bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma
Authors: Henriksen Hanne H. , McGarrity Sarah , SigurÐardóttir Rósa S. , Nemkov Travis , D’Alessandro Angelo , Palsson Bernhard O. , Stensballe Jakob , Wade Charles E. , Rolfsson Óttar , Johansson Pär I. 
Published: July 2019

Objective:
Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma.

Background:
We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial glycocalyx damage marker) in plasma have an increased mortality rate compared with patients with lower levels. Notably, we found that patients suffering from the same trauma severity could develop significantly different degrees of endothelial dysfunction as measured by syndecan-1.

Methods:
Prospective observational study of 20 trauma patients admitted to a Level 1 Trauma Centre and 20 healthy controls. Admission plasma syndecan-1 level and mass spectrometry were measured and analyzed by computational network analysis of our genome-scale metabolic model of the microvascular endothelial cell function.

Results:
Trauma patients had a significantly different endothelial metabolic profile compared with controls. Among the patients, 4 phenotypes were identified. Three phenotypes were independent of syndecan-1 levels. We developed genome-scale metabolic models representative of the observed phenotypes. Within these phenotypes, we observed differences in the cell fluxes from glucose and palmitate to produce Acetyl-CoA, and secretion of heparan sulfate proteoglycan (component of syndecan-1).

Conclusions:
We confirm that trauma patients have a significantly different metabolic profile compared with controls. A minimum of 4 shock-induced endotheliopathy phenotypes were identified, which were independent of syndecan-1level (except 1 phenotype) verifying that the endothelial response to trauma is heterogeneous and most likely driven by a genetic component. Moreover, we introduced a new research tool in trauma by using metabolic systems biology, laying the foundation for personalized medicine.
Trends of Burn Injury in the United States
Authors: Crowe Christopher S. , Massenburg Benjamin B. , Morrison Shane D. , Naghavi Mohsen , Pham Tam N. , Gibran Nicole S. 
Published: July 2019

Objective:
The aim of this study is to report patterns of burn injury within the United States from 1990 to 2016 with regard to age, sex, geography, and year.

Summary Background Data:
Advances in the management of burn injuries as well as successful public health efforts have contributed to reductions in the annual incidence and mortality of burns. However, several studies suggest that these reductions are not equally distributed throughout the US population.

Main Outcomes and Measures:
The Global Burden of Disease Study 2016 was utilized to collect incidence, mortality, disability-adjusted life years (DALYs), and years lived with disability (YLD) from 1990 to 2016. All measures were computed with 95% uncertainty intervals (UI).

Results:
The overall incidence of burn injury in the United States has decreased from 215 (95% UI, 183–246) to 140 (95% UI, 117–161) per 100,000. However, the relative mortality of burn injury has been fixed over the 26-year study period. Alaska had the highest rates of burn incidence in 1990 and 2016, closely followed by southeastern states. When adjusted for incidence, relative mortality in 1990 was highest in Alabama and Mississippi and the mortality–incidence ratio increased for these states in 2016. In addition, 35 states also demonstrated an increase in the relative mortality of burn injury during the study period.

Conclusions:
Regional trends of burn incidence and mortality are highly variable and are likely due to a multitude of factors. Addressing these disparities will require close examination of the contributing factors of burn injury and severity.
Life-supporting Kidney Xenotransplantation From Genetically Engineered Pigs in Baboons: A Comparison of Two Immunosuppressive Regimens
Authors: Yamamoto Takayuki , Hara Hidetaka , Foote Jeremy , Wang Liaoran , Li Qi , Klein Edwin C. , Schuurman Hendrik Jan , Zhou Hongmin , Li Juan , Tector A. Joseph , Zhang Zhongqiang , Ezzelarab Mohamed , Lovingood Ray , Ayares David , Eckhoff Devin E. , Cooper David K.C. , Iwase Hayato 
Published: July 2019

Background.
The aims of this study were to evaluate the efficacy of US Food and Drug Administration-approved drugs in genetically engineered pig-to-baboon kidney xenotransplantation and compare the results with those using an anti-CD40 monoclonal antibody (mAb)-based regimen.

Methods.
Ten life-supporting kidney transplants were carried out in baboons using α1,3-galactosyltransferase gene-knockout/CD46 pigs with various other genetic manipulations aimed at controlling coagulation dysregulation. Eight transplants resulted in informative data. Immunosuppressive therapy consisted of induction with antithymocyte globulin and anti-CD20mAb, and maintenance based on either (1) CTLA4-Ig and/or tacrolimus (+rapamycin or mycophenolate mofetil) (GroupA [US Food and Drug Administration-approved regimens], n = 4) or (2) anti-CD40mAb + rapamycin (GroupB, n = 4). All baboons received corticosteroids, interleukin-6R blockade, and tumor necrosis factor-α blockade. Baboons were followed by clinical and laboratory monitoring of kidney function, coagulation, and immune parameters. At euthanasia, morphological and immunohistochemical studies were performed on the kidney grafts.

