bluuebunny/crossref_metadata_2025_split huggingface dataset:
Megalin/lipoprotein receptor-related protein 2 autoimmunity and kidney disease
Authors: Perez-Gomez Maria V , Sanchez-Niño Maria D , Ortiz Alberto 
Published: January 2020

AbstractIn this issue of Clinical Kidney Journal, Gamayo et al. describe two cases of anti-low-density lipoprotein receptor-related protein 2 (LRP2) nephropathy. This is a recently described entity that has features of both tubulointerstitial disease and segmental membranous nephropathy. The originality of the present report consists of the association of a disease thought to be rare (only 13 in prior described patients, 11 in the past year) with B-cell lymphoproliferative disease. Together with the finding of a third case among 224 elderly patients studied, this raises the issue of the underdiagnoses of LRP2 nephropathy, on top of the potential association to B-cell malignancy. We now put these findings in context within the wider frame of autoimmunity against megalin/LRP2 and related antigens such as Fx1A and CD69.
Discrepancy between Cardiac Troponin Assays Due to Endogenous Antibodies
Authors: Lam Leo , Aspin Lisa , Heron Robert Campbell , Ha Leah , Kyle Campbell 
Published: January 2020

Abstract

Background
Despite well-described analytical effects of autoantibodies against cardiac troponin (cTn) I on experimental assays, no study has systematically examined their impact on cTn assays in clinical use. We determined the effects of endogenous antibodies on 5 different cTnI assays and a cTnT assay.

Methods
cTn was measured by 6 methods: Siemens hs-cTnI Centaur, Siemens hs-cTnI Vista, Abbott hs-cTnI Architect, Beckman hs-cTnI Access, Beckman cTnI Access, and Roche hs-cTnT Elecsys. Measurements were repeated on 5 assays (all except Siemens hs-cTnI Vista) following immunoglobulin depletion by incubation with protein A. Low recovery of cTnI (&lt;40%) following immunoglobulin depletion was considered positive for macro-cTnI. Protein A findings were validated by gel filtration chromatography and polyethylene glycol precipitation.

Results
In a sample of 223 specimens selected from a community laboratory that uses the Siemens hs-cTnI Centaur assay and from which cTn was requested, 76% of samples demonstrated increased cTnI (median, 88 ng/L; interquartile range, 62–204 ng/L). Macro-cTnI was observed in 123 (55%) of the 223 specimens. Comparisons of cTnI assays markedly improved once patients with macro-cTnI were removed. Passing-Bablok regression analysis between hs-cTnI assays demonstrated different slopes for patients with and without macro-cTnI. In patients with macro-cTnI, 89 (72%) showed no effect on the recovery of cTnT, whereas 34 (28%) had reduced recovery of cTnT. The proportion of results above the manufacturers' 99th percentile varied with the cTn assay and macro-cTnI status.

Conclusion
We suggest that the observed discrepancy between hs-cTnI assays may be attributed in part to the presence of macro-cTnI.
Dyadic imbalance in networks
Authors: Burghardt Keith , Maoz Zeev 
Published: January 2020

AbstractThe study of balance in signed networks has been a key topic for over 80 years. Starting with Heider’s theory of structural balance and Harary’s balance theorem, the measurement and understanding of structural balance in networks has grown exponentially. Most theoretical and empirical studies, however, focus on balance on the network as a whole, even though the degree of balance may strongly vary within the network. Our study makes two key contributions to this literature. First, we offer a methodology for measuring balance between nodes in a network. We show that dyadic (im)balance reveals significant information about localized balance that is not apparent in a global metric of balance. Second, we show that this metric can be applied to data containing multiple relations, for example, friendship, enmity, trade and fights, which reveals balance and imbalance otherwise hidden when focusing on only two relations (e.g. friends and enemies). Namely, while balance typically involves unweighted signed networks, multiple relations can naturally be condensed into a weighted signed network where positive (negative) weights correspond to a sum of positive (negative) relations between nodes. Our dyadic imbalance metric can then be applied to this and any other weighted signed network. These findings are illustrated with an international relations network as well as a network on roll call votes in the US Senate and compared to a null model that preserves network structure. We find weak agreement with Heider’s balance theory, including imbalance that decreases in time, and imbalance that is generally lower than our null model.
Association between physical activity and risk of incident arrhythmias in 402 406 individuals: evidence from the UK Biobank cohort
Authors: Elliott Adrian D , Linz Dominik , Mishima Ricardo , Kadhim Kadhim , Gallagher Celine , Middeldorp Melissa E , Verdicchio Christian V , Hendriks Jeroen M L , Lau Dennis H , La Gerche Andre , Sanders Prashanthan 
Published: January 2020

Abstract

Aims
Physical activity reduces cardiovascular disease burden and mortality, although its relationship with cardiac arrhythmias is less certain. The aim of this study was to assess the association between self-reported physical activity and atrial fibrillation (AF), ventricular arrhythmias and bradyarrhythmias, across the UK Biobank cohort.

