3,933 research outputs found
Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using Tc-99m-HMPAO
Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with Tc-99m-HMPAO under physiologic conditions and monitored in vivo distribution of Tc-99m-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with Tc-99m-HMPAO for 1 hr incubation, followed by removal of free Tc-99m-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with Tc-99m-HMPAO, the radiochemical purity of Tc-99m-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in Tc-99m-HMPAO-ENVs. Tc-99m-HMPAOENVs showed high serum stability (90%) which was similar to that in phosphate buffered saline until 5 hr. SPECT/CT images of the mice injected with Tc-99m-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with Tc-99m-HMPAO showed high brain uptake until 5 hr. Our noninvasive imaging of radiolabeled-ENVs promises better understanding of the in vivo behavior of exosomes for upcoming biomedical application.114327Ysciescopu
Drug-disease Graph: Predicting Adverse Drug Reaction Signals via Graph Neural Network with Clinical Data
Adverse Drug Reaction (ADR) is a significant public health concern
world-wide. Numerous graph-based methods have been applied to biomedical graphs
for predicting ADRs in pre-marketing phases. ADR detection in post-market
surveillance is no less important than pre-marketing assessment, and ADR
detection with large-scale clinical data have attracted much attention in
recent years. However, there are not many studies considering graph structures
from clinical data for detecting an ADR signal, which is a pair of a
prescription and a diagnosis that might be a potential ADR. In this study, we
develop a novel graph-based framework for ADR signal detection using healthcare
claims data. We construct a Drug-disease graph with nodes representing the
medical codes. The edges are given as the relationships between two codes,
computed using the data. We apply Graph Neural Network to predict ADR signals,
using labels from the Side Effect Resource database. The model shows improved
AUROC and AUPRC performance of 0.795 and 0.775, compared to other algorithms,
showing that it successfully learns node representations expressive of those
relationships. Furthermore, our model predicts ADR pairs that do not exist in
the established ADR database, showing its capability to supplement the ADR
database.Comment: To appear at PAKDD 202
Isolation and Mechanical Measurements of Myofibrils from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Summary: Tension production and contractile properties are poorly characterized aspects of excitation-contraction coupling of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Previous approaches have been limited due to the small size and structural immaturity of early-stage hiPSC-CMs. We developed a substrate nanopatterning approach to produce hiPSC-CMs in culture with adult-like dimensions, T-tubule-like structures, and aligned myofibrils. We then isolated myofibrils from hiPSC-CMs and measured the tension and kinetics of activation and relaxation using a custom-built apparatus with fast solution switching. The contractile properties and ultrastructure of myofibrils more closely resembled human fetal myofibrils of similar gestational age than adult preparations. We also demonstrated the ability to study the development of contractile dysfunction of myofibrils from a patient-derived hiPSC-CM cell line carrying the familial cardiomyopathy MYH7 mutation (E848G). These methods can bring new insights to understanding cardiomyocyte maturation and developmental mechanical dysfunction of hiPSC-CMs with cardiomyopathic mutations. : In this article, Pioner and colleagues reported contractile properties of isolated myofibrils from hiPSC-CMs with highly mature morphology. This approach permits quantitative assessment of maturation and contractile properties of hiPSC-CMs and can be used to study the development of contractile dysfunction in genetically based cardiac diseases. The authors present a patient-derived cell line carrying a novel familial cardiomyopathy MYH7 mutation (E848G)
Light Higgsino in Heavy Gravitino Scenario with Successful Electroweak Symmetry Breaking
We consider, in the context of the minimal supersymmetric standard model, the
case where the gravitino weighs 10^6 GeV or more, which is preferred by various
cosmological difficulties associated with unstable gravitinos. Despite the
large Higgs mixing parameter B together with the little hierarchy to other soft
supersymmetry breaking masses, a light higgsino with an electroweak scale mass
leads to successful electroweak symmetry breaking, at the price of fine-tuning
the higgsino mixing mu parameter. Furthermore the light higgsinos produced at
the decays of gravitinos can constitute the dark matter of the universe. The
heavy squark mass spectrum of O(10^4) GeV can increase the Higgs boson mass to
about 125 GeV or higher.Comment: 13 pages, 3 figures; v2: version to appear in JHE
Persuasiveness of eWOM communications: Literature review and suggestions for future research
YesElectronic word-of-mouth (eWOM) plays an important part in consumer purchase decision. The way consumers perceive the persuasiveness of eWOM message can affect their attitude, and purchase intention, and hence sales. Thus, the topic of persuasiveness of eWOM communications has received much attention from scholars. The objective of this paper is to provide a brief review of the existing literature related to the effectiveness of eWOM communications and offer an overview of the determinants of eWOM persuasiveness. This paper contributes to the existing eWOM literature by reviewing the existing studies on eWOM communications, identifying gaps in the current research and providing directions for future research
The mu problem and sneutrino inflation
We consider sneutrino inflation and post-inflation cosmology in the singlet
extension of the MSSM with approximate Peccei-Quinn(PQ) symmetry, assuming that
supersymmetry breaking is mediated by gauge interaction. The PQ symmetry is
broken by the intermediate-scale VEVs of two flaton fields, which are
determined by the interplay between radiative flaton soft masses and higher
order terms. Then, from the flaton VEVs, we obtain the correct mu term and the
right-handed(RH) neutrino masses for see-saw mechanism. We show that the RH
sneutrino with non-minimal gravity coupling drives inflation, thanks to the
same flaton coupling giving rise to the RH neutrino mass. After inflation,
extra vector-like states, that are responsible for the radiative breaking of
the PQ symmetry, results in thermal inflation with the flaton field, solving
the gravitino problem caused by high reheating temperature. Our model predicts
the spectral index to be n_s\simeq 0.96 due to the additional efoldings from
thermal inflation. We show that a right dark matter abundance comes from the
gravitino of 100 keV mass and a successful baryogenesis is possible via
Affleck-Dine leptogenesis.Comment: 27 pages, no figures, To appear in JHE
The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake
We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms
Jejunal Variceal Bleeding Successfully Treated with Percutaneous Coil Embolization
A 52-yr-old male with alcoholic liver cirrhosis was hospitalized for hematochezia. He had undergone small-bowel resection due to trauma 15 yr previously. Esophagogastroduodenoscopy showed grade 1 esophageal varices without bleeding. No bleeding lesion was seen on colonoscopy, but capsule endoscopy showed suspicious bleeding from angiodysplasia in the small bowel. After 2 weeks of conservative treatment, the hematochezia stopped. However, 1 week later, the patient was re-admitted with hematochezia and a hemoglobin level of 5.5 g/dL. Capsule endoscopy was performed again and showed active bleeding in the mid-jejunum. Abdominal computed tomography revealed a varix in the jejunal branch of the superior mesenteric vein. A direct portogram performed via the transhepatic route showed portosystemic collaterals at the distal jejunum. The patient underwent coil embolization of the superior mesenteric vein just above the portosystemic collaterals and was subsequently discharged without re-bleeding. At 8 months after discharge, his condition has remained stable, without further bleeding episodes
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