bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is there an optimal organ acceptance rate for pediatric heart transplantation: “A sweet spot”?
Authors: Park Chun Soo , Villa Chet R. , Lorts Angela , Chin Clifford , Tweddell James S. , Zafar Farhan , Morales David L. S. 
Published: January 2018

AbstractDespite a limited supply of donors, potential donor hearts are often declined for subjective concerns regarding organ quality. This analysis will investigate the relationship between donor heart AR and patient outcome at pediatric transplant centers. The UNOS database was used to identify all match runs for pediatric candidates (age < 18 years) from 2008 through March 2015 in which a heart offer was ultimately placed. Centers which received ≥10 offers/y were included (10 634 offers, 38 centers). Transplant centers were stratified based on their AR: low (<20%, n = 13), medium (20%‐40%, n = 16), or high (>40%, n = 9). Low AR centers experienced worse negative WL outcome compared with medium (P = .022) and high (P = .004) AR centers. Low AR centers had similar post‐transplant graft survival to medium (P = .311) or high (P = .393) AR centers; however, medium AR centers had better post‐transplant graft survival than high AR centers (P = .037). E‐F survival from listing regardless of transplant was worse for low AR centers compared with medium (P < .001) or high (P = .001) AR centers. Low AR centers experience worse WL outcomes without improvement in post‐transplant outcomes. High AR centers experience higher post‐transplant graft failure than medium AR centers. AR of 20%‐40% appears to have optimal WL and post‐transplant outcomes.
Did parents have it right all along? Parents, risk, and living kidney donation: Revisiting the arguments for and against parental living donation of kidneys
Authors: Freeman M. A. , Wightman A. G. 
Published: January 2018

AbstractHistorically, living kidney donation has been justified in part by our belief that living donors face minimal risks of subsequent disease. Recent research has brought that presumption into question, particularly for younger donors including parents. In light of this finding, we re‐examine many of the traditional arguments both for and against the practice of parental living kidney donation. We then propose an alternative framework in which the burden of having a child with end‐stage kidney disease can be considered as an illness experienced by the potential donor parent. We believe this allows a more straightforward, as well as more accurate, assessment of the risks and benefits of donation for the potential parental donor. This assessment might then be used to best inform the decision whether or not to proceed with kidney donation using a shared decision‐making model, while reflecting the appropriate ethical roles of both the potential donor and the transplantation program.
Trends in pediatric liver transplant donors and deceased donor circumstance of death in the United States, 2002‐2015
Authors: Yoeli Dor , Goss Matthew , Galván Nhu. Thao N. , Desai Moreshwar S. , Miloh Tamir A. , Rana Abbas 
Published: January 2018

AbstractWhile much of the discussion regarding expanding the donor pool for pediatric liver transplantation has surrounded the use of technical variant grafts, little attention has been directed toward changes in the deceased donor population. The aim of this study was to investigate trends in the circumstance of the death of deceased donors used for pediatric liver transplantation. All pediatric liver transplant recipients transplanted between 2002 and 2015 were identified in the UNOS database and were categorized based on the donor circumstance of death. There was no significant correlation between year of transplantation and number of pediatric liver transplants performed, pediatric donors, split livers, or living donors. There was a significant downward trend in donors from motor vehicle fatalities and an upward trend in suicide, non‐MVA, and death due to natural causes. There was also an upward trend in drowning, one of the most common mechanisms of death among non‐MVA in 2015. While the number of donors who died in MVA has fallen, the number of deceased donors who died from suicide, natural causes, and non‐MVA, especially drowning, has increased, maintaining the overall number of pediatric deceased donor livers transplanted.
Influence of visible light on cutaneous hyperchromias: Clinical efficacy of broad‐spectrum sunscreens
Authors: Martini Ana Paula M. , Maia Campos Patricia M. B. G. 
Published: January 2018