Methods and results
We included 402 406 individuals (52.5% female), aged 40–69 years, with over 2.8 million person-years of follow-up who underwent self-reported physical activity assessment computed in metabolic equivalent-minutes per week (MET-min/wk) at baseline, detailed physical assessment and medical history evaluation. Arrhythmia episodes were diagnosed through hospital admissions and death reports. Incident AF risk was lower amongst physically active participants, with a more pronounced reduction amongst female participants [hazard ratio (HR) for 1500 vs. 0 MET-min/wk: 0.85, 95% confidence interval (CI) 0.74–0.98] than males (HR for 1500 vs. 0 MET-min/wk: 0.90, 95% CI 0.82–1.0). Similarly, we observed a significantly lower risk of ventricular arrhythmias amongst physically active participants (HR for 1500 MET-min/wk 0.78, 95% CI 0.64–0.96) that remained relatively stable over a broad range of physical activity levels between 0 and 2500 MET-min/wk. A lower AF risk amongst female participants who engaged in moderate levels of vigorous physical activity was observed (up to 2500 MET-min/wk). Vigorous physical activity was also associated with reduced ventricular arrhythmia risk. Total or vigorous physical activity was not associated with bradyarrhythmias.

Conclusion
The risk of AF and ventricular arrhythmias is lower amongst physically active individuals. These findings provide observational support that physical activity is associated with reduced risk of atrial and ventricular arrhythmias.
Data detectives, self-love, and humility: a research parasite's perspective
Authors: Duvallet Claire 
Published: January 2020

Abstract
Secondary analysis solidifies and expands upon scientific knowledge through the re-analysis of existing datasets. However, researchers performing secondary analyses must develop specific skills to be successful and can benefit from adopting some computational best practices. Recognizing this work is also key to building and supporting a community of researchers who contribute to the scientific ecosystem through secondary analyses. The Research Parasite Awards are one such avenue, celebrating outstanding contributions to the rigorous secondary analysis of data. As the recipient of a 2019 Junior Research Parasite Award, I was asked to provide some perspectives on life as a research parasite, which I share in this commentary.
The draft nuclear genome assembly of Eucalyptus pauciflora: a pipeline for comparing de novo assemblies
Authors: Wang Weiwen , Das Ashutosh , Kainer David , Schalamun Miriam , Morales-Suarez Alejandro , Schwessinger Benjamin , Lanfear Robert 
Published: January 2020

Abstract

Background
Eucalyptus pauciflora (the snow gum) is a long-lived tree with high economic and ecological importance. Currently, little genomic information for E. pauciflora is available. Here, we sequentially assemble the genome of Eucalyptus pauciflora with different methods, and combine multiple existing and novel approaches to help to select the best genome assembly.

Findings
We generated high coverage of long- (Nanopore, 174×) and short- (Illumina, 228×) read data from a single E. pauciflora individual and compared assemblies from 5 assemblers (Canu, SMARTdenovo, Flye, Marvel, and MaSuRCA) with different read lengths (1 and 35 kb minimum read length). A key component of our approach is to keep a randomly selected collection of ~10% of both long and short reads separated from the assemblies to use as a validation set for assessing assemblies. Using this validation set along with a range of existing tools, we compared the assemblies in 8 ways: contig N50, BUSCO scores, LAI (long terminal repeat assembly index) scores, assembly ploidy, base-level error rate, CGAL (computing genome assembly likelihoods) scores, structural variation, and genome sequence similarity. Our result showed that MaSuRCA generated the best assembly, which is 594.87 Mb in size, with a contig N50 of 3.23 Mb, and an estimated error rate of ~0.006 errors per base.

