bluuebunny/crossref_metadata_2025_split huggingface dataset:
Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library
Authors: Liu Qianyun , Cai Chenguang , Huang Yanyan , Zhou Li , Guan Yanbin , Fu Shiying , Lin Youyou , Yang Ting , Wan Nanyan , Zhang Fengzhi , Sun Qi , Bai Ying , Chen Yu , Liang Xiaohua , Yan Huan , Zhang Zhen , Lan Ke , Chen Yu , Li Xiang , Hou Shin-Chen , Xiong Yi 
Published: August 2021

AbstractSARS-CoV-2 infection is initiated with Spike glycoprotein binding to the receptor of human angiotensin converting enzyme 2 via its receptor binding domain. Blocking this interaction is considered as an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody, VHH60, directly produced from a humanized synthetic nanobody library. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein with a KDof 2.56 nM, inhibits infections of both live SARS-CoV-2 and pseudotyped viruses harboring wildtype, escape mutations and prevailing variants at nanomolar level. VHH60 also suppresses SARS-CoV-2 infection and propagation 50-fold better and protects mice from death two times longer than that of control group after live virus inoculation on mice. VHH60 therefore is a powerful synthetic nanobody with a promising profile for disease control against COVID19.
Evaluation of the Liberty16 mobile real time PCR device for use with the SalivaDirect assay for SARS-CoV-2 testing
Authors: Yolda-Carr Devyn , Thammavongsa Darani A. , Vega Noel , Turner Susan J. , Pickering Paul J. , Wyllie Anne L. 
Published: August 2021

AbstractThe COVID-19 pandemic has highlighted the need and benefits for all communities to be permitted timely access to on-demand screening for infectious respiratory diseases. This can be achieved with simplified testing approaches and affordable access to core resources. While RT-qPCR-based tests remain the gold standard for SARS-CoV-2 detection due to their high sensitivity, implementation of testing requires high upfront costs to obtain the necessary instrumentation. This is particularly restrictive in low-resource settings. The Ubiquitome Liberty16 system was developed as an inexpensive, portable, battery-operated single-channel RT-qPCR device with an associated iPhone app to simplify assay set-up and data reporting. When coupled with the SalivaDirect protocol for testing saliva samples for SARS-CoV-2, the Liberty16 device yielded a limit of detection (LOD) of 12 SARS-CoV-2 RNA copies/µL, comparable to the upper end of the LOD range for the standard SalivaDirect protocol when performed on larger RT-qPCR instruments. While further optimization may deliver even greater sensitivity and assay speed, findings from this study indicate that small portable devices such as the Liberty16 can deliver reliable results and provide the opportunity to further increase access to gold standard SARS-CoV-2 testing.
Comparison of Ferroptosis Related Genes expression in Human Oral Squamous Cell Carcinoma and Normal oral tissues
Authors: Thavarajah Rooban , Joshua Elizabeth , Ranganathan Kannan 
Published: August 2021

ABSTRACTIntroductionEvasion of programmed cell death (PCD) is a hall mark of oncogenesis. There are different types of PCD. Iron related PCD, ferroptosis is being increasingly associated with neoplastic process. There are very few reports that investigate the role of ferroptosis in Oral Squamous Cell Carcinoma (OSCC). An attempt is made to compare the ferroptosis related genes(FRGs) expression in human OSCC and normal oral tissues.Materials and MethodsGene Expression Omnibus repository was scanned for OSCC mRNA datasets along with normal control tissues. Datasets fulfilling inclusion and exclusion criteria as well as that fulfilled the statistical correlation requirements were considered for this study. Differentially expressed mRNAs were identified. From the literature and ferroptosis database, FRGs were identified and those FRGs were differentially expressed were validated using The Human Cancer Genome dataset.ResultsIn all 44 FRGs were identified to be differentially expressed between OSCC and control tissues. Of the 44, 21 were that promoted ferroptosis including 18 drivers of ferroptosis. Of the 21 FRGs that drives ferroptosis, 9 were found significantly elevated in controls while the remaining 12 were elevated in OSCC. The role of the differentially expressed FRGs were also studied. Of the 44 FRGs, 36 were validated using the human cancer genome dataset.Discussion and ConclusionDrivers and suppressors of ferroptosis were differentially expressed in OSCC and controls. This reflects that ferroptosis has a dual role in oncogenesis – both as a promoter and a suppressor. The identified specific FRGs in this studied would help to understand the role of PCD in OSCC progression and help in designing better treatment.
The Normative Modeling Framework for Computational Psychiatry
Authors: Rutherford Saige , Kia Seyed Mostafa , Wolfers Thomas , Fraza Charlotte , Zabihi Mariam , Dinga Richard , Berthet Pierre , Worker Amanda , Verdi Serena , Ruhe Henricus G. , Beckmann Christian F. , Marquand Andre F. 
Published: August 2021

