bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute kidney injury in renal transplant recipients undergoing cardiac surgery
Authors: Hundemer Gregory L , Srivastava Anand , Jacob Kirolos A , Krishnasamudram Neeraja , Ahmed Salman , Boerger Emily , Sharma Shreyak , Pokharel Kapil K , Hirji Sameer A , Pelletier Marc , Safa Kassem , Kulvichit Win , Kellum John A , Riella Leonardo V , Leaf David E 
Published: March 2020

AbstractBackgroundAcute kidney injury (AKI) is a key risk factor for chronic kidney disease in the general population, but has not been investigated in detail among renal transplant recipients (RTRs). We investigated the incidence, severity and risk factors for AKI following cardiac surgery among RTRs compared with non-RTRs with otherwise similar clinical characteristics.MethodsWe conducted a retrospective cohort study of RTRs (n = 83) and non-RTRs (n = 83) who underwent cardiac surgery at two major academic medical centers. Non-RTRs were matched 1:1 to RTRs by age, preoperative (preop) estimated glomerular filtration rate and type of cardiac surgery. We defined AKI according to Kidney Disease: Improving Global Outcomes criteria.ResultsRTRs had a higher rate of AKI following cardiac surgery compared with non-RTRs [46% versus 28%; adjusted odds ratio 2.77 (95% confidence interval 1.36–5.64)]. Among RTRs, deceased donor (DD) versus living donor (LD) status, as well as higher versus lower preop calcineurin inhibitor (CNI) trough levels, were associated with higher rates of AKI (57% versus 33% among DD-RTRs versus LD-RTRs; P = 0.047; 73% versus 36% among RTRs with higher versus lower CNI trough levels, P = 0.02). The combination of both risk factors (DD status and higher CNI trough level) had an additive effect (88% AKI incidence among patients with both risk factors versus 25% incidence among RTRs with neither risk factor, P = 0.004).ConclusionsRTRs have a higher risk of AKI following cardiac surgery compared with non-RTRs with otherwise similar characteristics. Among RTRs, DD-RTRs and those with higher preop CNI trough levels are at the highest risk.
MYB–bHLH–TTG1 Regulates Arabidopsis Seed Coat Biosynthesis Pathways Directly and Indirectly via Multiple Tiers of Transcription Factors
Authors: Li Song Feng , Allen Patrick J , Napoli Ross S , Browne Richard G , Pham Hanh , Parish Roger W 
Published: March 2020

Abstract
MYB–bHLH–WDR (MBW) transcription factor (TF) complexes regulate Arabidopsis seed coat development including mucilage and tannin biosynthesis. The R2R3 MYBs MYB5, MYB23 and TRANSPARENT TESTA2 (TT2) participate in the MBW complexes with the WD-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1). These complexes regulate GLABRA2 (GL2) and TTG2 expression in developing seeds. Microarray transcriptome analysis of ttg1-1- and wild-type (Ler) developing seeds identified 246 TTG1-regulated genes, which include all known metabolic genes of the tannin biosynthetic pathway. The first detailed TTG1-dependent metabolic pathways could be proposed for the biosynthesis of mucilage, jasmonic acid (JA) and cuticle including wax ester in developing seeds. We also assigned many known and previously uncharacterized genes to the activation/inactivation of hormones, plant immunity and nutrient transport. The promoters of six cuticle pathway genes were active in developing seeds. Expression of 11 genes was determined in the developing seeds of the combinatorial mutants of MYB5, MYB23 and TT2, and in the combinatorial mutants of GL2, HOMEODOMAIN GLABROUS2 (HDG2) and TTG2. These six TFs positively co-regulated the expression of four repressor genes while three of the six TFs repressed the wax biosynthesis genes examined, suggesting that the three TFs upregulate the expression of these repressor genes, which, in turn, repress the wax biosynthesis genes. Chromatin immunoprecipitation analysis identified 21 genes directly regulated by MYB5 including GL2, HDG2, TTG2, four repressor genes and various metabolic genes. We propose a multi-tiered regulatory mechanism by which MBWs regulate tannin, mucilage, JA and cuticle biosynthetic pathways.
On Non-Eliminative Structuralism. Unlabeled Graphs as a Case Study, Part B†
Authors: Leitgeb Hannes 
Published: March 2020

