bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adequacy of Initial Everolimus Dose, With and Without Calcineurin Inhibitors, in Kidney Transplant Recipients
Authors: Felipe Claudia , Ferreira Alexandra , Bessa Adrieli , Abait Tamiris , Perez Juliana D. , Casarini Dulce Elena , Medina-Pestana Jose , Tedesco Helio 
Published: December 2017

Background:
This study investigates the adequacy of initial everolimus (EVR) dose, with and without calcineurin inhibitors (CNI), in kidney transplant recipients.

Methods:
This retrospective cohort analysis involved data from 305 kidney transplant recipients participating in 3 randomized trials receiving reduced dose cyclosporin A (CsA) combined with EVR 0.75 mg BID (CSA/EVR0.75, N = 32) or 1.5 mg BID (CSA/EVR1.5, N = 31), reduced dose tacrolimus (TAC) combined with EVR 1.5 mg BID (TAC0.05/EVR1.5, N = 83), standard dose TAC combined with EVR 1.5 mg BID (TAC0.1/EVR1.5, N = 93), and EVR 1.5 mg BID (EVR1.5, N = 66) with TAC introduction after day 5. The adequacy of the initial EVR dose, based on EVR whole blood trough between 3 and 8 ng/mL, was compared using first EVR blood concentrations obtained at day 3 after transplantation.

Results:
Recipient age, proportion of patients with diabetes mellitus, and proportion of grafts from living donors were different among the groups. Dose-corrected EVR concentrations were higher in patients receiving CsA than in those receiving TAC or no calcineurin inhibitors (6.7 ± 5.9 versus 5.4 ± 2.2 versus 2.4 ± 0.8 versus 2.5 ± 0.9 versus 2.2 ± 0.7, P = 0.000). No differences were observed comparing dose adjusted EVR concentrations combined with TAC or alone (P = 0.073). The proportion of patients with EVR concentration below <3 ng/mL was lower when EVR was combined with CsA (25 versus 3 versus 43 versus 33 versus 50%, P = 0.000). Later introduction of TAC did not influence EVR concentrations. There were no differences in mean CsA concentrations comparing patients receiving EVR 0.75 or 1.5 mg BID (240 ± 143 versus 213 ± 105 ng/mL). On the other hand, mean TAC concentrations were higher according to the initial TAC dose regimen (6.4 ± 3.9 versus 9.8 ± 5.9 ng/mL).

Conclusions:
In de novo kidney transplant recipients, the choice of the initial dose of EVR should consider the type of calcineurin inhibitor to reach target EVR concentration within the first week in a higher proportion of patients, maximizing the efficacy/toxicity profile.
Simulation of the Emergency Department Care Process for Pediatric Traumatic Brain Injury
Authors: Ajdari Ali , Boyle Linda Ng , Kannan Nithya , Wang Jin , Rivara Frederick P. , Vavilala Monica S. 
Published: December 2017

ABSTRACT
The treatment of patients in the emergency department (ED) with severe pediatric traumatic brain injury (TBI) is challenging, and treatment process strategies that facilitate good outcomes are not well documented. The overall objective of this study was to identify factors that can affect the care process associated with pediatric TBI. This objective was achieved using a discrete-event simulation model of patients with TBI as they progress through the ED treatment process of a Level I trauma center. This model was used to identify areas where the ED length of stay can be reduced. The number of patients arriving at any given time was also varied in the simulation model to observe the impact to bed allocation policies and changes in staff and equipment. The findings showed that implementing changes in the ED (i.e., availability of two computerized tomography scanners, formation of resuscitation teams that included eight staff personnel, and modifying the bed allocation policy) could result in a 17% reduction in the mean ED length of stay. The study outcomes would be of interest to those (e.g., health administrators, health managers, and physicians) who can make decisions related to the treatment process in an ED.
Pediatric Adverse Event Rates Associated With Inexperience in Teaching Hospitals: A Multilevel Analysis
Authors: Dynan Linda , Goudie Anthony , Brady Patrick W. 
Published: December 2017

