bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter comparison of the Cobas 6800 system with the RealStar RT-PCR kit for the detection of SARS-CoV-2
Authors: Wirden Marc , Feghoul Linda , Bertine Mélanie , Nere Marie-Laure , Le Hingrat Quentin , Abdi Basma , Boutolleau David , Ferre Valentine Marie , Jary Aude , Delaugerre Constance , Marcelin Anne-Genevieve , Descamps Diane , Legoff Jérôme , Visseaux Benoit , Chaix Marie-Laure 
Published: July 2020

ABSTRACTBackgroundRT-PCR testing is crucial in the diagnostic of SARS-CoV-2 infection. The use of reliable and comparable PCR assays is a cornerstone to allow use of different PCR assays depending on the local equipment. In this work, we provide a comparison of the Cobas® (Roche) and the RealStar® assay (Altona).MethodsAssessment of the two assays was performed prospectively in three reference Parisians hospitals, using 170 clinical samples. They were tested with the Cobas® assay, selected to obtain a distribution of cycle threshold (Ct) as large as possible, and tested with the RealStar assay with three largely available extraction platforms: QIAsymphony (Qiagen), MagNAPure (Roche) and NucliSENS-easyMag (BioMérieux).ResultsOverall, the agreement (positive for at least one gene) was 76%. This rate differed considerably depending on the Cobas Ct values for gene E: below 35 (n = 91), the concordance was 99%. Regarding the positive Ct values, linear regression analysis showed a determination correlation (R2) of 0.88 and the Deming regression line revealed a strong correlation with a slope of 1.023 and an intercept of -3.9. Bland-Altman analysis showed that the mean difference (Cobas® minus RealStar®) was + 3.3 Ct, with a SD of + 2.3 Ct.ConclusionsIn this comparison, both RealStar® and Cobas® assays provided comparable qualitative results and a high correlation when both tests were positive. Discrepancies exist after 35 Ct and varied depending on the extraction system used for the RealStar® assay, probably due to a low viral load close to the detection limit of both assays.
Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa
Authors: Reddy Krishna P. , Shebl Fatma M. , Foote Julia H. A. , Harling Guy , Scott Justine A. , Panella Christopher , Flanagan Clare , Hyle Emily P. , Neilan Anne M. , Mohareb Amir M. , Bekker Linda-Gail , Lessells Richard J. , Ciaranello Andrea L. , Wood Robin , Losina Elena , Freedberg Kenneth A. , Kazemian Pooyan , Siedner Mark J. 
Published: July 2020

ABSTRACTBackgroundHealthcare resource constraints in low and middle-income countries necessitate selection of cost-effective public health interventions to address COVID-19.MethodsWe developed a dynamic COVID-19 microsimulation model to evaluate clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal, South Africa. Interventions assessed were Healthcare Testing (HT), where diagnostic testing is performed only for those presenting to healthcare centres; Contact Tracing (CT) in households of cases; Isolation Centres (IC), for cases not requiring hospitalisation; community health worker-led Mass Symptom Screening and diagnostic testing for symptomatic individuals (MS); and Quarantine Centres (QC), for contacts who test negative. Given uncertainties about epidemic dynamics in South Africa, we evaluated two main epidemic scenarios over 360 days, with effective reproduction numbers (Re) of 1·5 and 1·2. We comparedHT, HT+CT, HT+CT+IC, HT+CT+IC+MS, HT+CT+IC+QC, andHT+CT+IC+MS+QC, considering strategies with incremental cost-effectiveness ratio (ICER) <US$1,290/year-of-life saved (YLS) to be cost-effective.FindingsWith Re1·5,HTresulted in the most COVID-19 deaths and lowest costs over 360 days. Compared withHT, HT+CT+IC+MSreduced mortality by 76%, increased costs by 16%, and was cost-effective (ICER $350/YLS).HT+CT+IC+MS+QCprovided the greatest reduction in mortality, but increased costs by 95% compared withHT+CT+IC+MSand was not cost-effective (ICER $8,000/YLS). With Re1·2,HT+CT+IC+MSwas the least costly strategy, andHT+CT+IC+MS+QCwas not cost-effective (ICER $294,320/YLS).InterpretationIn South Africa, a strategy of household contact tracing, isolation, and mass symptom screening would substantially reduce COVID-19 mortality and be cost-effective. Adding quarantine centres for COVID-19 contacts is not cost-effective.FundingRoyal Society, Wellcome Trust, National Institutes of Health
Male gender and kidney illness associated with an increased risk of severe laboratory-confirmed coronavirus disease
Authors: Murillo-Zamora Efrén , Trujillo Xóchitl , Huerta Miguel , Ríos-Silva Mónica , Mendoza-Cano Oliver 
Published: July 2020

