bluuebunny/crossref_metadata_2025_split huggingface dataset:
A unique SARS-CoV-2 spike protein P681H strain detected in Israel
Authors: Zuckerman Neta S. , Fleishon Shay , Bucris Efrat , Bar-Ilan Dana , Linial Michal , Bar-Or Itay , Indenbaum Victoria , Weil Merav ,   Israel National Consortium for SARS-CoV-2 sequencing, Mendelson Ella , Mandelboim Michal , Mor Orna 
Published: March 2021

AbstractRoutine detection, surveillance and reporting of SARS-CoV-2 novel variants is important, as these threaten to hinder vaccination efforts. Herein we report a local novel strain that includes a non-synonymous mutation in the spike (S) protein - P681H and additional synonymous mutations. The P681H Israeli strain has not been associated with higher infection rates and was neutralized by sera from vaccinated individuals in comparable levels to the B.1.1.7 strain and a non-P681H strain from Israel.
Emergence of a SARS-CoV-2 E484K variant of interest in Arizona
Authors: Skidmore Peter T. , Kaelin Emily A. , Holland LaRinda A. , Maqsood Rabia , Wu Lily I. , Mellor Nicholas J. , Blain Joy M. , Harris Valerie , LaBaer Joshua , Murugan Vel , Lim Efrem S. 
Published: March 2021

AbstractSARS-CoV-2 is locked in a high-stakes arms race between the dynamics of rising population immunity and escape mutations. The E484K mutation in the spike protein reduces neutralization by post-vaccination sera and monoclonal antibody therapeutics. We detected the emergence of an E484K harboring variant B.1.243.1 from a common circulating variant (B.1.243) in the United States. In contrast to other instances when the E484K mutation was acquired independently in the parental lineage, genomic surveillance indicates that the B.1.243.1 variant of interest is in the process of being established in Arizona and beginning to cross state borders to New Mexico and Texas. Genomic, epidemiologic and phylogenetic evidence indicates that the B.1.243.1 variant of interest is poised to emerge. These findings demonstrate the critical need to continue tracking SARS-CoV-2 in real-time to inform public health strategies, diagnostics, medical countermeasures and vaccines.
Machine learning-optimized Combinatorial MRI scale (COMRISv2) correlates highly with cognitive and physical disability scales in Multiple Sclerosis patients
Authors: Kelly Erin , Varosanec Mihael , Kosa Peter , Sandford Mary , Prchkovska Vesna , Moreno-Dominguez David , Bielekova Bibiana 
Published: March 2021

AbstractComposite MRI scales of central nervous system tissue destruction correlate stronger with clinical outcomes than their individual components in multiple sclerosis (MS) patients. Using machine learning (ML), we previously developed Combinatorial MRI scale (COMRISv1) solely from semi-quantitative (semi-qMRI) biomarkers. Here, we asked how much better COMRISv2 might become with the inclusion of quantitative (qMRI) volumetric features and employment of more powerful ML algorithm.The prospectively acquired MS patients, divided into training (n=172) and validation (n=83) cohorts underwent brain MRI imaging and clinical evaluation. Neurological examination was transcribed to NeurEx app that automatically computes disability scales. qMRI features were computed by LesionTOADS algorithm. Modified random forest pipeline selected biomarkers for optimal model(s) in the training cohort.COMRISv2 models validated moderate correlation with cognitive disability (Rho = 0.674; Linh’s concordance coefficient [CCC] = 0.458; p<0.001) and strong correlations with physical disability (Spearman Rho = 0.830-0.852; CCC = 0.789-0.823; p<0.001). The NeurEx led to the strongest COMRISv2 model. Addition of qMRI features enhanced performance only of cognitive disability model, likely because semi-qMRI biomarkers measure infratentorial injury with greater accuracy.COMRISv2 models predict most granular clinical scales in MS with remarkable criterion validity, expanding scientific utilization of cohorts with missing clinical data.
Joint associations between objectively measured physical activity volume and intensity with body-fatness. The Fenland Study
Authors: Lindsay Tim , Wijndaele Katrien , Westgate Kate , Dempsey Paddy , Strain Tessa , De Lucia Rolfe Emanuella , Forouhi Nita G , Griffin Simon , Wareham Nick J , Brage Søren 
Published: March 2021

