bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review of Molecular Autopsy Studies in Sudden Infant Death Cases
Authors: Martin Lorna , Ramesar Raj , Heathfield Laura 
Published: August 2018

AbstractSudden unexpected death is an upsetting event, which can remain unexplained even after post-mortem investigation. Internationally, molecular autopsies have shown to resolve up to 44% of unexplained cases; however, it is currently unclear how many of these were infants. This systematic literature review showed that significantly fewer infant cases were resolved (median: 4%) compared with cohorts of 1 to 45 years old (median: 32%). Further, no study involving indigenous African participants has yet been published. Overall, molecular autopsies hold immense value to living family members and is motivation to explore new avenues in infant cohorts.
Use of Vascularized Fibular Free Flap in the Reconstruction of the Femur in Pediatric and Adolescent Bone Sarcomas: Complications and Functional Outcome
Authors: Sherbiny Magdy , Kamal Nehal , Ghoneimy Ahmed 
Published: August 2018

Background Most reports on skeletal reconstruction using vascularized fibular free flap include patients with varying age groups and anatomic locations. This study has limited the inclusion criteria to pediatric and adolescent patients diagnosed with bone sarcoma of the femoral shaft.
Methods Forty-one patients, diagnosed with a malignant bone tumor of the femoral shaft (21 Ewing's sarcomas and 20 osteosarcomas), were locally treated by joint sparing wide resection and reconstruction using a vascularized fibular free flap. All clinical and radiographic data were reviewed for graft healing and hypertrophy as well as oncologic and functional outcome.
Results The mean follow-up period was 48.7 months (12–104 months). The mean age at presentation was 10.3 years (5–17 years). The average length of the resected femoral shaft was 19.2 cm (15–24 cm) and the average length of the harvested fibula was 17.4 cm (15–21 cm). The mean time to union was 4.8 months (1–6 months) and the mean hypertrophy index was 78% (15.5–184%). Complications included 12 fractures (33.3%), 5 non-unions (13.8%), and 5 failures of graft hypertrophy (13.8%). At the latest clinical evaluation, the mean MSTS score was 81% (56–100%) and the mean limb length inequality was 4.75 cm (3–11 cm).
Conclusion Despite the high functional demand and deleterious effect of chemotherapy on bone healing, reconstruction of the femur by vascularized fibular free flap in pediatric bone sarcomas can lead to a good functional outcome. Complications, such as fracture and non-union, can be successfully treated by revision of fixation and autologous iliac crest grafting.
Level of Evidence IV.
Microsurgery Training Resource Variation among US Integrated Plastic Surgery Residency Programs
Authors: Mueller Melissa , Pourtaheri Navid , Evans Gregory 
Published: August 2018

Background Given emerging focus on competency-based surgical training and work-hour limitations, surgical skills laboratories play an increasingly important role in resident education. This study was designed to investigate educational opportunities in microsurgery across integrated residency programs.
Methods Senior residents (PGY 4–6) at integrated plastic surgery programs were surveyed during the 2016 to 2017 academic year to determine each program's access to: training microscopes and anastomosis models, video-based skills assessment, pre-requisite skills exams, flap courses, or a formal microsurgical training curriculum. Programs were stratified based on large size (>18 residents) and presence of microsurgery fellows. Chi-squared analysis was performed with p < 0.05 to assess statistical significance.
Results Survey responses were collected from 32 of 60 eligible programs (53% response rate). Sixty-nine percent provide access to one to two training microscopes, 25% provide three or more, and 6% provide none. Sixty-nine percent of programs train anastomosis with nonliving prosthetics, 66% with living biologics, and 50% with nonliving biologics. Large program size or having microsurgical fellows was not associated with increased access to training microscopes or specific anastomosis models. Programs without microsurgery fellows reported more often that a formal microsurgery curriculum would be helpful (90 vs. 58% of programs with fellows, p = 0.0003). Respondents who indicated that creating a formal curriculum would not be helpful elaborated that their program already has a formal curriculum or a high volume of microsurgery cases.
Conclusion This study demonstrates the current variation in microsurgery training at integrated plastic surgery residency programs. A formal microsurgical training curriculum is commonly viewed as being helpful, particularly at programs without microsurgery fellows.
Enzymatic characterization of an extracellular glucoamylase from Tricholoma matsutake and its cloning and secretory expression in Pichia pastoris
Authors: Onuma Hiroki , Uchiyama Hiroto , Hara Kento , Fukuta Yasuhisa , Shirasaka Norifumi 
Published: August 2018