ABSTRACT
High adverse event rates are a signal of potentially low-quality care that imposes burdens on patients, families, and hospitals. In this article, we examine the relationship between the distinct characteristics of teaching hospitals with adverse event rates among pediatric patients, controlling for patient complexity and severity using 2009–2011 Nationwide Inpatient Sample data from the Agency for Healthcare Research and Quality. We hypothesize that adverse event rates increase with the availability of more complex services and technologies (transplantation and pediatric open-heart surgery); increase as experience of providers decreases (July effect); and increase with residents per bed, a measure of both average provider inexperience and congestion. Using multilevel analysis, we find empirical evidence in support of our three hypotheses. We find that in environments where more learning occurs, more mistakes are made. Identifying high-performing hospitals with large residency programs and complex service lines that have made progress in patient safety and then studying how they have done so should become a priority. These findings should then be adapted within other hospitals through publicly funded mechanisms to improve the quality of care for all children.
Evaluation of a Dedicated Tobacco Cessation Support Service for Thoracic Cancer Center Patients
Authors: Amato Katharine A. , Reid Mary E. , Ochs-Balcom Heather M. , Giovino Gary A. , Bansal-Travers Maansi , Warren Graham W. , Mahoney Martin C. , Hyland Andrew J. 
Published: December 2017

Context:
Cancer patients' continued tobacco use results in poorer therapeutic outcomes including decreased quality of life and survival.

Objective:
To assess reach and impact of a free, opt-out, telephone-based tobacco cessation program for thoracic cancer center patients.

Design:
Observational study.

Setting:
Comprehensive Cancer Center in Western New York.

Participants:
Current or recent (within past 30 days) tobacco-using thoracic cancer center patients referred to a tobacco cessation support service between October 2010 and October 2012 at a Comprehensive Cancer Center (n = 942/1313 referrals were eligible for cessation support).

Intervention:
A free, opt-out, telephone-based cessation service that was implemented as standard of care. Cessation specialists had patient-guided conversations that assessed readiness to quit; methods used in the past provided cessation strategies and worked to set up a quit date. There was an average of 35.9 days between referral and first contact.

Main Outcome Measures:
Program reach (referral and participation rates) and impact (as self-reported cessation outcomes measured twice after referral).

Results:
Of 942 patients, 730 (77.5%) referred to and called by a tobacco cessation service participated in at least 1 cessation support call, of which 440 of 730 (60.3%) were called for follow-up and 89.5% (394/440) participated. In total, 20.2% (69/342) of current smokers at referral reported at least 7-day abstinence at follow-up. Among current smokers at referral and first contact, being married (odds ratio [OR] = 2.05; 95% confidence interval [CI], 1.01-4.18) and having a lower Eastern Cooperative Oncology Group (ECOG) performance score (OR = 4.05; 95% CI, 1.58-10.39) were associated with quitting at follow-up, after controlling for demographic, clinical, and health behavior characteristics.

Conclusions:
Our results demonstrate that 78% of thoracic cancer center patients, if contacted, participated at least once in this cessation support service; for current smokers at referral and first contact, being married and having a lower ECOG performance score were associated with self-reported quitting at follow-up. Other organizations may find our results useful while implementing a systematic way to identify tobacco-using patients as part of routine care and to improve available cessation support services.
Brain Volumes and Longitudinal Cognitive Change
Authors: Vibha Deepti , Tiemeier Henning , Mirza Saira S. , Adams Hieab H.H. , Niessen Wiro J. , Hofman Albert , Prasad Kameshwar , van der Lugt Aad , Vernooij Meike W. , Ikram Mohammad A. 
Published: December 2017

Objective:
To investigate the association of brain volumes, white matter lesion (WML) volumes, and lacunes, with cognitive decline in a population-based cohort of nondemented persons.

