bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the risk of first intravenous immunoglobulin unresponsiveness in non-Asian patients with Kawasaki disease
Authors: Piram Maryam , Darce Bello Martha , Tellier Stéphanie , Di Filippo Sylvie , Boralevi Franck , Madhi Fouad , Meinzer Ulrich , Cimaz Rolando , Piedvache Celine , Koné-Paut Isabelle 
Published: February 2020

AbstractAbout 10–20% of patients with Kawasaki disease (KD) are unresponsive to intravenous immunoglobulin (IVIg) and are at increased risk of coronary artery abnormalities (CAAs). Early identification is critical to initiate aggressive therapies, but available scoring systems lack sensitivity in non-Japanese populations. We investigated the accuracy of 3 Japanese scoring systems and studied factors associated with IVIg unresponsiveness in a large multiethnic French population of children with KD to build a new scoring system. Children admitted for KD between 2011–2014 in 65 centers were enrolled. Factors associated with second line-treatment; i.e. unresponsiveness to initial IVIg treatment, were analyzed by multivariate regression analysis. The performance of our score and the Kobayashi, Egami and Sano scores were compared in our population and in ethnic subgroups. Overall, 465 children were reported by 84 physicians; 425 were classified with KD (55% European Caucasian, 12% North African/Middle Eastern, 10% African/Afro-Caribbean, 3% Asian and 11% mixed). Eighty patients (23%) needed second-line treatment. Japanese scores had poor performance in our whole population (sensitivity 14–61%). On multivariate regression analysis, predictors of secondary treatment after initial IVIG were hepatomegaly, ALT level ≥30 IU/L, lymphocyte count <2400/mm3 and time to treatment <5 days. The best sensitivity (77%) and specificity (60%) of this model was with 1 point per variable and cut-off ≥2 points. The sensitivity remained good in our 3 main ethnic subgroups (74–88%). We identified predictors of IVIg resistance and built a new score with good sensitivity and acceptable specificity in a non-Asian population.
Immune correlates of postexposure vaccine protection against Marburg virus
Authors: Woolsey Courtney , Jankeel Allen , Matassov Demetrius , Geisbert Joan B. , Agans Krystle N. , Borisevich Viktoriya , Cross Robert W. , Deer Daniel J. , Fenton Karla A. , Latham Theresa E. , Gerardi Cheryl S. , Mire Chad E. , Eldridge John H. , Messaoudi Ilhem , Geisbert Thomas W. 
Published: February 2020

AbstractPostexposure immunization can prevent disease and reduce transmission following pathogen exposure. The rapid immunostimulatory properties of recombinant vesicular stomatitis virus (rVSV)-based vaccines make them suitable postexposure treatments against the filoviruses Ebola virus and Marburg virus (MARV); however, the mechanisms that drive this protection are undefined. Previously, we reported 60–75% survival of rhesus macaques treated with rVSV vectors expressing MARV glycoprotein (GP) 20–30 minutes after a low dose exposure to the most pathogenic variant of MARV, Angola. Survival in this model was linked to production of GP-specific antibodies and lower viral load. To confirm these results and potentially identify novel correlates of postexposure protection, we performed a similar experiment, but analyzed plasma cytokine levels, frequencies of immune cell subsets, and the transcriptional response to infection in peripheral blood. In surviving macaques (80–89%), we observed induction of genes mapping to antiviral and interferon-related pathways early after treatment and a higher percentage of T helper 1 (Th1) and NK cells. In contrast, the response of non-surviving macaques was characterized by hypercytokinemia; a T helper 2 signature; recruitment of low HLA-DR expressing monocytes and regulatory T-cells; and transcription of immune checkpoint (e.g., PD-1, LAG3) genes. These results suggest dysregulated immunoregulation is associated with poor prognosis, whereas early innate signaling and Th1-skewed immunity are important for survival.
A salivary metabolite signature that reflects gingival host-microbe interactions: instability predicts gingivitis susceptibility
Authors: Fernandez-Gutierrez Marcela M. , Imangaliyev Sultan , Prodan Andrei , Loos Bruno G. , Keijser Bart J. F. , Kleerebezem Michiel 
Published: February 2020

AbstractSeveral proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual’s gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.
Hyperproliferation is the main driver of metabolomic changes in psoriasis lesional skin
Authors: Pohla Liis , Ottas Aigar , Kaldvee Bret , Abram Kristi , Soomets Ursel , Zilmer Mihkel , Reemann Paula , Jaks Viljar , Kingo Külli 
Published: February 2020