AbstractNormative modeling is an emerging and innovative framework for mapping individual differences at the level of a single subject or observation in relation to a reference model. It involves charting centiles of variation across a population in terms of mappings between biology and behavior which can then be used to make statistical inferences at the level of the individual. The fields of computational psychiatry and clinical neuroscience have been slow to transition away from patient versus “healthy” control analytic approaches, likely due to a lack of tools designed to properly model biological heterogeneity of mental disorders. Normative modeling provides a solution to address this issue and moves analysis away from case-control comparisons that rely on potentially noisy clinical labels. In this article, we define a standardized protocol to guide users through, from start to finish, normative modeling analysis using the Predictive Clinical Neuroscience toolkit (PCNtoolkit). We describe the input data selection process, provide intuition behind the various modeling choices, and conclude by demonstrating several examples of down-stream analyses the normative model results may facilitate, such as stratification of high-risk individuals, subtyping, and behavioral predictive modeling. The protocol takes approximately 1-3 hours to complete.
Suppression of influenza virus infection by rhinovirus interference at the population, individual and cellular levels
Authors: Tao Kin P , Chong Marc , Pun Jason CS , Tsun Joseph GS , Chow Samuel MW , Ng Calvin SH , Wang Maggie HT , Chan Zigui , Chan Paul KS , Li Albert M , Chan Renee WY 
Published: August 2021

AbstractBackgroundInvestigations of the natural viral interference effect between rhinovirus (RV) and influenza virus (IV) were conducted in temperate regions. We conducted an epidemiological study in Hong Kong, a major epicentre of influenza virus in the sub-tropical region. RV is the most prevalent respiratory virus year-round and causes asymptomatic to mild symptoms while IV infection exerts a great burden of public health. We aimed to examine the correlation of RV prevalence against IV activity.MethodsNasopharyngeal aspirates (NPA) collected from patients hospitalized in the regional hospitals from 2015 to 2019 were examined for the presence of respiratory viruses. The correlation of the monthly prevalence between all pairs of virus infection, the co-infection rate and the temporal interference of RV and IV were tested. The viral interference was validatedin vitroby conducting sequential RV and IV infection in the well-differentiated primary human airway epithelial cells.FindingsA total of 112,926 NPA were evaluated, and the Enterovirus/RV was the most prevalent respiratory virus detected. The negative correlation between EV/RV and IVs prevalence was independent of age and meteorological factors. Co-infection of EV/RV and IV was significantly less when compared with other virus pairs. Prior exposure to RV inhibited the replication of influenza A, B and oseltamivir-resistance stainin vitroand the inhibition is replication dependent.InterpretationEpidemiological surveillance and the sequential infectionin vitrosuggested viral interference between EV/RV and IV operated at the population, individual and cellular levels.FundingThis study was supported by the General Research Fund (Ref: 24107017 and 14103119 to RWYC), Health and Medical Research Fund (Ref: COVID190112 to RWYC) and the Chinese University Direct Grant for Research (Ref: 2019.073 to RWYC).
Acute kidney injury after liver resection: A systematic review, meta-analysis and metaregression of factors affecting it
Authors: Vasavada Bhavin , Patel Hardik 
Published: August 2021

