bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral tropism and detection of clade 2.3.4.4b H5N8 highly pathogenic avian influenza viruses in feathers of ducks and geese
Authors: Gaide Nicolas , Foret-Lucas Charlotte , Figueroa Thomas , Vergne Timothée , Lucas Marie-Noëlle , Robertet Luc , Souvestre Marie , Croville Guillaume , Le Loc’h Guillaume , Delverdier Maxence , Guérin Jean-Luc 
Published: March 2021

AbstractHighly Pathogenic Avian Influenza viruses (HPAIVs) display a tissue pantropism, which implies a possible spread in feathers. HPAIV detection from feathers had been evaluated for H5N1 or H7N1 HPAIVs. It was suggested that viral RNA loads could be equivalent or higher in samples of immature feather compared to tracheal (TS) or cloacal swabs (CS). We investigated the suitability of feathers for the detection of clade 2.3.4.4b H5N8 HPAIV in ducks and geese field samples. In the six H5N8 positive flocks that were included in this study, TS, CS and immature wing feathers were taken from at least 10 birds. Molecular loads were then estimated using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) targetting H5 and M genes. In all flocks, viral loads were at least equivalent between feather and swab samples and in most cases up to 103 higher in feathers. Bayesian modelling confirmed that, in infected poultry, RT-qPCR was much more likely to be positive when applied on a feather sample only (estimated sensitivity between 0.89 and 0.96 depending on the positivity threshold) than on a combination of a tracheal and a cloacal swab (estimated sensitivity between 0.45 and 0.68 depending on the positivity threshold). Viral tropism and lesions in feathers were evaluated by histopathology and immunohistochemistry. Epithelial necrosis of immature feathers and follicles was observed concurrently with positive viral antigen detection and leukocytic infiltration of pulp. Accurate detection of clade 2.3.4.4b HPAIVs in feather samples were finally confirmed with experimental H5N8 infection on 10-week-old mule ducks, as viral loads at 3, 5 and 7 days post-infection were higher in feathers than in tracheal or cloacal swabs. However, feather samples were associated with lower viral loads than tracheal swabs at day 1, suggesting better detectability of the virus in feathers in the later course of infection. These results, based on both field cases and experimental infections, suggest that feather samples should be included in the toolbox of samples for detection of clade 2.3.4.4b HPAI viruses, at least in ducks and geese.
Bone marrow stromal cells from MDS and AML patients show increased adipogenic potential with reduced Delta-like-1 expression
Authors: Weickert Marie-Theresa , Hecker Judith S. , Buck Michèle C. , Schreck Christina , Rivière Jennifer , Schiemann Matthias , Schallmoser Katharina , Bassermann Florian , Strunk Dirk , Oostendorp Robert A. J. , Götze Katharina S. 
Published: March 2021

AbstractMyelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell disorders with a poor prognosis, especially for elderly patients. Increasing evidence suggests that alterations in the non-hematopoietic microenvironment (bone marrow niche) can contribute to or initiate malignant transformation and promote disease progression. One of the key components of the bone marrow (BM) niche are BM stromal cells (BMSC) that give rise to osteoblasts and adipocytes. It has been shown that the balance between these two cell types plays an important role in the regulation of hematopoiesis. However, data on the number of BMSC and the regulation of their differentiation balance in the context of hematopoietic malignancies is scarce. We established a stringent flow cytometric protocol for the prospective isolation of a CD73+ CD105+ CD271+ BMSC subpopulation from uncultivated cryopreserved BM of MDS and AML patients as well as age-matched healthy donors. BMSC from MDS and AML patients showed a strongly reduced frequency of CFU-F (colony forming unit-fibroblast). Moreover, we found an altered phenotype and reduced replating efficiency upon passaging of BMSC from MDS and AML samples. Expression analysis of genes involved in adipo- and osteogenic differentiation as well as Wnt- and Notch-signalling pathways showed significantly reduced levels of DLK1, an early adipogenic cell fate inhibitor in MDS and AML BMSC. Matching this observation, functional analysis showed significantly increased in vitro adipogenic differentiation potential in BMSC from MDS and AML patients. Overall, our data show BMSC with a reduced CFU-F capacity, and an altered molecular and functional profile from MDS and AML patients in culture, indicating an increased adipogenic lineage potential that is likely to provide a disease-promoting microenvironment.
Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults
Authors: van Hoffen Els , Mercenier Annick , Vidal Karine , Benyacoub Jalil , Schloesser Joyce , Kardinaal Alwine , Lucas-van de Bos Elly , van Alen Ingrid , Roggero Iris , Duintjer Kim , Berendts Anneke , Albers Ruud , Kleerebezem Michiel , ten Bruggencate Sandra 
Published: March 2021