AbstractSystematic understanding of the metabolite signature of diseases may lead to a closer understanding of the disease pathogenesis and ultimately to the development of novel therapies and diagnostic tools. Here we compared for the first time the full metabolomic profiles of lesional and non-lesional skin biopsies obtained from plaque psoriasis patients and skin samples of healthy controls. Significant differences in the concentration levels of 29 metabolites were identified that provide several novel insights into the metabolic pathways of psoriatic lesions. The metabolomic profile of the lesional psoriatic skin is mainly characterized by hallmarks of increased cell proliferation. As no significant differences were identified between non-lesional skin and healthy controls we conclude that local inflammatory process that drives the increased cell proliferation is the main cause of the identified metabolomic shifts.
A semi-automated technique for adenoma quantification in the ApcMin mouse using FeatureCounter
Authors: Shepherd Amy L. , Smith A. Alexander T. , Wakelin Kirsty A. , Kuhn Sabine , Yang Jianping , Eccles David A. , Ronchese Franca 
Published: February 2020

AbstractColorectal cancer is a major contributor to death and disease worldwide. The ApcMin mouse is a widely used model of intestinal neoplasia, as it carries a mutation also found in human colorectal cancers. However, the method most commonly used to quantify tumour burden in these mice is manual adenoma counting, which is time consuming and poorly suited to standardization across different laboratories. We describe a method to produce suitable photographs of the small intestine of ApcMin mice, process them with an ImageJ macro, FeatureCounter, which automatically locates image features potentially corresponding to adenomas, and a machine learning pipeline to identify and quantify them. Compared to a manual method, the specificity (or True Negative Rate, TNR) and sensitivity (or True Positive Rate, TPR) of this method in detecting adenomas are similarly high at about 80% and 87%, respectively. Importantly, total adenoma area measures derived from the automatically-called tumours were just as capable of distinguishing high-burden from low-burden mice as those established manually. Overall, our strategy is quicker, helps control experimenter bias, and yields a greater wealth of information about each tumour, thus providing a convenient route to getting consistent and reliable results from a study.
Color-specific porosity in double pigmented natural 3d-nanoarchitectures of blue crab shell
Authors: Nekvapil Fran , Pinzaru Simona Cintă , Barbu–Tudoran Lucian , Suciu Maria , Glamuzina Branko , Tamaș Tudor , Chiș Vasile 
Published: February 2020

Abstract3D-engineered nano-architectures with various functionalities are still difficult to obtain and translate for real-world applications. However, such nanomaterials are naturally abundant and yet wasted, but could trigger huge interest for blue bioeconomy, provided that our understanding of their ultrastructure-function is achieved. To date, the Bouligand pattern in crustaceans shell structure is believed to be unique. Here we demonstrated that in blue crab Callinectes sapidus, the 3D-nanoarchitecture is color-specific, while the blue and red-orange pigments interplay in different nano-sized channels and pores. Thinnest pores of about 20  nm are found in blue shell. Additionally, the blue pigment co-existence in specific Bouligand structure is proved for the green crab Carcinus aestuarii, although the crab does not appear blue. The pigments interplay, simultaneously detected by Raman spectroscopy in color-specific native cuticles, overturns our understanding in crustaceans coloration and may trigger the selective use of particular colored natural nanoarchitectures for broaden area of applications.
Local transplantation of adipose-derived stem cells has a significant therapeutic effect in a mouse model of rheumatoid arthritis
Authors: Ueyama Hideki , Okano Tadashi , Orita Kumi , Mamoto Kenji , Ii Masaaki , Sobajima Satoshi , Iwaguro Hideki , Nakamura Hiroaki 
Published: February 2020

