bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polypharmacy, potentially inappropriate medication and pharmacogenomics drug exposure in the Rhineland Study
Authors: de Vries Folgerdiena M. , Stingl Julia C. , Breteler Monique M.B. 
Published: November 2020

AimHigh medication use may contribute to the efficiency of drug therapy in general, but it could also increase the burden of adverse drug reactions. We aimed to assess medication use and the prevalence of three risk factors for adverse drug reactions: the use of polypharmacy, potentially inappropriate medication in the elderly and pharmacogenomic polymorphisms affecting the metabolism of drugs.MethodsCross‐sectional interview‐based medication data (including over‐the‐counter drugs) was collected in a large population‐based cohort (≥30 years of age) in Bonn, Germany.ResultsAnalyses were based on the first 5000 participants of the Rhineland Study (mean age 55 years, 57% women). Of our participants, 66.0% reported the use of a drug regularly, which increased to 87.4% in participants aged ≥65 years (n = 1301). The rates of use of polypharmacy, potentially inappropriate medication and pharmacogenomic drugs were 15.9%, 6.4% and 20.5%, respectively. In participants <65 years, 16.0% (95% CI 14.8, 17.3) had at least one risk factor. In participants aged ≥65 years, 54.1% (95% CI 51.4, 56.8) had at least one and 27.4% (95% CI 25.0, 29.9) had at least two risk factors. Extrapolating these numbers to the German population implies that around 9 million of the 17 million individuals aged 65 years or older are potentially at an elevated risk for adverse drug reactions, of which 4.6 million are at a potentially highly elevated risk for adverse drug reactions.ConclusionOur study shows that drug use is common and the individual risk for an adverse drug reaction in our population is high. This suggests room for improvement in general medication use.
Drug‐drug interaction of atazanavir on UGT1A1‐mediated glucuronidation of molidustat in human
Authors: van der Mey Dorina , Gerisch Michael , Jungmann Natalia A. , Kaiser Andreas , Yoshikawa Kenichi , Schulz Simone , Radtke Martin , Lentini Silvia 
Published: November 2020

AbstractMolidustat is an oral inhibitor of hypoxia‐inducible factor (HIF) prolyl‐hydroxylase enhancing the erythropoietin (EPO) response to HIF; it is in clinical development for the treatment of anaemia related to chronic kidney disease. The predominant role of glucuronidation for molidustat clearance (formation of N‐glucuronide metabolite M1) and subsequent renal excretion was confirmed in a human mass balance study, with about 85% of the drug being excreted as M1 in urine. The inhibitory effects of 176 drugs and xenobiotics from various compound classes on the UGT‐mediated glucuronidation of molidustat in human liver microsomes (HLMs) were investigated. Based on preclinical findings, glucuronidation of molidustat was predominantly mediated by the 5'‐diphospho‐glucuronosyltransferase (UGT) isoform UGT1A1. Therefore, atazanavir, which is a potent inhibitor of UGT1A1, was chosen for the evaluation of pharmacokinetics and EPO release following a single oral dose of 25 mg molidustat. Molidustat exposure increased about twofold upon coadministration with atazanavir when considering area under plasma concentration‐time curve from zero to infinity (AUC) and maximum plasma concentration (Cmax). Baseline‐corrected increase of EPO was 14% and 34% for Cmax and AUC (calculated over 24 hours), respectively. Coadministration of molidustat and atazanavir was well tolerated.
From one new law to (many) new practices? Multidisciplinary teams re‐constructing the meaning of a new disability law
Authors: Caillaud Sabine , Haas Valérie , Castro Paula 
Published: November 2020

