requires information that may not be available when the biopsy is performed. Fine needle aspiration cytology (FNAC) is successfully used in lymph nodes (LNs) in combination with different ancillary techniques and might be used to assess the phenotypic and genetic profile of specific targets and to get key information for therapy, in different phases and stages of the disease, with the option to re‐check the same target over time, without surgical excision. This brief review describes LN‐FNAC diagnostic criteria, current therapies for lymphomas and the potential role of LN‐FNAC in selecting non‐Hodgkin lymphomas patients for specific targeted treatments.
Unravelling Church Land: Transformations in the Relations between Church, State and Community in Uganda
Authors: Alava Henni , Shroff Catrine
Published: April 2019

Christian churches control substantial areas of land in Africa. While intensifying struggles over their holdings are partly due to the increased pressure on land in general, they also reflect transformations in the relations through which churches’ claims to land are legitimized, the increased association of churches with business, and churches’ unique positioning as both institutions and communities. This article presents the trajectory of relations between church, state and community in Uganda from the missionary acquisition of land in the colonial era to the unravelling of church landholding under Museveni. Drawing on long‐term ethnographic fieldwork, the authors argue that claims to church land in contemporary Uganda draw on: 1) notions of belonging to the land; 2) views about the nature of churches as communities; 3) discontent regarding whether customary land owners gave churches user rights or ownership; and 4) assessment of the churches’ success in ensuring that the land works for the common good. The article develops a novel approach to analysing the changing meaning of the landholdings of religious institutions, thus extending ongoing discussions about land, politics, development and religion in Africa.
The cost of diabetic foot ulcers and amputations to the National Health Service in England
Authors: Kerr M. , Barron E. , Chadwick P. , Evans T. , Kong W. M. , Rayman G. , Sutton‐Smith M. , Todd G. , Young B. , Jeffcoate W. J.
Published: April 2019

Aim

To estimate the healthcare costs of diabetic foot disease in England.

Methods

Patient‐level data sets at a national and local level, and evidence from clinical studies, were used to estimate the annual cost of health care for foot ulceration and amputation in people with diabetes in England in 2014–2015.

Results

The cost of health care for ulceration and amputation in diabetes in 2014–2015 is estimated at between £837 million and £962 million; 0.8% to 0.9% of the National Health Service (NHS) budget for England. More than 90% of expenditure was related to ulceration, and 60% was for care in community, outpatient and primary settings. For inpatients, multiple regression analysis suggested that ulceration was associated with a length of stay 8.04 days longer (95% confidence interval 7.65 to 8.42) than that for diabetes admissions without ulceration.

Conclusions

Diabetic foot care accounts for a substantial proportion of healthcare expenditure in England, more than the combined cost of breast, prostate and lung cancers. Much of this expenditure arises through prolonged and severe ulceration. If the NHS were to reduce the prevalence of diabetic foot ulcers in England by one‐third, the gross annual saving would be more than £250 million. Diabetic foot ulceration is a large and growing problem globally, and it is likely that there is potential to improve outcomes and reduce expenditure in many countries.
Why is education performance so different across Latvian schools?
Authors: Krasnopjorovs Olegs
Published: April 2019

This paper aims to identify the school characteristics consistently associated with better performance of pupils in state exams in Latvia and understand the reasons behind substantial exam score gap between urban and rural schools. We find that exam scores are positively related to school size and teacher salaries, but negatively related to teacher age. Oaxaca–Ransom decomposition shows that the whole urban–rural exam score gap can be attributed to a few observable characteristics of schools, teachers and pupils.