AbstractObjectiveTo identify factors predicting severe coronavirus disease 2019 (COVID-19) in adolescent and adult patients with laboratory-positive (quantitative reverse-transcription polymerase chain reaction) infection.MethodsA retrospective cohort study took place, and data from 740 subjects, from all 32 states of Mexico, were analyzed. The association between the studied factors and severe (dyspnea requiring hospital admission) COVID-19 was evaluated through risk ratios (RRs) and 95% confidence intervals (CIs).ResultsSevere illness was documented in 28% of participants. In multiple analysis, male gender (RR = 1.13, 95% CI 1.06 - 1.20), advanced age ([reference: 15 - 29 years old] 30 - 44, RR = 1.02, 95% CI 0.94 - 1.11; 45 - 59, RR = 1.26, 95% CI 1.15 - 1.38; 60 years or older, RR = 1.44, 95% CI 1.29 - 1.60), chronic kidney disease (RR = 1.31, 95% CI 1.04 - 1.64) and thoracic pain (RR = 1.16, 95% CI 1.10 - 1.24) were associated with an increased risk of severe disease.ConclusionsTo the best of our knowledge, this is the first study evaluating predictors of COVID-19 severity in a large subset of the Latin-American population. It is also the first in documenting gender-related differences regarding the severity of the illness. These results may be useful for health care protocols for the early detection and management of COVID-19 patients that may benefit from opportune and specialized supportive medical treatment.
Resting-state fMRI Connectivity between Semantic and Phonologic Regions of Interest May Inform Language Targets in Aphasia
Authors: Ramage Amy E. , Aytur Semra , Ballard Kirrie J. 
Published: July 2020

PurposeBrain imaging has provided puzzle pieces in the understanding of language. In neurologically healthy populations, structure of certain brain regions is associated with particular language functions (e.g., semantics, phonology). In studies on focal brain damage, certain brain regions or connections are considered sufficient or necessary for a given language function. However, few of these account for the effects of lesioned tissue on the functional dynamics of the brain for language processing. Here, functional connectivity amongst semantic-phonologic regions of interest (ROIs) is assessed to fill a gap in our understanding about the neural substrates of impaired language and whether connectivity strength can predict language performance on a clinical tool in individuals with aphasia.MethodClinical assessment of language, using the Western Aphasia Battery-Revised (WAB-R), and resting-state fMRI data were obtained for 30 individuals with chronic aphasia secondary to left hemisphere stroke and 18 age-matched healthy controls. Functional connectivity (FC) between bilateral ROIs was contrasted by group and used to predict WAB-R scores.ResultsNetwork coherence was observed in healthy controls and participants with stroke. The left-right premotor cortex connection was stronger in healthy controls, as reported by New et al. (2015) in the same data set. FC of (1) bilateral connections between temporal regions, in the left hemisphere and bilaterally, predicted lexical semantic processing for Auditory Comprehension and (2) ipsilateral connections between temporal and frontal regions in both hemispheres predicted access to semantic-phonologic representations and processing for verbal production.ConclusionsNetwork connectivity of brain regions associated with semantic-phonologic processing is predictive of language performance in post-stroke aphasia. The most predictive connections involved right hemisphere ROIs – particularly those for which structural adaptions are known to associate with recovered word retrieval performance. Predictions may be made, based on these findings, about which connections have potential as targets for neuroplastic functional changes with intervention in aphasia.
Implications of the COVID-19 San Francisco Bay Area Shelter-in-Place Announcement: A Cross-Sectional Social Media Survey
Authors: Elser Holly , Kiang Mathew V. , John Esther M. , Simard Julia F. , Bondy Melissa , Nelson Lorene M. , Chen Wei-ting , Linos Eleni 
Published: July 2020

