bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of Deceased Organ Donation Activity Versus Efficiency Over a 15-year Period: An International Comparison
Authors: Weiss Julius , Elmer Andreas , Mahíllo Beatriz , Domínguez-Gil Beatriz , Avsec Danica , Nanni Costa Alessandro , Haase-Kromwijk Bernadette J.J.M. , Laouabdia Karim , Immer Franz F. 
Published: April 2018

Background
The donation rate (DR) per million population is not ideal for an efficiency comparison of national deceased organ donation programs. The DR does not account for variabilities in the potential for deceased donation which mainly depends on fatalities from causes leading to brain death. In this study, the donation activity was put into relation to the mortality from selected causes. Based on that metric, this study assesses the efficiency of different donation programs.

Methods
This is a retrospective analysis of 2001 to 2015 deceased organ donation and mortality registry data. Included are 27 Council of Europe countries, as well as the United States. A donor conversion index (DCI) was calculated for assessing donation program efficiency over time and in international comparisons.

Results
According to the DCI and of the countries included in the study, Spain, France, and the United States had the most efficient donation programs in 2015. Even though mortality from the selected causes decreased in most countries during the study period, differences in international comparisons persist. This indicates that the potential for deceased organ donation and its conversion into actual donation is far from being similar internationally.

Conclusions
Compared with the DR, the DCI takes into account the potential for deceased organ donation, and therefore is a more accurate metric of performance. National donation programs could optimize performance by identifying the areas where most potential is lost, and by implementing measures to tackle these issues.
Heavy Alcohol Use Among Deceased Donors Does Not Impact Recipient Outcomes After Liver Transplantation
Authors: Arora Sumant S. , Chahal Khushdeep S. , Axley Page , Eckhoff Devin E. , Kuo Yong-Fang , Satapathy Sanjaya K. , Wiesner Russell , Singal Ashwani K. 
Published: April 2018

Background
Data on liver transplant (LT) outcomes using deceased donors with heavy drinking (HD) (>2 drinks per day) are scanty.

Methods
Using the United Network for Organ Sharing database (2002-2014), we examined outcomes after LT in adults comparing deceased HD donors with non-HD (ND) donors.

Results
Of 56 182 first LTs performed in the United States for 10 common indications using deceased donors, 47 882 with available information on alcohol use were analyzed. Of these 47 882 LT recipients, 7298 (15%) were from HD donors, with similar proportion over time (2002-2014, Armitage trend test P = 0.75) and for recipient liver disease etiology (χ2
P = 0.42). Proportion of liver organ used for LT was lower for HD donors compared with ND donors (63% vs 78%; P < 0.001). Five-year outcomes on first LT comparing 7166 HD donors and 21 498 ND donors matched based on propensity score were similar for liver graft (73.7% vs 73.7%, log rank P = 0.98) and patient survival (77.6% vs 77.0%, P = 0.36). On Cox regression analysis, history of HD in deceased donors did not affect liver graft 1.02 (0.97-1.08) or patient survival 1.03 (0.97-1.09).

Conclusions
Among LT recipients using select liver grafts, history of HD in deceased donors does not impact outcomes after LT.
State of the Art: Role of the Dendritic Cell in Induction of Allograft Tolerance
Authors: Rosen Sarah J. , Harris Paul E. , Hardy Mark A. 
Published: April 2018

Abstract
Despite decades of research, the induction and maintenance of long-term allograft tolerance without immunosuppression remains an elusive goal in the field of solid organ and cell transplantation. Immunosuppressive medications frequently prevent or minimize acute cellular rejection but have failed to halt antidonor antibody production and chronic organ rejection. Past efforts aimed at promoting lasting allograft tolerance have focused primarily on peripheral T-cell depletion, augmentation of regulatory T cells, or induction via simultaneous hematopoietic stem cell transplantation and facilitation of donor chimerism. So far, none of these methods have led to consistently safe, feasible and long lasting donor organ acceptance. Over the course of the past 4 decades, the study of a unique population of antigen-presenting cells known as dendritic cells has shown promise for breaking new ground in achieving indefinite allograft survival without immunosuppression and its associated adverse effects. In this review, we discuss the discovery and early investigations of dendritic cells and chronicle some of the key studies demonstrating their role in transplantation, particularly in indirect allorecognition, the immunologic pathway thought to drive chronic rejection and perhaps tolerance induction.
Outcomes After Cardiac Transplant for Wild Type Transthyretin Amyloidosis
Authors: Rosenbaum Andrew N. , AbouEzzeddine Omar F. , Grogan Martha , Dispenzieri Angela , Kushwaha Sudhir , Clavell Alfredo , Daly Richard C. , Edwards Brooks S. 
Published: April 2018

