bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAD‐sequencing for estimating genomic relatedness matrix‐based heritability in the wild: A case study in roe deer
Authors: Gervais Laura , Perrier Charles , Bernard Maria , Merlet Joël , Pemberton Josephine M. , Pujol Benoit , Quéméré Erwan 
Published: May 2019

AbstractEstimating the evolutionary potential of quantitative traits and reliably predicting responses to selection in wild populations are important challenges in evolutionary biology. The genomic revolution has opened up opportunities for measuring relatedness among individuals with precision, enabling pedigree‐free estimation of trait heritabilities in wild populations. However, until now, most quantitative genetic studies based on a genomic relatedness matrix (GRM) have focused on long‐term monitored populations for which traditional pedigrees were also available, and have often had access to knowledge of genome sequence and variability. Here, we investigated the potential of RAD‐sequencing for estimating heritability in a free‐ranging roe deer (Capreolous capreolus) population for which no prior genomic resources were available. We propose a step‐by‐step analytical framework to optimize the quality and quantity of the genomic data and explore the impact of the single nucleotide polymorphism (SNP) calling and filtering processes on the GRM structure and GRM‐based heritability estimates. As expected, our results show that sequence coverage strongly affects the number of recovered loci, the genotyping error rate and the amount of missing data. Ultimately, this had little effect on heritability estimates and their standard errors, provided that the GRM was built from a minimum number of loci (above 7,000). Genomic relatedness matrix‐based heritability estimates thus appear robust to a moderate level of genotyping errors in the SNP data set. We also showed that quality filters, such as the removal of low‐frequency variants, affect the relatedness structure of the GRM, generating lower h2 estimates. Our work illustrates the huge potential of RAD‐sequencing for estimating GRM‐based heritability in virtually any natural population.
Probe‐based confocal laser endomicroscopy for rapid on‐site evaluation of transbronchial biopsy specimens
Authors: Takemura Masao , Kurimoto Noriaki , Hoshikawa Masahiro , Maeno Toshitaka , Hisada Takeshi , Kurabayashi Masahiko , Inoue Takeo , Miyazawa Teruomi , Mineshita Masamichi 
Published: May 2019

BackgroundProbe‐based confocal laser endomicroscopy (pCLE) is a novel, noninvasive technology that provides real‐time lung imaging during bronchoscopy. pCLE shows the elastic fiber network without the use of a fluorescent dye. Elastic fibers produce argon laser‐induced autofluorescence at a wavelength of 488 nm, but tumor cells do not produce autofluorescence at this wavelength. As a result, the tumor cells cannot be observed directly. Therefore, we stained transbronchial biopsy (TBB) specimens with acriflavine to evaluate the benign and malignant structures using pCLE of ex vivo samples and to determine whether rapid histopathological diagnosis of TBB specimens could be made via pCLE.MethodsAfter bronchoscopy, 36 TBB specimens were stained with acriflavine and observed using pCLE. Benign and malignant lesions were classified by cell density and nuclear magnitude disparity.ResultsWe defined the confocal laser endomicroscopic atypia classification from the findings of the cells. The sensitivity for malignancy was 91.3%, and the specificity was 76.9%. Both inter‐observer (κ = 0.48) and intra‐observer (κ = 0.57) agreement confirmed moderate agreement.ConclusionpCLE with acriflavine staining was useful to differentiate malignant from benign TBB specimens, and might be useful as a substitute for rapid on‐site evaluation of histopathological diagnosis.
Use of a filter cartridge combined with intra‐cartridge bead‐beating improves detection of microbial DNA from water samples
Authors: Ushio Masayuki 
Published: May 2019

Abstract

Microbial communities play an important role in driving the dynamics of aquatic ecosystems. As difficulties in DNA sequencing faced by microbial ecologists are continuously being reduced, sample collection methods and DNA extraction protocols are becoming more critical to the outcome of any sequencing study.

In the present study, I added a manual, intra‐cartridge, bead‐beating step in the protocol using a DNeasy® Blood & Tissue kit for DNA extraction from a filter cartridge without breaking the cartridge unit (“Beads” method) and compared its performance with those of two other protocols (“NoBeads” method, which was similar to the Beads method but without the bead‐beating step and “PowerSoil” method, which followed the manual of the DNeasy® PowerSoil kit after breaking apart the filter cartridge). Water samples were collected from lake, river, pond and coastal ecosystems in Japan and DNA was extracted using the three protocols. Then, the V4 region of prokaryotic 16S rRNA genes was amplified. In the library preparation process, internal standard DNAs were included to estimate the number of DNA copies. The DNA library was sequenced using Illumina MiSeq and sequences were analysed using the amplicon sequence variant (ASV) approach.

