bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial
Authors: Jagannathan Prasanna , Andrews Jason R. , Bonilla Hector , Hedlin Haley , Jacobson Karen B. , Balasubramanian Vidhya , Purington Natasha , Kamble Savita , de Vries Christiaan R. , Quintero Orlando , Feng Kent , Ley Catherine , Winslow Dean , Newberry Jennifer , Edwards Karlie , Hislop Colin , Choong Ingrid , Maldonado Yvonne , Glenn Jeffrey , Bhatt Ami , Blish Catherine , Wang Taia , Khosla Chaitan , Pinsky Benjamin A. , Desai Manisha , Parsonnet Julie , Singh Upinder 
Published: March 2021

AbstractType III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.
Diffusion in dense supercritical methane from quasi-elastic neutron scattering measurements
Authors: Ranieri Umbertoluca , Klotz Stefan , Gaal Richard , Koza Michael Marek , Bove Livia E. 
Published: March 2021

AbstractMethane, the principal component of natural gas, is an important energy source and raw material for chemical reactions. It also plays a significant role in planetary physics, being one of the major constituents of giant planets. Here, we report measurements of the molecular self-diffusion coefficient of dense supercritical CH4 reaching the freezing pressure. We find that the high-pressure behaviour of the self-diffusion coefficient measured by quasi-elastic neutron scattering at 300 K departs from that expected for a dense fluid of hard spheres and suggests a density-dependent molecular diameter. Breakdown of the Stokes–Einstein–Sutherland relation is observed and the experimental results suggest the existence of another scaling between self-diffusion coefficient D and shear viscosity η, in such a way that Dη/ρ=constant at constant temperature, with ρ the density. These findings underpin the lack of a simple model for dense fluids including the pressure dependence of their transport properties.
SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself
Authors: Ferreira-Gomes Marta , Kruglov Andrey , Durek Pawel , Heinrich Frederik , Tizian Caroline , Heinz Gitta Anne , Pascual-Reguant Anna , Du Weijie , Mothes Ronja , Fan Chaofan , Frischbutter Stefan , Habenicht Katharina , Budzinski Lisa , Ninnemann Justus , Jani Peter K. , Guerra Gabriela Maria , Lehmann Katrin , Matz Mareen , Ostendorf Lennard , Heiberger Lukas , Chang Hyun-Dong , Bauherr Sandy , Maurer Marcus , Schönrich Günther , Raftery Martin , Kallinich Tilmann , Mall Marcus Alexander , Angermair Stefan , Treskatsch Sascha , Dörner Thomas , Corman Victor Max , Diefenbach Andreas , Volk Hans-Dieter , Elezkurtaj Sefer , Winkler Thomas H. , Dong Jun , Hauser Anja Erika , Radbruch Helena , Witkowski Mario , Melchers Fritz , Radbruch Andreas , Mashreghi Mir-Farzin 
Published: March 2021

AbstractThe pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.
Single strain control of microbial consortia
Authors: Fedorec Alex J. H. , Karkaria Behzad D. , Sulu Michael , Barnes Chris P. 
Published: March 2021

AbstractThe scope of bioengineering is expanding from the creation of single strains to the design of microbial communities, allowing for division-of-labour, specialised sub-populations and interaction with “wild” microbiomes. However, in the absence of stabilising interactions, competition between microbes inevitably leads to the removal of less fit community members over time. Here, we leverage amensalism and competitive exclusion to stabilise a two-strain community by engineering a strain of Escherichia coli which secretes a toxin in response to competition. We show experimentally and mathematically that such a system can produce stable populations with a composition that is tunable by easily controllable parameters. This system creates a tunable, stable two-strain consortia while only requiring the engineering of a single strain.
Topological protection versus degree of entanglement of two-photon light in photonic topological insulators
Authors: Tschernig Konrad , Jimenez-Galán Álvaro , Christodoulides Demetrios N. , Ivanov Misha , Busch Kurt , Bandres Miguel A. , Perez-Leija Armando 
Published: March 2021

