bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis
Authors: Papamichael K. , Rakowsky S. , Rivera C. , Cheifetz A. S. , Osterman M. T. 
Published: December 2017

SummaryBackgroundEndoscopic and histologic healing are emerging as new therapeutic goals in ulcerative colitis (UC), as these endpoints are associated with less relapse, hospitalization and colectomy.AimTo investigate the association of serum infliximab trough concentrations during maintenance therapy with endoscopic or histologic healing in UC.MethodsIn this multi‐center retrospective cohort study, we included consecutive patients with moderate‐to‐severe UC on infliximab maintenance therapy who had an endoscopic evaluation and underwent therapeutic drug monitoring within three months of the colonoscopy, between February 2008 and March 2016. Per event analysis was performed. Endoscopic healing was defined as Mayo endoscopic sub‐score of ≤1. Histologic healing was defined as no or only focal mild active inflammation.ResultsSeventy colonoscopies from 56 patients were evaluated. Infliximab trough concentrations (median [interquartile range]) were significantly higher in patients with endoscopic (11.3 [7.6‐14.5] vs 6.3 [0‐9.8] μg/mL, P < .001) or histologic (11.1 [6.7‐14.5] vs 6.7 [0‐9.9] μg/mL, P = .002) healing, respectively, compared to patients without healing. Receiver‐operating characteristic analyses identified infliximab trough concentration thresholds of 7.5 (area under the curve [AUC]: 0.758) and 10.5 (AUC: 0.721) μg/mL to be associated with endoscopic and histologic healing, respectively. Multiple logistic regression analysis identified infliximab trough concentration ≥7.5 (P = .013; odds ratio [OR]: 4.3; 95% confidence intervals [CI]: 1.4‐13.3) and ≥10.5 μg/mL (P = .013; OR: 3.8; 95% CI: 1.3‐11) as independent factors associated with endoscopic and histologic healing, respectively.ConclusionsThis study demonstrated that infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in patients with UC.
Obesity and type 2 diabetes are important risk factors underlying previously undiagnosed cirrhosis in general practice: a cross‐sectional study using transient elastography
Authors: Harman D. J. , Ryder S. D. , James M. W. , Wilkes E. A. , Card T. R. , Aithal G. P. , Guha I. N. 
Published: December 2017

SummaryBackgroundRising cirrhosis incidence and mortality in the United Kingdom has been attributed predominantly to excess alcohol consumption. However, metabolic risk factors such as Type 2 diabetes and obesity may also be important.AimTo screen at‐risk individuals in general practice for undetected cirrhosis using transient elastography and study the risk factors underlying these cases.MethodsThe study was undertaken in 4 general practices (adult patient population 20 868) between February 2012 and September 2014. Patients with defined risk factors for chronic liver disease (hazardous alcohol use and/or Type 2 diabetes) were identified from the General Practice electronic records and invited for transient elastography. Elevated liver stiffness was defined as ≥8 kPa. Cirrhosis was confirmed by established histological, radiological and biochemical methods.ResultsTwo thousand three hundred and sixty eight patients were invited for transient elastography and 899/919 who attended (97.8%) had valid measurements. Of these 230 patients had elevated liver stiffness (25.6%) and 27 had cirrhosis (2.9%). Risk factors for new cirrhosis diagnoses were obesity and/or Type 2 diabetes in 16 patients (59.3%), alcohol alone in 3 (11.1%) and both alcohol and obesity and/or diabetes in eight (29.6%). Presence of cirrhosis was significantly increased in obese patients with Type 2 diabetes or hazardous alcohol use compared to non‐obese (odds ratio 9.4 [95% CI 2.2‐40.9] and 5.6 [95% CI 1.6‐19.7] respectively).ConclusionsThe number of new cases of cirrhosis diagnosed clearly demonstrates that existing estimates of prevalence are likely to be gross underestimates. Obesity was an important risk factor for cirrhosis within both alcohol users and diabetics.
Targeted vs systematic robot‐assisted transperineal magnetic resonance imaging‐transrectal ultrasonography fusion prostate biopsy
Authors: Mischinger Johannes , Kaufmann Sascha , Russo Giorgio I. , Harland Niklas , Rausch Steffen , Amend Bastian , Scharpf Marcus , Loewe Lorenz , Todenhoefer Tilman , Notohamiprodjo Mike , Nikolaou Konstantin , Stenzl Arnulf , Bedke Jens , Kruck Stephan 
Published: December 2017

