bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiological, Clinical Characteristics and Risk Factors for Severe Condition and ICU Admission of COVID-19 Patients of Early Stage in China: A review
Authors: Fu Qinwei , Wu Wenjuan , Liu Yang , Huang Heyin , Zhang Peihai , Li Xinrong , Liu Ying , Zhang Lanzhi , Yang Hui , Zhang Xin , Zhang Qinxiu , Huang Chaolin 
Published: February 2021

ABSTRACTObjectiveSome retrospective studies reporting epidemiological, clinical characteristics of COVID-19 patients of early stage were published. We aim to provide an overview of epidemiological and clinical characteristics of the COVID-19 patients, and identification, treatment of early stage, especially for the patients with poor prognosis.Data SourcesPubMed, CNKI and Google Scholar.Study SelectionWe searched for published retrospective studies that described epidemiological and clinical characteristics of confirmed COVID-19 patients in China by April 14th, 2020 with search terms. Some studies were excluded according to criteria. Finally, 53 studies were included.Data ExtractionCharacteristics of the COVID-19 patients available from included articles were extracted, reorganized and recorded into electronic data forms.Data SynthesisCharacteristics of patients in the included studies were summarized and analyzed for median-interquartile ranges and univariable odds ratio.ConclusionThis study summarized, analyzed and compared epidemiological, clinical characteristics and estimated univariable risk factors among confirmed COVID-19 patients either in former epicenter, in severe condition, with ICU admission or not of early stage. Higher proportions of patients were found to have older age and more comorbidities, typical characteristics on admission and complications either in former epicenter, with severe condition or ICU admission. No evidence showed that patients who were male or had smoking history had higher susceptibility, but they were significant risk factors for severe condition. Some self-implementable traditional Chinese medicine therapies conducted for immunity improvement, control of comorbidities and reduction of some medicine intake. Limited evidence revealed that some characteristics of the disease might be changing with human-to-human transmission, and more research, especially international collaboration, is needed.Copyright form disclosureThe authors have disclosed that they do not have any potential conflicts of interest.
Epidemiological dynamics of the incidence of COVID-19 in children and the relationship with the opening of schools in Catalonia (Spain)
Authors: Perramon Aida , Soriano-Arandes Antoni , Pino David , Lazcano Uxue , Andrés Cristina , Català Martí , Gatell Anna , Carulla Mireia , Canadell Dolors , Ricós Gemma , Riera-Bosch Ma Teresa , Burgaya Silvia , Salvadó Olga , Cantero Javier , Vilà Mònica , Poblet Miriam , Sánchez Almudena , Ma Ristol Anna , Serrano Pepe , Antón Andrés , Prats Clara , Soler-Palacin Pere 
Published: February 2021

AbstractHere we analyse the epidemiological trend of the incidence of COVID-19 in children in Catalonia (Spain) during the first 20 weeks of the 2020-2021 school year. This study demonstrates that while schools were open the incidence rate among children remained significantly lower than in general population, despite a greater diagnostic effort in children. These results suggest that schools have not played a significant role in the SARS-CoV-2 dissemination in Catalonia.
Teaching an Old Dog New Tricks: Serum Troponin T as a Biomarker in Amyotrophic Lateral Sclerosis
Authors: Castro-Gomez Sergio , Radermacher Barbara , Tacik Pawel , Mirandola Sandra R. , Heneka Michael T. , Weydt Patrick 
Published: February 2021

AbstractAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Diagnosis, management and therapeutic trials are hampered by a lack of informative biomarkers. Troponins (Tn) are components of skeletal and cardiac muscles. Acute elevation of cardiac isoforms of troponin I (cTnI) and T (cTnT) in serum indicates myocardial injury. Case reports suggested that serum levels of cTnT, but not cTnI are chronically elevated in ALS and other neuromuscular disorders.Using standard clinical laboratory methodologies we studied serum troponin levels in a multicentric cross-sectional cohort of 75 ALS patients and sixty controls (DESCRIBE-ALS cohort) and in a real-world cohort of 179 consecutive patients from our ALS clinic at the University Hospital Bonn.We found that serum cTnT, is elevated in >60% of ALS patients while cTnI is always normal. Serum cTnT levels increase over time and correlate with disease severity as measured with the revised ALS FRS score. There was no correlation with the phosphorylated neurofilament heavy chain (pNfH) levels in the cerebrospinal fluid. We propose that cTnT elevations in ALS are of non-cardiac origin and may serve as a proxy of lower motor neuron or skeletal muscle involvement. They potentially help to stratify patients according to lower motoneuron involvement. Further research will determine the biological origin of the cTnT elevation and its validity as a diagnostic and/or prognostic marker. Our finding also serves as a reminder to interpret cTnT with caution elevations in patients with neuromuscular diseases.
Detection of a biolistic delivery of fluorescent markers and CRISPR/Cas9 to the pollen tube
Authors: Nagahara Shiori , Higashiyama Tetsuya , Mizuta Yoko 
Published: February 2021

AbstractIn recent years, genome-editing techniques, such as the CRISPR/Cas9 system, have been highlighted as a new approach to plant breeding.Agrobacterium-mediated transformation has been widely utilized to generate transgenic plants by introducing plasmid DNA containing CRISPR/Cas9 into plant cells. However, this method is generally applicable to a limited range of plants, such as model species. To overcome this limitation, we developed a method to genetically modify male germ cells without the need forAgrobacterium-mediated transfection and tissue culture, by using tobacco as a model. In this study, plasmid DNA containing sequences of Cas9, guide RNA, and fluorescent reporter was introduced into pollen using a biolistic delivery system. Based on the transient expression of fluorescent reporters, theArabidopsis UBQ10promoter was found to be the most suitable for driving expression of the delivered gene in pollen tubes. We also evaluated delivery efficiency in male germ cells in the pollen by expression of the introduced fluorescent marker. Mutations were detected in the target gene in the genomic DNA extracted from CRISPR/Cas9 introduced pollen tubes but were not detected in the negative control. Bombarded pollen germinated pollen tubes on the stigma and produced two sperm cells within the pistil. We also observed ovules showing fluorescence derived from bombarded pollen. The findings of this study provide important insights into the editing of pollen tube genomes and the delivery of genome-modified male germ cells for seed production.
Perception of invisible masked objects in early infancy
Authors: Nakashima Yusuke , Kanazawa So , Yamaguchi Masami K. 
Published: February 2021

AbstractRecurrent loops in the visual cortex play a critical role in visual perception, which is likely not mediated by purely feedforward pathways. However, the development of recurrent loops is poorly understood. The role of recurrent processing has been studied using visual backward masking, a perceptual phenomenon in which a visual stimulus is rendered invisible by a following mask, possibly because of the disruption of recurrent processing. Anatomical studies have reported that recurrent pathways are immature in early infancy. This raises the possibility that younger infants process visual information mainly in a feedforward manner, and thus, they might be able to perceive visual stimuli that adults cannot see because of backward masking. Here, we show that infants under 7 months of age are immune to visual backward masking and that masked stimuli remain visible to younger infants while older infants cannot perceive them. These results suggest that recurrent processing is immature in infants under 7 months and that they are able to perceive objects even without recurrent processing. Our findings indicate that the algorithm for visual perception drastically changes in the second half of the first year of life.
Single-Domain SARS-CoV-2 S1 and RBD Antibodies Isolated from Immunized Llama Effectively Bind Targets of the Wuhan, UK, and South African Strains in vitro
Authors: Yemane Divora , Lu Ivan , Tiahjono Winson , Rubidoux Lauren , Hussain Abbas , Cancilla John C. , Duggan Erika , Shaner Nathan C. , Nakanishi Nobuki , Wang Jiwu 
Published: February 2021