AbstractTopological insulators combine insulating properties in the bulk with scattering-free transport along edges, supporting dissipationless unidirectional energy and information flow even in the presence of defects and disorder. The feasibility of engineering quantum Hamiltonians with photonic tools, combined with the availability of entangled photons, raises the intriguing possibility of employing topologically protected entangled states in optical quantum computing and information processing. However, while two-photon states built as a product of two topologically protected single-photon states inherit full protection from their single-photon “parents”, a high degree of non-separability may lead to rapid deterioration of the two-photon states after propagation through disorder. In this work, we identify physical mechanisms which contribute to the vulnerability of entangled states in topological photonic lattices. Further, we show that in order to maximize entanglement without sacrificing topological protection, the joint spectral correlation map of two-photon states must fit inside a well-defined topological window of protection.
Replicating bacterium-vectored vaccine expressing SARS-CoV-2 Membrane and Nucleocapsid proteins protects against severe COVID-19-like disease in hamsters
Authors: Jia Qingmei , Bielefeldt-Ohmann Helle , Maison Rachel M. , Masleša-Galić Saša , Cooper Sarah K. , Bowen Richard A. , Horwitz Marcus A. 
Published: March 2021

AbstractTo generate an inexpensive readily manufactured COVID-19 vaccine, we employed the LVS ΔcapB vector platform, previously used to generate potent candidate vaccines against Select Agent diseases tularemia, anthrax, plague, and melioidosis. Vaccines expressing SARS-CoV-2 structural proteins are constructed using the LVS ΔcapB vector, a highly attenuated replicating intracellular bacterium, and evaluated for efficacy in golden Syrian hamsters, which develop severe COVID-19-like disease. Hamsters immunized intradermally or intranasally with a vaccine co-expressing the Membrane and Nucleocapsid proteins and challenged 5 weeks later with a high dose of SARS-CoV-2 are protected against severe weight loss and lung pathology and show reduced viral loads in the oropharynx and lungs. Protection correlates with anti-Nucleocapsid antibody. This potent vaccine should be safe; inexpensive; easily manufactured, stored, and distributed; and given the high homology between Membrane and Nucleocapsid proteins of SARS-CoV and SARS-CoV-2, potentially serve as a universal vaccine against the SARS subset of pandemic causing β-coronaviruses.
Highest risk abandoned, lost and discarded fishing gear
Authors: Gilman Eric , Musyl Michael , Suuronen Petri , Chaloupka Milani , Gorgin Saeid , Wilson Jono , Kuczenski Brandon 
Published: March 2021

AbstractDerelict abandoned, lost and discarded fishing gear have profound adverse effects. We assessed gear-specific relative risks from derelict gear to rank-order fishing methods based on: derelict gear production rates, gear quantity indicators of catch weight and fishing grounds area, and adverse consequences from derelict gear. The latter accounted for ghost fishing, transfer of microplastics and toxins into food webs, spread of invasive alien species and harmful microalgae, habitat degradation, obstruction of navigation and in-use fishing gear, and coastal socioeconomic impacts. Globally, mitigating highest risk derelict gear from gillnet, tuna purse seine with fish aggregating devices, and bottom trawl fisheries achieves maximum conservation gains. Locally, adopting controls following a sequential mitigation hierarchy and implementing effective monitoring, surveillance and enforcement systems are needed to curb derelict gear from these most problematic fisheries. Primary and synthesis research are priorities to improve future risk assessments, produce the first robust estimate of global derelict gear quantity, and assess the performance of initiatives to manage derelict gear. Findings from this first quantitative estimate of gear-specific relative risks from derelict gear guide the allocation of resources to achieve the largest improvements from mitigating adverse effects of derelict gear from the world’s 4.6 million fishing vessels.
Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis
Authors: Oveland Eystein , Ahmad Intakhar , Lereim Ragnhild Reehorst , Kroksveen Ann Cathrine , Barsnes Harald , Guldbrandsen Astrid , Myhr Kjell-Morten , Bø Lars , Berven Frode S. , Wergeland Stig 
Published: March 2021

AbstractTwo pathophysiological different experimental models for multiple sclerosis were analyzed in parallel using quantitative proteomics in attempts to discover protein alterations applicable as diagnostic-, prognostic-, or treatment targets in human disease. The cuprizone model reflects de- and remyelination in multiple sclerosis, and the experimental autoimmune encephalomyelitis (EAE, MOG1-125) immune-mediated events. The frontal cortex, peripheral to severely inflicted areas in the CNS, was dissected and analyzed. The frontal cortex had previously not been characterized by proteomics at different disease stages, and novel protein alterations involved in protecting healthy tissue and assisting repair of inflicted areas might be discovered. Using TMT-labelling and mass spectrometry, 1871 of the proteins quantified overlapped between the two experimental models, and the fold change compared to controls was verified using label-free proteomics. Few similarities in frontal cortex between the two disease models were observed when regulated proteins and signaling pathways were compared. Legumain and C1Q complement proteins were among the most upregulated proteins in cuprizone and hemopexin in the EAE model. Immunohistochemistry showed that legumain expression in post-mortem multiple sclerosis brain tissue (n = 19) was significantly higher in the center and at the edge of white matter active and chronic active lesions. Legumain was associated with increased lesion activity and might be valuable as a drug target using specific inhibitors as already suggested for Parkinson’s and Alzheimer’s disease. Cerebrospinal fluid levels of legumain, C1q and hemopexin were not significantly different between multiple sclerosis patients, other neurological diseases, or healthy controls.
Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
Authors: Turubanova Victoria D. , Mishchenko Tatiana A. , Balalaeva Irina V. , Efimova Iuliia , Peskova Nina N. , Klapshina Larisa G. , Lermontova Svetlana A. , Bachert Claus , Krysko Olga , Vedunova Maria V. , Krysko Dmitri V. 
Published: March 2021

