bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pharmacogenomics of inhaled corticosteroids and lung function decline in COPD
Authors: Obeidat Ma'en , Faiz Alen , Li Xuan , van den Berge Maarten , Hansel Nadia N. , Joubert Philippe , Hao Ke , Brandsma Corry-Anke , Rafaels Nicholas , Mathias Rasika , Ruczinski Ingo , Beaty Terri H. , Barnes Kathleen C. , Man S.F. Paul , Paré Peter D. , Sin Don D. 
Published: September 2019

Inhaled corticosteroids (ICS) are widely prescribed for patients with chronic obstructive pulmonary disease (COPD), yet have variable outcomes and adverse reactions, which may be genetically determined. The primary aim of the study was to identify the genetic determinants for forced expiratory volume in 1 s (FEV1) changes related to ICS therapy.In the Lung Health Study (LHS)-2, 1116 COPD patients were randomised to the ICS triamcinolone acetonide (n=559) or placebo (n=557) with spirometry performed every 6 months for 3 years. We performed a pharmacogenomic genome-wide association study for the genotype-by-ICS treatment effect on 3 years of FEV1 changes (estimated as slope) in 802 genotyped LHS-2 participants. Replication was performed in 199 COPD patients randomised to the ICS, fluticasone or placebo.A total of five loci showed genotype-by-ICS interaction at p<5×10−6; of these, single nucleotide polymorphism (SNP) rs111720447 on chromosome 7 was replicated (discovery p=4.8×10−6, replication p=5.9×10−5) with the same direction of interaction effect. ENCODE (Encyclopedia of DNA Elements) data revealed that in glucocorticoid-treated (dexamethasone) A549 alveolar cell line, glucocorticoid receptor binding sites were located near SNP rs111720447. In stratified analyses of LHS-2, genotype at SNP rs111720447 was significantly associated with rate of FEV1 decline in patients taking ICS (C allele β 56.36 mL·year−1, 95% CI 29.96–82.76 mL·year−1) and in patients who were assigned to placebo, although the relationship was weaker and in the opposite direction to that in the ICS group (C allele β −27.57 mL·year−1, 95% CI −53.27– −1.87 mL·year−1).The study uncovered genetic factors associated with FEV1 changes related to ICS in COPD patients, which may provide new insight on the potential biology of steroid responsiveness in COPD.
The effects of marijuana smoking on lung function in older people
Authors: Tan Wan C. , Bourbeau Jean , Aaron Shawn D. , Hogg James C. , Maltais François , Hernandez Paul , Marciniuk Darcy D. , Chapman Kenneth R. , To Teresa , FitzGerald J. Mark , Walker Brandie L. , Road Jeremy , Zheng Liyun , Zhou Guohai , Yau Trevor , Benedetti Andrea , O'Donnell Denis , Sin Don D. 
Published: September 2019

BackgroundPrevious studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear.MethodsWe determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV1in a subset of 1285 males and females, aged ≥40 years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV1was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20 pack-years and >20 joint-years, respectively.Results∼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55–3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV1by 29.5 mL·year−1(p=0.0007) and 21.1 mL·year−1(p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31 mL·year−1(p<0.0001).InterpretationHeavy marijuana smoking increases the risk of COPD and accelerates FEV1decline in concomitant tobacco smokers beyond that observed with tobacco alone.
Subtyping of Primary Aldosteronism in the AVIS-2 Study: Assessment of Selectivity and Lateralization
Authors: Rossitto Giacomo , Amar Laurence , Azizi Michel , Riester Anna , Reincke Martin , Degenhart Christoph , Widimsky Jiri , Naruse Mitsuhide , Deinum Jaap , Schultzekool Leo , Kocjan Tomaz , Negro Aurelio , Rossi Ermanno , Kline Gregory , Tanabe Akiyo , Satoh Fumitoshi , Rump Lars Christian , Vonend Oliver , Willenberg Holger S , Fuller Peter , Yang Jun , Nian Chee Nicholas Yong , Magill Steven B , Shafigullina Zulfiya , Quinkler Marcus , Oliveras Anna , Chang Chin-Chen , Wu Vin Cent , Somloova Zusana , Maiolino Giuseppe , Barbiero Giulio , Battistel Michele , Lenzini Livia , Quaia Emilio , Pessina Achille Cesare , Rossi Gian Paolo 
Published: September 2019

Abstract

Context
Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients.

Objectives
To investigate in a real-life study the rate of bilateral success and identification of unilateral aldosteronism and their impact on blood pressure outcomes in PA subtyped by AVS.

Design and settings
In a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study), we investigated how different cut-off values of the selectivity index (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism, and blood pressure outcomes.