AbstractThe spreading of SARS-CoV-2 variants has become a major challenge of the current fight against the pandemic. Of particular concerns are the strains that have arisen from the United Kingdom (UK) and South Africa. The UK variant spreads rapidly and is projected to overtake the original strain in the US as early as in March 2021, while the South African variant appears to evade some effects of the current vaccines. Potential false-negative diagnosis using currently available antigen kits that may not recognize these variants could cause another wave of community infection. Therefore, it is imperative that antibodies used in the detection kits are validated for binding against these variants. Here we report that the nanoantibodies (nAbs in our terminology, also referred to as VHH fragments, single domain antibodies, nanobodies™) that we have developed for rapid antigen detection test bind the receptor binding domain (RBD) of the S1 protein from the original COVID-SARS-2 virus as well as those from the UK and South African variants. This finding validates our antibodies used in our assay for the detection of these major variant strains.
Reexamination of N-terminal domains of Syntaxin-1 in vesicle fusion from central murine synapses
Authors: Vardar Gülçin , Salazar-Lázaro Andrea , Brockmann Marisa , Weber-Boyvat Marion , Zobel Sina , Kumbol Victor Wumbor-Apin , Trimbuch Thorsten , Rosenmund Christian 
Published: February 2021

AbstractSyntaxin-1 (STX1) and Munc18-1 are two requisite components of synaptic vesicular release machinery, so much so synaptic transmission cannot proceed in their absence. They form a tight binary complex through two major binding modes: one through STX1’s N-peptide, the other through STX1’s closed conformation driven by its Habc-domain. However, physiological roles of these two reportedly different binding modes in synapses are still controversial. Here we characterized the roles of STX1’s N-peptide, Habc-domain, and open conformation with and without N-peptide deletion using our STX1-null mouse model system and exogenous reintroduction of STX1A mutants. We show, on the contrary to the general view, that the Habc-domain is absolutely required and N-peptide is dispensable for synaptic transmission. However, STX1’s N-peptide plays a regulatory role, particularly in the Ca2+-sensitivity and the short-term plasticity of vesicular release, whereas STX1’s open conformation governs the vesicle fusogenicity. Strikingly, we also show that neurotransmitter release still proceeds when both the interaction modes between STX1 and Munc18-1 are presumably intervened together, necessitating a refinement of the conceptualization of STX1–Munc18-1 interaction.
Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases
Authors: Deakin Claire T. , Cornish Georgina H. , Ng Kevin W. , Faulkner Nikhil , Bolland William , Panova Veera , Hope Joshua , Rosa Annachiara , Harvey Ruth , Hussain Saira , Earl Christopher , Jebson Bethany R. , Wilkinson Meredyth G.Ll. , Marshall Lucy R. , O’Brien Kathryn , Rosser Elizabeth C. , Radziszewska Anna , Peckham Hannah , Heaney Judith , Rickman Hannah , Paraskevopoulou Stavroula , Houlihan Catherine F. , Spyer Moira J. , Gamblin Steve J. , McCauley John , Nastouli Eleni , Cherepanov Peter , Ciurtin Coziana , Wedderburn Lucy R. , Kassiotis George 
Published: February 2021

AbstractDifferences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction or suppression unknown. Here, we examined the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. Despite immune dysfunction and immunosuppressive treatment, JIA, JDM and JSLE patients mounted comparable or stronger responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM and JSLE patients, arguing against increased exposure. Consequently, autoimmune rheumatic diseases and their treatment were associated with a favourable ratio of spike to nucleoprotein antibodies.
Corollary discharge prevents signal distortion and enhances sensing during locomotion
Authors: Skandalis Dimitri A. , Lunsford Elias T. , Liao James C. 
Published: February 2021