AbstractThe immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger effective anti-tumor immunity. Only a few photosensitizers are known to induce ICD and, therefore, there is a need for development of new photosensitizers that can induce ICD. The purpose of this work was to analyze whether photosensitizers developed in-house from porphyrazines (pz I and pz III) can induce ICD in vitro and in vivo when used in PDT. We indetified the optimal concentrations of the photosensitizers and found that, at a light dose of 20 J/cm2(λex615–635 nm), both pz I and pz III efficiently induced cell death in cancer cells. We demonstrate that pz I localized predominantly in the Golgi apparatus and lysosomes while pz III in the endoplasmic reticulum and lysosomes. The cell death induced by pz I-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) but not by ferrostatin-1 and DFO (ferroptosis inhibitors) or by necrostatin-1 s (necroptosis inhibitor). By contrast, the cell death induced by pz III-PDT was inhibited by z-VAD-fmk and by the necroptosis inhibitor, necrostatin-1 s. Cancer cells induced by pz I-PDT or pz III-PDT released HMGB1 and ATP and were engulfed by bone marrow-derived dendritic cells, which then matured and became activated in vitro. We demonstrate that cancer cells, after induction of cell death by pz I-PDT or pz III-PDT, are protective when used in the mouse model of prophylactic tumor vaccination. By vaccinating immunodeficient mice, we prove the role of the adaptive immune system in protecting against tumours. All together, we have shown that two novel porphyrazines developed in-house are potent ICD inducers that could be effectively applied in PDT of cancer.
Characterization of a novel mCH3 conjugated anti-PcrV scFv molecule
Authors: Komijani Samira , Bayat Elham , Rismani Elham , Hosseini Soma , Moazzami Reza , Nematollahi Leila , Sardari Soroush , Talebkhan Yeganeh , Davami Fatemeh , Barkhordari Farzaneh , Hosseini Fakhrisadat , Jahandar Hoda 
Published: March 2021

AbstractPseudomonas aeruginosa(PA) is a leading cause of nosocomial infections and death in cystic fibrosis patients. The study was conducted to evaluate the physicochemical structure, biological activity and serum stability of a recombinant anti-PcrV single chain variable antibody fragment genetically attached to the mCH3cc domain. The stereochemical properties of scFv-mCH3 (YFL001) and scFv (YFL002) proteins as well as molecular interactions towardsPseudomonas aeruginosaPcrV were evaluated computationally. The subcloned fragments encoding YFL001 and YFL002 in pET28a were expressed within theE. coliBL21-DE3 strain. After Ni–NTA affinity chromatography, the biological activity of the proteins in inhibition of PA induced hemolysis as well as cellular cytotoxicity was assessed. In silico analysis revealed the satisfactory stereochemical quality of the models as well as common residues in their interface with PcrV. The structural differences of proteins through circular dichroism spectroscopy were confirmed by NMR analysis. Both proteins indicated inhibition of ExoU positive PA strains in hemolysis of red blood cells compared to ExoU negative strains as well as cytotoxicity effect on lung epithelial cells. The ELISA test showed the longer serum stability of the YFL001 molecule than YFL002. The results were encouraging to further evaluation of these two scFv molecules in animal models.
Experimental study on variation law of electrical parameters and temperature rise effect of coal under DC electric field
Authors: Yang Yunpeng , Wen Zhihui , Si Leilei , Xu Xiangyu 
Published: March 2021

