bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased Macrophage Autophagy Promotes Liver Injury and Inflammation from Alcohol
Authors: Ilyas Ghulam , Cingolani Francesca , Zhao Enpeng , Tanaka Kathryn , Czaja Mark J. 
Published: April 2019

BackgroundOne mechanism underlying the development of alcoholic liver disease is overactivation of the innate immune response. Recent investigations indicate that the lysosomal pathway of autophagy down‐regulates the inflammatory state of hepatic macrophages, suggesting that macrophage autophagy may regulate innate immunity in alcoholic liver disease. The function of macrophage autophagy in the development of alcoholic liver disease was examined in studies employing mice with a myeloid‐specific decrease in autophagy.MethodsLittermate control and Atg5Δmye mice lacking Atg5‐dependent myeloid autophagy were administered a Lieber–DeCarli control (CD) or ethanol diet (ED) alone or together with lipopolysaccharide (LPS) and examined for the degree of liver injury and inflammation.ResultsKnockout mice with decreased macrophage autophagy had equivalent steatosis but increased mortality and liver injury from ED alone. Increased liver injury and hepatocyte death also occurred in Atg5Δmye mice administered ED and LPS in association with systemic inflammation as indicated by elevated serum levels of proinflammatory cytokines. Hepatic macrophage and neutrophil infiltration were unaffected by decreased autophagy, but levels of proinflammatory cytokine gene induction were significantly increased in the livers but not adipose tissue of knockout mice treated with ED and LPS. Inflammasome activation was increased in ED/LPS‐treated knockout mice resulting in elevated interleukin (IL)‐1β production. Increased IL‐1β promoted alcoholic liver disease as liver injury was decreased by the administration of an IL‐1 receptor antagonist.ConclusionsMacrophage autophagy functions to prevent liver injury from alcohol. This protection is mediated in part by down‐regulation of inflammasome‐dependent and inflammasome‐independent hepatic inflammation. Therapies to increase autophagy may be effective in this disease through anti‐inflammatory effects on macrophages.
Thinking bigger: How early‐life environmental exposures shape the gut microbiome and influence the development of asthma and allergic disease
Authors: Sbihi Hind , Boutin Rozlyn CT. , Cutler Chelsea , Suen Mandy , Finlay B. Brett , Turvey Stuart E. 
Published: April 2019

AbstractImbalance, or dysbiosis, of the gut microbiome of infants has been linked to an increased risk of asthma and allergic diseases. Most studies to date have provided a wealth of data showing correlations between early‐life risk factors for disease and changes in the structure of the gut microbiome that disrupt normal immunoregulation. These studies have typically focused on one specific risk factor, such as mode of delivery or early‐life antibiotic use. Such “micro‐level” exposures have a considerable impact on affected individuals but not necessarily the whole population. In this review, we place these mechanisms under a larger lens that takes into account the influence of upstream “macro‐level” environmental factors such as air pollution and the built environment. While these exposures likely have a smaller impact on the microbiome at an individual level, their ubiquitous nature confers them with a large influence at the population level. We focus on features of the indoor and outdoor human‐made environment, their microbiomes and the research challenges inherent in integrating the built environment microbiomes with the early‐life gut microbiome. We argue that an exposome perspective integrating internal and external microbiomes with macro‐level environmental factors can provide a more comprehensive framework to define how environmental exposures can shape the gut microbiome and influence the development of allergic disease.
Periostin: An emerging biomarker for allergic diseases
Authors: Izuhara Kenji , Nunomura Satoshi , Nanri Yasuhiro , Ono Junya , Takai Masayuki , Kawaguchi Atsushi 
Published: April 2019

