bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic intermittent nicotine delivery with lung alveolar region-targeted aerosol technology produces circadian blood pharmacokinetics in rats resembling human smokers
Authors: Shao Xuesi M. , Liu Siyu , Lee Eon S. , Fung David , Pei Hua , Liang Jing , Mudgway Ross , Zhang Jingxi , Feldman Jack L. , Zhu Yifang , Louie Stan , Xie Xinmin S 
Published: September 2017

AbstractIntroductionCigarette smoke is an aerosol containing microparticles that carry nicotine into lung alveolar region where nicotine is rapidly absorbed into circulation. Nicotine exposure in smokers is a chronic intermittent process, with intake during wakefulness and abstinence during sleep resulting in circadian fluctuation of blood nicotine levels. Here we present a smoking-relevant nicotine exposure device and rodent model.MethodsWe developed a computer controlled integrated platform where freely moving rodents can be exposed to episodic nicotine aerosol on an investigator-designed schedule. Rats were exposed to nicotine aerosol once every half hr in the dark phase of 12/12-hr dark/light cycles for 10 days. Plasma nicotine and its metabolite cotinine levels were determined with a LC-MS/MS method.ResultsWe characterized the aerosol in the breathing zone of the rodent exposure chamber. The droplet size distribution was within the respirable diameter range. The system can generate a wide range of nicotine concentrations in air that meet a variety of experimental needs. We optimized the parameters of aerosol generation and exposure: plasma nicotine and cotinine concentrations reached 30-35 ng/ml and 190-240 ng/ml, respectively. The nicotine levels and circadian patterns resembled the pharmacokinetic pattern of human smokers.ConclusionsWe developed an aerosol system that can produce chronic intermittent nicotine exposure in unanesthetized and unrestrained rodents with route of administration and circadian blood pharmacokinetics resembling human smokers. This methodology is a novel tool for studies of behavior, pharmacology and toxicology of chronic nicotine exposure, nicotine addiction, tobacco-related diseases, teratogenicity, and for discovery of therapeutics.ImplicationsWe developed a method and an alveolar region-targeted aerosol system that provides chronic intermittent nicotine exposure in rodents. The method produces clinically relevant animal models with the route of administration and circadian pharmacokinetics resembling human smokers. This method is a novel tool for understanding the health effects of chronic nicotine exposures such as with tobacco cigarettes, E-cigarettes and other tobacco products, for studies of pharmacology, toxicology, nicotine addiction, tobacco-related diseases, and for discovery of medications.
The architecture and design of ecological null models
Authors: Ladau Joshua 
Published: September 2017

AbstractMany questions in ecology are best addressed using observational data because they concern spatial or temporal scales where experimentation is impractical. Null models, which make predictions in the absence of a particular ecological mechanism, are instrumental for making inferences in these situations, but which null models to use or how to best test them is often unclear; this ambiguity is problematic because different null models and tests can yield different results, suggesting contradictory ecological mechanisms. To address these challenges, this paper presents an overar ching framework for the development and testing of null models, in which desirable models and tests are obtained as solutions to mathematical optimization problems. As an example of how the framework can be applied, this paper shows how it can be used to design null model tests to check for effects of interspecific interactions on species co-occurrence patterns. A minimal sufficient statistic (metric) for effects of interspecific interactions is derived, which achieves the maximal level of data compression without losing information present in the data about interspecific in teractions. Existing, intuitive statistics are shown to lack this property. The paper then derives a statistical hypothesis test that has the greatest possible power (sen sitivity) for detecting effects of competition and facilitation given a controlled false positive rate. This test is shown numerically to improve greatly over existing tests. The optimization paradigm allows the most accurate inferences possible, and should be applicable throughout ecology where null models are used to make inferences.
PharmacoDB: an integrative database for miningin vitrodrug screening studies
Authors: Smirnov Petr , Kofia Victor , Maru Alexander , Freeman Mark , Ho Chantal , El-Hachem Nehme , Adam George-Alexandru , Ba-alawi Wail , Safikhani Zhaleh , Haibe-Kains Benjamin 
Published: September 2017