Results
AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs, the rate of identified unilateral PA leading to adrenalectomy was as low as &lt;25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulated conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cut-offs ≥ 2.0, but reduced lateralization rates (P &lt; 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria.

Conclusion
Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test. (J Clin Endocrinol Metab XX: 0-0, 2020)
In utero Bisphenol A Exposure Is Linked with Sex Specific Changes in the Transcriptome and Methylome of Human Amniocytes
Authors: Bansal Amita , Robles-Matos Nicole , Wang Paul Zhiping , Condon David E , Joshi Apoorva , Pinney Sara E 
Published: September 2019

AbstractContextPrenatal exposure to bisphenol A (BPA) is linked to obesity and diabetes but the molecular mechanisms driving these phenomena are not known. Alterations in deoxyribonucleic acid (DNA) methylation in amniocytes exposed to BPA in utero represent a potential mechanism leading to metabolic dysfunction later in life.ObjectiveTo profile changes in genome-wide DNA methylation and expression in second trimester human amniocytes exposed to BPA in utero.DesignA nested case-control study was performed in amniocytes matched for offspring sex, maternal race/ethnicity, maternal age, gestational age at amniocentesis, and gestational age at birth. Cases had amniotic fluid BPA measuring 0.251 to 23.74 ng/mL. Sex-specific genome-wide DNA methylation analysis and RNA-sequencing (RNA-seq) were performed to determine differentially methylated regions (DMRs) and gene expression changes associated with BPA exposure. Ingenuity pathway analysis was performed to identify biologically relevant pathways enriched after BPA exposure. In silico Hi-C analysis identified potential chromatin interactions with DMRs.ResultsThere were 101 genes with altered expression in male amniocytes exposed to BPA (q &lt; 0.05) in utero, with enrichment of pathways critical to hepatic dysfunction, collagen signaling and adipogenesis. Thirty-six DMRs were identified in male BPA-exposed amniocytes and 14 in female amniocyte analysis (q &lt; 0.05). Hi-C analysis identified interactions between DMRs and 24 genes with expression changes in male amniocytes and 12 in female amniocytes (P &lt; 0.05).ConclusionIn a unique repository of human amniocytes exposed to BPA in utero, sex-specific analyses identified gene expression changes in pathways associated with metabolic disease and novel DMRs with potential distal regulatory functions.
Colocalization of Polycystic Ovary Syndrome Candidate Gene Products in Theca Cells Suggests Novel Signaling Pathways
Authors: Kulkarni Rewa , Teves Maria E , Han Angela X , McAllister Jan M , Strauss Jerome F 
Published: September 2019

Abstract
Genome-wide association studies identified loci associated with polycystic ovary syndrome (PCOS), including those near the LH receptor gene (LHCGR), a clathrin-binding protein (DENND1A) that functions as a guanine nucleotide exchange factor, and the gene encoding RAB5B, a GTPase involved in vesicular trafficking. We proposed that these three PCOS loci could be assembled into a functional network that contributes to altered gene expression in theca cells, resulting in increased androgen synthesis. The functional significance of this network was supported by our discovery that a truncated protein splice variant of the DENND1A gene, termed DENND1A.V2, is elevated in PCOS theca cells, and that forced expression of DENND1A.V2 in normal theca cells increased CYP11A1 and CYP17A1 expression and androgen synthesis, a hallmark of PCOS. In this study, we demonstrate the colocalization of LHCGR, DENND1AV.2, and RAB5B proteins in various cellular compartments in normal and PCOS theca cells by immunofluorescence. Human chorionic gonadotropin and forskolin stimulation was shown to affect the cytoplasmic distribution of LHCGR, DENND1A.V2, and RAB5B. DENND1A.V2 accumulated in the nuclei of the theca cells. Moreover, PCOS theca cells, following forskolin treatment, had a significantly greater relative abundance of nuclear DENND1A.V2. RAB5B also accumulated in the nuclei of PCOS theca cells treated with forskolin. In contrast, LHCGR did not enter the nucleus. This cytological evidence, and the previously reported increase in androgen biosynthesis with forced expression of DENND1A.V2 in normal theca cells, raises the possibility that DENND1A.V2 and RAB5B participate in increasing transcription of genes involved in androgen synthesis.
Prehospital Management of Acute Addison Disease: Audit of Patients Attending a Referral Hospital in a Regional Area
Authors: Goubar Thomas , Torpy David J , McGrath Shaun , Rushworth R Louise 
Published: September 2019