Conclusions
We report a draft genome of E. pauciflora, which will be a valuable resource for further genomic studies of eucalypts. The approaches for assessing and comparing genomes should help in assessing and choosing among many potential genome assemblies from a single dataset.
Incidence Rates for Surgery in Crohn’s Disease Have Decreased: A Population-based Time-trend Analysis
Authors: Dittrich Alexandra E , Sutton Reed Taylor , Haynes Kate , Wang Haili , Fedorak Richard N , Kroeker Karen I 
Published: January 2020

AbstractBackgroundMany Crohn’s disease (CD) patients will undergo surgery over the course of their life. It is thought that with the introduction of disease-modifying agents like anti-TNF therapy, there would be a population-level decrease in the need for surgery. This time-trend study aimed to assess the changes in surgical rates following the induction of anti-TNF therapy.MethodsAdult CD patients who underwent abdominal surgery (identified by administrative coding) between January of 1996 and December of 2013 at 1 of the 4 Edmonton-area hospitals were included. Patient charts were manually reviewed to confirm diagnosis and gather demographic and disease-related data. Population-adjusted annual incidence rates for IBD surgery were calculated by dividing the number of surgeries by estimates for total population of CD patients in Edmonton. Time-trend analysis was conducted to identify change points, calculate annual percent change (APC), and associated 95% confidence intervals (CIs).ResultsA total of 1410 patients with Crohn’s disease underwent surgery for their disease. The surgical rate decreased by 8.4% each year (95% CI, −9.6% to −7.3%). There was a 36.2% increase in the use of anti-TNF therapy per year (95% CI, 31.3% to 41.5%). Changes in modifiable risk factors for surgery were also seen, including the proportion of active smokers decreasing by 2.2% per year (95% CI, −3.7% to −0.6%).ConclusionsAlthough anti-TNF therapy seems to play a role, the decrease in surgical trends is likely multifactorial, owing to a decline in smoking trends, earlier diagnosis, earlier treatment, improved patient education, and changes in clinical practice.
Novel Histone Deacetylase 6 Inhibitor CKD-506 Inhibits NF-κB Signaling in Intestinal Epithelial Cells and Macrophages and Ameliorates Acute and Chronic Murine Colitis
Authors: Lee Jung Won , Lee Soung-Min , Chun Jaeyoung , Im Jong Pil , Seo Su-Kil , Ha Nina , il Choi Young , Kim Joo Sung 
Published: January 2020

AbstractBackgroundSelective blocking of HDAC6 has become a promising strategy in treating inflammatory bowel disease. CKD-506 is a novel isoform-selective inhibitor of histone deacetylase 6. The present study was performed to evaluate the effect of CKD-506 on the NF-κB signaling pathway in intestinal epithelial cells (IECs) and macrophages and on murine models of acute and chronic colitis.MethodsRAW264RAW264.7 murine macrophages and COLO 205 human IECs were pretreated with CKD-506 and then stimulated with lipopolysaccharides (LPS). Cytokine expression of TNF-α, interleukin (IL)-6, IL-8, and IL-10 was measured by ELISA. The effect of CKD-506 on NF-κB signaling was evaluated by Western blotting of IκBα phosphorylation/degradation and electrophoretic mobility shift assay. In vivo studies were performed using a dextran sulfate sodium (DSS)–induced acute colitis model, a chronic colitis model in IL-10 knockout mice, and an adoptive transfer model. Colitis was quantified by the disease activity index, colon length, and histopathologic evaluation.ResultsCKD-506 suppressed the expression of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α in IECs and macrophages. CKD-506 strongly inhibited IκBα phosphorylation/degradation and the DNA-binding activity of NF-κB. Oral administration of CKD-506 attenuated DSS-induced acute colitis and chronic colitis in IL-10-/- and adoptive transfer models. CKD-506 ameliorated weight loss, disease activity, and histopathologic score in colitis mice and downregulated IκBα phosphorylation and pro-inflammatory cytokine production significantly.ConclusionsCKD-506 blocked NF-κB signaling in IECs and macrophages and ameliorated experimental acute and chronic murine colitis models, which suggests that CKD-506 is a promising candidate for inflammatory bowel disease treatment as a small molecular medicine.
Aortic valve-sparing root replacement (David): learning curve and impact on outcome
Authors: Beckmann Erik , Martens Andreas , Krueger Heike , Kaufeld Tim , Korte Wilhelm , Stettinger Alissa , Haverich Axel , Shrestha Malakh Lal 
Published: January 2020

Abstract

OBJECTIVES
Aortic valve-sparing root replacement (David procedure) offers the benefit of preserving the native aortic valve but is often criticized for being technically challenging and time-consuming. We analysed whether the surgeon’s level of experience affects the early and long-term outcome after the David procedure.

