bluuebunny/crossref_metadata_2025_split huggingface dataset:
One-Seq: A Highly Scalable Sequencing-Based Diagnostic for SARS-CoV-2 and Other Single-Stranded Viruses
Authors: Dai Mingjie , Ma Wenzhe , Kang Hong , Sonnett Matthew , Church George M. , Kirschner Marc W. 
Published: April 2021

AbstractThe management of pandemics such as COVID-19 requires highly scalable and sensitive viral diagnostics, together with variant identification. Next-generation sequencing (NGS) has many attractive features for highly multiplexed testing, however current sequencing-based methods are limited in throughput by early processing steps on individual samples (e.g. RNA extraction and PCR amplification). Here we report a new method, “One-Seq”, that eliminates the current bottlenecks in scalability by enabling early pooling of samples, before any extraction or amplification steps. To enable early pooling, we developed a one-pot reaction for efficient reverse transcription (RT) and upfront barcoding in extraction-free clinical samples, and a “protector” strategy in which carefully designed competing oligonucleotides prevent barcode crosstalk and preserve detection of the high dynamic range of viral load in clinical samples. This method is highly sensitive, achieving a limit of detection (LoD) down to 2.5 genome copy equivalent (gce) in contrived RT samples, 10 gce in multiplexed sequencing, and 2-5 gce with multi-primer detection, suggesting an LoD of 200-500 gce/ml for clinical testing. In clinical specimens, One-Seq showed quantitative viral detection against clinical Ct values with 6 logs of linear dynamic range and detection of SARS-CoV-2 positive samples down to ∼360 gce/ml. In addition, One-Seq reports a number of hotspot viral mutations at equal scalability at no extra cost. Scaling up One-Seq would allow a throughput of 100,000-1,000,000 tests per day per single clinical lab, at an estimated amortized reagent cost of $1.5 per test and turn-around time of 7.5-15 hr.
Community’s misconception about COVID-19 and its associated factors: Evidence from a cross-sectional study in Bangladesh
Authors: Bakebillah Md. , Billah Md. Arif , Wubishet Befikadu L. , Khan Md. Nuruzzaman 
Published: April 2021

AbstractIntroductionMisconception about COVID-19 has been spread out broadly that the World Health Organization declared it as a major challenge in the fight against the disease. This study aimed to assess common misconceptions about COVID-19 among the rural people of Bangladesh and its associated socio-demographic and media related factors.MethodsData were collected from 210 respondents selected from three unions of Satkhira District, Bangladesh.The dependent variable was misconception about COVID-19 (Yes, No) which was generated based on the respondents’ responses to six questions on common misconceptions of COVID-19. Explanatory variables were respondents’ socio-demographic characteristics, mass media and social media use habits. Descriptive statistics were used to describe the characteristics of the respondents. Univariate and multivariate logistic regression models were used to determine the factors associated with misconception about COVID-19.ResultsMisconceptions about COVID-19 were found among more than half of the total respondents. More than 50% of the respondents reported they consider COVID-19 as a punishment from God. Besides, most of the respondents reported that they do not think COVID-19 is dangerous (59%), and COVID-19 is a disease (19%). Around 7% of the total respondents reported they consider this virus as a part of a virus war (7.2%). Bivariate analysis found that socio-demographic characteristics of the respondents and factors related to social and mass media were significantly associated with misconception. However, when all the factors included together in the multivariate model, the likelihood of misconception was lower among secondary (AOR, 0.33, 95% CI, 0.13-0.84) and tertiary (AOR, 0.29, 95% CI, 0.09-0.92) educated respondents compared to respondents with primary education.ConclusionThis study obtained a very higher percentage of the rural people of Bangladesh having one or more misconceptions related to COVID-19. This could be a potential challenge in the fight against the pandemic. Effective use of mass and social media to communicate evidence based information on COVID-19 as well as to educate the public about COVID-19 is important.
Reliability of Spike Gene Target Failure for ascertaining SARS-CoV-2 lineage B.1.1.7 prevalence in a hospital setting
Authors: Guerra-Assunção José Afonso , Randell Paul A. , Boshier Florencia A. T. , Crone Michael A. , Pang Juanita , Mahungu Tabitha , Freemont Paul S. , Breuer Judith 
Published: April 2021