AbstractContextAdrenal crisis (AC) causes morbidity and mortality in patients with Addison disease [primary adrenal insufficiency (PAI)]. Patient-initiated stress dosing (oral or parenteral hydrocortisone) is recommended to avert ACs. Although these should be effective, the continued incidence of ACs remains largely unexplained.MethodsAudit of all attendances between 2000 and 2017 of adult patients with treated PAI to one large regional referral center in New South Wales, Australia. Measurements were those taken on arrival at hospital.ResultsThere were 252 attendances by 56 patients with treated PAI during the study period. Women comprised 60.7% (n = 34) of the patients. The mean age of attendees was 53.7 (19.6) years. Nearly half (45.2%, n = 114) of the patients had an infection. There were 61 (24.2%) ACs diagnosed by the treating clinician. Only 17.9% (n = 45) of the hospital presentations followed any form of stress dosing. IM hydrocortisone was used prior to presentation 7 (2.8%) attendances only. Among patients with a clinician-diagnosed AC, only 32.8% (n = 20) had used stress dosing before presentation. Vomiting was reported by 47.6% (n = 120) of the patients but only 33 (27.5%) of these attempted stress dosing and 5 patients with vomiting used IM hydrocortisone. The number of prior presentations was an independent predictor of use of stress doses [1.05 (1.01, 1.09)].ConclusionDose-escalation strategies are not used universally or correctly by unwell patients with PAI; many patients do not use IM or subcutaneous hydrocortisone injections. Previous hospital treatment increases the likelihood of stress dosing, and hospital attendance offers the opportunity for reinforcement of prevention strategies.
Medroxyprogesterone acetate alters the vaginal microbiota and microenvironment in women and increases susceptibility to HIV-1 in humanized mice
Authors: Wessels Jocelyn M. , Lajoie Julie , Cooper Maeve I. J. Hay , Omollo Kenneth , Felker Allison M. , Vitali Danielle , Dupont Haley A. , Nguyen Philip V. , Mueller Kristen , Vahedi Fatemeh , Kimani Joshua , Oyugi Julius , Cheruiyot Juliana , Mungai John N. , Deshiere Alexandre , Tremblay Michel J. , Mazzulli Tony , Stearns Jennifer C. , Ashkar Ali A. , Fowke Keith R. , Surette Michael G. , Kaushic Charu 
Published: September 2019

ABSTRACT
The hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores &lt;7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA-mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.
This article has an associated First Person interview with the first author of the paper.
Anharmonic Vibrational Analysis of Dihalogenomethanes and Dihalogenoethanes by Density-Functional Theory Calculations
Authors: Furuya Kazuhiko , Sakamoto Akira , Tasumi Mitsuo 
Published: September 2019

Abstract
The anharmonic vibrational wavenumbers of dihalogeno-methanes CH2X2 and 1,2-dihalogenoethanes CH2XCH2X (X: F, Cl, and Br) were calculated by using hybrid and double-hybrid density-functional methods. For comparison of the methods of calculation, the molecular-orbital method at the CCSD(T) level was also tested for CH2F2 and CH2Cl2. It was found that the hybrid-type B3LYP functional method was not satisfactory for calculating anharmonic vibrational wavenumbers. It was possible to improve the B3LYP functional method by altering the coefficients of the energy formula for CH2F2, but the set of obtained coefficients was not transferrable to CH2Cl2. The double-hybrid-type B2PLYP functional method with carefully chosen sets of basis functions gave molecular structures and anharmonic vibrational wavenumbers in good agreement with the published experimental values. The molecular-orbital method at the CCSD(T) level gave calculated results comparable with (or even better than) those by the B2PLYP functional method. However, the cost of computation by the B2PLYP functional method is far lower than that by the molecular-orbital method at the CCSD(T) level. The B2PLYP functional method, which has the advantage of giving satisfactory results with relatively low costs of computation, may become a realistic approach for anharmonic vibrational analyses of relatively large molecules in general.
The nature of symbols, the principles of their research in consciousness, and the peculiarities of the symbolic perception of cadets at Moscow University of the Ministry of Internal Affairs of Russia named after V.Ya. Kikotya
Authors: Иванов Роман , Ivanov Roman 
Published: September 2019