AbstractBackground/ObjectivesPhysical activity energy expenditure (PAEE) represents the total volume of all physical activity. This can be accumulated as different underlying intensity profiles. Although volume and intensity have been studied in isolation, less is known about their joint association with health. We examined this association with body-fatness in a population-based sample of middle-aged British women and men.Methods6148 women and 5320 men from the Fenland study with objectively-measured physical activity from individually calibrated combined heart rate and movement sensing and DXA-derived body-fat percentage (BF%) were included in the analyses. We used linear and compositional isocaloric substitution analysis to examine associations of PAEE and its intensity composition with body-fatness. Sex-stratified models were adjusted for socio-economic and dietary covariates.ResultsPAEE was inversely associated with body-fatness in women (beta=-0.16 (95%CI: −0.17; −0.15) BF% per kJ·day-1·kg-1) and men (beta=−0.09 (95%CI: −0.10; −0.08) BF% per kJ·day-1·kg-1). Intensity composition was significantly associated with body-fatness, beyond that of PAEE; the reallocation of energy to vigorous physical activity (>6 METs) from other intensities was associated with less body-fatness, whereas light activity (1.5-3 METs) was positively associated. However, light activity was the main driver of overall PAEE volume, and the relative importance of intensity was marginal compared to that of volume; the difference between PAEE in tertile 1 and 2 in women was associated with 3 percentage-point lower BF%. Higher vigorous physical activity in the same group to the maximum observed value was associated with 1 percentage-point lower BF%.ConclusionsIn this large, population-based cohort study with objective measures, PAEE was inversely associated with body-fatness. Beyond the PAEE association, greater levels of intense activity were also associated with lower body-fatness. This contribution was marginal relative to PAEE. These findings support current guidelines for obesity prevention which emphasise moving more over the specific intensity or duration of that activity.
Mental health in relation to changes in sleep, exercise, alcohol and diet during the COVID-19 pandemic: examination of four UK cohort studies
Authors: Villadsen Aase , Patalay Praveetha , Bann David 
Published: March 2021

AbstractBackgroundResponses to the COVID-19 pandemic have included lockdowns and social distancing with considerable disruptions to people’s lives. These changes may have particularly impacted on those with mental health problems, leading to a worsening of inequalities in the behaviours which influence health.MethodsWe used data from four national longitudinal British cohort studies (N=10,666). Respondents reported mental health (psychological distress and anxiety/depression symptoms) and health behaviours (alcohol, diet, physical activity, and sleep) before and during the pandemic. Associations between pre-pandemic mental ill-health and pandemic mental ill-health and health behaviours were examined using logistic regression; pooled effects were estimated using meta-analysis.ResultsWorse mental health was related to adverse health behaviours; effect sizes were largest for sleep, exercise and diet, and weaker for alcohol. The associations between poor mental health and adverse health behaviours were larger during the May lockdown than pre-pandemic. In September, when restrictions had eased, inequalities had largely reverted to pre-pandemic levels. A notable exception was for sleep, where differences by mental health status remained high. Risk differences for adverse sleep for those with the highest level of prior mental ill-health compared to those with the lowest, were 21.2% (95% CI: 16.2, 26.2) before lockdown, 25.5% (20.0, 30.3) in May, and 28.2% (21.2, 35.2) in September.ConclusionsTaken together, our findings suggest that mental health is an increasingly important factor in health behaviour inequality in the COVID era. The promotion of mental health may thus be an important component of improving post-COVID population health.
Prevalence and associated factors with mental health outcomes among interns and residents physicians during COVID-19 epidemic in Panama: a cross-sectional study
Authors: Espinosa-Guerra Edward A. , Rodríguez-Barría Edgar R. , Donnelly Christl A. , Carrera Jean-Paul 
Published: March 2021