Methods:
Within the Rotterdam Study, 3624 participants underwent brain magnetic resonance imaging. Cognition was evaluated at baseline (2005 to 2009) and at the follow-up visit (2011 to 2013). We used a test battery that tapped into domains of executive function, information processing speed, motor speed, and memory. The volumetric measures assessed were total brain volume, lobar (gray matter and white matter) volumes, and hippocampal volumes. We also studied the association of WML volumes and lacunes with cognitive decline using linear regression models.

Results:
Total brain volume was associated with decline in global cognition, information processing, and motor speed (P<0.001) in analyses controlled for demographic and vascular factors. Specifically, smaller frontal and parietal lobes were associated with decline in information processing and motor speed, and smaller temporal and parietal lobes were associated with decline in general cognition and motor speed (P<0.001 for all tests). Total WML volume was associated with decline in executive function. Lobar WML volume, hippocampal volume, and lacunes were not associated with cognitive decline.

Conclusions:
Lower brain volume is associated with subsequent cognitive decline. Although lower total brain volume was significantly associated with decline in global cognition, specific lobar volumes were associated with decline in certain cognitive domains.
The current place of epilepsy surgery
Authors: Engel Jerome 
Published: December 2017

Purpose of review
Three randomized controlled trials demonstrate that surgical treatment is safe and effective for drug-resistant epilepsy (DRE), yet fewer than 1% of patients are referred for surgery. This is a review of recent trends in surgical referral for DRE, and advances in the field. Reasons for continued underutilization are discussed.

Recent findings
Recent series indicate no increase in surgical referral for DRE over the past two decades. One study suggests that decreased referrals to major epilepsy centers can be accounted for by increased referrals to low-volume nonacademic hospitals where results are poorer, and complication rates higher. The increasing ability of high-resolution MRI to identify small neocortical lesions and an increase in pediatric surgeries, in part, explain a relative greater decrease in temporal lobe surgeries. Misconceptions continue to restrict referral. Consequently, advocacy for referral of all patients with DRE to epilepsy centers that offer specialized diagnosis and other alternative treatments, as well as psychosocial support, is recommended. Recent advances will continue to improve the safety and efficacy of surgical treatment and expand the types of patients who benefit from surgical intervention.

Summary
Surgical treatment for epilepsy remains underutilized, in part because of persistent misconceptions. Rather than promote referral for surgery, it would be more appropriate to advocate that all patients with DRE deserve a consultation at a full-service epilepsy center that offers many options for eliminating or reducing disability.
Quantifying biases in test-negative studies of vaccine effectiveness
Authors: Lewnard Joseph A. , Tedijanto Christine , Cowling Benjamin J. , Lipsitch Marc 
Published: December 2017

ABSTRACTTest-negative designs have become commonplace in assessments of seasonal influenza vaccine effectiveness. Vaccine effectiveness is measured from the exposure odds ratio (OR) of vaccination among individuals seeking treatment for acute respiratory illness and receiving a laboratory test for influenza infection. This approach is widely believed to correct for differential healthcare-seeking behavior among vaccinated and unvaccinated persons. However, the relation of the measured OR to true vaccine effectiveness is poorly understood. We derive the OR under circumstances of real-world test-negative studies. The OR recovers the true vaccine direct effect when two conditions are met: (1) that individuals’ vaccination decisions are uncorrelated with exposure or susceptibility to infection, and (2) that vaccination confers “all-or-nothing” protection (whereby certain individuals have no protection while others are perfectly protected). Biased effect size estimates arise if either condition is unmet. Such bias may suggest misleading associations of the OR with time since vaccination or the force of infection of influenza. The test-negative design may also fail to correct for differential healthcare-seeking behavior among vaccinated and unvaccinated persons without stringent criteria for enrollment and testing. Our findings demonstrate a need to reassess how data from test-negative studies are interpreted for policy decisions conventionally based on causal inferences.
Genome-Epigenome Interactions Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Herrera Santiago , de Vega Wilfred C. , Ashbrook David , Vernon Suzanne D. , McGowan Patrick O. 
Published: December 2017

ABSTRACTMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an example of a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as with specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, the association between DNA methylation and genetic background in relation to the ME/CFS is currently unknown. In this study we explored this association by characterizing the genomic (~4.3 million SNPs) and epigenomic (~480 thousand CpG loci) variability between populations of ME/CFS patients and healthy controls. We found significant associations of methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism. Finally, we found significant correlations of genotypes with methylation phenotypes associated with ME/CFS. The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS.
Comprehensive Cell Type Specific Transcriptomics of the Human Kidney
Authors: Sivakamasundari V , Bolisetty Mohan , Sivajothi Santhosh , Bessonett Shannon , Ruan Diane , Robson Paul 
Published: December 2017

AbstractThe human kidney is a complex organ composed of specialized cell types. To better define this cellular complexity, we profiled the individual transcriptomes of 22,469 normal human kidney cells, identifying 27 cell types. We describe three distinct endothelial cell populations, a novel subset of intercalated cells, interstitial macrophage and dendritic cells, and identify numerous novel cell-type-specific markers, many validated using imaging mass cytometry and immunohistochemistry. Receptor-ligand analysis revealed previously unknown intercalated-endothelial and intercalated-distal nephron interactions, suggesting a role in maintenance of vascular integrity and intercalated cell survival. Notably, kidney disease-associated genes were largely expressed in proximal tubules, podocytes, endothelial and myeloid cells, highlighting an underappreciated role for endothelial cells in kidney pathologies. Our analysis also provides a resource of cell type enriched markers, solute carriers, channels and lncRNAs. In summary, this cell-type-specific transcriptome resource provides the foundation for a comprehensive understanding of kidney function and dysfunction at single cell resolution.
Inferring Phylogenetic Networks Using PhyloNet
Authors: Wen Dingqiao , Yu Yun , Zhu Jiafan , Nakhleh Luay 
Published: December 2017

AbstractPhyloNet was released in 2008 as a software package for representing and analyzing phylogenetic networks. At the time of its release, the main functionalities in PhyloNet consisted of measures for comparing network topologies and a single heuristic for reconciling gene trees with a species tree. Since then, PhyloNet has grown significantly. The software package now includes a wide array of methods for inferring phylogenetic networks from data sets of unlinked loci while accounting for both reticulation (e.g., hybridization) and incomplete lineage sorting. In particular, PhyloNet now allows for maximum parsimony, maximum likelihood, and Bayesian inference of phylogenetic networks from gene tree estimates. Furthermore, Bayesian inference directly from sequence data (sequence alignments or bi-allelic markers) is implemented. Maximum parsimony is based on an extension of the “minimizing deep coalescences” criterion to phylogenetic networks, whereas maximum likelihood and Bayesian inference are based on the multispecies network coalescent. All methods allow for multiple individuals per species. As computing the likelihood of a phylogenetic network is computationally hard, PhyloNet allows for evaluation and inference of networks using a pseudo-likelihood measure. PhyloNet summarizes the results of the various analyses, and generates phylogenetic networks in the extended Newick format that is readily viewable by existing visualization software, [phylogenetic networks; reticulation; incomplete lineage sorting; multispecies network coalescent; Bayesian inference; maximum likelihood; maximum parsimony.]
HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells
Authors: Abel Ethan V. , Goto Masashi , Magnuson Brian , Abraham Saji , Ramanathan Nikita , Hotaling Emily , Alaniz Anthony A. , Kumar-Sinha Chandan , Dziubinski Michele L. , Urs Sumithra , Wang Lidong , Shi Jiaqi , Waghray Meghna , Ljungman Mats , Crawford Howard C. , Simeone Diane M. 
Published: December 2017