AbstractThe appearance of the SARS-CoV-2 lineage B.1.1.7 in the UK in late 2020, associated with faster transmission, sparked the need to find effective ways to monitor its spread. The set of mutations that characterise this lineage include a deletion in position 69 and 70 of the spike protein, which is known to be associated with Spike Gene Target Failure (SGTF) in a commonly used three gene diagnostic qPCR assay. The lower cost and faster turnaround times compared to whole genome sequencing make the use of qPCR for monitoring of the variant spread an attractive proposition. However, there are several potential issues with this approach. Here we use 826 SARS-CoV-2 samples collected in a hospital setting as part of the Hospital Onset COVID Infection (HOCI) study where qPCR was used for viral detection, followed by whole genome sequencing (WGS), to identify the factors to consider when using SGTF to infer lineage B.1.1.7 prevalence in a hospital setting, with potential implications for locations where this variant has recently been introduced.
Clinical malaria incidence following an outbreak in Ecuador was predominantly associated withPlasmodium falciparumwith recombinant variant antigen gene repertoires
Authors: Ruybal-Pesántez Shazia , Sáenz Fabian E. , Deed Samantha , Johnson Erik K. , Larremore Daniel B. , Vera-Arias Claudia A. , Tiedje Kathryn E. , Day Karen P. 
Published: April 2021

AbstractTo better understand the factors underlying the continued incidence of clinical episodes of falciparum malaria in E-2020 countries targeting elimination, we have characterisedPlasmodium falciparumdisease transmission dynamics after a clonal outbreak on the northwest coast of Ecuador over a period of two years. We apply a novel, high-resolution genotyping method, the “varcode” based on a single PCR to fingerprint the DBLα region of the 40-60 members of the variant surface antigen-encodingvarmultigene family.Vargenes are highly polymorphic within and between genomes, withvarrepertoires rapidly evolving by outcrossing during the obligatory sexual phase ofP. falciparumin the mosquito. The continued incidence of clinical malaria after the outbreak in Ecuador provided a unique opportunity to usevarcodes to document parasite microevolution and explore signatures of local disease transmission on the time scale of months to two years post-outbreak. We identified nine geneticvarcodes circulating locally with spatiotemporal parasite genetic relatedness networks revealing that diversification of the clonal outbreak parasites by sexual recombination was associated with increased incidence of clinical episodes of malaria. Whether this was due to chance, immune selection or sexual recombination per se is discussed. Comparative analyses to other South American parasite populations whereP. falciparumtransmission remains endemic elucidated the possible origins of Ecuadorianvarcodes. This analysis demonstrated that the majority of clinical cases were due to local transmission and not importation. Nonetheless, some of thevarcodes that were unrelated to the outbreakvarcode were found to be genetically related to other South American parasites. Our findings demonstrate the utility of thevarcode as a high-resolution surveillance tool to spatiotemporally track disease outbreaks using variant surface antigen genes and resolve signatures of recombination in an E-2020 setting nearing elimination.
Facemask usage during the COVID-19 pandemic among people with primary ciliary dyskinesia: a participatory project
Authors: Pedersen Eva SL , Collaud Eugenie NR , Mozun Rebeca , Dexter Katie , Kruljac Catherine , Silberschmidt Hansruedi ,   COVID-PCD patient advisory group, Lucas Jane S , Goutaki Myrofora , Kuehni Claudia E 
Published: April 2021