SummaryIntroductionCutaneous hyperchromias are disorders of skin pigmentation involving increased melanin production and its irregular accumulation in skin cells. The use of sunscreens is fundamental for the control of hyperchromias by reducing the stimulation of pigmentation, as melanin synthesis is mainly stimulated by solar radiation. Many studies have demonstrated that visible light can induce significant skin damage. Considering the effects of visible light, effective photoprotection should not be limited only to UV protection but should also involve visible and infrared protection.ObjectiveThe aim of this study was to evaluate the efficacy of UV‐VIS sunscreens in protecting skin against damages caused by solar radiation and the influence of visible light on the appearance of cutaneous hyperchromias.MethodsForty volunteers aged 18 to 39 years with skin hyperpigmentation participated in the study. To evaluate the efficacy of the formulations developed, the percentage of hyperpigmented area was evaluated using high‐resolution images—Visioface® Quick (Courage‐Khazaka, Germany) and the analysis of epidermal pigmentation was performed by RCM—Vivascope® 1500 (Lucid, USA). Also, the melanin index was determined using the Mexameter® M X16 colorimeter (Courage‐Khazaka, Germany).ResultsThe developed formulations were effective in the reduction in melanin index, epidermal pigmentation, and percentage of hyperpigmented area.ConclusionFinally, this study discusses how the combination of UV filters and pigments can protect the skin from solar radiation and reduces skin hyperpigmentations.
Zinc treatment of hydroponically grown barley plants causes a reduction in root and cell hydraulic conductivity and isoform‐dependent decrease in aquaporin gene expression
Authors: Gitto Aurora , Fricke Wieland 
Published: January 2018

The cellular and molecular basis of a reduction in root water uptake in plants exposed to heavy metals such as zinc (Zn) is poorly studied. The aim of the present study on hydroponically grown barley (Hordeum vulgare) was to test whether any reduction in root hydraulic conductivity (Lp) in response to Zn treatment is accompanied by a reduction in cell Lp and gene expression level of aquaporin (AQP) isoforms. Plants were grown in the presence of 0.25 μM, (control), 0.1 and 1 mM Zn in the root medium and analysed when they were 16–18 days old. Root and cell Lp was determined through exudation and cell pressure probe analyses, respectively, and gene expression of five candidate AQPs was analysed [real time quantitative polymerase chain reaction (PCR)]. Zinc treatments caused significant reductions (25–83%) in transpiration rate, root and shoot fresh weight, surface area and stomatal conductance. Zinc concentrations in tissues increased more than 100‐fold. Root Lp decreased by 24% (0.1 mM Zn) and 58% (1 mM Zn), while cell Lp decreased by 45 and 71%, respectively. Gene expression of AQPs decreased by 14–80%; decreases were statistically significant for HvPIP1;3, HvPIP2;4 and HvPIP2;5. Turgor in root cortex cells was not reduced by Zn treatments. It is concluded that reductions in plant water flow in response to Zn treatment are facilitated through decreases in root (Lp) and shoot (stomata) hydraulics. The decrease in root Lp is facilitated through reductions in cell Lp and AQP gene expression and may also reflect increased suberization in the endodermis.
Safety and efficacy of foscarnet for the management of ganciclovir‐resistant or refractory cytomegalovirus infections: A single‐center study
Authors: Pierce Brett , Richardson Chad L. , Lacloche Lisa , Allen Anne , Ison Michael G. 
Published: January 2018

AbstractBackgroundInfection with cytomegalovirus (CMV) is an important cause of morbidity and mortality following solid organ transplantation. Resistance to ganciclovir can rarely develop via mutations in UL97 or UL54. There are limited published studies assessing the safety and efficacy of foscarnet for the management of ganciclovir‐resistant or refractory cytomegalovirus infection and many centers are reluctant to utilize this important therapy because of concerns about toxicity.MethodsSolid organ recipients transplanted between January 1, 2006 and December 31, 2014 who received at least 1 dose of foscarnet were retrospectively reviewed to assess treatment outcomes, tolerability, and safety of foscarnet.ResultsTen of 31 (32.3%) patients who received foscarnet during the study period died during treatment with foscarnet, whereas all 21 surviving recipients successfully cleared infection. Of these surviving patients, 3 (14.3%) developed significant renal dysfunction, defined as >25% decline in estimated glomerular filtration rate during treatment; one‐third had definitive renal biopsy results consistent with foscarnet‐induced toxicity.ConclusionAlthough mortality was high in this population, foscarnet use, with proper precautions, was generally safe and significant renal dysfunction was lower than previously reported in other sources, even with extended use.
Network geometry of evidence from randomised controlled trials addressing donor selection and source of haematopoietic progenitor cells used in allogeneic transplantation: a systematic scoping review
Authors: Monaghan M. , Rizk M. , Pilon S. , Iyengar A. , Shorr R. , Tay J. , Maze D. , Bredeson C. , Hutton B. , Allan D. S. 
Published: January 2018