AbstractAdipose-derived stem cells (ADSCs) have anti-inflammatory and regenerative properties. The purpose of this study was to investigate the effect of locally administered ADSCs in a rheumatoid arthritis (RA) mouse model. In an in vivo experiment, single-cell ADSCs and three dimensionally-cultured ADSC spheroids were injected intra-articularly into the knees of RA model mice and histologically assessed. Marked improvement of synovial inflammation and articular cartilage regeneration was found in ADSC-treated mice. Proliferation, migration, and apoptosis assays of synovial fibroblasts incubated with single-cell and spheroid ADSCs were performed. The expression levels of total cytokine RNA in ADSC single cells, spheroids, and ADSC-treated inflammatory synovial fibroblasts were also evaluated by quantitative reverse transcription PCR. ADSCs suppressed the proliferation and migration of activated inflammatory cells and downregulated inflammatory cytokines. TSG-6 and TGFβ1 were significantly upregulated in ADSCs compared to controls and TGFβ1 was significantly upregulated in ADSC spheroids compared to single cells. The apoptosis rate of ADSC spheroids was significantly lower than that of single-cell ADSCs. These results indicated that intra-articular administration of ADSC single cells and spheroids was effective in an RA mouse model, offering a novel approach for the development of effective localized treatments for patients with RA.
Diagnostic ability of vessel density measured by spectral-domain optical coherence tomography angiography for glaucoma in patients with high myopia
Authors: Lee Kwanghyun , Maeng Kyung Joo , Kim Joo Yeon , Yang Heon , Choi Wungrak , Lee Sang Yeop , Seong Gong Je , Kim Chan Yun , Bae Hyoung Won 
Published: February 2020

AbstractAlthough early glaucoma detection is important to prevent visual loss due to disease progression, its clinical diagnosis in highly myopic eyes is still difficult. Many studies using optical coherence tomography (OCT) angiography (OCTA) reported decreased vessel density (VD) in glaucomatous eyes compared to normal eyes. We evaluated the diagnostic ability of peripapillary VD and macular VD measured by OCTA, comparing them with conventional valuables such as peripapillary retinal nerve fibre layer (RNFL) thickness and macular ganglion cell-inner plexiform layer (GCIPL) thickness measured by OCT. We also calculated the average VD ratio (VDR) (average outer macular VD/average inner macular VD), superior VDR (superior outer macular VD/average inner macular VD), and inferior VDR (inferior outer macular VD/average inner macular VD). Totally, 169 eyes from 169 subjects were enrolled. Among OCTA measurements, the best diagnostic parameters were average VDR (AUROC: 0.852 and 0.909) and inferior VDR (AUROC: 0.820 and 0.941) in nonhighly and highly myopic eyes, respectively. Inferior VDR showed better diagnostic ability than most of the other OCT measurements including peripapillary RNFL thickness and macular GCIPL thickness in highly myopic eyes. Accordingly, OCTA measurements can be useful for diagnosing glaucoma in highly myopic eyes, especially when using calculated indices such as average VDR or inferior VDR.
Antifreeze protein complements cryoprotective dehydration in the freeze-avoiding springtail Megaphorura arctica
Authors: Graham Laurie A. , Boddington Marie E. , Holmstrup Martin , Davies Peter L. 
Published: February 2020

AbstractThe springtail, Megaphorura arctica, is freeze-avoiding and survives sub-zero temperatures by cryoprotective dehydration. At the onset of dehydration there is some supercooling of body fluids, and the danger of inoculative freezing, which would be lethal. To see if the springtails are protected by antifreeze proteins in this pre-equilibrium phase, we examined extracts from cold-acclimated M. arctica and recorded over 3 °C of freezing point depression. Proteins responsible for this antifreeze activity were isolated by ice affinity. They comprise isoforms ranging from 6.5 to 16.9 kDa, with an amino acid composition dominated by glycine (>35 mol%). Tryptic peptide sequences were used to identify the mRNA sequence coding for the smallest isoform. This antifreeze protein sequence has high similarity to one characterized in Hypogastrura harveyi, from a different springtail order. If these two antifreeze proteins are true homologs, we suggest their origin dates back to the Permian glaciations some 300 million years ago.
Challenges in the serological evaluation of dogs clinically suspect for canine leishmaniasis
Authors: Santarém Nuno , Sousa Susana , Amorim Célia G. , de Carvalho Nuno Lima , de Carvalho Hugo Lima , Felgueiras Óscar , Brito Margarida , da Silva Anabela Cordeiro 
Published: February 2020