AbstractAimThis systematic review and meta-analysis aimed to study the incidence of acute kidney injury after liver resection and to analyze various factors affecting it by metaregression analysis.MethodsThe study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (2020) and MOOSE guidelines. The meta-analysis was done using Review Manager 5.4 and the JASP Team (2020). JASP (Version 0.14.1)(University of Amsterdam). Weighted percentage incidence with 95% confidence intervals were used. Univariate metaregression was done by DerSimonian-Laird methods. Factors with a p-value less than 0.05 in the univariate metaregression model were entered in the multivariate metaregression model. Heterogeneity was assessed using the Higgins I2 test. The random-effects model was used in meta-analysis.ResultsTotal 14 studies including 15510 patients were included in the final analysis. 1247 patients developed Acute Kidney Injury. Weighted Acute kidney injury percentage after liver resection was 15% with a 95% confidence interval of 11%-19%. On univariate metaregression analysis major hepatectomy (p=0.001), Underlying cirrhosis of liver (p=0.031), AKIN definition used (0.017), male sex (p<0.001), open surgery (p=0.032), underlying diabetes (0.026). On multivariate metaregression analysis major hepatectomy (p=0.003), underlying cirrhosis (p<0.001), male sex (p<0.001), AKIN classification used for defining acute kidney injury (p < 0.001, independently predicted heterogeneity and hence acute kidney injury.ConclusionLiver resection is associated with a high incidence of acute kidney injury. Major hepatectomy, male sex, underlying cirrhosis were independently predicting acute kidney injury.
Diagnosing COVID-19 in human serum using Raman spectroscopy: a preliminary study
Authors: Goulart Ana Cristina Castro , Silveira Landulfo , Carvalho Henrique Cunha , Dorta Cristiane Bissoli , Pacheco Marcos Tadeu T. , Zângaro Renato Amaro 
Published: August 2021

AbstractThis preliminary study proposed the diagnosis of COVID-19 by means of Raman spectroscopy. Samples of blood serum from 10 patients positive and 10 patients negative for COVID-19 by RT-PCR RNA and ELISA tests were analyzed. Raman spectra were obtained with a dispersive Raman spectrometer (830 nm, 350 mW) in triplicate, being submitted to exploratory analysis with principal component analysis (PCA) to identify the spectral differences and discriminant analysis with PCA (PCA-DA) and partial least squares (PLS-DA) for classification of the blood serum spectra into Control and COVID-19. The spectra of both groups positive and negative for COVID-19 showed peaks referred to the basal constitution of the serum (mainly albumin). The difference spectra showed decrease in the peaks referred to proteins and amino acids for the group positive. PCA variables showed more detailed spectral differences related to the biochemical alterations due to the COVID-19 such as increase in lipids, nitrogen compounds (urea and amines/amides) and nucleic acids, and decrease of proteins and amino acids (tryptophan) in the COVID-19 group. The discriminant analysis applied to the principal component loadings (PC 2, PC 4, PC 5 and PC 6) could classify spectra with 87% sensitivity and 100% specificity compared to 95% sensitivity and 100% specificity indicated in the RT-PCR kit leaflet, demonstrating the possibilities of a rapid, label-free and costless technique for diagnosing COVID-19 infection.
Fully Human Antibody Immunoglobulin from Transchromosomic Bovines is Potent Against SARS-CoV-2 Variant Pseudoviruses
Authors: Luke Thomas , Wu Hua , Egland Kristi A , Sullivan Eddie J , Bausch Christoph L 
Published: August 2021

AbstractSAB-185 is a fully human polyclonal anti-SARS-CoV-2 immunoglobulin produced from the plasma of transchromosomic bovines that are hyperimmunized with recombinant SARS-CoV-2 Wuhan-Hu-1 Spike protein. SAB-185 is being evaluated for efficacy in aphase 3 clinical trial. The World Health Organization (WHO) has identified multiple Variants-of-Concern and Variants-of-Interest (VOC/VOI) that have mutations in their Spike protein that appear to increase transmissibility and/or reduce the effectiveness of therapeutics and vaccines, among other parameters of concern. SAB-185 was evaluated using lentiviral-based pseudovirus assays performed in a BSL2 environment that incorporates stable or transient cell lines that express human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The results indicate that SAB-185 retained neutralization potency against multiple SARS-CoV-2 pseudovirus variants, including the Delta, Kappa, Lambda and Omicron variants, that have or are supplanting other VOC/VOI in many countries and regions around the world.
3D single molecule localization microscopy reveals the topography of the immunological synapse at isotropic precision below 15 nm
Authors: Velas Lukas , Brameshuber Mario , Huppa Johannes B. , Kurz Elke , Dustin Michael L. , Zelger Philipp , Jesacher Alexander , Schütz Gerhard J. 
Published: August 2021