Background
The true prevalence of heart failure due to wild type transthyretin amyloidosis (ATTRwt) is likely underestimated. There is a paucity of data with regard to the management of ATTRwt-related advanced heart failure and the natural history of extracardiac ATTRwt.

Methods
We conducted a retrospective cohort study of patients undergoing cardiac transplant (HTx) for ATTRwt at a single institution. Comprehensive clinical data, including baseline hemodynamic and echocardiographic characteristics, and posttransplant outcomes, were obtained.

Results
Seven patients with ATTRwt underwent HTx between 2007 and 2015. All patients were male with a mean age of 66 ± 9. Patients had a reduced ejection fraction (mean, 37 ± 14%) and elevated filling pressures pre-HTx (mean pulmonary capillary wedge pressure 22 ± 7 mm Hg) before HTx. Three-year survival was 100%; 1 patient died of pancreatic cancer 45 months post-HTx (1 death per 30.8 patient-years). Oxygen consumption (Δ +6.8 ± 4.9 mL·kg−1·min−1) and 6-minute walk distances (Δ +189 ± 60 m) improved. Symptomatic gastrointestinal involvement (n = 2) and peripheral nerve involvement (n = 4) by ATTRwt developed late.

Conclusions
This is the first report of a series of ATTRwt patients receiving HTx in which excellent outcomes are demonstrated. Although cardiac death is averted, systemic manifestations of ATTRwt may develop posttransplantation.
Role of MRCP in Diagnosing Biliary Anastomotic Strictures After Liver Transplantation: A Single Tertiary Care Center Experience
Authors: Akbar Ali , Tran Quynh T. , Nair Satheesh P. , Parikh Salil , Bilal Muhammad , Ismail Mohammed , Vanatta Jason M. , Eason James D. , Satapathy Sanjaya K. 
Published: April 2018

Background
Biliary strictures (BS) are common complication after liver transplantation. We aimed to determine the accuracy of magnetic resonance cholagiopancreatography (MRCP) in diagnosing BS in liver transplant recipients (LTRs) when compared to direct cholangiographic methods (endoscopic resonance cholagiopancreatography [ERCP] and/or percutaneous transhepatic cholangiography [PTC]).

Methods
Retrospective chart review of 910 LTRs (July 2008 to April 2015) was performed, and a total of 39 patients with duct-to-duct anastomosis (22 males; 56.4%; mean age, 52.8 ± 8.3 years) were included who had an MRCP followed by either ERCP and/or PTC within 4 weeks. A cholangiographic narrowing (on ERCP and/or PTC) that required balloon dilation and/or stent placement was considered a BS and was considered clinically significant if the intervention resulted in at least 30% improvement of bilirubin within 2 weeks. Sensitivity, specificity, accuracy, positive predictive values and negative predictive values of MRCP in diagnosing BS were calculated.

Results
Magnetic resonance cholagiopancreatography showed anastomotic BS in 17 of 39 patients, and subsequent ERCP and/or PTC revealed a total of 25 BS (positive predictive value of 0.94). Nine BS on cholangiography (ERCP, 8; PTC, 1) were not detected on earlier MRCP (sensitivity, 0.64; 95% CI, 0.45-0.82); 2 were clinically significant BS and 6 of the remaining 7 had no improvement in their liver function test with biliary intervention. Thirteen LTRs had no BS on either modality (specificity, 0.93; 95% CI, 0.66-0.99). The negative predictive value of MRCP was 0.59 for cholangiographic BS. The overall accuracy of MRCP is 0.74 (exact 95% CI, 0.58-0.87). Inclusion of age, race, and alanine aminotransferase level improved the predictive value of MRCP (area under the curve = 0.94, 95% CI: 0.86-1.00).