AbstractAn experimental human challenge model with an attenuated diarrheagenic Escherichia coli (E. coli) strain has been used in food intervention studies aimed to increase resistance to E. coli infection. This study was designed to refine and expand this challenge model. In a double-blind study, healthy male subjects were orally challenged with 1E10 or 5E10 colony-forming units (CFU) of E. coli strain E1392/75-2A. Three weeks later, subjects were rechallenged with 1E10 CFU of E. coli. Before and after both challenges, clinical symptoms and infection- and immune-related biomarkers were analyzed. Subset analysis was performed on clinically high- and low-responders. Regardless of inoculation dose, the first challenge induced clinical symptoms for 2–3 days. In blood, neutrophils, CRP, CXCL10, and CFA/II-specific IgG were induced, and in feces calprotectin and CFA/II-specific IgA. Despite clinical differences between high- and low-responders, infection and immune biomarkers did not differ. The first inoculation induced protection at the second challenge, with a minor clinical response, and no change in biomarkers. The refined study design resulted in a larger dynamic range of symptoms, and identification of biomarkers induced by a challenge with the attenuated E. coli strain E1392/75-2A, which is of value for future intervention studies. Addition of a second inoculation allows to study the protective response induced by a primary infection.Clinicaltrials.gov registration: NCT02541695 (04/09/2015).
Mueller polarimetric imaging for fast macroscopic mapping of microscopic collagen matrix remodeling by smooth muscle cells
Authors: Chashchina Olga , Mezouar Hachem , Vizet Jérémy , Raoux Clothilde , Park Junha , Ramón-Lozano Clara , Schanne-Klein Marie-Claire , Barakat Abdul I. , Pierangelo Angelo 
Published: March 2021

AbstractSmooth muscle cells (SMCs) are critical players in cardiovascular disease development and undergo complex phenotype switching during disease progression. However, SMC phenotype is difficult to assess and track in co-culture studies. To determine the contractility of SMCs embedded within collagen hydrogels, we performed polarized light imaging and subsequent analysis based on Mueller matrices. Measurements were made both in the absence and presence of endothelial cells (ECs) in order to establish the impact of EC-SMC communication on SMC contractility. The results demonstrated that Mueller polarimetric imaging is indeed an appropriate tool for assessing SMC activity which significantly modifies the hydrogel retardance in the presence of ECs. These findings are consistent with the idea that EC-SMC communication promotes a more contractile SMC phenotype. More broadly, our findings suggest that Mueller polarimetry can be a useful tool for studies of spatial heterogeneities in hydrogel remodeling by SMCs.
Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding
Authors: Nguyen Brian , Ma Rui , Tang Wai Kwan , Shi Dashuang , Tolia Niraj H. 
Published: March 2021

AbstractPlasmodium falciparum harbors group 1 and group 2 chaperonin systems to mediate the folding of cellular proteins in different cellular locations. Two distinct group 1 chaperonins operate in the organelles of mitochondria and apicoplasts, while group 2 chaperonins function in the cytosol. No structural information has been reported for any chaperonin from plasmodium. In this study, we describe the crystal structure of a double heptameric ring Plasmodium falciparum mitochondrial chaperonin 60 (Cpn60) bound with ATP, which differs significantly from any known crystal structure of chaperonin 60. The structure likely represents a unique intermediate state during conformational conversion from the closed state to the opened state. Three of the seven apical domains are highly dynamic while the equatorial domains form a stable ring. The structure implies large movements of the apical domain in the solution play a role in nucleotide-dependent regulation of substrate binding and folding. A unique 26–27 residue insertion in the equatorial domain of Plasmodium falciparum mitochondrial chaperonin greatly increases both inter-ring and intra-ring subunit–subunit interactions. The present structure provides new insights into the mechanism of Cpn60 in chaperonin assembly and function.
Modeling preeclampsia using human induced pluripotent stem cells
Authors: Horii Mariko , Morey Robert , Bui Tony , Touma Ojeni , Nelson Katharine K. , Cho Hee-Young , Rishik Hannah , Laurent Louise C. , Parast Mana M. 
Published: March 2021