ABSTRACTRecent pharmacogenomic studies profiled large panels of cancer cell lines against hundreds of approved drugs and experimental chemical compounds. The overarching goal of these screens is to measure sensitivity of cell lines to chemical perturbation, correlate these measures to genomic features, and thereby develop novel predictors of drug response. However, leveraging this valuable data is challenging due to the lack of standards for annotating cell lines and chemical compounds, and quantifying drug response. Moreover, it has been recently shown that the complexity and complementarity of the experimental protocols used in the field result in high levels of technical and biological variation in thein vitropharmacological profiles. There is therefore a need for new tools to facilitate rigorous comparison and integrative analysis of large-scale drug screening datasets. To address this issue, we have developed PharmacoDB (pharmacodb.pmgenomics.ca), a database integrating the largest pharmacogenomic studies published to date. Here, we describe how the curation of cell line and chemical compound identifiers maximizes the overlap between datasets and how users can leverage such data to compare and extract robust drug phenotypes. PharmacoDB provides a unique resource to mine a compendium of curated pharmacogenomic datasets that are otherwise disparate and difficult to integrate.Key pointsCuration of cell line and drug identifiers in the largest pharmacogenomic studies published to dateUniform processing of drug sensitivity data to reduce heterogeneity across studiesMultiple drug response summary metrics enabling visual comparison and integrative analysis
Soil fungal abundance and plant functional traits drive fertile island formation in global drylands
Authors: Ochoa‐Hueso Raúl , Eldridge David J. , Delgado‐Baquerizo Manuel , Soliveres Santiago , Bowker Matthew A. , Gross Nicolas , Le Bagousse‐Pinguet Yoann , Quero José L. , García‐Gómez Miguel , Valencia Enrique , Arredondo Tulio , Beinticinco Laura , Bran Donaldo , Cea Alex , Coaguila Daniel , Dougill Andrew J. , Espinosa Carlos I. , Gaitán Juan , Guuroh Reginald T. , Guzman Elizabeth , Gutiérrez Julio R. , Hernández Rosa M. , Huber‐Sannwald Elisabeth , Jeffries Thomas , Linstädter Anja , Mau Rebecca L. , Monerris Jorge , Prina Aníbal , Pucheta Eduardo , Stavi Ilan , Thomas Andrew D. , Zaady Eli , Singh Brajesh K. , Maestre Fernando T. 
Published: September 2017

Abstract

Dryland vegetation is characterized by discrete plant patches that accumulate and capture soil resources under their canopies. These “fertile islands” are major drivers of dryland ecosystem structure and functioning, yet we lack an integrated understanding of the factors controlling their magnitude and variability at the global scale.

We conducted a standardized field survey across 236 drylands from five continents. At each site, we measured the composition, diversity and cover of perennial plants. Fertile island effects were estimated at each site by comparing composite soil samples obtained under the canopy of the dominant plants and in open areas devoid of perennial vegetation. For each sample, we measured 15 soil variables (functions) associated with carbon, nitrogen and phosphorus cycling and used the relative interaction index to quantify the magnitude of the fertile island effect for each function. In 80 sites, we also measured fungal and bacterial abundance (quantitative PCR) and diversity (Illumina MiSeq).

The most fertile islands, i.e. those where a higher number of functions were simultaneously enhanced, were found at lower elevation sites with greater soil pH values and sand content under semiarid climates, particularly at locations where the presence of tall woody species with a low‐specific leaf area increased fungal abundance beneath plant canopies, the main direct biotic controller of the fertile island effect in the drylands studied. Positive effects of fungal abundance were particularly associated with greater nutrient contents and microbial activity (soil extracellular enzymes) under plant canopies.