ABSTRACTBackgroundThe U.S. has experienced an unprecedented number of shelter-in-place orders throughout the COVID-19 pandemic. There is limited empirical research that examines the impact of these orders. We aimed to rapidly ascertain whether social distancing; difficulty with daily activities (obtaining food, essential medications and childcare); and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of shelter-in-place orders for seven counties in the San Francisco Bay Area.MethodsWe conducted an online, cross-sectional social media survey from March 14 – April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area and elsewhere in the U.S.ResultsThe percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty with obtaining food, hand sanitizer, and medications, particularly with obtaining food for both respondents from the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the shelter-in-place announcement.ConclusionThese results capture early changes in attitudes, behaviors, and difficulties. Further research that specifically examines social, economic, and health impacts of COVID-19, especially among vulnerable populations, is urgently needed.
Computational Analysis of the Metal Selectivity of Matrix Metalloproteinase 8
Authors: Long Zheng 
Published: July 2020

AbstractMatrix metalloproteinase (MMP) is a class of metalloenzyme that cleaves peptide bonds in extracellular matrices. Their functions are important in both health and disease of animals. Here using quantum mechanics simulations of the MMP8 protein, the coordination chemistry of different metal cofactors is examined. Comparisons found that Jhan-Teller effects in Cu(II) destabilize the wild-type MMP8 but a histidine to glutamine mutation at residue number 197 can potentially allow the MMP8 protein to utilize Cu(II) in reactions. Simulations also demonstrates the requirement of a conformational change in the ligand before enzymatic cleavage. The insights provided in here will assist future protein engineering efforts utilizing the MMP8 protein.
Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacyin vivo
Authors: Li Maohua , Zhao Rongqing , Chen Jianxin , Tian Wenzhi , Xia Chenxi , Liu Xudong , Li Yingzi , Yan Yuyuan , Li Song , Sun Hunter , Shen Tong , Ren Wenlin , Sun Le 
Published: July 2020

AbstractSome cancer patients treated with Atezolizumab, PD-L1 antibody drug launched by Genentech, quickly developed anti-drug antibody (ADA), led to loss of efficacy. This was likely due to the heavy aggregation of Atezolizumab, caused by mutation of N297A for removing unwanted antibody-dependent cytotoxicity (ADCC) of IgG1 antibody drug. Here, we developed a new version of Atezolizumab (Maxatezo), which was demonstrated better anti-tumor efficacyin vivo. In Atezolizumab, we mutated 297A to 297N back to bring back the glycosylation, and inserted a short sequence GGGS between G237 and G238 in the hinge region of the IgG1 heavy chain. Our data shown that insertion of GGGS, without altering the anti-PD-L1 antibody affinity and inhibitory activity, completely abolished the ADCC activity, as same as Atezolizumab. Moreover, the insertion of GGGS, without altering the glycosylation profile of IgG1, increased the yields of anti-PD-L1 antibody considerately. Additionally, glycosylation improved the stability yet reduced the amounts of aggregations in the antibody solutions. In turn, the level of ADA in animals treated with Maxatezo was 70% lower than the ones treated with Atezolizumab. Most importantly, at the same 10mg/kg dose, the anti-tumor activity of Maxatezo had attained 98% compared to that of Atezolizumab at 68%.
Lung-to-ear sound transmission does not improve directional hearing in green treefrogs (Hyla cinerea)
Authors: Christensen-Dalsgaard Jakob , Lee Norman , Bee Mark A. 
Published: July 2020