This paper explores how a new French law incorporating a new conceptualization of disability formulated at the international level by the WHO is appropriated at the local level by multidisciplinary teams of professionals in charge of the assessment of disability. Drawing on social representations theory, its concept of cognitive polyphasia and its conceptualization of legal innovation, the paper specifically examines how the teams deal with the tensions between the old and the new models of disability and how the group dynamic is associated with how they do this: by hybridization of old and new models, by selective prevalence according to context, or by displacement of one model. Focus groups with the teams (n = 65 from 10 groups), analysed with indicators of interaction, bring evidence of the three forms. They show how different groups, by drawing differently, depending on their relational dynamics, from a variety of meaning systems circulating at the cultural level, reach different decisions that may lead to different practices in the local implementation of the same laws. We finish by discussing how social representations theory, linking the cultural/global and the interactional/local levels, can enhance our understanding of how socio‐psychological processes intervening in the appropriation of legal innovations may produce different practical implementations of the same new laws.
Higher‐Order Time Integration for Deformable Solids
Authors: Löschner Fabian , Longva Andreas , Jeske Stefan , Kugelstadt Tassilo , Bender Jan 
Published: November 2020

AbstractVisually appealing and vivid simulations of deformable solids represent an important aspect of physically based computer animation. For the temporal discretization, it is customary in computer animation to use first‐order accurate integration methods, such as Backward Euler, due to their simplicity and robustness. Although there is notable research on second‐order methods, their use is not widespread. Many of these well‐known methods have significant drawbacks such as severe numerical damping or scene‐dependent time step restrictions to ensure stability. In this paper, we discuss the most relevant requirements on such methods in computer animation and motivate the interest beyond first‐order accuracy. Keeping these requirements in mind, we investigate several promising methods from the families of diagonally implicit Runge‐Kutta (DIRK) and Rosenbrock methods which currently do not appear to have considerable popularity in this field. We show that the usage of such methods improves the visual quality of physical animations. In addition, we demonstrate that they allow distinctly more control over damping at lower computational cost than classical methods. As part of our theoretical contribution, we review aspects of simulations that are often considered more intricate with higher‐order methods, such as contact handling. To this end, we derive an implicit linearized contact model based on a predictor‐corrector approach that leads to consistent behavior with higher‐order integrators as predictors. Our contact model is well suited for the simulation of stiff, nonlinear materials with the integration methods presented in this paper and more common methods such as Backward Euler alike.
A Finite Element Formulation of Baraff‐Witkin Cloth
Authors: Kim Theodore 
Published: November 2020

AbstractThe Baraff‐Witkin [BW98] model has been a popular formulation for cloth for 20 years. However, its relationship to the finite element method (FEM) has always been unclear, because the model resists being written as an isotropic, hyperelastic strain energy. In this paper, we show that this is because the Baraff‐Witkin model is actually a coupled anisotropic strain energy. We show that its stretching term approximates the isotropic As‐Rigid‐As‐Possible (ARAP) energy, and its shearing term is a cross‐fiber coupling energy common in biomechanics. While it has been known empirically for some time that the model can produce indefinite force Jacobians, the conditions under which they occur has never been clear. Our formulation enables a complete eigenanalysis that precisely characterizes exactly when indefiniteness occurs, and leads to fast, analytic, semi‐positive‐definite projection methods. Finally, our analysis suggests a generalized Baraff‐Witkin energy with non‐orthogonal warp and weft directions.
How decisions about fitting species distribution models affect conservation outcomes
Authors: Muscatello Angela , Elith Jane , Kujala Heini 
Published: November 2020

AbstractSpecies distribution models (SDMs) are increasingly used in conservation and land‐use planning as inputs to describe biodiversity patterns. These models can be built in different ways, and decisions about data preparation, selection of predictor variables, model fitting, and evaluation all alter the resulting predictions. Commonly, the true distribution of species is unknown and independent data to verify which SDM variant to choose are lacking. Such model uncertainty is of concern to planners. We analyzed how 11 routine decisions about model complexity, predictors, bias treatment, and setting thresholds for predicted values altered conservation priority patterns across 25 species. Models were created with MaxEnt and run through Zonation to determine the priority rank of sites. Although all SDM variants performed well (area under the curve >0.7), they produced spatially different predictions for species and different conservation priority solutions. Priorities were most strongly altered by decisions to not address bias or to apply binary thresholds to predicted values; on average 40% and 35%, respectively, of all grid cells received an opposite priority ranking. Forcing high model complexity altered conservation solutions less than forcing simplicity (14% and 24% of cells with opposite rank values, respectively). Use of fewer species records to build models or choosing alternative bias treatments had intermediate effects (25% and 23%, respectively). Depending on modeling choices, priority areas overlapped as little as 10–20% with the baseline solution, affecting top and bottom priorities differently. Our results demonstrate the extent of model‐based uncertainty and quantify the relative impacts of SDM building decisions. When it is uncertain what the best SDM approach and conservation plan is, solving uncertainty or considering alterative options is most important for those decisions that change plans the most.
Skin tape stripping identifies gene transcript signature associated with allergic contact dermatitis
Authors: Tam Idy , Hill Kathryn R. , Park Jin M. , Yu JiaDe 
Published: November 2020

AbstractBackgroundAllergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) are common skin conditions with an overlapping clinical and histological appearance, but distinct underlying mechanisms. Patch testing is the gold standard for ACD diagnosis, yet the interpretation of its results may be confounded by weak and varying macroscopic reactions.ObjectiveTo examine whether gene transcript profiling of RNA sampled from patch tested patient skin by tape stripping (TS) could differentiate ACD from ICD and the baseline skin state (control)MethodsNine patients (seven females, two males; mean age 38.6 years, range 24–72 years) with confirmed ACD through patch testing were recruited. Total RNA was isolated from TS samples and relative transcript abundance was determined by quantitative real‐time polymeraise chain reaction using 39 gene‐specific primers.ResultsTS captured gene transcripts derived from diverse skin cell types, including not only keratinocytes, but also epidermal and dermal antigen‐presenting cells. Among the genes analysed in transcript profiling, genes encoding epidermal barrier components and inflammatory mediators exhibited changes in transcript abundance in ACD skin compared to ICD or control skin.ConclusionsOur findings reveal the potential of skin TS for non‐invasive biopsy during patch testing and molecular marker‐based ACD diagnosis.
Differential risk factor profile of diabetes and atherosclerosis in rural, sub‐urban and urban regions of South India: The KMCH‐Non‐communicable disease studies
Authors: Velmurugan Ganesan , Mohanraj Sundaresan , Dhivakar Mani , Veerasekar Ganesh , Brag‐Gresham Jennifer , He Kevin , Alexander Thomas , Cherian Mathew , Saran Rajiv , Pradeep Thalappil , Swaminathan Krishnan 
Published: November 2020

AbstractAimsSouth Asia has emerged rapidly as an epicentre of non‐communicable diseases (NCDs) specifically diabetes and cardiovascular diseases. The prevalence rate, risk factors and aetiology of NCDs in different socio‐demographic settings are not clearly understood. This study was performed to assess the prevalence of diabetes and atherosclerosis and their risk factors in urban, sub‐urban and rural communities of South India.MethodsThree communities [Nallampatti (rural), Thadagam (sub‐urban) and Kalapatti (urban)] in South India were selected for participation in the KMCH‐NCD Studies. Study volunteers were administered a detailed questionnaire, underwent anthropometric measurements, clinical measurements including blood pressure, glycated haemoglobin (HbA1c), non‐fasting lipid profile and serum creatinine. Carotid intima‐media thickness was measured using B‐mode ultrasound. Multiple logistic regression analyses were performed to understand the association of risk factors with diabetes and atherosclerosis.ResultsA total of 2976 native participants, ≥20 years of age were screened. The prevalence of diabetes was 16%, 26% and 23% respectively in the rural, sub‐urban and urban study populations. Association of obesity with diabetes was observed in only urban population while hypertension and dyslipidaemia showed association in both urban and semi‐urban populations. Association of diabetes with atherosclerosis was observed in urban and semi‐urban populations. Hypertension in semi‐urban and obesity and dyslipidaemia in urban population showed association with atherosclerosis.ConclusionsDiabetes and atherosclerosis burden reported in the three different communities were higher than previous reports, especially in rural and sub‐urban regions. No traditional risk factor is identified to be associated with prevalence of diabetes and atherosclerosis in rural population. These findings suggest an urgent need for investigation into the role of non‐traditional risk factors like environmental or occupational exposures may help to better understand the aetiology of diseases in non‐urbanized communities.
Effectiveness and safety of sodium‐glucose co‐transporter‐2 inhibitors compared with dipeptidyl peptidase‐4 inhibitors in older adults with type 2 diabetes: A nationwide population‐based study
Authors: Han Seung Jin , Ha Kyoung Hwa , Lee Nami , Kim Dae Jung 
Published: November 2020