ABSTRACTT-cells engage with antigen-presenting cells in search for antigenic peptides and form transient interfaces termed immunological synapses. A variety of protein-protein interactions in trans-configuration defines the topography of the synapse and orchestrates the antigen-recognition process. In turn, the synapse topography affects receptor binding rates and the mutual segregation of proteins due to size exclusion effects. For better understanding it is hence critical to map the 3D topography of the immunological synapse at high precision. Current methods, however, provide only rather coarse images of the protein distribution within the synapse, which do not reach the dimension of the protein ectodomains. Here, we applied supercritical angle fluorescence microscopy combined with defocused imaging, which allows 3-dimensional single molecule localization microscopy (3D-SMLM) at an isotropic localization precision below 15 nm. Experiments were performed on hybrid synapses between primary T-cells and functionalized glass-supported lipid bilayers. We used 3D-SMLM to quantify the cleft size within the synapse by mapping the position of the T-cell receptor (TCR) with respect to the supported lipid bilayer, yielding average distances of 18 nm up to 31 nm for activating and non-activating bilayers, respectively.
Glue genes are subjected to diverse selective forces during Drosophila development
Authors: Borne Flora , Kulathinal Rob J. , Courtier-Orgogozo Virginie 
Published: August 2021

AbstractMolecular evolutionary studies usually focus on genes with clear roles in adult fitness or on developmental genes expressed at multiple time points during the life of the organism. Here, we examine the evolutionary dynamics of Drosophila glue genes, a set of eight genes tasked with a singular primary function during a specific developmental stage: the production of glue that allows animal pupa to attach to a substrate for several days during metamorphosis. Using phenotypic assays and available data from transcriptomics, PacBio genomes, and genetic variation from global populations, we explore the selective forces acting on the glue genes within the cosmopolitanD. melanogasterspecies and its five closely related species,D. simulans, D. sechellia, D. mauritiana, D. yakuba, andD. teissieri. We observe a three-fold difference in glue adhesion between the least and the most adhesiveD. melanogasterstrain, indicating a strong genetic component to phenotypic variation. These eight glue genes are among the most highly expressed genes in salivary glands yet they display no notable codon bias. New copies ofSgs3andSgs7are found inD. yakubaandD. teissieriwith theSgs3coding sequence evolving rapidly after duplication in theD. yakubabranch. Multiple sites along the various glue genes appear to be constrained. Our population genetics analysis inD. melanogastersuggests signs of local adaptive evolution forSgs3, Sgs5andSgs5bisand traces of selective sweeps forSgs1, Sgs3, Sgs7andSgs8. Our work shows that stage-specific genes can be subjected to various dynamic evolutionary forces. (249 words)Significance statementDrosophila larvae produce a glue to stick themselves to a substrate for several days during metamorphosis. Here we observe wide variation in stickiness amongDrosophila melanogasterstrains and we analyze the molecular evolution of eight glue genes. We find several recent gene duplications and heterogenous rates of evolution among these genes.
A photo-switchable assay system for dendrite degeneration and repair inDrosophila melanogaster
Authors: Liu Han-Hsuan , Hsu Chien-Hsiang , Jan Lily Y. , Jan Yuh-Nung 
Published: August 2021

ABSTRACTNeurodegeneration arising from aging, injury or disease has devastating health consequences. Whereas neuronal survival and axon degeneration have been studied extensively, much less is known about how neurodegeneration impacts dendrites. To develop an assay for dendrite degeneration and repair in theDrosophilaperipheral nervous system, we used photo-switchable caspase-3 (caspase-LOV) to induce neuronal damage with tunable severity by adjusting illumination duration, thereby revealing cell type-specific responses to caspase-3 induced dendrite degeneration in dendrite arborization (da) neurons. To ask whether mechanisms underlying axon degeneration also govern dendrite degeneration, we tested the involvement of the Wallerian degeneration pathway by examining the effects of expressing the mouse Wallerian degeneration slow (WldS) protein and knockdown of theDrosophilasterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein (dSarm1) and Axundead (Axed) in class 4 da neurons. Here we report WldSexpression or knockdown of dSarm1 improved dendrite repair following caspase- 3 induced dendrite degeneration. Whereas both dSarm1 and Axed were required for thermal nocifensive behavior in uninjured animals, WldSexpression improved the recovery of thermal nocifensive behavior that was impaired by chronic low-level of caspase-LOV activity. By establishing ways to induce graded dendrite degeneration, we uncover a protective role of WldSin caspase-3 induced dendrite degeneration and repair.
OPAM, an Open source, 3D printed Low-cost Micro-Manipulator for Single Cell Manipulation
Authors: Xu Jiang , Du Zhuowei , Liu Paul , Kou Yi , Chen Lin 
Published: August 2021