SUMMARYBackground and MethodsA scoping review of randomised controlled trials (RCTs) addressing source of cells and choice of donor for allogeneic haematopoietic cell transplantation (HCT) was performed to create a network of best evidence that allows us to identify new potential indirect comparisons for the strategic development of future studies that connect to the existing evidence network.ResultsA total of 19 eligible RCTs (2589 total patients) were identified. Nine studies (1566 patients) compared clinical outcomes following the use of peripheral blood progenitor cells (PBPCs) with bone marrow (BM) from matched related donors (eight studies) or matched unrelated donors (one study). The remaining studies compared BM or PBPCs with various methods of BM stimulation or manipulation (six studies), compared different methods of surface molecule‐based selection and/or depletion of grafts (two studies) or compared the optimal number of units for paediatric cord blood transplantation (two studies). No published RCTs compared different types of donors. The geometry of the evidence network was analysed to identify opportunities for potential novel indirect comparisons and to identify opportunities to expand the network. Few indirect comparisons are currently feasible due to small sample size and heterogeneity in patient diagnoses and demographics between treatment nodes in the network.ConclusionMore RCTs that enrol greater numbers of similar patients are needed to leverage the current evidence network concerning donor choice and source of cells used in allogeneic HCT.
Centromeric DNA characterization in the model grass Brachypodium distachyon provides insights on the evolution of the genus
Authors: Li Yinjia , Zuo Sheng , Zhang Zhiliang , Li Zhanjie , Han Jinlei , Chu Zhaoqing , Hasterok Robert , Wang Kai 
Published: January 2018

SummaryBrachypodium distachyon is a well‐established model monocot plant, and its small and compact genome has been used as an accurate reference for the much larger and often polyploid genomes of cereals such as Avena sativa (oats), Hordeum vulgare (barley) and Triticum aestivum (wheat). Centromeres are indispensable functional units of chromosomes and they play a core role in genome polyploidization events during evolution. As the Brachypodium genus contains about 20 species that differ significantly in terms of their basic chromosome numbers, genome size, ploidy levels and life strategies, studying their centromeres may provide important insight into the structure and evolution of the genome in this interesting and important genus. In this study, we isolated the centromeric DNA of the B. distachyon reference line Bd21 and characterized its composition via the chromatin immunoprecipitation of the nucleosomes that contain the centromere‐specific histone CENH3. We revealed that the centromeres of Bd21 have the features of typical multicellular eukaryotic centromeres. Strikingly, these centromeres contain relatively few centromeric satellite DNAs; in particular, the centromere of chromosome 5 (Bd5) consists of only ~40 kb. Moreover, the centromeric retrotransposons in B. distachyon (CRBds) are evolutionarily young. These transposable elements are located both within and adjacent to the CENH3 binding domains, and have similar compositions. Moreover, based on the presence of CRBds in the centromeres, the species in this study can be grouped into two distinct lineages. This may provide new evidence regarding the phylogenetic relationships within the Brachypodium genus.
Grapevine field experiments reveal the contribution of genotype, the influence of environment and the effect of their interaction (G×E) on the berry transcriptome
Authors: Dal Santo Silvia , Zenoni Sara , Sandri Marco , De Lorenzis Gabriella , Magris Gabriele , De Paoli Emanuele , Di Gaspero Gabriele , Del Fabbro Cristian , Morgante Michele , Brancadoro Lucio , Grossi Daniele , Fasoli Marianna , Zuccolotto Paola , Tornielli Giovanni Battista , Pezzotti Mario 
Published: January 2018