AbstractBackgroundFacemasks help prevent transmission of SARS-CoV-2 and are particularly important for people with chronic respiratory disease such as primary ciliary dyskinesia (PCD). We studied the usage of facemasks and its consequences among people with PCD in an international context.MethodsWe used data from COVID-PCD, an international observational cohort study which collects longitudinal data from people with PCD during the COVID-19 pandemic via weekly online questionnaires. An online questionnaire investigating use of facemasks was posted in October 2020. It asked about frequency of facemask usage in different public places, problems experienced with use of facemasks, affordability of masks, and beliefs regarding their effectiveness.Results282 participants (50%) completed the questionnaire. Participants came from 27 different countries; median age was 32 years (interquartile range 17-48), and 63% were female. Almost all wore a facemask whenever they left their house. In addition, many avoided public places altogether. For example, 159 (57%) did not use public transport at all, 108 (39%) always wore a facemask in public transport, 4 (1%) sometimes, and 7 (3%) never. 81% agreed with the statement that facemasks protect the person who wears the mask, and 91% agreed that facemasks protect others. One third reported that it was uncomfortable to wear a mask because of their runny nose, 31% because of cough, and 22% because of difficulty breathing. Participants less often wore facemasks in public when there was no national requirement. Only two persons had a personal exemption from wearing a facemask prescribed by a physician.ConclusionsThis international study found that people with PCD carefully shield themselves, and most wear facemasks everywhere in public. People who did not wear facemasks in public came from countries without a national facemask requirement. National policies mandating facemask use in public are important for universal use to protect high-risk populations from SARS-CoV-2 infections.
Consistent Tumorigenesis with Self-Assembled Hydrogels Enables High-powered Murine Cancer Studies
Authors: Grosskopf Abigail K. , Correa Santiago , Baillet Julie , Maikawa Caitlin L. , Gale Emily C. , Brown Ryanne A. , Appel Eric A. 
Published: April 2021

AbstractPreclinical cancer research is heavily dependent on allograft and xenograft models, but current approaches to tumor inoculation yield inconsistent tumor formation and growth, ultimately wasting valuable resources (e.g., animals, time, and money) and limiting experimental progress. Here we demonstrate a method for tumor inoculation using self-assembled hydrogels to reliably generate tumors with low variance in growth. The observed reduction in model variance enables smaller animal cohorts, improved effect observation and higher powered studies.
Chromosome evolution and the genetic basis of agronomically important traits in greater yam
Authors: Bredeson Jessen V. , Lyons Jessica B. , Oniyinde Ibukun O. , Okereke Nneka R. , Kolade Olufisayo , Nnabue Ikenna , Nwadili Christian O. , Hřibová Eva , Parker Matthew , Nwogha Jeremiah , Shu Shengqiang , Carlson Joseph , Kariba Robert , Muthemba Samuel , Knop Katarzyna , Barton Geoffrey J. , Sherwood Anna V. , Lopez-Montes Antonio , Asiedu Robert , Jamnadass Ramni , Muchugi Alice , Goodstein David , Egesi Chiedozie N. , Featherston Jonathan , Asfaw Asrat , Simpson Gordon G. , Doležel Jaroslav , Hendre Prasad S. , Van Deynze Allen , Kumar Pullikanti Lava , Obidiegwu Jude E. , Bhattacharjee Ranjana , Rokhsar Daniel S. 
Published: April 2021

AbstractThe nutrient-rich tubers of the greater yamDioscorea alataL. provide food and income security for millions of people around the world. Despite its global importance, however, greater yam remains an “orphan crop.” Here we address this resource gap by presenting a highly-contiguous chromosome-scale genome assembly of greater yam combined with a dense genetic map derived from African breeding populations. The genome sequence reveals an ancient lineage-specific genome duplication, followed by extensive genome-wide reorganization. Using our new genomic tools we find quantitative trait loci for susceptibility to anthracnose, a damaging fungal pathogen of yam, and several tuber quality traits. Genomic analysis of breeding lines reveals both extensive inbreeding as well as regions of extensive heterozygosity that may represent interspecific introgression during domestication. These tools and insights will enable yam breeders to unlock the potential of this staple crop and take full advantage of its adaptability to varied environments.
Procyanidin C1 is a natural agent with senolytic activity against aging and age-related diseases
Authors: Xu Qixia , Fu Qiang , Li Zi , Liu Hanxin , Wang Ying , Lin Xu , He Ruikun , Zhang Xuguang , Campisi Judith , Kirkland James L. , Sun Yu 
Published: April 2021