AbstractBackgroundA new coronavirus SARS-CoV-2 was associated with a newly identified respiratory syndrome, COVID-19 in Wuhan, China, in early December 2019. SARS-CoV-2 rapidly spread across the globe resulting in 117 million cases and 2.59 million deaths by March 2021. Rapidly increased numbers of COVID-19 cases overwhelmed public health systems across the world, imposing increased working hours and workloads for health care workers. Here, we have evaluated the prevalence of health outcomes and associated factors of interns and resident physicians in Panama.MethodsA cross-sectional study was undertaken during July 23, 2020, to August 13, 2020, to evaluate the prevalence of health outcomes and associated factors in interns and residents across Panama. Snowball sampling was used to recruit participants. Then an electronic questionnaire with scales to evaluate anxiety disorders (GAD-7), depression (PHQ-9) and post-traumatic stress (IES-R) was evaluated. In addition, socio-demographic variables, clinical history of mental disorders and COVID-19 exposure were evaluated. Independent analyses for each mental health outcome were undertaken using a logistic regression analysis.ResultsA total of 517/1205 (42.9%) interns and residents were nationwide recruited. Of these 274 (53.0%) were interns and 243 (47.0%) residents. The overall prevalence of depression symptoms was 25.3%, 13.7% anxiety and 12.2% post-traumatic stress. At least, 9.3% participants reported having suicidal ideation.The most parsimonious model showed females had a higher prevalence of mental health disorders, in all results and the married participants were more likely to present depression (OR, 1.73; 95% CI, 1.03-2.91; P = 0.039) or at least one alteration to mental health (OR, 1.66; 95% CI, 1.03-2.68; P = 0.039). Resident physicians in surgical specialties were less likely to have post-traumatic stress (OR, 0.20; 95% CI, 0.06-0.63; P = 0.006) or at least one mental health disturbance (OR, 0.46; 95% CI, 0.26-0.83; P = 0.010). A history of psychological trauma and psychiatric pathology were risk factors for most of the disorders investigated.ConclusionsA high prevalence of mental health disorders was found, showing the need to mitigate this emotional burden among healthcare workers in the current context of the COVID-19 pandemic.
Kenyan Traditional Medicine: Exploring Old Solutions to the Modern Antibacterial Crises Through Natural Products Chemistry
Authors: Ndegwa Fidensio K. , Kondam Chaitanya , Ghose Debarati , Esan Taiwo E. , Waxali Zohra Sattar , Miller Margaret E. , Meganathan Rangaswamy , Gikonyo Nicholas K. , Mbugua Paul K. , Okemo Paul O. , Hagen Timothy J. 
Published: March 2021

AbstractInfectious diseases are a major cause of morbidity and mortality around the world, accounting for approximately 50% of all deaths in tropical countries. Despite remarkable progress in the field of microbiology, inability to control or mitigate, epidemics caused by drug-resistant microorganisms pose a serious health hazard to the global population. New therapeutic strategies must be developed as a global initiative for the prevention and control of infectious diseases. This study focuses on Kenyan medicinal plants and their activity against bacteria. Plant extracts obtained from seven Kenyan plants used in traditional medicine, were screened for their antibacterial activity againstEscherichia coli,Pseudomonas aeruginosa, Bacillus cereus, and Mycobacterium smegmatis. Extracts from all these plants showed antibacterial activity against at least one of the tested organisms at a concentration of 2 mg/mL. Chemical screening showed the presence of different classes of phytochemicals such as alkaloids, terpenes, tannins, in some active extracts.
Accessory genomic epidemiology of co-circulating Acinetobacter baumannii clones
Authors: Mateo-Estrada Valeria , Fernández-Vázquez José Luis , Moreno-Manjón Julia , Hernández-González Ismael L. , Rodríguez-Noriega Eduardo , Morfín-Otero Rayo , Alcántar-Curiel María Dolores , Castillo-Ramírez Santiago 
Published: March 2021