AbstractAimTo examine the real‐world cardiovascular effectiveness and safety associated with sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor compared with dipeptidyl peptidase‐4 (DPP‐4) inhibitor treatment in older adults with type 2 diabetes.Materials and MethodsIn this retrospective cohort study, older adults with type 2 diabetes (aged ≥65 years) were identified in the Korean National Health Insurance Service database from September 2014 to December 2016. In total, 408 506 new users of an SGLT2 inhibitor or DPP‐4 inhibitor were propensity score matched. Cox regression was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for outcomes of interest: hospitalization for heart failure (HHF), all‐cause death, myocardial infarction, stroke, diabetic ketoacidosis (DKA), bone fracture, severe hypoglycaemia, genital infection and urinary tract infection (UTI).ResultsCompared with DPP‐4 inhibitors, new users of SGLT2 inhibitors had a lower risk of HHF (HR 0.86; 95% CI 0.76‐0.97), all‐cause death (HR 0.85; 95% CI 0.75‐0.98) and stroke (HR 0.86; 95% CI 0.77‐0.97), but a similar risk of myocardial infarction (HR 0.95; 95% CI 0.77‐1.19). The risks of DKA, bone fracture and severe hypoglycaemia were similar between both groups, although genital infection (HR 2.44; 95% CI 2.22‐2.67) and UTI (HR 1.05; 95% CI 1.00‐21.11) were more frequent among new users of SGLT2 inhibitors compared with DPP‐4 inhibitors.ConclusionOur findings suggest that initiation of SGLT2 inhibitors offers cardiovascular disease protection and can be used safely in older adults with type 2 diabetes.
Results from the Effects of MEtformin on cardiovasculaR function in AdoLescents with type 1 Diabetes (EMERALD) study: A brief report of kidney and inflammatory outcomes
Authors: Tommerdahl Kalie L. , Bjornstad Petter , Kendrick Jessica , Cree‐Green Melanie , Baumgartner Amy D. , Pyle Laura , Reusch Jane E. B. , Nadeau Kristen J. 
Published: November 2020

AbstractYouth with type 1 diabetes (T1D) demonstrate insulin resistance, independently of glycaemia, when compared to normoglycaemic peers. Insulin resistance increases the risk of cardiovascular disease and diabetic kidney disease, factors also associated with systemic inflammation. We evaluated the effect of metformin on markers of inflammation and diabetic kidney disease in adolescents with T1D. EMERALD, a double‐blind, randomized, placebo‐controlled trial of 3 months of metformin in 48 participants aged 12–21 years with T1D, included baseline and follow‐up assessments of serum creatinine and cystatin C to estimate glomerular filtration rate (eGFR), aspartate aminotransferase, alanine aminotransferase, high‐sensitivity C‐reactive protein, white blood count, platelets, adiponectin, leptin, and urine albumin: creatinine ratio (UACR). Metformin was associated with a 13.9 mL/min/1.73 m2 (95% confidence interval 4.7–23.1 mL/min/1.73 m2) increase in estimated GFR by serum creatinine versus placebo (P ≤ 0.01), with a significant difference remaining after multivariable adjustments (P = 0.03). Whereas eGFR measured by serum creatinine increased significantly after metformin treatment, no differences were observed in cystatin C, UACR, or systemic inflammatory markers. Additional studies with directly measured GFR in response to metformin in T1D are needed.
Weight‐loss response to naltrexone/bupropion is modulated by the Taq1A genetic variant near DRD2 (rs1800497): A pilot study
Authors: Mullally Jamie A. , Chung Wendy K. , LeDuc Charles A. , Reid Tirissa J. , Febres Gerardo , Holleran Steven , Ramakrishnan Rajasekhar , Korner Judith 
Published: November 2020