AbstractAging causes functional decline of multiple organs and increases the risk of age-related pathologies. In advanced lives, accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP), promotes chronic inflammation and causes diverse conditions. Here we report the frontline outcome of screening a natural product library with human primary stromal cells as an experimental model. Multiple candidate compounds were assayed, and grape seed extract (GSE) was selected for further investigation due to its leading capacity in targeting senescent cells. We found procyanidin C1 (PCC1), a polyphenolic component, plays a critical role in mediating the antiaging effects of GSE. PCC1 blocks the SASP expression when used at low concentrations. Importantly, it selectively kills senescent cells upon application at higher concentrations, mainly by enhancing production of reactive oxygen species (ROS) and disturbing mitochondrial membrane potential, processes accompanied by upregulation of Bcl-2 family pro-apoptotic factors Puma and Noxa in senescent cells. PCC1 depletes senescent cells in treatment-damaged tumor microenvironment (TME) and enhances therapeutic efficacy when combined with chemotherapy in preclinical assays. Intermittent administration of PCC1 to both senescent cell-implanted mice and naturally aged animals alleviated physical dysfunction and prolonged post-treatment survival, thus providing substantial benefits in late life stage. Together, our study identifies PCC1 as a distinct natural senolytic agent, which may be exploited to delay aging and control age-related pathologies in future medicine.
DEPDC1/ EEF1A1 complex promotes the progression of human osteosarcoma via downregulation of FOXO3a
Authors: Shen Lin , Li Han , Zhang Aijun , Liu Ronghan , Zhou Chendan , Zhang Ying , Zhao Kai , Bretches Morgan , Lu Laitong , Yang Shang-You , Ning Bin 
Published: April 2021

AbstractThere are currently lack of effective therapeutic strategies for osteosarcoma, primarily due to insufficient understanding of the underlying mechanisms of the tumor cells. This study deciphers a potentially critical interplay of DEPDC1–EEF1A1–FOXO3a axis during the osteosarcoma progression. Bioinformatics analysis of documented 25,035 genes for differentially expressed genes were accompanied by transcriptional and translational examinations of clinical osteosarcoma specimens and osteosarcoma cell lines to assess the roles and interactions of DEP domain-containing 1 (DEPDC1), Elongation Factor 1-alpha 1 (EEF1A1), and FOXO3a in the tumor cells proliferation and prognosis. Gene expression profile analysis and clinical tests revealed highly expressed DEPDC1 in human osteosarcoma cells and tumor tissues. Vector-mediated silence of DEPDC1 resulted in halted osteosarcoma cell proliferation, promoted apoptosis, and ceased tumor metastasis. Immunoprecipitation assay confirmed that EEF1A1 directly bind to DEPDC1 protein through three binding regions. Further, DEPDC1/EEF1A1 complex significantly decreased the expression of FOXO3a at transcription and translation levels, which subsequently promoted the proliferation of osteosarcoma cells and tumor metastasis. Correlation studies exhibited that overexpression of DEPDC1/EEF1A1 complex in the clinical specimens negatively correlated with the patient survival rate. In conclusion, DEPDC1-EEF1A1–FOXO3a axis plays as a critical pathway that regulates the progression and prognosis of osteosarcoma.
A Focal Adhesion Filament Cross-correlation Kit for fast, automated segmentation and correlation of focal adhesions and actin stress fibers in cells
Authors: Hauke Lara , Narasimhan Shwetha , Primeßnig Andreas , Kaverina Irina , Rehfeldt Florian 
Published: April 2021

AbstractFocal adhesions (FAs) and associated actin stress fibers (SFs) form a complex mechanical system that mediates bidirectional interactions between cells and their environment. This linked network is essential for mechanosensing, force production and force transduction, thus directly governing cellular processes like polarization, migration and extracellular matrix remodeling. We introduce a tool for fast and robust coupled analysis of both FAs and SFs named the Focal Adhesion Filament Cross-correlation Kit (FAFCK). Our software can detect and record location, axes lengths, area, orientation, and aspect ratio of focal adhesion structures as well as the location, length, width and orientation of actin stress fibers. This enables users to automate analysis of the correlation of FAs and SFs and study the stress fiber system in a higher degree, pivotal to accurately evaluate transmission of mechanocellular forces between a cell and its surroundings. The FAFCK is particularly suited for unbiased and systematic quantitative analysis of FAs and SFs necessary for novel approaches of traction force microscopy that uses the additional data from the cellular side to calculate the stress distribution in the substrate. For validation and comparison with other tools, we provide datasets of cells of varying quality that are labelled by a human expert. Datasets and FAFCK are freely available as open source under the GNU General Public License.Author summaryOur novel Focal Adhesion Filament Cross-correlation Kit (FAFCK) allows for fast, reliable, unbiased, and systematic detection of focal adhesions and actin stress fibers in cells and their mutual correlation. Detailed analysis of these structures which are both key elements in mechano-sensing and force transduction will help tremendously to improve quantitative analysis of mechanocellular experiments, key to understanding the complex interplay between cells and the extracellular matrix. In particular, sophisticated analysis methods such as model-based traction force microscopy will benefit from correlating the detailed datasets of stress fibers and focal adhesions.
Neuropilin-1 Mediates SARS-CoV-2 Infection in Bone Marrow-derived Macrophages
Authors: Gao Junjie , Mei Hong , Sun Jing , Li Hao , Huang Yuege , Tang Yanhong , Duan Linwei , Liu Delin , Wang Qiyang , Gao Youshui , Song Ke , Zhao Jincun , Zhang Changqing , Liu Jia 
Published: April 2021