ABSTRACT
A glucoamylase from the ectomycorrhizal fungus Tricholoma matsutake (TmGLA) was purified 33.2-fold to homogeneity as a single monomeric glycoprotein with a molecular mass of 63.9 kDa. Maximum activity was observed at 60°C and pH 5.0. The enzyme is active down to 50°C and in the pH range of 4.0–6.0, and its activity is strongly inhibited by Ag+. It degrades α-1,4- and α-1,6-glycosidic linkages in various polysaccharides. Its gene (TmGlu1) was cloned using information from the enzyme’s internal amino acid sequences and the whole genome sequence of T. matsutake NBRC 30605. The deduced amino acid sequence showed clear homology with those of GH family 15 proteins. Pichia pastoris transformed with TmGlu1 secreted the active enzyme in a glycosylated form, and its characteristics were the same as the native enzyme.
Responses of the chloroplast glyoxalase system to high CO2 concentrations
Authors: Shimakawa Ginga , Ifuku Kentaro , Suzuki Yuji , Makino Amane , Ishizaki Kimitsune , Fukayama Hiroshi , Morita Ryutaro , Sakamoto Katsuhiko , Nishi Akiko , Miyake Chikahiro 
Published: August 2018

ABSTRACT
Sugar metabolism pathways such as photosynthesis produce dicarbonyls, e.g. methylglyoxal (MG), which can cause cellular damage. The glyoxalase (GLX) system comprises two enzymes GLX1 and GLX2, and detoxifies MG; however, this system is poorly understood in the chloroplast, compared with the cytosol. In the present study, we determined GLX1 and GLX2 activities in spinach chloroplasts, which constituted 40% and 10%, respectively, of the total leaf glyoxalase activity. In Arabidopsis thaliana, five GFP-fusion GLXs were present in the chloroplasts. Under high CO2 concentrations, where increased photosynthesis promotes the MG production, GLX1 and GLX2 activities in A. thaliana increased and the expression of AtGLX1-2 and AtGLX2-5 was enhanced. On the basis of these findings and the phylogeny of GLX in oxygenic phototrophs, we propose that the GLX system scavenges MG produced in chloroplasts during photosynthesis.
Plasmid copy number mutation in repA gene encoding RepA replication initiator of cryptic plasmid pHM1519 in Corynebacterium glutamicum
Authors: Hashiro Shuhei , Yasueda Hisashi 
Published: August 2018

ABSTRACT
Cryptic plasmid pHM1519 is a rolling-circular replication mode plasmid of the pCG1 plasmid family in coryneform bacteria. The derived shuttle vector pPK4 is maintained at about 40–50 copies per chromosome in Corynebacterium glutamicum 2256 (ATCC 13869). We found that a mutation (designated copA1) within the repA gene encoding essential initiator protein RepA of the pHM1519-replicon increased the copy number of the mutant plasmid to about 800 copies per chromosome. The mutation was a single G to A base transition, which changed Gly to Glu at position 429 of the amino acid sequence of RepA. In silico secondary structure prediction of RepA suggested that Gly429 is situated in a disordered region in a helix-turn-helix motif, which is a typical DNA-binding domain. This study shows the first example of a high copy number of a C. glutamicum cryptic plasmid caused by an altered replication initiator protein.
Predictive cluster level surrogacy in the presence of interference
Authors: Gabriel Erin E , Follmann Dean A 
Published: August 2018