ObjectiveTo evaluate the performance of transperineal robot‐assisted (RA) targeted (TB) and systematic (SB) prostate biopsy in primary and repeat biopsy settings.Patients and MethodsPatients underwent RA biopsy between 2014 and 2016. Before RA‐TB, multiparametric magnetic resonance imaging (mpMRI) was performed. Prostate lesions were scored (Prostate Imaging, Reporting and Data System, version 2) and used for RA‐TB planning. In addition, RA‐SB was performed. Available, whole‐gland pathology was analysed.ResultsIn all, 130 patients were biopsy naive and 72 had had a previous negative transrectal ultrasonography‐guided biopsy. In total, 202 patients had suspicious mpMRI lesions. Clinically significant prostate cancer was found in 85% of all prostate cancer cases (n = 123). Total and clinically significant prostate cancer detection rates for RA‐TB vs RA‐SB were not significantly different at 77% vs 84% and 80% vs 82%, respectively. RA‐TB demonstrated a better sampling performance compared to RA‐SB (26.4% vs 13.9%; P < 0.001).ConclusionTransperineal RA‐TB and ‐SB showed similar clinically significant prostate cancer detection rates in primary and repeat biopsy settings. However, RA‐TB offered a 50% reduction in biopsy cores. Omitting RA‐SB is associated with a significant risk of missing clinically significant prostate cancer.
Allergens produce serine proteases‐dependent distinct release of metabolite DAMPs in human bronchial epithelial cells
Authors: Ramu S. , Menzel M. , Bjermer L. , Andersson C. , Akbarshahi H. , Uller L. 
Published: December 2017

SummaryBackgroundThe respiratory epithelium is a major site for disease interaction with inhaled allergens. Additional to IgE‐dependent effects, allergens contain proteases that may stimulate human bronchial epithelial cells (HBECs) through protease‐activated receptors, causing the release of mediators important in driving Th2‐mediated immune responses.ObjectiveWe aimed to investigate whether different allergens induce metabolite DAMPs such as ATP and uric acid (UA) release in HBECs.MethodsHBECs (BEAS‐2B cell line) were exposed to different allergen extracts; house dust mite (HDM), Alternaria alternata, Artemisia vulgaris and Betula pendula and UA, ATP, IL‐8 and IL‐33 release were measured. Allergen extracts were heat‐inactivated or pre‐incubated with serine (AEBSF) or cysteine (E64) protease inhibitors to study the involvement of protease activity in ATP, UA and IL‐8 release. HDM‐induced release of UA was studied in a mouse model of allergic inflammation.ResultsAll allergens caused dose‐dependent rapid release of ATP and IL‐8, but only HDM induced UA release from HBECs. HDM also caused release of UA in vivo in our mouse model of allergic inflammation. ATP release by all 4 allergen extracts was significantly reduced by heat‐inactivation and by serine protease inhibitors. Similarly, the HDM‐induced UA release was also abrogated by heat‐inactivation of HDM extract and dependent on serine proteases. Furthermore, allergen‐induced IL‐8 mRNA expression was inhibited by serine protease inhibitors.Conclusions and Clinical RelevanceATP was released by all 4 allergens in HBECs supporting the role of ATP involvement in asthma pathology. However, HDM stands out by its capacity to cause UA release, which is of interest in view of the proposed role of UA in early initiation of allergic asthma. Although serine proteases may be involved in the activity of all the studied allergens, further work is warranted to explain the differences between HDM and the other 3 allergens regarding the effects on UA release.
Cross‐sectional follow‐up of voice outcomes in children who have a history of airway reconstruction surgery
Authors: Cohen W. , Wynne D.M. , Lloyd S. , Townsley R.B. 
Published: December 2017

