bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antithymocyte Globulin Versus Interleukin-2 Receptor Antagonist in Kidney Transplant Recipients With Hepatitis C Virus
Authors: Bae Sunjae , Durand Christine M. , Garonzik-Wang Jacqueline M. , Chow Eric K.H. , Kucirka Lauren M. , McAdams-DeMarco Mara A. , Massie Allan B. , Al Ammary Fawaz , Coresh Josef , Segev Dorry L. 
Published: September 2019

Background.Hepatitis C virus-positive (HCV+) kidney transplant (KT) recipients are at increased risks of rejection and graft failure. The optimal induction agent for this population remains controversial, particularly regarding concerns that antithymocyte globulin (ATG) might increase HCV-related complications.Methods.Using Scientific Registry of Transplant Recipients and Medicare claims data, we studied 6780 HCV+ and 139 681 HCV− KT recipients in 1999–2016 who received ATG or interleukin-2 receptor antagonist (IL2RA) for induction. We first examined the association of recipient HCV status with receiving ATG (versus IL2RA) using multilevel logistic regression. Then, we studied the association of ATG (versus IL2RA) with KT outcomes (rejection, graft failure, and death) and hepatic complications (liver transplant registration and cirrhosis) among HCV+ recipients using logistic and Cox regression.Results.HCV+ recipients were less likely to receive ATG than HCV− recipients (living donor, adjusted odds ratio [aOR] =0.640.770.91; deceased donor, aOR =0.710.810.92). In contrast, HCV+ recipients who received ATG were at lower risk of acute rejection compared to those who received IL2RA (1-y crude incidence = 11.6% versus 12.6%; aOR =0.680.820.99). There was no significant difference in the risks of graft failure (adjusted hazard ratio [aHR] =0.861.001.17), death (aHR =0.850.951.07), liver transplant registration (aHR =0.580.971.61), and cirrhosis (aHR =0.730.921.16).Conclusions.Our findings suggest that ATG, as compared to IL2RA, may lower the risk of acute rejection without increasing hepatic complications in HCV+ KT recipients. Given the higher rates of acute rejection in this population, ATG appears to be safe and reasonable for HCV+ recipients.
Late Graft Loss After Kidney Transplantation: Is “Death With Function” Really Death With a Functioning Allograft?
Authors: Gaston Robert S. , Fieberg Ann , Helgeson Erika S. , Eversull Jason , Hunsicker Lawrence , Kasiske Bertram L. , Leduc Robert , Rush David , Matas Arthur J. ,   for the DeKAF Investigators*
Published: September 2019

Background.
About half of late kidney allograft losses are attributed to death with function (DWF), a poorly characterized outcome. An ongoing question is whether DWF is a consequence of chronic allograft dysfunction. Using the prospective Long-term Deterioration of Kidney Allograft Function study database, we sought to better define the impact, phenotype, and clinical course of DWF in the current era.

Methods.
Three thousand five hundred eighty-seven kidney recipients with functional grafts at 90 days post-transplant were followed prospectively for a median of 5.2 years.

Results.
Characteristics at transplantation in those with DWF (N = 350, 9.8%) differed from those who otherwise lost their grafts (death-censored graft failure [DC-GF], N = 295, 8.2%) or maintained function (N = 2942, 82.0%); DWF patients were older, sicker, and had been on dialysis longer, with more preexisting cardiovascular disease, whereas DC-GF patients experienced more early rejection, more acute rejection after 90 days, and a clinically significant decrease in kidney function before graft failure. In contrast, the clinical course after transplantation in DWF patients did not differ before death from those who maintained function throughout.