The article deals with the nature of the symbol, its influence on the perception, thinking and consciousness of man. Relevance of the use of such knowledge in the educational process of cadets of the Moscow University named after V. J. Kikot. In parallel, the properties of the object of study - a symbol for possible further clarification of the basic concept of the symbol and its consideration in the structure of symbolic perception and thinking of man. The subject of the study is the study of the properties of symbols of their compatibility, the search for symbolic correlations. For this purpose the research methodology based on the intersection of several social and psychological classifications, such scientists as G. Spencer, J. G. was outlined. Meade, K. G. Jung. Based on this technique, a pilot psychological test was developed and conducted, the results of which were the basis for some important theoretical interpretations.
The novelty of the study lies in the interpretation of symbol and symbolic thinking (as opposed to the concept and logical thinking) more widely. This system combines the processes of perception, thinking conscious and subconscious processes. As an example, we can speculatively assume that building a chain of monotonous (for some reason, not always having logical connections) symbols can be considered thinking processes different from classical logic. The explanation of the processes of human thinking through the symbolic structure of consciousness can more accurately describe the motives and actions of a person in a particular situation.
The results of this study can be included in seminars on the disciplines of Psychology in the activities of police officers, Socio-psychological training of professional communication, a Workshop on the psychology of communication.
Pigmentocracia: classe, raça e gênero no sistema de bem-estar social sul-africano
Authors: Barbosa Filho Evandro Alves , Vieira Ana Cristina De Souza , Rocha Solange 
Published: September 2019

O artigo analisa como as relações sociais de classe, raça e gênero presentes na formação social da África do Sul resultaram na constituição de um sistema de bem-estar social pigmentocrático. O estudo é qualitativo e se fundamenta na teoria da consubstancialidade das relações sociais de classe, raça e gênero produzida pela sociologia crítica sul-africana. Para o levantamento dos corpora foram realizadas revisão de literatura e análise de documentos oficiais. Foram analisados documentos produzidos desde o fim do período colonial até o ano de 1996. O estudo identificou que as relações de segregação engendraram um amplo sistema de bem-estar social orientado à ascensão e proteção social das famílias brancas. Enquanto isso, negros, mestiços e asiáticos se tornaram cada vez mais destituídos de direitos. Mesmo com o fim do apartheid, o sistema de bem-estar social sul-africano continua (re)produzindo a pigmentocracia, a partir das condicionalidades neoliberais que orientaram a transição à democracia. Palavras-Chave: África do Sul; bem-estar social; classe; raça e gênero; consubstancialidade das relações sociais.
Epileptic seizure recognition using EEG wavelet decomposition based on nonlinear and statistical features with support vector machine classification
Authors: Nabil Dib , Benali Radhwane , Bereksi Reguig Fethi 
Published: September 2019

AbstractEpileptic seizure (ES) is a neurological brain dysfunction. ES can be detected using the electroencephalogram (EEG) signal. However, visual inspection of ES using long-time EEG recordings is a difficult, time-consuming and a costly procedure. Thus, automatic epilepsy recognition is of primary importance. In this paper, a new method is proposed for automatic ES recognition using short-time EEG recordings. The method is based on first decomposing the EEG signals on sub-signals using discrete wavelet transform. Then, from the obtained sub-signals, different non-linear parameters such as approximate entropy (ApEn), largest Lyapunov exponents (LLE) and statistical parameters are determined. These parameters along with phase entropies, calculated through higher order spectrum analysis, are used as an input vector of a multi-class support vector machine (MSVM) for ES recognition. The proposed method is evaluated using the standard EEG database developed by the Department of Epileptology, University of Bonn, Germany. The evaluation is carried out through a large number of classification experiments. Different statistical metrics namely Sensitivity (Se), Specificity (Sp) and classification accuracy (Ac) are calculated and compared to those obtained in the scientific research literature. The obtained results show that the proposed method achieves high accuracies, which are as good as the best existing state-of-the-art methods studied using the same EEG database.
Assimilation, hybridity and encountering. The cinematic representation of queer migrants from Muslim backgrounds living in Europe
Authors: Coll-Planas Gerard 
Published: September 2019

AbstractMuslim migrants are the counter-figures through whom the modern Western identity is shaped. In Islamophobic discourses, they are constructed as inherently sexist and homophobic. In this ideological context, queer migrants coming from Muslim countries occupy an intersectional social location between Islamophobia and homophobia. In this paper we analyze the cinematic representation of queer migrants living in Europe coming from Muslim backgrounds. The aim of the paper is to analyze whether the films reproduce or subvert the Western “gay narrative”. The corpus of analysis is made up of 19 films which were studied through a process of categorization of the relevant fragments in a matrix. The films are classified in three categories according to their approach. The first gathers those films that hold an assimilationist discourse, according to which queer migrants should embrace the Western “gay narrative” and abandon the values of the communities of origin. In the second category, the films propose a hybrid perspective in which characters merge elements from both the country of residence and the cultural background of origin in the exploration of their sexuality and gender. The films in the third category revolve around a metaphorical relationship between a queer migrant and a native person, promoting a reflection on the possibilities of transformative encounters that break the boundaries between supposedly opposed social groups.