AbstractCanine leishmaniasis is a major veterinary issue and also a public health challenge due to its zoonotic potential. In this context, serological evaluation is essential for Canine leishmaniasis management. Several serological alternatives, such as rapid diagnostic tests, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence antibody test (IFAT), are well established. In fact, the capacity of distinct tests and antigens, evaluated by their sensitivity and specificity, to detect disease is normally considered sufficient for diagnosing Canine leishmaniasis. In this context, we evaluated the seropositivity using 8 different serological tests (ELISA with Leishmania recombinant proteins (rK39, LicTXNPx); soluble promastigote Leishmania antigens (SPLA); commercial ELISA test) in 82 clinically suspect animals from Northern Portugal. The obtained serological data originated 50% of inconclusive serological information with a mixture of seropositive and seronegative results for individual animals. Cut-off independent risk groups were then generated from the serological data to evaluate the clustering of the samples. This analysis originated risk groups that correlated with the most seropositive samples, suggesting that this method might be used, in a cut-off independent manner, to improve conventional serological evaluation. Ultimately, given that no test prioritization exists, the use of any single serological test increases the potential for misdiagnosis, along with all associated risks for the dog as well as public health. The use of a cut-off independent analysis has the potential to improve the predictive values of these tests, enabling a more accurate evaluation of the dog’s condition.
Transcytosis of Bacillus subtilis extracellular vesicles through an in vitro intestinal epithelial cell model
Authors: Rubio Ana Paula Domínguez , Martínez Jimena , Palavecino Marcos , Fuentes Federico , López Christian Miquel Sánchez , Marcilla Antonio , Pérez Oscar Edgardo , Piuri Mariana 
Published: February 2020

AbstractBacterial EVs have been related to inter-kingdom communication between probiotic/pathogenic bacteria and their hosts. Our aim was to investigate the transcytosis process of B. subtilis EVs using an in vitro intestinal epithelial cell model. In this study, using Confocal Laser Scanning Microscopy, we report that uptake and internalization of CFSE-labeled B. subtilis EVs (115 nm ± 27 nm) by Caco-2 cells are time-dependent. To study the transcytosis process we used a transwell system and EVs were quantified in the lower chamber by Fluorescence and Nanoparticle Tracking Analysis measurements. Intact EVs are transported across a polarized cell monolayer at 60–120 min and increased after 240 min with an estimated average uptake efficiency of 30% and this process is dose-dependent. EVs movement into intestinal epithelial cells was mainly through Z axis and scarcely on X and Y axis. This work demonstrates that EVs could be transported across the gastrointestinal epithelium. We speculate this mechanism could be the first step allowing EVs to reach the bloodstream for further delivery up to extraintestinal tissues and organs. The expression and further encapsulation of bioactive molecules into natural nanoparticles produced by probiotic bacteria could have practical implications in food, nutraceuticals and clinical therapies.
Aktueller Stellenwert der kontrastverstärkten Echokardiografie
Authors: Helfen Andreas 
Published: February 2020

ZusammenfassungDie Echokardiografie mit lungengängigen Ultraschallkontrastmitteln stellt eine gut etablierte Methode dar, um die Limitationen der nicht kontrastverstärkten Echokardiografie infolge von Artefakten oder eines eingeschränkten Schallfensters zu minimieren. Es werden die aktuellen Empfehlungen zum Einsatz von lungengängigen Kontrastmitteln bei der regionalen Wandbewegungsanalyse, der Messung der Ejektionsfraktion, bei Thromben und Tumoren sowie bei der Perfusionsechokardiografie dargestellt.
Auto-Regulation of the Thyroid Gland Beyond Classical Pathways
Authors: Brix Klaudia , Szumska Joanna , Weber Jonas , Qatato Maria , Venugopalan Vaishnavi , Al-Hashimi Alaa , Rehders Maren 
Published: February 2020