Conclusions
Magnetic resonance cholagiopancreatography has high specificity but low sensitivity in diagnosing cholangiographic BS in LTRs, although the predictive value further improved with inclusion of age, race, and alanine aminotransferase. Clinical significance of BS in LTRs not identified on MRCP is questionable because ERCP with intervention did not improve their liver function tests in the vast majority.
No evidence of functional co-adaptation between clustered microRNAs
Authors: Marco Antonio 
Published: April 2018

ABSTRACTA significant fraction of microRNA loci are organized in genomic clusters. The origin and evolutionary dynamics of these clusters have been extensively studied, although different authors have come to different conclusions. In a recent paper, it has been suggested that microRNAs in the same clusters evolve to target overlapping sets of genes. The authors interpret this as functional co- adaptation between clustered microRNAs. Here I reanalyze their results and I show that the observed overlap is mostly due to two factors: similarity between two seed sequences of a pair of clustered microRNAs, and the expected high number of common targets between pairs of microRNAs that have a large number of targets each. After correcting for these factors, I observed that clustered microRNAs from different microRNA families do not share more targets than expected by chance. During an exchange of correspondence and manuscripts, the authors of the original report acknowledged that the permutation methods they performed was not the method they described in their original paper. Here I show that the new permutation test proposed is biased and leads to systematic errors of the first kind, which will explain why the p-values reported were extremely (and unrealistically) low. I also discuss how to investigate the evolutionary dynamics of clustered microRNAs and their targets. In conclusion, there is no evidence of widespread functional co-adaptation between clustered microRNAs.
Pan-cancer analysis of transcriptional metabolic dysregulation using The Cancer Genome Atlas
Authors: Rosario SR , Long MD , Affronti HC , Rowsam AM , Eng KH , Smiraglia DJ 
Published: April 2018

AbstractUnderstanding the levels of metabolic dysregulation in different disease settings is vital for the safe and effective incorporation of metabolism-targeted therapeutics in the clinic. Using transcriptomic data from 10,704 tumor and normal samples from The Cancer Genome Atlas, across 26 disease sites, we developed a novel bioinformatics pipeline that distinguishes tumor from normal tissues, based on differential gene expression for 114 metabolic pathways. This pathway dysregulation was confirmed in separate patient populations, further demonstrating the robustness of this approach. A bootstrapping simulation was then applied to assess whether these alterations were biologically meaningful, rather than expected by chance. We provide distinct examples of the types of analysis that can be accomplished with this tool to understand cancer specific metabolic dysregulation, highlighting novel pathways of interest in both common and rare disease sites. Utilizing a pathway mapping approach to understand patterns of metabolic flux, differential drug sensitivity, can accurately be predicted. Further, the identification of Master Metabolic Transcriptional Regulators, whose expression was highly correlated with pathway gene expression, explains why metabolic differences exist in different disease sites. We demonstrate these also have the ability to segregate patient populations and predict responders to different metabolism-targeted therapeutics.
DNA profiling reveals Neobenedenia girellae as the primary culprit in global fisheries and aquaculture
Authors: Brazenor Alexander K. , Bertozzi Terry , Miller Terrence L. , Whittington Ian D. , Hutson Kate S. 
Published: April 2018

ABSTRACTAccurate identification of parasite species and strains is crucial to mitigate the risk of epidemics and emerging disease. Species of Neobenedenia are harmful monogenean ectoparasites that infect economically important bony fishes in aquaculture worldwide, however, the species boundaries between two of the most notorious taxa, N. melleni and N. girellae, has been a topic of contention for decades. Historically, identifications of Neobenedenia isolates have overwhelmingly been attributed to N. melleni, and it has been proposed that N. girellae is synonymous with N. melleni. We collected 33 Neobenedenia isolates from 22 host species spanning nine countries and amplified three genes including two nuclear (Histone 3 and 28S rDNA) and one mitochondrial (cytochrome b). Four major clades were identified using Maximum Likelihood and Bayesian inference analyses; clades A-D corresponding to N. girellae, N. melleni, N. longiprostata and N. pacifica respectively. All unidentified isolates and the majority of Neobenedenia sequences from GenBank fell into clade A. The results of this study indicate that N. girellae is a separate species to N. melleni, and that a large proportion of previous samples identified as N. melleni may be erroneous and a revision of identifications is needed.The large diversity of host species that N. girellae is able to infect as determined in this study and the geographic range in which it is present (23.8426° S and 24.1426° N) makes it a globally cosmopolitan species and a threat to aquaculture industries around the world.
Testing the causal effects between subjective wellbeing and physical health using Mendelian randomisation
Authors: Wootton Robyn E , Lawn Rebecca B , Millard Louise A C , Davies Neil M , Taylor Amy E , Munafò Marcus R , Timpson Nicholas J , Davis Oliver S P , Smith George Davey , Haworth Claire M A 
Published: April 2018