Synthesis. Our results show that the formation of fertile islands in global drylands largely depends on: (1) local climatic, topographic and edaphic characteristics, (2) the structure and traits of local plant communities and (3) soil microbial communities. Our study also has broad implications for the management and restoration of dryland ecosystems worldwide, where woody plants are commonly used as nurse plants to enhance the establishment and survival of beneficiary species. Finally, our results suggest that forecasted increases in aridity may enhance the formation of fertile islands in drylands worldwide.
How fast can China grow? The Middle Kingdom's prospects to 2030
Authors: Bailliu Jeannine , Kruger Mark , Toktamyssov Argyn , Welbourn Wheaton 
Published: September 2017

AbstractGiven its size and importance for global commodity markets, the question of how fast China can grow over the medium term is an important one. Using a Cobb–Douglas production function, we decompose the growth of trend GDP into those of the capital stock, labour, human capital and total factor productivity (TFP) and then forecast trend output growth out to 2030 using a bottom‐up approach based on forecasts that we build for each one of these factors. Our paper distinguishes itself from existing work in that we construct a forecast of Chinese TFP growth based on the aggregation of forecasts of its key determinants. In addition, our analysis is based on a carefully constructed estimate of the Chinese productive capital stock and a measure of human capital (based on Chinese wage survey data) that better reflects the returns to education in China. Our results suggest that Chinese GDP growth will slow from around 7% currently to approximately 5% by 2030, consistent with a gradual rebalancing of the Chinese economy characterized by a decline in the investment rate. Moreover, our findings underscore the growing importance of TFP growth as a driver of Chinese growth.
Impact of Statins on Arteriovenous Fistulas Outcomes: A Meta‐Analysis
Authors: Wan Qingsong , Li Li , Yang Shikun , Chu Fenfen 
Published: September 2017

AbstractStatins are effective lipid‐lowering drugs with beneficial pleiotropic effects for vascular remodeling processes, statins may have a beneficial effect on the function of arteriovenous fistulas (AVFs) in hemodialysis (HD) patients. Therefore, we performed this systematic review to assess the protective effects of statin therapy in HD patients. The randomized controlled trials (RCTs) or quasi‐RCTs and retrospective cohort studies (RCS) of statin therapy for the function of AVFs in HD patients were searched from multiple databases. Relevant studies were screened according to predefined inclusion criteria and then pooled‐analyses were performed using RevMan 5.2 software. One RCT and six RCS containing 20 246 HD patients were included in this meta‐analysis, of whom 9847 were treated with statins and 10 399 were treated with placebo. Our meta‐analysis showed that there was no significant difference between statins and placebo groups, with those who received statin therapy showing similar AVF failure rates compared to control (pooled risk ratio = 0.89; 95% CI, 0.70 to 1.12, P = 0.32), and there was obvious evidence of statistical heterogeneity (P = 0.005; I2 = 68%). In addition, subgroup pooled analyses revealed that statin therapy did not ameliorate AVF failure in participants from the same racial background or similar sample size trials. There was no evidence that statins therapy could reduce the AVFs failure. However, due to methodological limitations and obvious statistical heterogeneity, high‐quality, long‐term and multicenter trials are required to fully elucidate the clinical value of statins administration for the outcomes of AVFs in HD patients.
Regional evidence and international recommendations to guide lipid management in Asian patients with type 2 diabetes with special reference to renal dysfunction
Authors: Lau Titus WL , Tan Kevin E.K. , Choo Jason C.J. , Ng Tsun‐Gun , Tavintharan Subramaniam , Chan Juliana C.N. 
Published: September 2017

AbstractThe anticipated increase in the prevalence and incidence of type 2 diabetes in Asia, and its associated cardiovascular–renal complications, will place a significant burden on patients, caregivers, and society. Despite the proven effectiveness of lipid management in reducing these complications, there are major treatment gaps, especially in Asian patients with young‐onset diabetes and chronic kidney disease (CKD). Recent international guidelines recommended the adoption of absolute risk estimation of atherosclerosis and cardiovascular disease to guide treatment intensity. These recommendations replaced the previous strategy of using low‐density lipoprotein cholesterol targets to guide initiation and intensification of lipid lowering, albeit still widely practiced in Asia. The latest guidelines also highlight the high risk of atherosclerosis and cardiovascular disease (ASCVD) for people with diabetes, who should be protected with statins, except for young patients without other risk factors, who will need yearly monitoring of blood lipid levels. Given the propensity of Asian patients with diabetes to develop CKD and the amplifying effect of CKD on ASCVD, the use of statins in Asian patients is particularly important. Due to interethnic differences in drug metabolism, rosuvastatin, which is largely cleared by the kidney, should be prescribed in low dosages (5–10 mg daily) in Asian populations. Conversely, epidemiological and experimental data confirm pleotropic and organ‐protective effects of atorvastatin, with proven safety in Asian populations within a daily dose range of 10–40 mg. Thus, there is a need for Asian countries to review and align their lipid‐lowering treatment guidelines to reduce the substantial burden of diabetes in the Asian region.
eSnail: A transcriptome‐based molecular resource of the central nervous system for terrestrial gastropods
Authors: Zhao Min , Wang Tianfang , Stewart Michael J. , Bose Utpal , Suwansa‐ard Saowaros , Storey Kenneth B. , Cummins Scott F. 
Published: September 2017

