bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Long-term Administration of Prostaglandin E1 on Morphological Changes in Ductus Arteriosus
Authors: Iwaki Ryuma , Matsuhisa Hironori , Minamisawa Susumu , Akaike Toru , Hoshino Masato , Yagi Naoto , Morita Kiyozo , Shinohara Gen , Kaneko Yukihiro , Yoshitake Syuichi , Takahashi Masashi , Tsukube Takuro , Oshima Yoshihiro 
Published: February 2020

AbstractThe morphological and histopathological effects of PGE1 infusion for ductus arteriosus were clarified through novel modality XPCT and immunohistochemical analyses, EP4, and LOX expression. Recognition of microstructural changes of ductal tissue induced by extended administration of PGE1 is profound to establish the safety usage of PGE1 for HLHS patients with staged Norwood repair.
Optimum Preparation of Candida albicans Cell Wall Extra (CAWE) for the Mouse Model of Kawasaki Disease
Authors: Yoshikane Yukako , Cho Tamaki , Koga Mitsuhisa , Haraoka Seiji , Ogawa Atsushi 
Published: February 2020

AbstractKawasaki disease is the most common acute systemic vasculitis of unknown etiology in children [1] and can cause inflammation of the coronary arteries leading to aneurysms. Candida albicans extract is one of the materials commonly used to induce coronary arteritis in a mouse model of Kawasaki disease [2, 3]. Here we report an optimized method for preparing C. albicans cell wall extra (CAWE).
The Endocardium as a Master Regulator of Ventricular Trabeculation
Authors: Qu Xianghu , Baldwin H. Scott 
Published: February 2020

AbstractVentricular chamber morphogenesis, characterized by trabeculae formation, is crucial for cardiac function and embryonic viability and depends on cellular interactions between the endocardium and myocardium. The ang1-Tie2 pathway is required for normal heart chamber development, but its molecular effectors are not well defined. Here we show that loss of Tie2 in endocardial cells (EC) results in mid-gestation lethality due to heart defects including hyperplastic myocardium trabeculation (fewer but thicker trabeculae), thinner compact myocardium and simplified endocardial network. The thicker trabeculae phenotype results from enhanced proliferation of trabecular cardiomyocytes. Meanwhile, endocardial loss of Tie2 reduces proliferation and production of ECs and impairs endocardial sprouting, which provides necessary support for trabecular assembly and extension, thus resulting in a dramatically simplified trabecular meshwork. These findings reveal two seemingly apposing functions of Tie2 in myocardium trabeculation: ensuring normal trabeculation by supporting EC proliferation and sprouting while preventing hypertrabeculation by inhibiting trabecular cardiomyocyte proliferation.
Cardiac Cell Specification by Defined Factors
Authors: Morita Yuika , Takeuchi Jun 
Published: February 2020

AbstractOur previous study has shown that Tbx5-Gata4-Baf60c-induced functional cardiomyocytes via the ectopic expression of Nkx2-5/Islet1 in the mesodermal cells, but not in the endodermal/ectodermal cells [1, 2] (Fig. 57.1). Mesp1 is one of the major transcriptional regulators specifying the mesodermal lineage, but it also induces skeletal muscle, hematopoietic and vascular cells as well as cardiac cells [3–5]. Eomesodermin (Eomes), an upstream player of Mesp1, regulates mesodermal cell lineages, but it does not have a potential for specification of cardiac cell fate from cardiovascular lineages either [6]. Therefore, the study of cardiac cell fate specification from the embryonic stem cells by the defined factors still remains at least two major questions.
Establishment of an In Vitro LQT3 model Using Induced Pluripotent Stem Cells from LQT3 Patient-Derived Cardiomyocytes
Authors: Furutani Yoshiyuki , Hayama Emiko , Kawaguchi Nanako , Katsube Yasuhiro , Oomichi Eiko , Shimada Mitsuyo , Inai Kei , Nakanishi Toshio 
Published: February 2020