AbstractPreeclampsia (PE) is a pregnancy-specific hypertensive disorder, affecting up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation of human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like cells, and then into both syncytiotrophoblast (STB)- and extravillous trophoblast (EVT)-like cells, and showed that it can model both normal and abnormal trophoblast differentiation. We have now applied this protocol to induced pluripotent stem cells (iPSC) derived from placentas of pregnancies with or without PE. While there were no differences in CTB induction or EVT formation, PE-iPSC-derived trophoblast showed a defect in syncytialization, as well as a blunted response to hypoxia. RNAseq analysis showed defects in STB formation and response to hypoxia; however, DNA methylation changes were minimal, corresponding only to changes in response to hypoxia. Overall, PE-iPSC recapitulated multiple defects associated with placental dysfunction, including a lack of response to decreased oxygen tension. This emphasizes the importance of the maternal microenvironment in normal placentation, and highlights potential pathways that can be targeted for diagnosis or therapy, while absence of marked DNA methylation changes suggests that other regulatory mechanisms mediate these alterations.
Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression
Authors: Kase Yutaro , Uzawa Katsuhiro , Wagai Sho , Yoshimura Shusaku , Yamamoto Jun-Ichiro , Toeda Yuriko , Okubo Megumi , Eizuka Keitaro , Ando Toshiaki , Nobuchi Takafumi , Kawasaki Kohei , Saito Tomoaki , Iyoda Manabu , Nakashima Dai , Kasamatsu Atsushi , Tanzawa Hideki 
Published: March 2021

AbstractExosomes are involved in a wide range of biological processes in human cells. Considerable evidence suggests that engineered exosomes (eExosomes) containing therapeutic agents can attenuate the oncogenic activity of human cancer cells. Despite its biomedical relevance, no information has been available for oral squamous cell carcinoma (OSCC), and therefore the development of specific OSCC-targeting eExosomes (octExosomes) is urgently needed. We demonstrated that exosomes from normal fibroblasts transfected with Epstein–Barr Virus Induced-3 (EBI3) cDNA were electroporated with siRNA of lymphocyte cytoplasmic protein 1 (LCP1), as octExosomes, and a series of experiments were performed to evaluate the loading specificity/effectiveness and their anti-oral cancer cell activities after administration of octExosomes. These experiments revealed that octExosomes were stable, effective for transferring siLCP1 into OSCC cells and LCP1 was downregulated in OSCC cells with octExosomes as compared with their counterparts, leading to a significant tumor-suppressive effect in vitro and in vivo. Here we report the development of a new valuable tool for inhibiting tumor cells. By engineering exosomes, siLCP1 was transferred to specifically suppress oncogenic activity of OSCC cells. Inhibition of other types of human malignant cells merits further study.
A modeling study to inform screening and testing interventions for the control of SARS-CoV-2 on university campuses
Authors: Lopman Ben , Liu Carol Y. , Le Guillou Adrien , Handel Andreas , Lash Timothy L. , Isakov Alexander P. , Jenness Samuel M. 
Published: March 2021

AbstractUniversity administrators face decisions about how to safely return and maintain students, staff and faculty on campus throughout the 2020–21 school year. We developed a susceptible-exposed-infectious-recovered (SEIR) deterministic compartmental transmission model of SARS-CoV-2 among university students, staff, and faculty. Our goals were to inform planning at our own university, Emory University, a medium-sized university with around 15,000 students and 15,000 faculty and staff, and to provide a flexible modeling framework to inform the planning efforts at similar academic institutions. Control strategies of isolation and quarantine are initiated by screening (regardless of symptoms) or testing (of symptomatic individuals). We explored a range of screening and testing frequencies and performed a probabilistic sensitivity analysis. We found that among students, monthly and weekly screening can reduce cumulative incidence by 59% and 87%, respectively, while testing with a 2-, 4- and 7-day delay between onset of infectiousness and testing results in an 84%, 74% and 55% reduction in cumulative incidence. Smaller reductions were observed among staff and faculty. Community-introduction of SARS-CoV-2 onto campus may be controlled with testing, isolation, contract tracing and quarantine. Screening would need to be performed at least weekly to have substantial reductions beyond disease surveillance. This model can also inform resource requirements of diagnostic capacity and isolation/quarantine facilities associated with different strategies.
Coherence of assistance and assisted maximally coherent states
Authors: Zhao Ming-Jing , Pereira Rajesh , Ma Teng , Fei Shao-Ming 
Published: March 2021