AbstractSARS-CoV-2 infection in human can cause medical complications across various tissues and organs. Despite of the advances to understanding the pathogenesis of SARS-CoV-2, its tissue tropism and interactions with host cells have not been fully understood. Existing clinical data have suggested possible SARS-CoV-2 infection in human skeleton system. In the present study, we found that authentic SARS-CoV-2 could efficiently infect human and mouse bone marrow-derived macrophages (BMMs) and alter the expression of macrophage chemotaxis and osteoclast-related genes. Importantly, in a mouse SARS-CoV-2 infection model that was enabled by the intranasal adenoviral (AdV) delivery of human angiotensin converting enzyme 2 (hACE2), SARS-CoV-2 was found to be present in femoral BMMs as determined byin situimmunofluorescence analysis. Using single-cell RNA sequencing (scRNA-Seq), we characterized SARS-CoV-2 infection in BMMs. Importantly, SARS-CoV-2 entry on BMMs appeared to be dependent on the expression of neuropilin-1 (NRP1) rather than the widely recognized receptor ACE2. It was also noted that unlike brain macrophages which displayed aging-dependent NRP1 expression, BMMs from neonatal and aged mice had constant NRP1 expression, making BMMs constantly vulnerable target cells for SARS-CoV-2. Furthermore, it was found that the abolished SARS-CoV-2 entry in BMM-derived osteoclasts was associated with the loss of NRP1 expression during BMM-to-osteoclast differentiation. Collectively, our study has suggested that NRP1 can mediate SARS-CoV-2 infection in BMMs, which precautions the potential impact of SARS-CoV-2 infection on human skeleton system.
Structural basis for silicon uptake by higher plants
Authors: van den Berg Bert , Pedebos Conrado , Bolla Jani R. , Robinson Carol V. , Baslé Arnaud , Khalid Syma 
Published: April 2021

AbstractMetalloids are elements with physical and chemical properties that are intermediate between metals and non-metals. Silicon (Si) is the most abundant metalloid in the Earth’s crust and occurs at high levels in many plants, especially those belonging to the Poaceae (grasses). Most of the world’s staple food crops such as rice, barley and maize accumulate silicon to high levels, resulting in resistance to abiotic and biotic stresses and consequently better plant growth and crop yields. The first step in silicon accumulation is the uptake of silicic acid (Si), the bioavailable from of silicon, by the roots, a process mediated by the structurally uncharacterised NIP subfamily of aquaporins. Here we present the X-ray crystal structure of the archetypal NIP family member fromOryza sativa(OsNIP2;1). While the OsNIP2;1 channel is closed in the crystal by intracellular loop D, unbiased molecular dynamics (MD) simulations reveal a rapid channel opening on sub-microsecond time scales. MD simulations further show how Si interacts with an extracellular five-residue selectivity filter that provides the main barrier for transmembrane diffusion. Our data provide a foundation for understanding and potential manipulation of metalloid selectivity of an important and understudied aquaporin subfamily.SignificanceMany of the world’s most important food crops such as rice, barley and maize accumulate silicon to high levels, resulting in better plant growth and crop yields. The first step in silicon accumulation is the uptake of silicic acid (Si) by the roots, a process mediated by the structurally uncharacterised NIP subfamily of aquaporins. Here, we present the X-ray crystal structure and molecular dynamics simulations of the archetypal NIP family member fromOryza sativa(OsNIP2;1) to visualise Si uptake. Our data provide a platform for improved understanding of Si uptake by plants that could be utilised,e.g., in silicon biofortification of important crops and potential alleviation of arsenic accumulation in the rice grain.