AbstractTo expand on emerging terrestrial gastropod molecular resources, we have undertaken transcriptome‐based sequencing of the central nervous system (CNS) from six ecologically invasive terrestrial gastropods. Focusing on snail species Cochlicella acuta and Helix aspersa and reticulated slugs Deroceras invadens, Deroceras reticulatum, Lehmannia nyctelia and Milax gagates, we obtained a total of 367,869,636 high‐quality reads and compared them with existing CNS transcript resources for the invasive Mediterranean snail, Theba pisana. In total, we obtained 419,289 unique transcripts (unigenes) from 1,410,569 assembled contigs, with blast search analysis of multiple protein databases leading to the annotation of 124,268 unigenes, of which 92,544 mapped to ncbi nonredundant protein databases. We found that these transcriptomes have representatives in most biological functions, based on comparison of gene ontology, kegg pathway and protein family contents, demonstrating a high range of transcripts responsible for regulating metabolic activities and molecular functions occurring within the CNS. To provide an accessible genetic resource, we also demonstrate the presence of 66,687 microsatellites and 304,693 single‐nucleotide variants, which can be used for the design of potentially thousands of unique primers for functional screening. An online “eSnail” database with a user‐friendly web interface was implemented to query all the information obtained herein (http://soft.bioinfo-minzhao.org/esnail). We demonstrate the usefulness of the database through the mining of molluscan neuropeptides. As the most comprehensive CNS transcriptome resource for terrestrial gastropods, eSnail may serve as a useful gateway for researchers to explore gastropod CNS function for multiple purposes, including for the development of biocontrol approaches.
Intensive vaginal dilation using adjuvant treatments in women with Mayer‐Rokitansky‐Kuster‐Hauser syndrome: retrospective cohort study
Authors: Ketheeswaran Ashradha , Morrisey Jennifer , Abbott Jason , Bennett Michael , Dudley Jan , Deans Rebecca 
Published: September 2017

AimsTo evaluate the effect of adjuvants during intensive vaginal dilator therapy for functional and anatomical neovagina creation in women with Mayer‐Rokitansky‐Kuster‐Hauser syndrome (MRKH).MethodsThis retrospective cohort study included 75 women with MRKH undergoing intensive vaginal dilator treatment between 2000 and 2014. One specialist nurse performed non‐surgical vaginal dilation aided by adjuvants, during inpatient admissions for several dilation sessions per day. Following discharge, women continued dilation at home and were advised to attend fortnightly follow‐up appointments.ResultsOutcomes from 68 women were analysed. The median age of starting treatment was 18 years (range: 13–36). There was a mean of 3 days per admission (range 1–5) with a median of 10 dilation sessions per admission. Adjuvant treatment was used by 48/68 (71%) women: oestriol cream 29/68 (43%), 50:50 nitrous oxide and oxygen 44/68 (65%), diazepam 8/68 (12%), lidocaine ointment 26/68 (39%), paracetamol 35/68 (51%) and naproxen 2/68 (3%). There were no statistically significant differences for changes in vaginal parameters. Women receiving adjuvants had a median increase of 4.5 cm (0.5–7 cm) in neovaginal length compared with women not receiving adjuvants who had a median increase of 3.25 cm (0–7 cm) during intensive treatment. Women who received adjuvants tolerated more dilation sessions per day (10 vs 6.5 median sessions respectively) than those who did not (P < 0.001). Of those with documented length at discharge, 42/56 (75%) women had an anatomical neovagina of 7 cm or greater length.ConclusionsVaginal dilation delivered by intensive treatment and supplemented by adjuvant treatments in a multi‐disciplinary centre is a rapid and effective method for creation of a neovagina in women with MRKH.
The prevalence of atopic dermatitis beyond childhood: A systematic review and meta‐analysis of longitudinal studies
Authors: Abuabara K. , Yu A. M. , Okhovat J.‐P. , Allen I. E. , Langan S. M. 
Published: September 2017