AbstractPeriostin is a matricellular protein as well as an extracellular matrix (ECM) protein belonging to the fasciclin family. Periostin plays important roles as a matricellular protein in the setting of allergic diseases by binding to several integrins on various cells. Since periostin is induced mainly by IL‐4 and IL‐13, signature type 2 cytokines, and it is highly expressed in the subepithelial regions of many chronic allergic diseases, periostin has emerged as a novel biomarker reflecting type 2 inflammation in allergic diseases. It has, moreover, been revealed that periostin has characteristics different from other type 2 biomarkers such as eosinophil count and fractional exhaled nitric oxide (FeNO), reflecting fibrosis or tissue remodeling. From this, we may say that serum periostin is a “chronic” type 2 biomarker, whereas FeNO and possibly the eosinophil count are “acute” type 2 biomarkers. In contrast, it is still uncertain how we can apply periostin measurement to the use of biologics for allergic diseases. By examining the roles of periostin in allergy and the utility and potential of periostin in developing diagnostics against allergic diseases, it is hoped that in the near future, we can develop a new strategy to treat allergic patients.
Interference in the anti‐Xa heparin activity assay due to hemolysis and icterus during pediatric extracorporeal life support
Authors: Khan Jenna , Chandler Wayne L. 
Published: April 2019

AbstractChromogenic anti‐Xa assays for unfractionated heparin monitoring (heparin activity) are susceptible to interference from hemolysis and icterus. The purpose of this study was to better understand the effect of hemolysis and icterus on anti‐Xa heparin activity and to predict the magnitude of the error. Increasing levels of hemoglobin and unconjugated bilirubin were added to pooled normal plasma or buffer containing known levels of heparin. Increased plasma hemoglobin or bilirubin produced falsely increased residual factor Xa activity as measured by the absorbance change (OD/min) in the Stago heparin activity assay. This increased absorbance change slope resulted in falsely lower estimates of heparin activity. The falsely lower heparin activity measurement occurred even when heparin was not present, indicating it was not due to heparin neutralization. In a sample containing 0.62 ± 0.06 U/mL heparin and 228 mg/dL hemoglobin, the measured heparin activity was 0.41 ± 0.03 U/mL, underestimating heparin activity by 0.21 ± 0.07 U/mL. Interference occurred if plasma hemoglobin was above 70 mg/dL or bilirubin was above 16 mg/dL, which happened in 16%–26% of samples from pediatric patients on extracorporeal life support (ECLS). In conclusion, hemolysis and icterus were common in ECLS patients, leading to underestimates of unfractionated heparin activity and potentially higher doses of heparin than intended. The magnitude of the heparin activity measurement error could be predicted based on plasma hemoglobin and bilirubin levels until these levels exceeded the technical limits of the assay, ~230 mg/dL hemoglobin and 55 mg/dL bilirubin.
Quantitative evaluation of primary retinitis pigmentosa patients using colour Doppler flow imaging and optical coherence tomography angiography
Authors: Wang Xiao‐Na , Zhao Qi , Li Dong‐Jun , Wang Zi‐Yang , Chen Wei , Li Yi‐Feng , Cui Rui , Shen Lin , Wang Ruikang K. , Peng Xiao‐Yan , Yang Wen‐Li 
Published: April 2019