AbstractObjectivesTo investigate whether the association between subjective wellbeing (subjective happiness and life satisfaction) and physical health is causal.DesignWe conducted two-sample bidirectional Mendelian randomisation between subjective wellbeing and six measures of physical health: coronary artery disease, myocardial infarction, total cholesterol, HDL cholesterol, LDL cholesterol and body mass index (BMI).ParticipantsWe used summary data from four large genome-wide association study consortia: CARDIoGRAMplusC4D for coronary artery disease and myocardial infarction; the Global Lipids Genetics Consortium for cholesterol measures; the Genetic Investigation of Anthropometric Traits consortium for BMI; and the Social Science Genetics Association Consortium for subjective wellbeing. A replication analysis was conducted using 337,112 individuals from the UK Biobank (54% female, mean age =56.87, SD=8.00 years at recruitment).Main outcome measuresCoronary artery disease, myocardial infarction, total cholesterol, HDL cholesterol, LDL cholesterol, BMI and subjective wellbeing.ResultsThere was evidence of a causal effect of BMI on subjective wellbeing such that each 1 kg/m2 increase in BMI caused a 0.045 (95%CI 0.006 to 0.084, p=0.023) SD reduction in subjective wellbeing. Replication analyses provided strong evidence of an effect of BMI on satisfaction with health (β=0.034 (95% CI: −0.042 to −0.026) unit decrease in health satisfaction per SD increase in BMI, p<2-16). There was no clear evidence of a causal effect between subjective wellbeing and the other physical health measures in either direction.ConclusionsOur results suggest that a higher BMI lowers subjective wellbeing. Our replication analysis confirmed this finding, suggesting the effect in middle-age is driven by satisfaction with health. BMI is a modifiable determinant and therefore, our study provides further motivation to tackle the obesity epidemic because of the knock-on effects of higher BMI on subjective wellbeing.
Animacy and real world size shape object representations in the human medial temporal lobes
Authors: Blumenthal Anna , Stojanoski Bobby , Martin Chris , Cusack Rhodri , Köhler Stefan 
Published: April 2018

ABSTRACTIdentifying what an object is, and whether an object has been encountered before, is a crucial aspect of human behavior. Despite this importance, we do not have a complete understanding of the neural basis of these abilities. Investigations into the neural organization of human object representations have revealed category specific organization in the ventral visual stream in perceptual tasks. Interestingly, these categories fall within broader domains of organization, with distinctions between animate, inanimate large, and inanimate small objects. While there is some evidence for category specific effects in the medial temporal lobe (MTL), it is currently unclear whether domain level organization is also present across these structures. To this end, we used fMRI with a continuous recognition memory task. Stimuli were images of objects from several different categories, which were either animate or inanimate, or large or small within the inanimate domain. We employed representational similarity analysis (RSA) to test the hypothesis that object-evoked responses in MTL structures during recognition-memory judgments also show evidence for domain-level organization along both dimensions. Our data support this hypothesis. Specifically, object representations were shaped by either animacy, real-world size, or both, in perirhinal and parahippocampal cortex, as well as the hippocampus. While sensitivity to these dimensions differed when structures when probed individually, hinting at interesting links to functional differentiation, similarities in organization across MTL structures were more prominent overall. These results argue for continuity in the organization of object representations in the ventral visual stream and the MTL.
Reward-related regions form a preferentially coupled system at rest
Authors: Huckins Jeremy F. , Adeyemo Babatunde , Miezin Fran M. , Power Jonathan D. , Gordon Evan M. , Laumann Timothy O. , Heatherton Todd F. , Petersen Steven E. , Kelley William M. 
Published: April 2018