Summary
Surrogate evaluation is a difficult problem that is made more so by the presence of interference. Our proposed procedure can allow for relatively easy evaluation of surrogates for indirect or spill-over clinical effects at the cluster level. Our definition of surrogacy is based on the causal-association paradigm (Joffe and Greene, 2009. Related causal frameworks for surrogate outcomes. Biometrics65, 530–538), under which surrogates are evaluated by the strength of the association between a causal treatment effect on the clinical outcome and a causal treatment effect on the candidate surrogate. Hudgens and Halloran (2008, Toward causal inference with interference. Journal of the American Statistical Association103, 832–842) introduced estimators that can be used for many of the marginal causal estimands of interest in the presence of interference. We extend these to consider surrogates for not just direct effects, but indirect and total effects at the cluster level. We suggest existing estimators that can be used to evaluate biomarkers under our proposed definition of surrogacy. In our motivating setting of a transmission blocking malaria vaccine, there is expected to be no direct protection to those vaccinated and predictive surrogates are urgently needed. We use a set of simulated data examples based on the proposed Phase IIb/III trial design of transmission blocking malaria vaccine to demonstrate how our definition, proposed criteria and procedure can be used to identify biomarkers as predictive cluster level surrogates in the presence of interference on the clinical outcome.
Establishment of a Macaca fascicularis gut microbiome gene catalog and comparison with the human, pig, and mouse gut microbiomes
Authors: Li Xiaoping , Liang Suisha , Xia Zhongkui , Qu Jing , Liu Huan , Liu Chuan , Yang Huanming , Wang Jian , Madsen Lise , Hou Yong , Li Junhua , Jia Huijue , Kristiansen Karsten , Xiao Liang 
Published: August 2018

Abstract
Macaca fascicularis, the cynomolgus macaque, is a widely used model in biomedical research and drug development as its genetics and physiology are close to those of humans. Detailed information on the cynomolgus macaque gut microbiota, the functional interplay between the gut microbiota and host physiology, and possible similarities to humans and other mammalians is very limited. The aim of this study was to construct the first cynomolgus macaque gut microbial gene catalog and compare this catalog to the human, pig, and mouse gut microbial gene catalogs. We performed metagenomic sequencing on fecal samples from 20 cynomolgus macaques and identified 1.9 million non-redundant bacterial genes of which 39.49% and 25.45% are present in the human and pig gut bacterial gene catalogs, respectively, whereas only 0.6% of the genes are present in the mouse gut bacterial gene catalog. By contrast, at the functional levels, more than 76% Kyoto Encyclopedia of Genes and Genomes orthologies are shared between the gut microbiota of all four mammalians. Thirty-two highly abundant bacterial genera could be defined as core genera of these mammalians. We demonstrated significant differences in the composition and functional potential of the gut microbiota as well as in the distribution of predicted bacterial phage sequences in cynomolgus macaques fed either a low-fat/high-fiber diet or a high-fat/low-fiber diet. Interestingly, the gut microbiota of cynomolgus macaques fed the high-fat/low-fiber diet became more similar to the gut microbiota of humans.
Opening of the Norway pout box: will it change the ecological impacts of the North Sea Norway pout fishery?
Authors: Bigné Matthieu , Nielsen J Rasmus , Bastardie François 
Published: August 2018

Abstract
The small-mesh Norway pout (Trisopterus esmarkii) fishery intensified in the northern North Sea during the 1970s. Concerns about juvenile gadoid bycatch led to the “Norway pout box” closure along the Scottish coast in 1977. To assess the justification of the box today and the potential current impacts of opening the box, we evaluate the closure effects on selected fish stocks by analysing high-resolution research survey and commercial fishery data. The species- and size-specific distribution patterns in relation to environmental influencing factors are analysed for Norway pout and important bycatch species inside and outside the box. Relative distribution of benthic habitats is compared between inside–outside areas according to fish occurrence and fishery spatial footprint. No area differences in fish size composition are observed. However, species abundance depends significantly on habitat and depth whose area distribution is not homogenous. The current fishery is mainly in deeper, muddy seabeds. Haddock (Melanogrammus aeglefinus) and whiting (Merlangius merlangus) density is higher in shallow and sandy habitats, with a relatively larger area coverage inside the box. If a box opening implies relatively more fishery in those habitats, then increased bycatch can be expected. Consequently, closure of certain benthic habitats may instead be better management, opening new fishing opportunities without risk.
Dredging-induced turbid plumes affect bio-irrigation and biogeochemistry in sediments inhabited by Lanice conchilega (Pallas, 1766)
Authors: Mestdagh Sebastiaan , Ysebaert Tom , Moens Tom , Van Colen Carl 
Published: August 2018