METHODS
From July 1993 to October 2015, a total of 582 patients underwent aortic valve-sparing David I procedure at our institution. A retrospective review with follow-up (mean follow-up time 8.6 ± 5.6 years) was performed. Statistical analysis of the surgeon’s level of experience was performed as a categorical variable, after patients were chronologically assigned to groups of tens. Study end points assessing the surgeon’s learning curve included both measures of patient outcome and measures of task efficiency. Study end points included both short- and long-term outcomes.

RESULTS
Analysis of task efficiency showed that there was a statistically significant inverse correlation between the surgeon’s level of experience and both cardiopulmonary bypass time (P = 0.026) and aortic cross-clamp time (P = 0.017). Analysis of patient outcome revealed that the incidence of aortic valve-related reoperation during follow-up showed a significant inverse correlation with the surgeon’s level of experience (P = 0.048). Cox regression analysis found that the surgeon’s level of experience (odds ratio 0.802, 95% confidence interval 0.673–0.957; P = 0.014) was a significant risk factor for aortic valve-related reoperation-free survival during follow-up.

CONCLUSIONS
There is a surgeon’s learning curve for aortic valve-sparing David procedure. The surgeon’s experience has a direct impact on both the perioperative outcome and the long-term performance of the aortic valve.
Evaluation of a fully automated bioinformatics tool to predict antibiotic resistance from MRSA genomes
Authors: Kumar Narender , Raven Kathy E , Blane Beth , Leek Danielle , Brown Nicholas M , Bragin Eugene , Rhodes Paul A , Parkhill Julian , Peacock Sharon J 
Published: January 2020

Abstract

Objectives
The genetic prediction of phenotypic antibiotic resistance based on analysis of WGS data is becoming increasingly feasible, but a major barrier to its introduction into routine use is the lack of fully automated interpretation tools. Here, we report the findings of a large evaluation of the Next Gen Diagnostics (NGD) automated bioinformatics analysis tool to predict the phenotypic resistance of MRSA.

Methods
MRSA-positive patients were identified in a clinical microbiology laboratory in England between January and November 2018. One MRSA isolate per patient together with all blood culture isolates (total n = 778) were sequenced on the Illumina MiniSeq instrument in batches of 21 clinical MRSA isolates and three controls.

Results
The NGD system activated post-sequencing and processed the sequences to determine susceptible/resistant predictions for 11 antibiotics, taking around 11 minutes to analyse 24 isolates sequenced on a single sequencing run. NGD results were compared with phenotypic susceptibility testing performed by the clinical laboratory using the disc diffusion method and EUCAST breakpoints. Following retesting of discrepant results, concordance between phenotypic results and NGD genetic predictions was 99.69%. Further investigation of 22 isolate genomes associated with persistent discrepancies revealed a range of reasons in 12 cases, but no cause could be found for the remainder. Genetic predictions generated by the NGD tool were compared with predictions generated by an independent research-based informatics approach, which demonstrated an overall concordance between the two methods of 99.97%.

Conclusions
We conclude that the NGD system provides rapid and accurate prediction of the antibiotic susceptibility of MRSA.
Evaluation of a New Skeletal Troponin I Assay in Patients with Idiopathic Inflammatory Myopathies
Authors: Bamberg Katriina , Mehtälä Laura , Arola Olli , Laitinen Seppo , Nordling Pauliina , Strandberg Marjatta , Strandberg Niko , Paltta Johanna , Mali Markku , Espinosa-Ortega Fabricio , Pirilä Laura , Lundberg Ingrid E , Savukoski Tanja , Pettersson Kim 
Published: January 2020

Abstract

Background
The current biomarkers for diagnosis and monitoring of injured and diseased skeletal muscles, such as creatine kinase (CK), have limited tissue specificity and incapability to differentiate between pathological and physiological changes. Thus, new biomarkers with improved diagnostic accuracy are needed. Our aim was to develop and validate a novel assay for skeletal troponin I (skTnI), and to assess its clinical performance in patients with idiopathic inflammatory myopathies (IIM).

Methods
A two-step fluoroimmunoassay was used to analyze samples from healthy reference individuals (n = 140), patients with trauma (n = 151), and patients with IIM (n = 61).