AbstractNeuroimaging studies have implicated a set of striatal and orbitofrontal cortex (OFC) regions that are commonly activated during reward processing tasks. Resting-state functional connectivity (RSFC) studies have demonstrated that the human brain is organized into several functional systems that show strong temporal coherence even in the absence of goal-directed tasks. Here we use seed-based and graph-theory RSFC approaches to characterize the systems-level organization of putative reward regions of at rest. Peaks of connectivity from seed-based RSFC patterns for the nucleus accumbens (NAcc, anatomically defined) and orbitofrontal cortex (OFC, functionally defined) were used to identify candidate reward regions which were merged with a previously used set of regions (Power et al., 2011). Graph-theory was then used to determine system-level membership for all regions. Several regions previously implicated in reward-processing (NAcc, lateral and medial OFC, and ventromedial prefrontal cortex) comprised a distinct, preferentially coupled system. This RSFC system is stable across a range of connectivity thresholds and shares strong overlap with meta-analyses of task-based reward studies. This reward system shares between-system connectivity with systems implicated in cognitive control and self-regulation, including the fronto-parietal, cingulo-opercular, and default systems. Further, differences may exist in the pathways through which control systems interact with key regions of this reward system. Whereas NAcc regions of the reward system are functionally connected to cingulo-opercular and default systems, OFC regions of the reward system show stronger connectivity with the fronto-parietal system. We propose that future work may be able to interrogate group or individual differences in connectivity profiles using the regions delineated in the current work to explore potential relationships to appetitive behaviors, self-regulation failure, and addiction.
Extraordinary genome instability and widespread chromosome rearrangements during vegetative growth
Authors: Möller Mareike , Habig Michael , Freitag Michael , Stukenbrock Eva H. 
Published: April 2018

AbstractThe haploid genome of the pathogenic fungusZymoseptoria triticiis contained on “core” and “accessory” chromosomes. While 13 core chromosomes are found in all strains, as many as eight accessory chromosomes show presence/absence variation and rearrangements among field isolates. We investigated chromosome stability using experimental evolution, karyotyping and genome sequencing. We report extremely high and variable rates of accessory chromosome loss during mitotic propagationin vitroandin planta. Spontaneous chromosome loss was observed in 2 to >50 % of cells during four weeks of incubation. Similar rates of chromosome loss in the closely relatedZ. ardabiliaesuggest that this extreme chromosome dynamic is a conserved phenomenon in the genus. Elevating the incubation temperature greatly increases instability of accessory and even core chromosomes, causing severe rearrangements involving telomere fusion and chromosome breakage. Chromosome losses do not impact the fitness ofZ. tritici in vitro, but some lead to increased virulence suggesting an adaptive role of this extraordinary chromosome instability.
RefSeq database growth influences the accuracy of k-mer-based species identification
Authors: Nasko Daniel J. , Koren Sergey , Phillippy Adam M. , Treangen Todd J. 
Published: April 2018

ABSTRACTAccurate species-level taxonomic classification and profiling of complex microbial communities remains a challenge due to homologous regions shared among closely related species and a sparse representation of non-human associated microbes in the database. Although the database undoubtedly has a strong influence on the sensitivity of taxonomic classifiers and profilers, to date, no study has carefully explored this topic on historical RefSeq releases and explored its impact on accuracy. In this study, we examined the influence of the database, over time, on k-mer based sequence classification and profiling. We present three major findings: (i) database growth over time resulted in more classified reads, but fewer species-level classifications and more species-level misclassifications; (ii) Bayesian re-estimation of abundance helped to recover species-level classifications when the exact target strain was present; and (iii) Bayesian reestimation struggled when the database lacked the target strain, resulting in a notable decrease in accuracy. In summary, our findings suggest that the growth of RefSeq over time has strongly influenced the accuracy of k-mer based classification and profiling methods, resulting in different classification results depending on the particular database used. These results suggest a need for new algorithms specially adapted for large genome collections and better measures of classification uncertainty.