Abstract
Building man-made structures in coastal seas are often preceded by dredging operations, inducing turbid plumes of suspended sediment. To study the effects of such high-concentration sediment plumes on the suspension-feeding polychaete Lanice conchilega, a laboratory experiment was performed, in which individuals of L. conchilega were exposed to natural seawater with a suspended sediment concentration (SSC) of ∼ 0.3 g l−1 and treatments with elevated SSC of 5 and 1 g l−1, representing concentrations in a dredging plume at the moment of sediment release and after initial dilution, respectively. We measured clearance rates of sediment particles, biogeochemical fluxes, and bio-irrigation. While clearance rates and nitrite efflux significantly increased in both treatments with elevated SSC compared with the control, bio-irrigation increased at 1 g l−1 but was lowest at 5 g l−1. It is suggested that piston pumping is intensified under intermediate concentrations to remove sediment, but ceases under high concentrations are due to sediment ingestion. By transporting oxygen into the sediment, bio-irrigation enhances aerobic microbial processes, among which nitrification. We conclude that short-term extreme suspended sediment concentrations can have a significant impact on the biogeochemistry of the seabed through changes in behaviour of L. conchilega.
An evolutionary perspective on the origin of the cardiovascular system of vertebrates
Authors: Oostra Roelof-Jan , Jensen Bjarke , Moorman Antoon F.M. 
Published: August 2018

Abstract
The origin of the cardiovascular system of vertebrates is inferred from comparisons of basal chordates but must also encompass bewildering discrepancies. Basal chordates like lancelets (cephalochordates) have a vascular pattern similar to that of a vertebrate embryo, but without a recognizable heart or myocardium. Instead, the ‘venous’ part of their circulation contains contractile vessels, located upstream and downstream of the liver. Tunicates (urochordates) have a tubular heart containing cardiomyocytes and enclosed by a pericardium. Their circulation is open and the dominant pacemaker activity can be at either end of the heart tube, causing blood flow to reverse periodically. Recent molecular investigations have proved that urochordates rather than cephalochordates are the closest living relatives of vertebrates. This implies that the cardiovascular peculiarities of lancelets may be primitive ancestral qualities and that the original building plan of the vertebrate circulation featured a post-hepatic as well as a pre-hepatic cardiac pump.
From epiblast to mesoderm: elaboration of a fate map for cardiovascular progenitors
Authors: Lopez-Sanchez Carmen , Garcia-Lopez Virginio , Schoenwolf Gary C. , Garcia-Martinez Virginio 
Published: August 2018

Abstract
The origin and migration of cardiovascular progenitors have been identified using multiple cell fate mapping techniques monitoring marked epiblast cells through time at carefully defined stages of early gastrulation. These studies have revealed that ordered groups of cells from the epiblast move into the anterior region of the primitive streak, and then migrate anterior laterally to define the first heart field in the mesodermal layer. Subsequently, the right and left components of the first heart field fuse into a single straight heart at the embryonic midline. Additional cells derived from the second heart field are added to the cardiac tube and contribute to further heart development. Heterotopic and heterochronic transplantation studies have revealed that cardiac precursor cells are plastic and do not form a specific subpopulation of the cardiac mesoderm. Specification of the heart fields occurs after ingression of precardiac cells through the primitive streak.
Cardiac fields and myocardial cell lineages
Authors: De Bono Christopher , Théveniau-Ruissy Magali , Kelly Robert G. 
Published: August 2018

Abstract
We focus on the origin of myocardial cells in the first and second heart fields in splanchnic mesoderm in the early embryo. Genetic lineage tracing using Cre recombinase activated conditional reporter genes has made a major contribution to our understanding of cardiac progenitor cells and will be discussed together with other experimental approaches to analysing cell lineages at the clonal level. Interactions between myocardial, epicardial and endocardial lineages are essential for coordinated function and homeostasis of the normal heart. Perturbation of heart field development and myocardial lineage contributions to the heart through developmental or acquired pathologies results in and modulates the progression of cardiac disease. Understanding the origin of myocardial lineages during embryonic development and how they converge to generate an integrated heart is thus a major biomedical objective. Furthermore, reactivation of developmental programmes is likely to be of major importance in strategies aimed at repair of the damaged heart.
Transcriptional regulation of early cardiovascular development
Authors: Fulcoli F. Gabriella , Baldini Antonio 
Published: August 2018