AbstractCardiomyocytes derived from induced pluripotent stem cells (iPSC) are used to evaluate the function and risk factors of genetic variations linked to congenital and adult heart diseases in human beings. Our purpose in this study was to establish an in vitro cardiac disease model from an immortalized B-cell line stock using patient-specific iPSC-derived cardiomyocytes. Long QT syndrome (LQTS) 3 is caused by a gain-of-function mutation in the SCN5A gene, resulting in a prolonged QT interval as well as the development of early after-depolarizations (EADs). We generated LQT3-iPSC lines from immortalized B-cell lines transformed from peripheral blood obtained from a 24-day-old male (patient #1) and an 11-year-old female (patient #2), both diagnosed with type-3 LQTS due to SCN5A missense mutation (patient #1: exon 28, G4868A, R1623Q; patient #2: exon 20, G3578A, R1193Q). Several control iPSC lines were also created from samples collected from healthy candidates (26–36-year-old male and female). In both the generated patient iPSC lines, mutated genes were not altered after reprogramming, and normal karyotypes were observed. The pluripotency of all these iPSC lines was proven by in vivo teratoma formation and the expression of pluripotent stem cell marker genes and proteins. To evaluate the electrophysiological properties at the multicellular level, we studied the iPSC-derived cardiac cell layers with a microelectrode array mapping system (MED 64, Alpha MED Scientific Inc.). The recorded extracellular electrograms were analyzed to measure the field-potential duration (FPD), which was normalized to account for variations in beating frequency, using Fridericia’s correction (FPDcF, analogous to the QTc interval in the electrocardiogram). FPDcF was observed to be longer in LQT3 patient-derived specimens when compared to that in healthy control specimens (patient #1: P < 0.05, N = 17 and patient #2: P < 0.0001, N = 19 when compared to healthy control N = 39). Moreover, EADs were observed in both LQT3 patient specimens after 15–30 nM of E-4031 was added exclusively to patient samples. The results indicated that LQT3 patient iPSC-derived cardiac cells expressed prolonged QT duration (a common pathophysiological feature of LQTS) and EAD development with marked arrhythmogenicity in our in vitro disease model system.
Genetic Assessments for Clinical Courses of Left Ventricle Noncompaction
Authors: Nogimori Yoshitsugu , Kato Akio , Sato Kazuhisa , Kitagawa Yosuke , Wakamiya Takuya , Ono Shin , Kim Ki-Sung , Yanagi Sadamitsu , Ueda Hideaki 
Published: February 2020

AbstractLeft ventricle noncompaction (LVNC) is a clinically heterogeneous disorder. Although several genetic mutations have been reported, only a little is known about its genotype–phenotype correlation. We report two cases of LVNC with different mutations and different clinical courses for each. Case 1 was a 15-year-old boy with atrial septum defect and pulmonary valve stenosis. He was diagnosed as LVNC when he was 3 years old, but his cardiac function was maintained and no medication was necessary. A 432 kb deletion in chromosome 8p 23.1, including GATA4, was found. Case 2 was a boy who was referred to our hospital at the age 6 for apparent right ventricle hypertrophy in electrocardiogram carried out for screening. We recognized severe pulmonary hypertension (PH) and LVNC with attenuated cardiac diastolic function and fair systolic function. In spite of medications for both heart failure and PH, the response was poor. A genetic investigation revealed a point mutation at exon 6 of TBX20, c.655-2A>G.
Elucidating the Pathogenesis of Congenital Heart Disease in the Era of Next-Generation Sequencing
Authors: Nakagama Yu , Inuzuka Ryo 
Published: February 2020

AbstractOver the last decade, genetic screening has become increasingly available for patients with congenital heart disease (CHD). Chromosomal microarray has proved to be promising, particularly in the diagnosis of syndromic CHDs, and is now considered first-tier cytogenetic testing [1]. Whole-exome sequencing (WES) is another approach for genetic screening aimed towards identifying single-gene mutations [2]. Trio- and pedigree-based WES facilitate the identification of de novo and compound heterozygous variants throughout the entire coding region. Filtering of variants based on allele frequency, in silico predictions and segregation status, effectively narrows down the putative mutation. Thus, application of next-generation sequencing (NGS) has the potential of enhancing gene discovery in CHD pathogenesis.
Extracellular Vesicles, MicroRNAs, and Pulmonary Hypertension
Authors: Chen Tianji , Raj J. Usha 
Published: February 2020