ObjectivesThis study reports vocal function in a cross‐section of children with subglottic stenosis. Each child had a history of laryngotracheal reconstruction and/or cricotracheal resection surgery. Vocal function was measured using laryngoscopy, acoustic analysis, perceptual evaluation and impact of voice on quality of life.DesignAll patients aged >5 years with history of laryngotracheal reconstruction and/or cricotracheal resection surgery at the Scottish National Complex Airways service were invited to participate.SettingData were gathered in the Royal Hospital for Children in Glasgow in a single outpatient appointment.ParticipantsTwelve of 56 former patients (aged 5‐27) provided a voice sample and eleven consented to awake laryngoscopy. All consented for detailed evaluation of their medical records.Main outcome measuresAcoustic analysis of fundamental frequency and pitch perturbation was conducted on sustained vowel [a]. Perceptual evaluation was conducted by 4 trained listeners on a series of spoken sentences. Impact on quality of life was measured using the paediatric voice‐related quality of life questionnaire. Laryngeal function was descriptively evaluated.ResultsFour children had normal voice acoustically, perceptually and in relation to voice‐related quality of life. One of these had vocal fold nodules unrelated to surgical history. Two other children had “near normal” vocal function, defined where most voice measurements fell within the normal range.ConclusionsNormal or “near normal” voice is a possible outcome for children who have had this surgery. Where there is an ongoing complex medical condition, voice outcome may be poorer.
Declining old‐forest species as a legacy of large trees lost
Authors: Jones Gavin M. , Keane John J. , Gutiérrez R. J. , Peery M. Zachariah 
Published: December 2017

AbstractAimGlobal declines in large old trees from selective logging have degraded old‐forest ecosystems, which could lead to delayed declines or losses of old‐forest‐associated wildlife populations (i.e., extinction debt). We applied the declining population paradigm and explored potential evidence for extinction debt in an old‐forest dependent species across landscapes with different histories of large tree logging.LocationMontane forests of the Sierra Nevada, California, USA.MethodsWe tested hypotheses about the influence of forest structure on territory extinction dynamics of the spotted owl (Strix occidentalis) using detection/non‐detection data from 1993 to 2011 across two land tenures: national forests, which experienced extensive large tree logging over the past century, and national parks, which did not.ResultsLarge tree/high canopy cover forest was the best predictor of extinction rates and explained 26%–77% of model deviance. Owl territories with more large tree/high canopy cover forest had lower extinction rates, and this forest type was ~4 times more prevalent within owl territories in national parks ( = 19% of territory) than national forests ( = 4% of territory). As such, predicted extinction probability for an average owl territory was ~2.5 times greater in national forests than national parks, where occupancy was declining () and stable (), respectively. Large tree/high canopy cover forest remained consistently low, but did not decline, during the study period on national forests while owl declines were ongoing—an observation consistent with an extinction debt.Main conclusionsIn identifying a linkage between large trees and spotted owl dynamics at a regional scale, we provide evidence suggesting past logging of large old trees may have contributed to contemporary declines in an old‐forest species. Strengthening protections for remaining large old trees and promoting their recruitment in the future will be critical for biodiversity conservation in the world's forests.
Invasion and migration of spatially self‐limiting gene drives: A comparative analysis
Authors: Dhole Sumit , Vella Michael R. , Lloyd Alun L. , Gould Fred 
Published: December 2017

AbstractRecent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical concerns. There has been a call for research on gene drive systems that are spatially and/or temporally self‐limiting. Here, we use a population genetics model to compare the expected characteristics of three spatially self‐limiting gene drive systems: one‐locus underdominance, two‐locus underdominance and daisy‐chain drives. We find large differences between these gene drives in the minimum release size required for successfully driving a payload into a population. The daisy‐chain system is the most efficient, requiring the smallest release, followed by the two‐locus underdominance system, and then the one‐locus underdominance system. However, when the target population exchanges migrants with a nontarget population, the gene drives requiring smaller releases suffer from higher risks of unintended spread. For payloads that incur relatively low fitness costs (up to 30%), a simple daisy‐chain drive is practically incapable of remaining localized, even with migration rates as low as 0.5% per generation. The two‐locus underdominance system can achieve localized spread under a broader range of migration rates and of payload fitness costs, while the one‐locus underdominance system largely remains localized. We also find differences in the extent of population alteration and in the permanence of the alteration achieved by the three gene drives. The two‐locus underdominance system does not always spread the payload to fixation, even after successful drive, while the daisy‐chain system can, for a small set of parameter values, achieve a temporally limited spread of the payload. These differences could affect the suitability of each gene drive for specific applications.
Reproductive suppression, birth defects, and periviable birth
Authors: Catalano Ralph , Bruckner Tim A. , Karasek Deborah , Yang Wei , Shaw Gary M. 
Published: December 2017