Conclusions.
DWF and DC-GF in kidney transplant recipients represent differing clinical phenotypes occurring in distinct patient populations. Reducing the impact of DWF requires better definition of causes and clinical course and then trials of therapies to improve outcomes. Composite endpoints in clinical trials that group DWF and DC-GF together may obscure important clinical findings.
Racial and Ethnic Disparities in Kidney Transplant Access Within a Theoretical Context of Medical Eligibility
Authors: Ku Elaine , Lee Brian K. , McCulloch Charles E. , Roll Garrett R. , Grimes Barbara , Adey Deborah , Johansen Kirsten L. 
Published: September 2019

Background.
Non-Hispanic black (NHB) and Hispanic patients have lower access to kidney transplantation compared to non-Hispanic whites (NHWs). We examined whether differences in the prevalence of comorbidities that affect eligibility for transplant contribute to disparities in receipt of transplantation.

Methods.
We performed a retrospective study of 986 019 adults who started dialysis between 2005 and 2014, according to the United States Renal Data System. We compared prevalence of comorbidities that could influence transplant eligibility by race/ethnicity. We examined time to first transplant by race/ethnicity in this overall cohort and in a very healthy sub-cohort without conditions that could be contraindications to transplantation.

Results.
During 2.3 years of mean follow-up, 64 892 transplants occurred. NHBs and Hispanics had a lower prevalence of medical barriers to transplantation at the time of dialysis initiation than NHWs, including age >70 years (26% in NHB versus 47% in NHW) and malignancy (4% in Hispanics versus 10% in NHWs). Access to transplant was 65% lower (95% CI, 0.33–0.37) in NHBs and 43% lower (95% CI, 0.54–0.62) in Hispanics (versus NHWs) in the first year after end-stage renal disease, but by Year 4, access to transplantation was not statistically significantly different between Hispanics or NHBs (versus NHWs). In our very healthy cohort, racial and ethnic disparities in access to transplantation persisted up to Year 5 in NHBs and Year 4 in Hispanics after end-stage renal disease onset.

Conclusions.
Differences in medical eligibility do not appear to explain racial/ethnic disparities in receipt of kidney transplantation and may mask the actual magnitude of the inequities that are present.
The Evolution of Monoclonal Gammopathy of Undetermined Significance in Kidney Transplant Recipients
Authors: Gagnon Marie-France , Cardinal Héloïse , Emond Jean-Pierre , Latour Mathieu , Lemieux Bernard 
Published: September 2019

Background.
It is unclear if immunosuppression increases the likelihood of malignant transformation of monoclonal gammopathy of undetermined significance (MGUS) and whether adverse renal outcomes in kidney transplant recipients with MGUS are more frequent.

Methods.
We performed a retrospective cohort study of kidney transplant recipients at the Centre Hospitalier de l’Université de Montréal between 2000 and 2016.

Results.
Among 755 study participants, 13 (1.7%) were found to have MGUS before transplant. Two evolved to smoldering multiple myeloma and 2 presented paraprotein-induced allograft injury from light chain deposition disease. Forty-six patients developed posttransplant MGUS (2.5% 5-y cumulative incidence) of which 1 progressed to multiple myeloma and 1 experienced kidney allograft loss from light chain deposition disease. None of the patients with a malignant transformation or paraprotein-induced renal disease after transplantation had had a systematic workup before transplantation to exclude hematologic malignancies and paraprotein-related kidney injury. Nine posttransplant MGUS (21%) were transient. Multivariable analysis revealed that age at transplant (hazard ratio 1.05 per 1-y increase, 95% confidence intervals, 1.02-1.08) and prior cytomegalovirus infection (hazard ratio 2.22, 95% confidence intervals, 1.07-4.58) were associated with the development of MGUS after transplantation. Of 7 posttransplant lymphoproliferative disorders, none were preceded by MGUS.