I found that, (a) the total prokaryotic DNA yields were highest with the Beads method, (b) the number of ASVs (a proxy for species richness) was also highest with the Beads method, (c) overall community compositions were significantly different among the three methods and (d) the number of method‐specific ASVs was highest with the Beads method. These results were generally robust across samples from all aquatic ecosystems examined.

In conclusion, the inclusion of a bead‐beating step performed inside the filter cartridge increased the DNA yield as well as the number of prokaryotic ASVs detected compared with the other two methods. Performing the bead‐beating step inside the filter cartridge causes no dramatic increase in either handling time or processing cost and it can reduce the potential contamination risk from the ambient air and/or other samples. Therefore, this method has the potential to become one of the major choices when one aims to extract aquatic microbial DNAs.
Exogenous progesterone for smoking cessation in men and women: a pilot double‐blind, placebo‐controlled randomized clinical trial
Authors: Tosun Nicole L. , Fieberg Ann M. , Eberly Lynn E. , Harrison Katherine A. , Tipp Angela R. , Allen Alicia M. , Allen Sharon S. 
Published: May 2019

Background and AimsIn some clinical studies men and women have been found to differ in their ability to quit smoking, perhaps as a result of progesterone. The primary aim of this study was to provide a preliminary test of whether progesterone (PRO), compared with placebo (PBO), was more effective for smoking cessation in men and women.DesignPilot double‐blind, placebo‐controlled randomized clinical trial.SettingMinneapolis/St Paul metro area, Minnesota, USA.ParticipantsA total of 216 participants were randomized, including 113 men (18–60 years; PRO = 56, PBO = 57) and 103 women (18–50 years, pre‐menopausal with self‐reported regular menstrual cycles; PRO = 51, PBO = 52).InterventionParticipants were randomized (1 : 1 within sex group) to either PRO (200 mg twice daily) or PBO. Participants were assigned a quit date approximately 7 days after starting medication (luteal phase for women) and were followed for 12 weeks to assess relapse.MeasurementsThe primary outcome was self‐reported 7‐day point prevalence abstinence (PPA) at week 4. Secondary outcomes included 7‐day PPA at weeks 8 and 12, prolonged abstinence, continuous abstinence, urine cotinine < 50 ng/ml, expired carbon monoxide ≤ 5 parts per million (p.p.m.) and days to relapse.FindingsThere was a significant difference in 7‐day PPA at week 4 among women [PRO: 18 (35.3%) versus PBO: 9 (17.3%), odds ratio (OR) = 2.61, 95% confidence interval (CI) = 1.04, 6.54, P = 0.041], but not among men [PRO: 13 (23.2%) versus PBO: 12 (21.1%), 1.13 (0.47, 2.76), P = 0.782]. There was some evidence that PRO delayed relapse in women (days to relapse; PRO: 20.5 ± 29.6 versus PBO: 14.3 ± 26.8, P = 0.03) but not in men (PRO: 13.4 ± 25.9 versus PBO: 13.3 ± 23.8, P = 0.69).ConclusionsOral micronized progesterone may aid smoking cessation in women.
Systematic review with meta‐analysis: ultra‐thin gastroscopy compared to conventional gastroscopy for the diagnosis of oesophageal varices in people with cirrhosis
Authors: Wickremeratne Tehara , Turner Stephanie , O'Beirne James 
Published: May 2019

SummaryBackgroundHaemorrhage from ruptured oesophageal varices is a common cause of death in people with cirrhosis. Guidelines recommend screening for varices at time of cirrhosis diagnosis and throughout the course of the disease. Conventional gastroscopy is the criterion standard for variceal screening; however, is invasive, costly, and carries risks related to use of sedation. Ultra‐thin gastroscopy (using endoscopes with a shaft diameter ≤6 mm) has been proposed as an alternative method of variceal screening that mitigates these risks.AimTo determine the diagnostic accuracy of ultra‐thin gastroscopy compared to conventional gastroscopy for the diagnosis of varices in people with cirrhosis.MethodsMEDLINE, EMBASE and Cochrane library databases were searched for studies that evaluated the accuracy of ultra‐thin gastroscopy compared to conventional gastroscopy in the diagnosis of oesophageal varices.ResultsTen studies, 7 in known cirrhosis, with 752 participants were included in this systematic review. The overall prevalence of oesophageal varices was 42%. On bivariate modelling, pooled estimates of sensitivity and specificity were 98% (95% CI 93%‐99%) and 96% (95% CI 91%‐99%) respectively. The positive and negative likelihood ratios were 28 (95% CI 10.7‐73.2) and 0.02 (95% CI 0.01‐0.72) respectively. Kappa coefficient for inter‐observer agreement for any varices ranged from 0.45 to 0.90. No serious adverse events related to ultra‐thin gastroscopy were reported.ConclusionsUltra‐thin gastroscopy is accurate in the diagnosis of oesophageal varices, safe and well tolerated. It is a valid alternative to conventional gastroscopy for the screening and surveillance of varices in people with cirrhosis.
Predicting biochemical recurrence and prostate cancer‐specific mortality after radical prostatectomy: comparison of six prediction models in a cohort of patients with screening‐ and clinically detected prostate cancer
Authors: Remmers Sebastiaan , Verbeek Jan F. M. , Nieboer Daan , van der Kwast Theo , Roobol Monique J. 
Published: May 2019