AbstractNaltrexone/bupropion (NB) is a US Food and Drug Administration‐approved antiobesity medication. Clinical trials have shown variable weight loss, with responders and non‐responders. NB is believed to act on central dopaminergic pathways to suppress appetite. The Taq1A polymorphism near DRD2 (rs1800497) is associated with the density of striatal dopamine D2 receptors, with individuals carrying the A allele (AA or AG; termed A1+) having 30%‐40% fewer dopamine binding sites than those who do not carry the A allele (GG; termed A1‐). We performed a pilot study to assess the association of the rs1800497 ANKK1 c.2137G > A (p.Glu713Lys) variant with weight loss with NB treatment in 33 subjects. Mean (SD) weight loss was 5.9% (3.2%) for the A1+ genotype group (n = 15) and 4.2% (4.2%) for the A1‐ genotype group (n = 18). The mean weight loss for the A1+ genotype group was significantly greater than the predefined clinically significant 4% weight‐loss target (one‐sample t‐test, P = .035), whereas the mean weight loss for the A1‐ genotype group was not (P = .85). Individuals with the A1+ genotype appear to respond better to NB than A1‐ individuals.
Inequalities in higher education in low‐ and middle‐income countries: A scoping review of the literature
Authors: Reinders Simone , Dekker Marleen , Falisse Jean‐Benoît 
Published: November 2020

AbstractMotivationHigher education is regarded as a key instrument to enhance socioeconomic mobility and reduce inequalities. Recent literature reviews have examined inequalities in the higher education systems of high‐income countries, but less is known about the situation in low‐ and middle‐income countries, where higher education is expanding fast.PurposeThe article reviews the academic literature on higher education in low‐ and middle‐income countries using a research framework inspired by social justice and capability approaches. It considers the financial, sociocultural, human and political resource domains on which people draw, and how they relate to access, participation and outcomes in higher education.MethodsA literature search for studies explicitly discussing in‐country inequalities in higher education revealed 22 publications. Substantial knowledge gaps remain, especially regarding the political (and decision‐making) side of inequalities; the ideologies and philosophies underpinning higher education systems; and the linkages between resource domains, both micro and macro.FindingsThe review highlights key elements for policy‐makers and researchers: (1) the financial lens alone is insufficient to understand and tackle inequalities, since these are also shaped by human and other non‐financial factors; (2) sociocultural constructs are central in explaining unequal outcomes; and (3) inequalities develop throughout one’s life and need to be considered during higher education, but also before and after. The scope of inequalities is wide, and the literature offers a few ideas for short‐term fixes, such as part‐time and online education.Policy implicationsInclusive policy frameworks for higher education should include explicit goals related to (in)equality, which are best measured in terms of the extent to which certain actions or choices are feasible for all. Policies in these frameworks, we argue, should go beyond providing financial support, and also address sociocultural and human resource constraints and challenges in retention, performance and labour market outcomes. Finally, they should consider relevant contextual determinants of inequalities.
How does conversion from forest to pasture affect the taxonomic and functional structure of the fish assemblages in Amazonian streams?
Authors: Cantanhêde Lorrane Gabrielle , Luiza‐Andrade Ana , Leão Híngara , Montag Luciano Fogaça de Assis 
Published: November 2020

AbstractClearing land for the establishment of pasture is the principal cause of deforestation in the Amazon basin. We investigated how stream habitats and the taxonomic and functional structure of the fish fauna respond to the effects of the conversion of forest to pasture in the eastern Brazilian Amazon. We sampled 13 streams located in areas of forest and 13 streams within a pasture matrix. The structure of the stream habitats, and the taxonomic and functional structure of the fish assemblages were compared between forest and pasture, using univariate and multivariate analyses. Species richness did not vary between environments, although abundance was greater in forest streams. Functional divergence was lower in the pasture streams, indicating a reduced degree of niche differentiation. The pasture streams presented a higher percentage of artificial shelters, such as pipes and plastic containers, and riffles, while the forest streams had greater canopy cover formed by large trees, and a denser substrate formed by leaf litter. Environmental variables influenced the distribution of species based on their functional traits. The greater canopy cover in forest streams benefitted benthic species. The ongoing increase in the area of pasture in the Amazon region is causing changes in stream habitats, and in the taxonomic and functional structure of the local fish assemblages. The impacted streams did not favour the occurrence of species with parental care or piscivorous, invertivorous, and benthic habits. Overall, protecting forests and the stream margins will promote adequate conditions to maintain the equilibrium of Amazonian stream ecosystems.