ABSTRACTAmphibians are unique among extant vertebrates in having middle ear cavities that are internally coupled to each other and to the lungs. In frogs, the lung-to-ear sound transmission pathway can influence the tympanum’s inherent directionality, but what role such effects might play in directional hearing remain unclear. In this study of the American green treefrog (Hyla cinerea), we tested the hypothesis that the lung-to-ear sound transmission pathway functions to improve directional hearing, particularly in the context of interspecific sexual communication. Using laser vibrometry, we measured the tympanum’s vibration amplitude in females in response to a frequency modulated sweep presented from 12 sound incidence angles in azimuth. Tympanum directionality was determined across three states of lung inflation (inflated, deflated, reinflated) both for a single tympanum in the form of the vibration amplitude difference (VAD) and for binaural comparisons in the form of the interaural vibration amplitude difference (IVAD). The state of lung inflation had negligible effects (typically less than 0.5 dB) on both VADs and IVADs at frequencies emphasized in the advertisement calls produced by conspecific males (834 Hz and 2730 Hz). Directionality at the peak resonance frequency of the lungs (1558 Hz) was improved by ≅ 3 dB for a single tympanum when the lungs were inflated versus deflated, but IVADs were not impacted by the state of lung inflation. Based on these results, we reject the hypothesis that the lung-to-ear sound transmission pathway functions to improve directional hearing in frogs.SUMMARY STATEMENTContrary to prevailing views on the mechanisms of hearing in frogs, the lung-to-ear pathway for sound transmission does not improve directional hearing in these vociferous vertebrates.
Anin-vitroBBB-on-a-chip open model of human blood-brain barrier enabling advanced optical imaging
Authors: Salman Mootaz , Marsh Graham , Küsters Ilja , Delincé Matthieu , Di Caprio Giuseppe , Upadhyayula Srigokul , de Nola Giovanni , Hunt Ronan , Ohashi Kazuka G. , Shimizu Fumitaka , Sano Yasuteru , Kanda Takashi , Obermeier Birgit , Kirchhausen Tom 
Published: July 2020

ABSTRACTWe describe here the design and implementation of anin-vitroBBB-on-a-chip open model system capable of reconstituting the microenvironment of the blood brain barrier. This system allows controlled unidirectional flow of nutrients and biologicals on the lumen of the artificial microvessel. This BBB-on-a-chip is suitable for high resolution electron microscopy and it is amenable for quantitative 3D live fluorescence imaging using spinning confocal disk or lattice light sheet microscopy (LLSM) to follow, for example the transcytosis across the BBB-like barrier of fluorescently-tagged biological, viruses or nanoparticles.
Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain:In silicoanalysis
Authors: Chukwudozie Onyeka S. , Chukwuanukwu Rebecca C. , Onyekachi Iroanya O. , Daniel Eze M. , Vincent Duru C. , Onaopemipo Dele-Alimi T. , Kehinde Busuyi D. , Taiwo Bankole T. , Perpetua Obi C. , Elizabeth Okinedo U. 
Published: July 2020

ABSTRACTThe novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we, therefore, designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of nucleocapsid protein that aid in viral replication. Promising antigenic B-cells and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and non-allergenic property. Two CD8+and Three CD4+T-cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and II alleles. With these selected epitopes, a non-allergenic chimeric peptide vaccine incapable of inducing a Type II hypersensitivity reaction was constructed. The molecular interaction between the toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally,in silicocloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.
Complete vertebrate mitogenomes reveal widespread gene duplications and repeats
Authors: Formenti Giulio , Rhie Arang , Balacco Jennifer , Haase Bettina , Mountcastle Jacquelyn , Fedrigo Olivier , Brown Samara , Capodiferro Marco , Al-Ajli Farooq O. , Ambrosini Roberto , Houde Peter , Koren Sergey , Oliver Karen , Smith Michelle , Skelton Jason , Betteridge Emma , Dolucan Jale , Corton Craig , Bista Iliana , Torrance James , Tracey Alan , Wood Jonathan , Uliano-Silva Marcela , Howe Kerstin , McCarthy Shane , Winkler Sylke , Kwak Woori , Korlach Jonas , Fungtammasan Arkarachai , Fordham Daniel , Costa Vania , Mayes Simon , Chiara Matteo , Horner David S. , Myers Eugene , Durbin Richard , Achilli Alessandro , Braun Edward L. , Phillippy Adam M. , Jarvis Erich D. ,   The Vertebrate Genomes Project Consortium
Published: July 2020