Results
The limit of detection was 1.2 ng/mL, and the upper reference limit (90th percentile) was 5.2 ng/mL. The median skTnI concentrations were &lt;limit of detection (LoD), 2.7 ng/mL, and 8.6 ng/mL in reference, trauma, and IIM cohorts, respectively. Differences in measured skTnI levels were statistically significant between all three study cohorts (Kruskal–Wallis P &lt; 0.001; Mann–Whitney P &lt; 0.001 for all). skTnI and CK had a strong positive correlation (Spearman’s r = 0.771, P &lt; 0.001), and the longitudinal changes in skTnI mirrored those observed with CK.

Conclusions
With the skTnI assay, patients with IIM were identified from healthy individuals and from patients with traumatic muscular injuries. When compared to CK, skTnI appeared to be more accurate in managing patients with low-grade IIM disease activities. The developed assay serves as a reliable analytical tool for the assessment of diagnostic accuracy of skTnI in the diagnosis and monitoring of myopathies.
CYP450-Mediated Metabolism of Mitragynine and Investigation of Metabolites in Human Urine
Authors: Basiliere Stephanie , Kerrigan Sarah 
Published: January 2020

Abstract
Mitragyna speciosa (Kratom) has emerged as a recreational drug and a substance of medicinal intrigue. Although the drug was initially used recreationally for its sedating and euphoric effects, more recently its use has been associated with the non-medically supervised treatment of opioid abstinence syndrome. Mitragynine is the principal pharmacologically active alkaloid in kratom. Although metabolites of mitragynine have been identified, the cytochrome P450 (CYP450) enzymes responsible for its biotransformation are still under investigation. The goal of this study was to contribute further knowledge regarding CYP450 activity as it relates to mitragynine. Recombinant cytochrome P450 enzymes (rCYPs) were used to investigate the isoforms involved in its metabolism. Biotransformational products were identified using liquid chromatography-quadrupole/time of flight-mass spectrometry. Four rCYP enzymes (2C18, 2C19, 2D6 and 3A4) were found to contribute to the metabolism of mitragynine. 7-Hydroxymitragynine (which has an affinity for the mu-opioid receptor &gt;10-folds that of morphine) was produced exclusively by 3A4. 9-O-demethylmitragynine, the most abundant metabolite in vitro (and the most prevalent metabolite in urine among kratom users) was produced by 2C19, 3A4 and 2D6. 16-Carboxymitragynine was produced by rCYPs 2D6, 2C19 and 2C18. 2C19 was solely responsible for the formation of 9-O-demethyl-16-carboxymitragynine. In vitro rCYP studies were compared with phase I metabolites in urine from cases involving mitragynine.
Reducing Barriers to Breast Imaging in Patients with Mobility Limitations
Authors: Bouhmam Houda , Romanoski Natasha L , Chetlen Alison L 
Published: January 2020

Abstract
Over 1 billion people worldwide live with a disability. Patients living with disability are often challenged by many barriers to healthcare access, especially preventive and screening services. The Americans with Disabilities Act of 1990 mandated that access to public accommodations related to medical care in the United States be available to all; however, many healthcare facilities fall short of meeting this requirement. Research studies suggest that women with chronic disabilities are less likely to undergo breast cancer screening due to financial, environmental, and physical limitations, as well as psychological barriers. There is scarcity of research on the needs of individuals with mobility impairments and the features of the barriers they face when accessing healthcare services, especially breast imaging services. The objective of this article is to illustrate the existing barriers to breast imaging services that individuals with mobility impairments face and to provide a list of guidelines to be used in clinical practice for breast care practices and medical staff working with patients who have mobility impairments.
The Economic Challenges of Dealing with Citrus Greening: The Case of Florida
Authors: Singerman Ariel , Rogers Michael E 
Published: January 2020

Abstract
While pest management decisions are made at the farm level, a distinctive characteristic of the pest management of invasive species is its public-good nature. Here, we examine the challenges that a vector-disease pathosystem such as Diaphorina citri Kuwayama (Hemiptera: Liviidae)—citrus greening, creates for the adoption of prevention and collective management practices from an economic perspective. Those economic challenges originate from the choices and behavior of individual growers, which can impact not only their own payoff but also the choices, behavior and payoffs of other growers; influencing, for example, the spread of the disease, the vector population dynamics, and the adoption of proposed scientific solutions. While for most people the economics of invasive species is limited to calculating damage or control costs, economics is more than that. Economics can provide insights on the interactions between human behavior and natural processes, enabling a better understanding of the rationale of individual growers’ choices, which are key for the design and implementation of effective public policies to deal with invasive pests and diseases.