SummaryChanges in the performance of genotypes in different environments are defined as genotype × environment (G×E) interactions. In grapevine (Vitis vinifera), complex interactions between different genotypes and climate, soil and farming practices yield unique berry qualities. However, the molecular basis of this phenomenon remains unclear. To dissect the basis of grapevine G×E interactions we characterized berry transcriptome plasticity, the genome methylation landscape and within‐genotype allelic diversity in two genotypes cultivated in three different environments over two vintages. We identified, through a novel data‐mining pipeline, genes with expression profiles that were: unaffected by genotype or environment, genotype‐dependent but unaffected by the environment, environmentally‐dependent regardless of genotype, and G×E‐related. The G×E‐related genes showed different degrees of within‐cultivar allelic diversity in the two genotypes and were enriched for stress responses, signal transduction and secondary metabolism categories. Our study unraveled the mutual relationships between genotypic and environmental variables during G×E interaction in a woody perennial species, providing a reference model to explore how cultivated fruit crops respond to diverse environments. Also, the pivotal role of vineyard location in determining the performance of different varieties, by enhancing berry quality traits, was unraveled.
An integrated multi‐layered analysis of the metabolic networks of different tissues uncovers key genetic components of primary metabolism in maize
Authors: Wen Weiwei , Jin Min , Li Kun , Liu Haijun , Xiao Yingjie , Zhao Mingchao , Alseekh Saleh , Li Wenqiang , de Abreu e Lima Francisco , Brotman Yariv , Willmitzer Lothar , Fernie Alisdair R. , Yan Jianbing 
Published: January 2018

SUMMARYPrimary metabolism plays a pivotal role in normal plant growth, development and reproduction. As maize is a major crop worldwide, the primary metabolites produced by maize plants are of immense importance from both calorific and nutritional perspectives. Here a genome‐wide association study (GWAS) of 61 primary metabolites using a maize association panel containing 513 inbred lines identified 153 significant loci associated with the level of these metabolites in four independent tissues. The genome‐wide expression level of 760 genes was also linked with metabolite levels within the same tissue. On average, the genetic variants at each locus or transcriptional variance of each gene identified here were estimated to have a minor effect (4.4–7.8%) on primary metabolic variation. Thirty‐six loci or genes were prioritized as being worthy of future investigation, either with regard to functional characterization or for their utility for genetic improvement. This target list includes the well‐known opaque 2 (O2) and lkr/sdh genes as well as many less well‐characterized genes. During our investigation of these 36 loci, we analyzed the genetic components and variations underlying the trehalose, aspartate and aromatic amino acid pathways, thereby functionally characterizing four genes involved in primary metabolism in maize.
Hypothalamic and liver transcriptome from two crucial life‐history stages in a migratory songbird
Authors: Sharma Aakansha , Singh Devraj , Das Subhajit , Kumar Vinod 
Published: January 2018

New Findings
What is the central question of this study?
What are the molecular underpinnings of the seasonal adaptation in a latitudinal migratory songbird?

What is the main finding and its importance?
We found changes in mRNA levels after a photoperiod‐induced alteration of seasonal state in a captive long‐distance latitudinal avian migrant. The hypothalamus and liver transcriptomes revealed genes involved in the regulatory and functional pathways between non‐migratory and migratory states. Our results provide insights into mechanisms underlying homeostasis during seasonal changes that are conserved across most species, including humans.