AbstractThis is Part B of an article that defends non-eliminative structuralism about mathematics by means of a concrete case study: a theory of unlabeled graphs. Part A motivated an understanding of unlabeled graphs as structures sui generis and developed a corresponding axiomatic theory of unlabeled graphs. Part B turns to the philosophical interpretation and assessment of the theory: it points out how the theory avoids well-known problems concerning identity, objecthood, and reference that have been attributed to non-eliminative structuralism. The part concludes by explaining how the theory relates to set theory, and what remains to be accomplished for non-eliminative structuralists.
Epistemic Judgement and Motivation
Authors: Boult Cameron , Köhler Sebastian 
Published: March 2020

Abstract
Is there an epistemic analogue of moral motivational internalism? The answer to this question has implications for our understanding of the nature of epistemic normativity. For example, some philosophers have argued from claims that epistemic judgement is not necessarily motivating to the view that epistemic judgement is not normative. This paper examines the options for spelling out an epistemic analogue of moral motivational internalism. It is argued that the most promising approach connects epistemic judgements to doxastic dispositions, which are related to motivation in a fairly tenuous sense. It is also argued that this approach currently lacks a plausible and informative account of the nature and workings of these doxastic dispositions, and, hence, an explanation of the range of phenomena internalist theses typically set out to explain. The most promising route for developing such an account, based on recent expressivist work, is investigated and found inadequate for the task.
DARE to be different? A novel approach for analysing diversity in collaborative research projects
Authors: Bone Frédérique , Hopkins Michael M , Ràfols Ismael , Molas-Gallart Jordi , Tang Puay , Davey Gail , Carr Antony M 
Published: March 2020

AbstractGrowth in collaborative research raises difficulties for those tasked with research evaluation, particularly in situations where outcomes are slow to emerge. This article presents the ‘Diversity Approach to Research Evaluation’ (DARE) as a novel way to assess how researchers engaged in knowledge creation and application work together as teams. DARE provides two important insights: first, it reveals the differences in background and experience between individual team members that can make research collaboration both valuable and challenging; second, DARE provides early insights into how team members are working together. DARE achieves these insights by analysing team diversity and cohesiveness in five dimensions, building on Boschma’s multi-dimensional concept of proximity. The method we propose combines narratives, maps, and indicators to facilitate the study of research collaboration. The article introduces the DARE method and pilots an initial operationalization through the study of two grant-funded biomedical research projects led by researchers in the UK. Suggestions for further development of the approach are discussed.
Policy Inertia, Election Uncertainty, and Incumbency Disadvantage of Political Parties
Authors: Chatterjee Satyajit , Eyigungor Burcu 
Published: March 2020

Abstract
We document that postwar U.S. elections show a strong pattern of “incumbency disadvantage”: if a party has held the presidency of the country or the governorship of a state for some time, that party tends to lose popularity in the subsequent election. We show that this fact can be explained by a combination of policy inertia and unpredictability in election outcomes. A quantitative analysis shows that the observed magnitude of incumbency disadvantage can arise in several different models of policy inertia. Normative and positive implications of policy inertia leading to incumbency disadvantage are explored.
Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy
Authors: Li Caiyu , Wang Xue , Bi Yajuan , Yu Heshui , Wei Jing , Zhang Yi , Han Lifeng , Zhang Youcai 
Published: March 2020

Abstract
Organic anion transporters 1 and 3 (OAT1 and OAT3) play a critical role in renal drug-drug interactions and are involved in the nephrotoxicity of many anionic xenobiotics. To date, relatively little is known about the interaction of natural compounds with OAT1 and OAT3. Of the 270 natural compounds screened in the present study, 21 compounds inhibited OAT1 and 45 compounds inhibited OAT3. Further concentration-dependent studies identified 7 OAT1 inhibitors and 10 OAT3 inhibitors with IC50 values of &lt;10 μM, and most of them were flavonoids, the most commonly ingested polyphenolic compounds in the diet and herbal products. Computational modeling of OAT1 and OAT3 revealed the important residues for the recognition of inhibitors. The two strong OAT inhibitors, namely wedelolactone and wogonin, were evaluated for their in vivo interactions with the OAT substrate aristolochic acid I (AAI), a natural compound causing aristolochic acid-induced nephropathy (AAN) in many species. The cytotoxicity of AAI increased in two OAT-overexpressing cell lines, with more cytotoxicity in OAT1-overexpressing cells, suggesting a more important role of OAT1 than OAT3 in AAN. Both wedelolactone and wogonin markedly increased serum AAI concentrations in AAI-treated rats and ameliorated kidney injuries in AAI-treated mice. To conclude, the present findings are of significant value in understanding natural compound-drug interactions and provide a natural source for developing treatments for AAN.
Development of an Improved T-cell Assay to Assess the Intrinsic Immunogenicity of Haptenic Compounds
Authors: Ogese Monday O , Watkinson Joel , Lister Adam , Faulkner Lee , Gibson Andrew , Hillegas Aimee , Sakatis Melanie Z , Park Brian Kevin , Naisbitt Dean J 
Published: March 2020