Results.
The median survival in GroupB was 186 days (range 90–260), which was significantly longer than in GroupA; median 14 days (range 12–32) (P < 0.01). Only GroupA baboons developed consumptive coagulopathy and the histopathological features of thrombotic microangiopathic glomerulopathy and interstitial arterial vasculitis.

Conclusions.
Recognizing that the pig donors in each group differed in some genetic modifications, these data indicate that maintenance immunosuppression including anti-CD40mAb may be important to prevent pig kidney graft failure.
Body Weight Parameters are Related to Morbidity and Mortality After Liver Transplantation: A Systematic Review and Meta-analysis
Authors: Beckmann Sonja , Drent Gerda , Ruppar Todd , Nikolić Nataša , De Geest Sabina 
Published: July 2019

Background.
Weight gain and obesity are well-known clinical issues in liver transplantation (LTx). However, their impacts on patient outcomes remain unclear, as only the impact of pre-LTx body mass index (BMI) on survival has been meta-analyzed. We summarized and synthesized the evidence on pre- and post-LTx body weight parameters’ relations with post-LTx outcomes such as survival, metabolic and cardiovascular comorbidities, and healthcare utilization.

Methods.
We followed the Cochrane Handbook for Systematic Reviews of Interventions’ recommendations. Quality was assessed via a 19-item instrument. Odds ratios and 95% confidence intervals were calculated for outcomes investigated in ≥5 studies.

Results.
Our meta-analysis included 37 studies. Patients with pre-LTx BMI ≥ 30 kg/m2 and BMI ≥ 35 kg/m2 had lower overall survival rates than those with pre-LTx normal weight (72.6% and 69.8% versus 84.2%; P = 0.02 and P = 0.03, respectively). Those with pre-LTx BMI ≥ 30 kg/m2 had worse overall graft survival than normal weight patients (75.8% and 85.4%; P = 0.003). Pre-LTx BMI and pre-LTx overweight were associated with new-onset diabetes (P < 0.001 and P = 0.015, respectively), but post-LTx BMI showed no relationship. No associations were evident with healthcare utilization.

Conclusions.
Patients with BMI values ≥30 kg/m2 had worse patient and graft survival than those with normal weight. Few of the reviewed studies examined post-LTx body weight parameters or other relevant outcomes such as cardiovascular comorbidities. High heterogeneity as well as diverse definitions and operationalizations of measurement and outcomes severely impeded comparability.
Diabetogenic Effects of Immunosuppression: An Integrative Analysis
Authors: Bhat Mamatha , Pasini Elisa , Das Aninditee , Baciu Cristina , Angeli Marc , Humar Atul , Watt Kymberly D. , Allard Johane 
Published: July 2019

Background.
Posttransplant diabetes mellitus (PTDM) affects up to 50% of solid organ transplant recipients and compromises long-term outcomes. The goal of this study was to investigate how immunosuppressants affect gene expression in a manner that increases diabetes risk, by performing integrative analysis on publicly available, high-throughput gene expression data.

Methods.
All high-throughput gene expression datasets of solid organ transplant recipients were retrieved from the Gene Expression Omnibus. Significantly dysregulated genes and pathways were determined, and those in common with type 2 diabetes were identified. THP-1 and HepG2 cells were exposed in vitro to tacrolimus, and validation of genes involved in insulin signaling and glucose metabolism was performed using specific arrays. These cells were then treated with the hypoglycemic agents, metformin, and insulin to assess for appropriate reversion of specific diabetogenic genes.

Results.
Insulin signaling and secretion were the most commonly dysregulated pathways that overlapped with diabetes in transplant recipients. KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro.

Conclusions.
We discovered that the significantly dysregulated genes in the context of immunosuppression are implicated in insulin signaling and insulin secretion, as a manifestation of pancreatic β-cell function. In vitro validation confirmed key diabetes-related genes in the context of immunosuppression. Further analysis and in vitro validation revealed that metformin optimally reverts diabetogenic genes dysregulated in the context of immunosuppression. The optimal therapeutic management of posttransplant diabetes mellitus needs to be further investigated, taking into account the mechanistic impact of immunosuppressants.
Survival Benefit of Liver Transplantation for Hepatocellular Carcinoma
Authors: Kanneganti Mounika , Mahmud Nadim , Kaplan David E. , Taddei Tamar H. , Goldberg David S. 
Published: July 2019

Background.
In the United States, nearly 30% of liver transplants (LT) are performed for hepatocellular carcinoma (HCC). Although overall long-term survival is highest with LT, there are limited data on the incremental survival benefit of LT versus other curative options (resection or ablation) due to shunting of patients towards LT.