AbstractSensory feedback during movement entails sensing a mix of externally- and self-generated stimuli (respectively, exafference and reafference). In many peripheral sensory systems, a parallel copy of the motor command, a corollary discharge, is thought to eliminate sensory feedback during behaviors. However, reafference has important roles in motor control, because it provides real-time feedback on the animal’s motions through the environment. In this case, the corollary discharge must be calibrated to enable feedback while avoiding negative consequences like sensor fatigue. The undulatory motions of fishes’ bodies generate induced flows that are sensed by the lateral line sensory organ, and prior work has shown these reafferent signals contribute to the regulation of swimming kinematics. Corollary discharge to the lateral line reduces the gain for reafference, but cannot eliminate it altogether. We develop a data-driven model integrating swimming biomechanics, hair cell physiology, and corollary discharge to understand how sensory modulation is calibrated during locomotion in larval zebrafish. In the absence of corollary discharge, lateral line afferent units exhibit the highly heterogeneous habituation rates characteristic of hair cell systems, typified by decaying sensitivity and phase distortions with respect to an input stimulus. Activation of the corollary discharge prevents habituation, reduces response heterogeneity, and regulates response phases in a narrow interval around the time of the peak stimulus. This suggests a synergistic interaction between the corollary discharge and the polarization of lateral line sensors, which sharpens sensitivity along their preferred axes. Our integrative model reveals a vital role of corollary discharge for ensuring precise feedback, including proprioception, during undulatory locomotion.
Cerebellar tDCS alters the perception of optic flow
Authors: Nankoo Jean-François , Madan Christopher R , Medina Omar , Makepeace Tyler , Striemer Christopher L. 
Published: February 2021

AbstractStudies have shown that the cerebellar vermis is involved in the perception of motion. However, it is unclear how the cerebellum influences motion perception. tDCS is a non-invasive brain stimulation technique that can reduce (through cathodal stimulation) or increase neuronal excitability (through anodal stimulation). To explore the nature of the cerebellar involvement on large-field global motion perception (i.e., optic flow-like motion), we applied tDCS on the cerebellar midline while participants performed an optic flow motion discrimination task. Our results show that anodal tDCS improves discrimination threshold for optic flow perception, but only for left-right motion in contrast to up-down motion discrimination. This result was evident within the first 10 minutes of stimulation and was also found post-stimulation. Cathodal stimulation did not have any significant effects on performance in any direction. The results show that discrimination of planar optic flow can be improved with tDCS of the cerebellar midline and provide further support for the role of the human midline cerebellum in the perception of optic flow.
Fibrin Polymer on the Surface of Biomaterial Implants Drives the Foreign Body Reaction
Authors: Balabiyev Arnat , Podolnikova Nataly P. , Kilbourne Jacquelyn A. , Baluch D. Page , Lowry David , Zare Azadeh , Ros Robert , Flick Matthew J. , Ugarova Tatiana P. 
Published: February 2021

ABSTRACTImplantation of biomaterials and medical devices in the body triggers the foreign body reaction (FBR) which is characterized by macrophage fusion at the implant surface leading to the formation of foreign body giant cells and the development of the fibrous capsule enveloping the implant. While adhesion of macrophages to the surface is an essential step in macrophage fusion and implanted biomaterials are known to rapidly acquire a layer of host proteins, a biological substrate that is responsible for this processin vivois unknown. Here we show that mice with genetically-imposed fibrinogen deficiency display a dramatic reduction of macrophage fusion on implanted biomaterials and are protected from the formation of fibrin-containing granulation tissue, a precursor of the fibrous capsule. Furthermore, macrophage fusion on biomaterials implanted in FibAEKmice that express a mutated form of fibrinogen incapable of thrombin-mediated polymerization was strongly reduced. Surprisingly, despite the lack of fibrin, the capsule was formed in FibAEKmice, although it had a different composition and distinct mechanical properties than that in wild-type mice. Specifically, while mononuclear α-SMA-expressing macrophages embedded in the capsule of both strains of mice secreted collagen, the amount of collagen and its density in the tissue of FibAEKmice was reduced. These data identify fibrin polymer as a key biological substrate driving the development of the FBR.
The Host Interactome of Spike Expands the Tropism of SARS-CoV-2
Authors: Bamberger Casimir , Pankow Sandra , Martínez-Bartolomé Salvador , Diedrich Jolene , Park Robin , Yates John 
Published: February 2021