AbstractCoherence and entanglement are fundamental concepts in resource theory. The coherence (entanglement) of assistance is the coherence (entanglement) that can be extracted assisted by another party with local measurement and classical communication. We introduce and study the general coherence of assistance. First, in terms of real symmetric concave functions on the probability simplex, the coherence of assistance and the entanglement of assistance are shown to be in one-to-one correspondence. We then introduce two classes of quantum states: the assisted maximally coherent states and the assisted maximally entangled states. They can be transformed into maximally coherent or entangled pure states with the help of another party using local measurement and classical communication. We give necessary conditions for states to be assisted maximally coherent or assisted maximally entangled. Based on these, a unified framework between coherence and entanglement including coherence (entanglement) measures, coherence (entanglement) of assistance, coherence (entanglement) resources is proposed. Then we show that the coherence of assistance as well as entanglement of assistance are strictly larger than the coherence of convex roof and entanglement of convex roof for all full rank density matrices. So all full rank quantum states are distillable in the assisted coherence distillation.
Bacterial profiling of Haemonchus contortus gut microbiome infecting Dohne Merino sheep in South Africa
Authors: Mafuna T. , Soma P. , Tsotetsi-Khambule A. M. , Hefer C. A. , Muchadeyi F. C. , Thekisoe O. M. M. , Pierneef R. E. 
Published: March 2021

AbstractA metagenomic approach was used to study the gut microbiome of Haemonchus contortus field strains and that of its predilection site, the abomasum of Dohne Merino sheep. The abomasum contents and H. contortus were collected from 10 naturally infected Dohne Merino sheep. The H. contortus specimens were classified and sexually differentiated using morphometric characters and was further confirmed through molecular identification. We investigated differences and similarities between the bacterial composition of the adult male and female H. contortus gut microbiomes, which were both dominated by bacteria from the Escherichia, Shigella, Vibrio and Halomonas genera. Major abundance variations were identified between the shared adult male and female H. contortus microbiomes. The results also revealed that Succiniclasticum, Rikenellaceae RC9 gut group and Candidatus Saccharimonas were the predominant genera in the Dohne Merino abomasum. This study provides insight into the highly diverse bacterial composition of the H. contortus gut microbiome and the Dohne Merino abomasum which needs to be studied further to explore the complex interactions of different gastrointestinal nematode microbiomes with the host.
Development of an optimized sample preparation method for quantification of free fatty acids in food using liquid chromatography-mass spectrometry
Authors: Park Hyejin , Song Woo-Young , Cha Hyeonjeon , Kim Tae-Young 
Published: March 2021

AbstractAccurate and precise determination of free fatty acid (FFA) contents is essential for quality control and assurance in food production. Herein, a mass spectrometric study was performed to develop a sample preparation protocol that can minimize exogenous FFA contamination during the quantification of FFA in food. The quantities of exogenous FFAs were measured using various combinations of seven pretreatment methods for a sample tube, three extraction methods, and four types of sample tubes. Methanol washing could effectively reduce exogenous palmitic acid (PA) and stearic acid (SA) by 73 and 64%, respectively, in contrast to furnace baking resulting in a decrease in the amount of PA and SA contaminants by 50 and 37%, respectively. A lower amount of FFA contaminants was extracted from glass tubes during comparative analysis of the four different sample tubes studied. A combination of a methanol-washed glass tube and chloroform extraction solvent was determined to be the optimal method for minimizing the error in FFA quantification. The optimized sample preparation protocol used for FFA quantification can lower the amount of foreign palmitic acid and stearic acid to the sub-nanomolar level in the analysis of FFAs in skimmed milk.
Penile secondary lesions: a rare entity detected by PET/CT
Authors: Davidson Tima , Domachevsky Liran , Giladi Yogev , Fridman Eddie , Dotan Zohar , Rosenzweig Barak , Leibowitz Raya , Ben Shimol Jennifer 
Published: March 2021