AbstractBackgroundThere are sparse and conflicting data regarding the long‐term clinical course of atopic dermatitis (AD). Although often described as a childhood disease, newer population‐based estimates suggest the prevalence of pediatric and adult disease may be similar.MethodsOur objective was to determine whether there is a decline in the prevalence of AD in population‐based cohorts of patients followed longitudinally beyond childhood. We conducted a systematic review and meta‐analysis including studies assessing AD prevalence across 3 or more points in time. The primary outcome was weighted overall risk difference (percentage decrease in AD prevalence).ResultsOf 2080 references reviewed, 7 studies with 13 515 participants were included. Participants were assessed at 3‐6 time points, ranging from age 3 months to 26 years. The percentage decrease in prevalence after age 12 was 1%, which was not significantly different from zero (95% confidence interval −2%‐5%). Similar results were found with other age cut‐offs.ConclusionThe prevalence of AD in longitudinal birth cohort studies is similar in childhood and adolescence/early adulthood.
The roadmap for allergology in Europe: The subspecialty of allergology as “stop‐over” on the way to a full specialty. An EAACI position statement
Authors: Gerth van Wijk R. , Eguiluz‐Gracia I. , Gayraud J. , Gutermuth J. , Hamelmann E. , Heffler E. , Popov T. A. , Schmid‐Grendelmeier P. , Tomazic P. V. , Tsilochristou O. , Muelleneisen N. 
Published: September 2017

AbstractThe vision of European Academy of Allergy and Clinical Immunology (EAACI) and the Union of European Medical Specialists Section and Board on allergology is to promote and to establish a full specialty of allergology in all European countries. In many European countries, a full specialty does not exist. In those countries, organ‐based (sub)specialists or paediatricians and internists with an expertise in allergology may deliver allergy care. There are no generally accepted requirements for the training of subspecialists available. To fill the gap between the need and availability of experienced and accredited physicians who can deliver optimal care to the allergic patients, the EAACI Specialty Committee proposes the minimal requirements for training and certification of subspecialists in allergology. This paper describes the required theoretical knowledge, skills, competences and training facilities (staff and institution). The subspecialist as described in this paper should ideally show the necessary competence in providing good quality care to patients in an environment lacking those full specialists in allergology or tertiary care paediatric subspecialists in allergy.
The pruritogenic mediator endothelin‐1 shifts the dendritic cell–T‐cell response toward Th17/Th1 polarization
Authors: Nakahara T. , Kido‐Nakahara M. , Ohno F. , Ulzii D. , Chiba T. , Tsuji G. , Furue M. 
Published: September 2017

AbstractEndothelin‐1 (ET‐1) is associated with skin diseases such as atopic dermatitis (AD) and psoriasis. ET‐1 is enhanced in the skin of patients AD and psoriasis. In addition, plasma levels of ET‐1 are elevated in AD and psoriasis. Although both AD and psoriasis are T‐cell–mediated skin diseases, the association between ET‐1 and the T‐cell immune response has not been clarified. To evaluate the role of ET‐1 in inflammatory skin disease, we sought to investigate the effects of ET‐1 on the functions of dendritic cells (DCs) and subsequent immune responses. For this purpose, we immunohistochemically confirmed the upregulation of ET‐1 in the epidermis of patients with AD or psoriasis. ET‐1 directly induced phenotypic maturation of bone marrow‐derived DCs (BMDCs). In addition, ET‐1 augmented the production of several cytokines and allogeneic stimulatory capacity of BMDCs. Interestingly, ET‐1–activated BMDCs primed T cells to produce Th1 and Th17 cytokines, but not Th2 cytokines. These findings indicate that ET‐1 polarizes the DC–T‐cell response toward Th17/1 differentiation and may augment the persistent course of inflammatory skin diseases.