Methods.
We performed a retrospective cohort study of patients aged 50–69 with cirrhosis and HCC in the Veterans Health Administration (population enriched with 3 curative treatments) from 2008 to 2016. The cohort was restricted to patients who received LT, resection, or ablation and a calculated model for end-stage liver disease score <15 at HCC diagnosis.

Results.
Among 2129 veterans in the analytic cohort, 658 (26.7%) received LT, 244 (11.5%) underwent resection, and 1317 (61.59%) received ablation. In multivariable models, patients who underwent resection (hazard ratio: 5.42; 95% confidence interval: 4.15-7.08) or ablation (hazard ratio: 5.50; 95% confidence interval: 4.51-6.71) had significantly increased hazards of death. However, in absolute terms, the incremental survival benefit of LT over resection or ablation was small, between 0.02 and 0.03 years at 1 year, 0.32–0.42 years at 3 years, and 1.04–1.24 years at 5 years follow-up. These results were consistent in sensitivity analyses accounting for possible immortal time bias, as well as a cohort restricted to early/intermediate stage HCC.

Conclusions.
Although LT is associated with significantly increased survival compared to resection and ablation, the absolute incremental survival benefit is small over a 5-year time horizon. Optimal selection of patients for LT is critical for maximizing utilization of a scarce resource.
Gender Disparities in Patients With Alcoholic Liver Disease Evaluated for Liver Transplantation
Authors: McElroy Lisa M. , Likhitsup Alisa , Scott Winder Gerald , Saeed Naba , Hassan Ammar , Sonnenday Christopher J. , Fontana Robert J. , Mellinger Jessica 
Published: July 2019

Background.
The morbidity and mortality from alcohol-related liver disease (ALD) is increasing in the United States. However, little is known about gender differences in evaluation and listing for liver transplantation (LT) in patients with ALD.

Methods.
This is a retrospective review of adult patients with ALD evaluated for LT at a single transplant center from January 1, 2010, to March 1, 2017. Univariate, multivariate, and time-series analyses were performed.

Results.
Among the 949 patients with ALD evaluated, mean age was 53 years, 84% were Caucasian, and 33% were women. The median model for end-stage liver disease score was similar between the genders. Women were less likely to be listed for LT (10% versus 19%; P < 0.05). The proportion of women not listed due to active substance use was significantly higher versus men (42% versus 35%; P < 0.05), while the frequency of medical contraindications was comparable between the genders. During a median follow-up of 416 days (range: 0–2784), listed women with ALD were less likely to undergo transplantation (42% versus 47%; P < 0.05).

Conclusions.
Men with ALD were 95% more likely to be listed and 105% more likely to be transplanted compared to women with ALD. While men had more lifetime substance use and related consequences, women had more psychiatric comorbidities and were less likely to be listed due to active alcohol and opioid use. Early detection and effective treatment of psychiatric and substance use disorders in women with ALD may improve their transplant eligibility.
Energetic disorder in perovskite/polymer solar cells and its relationship with the interfacial carrier losses
Authors: Yaghoobi Nia Narges , Méndez Maria , di Carlo Aldo , Palomares Emilio 
Published: July 2019

Previous reports have observed a direct relationship between the polymer poly(3-hexylthiophene) molecular weight (MW) and the perovskite solar cell (PSC) efficiency. Herein, we analyse how the differences in MW and the differences in energetic disorder influence the interfacial carrier losses in the PSCs under operation conditions and explain the observed differences.
This article is part of a discussion meeting issue ‘Energy materials for a low carbon future'.
Will organic thermoelectrics get hot?
Authors: Campoy-Quiles Mariano 
Published: July 2019

The generally low energy density from most heat sources—the Sun, Earth as well as most human activities—implies that solid-state thermoelectric devices are the most versatile heat harvesters since, unlike steam engines, they can be used on a small scale and at small temperature differences. In this opinion piece, we first discuss the materials requirements for the widespread use of thermoelectrics. We argue that carbon-based materials, such as conducting polymers and carbon nanotubes, are particularly suited for large area and low-temperature operation applications, as they are abundant, low-toxicity and easy to process. We combine experimentally observed macro-trends and basic thermoelectric relations to evaluate the major performance limitations of this technology thus far and propose a number of avenues to take the thermoelectric efficiency of organic materials beyond the state of the art. First, we emphasize how charge carrier mobility, rather than charge density, is currently limiting performance, and discuss how to improve mobility by exploiting anisotropy, high persistence length materials and composites with long and well-dispersed carbon nanotubes. We also show that reducing thermal conductivity could double efficiency while reducing doping requirements. Finally, we discuss several ways in which composites could further boost performance, introducing the concept of interface engineering to produce phonon stack-electron tunnel composites.
This article is part of a discussion meeting issue ‘Energy materials for a low carbon future'.
The effect of the genetic liability to autism spectrum disorder on emotion recognition in young unaffected probands from a population-based cohort
Authors: Wendt Frank R , Carvalho Carolina Muniz , Gelernter Joel , Polimanti Renato 
Published: July 2019