AbstractPulmonary hypertension (PH) is a devastating disease that results in a progressive increase in pulmonary vascular resistance, right ventricular failure, and ultimately death of patients. Recent advances in our understanding of pathogenesis of diseases, including PH, have led to the study of extracellular vesicles (EV) as mediators of disease. Subsets of EV are microvesicles (MV), exosomes (Exo), and apoptotic bodies, and they are released from a variety of cell types and carry cargo such as proteins and microRNAs (miR). MicroRNAs contained within these EV play an important role in disease including in the pathogenesis of PH as well as other lung diseases.
Roles of Tbx4 in the Lung Mesenchyme for Airway and Vascular Development
Authors: Uchida Keiko , Yoshida Yu , Kodo Kazuki , Yamagishi Hiroyuki 
Published: February 2020

AbstractThe T-box family genes are evolutionarily conserved transcription factors. In particular, Tbx4 and Tbx5 are closely conserved and play crucial roles in development and organogenesis. Tbx4 is essential for hindlimb and allantoic vessel formation [1]. It is also highly expressed in the lung mesenchyme (Fig. 8.1), initially expressed at embryonic day (E) 9.25 and later expressed throughout murine embryogenesis [2].
Magnetic quivers, Higgs branches, and 6d $$ \mathcal{N} $$ = (1, 0) theories — orthogonal and symplectic gauge groups
Authors: Cabrera Santiago , Hanany Amihay , Sperling Marcus 
Published: February 2020

Abstract
M5 branes on a D-type ALE singularity display various phenomena that introduce additional massless degrees of freedom. The M5 branes are known to fractionate on a D-type singularity. Whenever two fractional M5 branes coincide, tensionless strings arise. Therefore, these systems do not admit a low-energy Lagrangian description. Focusing on the 6-dimensional $$ \mathcal{N} $$
N
= (1, 0) world-volume theories on the M5 branes, the vacuum moduli space has two branches were either the scalar fields in the tensor multiplet or the scalars in the hypermultiplets acquire a non-trivial vacuum expectation value. As suggested in previous work, the Higgs branch may change drastically whenever a BPS-string becomes tensionless. Recently, magnetic quivers have been introduced with the aim to capture all Higgs branches over any point of the tensor branch. In this paper, the formalism is extended to Type IIA brane configurations involving O6 planes. Since the 6d $$ \mathcal{N} $$
N
= (1, 0) theories are composed of orthosymplectic gauge groups, the derivation rules for the magnetic quiver in the presence of O6 planes have to be conjectured. This is achieved by analysing the 6d theories for a single M5 brane on a D-type singularity and deriving the magnetic quivers for the finite and infinite gauge coupling Higgs branch from a brane configuration. The validity of the proposed derivation rules is underpinned by deriving the associated Hasse diagram. For multiple M5 branes, the approach of this paper provides magnetic quivers for all Higgs branches over any point of the tensor branch. In particular, an interesting infinite gauge coupling transition is found that is related to the SO(8) non-Higgsable cluster.
A R2R3-MYB gene-based marker for the non-darkening seed coat trait in pinto and cranberry beans (Phaseolus vulgaris L.) derived from ‘Wit-rood boontje’
Authors: Erfatpour M. , Pauls K. P. 
Published: February 2020

AbstractKey messageThe genePhvul.010G130600which codes for a MYB was shown to be tightly associated with seed coat darkening inPhaseolus vulgarisand a single nucleotide deletion in the allele in Wit-rood disrupts a transcription activation region that likely prevents its functioning in this non-darkening genotype.AbstractThe beige and white background colors of the seed coats of conventional pinto and cranberry beans turn brown through a process known as postharvest darkening (PHD). Seed coat PHD is attributed to proanthocyanidin accumulation and its subsequent oxidation in the seed coat. TheJgene is an uncharacterized classical genetic locus known to be responsible for PHD in common bean (P. vulgaris) and individuals that are homozygous for its recessive allele have a non-darkening (ND) seed coat phenotype. A previous study identified a major colorimetrically determined QTL for seed coat color on chromosome 10 that was associated with the ND trait. The objectives of this study were to identify a gene associated with seed coat postharvest darkening in common bean and understand its function in promoting seed coat darkening. Amplicon sequencing of 21 candidate genes underlying the QTL associated with the ND trait revealed a single nucleotide deletion (c.703delG) in the candidate genePhvul.010G130600in non-darkening recombinant inbred lines derived from crosses between ND ‘Wit-rood boontje’ and a regular darkening pinto genotype. In silico analysis indicated thatPhvul.010G130600encodes a protein with strong amino acid sequence identity (70%) with a R2R3-MYB-type transcription factorMtPAR, which has been shown to regulate proanthocyanidin biosynthesis inMedicago truncatulaseed coat tissue. The deletion in the ‘Wit-rood boontje’ allele ofPhvul.010G130600likely causes a translational frame shift that disrupts the function of a transcriptional activation domain contained in the C-terminus of the R2R3-MYB. A gene-based dominant marker was developed for the dominant allele ofPhvul.010G130600which can be used for marker-assisted selection of ND beans.
Functionality of primary hepatic non-parenchymal cells in a 3D spheroid model and contribution to acetaminophen hepatotoxicity
Authors: Bell Catherine C. , Chouhan Bhavik , Andersson Linda C. , Andersson Håkan , Dear James W. , Williams Dominic P. , Söderberg Magnus 
Published: February 2020