AbstractPurposeTo find the potential relation between changes in retinal large vessels and terminal vessels using colour Doppler flow imaging (CDFI) and optical coherence tomography angiography (OCTA) and to compare the respective advantages of CDFI and OCTA in evaluating vascular changes in retinitis pigmentosa (RP) patients.MethodsA prospective series of case study was conducted to enrol RP patients and age‐matched controls, who were, respectively, imaged by CDFI and OCTA. Repeatability and reproducibility of both CDFI and OCTA were performed among healthy volunteers. The central retinal artery (CRA) was detected by CDFI analysis to provide parameters of peak systolic velocity (PSV), end‐diastolic velocity (EDV) and time‐averaged maximum velocity (TAMV). Retinal parameters were evaluated from OCTA images, including vascular area density (VAD) of the superficial vascular layer, the fovea avascular zone (FAZ) area and retinal thickness. RP patients were separated into a high‐vision group and a low‐vision group, according to median vision (0.3, LogMAR 0.5). Multiple comparisons were used to analyse the data between groups. A correlation analysis was used to determine the correlation between CDFI and OCTA parameters.ResultsTwenty RP patients (40 eyes) and thirteen normal volunteers (26 eyes) were enrolled in this study. Repeatability and reproducibility of the measurements by CDFI had higher CVs, from 4.5% to 15.4%, than those measurements by OCTA (<5%). All the CDFI and OCTA parameters examined had significant reductions in RP patients compared to those in the controls (p < 0.01). Compared to the high‐vision group, the low‐vision group exhibited a statistically significant decrease in vascular parameters of the FAZ area, fovea VAD and parafovea nasal side VAD (p < 0.05); as well as in the parameters of the fovea thickness, and the parafovea nasal, superior and inferior side thickness (p < 0.05). From the correlation analysis, a significant association was found between the vision and CDFI parameters (PSV and time‐averaged maximum velocity (TAMX), p < 0.05), and the vision and OCTA parameters (FAZ area, fovea and nasal side VAD, retinal thickness in all sides, p < 0.05). PSV and TAMX of the CRA were closely related to the OCTA superficial VAD in all sides, whereas the CDFI parameters showed poor correlation with retinal thickness.ConclusionsColour Doppler flow imaging (CDFI) and OCTA parameters revealed a significant reduction in RP patients when compared to the controls. OCTA can detect vision‐related microvascular and thickness changes around the macula between high‐ and low‐vision groups, which happen earlier than the changes in large vessels. In addition to good repeatability and reproducibility, OCTA may have significant utility in the diagnosis and monitoring of disease progression in RP patients.
Dealing with Too Little: The Direct Experience of Scarcity does not Affect Snack Intake
Authors: van Rongen Sofie , Verkooijen Kirsten , de Vet Emely 
Published: April 2019

BackgroundThe experience of scarcity provides an explanation for the relatively unhealthy diets of people with low income. Causal evidence for an effect of direct experiences of scarcity on eating behaviour is lacking.MethodsTwo studies (N = 81, N = 115) tested and refined a self‐developed trade‐off task, in which participants' resources were restricted (scarcity condition) or unrestricted (no‐scarcity condition), for manipulating experiences of scarcity. Two further studies (N = 95, N = 122) were performed to test whether scarcity results in greater calorie consumption from snacks and lower self‐reported self‐regulation of eating.ResultsThe scarcity manipulation appeared successful. A significant main effect of scarcity on eating was not found; however, an interaction effect between hunger and scarcity bordered on significance, such that those in the scarcity condition consumed more calories under low hunger. In the second experiment, participants were instructed to eat prior to participation to lower their hunger level. No difference between conditions was found in calorie consumption and self‐regulation of eating.ConclusionAlthough the trade‐off task appeared to evoke scarcity experiences, the present research could not support the notion that these result in unhealthier eating. A more nuanced view of the influence of scarcity on eating is needed.
Dipeptidyl peptidase‐4 inhibitors lower the risk of autoimmune disease in patients with type 2 diabetes mellitus: A nationwide population‐based cohort study
Authors: Seong Jong‐Mi , Yee Jeong , Gwak Hye Sun 
Published: April 2019

AimsTo evaluate the real‐world effect of dipeptidyl peptidase‐4 inhibitor (DPP4i) on the incidence of autoimmune diseases (AD), including rheumatoid arthritis (RA), inflammatory bowel diseases, multiple sclerosis and systemic lupus erythematosus.MethodsWe identified new users of DPP4i (n = 497 619) or non‐DPP4i (n = 643 165) oral combination therapy between 1 January 2011 and 30 June 2015 among patients with type 2 diabetes mellitus in the Korean national health insurance claims database. Patients were followed from the date of initiation of combination therapy until AD outcome, censoring for treatment discontinuation or switching, death or end of study (31 August 2016). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for RA, inflammatory bowel diseases, other AD (multiple sclerosis and systemic lupus erythematosus), and the composite of all outcomes were estimated using propensity score (PS)‐adjusted Cox model.ResultsIn the PS‐weighted and PS‐matched analysis, the risk of incident RA was decreased for DPP4i initiators compared with non‐DPP4i initiators (aHR 0.67 [95% CI 0.49–0.92] and aHR 0.72 [95% CI 0.51–1.01], respectively). In both analyses, the risk of incident composite AD was also decreased for DPP4i initiators compared with non‐DPP4i initiators (aHR 0.82 [95% CI 0.68–0.99] and aHR 0.76 [95% CI 0.62–0.93], respectively).ConclusionsIn this large population‐based cohort study, upfront DPP4i combination therapy was associated with a lower risk of composite AD compared with initial non‐DPP4i combination therapy.
The Simplified PADUA REnal (SPARE) nephrometry system: a novel classification of parenchymal renal tumours suitable for partial nephrectomy
Authors: Ficarra Vincenzo , Porpiglia Francesco , Crestani Alessandro , Minervini Andrea , Antonelli Alessandro , Longo Nicola , Novara Giacomo , Giannarini Gianluca , Fiori Cristian , Simeone Claudio , Carini Marco , Mirone Vincenzo 
Published: April 2019