AbstractWe argue that reproductive suppression has clinical implications beyond its contribution to the burden of spontaneous abortion. We theorize that the incidence of births before the 28th week of gestation, which contribute disproportionately to infant morbidity and mortality, varies over time in part due to reproductive suppression in the form of selection in utero. We further theorize that the prevalence of structural birth defects among survivors to birth from conception cohorts gauges selection in utero. We based these theories on literature positing that natural selection conserved mechanisms that spontaneously abort “risky” pregnancies including those otherwise likely to yield infants with structural birth defects or small‐for‐gestational age males. We test our theory using high‐quality birth defect surveillance data. We identify 479,885 male infants exposed to strong selection defined as membership in conception cohorts ranked in the lowest quartile of odds of a birth defect among live‐born females. We estimate the risk of periviable birth among these infants as a function of selective pressure as well as of mother's race/ethnicity and age. We find that male infants from exposed conception cohorts exhibited 10% lower odds of periviable birth than males from other conception cohorts. Our findings support the argument that selection in utero has implications beyond its contribution to the burden of spontaneous abortion.
Effect of tannic acid on skin barrier function
Authors: Nakamura Tomoya , Yoshida Naoki , Yasoshima Mitsue , Kojima Yoshihiko 
Published: December 2017

AbstractIn this study, we investigated how tannic acid (TA) protects the skin from inflammation caused by external irritation. The effects of TA were evaluated using a mouse 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐induced skin inflammation model and a reconstructed human epidermal model. We then used Lucifer Yellow for visual confirmation of TA's suppression effect at the stratum corneum (SC) surface. TA treatment of the skin prevented Lucifer Yellow from permeating the skin. This result suggests that TA acts as a barrier against external stimulants such as TPA and artificial sweat on the SC surface.
Climate change leads to differential shifts in the timing of annual cycle stages in a migratory bird
Authors: Tomotani Barbara M. , van der Jeugd Henk , Gienapp Phillip , de la Hera Iván , Pilzecker Jos , Teichmann Corry , Visser Marcel E. 
Published: December 2017

AbstractShifts in reproductive phenology due to climate change have been well documented in many species but how, within the same species, other annual cycle stages (e.g. moult, migration) shift relative to the timing of breeding has rarely been studied. When stages shift at different rates, the interval between stages may change resulting in overlaps, and as each stage is energetically demanding, these overlaps may have negative fitness consequences. We used long‐term data of a population of European pied flycatchers (Ficedula hypoleuca) to investigate phenological shifts in three annual cycle stages: spring migration (arrival dates), breeding (egg‐laying and hatching dates) and the onset of postbreeding moult. We found different advancements in the timing of breeding compared with moult (moult advances faster) and no advancement in arrival dates. To understand these differential shifts, we explored which temperatures best explain the year‐to‐year variation in the timing of these stages, and show that they respond differently to temperature increases in the Netherlands, causing the intervals between arrival and breeding and between breeding and moult to decrease. Next, we tested the fitness consequences of these shortened intervals. We found no effect on clutch size, but the probability of a fledged chick to recruit increased with a shorter arrival‐breeding interval (earlier breeding). Finally, mark–recapture analyses did not detect an effect of shortened intervals on adult survival. Our results suggest that the advancement of breeding allows more time for fledgling development, increasing their probability to recruit. This may incur costs to other parts of the annual cycle, but, despite the shorter intervals, there was no effect on adult survival. Our results show that to fully understand the consequences of climate change, it is necessary to look carefully at different annual cycle stages, especially for organisms with complex cycles, such as migratory birds.
Nitrogen‐rich microbial products provide new organo‐mineral associations for the stabilization of soil organic matter
Authors: Kopittke Peter M. , Hernandez‐Soriano Maria C. , Dalal Ram C. , Finn Damien , Menzies Neal W. , Hoeschen Carmen , Mueller Carsten W. 
Published: December 2017