Conclusions.
Our results suggest that the identification of MGUS in a transplant candidate should lead to further investigations to exclude a plasma cell neoplasm and monoclonal gammopathy of renal significance before transplantation. MGUS arising after transplantation appears to carry a favorable evolution.
Genome Sequencing and Transcriptome Analysis Reveal Recent Species-specific Gene Duplications in the Plastic Gilthead Sea Bream
Authors: Pérez-Sánchez Jaume , Naya-Català Fernando , Soriano Beatriz , Piazzon M. Carla , Hafez Ahmed , Gabaldón Toni , Llorens Carlos , Sitjà-Bobadilla Ariadna , Calduch-Giner Josep A. 
Published: September 2019

AbstractGilthead sea bream is an economically important fish species that is remarkably well-adapted to farming and changing environments. Understanding the genomic basis of this plasticity will serve to orientate domestication and selective breeding towards more robust and efficient fish. To address this goal, a draft genome assembly was reconstructed combining short- and long-read high-throughput sequencing with genetic linkage maps. The assembled unmasked genome spans 1.24 Gb of an expected 1.59 Gb genome size with 932 scaffolds (∼732 Mb) anchored to 24 chromosomes that are available as a karyotype browser at www.nutrigroup-iats.org/seabreambrowser. Homology-based functional annotation, supported by RNA-seq transcripts, identified 55,423 actively transcribed genes corresponding to 21,275 unique descriptions with more than 55% of duplicated genes. The mobilome accounts for the 75% of the full genome size and it is mostly constituted by introns (599 Mb), whereas the rest is represented by low complexity repeats, RNA retrotransposons, DNA transposons and non-coding RNAs. This mobilome also contains a large number of chimeric/composite genes (i. e. loci presenting fragments or exons mostly surrounded by LINEs and Tc1/mariner DNA transposons), whose analysis revealed an enrichment in immune-related functions and processes. Analysis of synteny and gene phylogenies uncovered a high rate of species-specific duplications, resulting from recent independent duplications rather than from genome polyploidization (2.024 duplications per gene; 0.385 excluding gene expansions). These species-specific duplications were enriched in gene families functionally related to genome transposition, immune response and sensory responses. Additionally, transcriptional analysis of liver, skeletal muscle, intestine, gills and spleen supported a high number of functionally specialized paralogs under tissue-exclusive regulation. Altogether, these findings suggest a role of recent large-scale gene duplications coupled to tissue expression diversification in the evolution of gilthead sea bream genome during its successful adaptation to a changing and pathogen-rich environment. This issue also underscores a role of evolutionary routes for rapid increase of the gene repertoire in teleost fish that are independent of polyploidization. Since gilthead sea bream has a well-recognized plasticity, the current study will advance our understanding of fish biology and how organisms of this taxon interact with the environment.
GpABC: a Julia package for approximate Bayesian computation with Gaussian process emulation
Authors: Tankhilevich Evgeny , Ish-Horowicz Jonathan , Hameed Tara , Roesch Elisabeth , Kleijn Istvan , Stumpf Michael PH , He Fei 
Published: September 2019

ABSTRACTApproximate Bayesian computation (ABC) is an important framework within which to infer the structure and parameters of a systems biology model. It is especially suitable for biological systems with stochastic and nonlinear dynamics, for which the likelihood functions are intractable. However, the associated computational cost often limits ABC to models that are relatively quick to simulate in practice. We here present a Julia package, GpABC, that implements parameter inference and model selection for deterministic or stochastic models using i) standard rejection ABC or ABC-SMC, or ii) ABC with Gaussian process emulation. The latter significantly reduces the computational cost.URL: https://github.com/tanhevg/GpABC.jl
Epilepsy and neurobehavioral abnormalities in mice with aKCNB1pathogenic variant that alters conducting and non-conducting functions of KV2.1
Authors: Hawkins Nicole A. , Misra Sunita N. , Jurado Manuel , Vierra Nicholas C. , Nguyen Kimberly , Wren Lisa , George Alfred L. , Trimmer James S. , Kearney Jennifer A. 
Published: September 2019