ABSTRACTThe biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, PCSC depletion, and downregulation of OCT4 expression. Conversely, HNF1A overexpression increased PCSC numbers and tumorsphere formation in pancreatic cancer cells and drove PDA cell growth. Importantly, depletion of HNF1A in primary tumor xenografts impaired tumor growth and depleted PCSCsin vivo. Finally, we established an HNF1A-dependent gene signature in PDA cells that significantly correlated with reduced survivability in patients. These findings identify HNF1A as a central transcriptional regulator of the PCSC state and novel oncogene in pancreatic ductal adenocarcinoma.
Variations in δ13C of different plant organs: implications for post-photosynthetic fractionation
Authors: Zhang Yonge , Yu Xinxiao , Chen Lihua , Jia Guodong 
Published: December 2017

ABSTRACTCompared to photosynthetic fractionation, the mechanism of post-photosynthetic carbon isotope fractionation is not well understood. The aim of this study was to investigate post-photosynthetic fractionation in both above and below ground tissues and to evaluate potential hypotheses explaining differences in carbon isotope composition (δ13C) among different plant organs, which can provide valuable insights into plant physiology. The results revealed that there is no significant day-night difference inδ13C of twig phloem water soluble organic materials (WSOM), which could be explained by the unrestricted exchange of triose-phosphates between the chloroplast and cytoplasm and a time lag for carbohydrate exportation. Further, we found thatδ13C of twig phloem WSOM is more sensitive to plant water status than leaf WSOM. Analysis ofδ13C in different plant organs showed that the greatest13C enrichment was recorded in stem phloem. Divergences inδ13C of phloem WSOM among different plant organs were not likely to be explained by respiratory fractionation or time lag and were ascribed to transport of carbohydrates across organ boundaries and metabolic processes. Our study demonstrated that post-photosynthesis fractionation could not be ascribed to a single, unifying hypotheses; instead, it is the result of multiple processes.Highlightδ13C of twig phloem water soluble organic materials varied no clear diel pattern. In the leaf-twig-stem-root sequence, the greatest13C enrichment was recorded in stem phloem.
A simple spatially explicit neutral model explains range size distribution of reef fishes
Authors: Alzate Adriana , Janzen Thijs , Bonte Dries , Rosindell James , Etienne Rampal S. 
Published: December 2017

AbstractAimThe great variation in range sizes among species has fascinated ecologists for decades. In reef-associated fish species, which live in fragmented habitats and adopt a wide range of dispersal strategies, we may expect species with greater dispersal ability to spread over larger ranges. However, empirical evidence for such a positive relationship between dispersal and range size in reef fishes remains scarce. Here, we unveil the more nuanced role of dispersal on the range size distribution of reef associated fishes using empirical data and a novel spatially explicit model.LocationTropical Eastern PacificMajor taxa studiedReef-associated fishesMethodsWe estimated range size distributions for six different guilds of all reef-associated fishes with different dispersal abilities. We used a one-dimensional spatially explicit neutral model, which simulates the distribution of species along a linear coastline to explored the effect of dispersal, speciation and sampling on the distribution of range sizes. Our model adopts a more realistic gradual speciation process (protracted speciation) and incorporates important long distance dispersal events with a fat-tail dispersal kernel. We simulated our model using a highly efficient coalescence approach, which guarantees the metacommunity, is sampled at dynamic equilibrium. We fitted the model to the empirical data using an approximate Bayesian computation approach, with a sequential Monte Carlo algorithm.ResultsStochastic birth, death, speciation and dispersal events alone can accurately explain empirical range size distributions for six different guilds of tropical, reef-associated fishes. Variation in range size distributions among guilds are explained purely by differences in dispersal ability with the best dispersers covering larger ranges.Main conclusionsA simple combination of neutral processes with guild-specific dispersal ability provides a general explanation for both within- and across-guild range size variation. Our results support the theoretically expected, but empirically much debated, hypothesis that dispersal promotes range size.