AbstractThe SARS-CoV-2 virus causes severe acute respiratory syndrome (COVID-19) and has rapidly created a global pandemic. Patients that survive may face a slow recovery with long lasting side effects that can afflict different organs. SARS-CoV-2 primarily infects epithelial airway cells that express the host entry receptor Angiotensin Converting Enzyme 2 (ACE2) which binds to spike protein trimers on the surface of SARS-CoV-2 virions. However, SARS-CoV-2 can spread to other tissues even though they are negative for ACE2. To gain insight into the molecular constituents that might influence SARS-CoV-2 tropism, we determined which additional host factors engage with the viral spike protein in disease-relevant human bronchial epithelial cells (16HBEo−). We found that spike recruited the extracellular proteins laminin and thrombospondin and was retained in the endoplasmatic reticulum (ER) by the proteins DJB11 and FBX2 which support re-folding or degradation of nascent proteins in the ER. Because emerging mutations of the spike protein potentially impact the virus tropism, we compared the interactome of D614 spike with that of the rapidly spreading G614 mutated spike. More D614 than G614 spike associated with the proteins UGGT1, calnexin, HSP7A and GRP78/BiP which ensure glycosylation and folding of proteins in the ER. In contrast to G614 spike, D614 spike was endoproteolytically cleaved, and the N-terminal S1 domain was degraded in the ER even though C-terminal ‘S2 only’ proteoforms remained present. D614 spike also bound more laminin than G614 spike, which suggested that extracellular laminins may function as co-factor for an alternative, ‘S2 only’ dependent virus entry. Because the host interactome determines whether an infection is productive, we developed a novel proteome-based cell type set enrichment analysis (pCtSEA). With pCtSEA we determined that the host interactome of the spike protein may extend the tropism of SARS-CoV-2 beyond mucous epithelia to several different cell types, including macrophages and epithelial cells in the nephron. An ‘S2 only’ dependent, alternative infection of additional cell types with SARS-CoV-2 may impact vaccination strategies and may provide a molecular explanation for a severe or prolonged progression of disease in select COVID-19 patients.
Reporter gene assay for membrane fusion of extracellular vesicles
Authors: Somiya Masaharu , Kuroda Shun’ichi 
Published: February 2021

AbstractExtracellular vesicles (EVs) secreted by living cells are expected to deliver biological cargo molecules, including RNA and proteins, to the cytoplasm of recipient cells. There is an increasing need to understand the mechanism of intercellular cargo delivery by EVs. However, the lack of a feasible bioassay has hampered our understanding of the biological processes of EV uptake, membrane fusion, and cargo delivery to recipient cells. Here, we describe a reporter gene assay that can measure the membrane fusion efficiency of EVs during cargo delivery to recipient cells. When EVs containing tetracycline transactivator (tTA)-fused tetraspanins are internalized by recipient cells and fuse with cell membranes, the tTA domain is exposed to the cytoplasm and cleaved by protease to induce tetracycline responsive element (TRE)-mediated reporter gene expression in recipient cells. This assay (designated asEV-mediatedtetraspanin-tTAdelivery assay, ETTD assay), enabled us to assess the cytoplasmic cargo delivery efficiency of EVs in recipient cells. With the help of a vesicular stomatitis virus-derived membrane fusion protein, the ETTD assay could detect significant enhancement of cargo delivery efficiency of EVs. Furthermore, the ETTD assay could evaluate the effect of potential cargo delivery enhancers/inhibitors. Thus, the ETTD assay may contribute to a better understanding of the underlying mechanism of the cytoplasmic cargo delivery by EVs.