AbstractA. baumannii has become one of the most important multidrug resistant nosocomial pathogens all over the world. Nonetheless, very little is known about the diversity of A. baumannii lineages co-existing in hospital settings. Here, using whole-genome sequencing, epidemiological data and antimicrobial susceptibility tests, we uncover the transmission dynamics of extensive and multidrug resistant A. baumannii in a tertiary hospital for a decade. Our core genome phylogeny of almost 300 genomes suggests that there were several introductions of lineages from international clone 2 into the hospital. The molecular dating analysis shows that these introductions happened between 2004 and 2015. Furthermore, using the accessory genome, we show that these lineages were extensively disseminated across many wards in the hospital. Our results demonstrate that accessory genome variation can be a very powerful tool for conducting genomic epidemiology. We anticipate future studies employing the accessory genome as a phylogenomic marker over very short microevolutionary scales.
Thermoplasmonic nano-rupture of cells reveals Annexin V function in plasma membrane repair
Authors: Moreno-Pescador Guillermo S. , Aswad Dunya S. , Florentsen Christoffer D. , Bahadori Azra , Arastoo Mohammad R. , Danielsen Helena Maria D. , Heitmann Anne Sofie B. , Boye Theresa L. , Nylandsted Jesper , Oddershede Lene B. , Bendix Poul Martin 
Published: March 2021

AbstractMaintaining the integrity of the cell plasma membrane (PM) is critical for the survival of cells. While an efficient PM repair machinery can aid survival of healthy cells by preventing influx of extracellular calcium, it can also constitute an obstacle in drug delivery and photothermal therapy. We show how nanoscopic holes can be applied to the cell surface thus allowing identification of molecular components with a pivotal role in PM repair. Cells are punctured by locally heating gold nanostructures at the cell surface which causes nano-ruptures in cellular PMs. Recruitment of annexin V near the hole is found to locally reshape the ruptured plasma membrane. Experiments using model membranes, containing recombinant annexin V, provide further biophysical insight into the ability of annexin V to reshape edges surrounding a membrane hole. The thermoplasmonic method provides a general strategy to monitor the response to nanoscopic injuries to the cell surface.
Mass Cytometric and Transcriptomic Profiling of Epithelial-Mesenchymal Transitions in Human Mammary Cell Lines
Authors: Wagner Johanna , Masek Markus , Jacobs Andrea , Soneson Charlotte , Damond Nicolas , de Souza Natalie , Robinson Mark D. , Bodenmiller Bernd 
Published: March 2021

AbstractEpithelial-mesenchymal transition (EMT) equips breast cancer cells for metastasis and treatment resistance. Inhibition and elimination of EMT-undergoing cells are therefore promising therapy approaches. However, detecting EMT-undergoing cells is challenging due to the intrinsic heterogeneity of cancer cells and the phenotypic diversity of EMT programs. Here, we profiled EMT transition phenotypes in four non-cancerous human mammary epithelial cell lines using a FACS surface marker screen, RNA sequencing, and mass cytometry. EMT was induced in the HMLE and MCF10A cell lines and in the HMLE-Twist-ER and HMLE-Snail-ER cell lines by chronic exposure to TGFβ1 or 4-hydroxytamoxifen, respectively. We observed a spectrum of EMT transition phenotypes in each cell line and the spectrum varied across the time course. Our data provide multiparametric insights at single-cell level into the phenotypic diversity of EMT at different time points and in four human cellular models. These insights are valuable to better understand the complexity of EMT, to compare EMT transitions between the cellular models used herein, and for the design of EMT time course experiments.Mendeley Data: DOI: 10.17632/pt3gmyk5r2.1ArrayExpress Data: Accession number E-MTAB-9365
Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling
Authors: Light Taylor P. , Brun Delphine , Guardado-Calvo Pablo , Pederzoli Riccardo , Haouz Ahmed , Neipel Frank , Rey Felix , Hristova Kalina , Backovic Marija 
Published: March 2021