AbstractThis mini-review asks how self-regulation of the thyroid gland is realized at the cellular and molecular levels by canonical and non-canonical means. Canonical pathways of thyroid regulation comprise thyroid stimulating hormone-triggered receptor signaling. As part of non-canonical regulation, we hypothesized an interplay between protease-mediated thyroglobulin processing and thyroid hormone release into the circulation by means of thyroid hormone transporters like Mct8. We proposed a sensing mechanism by different thyroid hormone transporters, present in specific subcellular locations of thyroid epithelial cells, selectively monitoring individual steps of thyroglobulin processing, and thus, the cellular thyroid hormone status. Indeed, we found that proteases and thyroid hormone transporters are functionally inter-connected, however, in a counter-intuitive manner fostering self-thyrotoxicity in particular in Mct8- and/or Mct10-deficient mice. Furthermore, the possible role of the G protein-coupled receptor Taar1 is discussed, because we detected Taar1 at cilia of the apical plasma membrane of thyrocytes in vitro and in situ. Eventually, through pheno-typing Taar1-deficient mice, we identified a co-regulatory role of Taar1 and the thyroid stimulating hormone receptors. Recently, we showed that inhibition of thyroglobulin-processing enzymes results in disappearance of cilia from the apical pole of thyrocytes, while Taar1 is re-located to the endoplasmic reticulum. This pathway features a connection between thyrotropin-stimulated secretion of proteases into the thyroid follicle lumen and substrate-mediated self-assisted control of initially peri-cellular thyroglobulin processing, before its reinternalization by endocytosis, followed by extensive endo-lysosomal liberation of thyroid hormones, which are then released from thyroid follicles by means of thyroid hormone transporters.
Relationship of Renal Function in Mice to Strain, Sex and 177Lutetium-Somatostatin Receptor Ligand Treatment
Authors: Mohan Ajay-Mohan , Lukas Mathias , Albrecht Jakob , Dorau-Rutke Viktoria , Koziolek Eva J. , Huang Kai , Prasad Sonal , Brenner Winfried , Beindorff Nicola 
Published: February 2020

Abstract
Aim Aim of the study was to establish parameters for 99mTc-MAG3 SPECT renal uptake kinetics in healthy SCID mice as a function of mouse strain and sex and to evaluate the feasibility of this method for detecting 177Lu-somatostatin receptor ligand (177Lu-SRL) treatment effects on kidney function.
Materials and Methods Dynamic semi-stationary SPECT acquisitions (68 frames, total duration 35 min) was started prior to i. v. injection of 99mTc-MAG3 in 12 female and 12 male SCID mice. Additionally, 6 female SCID mice with neuroendocrine tumors were imaged 1–5 months after 177Lu-SRL (5 DOTATOC, 1 DOTA-JR11) treatment. Kidney function is expressed as maximum time to peak (Tmax), T50 and T25 in minutes (median [interquartile range]). Differences between groups were tested using the Mann-Whitney-U test, and SCID mouse parameters were compared with data for C57BL/6N mice from a recent publication.
Results Significant sex-based differences in Tmax between strains were observed (females: C57BL/6N 1.6 [1.4–1.7], SCID 1.4 [1.3–1.5], p = 0.05; males: C57BL/6N 1.4 [1.3–1.4], SCID 1.6 [1.4–1.7], p = 0.04). In C57BL/6N mice, females showed a later Tmax (p < 0.01) than males. SCID mice showed no difference (p = 0.14). Treated SCID mice showed no significant delay in Tmax (2.0 [1.4–2.7], p = 0.15) but a significant delay in T50 (p = 0.02) and T25 (p = 0.01) compared to healthy untreated mice.
Conclusion This study demonstrated significant sex-related differences between SCID and C57BL/6N mouse strains in kidney function. Establishment of normal values for different strains and sexes therefore is important for experimental therapy studies. Renal SPECT imaging with 99mTc-MAG3 was sufficiently sensitive to detect 177Lu-SRL treatment toxic effects on kidney function in SCID mice.
The Efficacy of the Comprehensive Use of Naphthalan and Non-Selective Chromotherapy in the Treatment of Patients with Gonarthrosis
Authors: Abramovich Stanislav G. , Drobyshev Victor A. , Koneva Elizaveta S. , Makhova Anna A. 
Published: February 2020

AbstractIn the last decade, a new direction of phototherapy – the non-selective chromotherapy (NSC) with Bioptron – has become widespread in clinical physiotherapy. The aim of the study was the scientific justification of the comprehensive treatment of patients with osteoarthritis of knee joints, including the combined use of refined naphthalan applications and irradiation with incoherent polarized Bioptron light. The article presents the results of the study which investigated the efficacy of the comprehensive treatment of osteoarthritis of knee joints in patients using the combined exposure to naphthalan applications with irradiation using the non-selective Bioptron chromotherapy in the sanatorium. 64 patients aged 40–69 years with stage 1–3 knee osteoarthritis were examined and treated. It was shown that the combined use of naphthalan and non-selective chromotherapy in patients with gonarthrosis reduces pain, improves the functional state of the affected knee joints and improves the quality of life of patients in the absence of adverse effects. A comparative analysis of the study results showed that the efficacy of the combined use of naphthalan and non-selective chromotherapy is superior to the isolated effect of naphthalan.