ObjectivesTo perform a comparison and external validation of three models predicting biochemical recurrence (BCR) and three models predicting prostate cancer (PCa)‐specific mortality (PCSM) in a screening setting, i.e. patients with screening‐detected PCa (S‐PCa) and in those with clinically detected PCa (C‐PCa).Subjects and MethodsWe retrospectively evaluated 795 men with S‐PCa, from the European Randomized Study of Screening for Prostate Cancer, Rotterdam, and 1123 men with C‐PCa initially treated with RP. The discriminative ability of the models was assessed according to the area under the curve (AUC) of the receiver‐operating characteristic, and calibration was assessed graphically using calibration plots.ResultsThe median (interquartile range [IQR]) follow‐up for the S‐PCa group was 10.4 (6.8–14.3) years and for the C‐PCa group it was 8.8 (4.8–12.9) years. A total of 123 men with S‐PCa (15%) and 389 men with C‐PCa (35%) experienced BCR. Of the men with S‐PCa and BCR, 24 (20%) died from PCa and 29 (23%) died from other causes. Of the men with C‐PCa and BCR, 68 (17%) died from PCa and 105 (27%) died from other causes. The discrimination of the models predicting BCR or PCSM was higher for men with S‐PCa (AUC: BCR 0.77–0.84, PCSM 0.60–0.77) than for the men with C‐PCa (AUC: BCR 0.75–0.79, PCSM 0.51–0.68) as a result of the similar patient characteristics of the men with S‐PCa in the present study and those of the cohorts used to develop these models. The risk of BCR was typically overestimated, while the risk of PCSM was typically underestimated.ConclusionPrediction models for BCR showed good discrimination and reasonable calibration for both men with S‐PCa and men with C‐PCa, and even better discrimination for men with S‐PCa. For PCSM, the evaluated models are not applicable in both settings of this Dutch cohort as a result of substantial miscalibration. This warrants caution when using these models to communicate future risks in other clinical settings.
Differences in trends in the use of robot‐assisted and open radical cystectomy and changes over time in peri‐operative outcomes among selected centres in North America and Europe: an international multicentre collaboration
Authors: Zamboni Stefania , Soria Francesco , Mathieu Romain , Xylinas Evanguelos , Abufaraj Mohammad , D`Andrea David , Tan Wei Shen , Kelly John D. , Simone Giuseppe , Gallucci Michele , Meraney Anoop , Krishna Suprita , Konety Badrinath R. , Antonelli Alessandro , Simeone Claudio , Baumeister Philipp , Mattei Agostino , Briganti Alberto , Gallina Andrea , Montorsi Francesco , Rink Michael , Aziz Atiqullah , Karakiewicz Pierre I. , Rouprêt Morgan , Koupparis Anthony , Scherr Douglas S. , Ploussard Guillaume , Sooriakumaran Prasanna , Shariat Shahrokh F. , Moschini Marco ,   the European Association of Urology ‐ Young Academic Urologists (EAU‐YAU), Urothelial carcinoma working group
Published: May 2019