AbstractIn addition to hepatocytes, the liver comprises a host of specialised non-parenchymal cells which are important to consider in the development of in vitro models which are both physiologically and toxicologically relevant. We have characterized a 3D co-culture system comprising primary human hepatocytes (PHH) and non-parenchymal cells (NPC) and applied it to the investigation of acetaminophen-induced toxicity. Firstly, we titrated ratios of PHH:NPC and confirmed the presence of functional NPCs via both immunohistochemistry and activation with both LPS and TGF-β. Based on these data we selected a ratio of 2:1 PHH:NPC for further studies. We observed that spheroids supplemented with NPCs were protected against acetaminophen (APAP) toxicity as determined by ATP (up to threefold difference in EC50 at day 14 compared to hepatocytes alone) and glutathione depletion, as well as miR-122 release. APAP metabolism was also altered in the presence of NPCs, with significantly lower levels of APAP-GSH detected. Expression of several CYP450 enzymes involved in the bioactivation of APAP was also lower in NPC-containing spheroids. Spheroids containing NPCs also expressed higher levels of miRNAs which have been implicated in APAP-induced hepatotoxicity, including miR-382 and miR-155 which have potential roles in liver regeneration and inflammation, respectively. These data indicate that the interaction between hepatocytes and NPCs can have significant metabolic and toxicological consequences important for the correct elucidation of hepatic safety mechanisms.
Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy
Authors: Wachowska Malgorzata , Stachura Joanna , Tonecka Katarzyna , Fidyt Klaudyna , Braniewska Agata , Sas Zuzanna , Kotula Iwona , Rygiel Tomasz Piotr , Boon Louis , Golab Jakub , Muchowicz Angelika 
Published: February 2020

AbstractIt was previously reported that the activation of antitumor immune response by photodynamic therapy (PDT) is crucial for its therapeutic outcome. Excessive PDT-mediated inflammation is accompanied by immunosuppressive mechanisms that protect tissues from destruction. Thus, the final effect of PDT strongly depends on the balance between the activation of an adoptive arm of immune response and a range of activated immunosuppressive mechanisms. Here, with flow cytometry and functional tests, we evaluate the immunosuppressive activity of tumor-associated myeloid cells after PDT. We investigate the antitumor potential of PDT combined with indoleamine 2,3-dioxygenase 1 (IDO) inhibitor in the murine 4T1 and E0771 orthotopic breast cancer models. We found that the expression of IDO, elevated after PDT, affects the polarization of T regulatory cells and influences the innate immune response. Our results indicate that, depending on a therapeutic scheme, overcoming IDO-induced immunosuppressive mechanisms after PDT can be beneficial or can lead to a systemic toxic reaction. The inhibition of IDO, shortly after PDT, activates IL-6-dependent toxic reactions that can be diminished by the use of anti-IL-6 antibodies. Our results emphasize that deeper investigation of the physiological role of IDO, an attractive target for immunotherapies of cancer, is of great importance.
Effectiveness and Usage Trends of Hemorrhage Control Interventions in Patients with Pelvic Fracture in Shock
Authors: Matsumoto Shokei , Funabiki Tomohiro , Hayashida Kei , Yamazaki Motoyasu , Ebihara Takayuki , Moriya Takashi 
Published: February 2020