AbstractVery little is understood about genetic mechanisms underlying the onset of spring migration in latitudinal avian migrants. To gain insight into the genetic architecture of the hypothalamus and liver tissues of a long‐distance migrant, we examined and compared the transcriptome profile of captive night‐migratory black‐headed buntings (Emberiza melanocephala) between photoperiod‐induced winter non‐migratory (WnM) and spring migratory (SM) life‐history states under short and long days, respectively. High‐throughput 454 pyrosequenced transcripts were mapped initially with reference to the genome of two phylogenetically close species, Taeniopygia guttata and Ficedula albicollis. The F. albicollis genome gave higher annotation results and was used for further analysis. A total of 216 (78 in hypothalamus; 138 in liver) genes were found to be expressed differentially between the WnM and SM life‐history states. These genes were enriched for physiological pathways that might be involved in the regulation of seasonal migrations in birds. For example, genes for the ATP binding pathway in the hypothalamus were expressed at a significantly higher level in SM than in the WnM life‐history state. Likewise, upregulated genes associated with the myelin sheath and focal adhesion were enriched in the hypothalamus, and those with cell‐to‐cell junction, intracellular protein transport, calcium ion transport and small GTPase‐mediated signal transduction were enriched in the liver. Many of these genes are a part of physiological pathways potentially involved in the regulation of seasonal migration in birds. These results show molecular changes at the regulatory and metabolic levels associated with seasonal transitions in a long‐distance migrant and provide the basis for future studies aimed at unravelling the genetic control of migration in birds.
Endothelial immune activation programmes cell‐fate decisions and angiogenesis by inducing angiogenesis regulator DLL4 through TLR4‐ERK‐FOXC2 signalling
Authors: Xia Sheng , Menden Heather L. , Korfhagen Thomas R. , Kume Tsutomu , Sampath Venkatesh 
Published: January 2018

Key points
The mechanisms by which bacteria alter endothelial cell phenotypes and programme inflammatory angiogenesis remain unclear.
In lung endothelial cells, we demonstrate that toll‐like receptor 4 (TLR4) signalling induces activation of forkhead box protein C2 (FOXC2), a transcriptional factor implicated in lymphangiogenesis and endothelial specification, in an extracellular signal‐regulated kinase (ERK)‐dependent manner.
TLR4‐ERK‐FOXC2 signalling regulates expression of the Notch ligand DLL4 and signals inflammatory angiogenesis in vivo and in vitro.
Our work reveals a novel link between endothelial immune signalling (TLR pathway) and a vascular transcription factor, FOXC2, that regulates embryonic vascular development.
This mechanism is likely to be relevant to pathological angiogenesis complicating inflammatory diseases in humans.
AbstractEndothelial cells (ECs) mediate a specific and robust immune response to bacteria in sepsis through the activation of toll‐like receptor (TLR) signalling. The mechanisms by which bacterial ligands released during sepsis programme EC specification and altered angiogenesis remain unclear. We postulated that the forkhead box protein C2 (FOXC2) transcriptional factor directs EC cell‐fate decisions and angiogenesis during TLR signalling. In human lung ECs, lipopolysaccharide (LPS) induced ERK phosphorylation, FOXC2, and delta‐like 4 (DLL4, the master regulator of sprouting angiogenesis expression) in a TLR4‐dependent manner. LPS‐mediated ERK phosphorylation resulted in FOXC2‐ERK protein ligation, ERK‐dependent FOXC2 serine and threonine phosphorylation, and subsequent activation of DLL4 gene expression. Chemical inhibition of ERK or ERK‐2 dominant negative transfection disrupted LPS‐mediated FOXC2 phosphorylation and transcriptional activation of FOXC2. FOXC2‐siRNA or ERK‐inhibition attenuated LPS‐induced DLL4 expression and angiogenic sprouting in vitro. In vivo, intraperitoneal LPS induced ERK and FOXC2 phosphorylation, FOXC2 binding to DLL4 promoter, and FOXC2/DLL4 expression in the lung. ERK‐inhibition suppressed LPS‐induced FOXC2 phosphorylation, FOXC2‐DLL4 promoter binding, and induction of FOXC2 and DLL4 in mouse lung ECs. LPS induced aberrant retinal angiogenesis and DLL4 expression in neonatal mice, which was attenuated with ERK inhibition. FOXC2+/− mice treated with LPS showed a mitigated increase in FOXC2 and DLL4 compared to FOXC2+/+ mice. These data reveal a new mechanism (TLR4‐ERK‐FOXC2‐DLL4) by which sepsis‐induced EC TLR signalling programmes EC specification and altered angiogenesis.