ObjectiveTo simplify the original Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification of renal tumours, generating a new system able to predict equally or better the risk of overall complications in patients undergoing partial nephrectomy (PN); and to test if the addition of the contact surface area (CSA) parameter improves the accuracy of the original PADUA and new Simplified PADUA REnal (SPARE) nephrometry classification systems.Patients and MethodsWe analysed the clinical records of 531 patients who underwent PN (open, laparoscopic and robot‐assisted) for renal tumours at five tertiary academic referral centres from January 2014 to December 2016. The ability of each variable included in the PADUA classification to predict overall complications was tested using binary logistic regression analysis. The variables that were not statistically significant were excluded from the SPARE classification. In addition to the original PADUA and SPARE systems, another two models were generated adding tumour CSA. Receiver operating characteristic curve analysis was used to compare the ability of the four different models to predict overall complications. Binary logistic regression was used to perform both univariable and multivariable analyses looking for predictors of postoperative complications. Linear regression analysis was used to identify independent predictors of absolute change in estimated glomerular filtration rate (eGFR; ACE).ResultsThe SPARE nephrometry score system including: (i) rim location, (ii) renal sinus involvement, (iii) exophytic rate, and (iv) tumour dimension; showed equal performance in comparison with the original PADUA score (area under the curve [AUC] 0.657 vs 0.664). Adding tumour CSA to the original PADUA (AUC 0.661) or to the SPARE (AUC 0.658) scores did not increase the accuracy of either system to predict overall complications. The SPARE system (odds ratio 1.2, 95% confidence interval 1.1–1.3) was an independent predictor of postoperative overall complications. Age (P < 0.001), body mass index (P < 0.001), Charlson Comorbidity Index (P = 0.02), preoperative eGFR (P < 0.001), and tumour CSA (P = 0.005) were independent predictors of ACE. Limitations include the retrospective design and the lack of central imaging review.ConclusionsThe new SPARE score is comprised of only four variables instead of the original six and its accuracy to predict overall complications is similar to that of the original PADUA score. Addition of tumour CSA was not associated with an increase in prognostic accuracy. The SPARE system could replace the original PADUA score to evaluate the complexity of tumours suitable for PN.
Phenology and floral synchrony of Rhizophora mangle along a natural salinity gradient
Authors: Peel Joanne R. , Golubov Jordan , Mandujano María C. , López‐Portillo Jorge 
Published: April 2019

AbstractRhizophora mangle is the most common species of mangrove within its range and a major component of coastal ecosystems in the tropics and subtropics. Its phenology is affected by seasonal variations in temperature, salinity, and precipitation, all of which may be altered by impending climate change. In this work, the monthly leaf, flower, and fruit phenology of R. mangle was assessed at three sites, along a natural salinity gradient for 12 months. We assessed phenological states using litter traps installed in mangrove stands, and by direct observation of leaf production at two sites, and flower, and fruit production at a single site. Phenological events were compared with seasonal climatic variations (in wind, rain, and temperature) to explore potential abiotic controls on the phenology of this species. Leaf shedding was lowest at the low salinity site. Leaf and stipule production showed a seasonal trend, decreasing during the cool and dry winter months. Flowering was highly seasonal and synchronous and peaked during the rainy season. Flowering was correlated with average temperature (r = 0.82; p < 0.05) at all three study sites, but was not correlated with precipitation. At the high‐salinity site, flowering was restricted to the rainy season. Fruit abortion was associated with wind speed (r = 0.79; p < 0.05). Flowering of R. mangle is induced by increasing temperatures and the onset of rains. Rising temperatures, drier summers, and more frequent and intense storms, due to climate change, may influence mangrove productivity, population dynamics, and floral synchrony.
The gender gap in university enrolment: Do parents play a role beyond investing in skills?
Authors: Foley Kelly 
Published: April 2019