ObjectivesTo compare trends in the use of robot‐assisted radical cystectomy (RARC) and changes over time in peri‐operative outcomes in selected North American and European centres.Materials and MethodsWe conducted a retrospective evaluation of 2401 patients treated with open radical cystectomy (ORC) or RARC for bladder cancer at 12 centres in North America and Europe between 2006 and 2018. We used the Kruskal–Wallis and chi‐squared test to evaluate differences between continuous and categorical variables.ResultsOverall, 49.5% of patients underwent RARC and 51.5% ORC. RARC became the most commonly performed procedure in contemporary patients, with an increase from 29% in 2006–2008 to 54% in 2015–2018 (P < 0.001). In the North American centres the use of RARC was higher than that of ORC from 2006, and remained stable over time, whereas in the European centres its use increased exponentially from 2% to 50%. In both groups patients who underwent RARC had less advanced T stages (P < 0.001), lower American Society of Anesthesiologists scores (P < 0.05), lower blood loss (P = 0.001) and shorter length of hospital stay (P < 0.05). No differences were found in early complications. Early readmission and re‐operation rates were worse for patients treated with RARC in the European centres; however, when contemporary patients only were considered, the statistical significance was lost.ConclusionThe present study shows that the use of RARC has constantly increased since its introduction, overtaking ORC in the most contemporary series. While RARC was more frequently performed than ORC since its introduction in the North American centres and its use remained substantially stable over time, its use increased exponentially in the European centres. The different trends in use of RARC/ORC and changes over time in peri‐operative outcomes between the North American and European centres can be attributed to the earlier introduction and spread of RARC in the former compared with the latter.
Lymph node count impacts survival following post‐chemotherapy retroperitoneal lymphadenectomy for non‐seminomatous testicular cancer: a population‐based analysis
Authors: Bhanvadia Raj R. , Rodriguez Joseph , Bagrodia Aditya , Eggener Scott E. 
Published: May 2019

ObjectiveTo evaluate the prognostic significance of lymph node count (LNC) at post‐chemotherapy retroperitoneal lymphadenectomy (PC‐RPLND) in metastatic non‐seminomatous germ cell tumour (NSGCT) using the Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB).Patients and methodsSEER (2000–2013, n = 572) and NCDB (2004–2013, n = 731) identified patients undergoing PC‐RPLND for Stage II and III NSGCT. Correlation between linear or categorial variables and LNC was conducted using Spearman's rank correlation or Kruskal–Wallis test by ranks. Patients were stratified by ≤20, 21–40, and >40 LNs for Kaplan–Meier analysis. Cox proportional hazards models evaluated the association of LNC at PC‐RPLND with overall mortality (OM) in the NCDB and cancer‐specific mortality (CSM) in the SEER database. The relationship between LNC and OM or CSM was also modelled as a non‐linear function to determine a threshold for survival benefit.ResultsAmongst all patients, the median (interquartile range) LNC was 17 (3–26) LNs in the NCDB, and 18 (6–31) LNs in the SEER database. More recent diagnosis year, higher hospital volume, higher median income, private insurance status, and positive LNC were associated with greater total LNC in one or both databases (P < 0.05). On Kaplan–Meier analysis, >40 LNs was associated with 5‐year cancer‐specific survival (CSS) of 99% and overall survival (OS) of 96%, whereas ≤20 LNs had a 5‐year CSS of 91% and OS of 78% (CSS, P = 0.04; OS, P < 0.01). Risk‐adjusted Cox model showed increasing LNC (per node) was inversely associated with OM (hazard ratio [HR] 0.96, 95% confidence interval [CI], 0.94–0.98; P < 0.01) and CSM (HR 0.96, 95% CI, 0.94–0.99; P = 0.01). Non‐linear modelling showed the greatest benefit in OM at between 10 and 20 LNs, but continued survival benefit for OM and CSM beyond 20 LNs.ConclusionsGreater LNC during PC‐RPLND appears to be associated with improved CSS and OS in NSGCT. Our data support the role of thorough RPLND for post‐chemotherapy metastatic NSGCT.
Hubert's multi‐rater kappa revisited
Authors: Martín Andrés Antonio , Álvarez Hernández María 
Published: May 2019

There is a frequent need to measure the degree of agreement among R observers who independently classify n subjects within K nominal or ordinal categories. The most popular methods are usually kappa‐type measurements. When R = 2, Cohen's kappa coefficient (weighted or not) is well known. When defined in the ordinal case while assuming quadratic weights, Cohen's kappa has the advantage of coinciding with the intraclass and concordance correlation coefficients. When R > 2, there are more discrepancies because the definition of the kappa coefficient depends on how the phrase ‘an agreement has occurred’ is interpreted. In this paper, Hubert's interpretation, that ‘an agreement occurs if and only if all raters agree on the categorization of an object’, is used, which leads to Hubert's (nominal) and Schuster and Smith's (ordinal) kappa coefficients. Formulae for the large‐sample variances for the estimators of all these coefficients are given, allowing the latter to illustrate the different ways of carrying out inference and, with the use of simulation, to select the optimal procedure. In addition, it is shown that Schuster and Smith's kappa coefficient coincides with the intraclass and concordance correlation coefficients if the first coefficient is also defined assuming quadratic weights.
Residual endogenous corticosteroid production in patients with adrenal insufficiency
Authors: Vulto Annet , Bergthorsdottir Ragnhildur , van Faassen Martijn , Kema Ido P. , Johannsson Gudmundur , van Beek André P. 
Published: May 2019