AbstractThe prediction of drug hypersensitivity is difficult due to the lack of appropriate models and known risk factors. In vitro naïve T-cell priming assays that assess immunogenicity have been developed. However, their application is limited due requirements for 2 batches of autologous dendritic cells (DC) and inconsistent results; a consequence of single well readouts when exploring reactions where compound-specific T-cell frequency is undefined. Hence, we aimed to develop an improved, but simplified assay, termed the T-cell multiple well assay (T-MWA), that permits assessment of drug-specific activation of naïve T cells, alongside analysis of the strength of the induced response and the number of cultures that respond. DC naïve T-cell coculture, depleted of regulatory T cells (Tregs), was conducted in up to 48 wells for 2 weeks with model haptens (nitroso sulfamethoxazole [SMX-NO], Bandrowski’s base [BB], or piperacillin [PIP]). Cultures were rechallenged with hapten and T-cell proliferation was measured using [3H]-thymidine incorporation. Priming of naïve T cells was observed with SMX-NO, with no requirement for DC during restimulation. Greater than 65% of cultures were activated with SMX-NO; with 8.0%, 30.8%, and 27.2% characterized as weak (stimulation index [SI] =1.5–1.9), moderate (SI = 2–3.9), and strong responses (SI &gt; 4), respectively. The number of responding cultures and strength of the response was reproducible when separate blood donations were compared. Coinhibitory checkpoint blockade increased the strength of the proliferative response, but not the number of responding cultures. Moderate to strong priming responses were detected with BB, whereas PIP stimulated only a small number of cultures to proliferate weakly. In drug-responsive cultures inducible CD4+CD25+FoxP3+CD127low Tregs were also identified. To conclude, the T-MWA offers improvements over existing assays and with development it could be used to study multiple HLA-typed donors in a single plate format.
Development and Application of TK6-derived Cells Expressing Human Cytochrome P450s for Genotoxicity Testing
Authors: Li Xilin , Chen Si , Guo Xiaoqing , Wu Qiangen , Seo Ji-Eun , Guo Lei , Manjanatha Mugimane G , Zhou Tong , Witt Kristine L , Mei Nan 
Published: March 2020

Abstract
Metabolism plays a key role in chemical genotoxicity; however, most mammalian cells used for in vitro genotoxicity testing lack effective metabolizing enzymes. We recently developed a battery of TK6-derived cell lines that individually overexpress 1 of 8 cytochrome P450s (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, and 3A4) using a lentiviral expression system. The increased expression and metabolic function of each individual CYP in each established cell line were confirmed using real-time PCR, Western blotting, and mass spectrometry analysis; the parental TK6 cells and empty vector (EV) transduced cells had negligible CYP levels. Subsequently, we evaluated these cell lines using 2 prototypical polyaromatic hydrocarbon mutagens, 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P), that require metabolic activation to exert their genotoxicity. DMBA-induced cytotoxicity, phosphorylation of histone H2A.X, and micronucleus formation were significantly increased in TK6 cells with CYP1A1, 1B1, 2B6, and 2C19 expression as compared with EV controls. B[a]P significantly increased cytotoxicity, DNA damage, and chromosomal damage in TK6 cells overexpressing CYP1A1 and 1B1 when compared with EV controls. B[a]P also induced micronucleus formation in TK6 cells expressing CYP1A2. These results suggest that our CYP-expressing TK6 cell system can be used to detect the genotoxicity of compounds requiring metabolic transformation.
Factors Associated With the Use of Supervised Consumption Facilities Among Women Who Inject Drugs in a Canadian Setting
Authors: Ickowicz Sarah , Grant Cameron , Nosova Ekaterina , Boyd Jade , Brar Rupinder , Milloy M.-J. , Hayashi Kanna , Nolan Seonaid 
Published: March 2020