AbstractWe introduce OPAM, an Open source, low-cost (under $150), 3D-Printed, stepper motor driven, Arduino based, single cell Micromanipulator (OPAM). Modification of a commercial stepper motor led to dramatically increased stability and maneuverability of the motor, based on which the micromanipulator was designed. All components of this micromanipulator can be 3D printed using an entry-level 3D printer and assembled with ease. With this single cell manipulator, successful targeted single cell capture and transfer was confirmed under the microscope, which showed great promise for single cell related experiments.
Sex-specific tuning of modular muscle activation patterns for locomotion in young and older adults
Authors: Santuz Alessandro , Janshen Lars , Brüll Leon , Munoz-Martel Victor , Taborri Juri , Rossi Stefano , Arampatzis Adamantios 
Published: August 2021

AbstractThere is increasing evidence that including sex as a biological variable is of crucial importance to promote rigorous, repeatable and reproducible science. In spite of this, the body of literature that accounts for the sex of participants in human locomotion studies is small and often produces controversial results. Here, we investigated the modular organization of muscle activation patterns for human locomotion using the concept of muscle synergies with a double purpose: i) uncover possible sex-specific characteristics of motor control and ii) assess whether these are maintained in older age. We recorded electromyographic activities from 13 ipsilateral muscles of the lower limb in young and older adults of both sexes walking (young and old) and running (young) on a treadmill. The data set obtained from the 215 participants was elaborated through non-negative matrix factorization to extract the time-independent (i.e., motor modules) and time-dependent (i.e., motor primitives) coefficients of muscle synergies. We found sparse sex-specific modulations of motor control. Motor modules showed a different contribution of hip extensors, knee extensors and foot dorsiflexors in various synergies. Motor primitives were wider (i.e., lasted longer) in males in the propulsion synergy for walking (but only in young and not in older adults) and in the weight acceptance synergy for running. Moreover, the complexity of motor primitives was similar in younger adults of both sexes, but lower in older females as compared to older males. In essence, our results revealed the existence of small but defined sex-specific differences in the way humans control locomotion and that these strategies are not entirely maintained in older age.
A DNA-structured mathematical model of cell-cycle progression in cyclic hypoxia
Authors: Celora Giulia L. , Bader Samuel B. , Hammond Ester M. , Maini Philip K. , Pitt-Francis Joe , Byrne Helen M. 
Published: August 2021

AbstractNew experimental data have shown how the periodic exposure of cells to low oxygen levels (i.e., cyclic hypoxia) impacts their progress through the cell-cycle. Cyclic hypoxia has been detected in tumours and linked to poor prognosis and treatment failure. While fluctuating oxygen environments can be reproducedin vitro, the range of oxygen cycles that can be tested is limited. By contrast, mathematical models can be used to predict the response to a wide range of cyclic dynamics. Accordingly, in this paper we develop a mechanistic model of the cell-cycle that can be combined within vitroexperiments, to better understand the link between cyclic hypoxia and cell-cycle dysregulation. A distinguishing feature of our model is the inclusion of impaired DNA synthesis and cell-cycle arrest due to periodic exposure to severely low oxygen levels. Our model decomposes the cell population into four compartments and a time-dependent delay accounts for the variability in the duration of the S phase which increases in severe hypoxia due to reduced rates of DNA synthesis. We calibrate our model against experimental data and show that it recapitulates the observed cell-cycle dynamics. We use the calibrated model to investigate the response of cells to oxygen cycles not yet tested experimentally. When the re-oxygenation phase is sufficiently long, our model predicts that cyclic hypoxia simply slows cell proliferation since cells spend more time in the S phase. On the contrary, cycles with short periods of re-oxygenation are predicted to lead to inhibition of proliferation, with cells arresting from the cell-cycle when they exit the S phase. While model predictions on short time scales (about a day) are fairly accurate (i.e, confidence intervals are small), the predictions become more uncertain over longer periods. Hence, we use our model to inform experimental design that can lead to improved model parameter estimates and validate model predictions.