ABSTRACTHuman herpesvirus 8 (HHV-8) is an oncogenic virus that enters cells by fusion of the viral and endosomal cellular membranes in a process mediated by viral surface glycoproteins. One of the cellular receptors hijacked by HHV-8 to gain access to cells is the EphA2 tyrosine kinase receptor, and the mechanistic basis of EphA2-mediated viral entry remains unclear. Using X-ray structure analysis, targeted mutagenesis and binding studies, we here show that the HHV-8 envelope glycoprotein complex gH/gL binds with sub-nanomolar affinity to EphA2 via molecular mimicry of the receptor’s cellular ligands, ephrins, revealing a pivotal role for the conserved gH residue E52 and the amino-terminal peptide of gL. Using FSI-FRET and cell contraction assays, we further demonstrate that the gH/gL complex also functionally mimics ephrin ligand by inducing EphA2 receptor association via its dimerization interface, thus triggering receptor signaling for cytoskeleton remodeling. These results now provide novel insight into the entry mechanism of HHV-8, opening avenues for the search of therapeutic agents that could interfere with HHV-8 related diseases.
Internalisation and biological activity of nucleic acids delivering cell-penetrating peptide nanoparticles is controlled by the biomolecular corona
Authors: Lorents Annely , Maloverjan Maria , Padari Kärt , Pooga Margus 
Published: March 2021

AbstractNucleic acid molecules can be transferred into cells to alter gene expression and, thus, alleviate certain pathological conditions. Cell-penetrating peptides (CPPs) are vectors that can be used for transfecting nucleic acids as well as many other compounds. CPPs associate nucleic acids non-covalently, forming stable nanoparticles and providing efficient transfection of cellsin vitro. However,in vivo, expected efficiency is achieved only in rare cases. One of the reasons for this discrepancy is formation of protein corona around nanoparticles, once they are exposed to a biological environment, e.g. blood stream. In this study, we compared CPP-nucleic acid nanoparticles formed in the presence of bovine, murine and human serum. We used Western blot and mass-spectrometry to identify the major constituents of protein corona forming around nanoparticles, showing that proteins involved in transport, haemostasis and complement system are its major components. We investigated physical features of nanoparticles, and measured their biological efficiency in splice-correction assay. We showed that protein corona constituents might alter the fate of nanoparticlesin vivo, e.g. by subjecting them to phagocytosis. We demonstrated that composition of protein corona of nanoparticles is species-specific that leads to dissimilar transfection efficiency and should be taken into account while developing delivery systems for nucleic acids.
Single-nuclei transcriptomes from human adrenal gland reveals distinct cellular identities of low and high-risk neuroblastoma tumors
Authors: Bedoya-Reina O.C. , Li W. , Arceo M. , Plescher M. , Bullova P , Pui H. , Kaucka M. , Kharchenko P. , Martinsson T. , Holmberg J. , Adameyko I. , Deng Q. , Larsson C. , Juhlin C.C. , Kogner P. , Schlisio S. 
Published: March 2021

AbstractChildhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. We studied single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compared tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles an unknown subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations revealed different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome.
Evaluation of the effect of hydrocortisone in 2D and 3D HEp-2 cell culture
Authors: Fonseca M.O. , Godoi B.H. , Da Silva N.S , Pacheco-Soares C. 
Published: March 2021

AbstractCancer is one of the diseases with the highest incidence globally and that associated with the patient’s emotional state, can act positively or negatively in the treatment. Cortisol is a principal primary stress hormone in the human body. The corticoids can increase cell proliferation and reactive oxygen species that contribute to DNA damage. Prolonged exposure to stress can contribute to tissues becoming insensitive to cortisol, the primary human stress hormone. This study explores cortisol’s influence on tumor cell development, particularly in human cells of carcinoma of the human laryngeal (HEp-2). HEp-2 cells were exposed to increasing cortisol (hydrocortisone) concentrations for 24 or 48 hours, and cytotoxicity (MTT assay) proliferation assay (crystal violet assay), and immunolabeled 3D culture for fibronectin and FAK were analyzed. The group treated with hydrocortisone showed a significant increase in mitochondrial activity, as for the evaluation by the violet crystal, the treated group showed similar behavior to the control. The 3D culture showed dispersed cells within 24 hours with reduced FAK labeling; however, no changes were observed within 48 hours. Although some cases favored corticosteroid use in cancer patients, a more detailed analysis is necessary before prescribing them.