AbstractBackgroundHemorrhage control for pelvic fractures remains challenging. There are several kinds of hemostatic interventions, including angiography/angioembolization (AG/AE), external fixation (EF), and resuscitative endovascular balloon occlusion of the aorta (REBOA). However, no large studies have been conducted for the comparative review of each intervention. In this study, we examined the usage trend of therapeutic interventions in Japan for patients with pelvic fractures in shock and the influence of these interventions on mortality.MethodsData of adult patients with pelvic fracture who were in shock were obtained from the Japanese Trauma Data Bank (2004–2014). The primary endpoint was the influence of each intervention (AG/AE, EF, and REBOA) on in‐hospital mortality. We also investigated the frequency of each intervention.ResultsA total of 3149 patients met all our inclusion criteria. Specifically, 1131 (35.9%), 496 (15.8%), and 256 (8.1%) patients underwent AG, EF, and REBOA interventions, respectively. Therapeutic AE was performed in 690 patients who underwent AG (61.0%). The overall mortality rate was 31.4%. Multiple regression analysis identified that AG/AE (OR 0.64, 95% CI 0.52–0.80) and EF (OR 0.75, 95% CI 0.58–0.98) were significantly associated with survival, whereas REBOA (OR 4.17, 95% CI 3.00–5.82) was significantly associated with worse outcomes.ConclusionsIn Japan, patients with pelvic fracture who were in shock had high mortality rates. AG/AE and EF were associated with decreased mortality. AG may benefit from the early detection of arterial bleeding, leading to decreased mortality of patients with pelvic fracture in shock.
Sustainability Models for Efficient Resource Use in the Context of Current Ecological and Social Pressures
Authors: Feiel Susanne 
Published: February 2020

AbstractThe basis of human societal existence is a complex interaction between social, environmental and industrial aspects resulting in the consumption of the environment for wealth generation. In combination with the actual scope of human industrial activity and population development this has led to a currently exceptional planetary situation, which is characterized by unprecedented environmental pressures. In order to develop a strategy on how industrial activity, especially the mineral raw materials sector and its downstream industries, can develop more sustainably, various sustainability models can combined provide orientation on where the journey should go.
Size dependency of variables influencing fire occurrence in Mediterranean forests of Eastern Spain
Authors: Peris-Llopis Marina , González-Olabarria José Ramón , Mola-Yudego Blas 
Published: February 2020

AbstractFires are among the most damaging disturbances to forests in the Mediterranean area. The study analyses the occurrence and characteristics of forest fires in Eastern Spain (1993–2015) to identify key variables related to burnt forest land, differentiating fires according to their burnt area. Data are retrieved from digital cartography, the Spanish Forest Map and data concerning fires. Based on previous research, the variables included are altitude, slope, aspect, fuel, species, population and road density. The fires are classified in small (5–50 ha), medium (50–500 ha) and large (> 500 ha). Four models are considered to explain the proportion of burnt area based on weighted generalized linear models: a general model and one per size class. The results highlight the different relations of similar variables with fires according to the size. When a single model is considered to explain all area burnt, the relationships are mainly driven by large fires. The larger area is burnt on forests with pine, bushes and small trees, whereas smaller fires tend to occur on lower altitude, low slope, high population and road densities. There are large differences in the variables according to the fire sizes, especially for the presence of pine (negative in the medium fires model but positive for the large fires model) and Pasture (which only explains the small fires). The models can be applied to analyse occurrence by fire size in Mediterranean areas, and the results can help elaborate fire prevention strategies and land-planning schemes.
Towards a relational paradigm in sustainability research, practice, and education
Authors: Walsh Zack , Böhme Jessica , Wamsler Christine 
Published: February 2020

AbstractRelational thinking has recently gained increasing prominence across academic disciplines in an attempt to understand complex phenomena in terms of constitutive processes and relations. Interdisciplinary fields of study, such as science and technology studies (STS), the environmental humanities, and the posthumanities, for example, have started to reformulate academic understanding of nature-cultures based on relational thinking. Although the sustainability crisis serves as a contemporary backdrop and in fact calls for such innovative forms of interdisciplinary scholarship, the field of sustainability research has not yet tapped into the rich possibilities offered by relational thinking. Against this background, the purpose of this paper is to identify relational approaches to ontology, epistemology, and ethics which are relevant to sustainability research. More specifically, we analyze how relational approaches have been understood and conceptualized across a broad range of disciplines and contexts relevant to sustainability to identify and harness connections and contributions for future sustainability-related work. Our results highlight common themes and patterns across relational approaches, helping to identify and characterize a relational paradigm within sustainability research. On this basis, we conclude with a call to action for sustainability researchers to co-develop a research agenda for advancing this relational paradigm within sustainability research, practice, and education.