Background:
Supervised consumption facilities (SCFs) are evidence-based harm reduction interventions that have been shown to reduce the risk of social and health-related harms associated with injection drug use. Previous qualitative studies have highlighted important motivations for SCF use among women who use drugs. However, factors associated with SCF use among women have not previously been evaluated.

Methods:
Data were obtained from 2 longitudinal community-recruited cohorts of people who use drugs in Vancouver, Canada between 2003 and 2017. Multivariable generalized estimating equations were used to calculate the odds of SCF use associated with social and structural risk factors for drug-related harm among women who reported injection drug use in the preceding 6-months.

Results:
A total of 795 participants were included in the study, contributing to 6302 interviews, with 602 participants (76%) reporting SCF use in at least one interview. Multivariable analysis demonstrated daily heroin and crystal methamphetamine injection (Adjusted Odds Ratio [AOR] = 1.32 and 1.65, respectively), injecting in public (AOR = 1.77), binge injection (AOR = 1.22) and lack of housing (AOR = 1.74) to be associated with SCF use.

Conclusions:
The current study demonstrates higher intensity patterns of drug use, including daily heroin and crystal methamphetamine injection, injecting in public and binge injection, as well as homelessness to be associated with SCF use among women. Future research should identify barriers to SCF use among women to minimize the risk of overdose and other drug-related harms.
Practice Makes Transfer Imperfect: Evidence From Auditory Learning
Authors: Zaltz Yael , Kishon-Rabin Liat , Karni Avi , Ari-Even Roth Daphne 
Published: March 2020

Background:Evidence from motor and visual studies suggests that the ability to generalize learning gains to untrained conditions decreases as the training progresses. This decrease in generalization was suggested to reflect a shift from higher to lower levels of neuronal representations of the task following prolonged training. In the auditory modality, however, the few studies that tested the influence of prolonging training on generalization ability showed no decrease and sometimes even an increase in generalization.Objective:To test the impact of extending training in a basic psychoacoustic task on the ability to generalize the gains attained in training to untrained conditions.Design:Eighty-two young adults participated in two experiments that differed in the specific training regimen. In both experiments, training was conducted using a difference limen for frequency (DLF) task with an adaptive forced-choice procedure, for either a single- or nine-session training. Following training, generalization to the untrained ear and to an untrained frequency was assessed.Results:(a) Training induced significant learning (i.e., smaller DLF thresholds) following a single session of training, and more so following nine training sessions; (b) results from the combined data from both experiments showed that the ability to generalize the learning gains to the untrained ear and frequency was limited after the extended DLF training; (c) larger improvements under the trained condition resulted in smaller generalization to the untrained conditions.Conclusions:The findings of increased specificity with training in the auditory modality support the notion that gradual changes, both quantitative and qualitative, occur in the neural representations of an auditory task during its acquisition. These findings suggest common underlying mechanisms in basic skill learning across different modalities.
Parent cognitive, behavioural, and affective factors and their relation to child pain and functioning in pediatric chronic pain: a systematic review and meta-analysis
Authors: Donnelly Theresa J. , Palermo Tonya M. , Newton-John Toby R.O. 
Published: March 2020