AbstractYoung men are far less likely than women to attend university across most OECD countries. I use data from the Youth in Transition Survey (YITS) to investigate this issue in the Canadian context, focusing on how parents might influence this gender gap. In particular, my goal is to isolate the incremental effect of parents’ valuations of education during the teenage years, holding constant the stock of skills acquired up to that point. To estimate this effect, I use a factor model based on a framework developed by Foley et al. (2014). My results confirm the importance of skills in determining the gender gap in university attendance. I also find that differences in the distribution of parental valuations of education account for 22% of the gender gap in the YITS data, pointing toward an important role that parents play, not accounted for in prior work.
Novel approaches for the design, delivery and administration of vaccine technologies
Authors: Wallis J , Shenton D P , Carlisle R C 
Published: April 2019

SummaryIt is easy to argue that vaccine development represents humankind’s most important and successful endeavour, such is the impact that vaccination has had on human morbidity and mortality over the last 200 years. During this time the original method of Jenner and Pasteur, i.e. that of injecting live-attenuated or inactivated pathogens, has been developed and supplemented with a wide range of alternative approaches which are now in clinical use or under development. These next-generation technologies have been designed to produce a vaccine that has the effectiveness of the original live-attenuated and inactivated vaccines, but without the associated risks and limitations. Indeed, the method of development has undoubtedly moved away from Pasteur’s three Is paradigm (isolate, inactivate, inject) towards an approach of rational design, made possible by improved knowledge of the pathogen–host interaction and the mechanisms of the immune system. These novel vaccines have explored methods for targeted delivery of antigenic material, as well as for the control of release profiles, so that dosing regimens can be matched to the time-lines of immune system stimulation and the realities of health-care delivery in dispersed populations. The methods by which vaccines are administered are also the subject of intense research in the hope that needle and syringe dosing, with all its associated issues regarding risk of injury, cross-infection and patient compliance, can be replaced. This review provides a detailed overview of new vaccine vectors as well as information pertaining to the novel delivery platforms under development.
Re‐osseointegration following reconstructive surgical therapy of experimental peri‐implantitis. A pre‐clinical in vivo study
Authors: Almohandes Ahmed , Carcuac Olivier , Abrahamsson Ingemar , Lund Henrik , Berglundh Tord 
Published: April 2019

AbstractObjectiveTo evaluate the effect of bone substitute materials on hard and soft tissue healing in reconstructive surgical therapy of experimental peri‐implantitis at implants with different surface characteristics.Material and methodsSix female, Labrador dogs were used. 3 months after tooth extraction, four implants with two different surface characteristics (A and B) were installed on each side of the mandible. Experimental peri‐implantitis was induced 3 months later. During surgical treatment of peri‐implantitis, the implants were cleaned with curettes and cotton pellets soaked in saline. The implant sites were allocated to one of four treatment categories; (a) Group C; no augmentation, (b) Group T1; bone defect filled with deproteinized bovine bone mineral (c) Group T2; bone defect filled with a biphasic bone graft material, (d) Group T3; bone defect filled as T1 and covered with a collagen membrane. Clinical and radiological examinations were performed, and biopsies were obtained and prepared for histological analysis 6 months after peri‐implantitis surgery.ResultsImplant B (smooth surface) sites showed significantly (a) larger radiographic bone level gain, (b) enhanced resolution of peri‐implantitis lesions, and (c) larger frequency of re‐osseointegration than implant A (moderately rough surface) sites. Implant B sites also showed superior preservation of the mucosal margin. Differences between bone substitute materials and control procedures were overall small with limited advantages for T1 and T2 sites.ConclusionHealing following reconstructive surgical treatment of experimental peri‐implantitis was superior around implants with a smooth surface than implants with a moderately rough surface. Benefits of using bone substitute materials during surgical therapy were overall small.