AbstractWhile penile metastases are rare, PET/CT has facilitated their detection. We aimed to describe penile secondary lesions (PSL) identified by PET/CT. We reviewed 18F-FDG and Ga68-PSMA PET/CT records performed in a single center during May 2012-March 2020, for PSL. Of 16,774 18F-FDG and 1,963 Ga68-PSMA-PET scans, PSL were found in 24(0.13%) men with a mean age of 74. PSMA detected PSL in 12 with prostate cancer; FDG identified PSL in 4 with lymphoma, 3 with colorectal cancer, 2 with lung cancer, and one each with bladder cancer, pelvic sarcoma, and leukemia. Mean SUVmax of PSL was 7.9 ± 4.2 with focal uptake in 13(54%). Mean lesion size was 16.5 ± 6.8 mm; 8 at the penile root, 4 along the shaft, and 1 at the glans. CT detected loss of the penile texture in 15(63%). PSL were observed only during relapse or follow-up of disseminated disease. Among those with prostate cancer, PSA varied widely. Fifteen (62.5%) died, at a mean 13.3 ± 15.9 months following PSL demonstration, nine had non-prostate malignancies. PET/CT identified and characterized PSL in a fraction of cancer patients, most commonly those with prostate cancer. PSL universally surfaced in advanced disease, and signaled high mortality, especially in non-prostate cancers.
Static and dynamic failure mechanisms of circular granite under the condition of water-heat cycles
Authors: Wang Chun , Li Xin-ru , Xie Mei-zhi , Xiong Zu-qiang , Wang Cheng , Wang Huai-bin , Zhan Shuai-fei , Hu Ya-chao 
Published: March 2021

AbstractBased on the engineering environment where rocks surrounding wellbores in energy storage areas are influenced by high temperature, cool and hot water, thermal stress etc. in the exploitation of hydrothermally geothermal energy, the experimental study on mechanical properties of ring granite under the static and dynamic loads in the water-heat condition was performed. The experimental results showed that when the ring granite was influenced by the inner diameters, heating temperatures, curing temperatures and heat recovery cycle times, the impact load-strain curves were nonlinear. However, the concave stages, platform stages and cliff-like drop stages appeared in the load-strain curves under the static loads. The radical peak loads decreased exponentially with the growth of the damage factors and the dynamic peak loads were far greater than the static peak loads. By analyzing the damage cracks and broken fragments, it was found that under the static and dynamic radical loads, the cracks generated in the ring specimens were tensile cracks and the failure mode was tensile failure. However, the dynamic failure was more aggressive than the static failure. Then, the apparent deformation modulus was defined to describe the deformation characteristics of ring granite before the radical peak loads. And it is found that the variation law of dynamic apparent deformation modulus is more dispersed than the changes of static apparent deformation modulus. Finally, based on the deformation and failure characteristics of ring granite obtained from the tests, the static and dynamic failure criteria considering whether the cracks along the loading direction were generated in the inner ring wall were deduced and verified by the corresponding tests.
The in vitro addition of idarucizumab to plasma samples from patients increases thrombin generation
Authors: Božič Mijovski Mojca , Malmström Rickard E. , Vene Nina , Antovic Jovan P. , Mavri Alenka 
Published: March 2021

AbstractDabigatran interferes with many coagulation tests. To overcome this obstacle the use of idarucizumab as an in vitro antidote to dabigatran has been proposed. The aim of this study was to test the effect of idarucizumab as an in vitro antidote to dabigatran in ex vivo plasma samples from routine clinical patients examined by a thrombin generation assay (TGA). From 44 patients with atrial fibrillation five blood samples were collected. Thrombin generation was measured in all samples before and after the addition of idarucizumab. When idarucizumab was added to baseline plasma (no dabigatran), it caused a significantly shorter Lag Time and Time to Peak Thrombin, and a higher Peak Thrombin and Endogenous Thrombin Potential (ETP) of TGA. Similar results were obtained when idarucizumab was added to dabigatran-containing plasma, with TGA parameters comparable to baseline + idarucizumab plasma, but not to baseline plasma. In summary, our study showed that in vitro addition of idarucizumab to plasma samples from patients increases thrombin generation. The use of idarucizumab to neutralize dabigatran in patient plasma samples as well as the clinical relevance of in vitro increased thrombin generation induced by idarucizumab needs further investigation.