AbstractDevelopmental and epileptic encephalopathies (DEE) are a group of severe epilepsies that usually present with intractable seizures, developmental delay and are at a higher risk for premature mortality. Numerous genes have been identified as a monogenic cause of DEE, includingKCNB1. The voltage-gated potassium channel KV2.1, encoded byKCNB1, is primarily responsible for delayed rectifier potassium currents that are important regulators of excitability in electrically excitable cells, including neurons and cardiomyocytes. Thede novopathogenic variantKCNB1-p.G379R was identified in an infant with epileptic spasms, atonic, focal and tonic-clonic seizures that were refractory to treatment with standard antiepileptic drugs. Previous work demonstrated deficits in potassium conductance, but did not assess non-conducting functions. To determine if the G379R variant affected clustering at endoplasmic reticulum-plasma membrane junctions KV2.1-G379R was expressed in HEK293T cells. KV2.1-G379R expression did not induce formation of endoplasmic reticulum-plasma membrane junctions, and co-expression of KV2.1-G379R with KV2.1-WT lowered induction of these structures relative to KV2.1-WT alone, suggesting a dominant negative effect. To model this variantin vivo, we introducedKcnb1G379Rinto mice using CRISPR/Cas9 genome editing. We characterized neurological and neurobehavioral phenotypes ofKcnb1G379R/+(Kcnb1R/+) andKcnb1G379R/G379R(Kcnb1R/R) mice, and screened for cardiac abnormalities. Immunohistochemistry studies on brains fromKcnb1+/+(WT), Kcnb1R/+andKcnb1R/Rmice revealed genotype-dependent differences in the levels and subcellular localization of KV2.1, with reduced plasma membrane expression of the KV2.1-G379R protein, consistent within vitrodata.Kcnb1R/+andKcnb1R/Rmice displayed profound hyperactivity, repetitive behaviors, impulsivity and reduced anxiety. In addition, bothKcnb1R/+andKcnb1R/Rmice exhibited abnormal interictal EEG abnormalities, including isolated spike and slow waves. Spontaneous seizure events were observed inKcnb1R/Rmice during exposure to novel environments and/or handling, while bothKcnb1R/+andKcnb1R/Rmutants were more susceptible to induced seizures.Kcnb1R/+andKcnb1R/Rmice exhibited prolonged rate-corrected QT interval on surface ECG recording. Overall, theKcnb1G379Rmice recapitulate many features observed in individuals with DEE due to pathogenic variants inKCNB1. This new mouse model ofKCNB1associated DEE will be valuable for improving the understanding of the underlying pathophysiology and will provide a valuable tool for the development of therapies to treat this pharmacoresistant DEE.
Testing Finch’s hypothesis: the role of organismal modularity on the escape from actuarial senescence
Authors: Bernard Connor , Compagnoni Aldo , Salguero-Gómez Roberto 
Published: September 2019

AbstractUntil recently, senescence was assumed to be a universal phenomenon. Evolutionary theories of senescence predict that no organism may escape the physiological decline that results in an increase in mortality risk and/or decline in fertility with age. However, evidence both in animals and plants has emerged in the last decade defying such predictions. Researchers are currently seeking mechanistic explanations for the observed variation in ageing trajectories.We argue that the historical view on the inevitability of senescence is due, in part, to the development of its classical theories, which targeted primarily unitary organisms. In unitary species, the integration of resources and functions is high, and adult size is determined. In contrast, the architecture of modular organisms is indeterminate and built upon repeated modules. The isolation of mortality risk in species like hydra (Hydra spp.) or creosote brush (Larrea tridentata) may explain their null or even negative senescence.Caleb Finch hypothesised three decades ago that species with the ability to compartmentalise risk may escape senescence. Here, we first review the evidence on organisms that slow down or even avoid senescence in the context of their architecture, along a continuum of unitarity-modularity. Then, we use open-access databases to comparatively analyse various moments of senescence and link longevity to the degree of anatomic modularity. Our analysis compares 138 plants and 151 animals. Our comparative analysis reveals that plant species that are more modular do indeed tend to escape from senescence more often than those that are unitary. The role of modularity in animal senescence is less clear.In light of novel support for Finch’s hypothesis across a large diversity of plant species, and with less conclusive findings in animals, we identify new research directions. We highlight opportunities related to age-dependent mortality factors. Other areas for further research include the role of modularity in relation to endocrine actions, and the costs of modular anatomies.“The actinozooid is a living thing which knows no time of youthful vigour, no waxing to a period of adult life, no waxing to senility – it knows no age – it practically knows no natural death.”– Wood-Jones (1912)
Audio-visual combination of syllables involves time-sensitive dynamics following from fusion failure
Authors: Bouton Sophie , Delgado-Saa Jaime , Olasagasti Itsaso , Giraud Anne-Lise 
Published: September 2019