AbstractJoule heats which are generated by coals in an applied electric field are directly correlated with variation resistivity of electrical parameters of coals. Moreover, the joule heating effect is closely related with microstructural changes and relevant products of coal surface. In the present study, a self-developed applied direct current (DC) field was applied onto an experimental system of coals to investigate variation resistivity of electrical parameters of highly, moderately and lowly metamorphic coal samples. Moreover, breakdown voltages and breakdown field intensities of above three coal samples with different metamorphic grades were tested and calculated. Variation resistivity of electrical parameters of these three coal samples in 2 kV and 4 kV DC fields were analyzed. Results show that internal current of all coal samples increases continuously and tends to be stable gradually after reaching the “inflection point” at peak. The relationship between temperature rise effect on anthracite coal surface in an applied DC field and electrical parameters was discussed. The temperature rise process on anthracite coal surface is composed of three stages, namely, slowly warming, rapid warming and slow cooling to stabilize. The temperature rise effect on anthracite coal surface lags behind changes of currents which run through coal samples. There’s uneven temperature distribution on anthracite coal surface, which is attributed to the heterogeneity of coal samples. In the experiment, the highest temperature on anthracite coal surface 65.8 ℃ is far belower than the lowest temperature for pyrolysis-induced gas production of coals 200 ℃. This study lays foundations to study microstructural changes and relevant products on coal surface in an applied DC field.
Concurrent validity of the short version of Montreal Cognitive Assessment (MoCA) for patients with stroke
Authors: Feng Yali , Zhang Jiaqi , Zhou Yi , Chen Bo , Yin Ying 
Published: March 2021

AbstractThe aim of the present study was to examine the concurrent validity of 2 Chinese versions of the short version of the Montreal Cognitive Assessment (MoCA) in patients with stroke, i.e., MoCA 5-minute protocol and National Institute for Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) 5-minute Protocol. A total of 54 patients and 27 healthy controls were enrolled in this study. In this study, the Neurobehavioural Cognitive Status Examination (NCSE) was used as an external criterion of cognitive impairment. We found that the 5-min protocol did not differ from the MoCA in differentiating patients with cognitive impairments from those without (area under the receiver operating characteristic curve, AUC, of 0.948 for the MoCA 5-min protocol v.s. 0.984 for MoCA, P = 0.097). These three assessments demonstrated equal performance in differentiating patients with stroke from controls. The Chinese version of the MoCA 5-min protocol can be used as a valid screening for patients with stroke.
Inhibitory properties of Chinese Herbal Formula SanHuang decoction on biofilm formation by antibiotic-resistant Staphylococcal strains
Authors: Zhang Shaoe , Wang Peizhao , Shi Xiaotao , Tan Honglue 
Published: March 2021

AbstractThe aim of this study was to explore the effect of Chinese herbal SanHuang decoction (SH) on biofilm formation of antibiotic-resistant Staphylococci on titanium surface, and to explore its mechanism. Biofilm-forming ATCC 35984, ATCC 43300 and MRSE 287 were used in this study. The MICs of SH and vancomycin against Staphylococci were determined by the broth microdilution method. Six groups were designed, namely control group (bacteria cultured with medium), 1/8MIC SH group (1MIC SH was diluted by 1/8 using TSB or saline), 1/4MIC SH group, 1/2MIC SH group, 1MIC SH group and vancomycin group (bacteria cultured with 1MIC vancomycin). The inhibitory effect on bacterial adhesion and biofilm formation were observed by the spread plate method, CV staining, SEM, and CLSM. Real-time PCR was performed to determine the effect of SH on the expression levels of ica AD and ica R gene in ATCC 35984 during the biofilm formation. The strains were found to be susceptible to SH and vancomycin with MIC of 38.75 mg/ml and 2.5 μg/ml, respectively. SH with 1 MIC and 1/2 MIC could inhibit the bacteria adhesion, showing only scattered adhesion from SEM. CLSM showed that SH with 1 MIC and 1/2 MIC inhibited the biofilm formation. The quantitative results of the spread plate method and CV staining showed that there was significant differences between the SH groups (P < 0.05). Further, with an increase in SH concentration, the inhibitory effect became more obvious when compared with control group. Among the groups, vancomycin had the strongest inhibitory effect on bacterial adhesion and biofilm formation (P < 0.01). With an increase in SH concentration, the expression levels of ica AD decreased, and the expression of ica R increased correspondingly (P < 0.05). In conclusions, SH can inhibit the biofilm formation of antibiotic-resistant Staphylococci. Its probable mechanistic activity may be through the inhibition of polysaccharide intercellular adhesin synthesis by down-regulating the expression of ica AD gene.