Abstract
Previous studies have demonstrated that parental cognitive, behavioral, and emotional factors are related to child functioning in children and adolescents with chronic pain. This is particularly important to understand how to potentially enhance the efficacy of psychological interventions for children by incorporating interventions targeting parents. We conducted a systematic review and meta-analysis to identify the specific parent factors that have been examined in the literature and to quantify the associations observed between parent factors and child pain and disability. A search of the electronic databases EMBASE, PsychINFO, Medline, and PubMed was conducted, using search terms related to chronic pain, pediatric population, and parents. Fifty-four studies met criteria and were included in the review. Parent pain catastrophizing and protective behavior were the most commonly assessed parental constructs in the literature. Meta-analyses were conducted for associations between parent pain catastrophizing, parent protective behaviors, parent anxiety and depression, and parent stress associated with parenting a child with chronic pain with child pain, disability, school functioning, and emotional functioning. Correlation coefficients were pooled using the random-effects model. A medium relationship was observed between higher protective behavior and poorer school functioning (r = −0.39), and small relationships were found between higher parent pain catastrophizing and increased child disability (r = 0.29); higher protective behaviors and increased child disability (r = 0.25); and increased parent depression and anxiety with increased child disability (r = 0.23 and r = 0.24, respectively). Future research is needed to investigate broader parent variables and overcome methodological weaknesses in this field.
Assessment and Interpretation of Vitamin and Trace Element Status in Sick Children
Authors:   ESPGHAN Committee on Nutrition, Gerasimidis Konstantinos , Bronsky Jiri , Catchpole Anthony , Embleton Nicholas , Fewtrell Mary , Hojsak Iva , Indrio Flavia , Hulst Jessie , Köglmeier Jutta , de Koning Barbara , Lapillonne Alexandre , Molgaard Christian , Moltu Sissel Jennifer , Norsa Lorenzo , Verduci Elvira , Domellöf Magnus 
Published: March 2020

ABSTRACTAssessment of vitamin and trace element status (VTE) is important in the clinical management of the sick child. In this position paper, we present the various assessment methods available to the clinical practitioner, and critically discuss pitfalls with interpretation of their results. There are 4 main approaches to assess the VTE body status of an individual patient including clinical examination, dietary assessment, and measurement of direct and indirect biomarkers of VTE in biological samples. Clinical signs of VTE deficiencies usually present only when body stores are substantially depleted and are often difficult to detect or differentiate from other nonnutrient‐related causes. In isolation, dietary assessment of micronutrients can be inaccurate and imprecise, in disease and in individual patient assessment but may be useful to complement findings from other VTE assessment methods. Use of biomarkers is the most common approach to assess VTE status in routine practice but in the presence of systemic inflammatory response and in the absence of appropriate paediatric reference intervals, interpretation of biomarker results might be challenging and potentially mislead clinical practice. The use of a multimodal approach, including clinical examination, dietary assessment, and laboratory biomarkers is proposed as the optimal way to ascertain the VTE status of individual patients. In the presence of acute inflammatory conditions, VTE measurements in plasma should be replaced by biomarkers not affected by systemic inflammatory response or delayed until inflammatory state is resolved.
Patterns of Primary, Specialty, Urgent Care, and Emergency Department Care in Children With Inflammatory Bowel Diseases
Authors: Michel Hilary K. , Noll Robert B. , Siripong Nalyn , Kim Sandra C. 
Published: March 2020

ABSTRACTObjectives:Pediatric patients with inflammatory bowel diseases (IBD) require treatment, monitoring, and health maintenance services. We described patterns of primary, specialty, emergency department (ED) and urgent care delivery, and explored patient‐ and system‐related variables that impact ED/urgent care utilization.Methods:We conducted a cross sectional survey of parents of children with IBD at a large tertiary children's hospital.Results:One hundred sixty‐one parents completed the survey (75% response). Mean patient age 13.9 years (51% boys); 80% Crohn disease, 16% ulcerative colitis, 4% IBD‐unspecified. Mean disease duration 4 years (standard deviation [SD] 2.7). Thirty percent had at least 1 other chronic disease, 31% had a history of IBD‐related surgery. Parents were predominantly Caucasian (94%), well‐educated (61% bachelor's degree/higher), part of a 2‐parent household (79%) living in a suburban setting (57%). Seventy‐seven percent of patients had private insurance. In the past year, most children had 1 to 2 IBD‐related office visits (54%) with their gastroenterology (GI) doctor and no IBD‐related hospitalizations (79%). Eighty‐eight percent (N = 141) had a primary care provider (PCP), and most (70%) saw their PCP 1 to 2 times. Even so, 86% (N = 139) received medical care from places other than their PCP or GI doctor; 27% in the ED and 45% at urgent care. Children of parents with less than a bachelor's degree, families that lived further from their GI doctor, and children who saw their PCP more often were more likely to utilize ED/urgent care.Conclusions:ED/urgent care utilization in pediatric patients with IBD was greater than expected, potentially contributing to fragmented, costly care and worse outcomes.