AbstractWe investigated how ASD genetic risk relates to neurodevelopmental features (491 traits tested) via polygenic risk scoring (PRS) in 4,309 young non-ASD probands from the Philadelphia Neurodevelopmental Cohort. ASD PRS most strongly associated with the ability to correctly identify angry facial emotions in youths aged 11-17 years (R2=1.06%, p=1.38×10−7) and replicated similarly in older probands (>18 years) (R2=0.55%, p=0.036). The association in 11- to-17-year-old probands was independent of other psychiatric disorders, brain imaging phenotypes, and educational attainment. ASD PRS also associated with proband-reported emotionality and connectedness with others. The proband-reported irritability trait was highly correlated with angry facial emotion recognition (r2=0.159, p=2.74×10−5) but was independently associated with ASD PRS (R2=1.20%, p=1.18×10−4). Several informant-reported (i.e., typically mother-reported) traits were predicted by the proband’s ASD PRS, including duration of fear (R2=0.156%, p=0.001). These data indicate how genetic liability to ASD may influence neurodevelopment in the general population, especially the development of emotional intelligence.
Bayesian spatial modelling of childhood cancer incidence in Switzerland using exact point data: A nationwide study during 1985-2015
Authors: Konstantinoudis Garyfallos , Schuhmacher Dominic , Ammann Roland A , Diesch Tamara , Kuehni Claudia E , Spycher Ben D ,   for the Swiss Paediatric Oncology Group and the Swiss National Cohort Study Group
Published: July 2019

AbstractBackgroundThe aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. We investigated the spatial variation of childhood cancers in Switzerland using exact geocodes of place of residence.MethodsWe included 5,947 children diagnosed with cancer during 1985-2015 at age 0-15 from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardization to adjust for age and year of diagnosis. We examined whether the modelled spatial variation of risk can be explained by ambient air concentration of NO2, natural background radiation, area-based socio-economic position (SEP), linguistic region, years of existing general cancer registration in the canton or degree of urbanization.ResultsFor all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for CNS tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was evidence of an association of background radiation and SEP with incidence of CNS tumours, (1.19;0.98-1.40) and (1.6;1-1.13) respectively.ConclusionOf the investigated diagnostic groups, childhood CNS tumours show the largest spatial variation in Switzerland. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role.
Impact of a regional educational advertising campaign on harm perceptions of e-cigarettes, prevalence of e-cigarette use, and quit attempts among smokers
Authors: Tattan-Birch Harry , Jackson Sarah E , Ide Charlotte , Bauld Linda , Shahab Lion 
Published: July 2019

ABSTRACTBackgroundWe evaluated how effective an advertising campaign that was piloted by Cancer Research UK in January/February 2018 was at promoting quit attempts by increasing awareness of the relative harms of e-cigarettes compared with smoking.MethodsAdults (≥16 years, n = 2217) living in Greater Manchester (campaign region) and Yorkshire & Humber and the North East of England (control regions) completed cross-sectional surveys immediately before and after the campaign period. Surveys measured socio-demographics, perceptions and use of e-cigarettes, and motivation and attempts to quit smoking. We tested interactions between time (pre, post) and region (campaign, control).Results36.7% (95% CI 33.0% – 40.6%) of those in the intervention region recognised the campaign. In the general population, interactions were non-significant for all outcomes except for perception of e-cigarettes as effective cessation aids, with smaller increases from pre-to post-campaign in the campaign (49.9% to 54.0%) compared with the control region (40.5% to 55.0%; OR = 0.66, 95% CI 0.45 – 0.98). Among smokers, motivation to quit increased in the intervention region (44.0% to 48.0%) but decreased in the control region (40.5% to 21.5%; OR = 2.97, 95% CI 1.25 – 7.16), with no other significant differences between regions over time. A Bayesian analysis confirmed that non-significant results were inconclusive.ConclusionsCompared with the control region, the campaign was associated with an increase in smokers’ motivation to quit but a smaller increase in adults’ perception of e-cigarettes as an effective cessation aid. There was insufficient evidence to determine whether the campaign affected other outcomes.