AbstractModern sequencing technologies should make the assembly of the relatively small mitochondrial genomes an easy undertaking. However, few tools exist that address mitochondrial assembly directly. As part of the Vertebrate Genomes Project (VGP) we have developed mitoVGP, a fully automated pipeline for similarity-based identification of mitochondrial reads and de novo assembly of mitochondrial genomes that incorporates both long (>10 kbp, PacBio or Nanopore) and short (100-300 bp, Illumina) reads. Our pipeline led to successful complete mitogenome assemblies of 100 vertebrate species of the VGP. We have observed that tissue type and library size selection have considerable impact on mitogenome sequencing and assembly. Comparing our assemblies to purportedly complete reference mitogenomes based on short-read sequencing, we have identified errors, missing sequences, and incomplete genes in those references, particularly in repeat regions. Our assemblies have also identified novel gene region duplications, shedding new light on mitochondrial genome evolution and organization.
Potassium starvation induces autophagy in yeast
Authors: Rangarajan Nambirajan , Kapoor Ishani , Li Shuang , Drossopoulos Peter , White Kristen K. , Madden Victoria J. , Dohlman Henrik G. 
Published: July 2020

ABSTRACTAutophagy is a conserved process that recycles cellular contents to promote survival. Although nitrogen starvation is the canonical inducer of autophagy, recent studies have revealed several other nutrients important to this process. In this study, we used a quantitative, high-throughput assay to identify potassium starvation as a new and potent inducer of autophagy. We found that potassium-dependent autophagy requires the core pathway kinases Atg1, Atg5, Vps34, as well as other components of Phosphatidylinositol 3-kinase Complex I. Transmission electron microscopy revealed abundant autophagosome formation in response to both stimuli. RNA sequencing indicated distinct transcriptional responses – nitrogen affects transport of ions such as copper while potassium targets the organization of other cellular components. Thus, nitrogen and potassium share the ability to influence metabolic supply and demand but do so in different ways. Both inputs promote catabolism through bulk autophagy, but inhibit cellular anabolism through distinct mechanisms.
Complementation cloning identifies the essentials of mammalian Mastl kinase activation
Authors: Erguven Mehmet , Karaca Ezgi , Diril M. Kasim 
Published: July 2020

ABSTRACTMastl is a mitotic kinase that is essential for error-free chromosome segregation. It is an atypical member of the AGC kinase family, possessing a unique non-conserved middle region (NCMR). The mechanism of its activation prior to mitosis has been extensively studied in Xenopus egg extracts. These studies found several residues (corresponding to T193 and T206 in the activation loop, and S861 in the C-terminal tail, i.e., C-tail of mouse Mastl) whose phosphorylations are crucial for enzymatic activation. To date, the significance of these phosphosites was not confirmed in live mammalian cells. Here, we utilize a complementation cloning approach to determine the essentials of mammalian Mastl kinase activity. We employed a tamoxifen-inducible conditional knockout system to delete the endogenous Mastl in mouse embryonic fibroblasts (MEF) and screened various mutants for their ability to complement its loss. MEFs, ectopically expressing different phosphorylation site mutants, were induced to undergo recombination-mediated knockout in their endogenous Mastl loci. S861A and S861D mutants were able to complement endogenous Mastl loss with proliferation rates comparable to WT. In parallel, we examined the available protein kinase structures having a phosphorylated C-tail. Among the published states, two distinct positionings of the C-tail phosphoresidue were observed. Energetic analysis of these states revealed that only one conformation highly contributes to the C-tail docking. Our in-depth sequence and structure analysis showed that Mastl pS861 does not belong to the conformational state, where the phosphoresidue contributes to the C-tail docking. The C-tail of Mastl is relatively short and it lacks the hydrophobic (HF) motif. In other AGC kinases, the C-tail phosphosite aids the anchoring of this motif over the N-lobe, leading to the final step of kinase activation. Together with the lack of HF motif in Mastl, our results suggest that phosphorylation of the C-tail turn motif phosphosite (S861) is auxiliary and is dispensable for mammalian Mastl kinase function. Furthermore, we demonstrated that complementation cloning is a powerful approach for screening the determinants of an essential protein’s functioning.