Abstract
The two major cardiac cell lineages of the vertebrate heart, the first and second cardiac fields (FHF and SHF), have different developmental ontogeny and thus different transcription programs. Most remarkably, the fate of cardiac progenitors (CPs) of the FHF is restricted to cardiomyocyte differentiation. In contrast, SHF CPs, which are specified independently, are maintained in a multipotent state for a relatively longer developmental time and can differentiate into multiple cell types. The identity of the transcription factors and regulatory elements involved in progenitor cell programming and fate are only now beginning to emerge. Apparent inconsistencies between studies based on tissue culture and in vivo embryonic studies confirm that the ontogeny of cardiac progenitors is strongly driven or affected by regionalization, and thus by the signals that they receive in different regions. This chapter summarizes current knowledge about transcription factors and mechanisms driving CP ontogeny, with special focus on SHF development.
The developmental origin of myocardium at the venous pole of the heart
Authors: van Wijk Bram , Barnett Phil , van den Hoff Maurice J.B. 
Published: August 2018

Abstract
The focus of this chapter is an evaluation of the developmental origin of the myocardial component of the venous pole. The venous pole has a complex morphological architecture, reflecting its embryological and evolutionary development from several component parts. We describe the developmental changes observed in the architecture of the inflow of the heart and the large vessels that drain into the venous pole. As the formation of the proepicardium and the epicardial-derived cells are intimately connected to the forming inflow, this topic will also be covered. We compare the development of the inflow in chicken, mouse, and human. We then review the results obtained using the two-component genetic mouse system Cre-LoxP with respect to the myocardial components added to the forming cardiac inflow. These data are discussed within the now discriminated first, second, and third heart fields.
Cardiac growth I: Cardiomyocyte proliferation
Authors: Meilhac Sigolène M. 
Published: August 2018

Abstract
Efficient contraction of the heart depends on the size and oriented architecture of the myocardium. This is severely compromised by myocardial infarction or in cardiomyopathies. Deciphering the mechanisms underlying heart growth has attracted much attention over the past decade, after the demonstration that the mammalian heart has some potential to regenerate, thus raising hopes that heart repair may become a reality. The mechanisms of cardiac growth during development have been well studied in the mouse model, taking advantage of sophisticated genetic engineering and new tools for tracking cell lineages and behaviour. We discuss the current view of the intrinsic regulation of cardiomyocyte behaviour, as well as how it is modulated by interplay with other cardiac cell types or with the environment. Such fundamental knowledge is important for understanding the origin of congenital heart defects and for the development of novel strategies of heart repair.
Cardiac growth II: Cardiomyocyte polarization
Authors: Zaffran Stéphane 
Published: August 2018

Abstract
During vertebrate embryogenesis, the planar cell polarity (PCP) signalling pathway is responsible for cell movements essential for convergent extension during gastrulation, neural tube closure, neural crest cell migration, and heart morphogenesis. In the heart, the non-canonical Wnt/PCP pathway regulates cell polarity, cell shape, and cell dynamics during formation of the cardiac crescent and deployment of second heart field cardiac progenitors to the poles of the heart tube. PCP signalling is also essential for the establishment of left–right patterning in the early embryo. This chapter reviews our current understanding of PCP signalling in heart morphogenesis and how it affects the pathogenesis of congenital heart diseases.
Defining cardiac domains from the inside: NOTCH in endocardial–myocardial interactions
Authors: D’Amato Gaetano , Luxán Guillermo , de la Pompa José Luis 
Published: August 2018

Abstract
In this chapter we illustrate the signalling interactions of the endocardium with the other cardiac tissues to coordinate cardiac development. First, we describe the developmental origins of the endocardium. Then we focus on the Notch pathway because of its unique signalling activity in the endocardium, and briefly describe the elements of this signalling mechanism and the key cardiogenic processes that require endocardial Notch signalling: patterning of the early embryonic endocardium into prospective territories for valves and ventricular chambers, early valve formation, ventricular trabeculation, and compaction. Finally, we discuss how Notch dysfunction in the endocardium results in cardiac structural malformations that can lead to congenital heart disease.