AbstractIn face-to-face communication, audio-visual (AV) stimuli can be fused, combined or perceived as mismatching. While the left superior temporal sulcus (STS) is admittedly the locus of AV integration, the process leading to combination is unknown. Analysing behaviour and time-/source-resolved human MEG data, we show that while fusion and combination both involve early detection of AV physical features discrepancy in the STS, combination is associated in with activity of AV asynchrony-sensitive regions (auditory and inferior frontal cortices). Based on dynamic causal modelling, and neural signal decoding, we further show that AV speech integration outcome primarily depends on whether the STS can quickly converge onto an existing multimodal syllable representation, and that combination results from subsequent temporal processing, presumably re-ordering, of discrepant AV stimuli.
Modern human alleles differentially regulate gene expression across brain regions: implications for brain evolution
Authors: Andirkó Alejandro , Boeckx Cedric 
Published: September 2019

AbstractThe availability of high-coverage genomes of our extinct relatives, the Neanderthals and Denisovans, and the emergence of large, tissue-specific databases of modern human genetic variation, offer the possibility of probing the evolutionary trajectory of heterogenous structures of great interest, such as the brain. Using the GTEx cis-eQTL dataset and an extended catalog ofHomo sapiens-specific alleles relative to Neanderthals and Denisovans, we generated a dataset of nearly fixed,Homo sapiens-derived alleles that affect the regulation of gene expression across 15 brain (and brain related) structures. The list of variants obtained reveals enrichments in regions of the modern human genome showing putative signals of positive selection relative to archaic humans, and bring out the highly derived status of the cerebellum. Additionally, we complement previous literature on the expression effects of ancestral alleles in theHomo sapiensbrain by pointing at a downregulation bias caused by linkage disequilibrium.
Estimating Northern Fur Seal Pup Production: A Case Study of Batch Mark Abundance Estimation
Authors: Johnson Devin S. , Towell Rod G. , Baker Jason D. 
Published: September 2019

AbstractWe describe a hierarchical N-mixture model for estimating northern fur seal pup production from batch mark-resight data. Our goal was to improve upon a traditional design-based estimation method used for over 50 years. To this end, we propose a hierarchical N-mixture model to account for differences in animal availability for resighting and observer detection probabilities. A Bayesian approach is used for inference with three separate methods proposed for necessary computations. First a straightforward posterior sample is drawn using MCMC. This was considered the gold standard for this analysis. However, we also consider an approximate model-based on Gaussian approximation of the Poisson and binomial distributions used in the exact hierarchical model. By using the Gaussian approximations, analytic integration can be used to marginalize over latent components. Inference can then be made by maximizing the posterior to find the mode. Following this we investigate both delta-method and parametric bootstrap approaches for calculating abundance and the associated standard errors with batch sampling data collected on northern fur seals in 2016. Each of the three newly proposed methods produced virtually identical estimates and standard errors. In addition, the parametric bootstrap approximation to a posterior sample was also virtually the same as the MCMC derived sample. There were a handful of small differences in the point estimates of abundance but these were not large enough to be especially notable. There were some noticeable differences in uncertainty estimates. The production estimate coefficients of variation ranged from 2.5–9.5% for the model-based estimates, but 0.0–12.5% for the design-based estimates. The design-based estimates of uncertainty were more volatile using the design-based method with some standard error estimates unreasonably small. Through a case study we have provided support for using Gaussian approximation inN-mixture type models when abundance is relatively large. These situations are typically challenging for fitting models using any sort of marginalization because there is no analytic solution for the exact models. However, when abundances are large using a Gaussian approximated model allows for analytic integration over latent abundance states which can greatly facilitate methodology such as maximum likelihood or posterior inference.