AbstractObjectiveThis study aimed at comparing precursors of endogenous corticosteroid production in patients with primary adrenal insufficiency and in secondary adrenal insufficiency.DesignTwenty patients with primary adrenal insufficiency and matched controls and 19 patients with secondary adrenal insufficiency participated in this ancillary analysis of two different studies.Patients and measurementsPatients with primary adrenal insufficiency were on stable hydrocortisone and fludrocortisone therapy. Patients with secondary adrenal insufficiency received two different doses of hydrocortisone in a randomized crossover study. Main outcome measures were concentrations of precursors of cortisol and aldosterone measured by LC‐MS/MSResultsCompared to controls, progressively lower concentrations of the glucocorticoid precursors 11‐deoxycortisol, 11‐deoxycorticosterone and corticosterone concentrations were found in patients with secondary adrenal insufficiency on lower hydrocortisone dose, secondary adrenal insufficiency on higher hydrocortisone dose and primary adrenal insufficiency, respectively. Half of the primary adrenal insufficient patients showed evidence of residual endogenous cortisol or aldosterone synthesis, as determined by quantifiable 11‐deoxycortisol, 11‐deoxycorticosterone and corticosterone concentrations. In secondary adrenal insufficient patients with higher endogenous cortisol production, as indicated by 11‐deoxycortisol concentrations above the median, no increased cortisol exposure was observed both by plasma pharmacokinetic parameters and 24‐hour free cortisol excretion in urine.ConclusionsAdrenal corticosteroid production is likely to continue during treatment in a considerable percentage of patients with both primary and secondary adrenal insufficiency. In patients with secondary adrenal insufficiency, this synthesis appears to be sensitive to the dose of hydrocortisone. However, the residual corticosteroid concentrations were quantitatively low and its clinical significance remains therefore to be determined.
Brain structure mediates the association between socioeconomic status and attention‐deficit/hyperactivity disorder
Authors: Machlin Laura , McLaughlin Katie A. , Sheridan Margaret A. 
Published: May 2019

AbstractLow socioeconomic status (SES) is associated with greater risk for symptoms of attention‐deficit/hyperactivity disorder (ADHD). One mechanism through which SES may confer risk for ADHD is by influencing brain structure. Alterations to cortical thickness, surface area and subcortical volume have been associated with low SES and with the presence of ADHD across multiple studies. The current study examined whether cortical thickness, surface area or subcortical volume mediate the associations between SES and ADHD in youth 3–21 years old (N = 874) from the Pediatric Imaging, Neurocognition and Genetics Study. Freesurfer was used to estimate cortical thickness, surface area and subcortical volume from structural magnetic resonance imaging. Parents reported on demographics, family SES, ADHD diagnoses and the presence of child attention problems. Statistical mediation was assessed using a bootstrap resampling procedure. Controlling for parental ADHD, child age, gender, birth weight and scanner, children in low SES families were more likely to be in the ADHD group. Consistent with previous reports in this sample, low SES was associated with reduced surface area across the frontal lobe and reduced subcortical volume in the amygdala, cerebellum, hippocampus and basal ganglia. Of these regions, a significant indirect effect of SES on ADHD status through subcortical volume was observed for the left cerebellum (95% confidence interval: 0.004, 0.022), the right cerebellum (95% confidence interval: 0.006, 0.025), and the right caudate (95% confidence interval: 0.002, 0.022). Environmentally mediated changes in the cerebellum and the caudate may be neurodevelopmental mechanisms explaining elevated risk of ADHD in children in low SES families.
Human rights protection and foreign direct investment: The case of post‐socialist countries
Authors: Lewczuk Anna 
Published: May 2019

AbstractThe main aim of the paper is to evaluate the impact of respect for human rights in post‐socialist countries on the volume of foreign direct investment (FDI). The methodology used in the study consists of the two econometric model specifications–GMM spatial panel Durbin error model and panel gravity ordinary least squares model. The main results indicate a positive and significant relationship between respect for human rights and foreign investment. The outcomes of the spatial model suggest the presence of competition and reinforcement effects of particular kinds of human rights on FDI as well as significance of the ‘human rights distance’.