AbstractUnderstanding the cycling of C and N in soils is important for maintaining soil fertility while also decreasing greenhouse gas emissions, but much remains unknown about how organic matter (OM) is stabilized in soils. We used nano‐scale secondary ion mass spectrometry (NanoSIMS) to investigate the changes in C and N in a Vertisol and an Alfisol incubated for 365 days with 13C and 15N pulse labeled lucerne (Medicago sativa L.) to discriminate new inputs of OM from the existing soil OM. We found that almost all OM within the free stable microaggregates of the soil was associated with mineral particles, emphasizing the importance of organo‐mineral interactions for the stabilization of C. Of particular importance, it was also found that 15N‐rich microbial products originating from decomposition often sorbed directly to mineral surfaces not previously associated with OM. Thus, we have shown that N‐rich microbial products preferentially attach to distinct areas of mineral surfaces compared to C‐dominated moieties, demonstrating the ability of soils to store additional OM in newly formed organo‐mineral associations on previously OM‐free mineral surfaces. Furthermore, differences in 15N enrichment were observed between the Vertisol and Alfisol presumably due to differences in mineralogy (smectite‐dominated compared to kaolinite‐dominated), demonstrating the importance of mineralogy in regulating the sorption of microbial products. Overall, our findings have important implications for the fundamental understanding of OM cycling in soils, including the immobilization and storage of N‐rich compounds derived from microbial decomposition and subsequent N mineralization to sustain plant growth.
Screening for human papillomavirus, cervical cytological abnormalities and associated risk factors in HIV‐positive and HIV‐negative women in Rwanda
Authors: Mukanyangezi MF , Sengpiel V , Manzi O , Tobin G , Rulisa S , Bienvenu E , Giglio D 
Published: December 2017

ObjectivesCervical cancer is the major cause of death from cancer in Africa. We wanted to assess the prevalence of human papillomavirus (HPV) infections and associated risk factors and to determine whether HPV testing could serve as a screening method for squamous intraepithelial lesions (SILs) in Rwanda. We also wanted to obtain a broader understanding of the underlying risk factors for the establishment of HPV infection in Rwanda.MethodsA total of 206 HIV‐positive women, 172 HIV‐negative women and 22 women with unknown HIV status were recruited at the University Teaching Hospitals of Kigali (UTHK) and of Butare (UTHB) in Rwanda. Participants underwent an interview, cervical sampling for a Thinprep Pap test and a screening test analysing 37 HPV strains.ResultsOnly 27% of HIV‐positive women and 7% of HIV‐negative women had been screened for cervical cancer before. HPV16 and HPV52 were the most common HPV strains. HIV‐positive women were more commonly infected with high‐risk (HR) HPV and multitype HPV than HIV‐negative women. The sensitivity was 78% and the specificity 87% to detect high‐grade SIL (HSIL) with HPV screening. Among HIV‐negative women, being divorced was positively associated with HR‐HPV infection, while hepatitis B, Trichomonas vaginalis infection and HR‐HPV infection were factors positively associated with SILs. Ever having had gonorrhoea was positively associated with HR‐HPV infection among HIV‐positive women. HR‐HPV infection and the number of live births were positively associated with SILs.ConclusionsThe currently used quadrivalent vaccine may be insufficient to give satisfactory HPV coverage in Rwanda. HPV Screening may be effective to identify women at risk of developing cervical cancer, particularly if provided to high‐risk patients.
Evaluating antidisease immunity to malaria and implications for vaccine design
Authors: Ademolue Temitope W. , Awandare Gordon A. 
Published: December 2017

SummaryImmunity to malaria could be categorized broadly as antiparasite or antidisease immunity. While most vaccine research efforts have focused on antiparasite immunity, the evidence from endemic populations suggest that antidisease immunity is an important component of natural immunity to malaria. The processes that mediate antidisease immunity have, however, attracted little to no attention, and most interests have been directed towards the antibody responses. This review evaluates the evidence for antidisease immunity in endemic areas and discusses the possible mechanisms responsible for it. Given the key role that inflammation plays in the pathogenesis of malaria, regulation of the inflammatory response appears to be a major mechanism for antidisease immunity in naturally exposed individuals.