bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional and comparative genome analysis reveals clade-specific genome innovations in the killer fungusCandida auris
Authors: Narayanan Aswathy , Vadnala Rakesh Netha , Ganguly Promit , Selvakumar Pavitra , Rudramurthy Shivaprakash M , Prasad Rajendra , Chakrabarti Arunaloke , Siddharthan Rahul , Sanyal Kaustuv 
Published: February 2021

AbstractThe thermotolerant multidrug-resistant ascomyceteCandida aurisrapidly emerged since 2009 and simultaneously evolved in different geographical zones worldwide, causing superficial as well as systemic infections. The molecular events that orchestrated this sudden emergence of the killer fungus remain mostly elusive. Here, we identify centromeres inC. aurisand related species, using a combined approach of chromatin immunoprecipitation and comparative genomic analyses. We find thatC. aurisand multiple other species in theClavispora/Candidaclade shared a conserved small regional centromere landscape lacking pericentromeres. Further, a centromere inactivation event led to karyotypic alterations in this species complex. Inter-species genome analysis identified several structural chromosomal changes around centromeres. In addition, centromeres are found to be rapidly evolving loci among the different geographical clades of the same species ofC. auris. Finally, we reveal an evolutionary trajectory of the unique karyotype associated with clade 2 that consists of the drug susceptible isolates ofC. auris.
Diagnostic accuracy of Panbio™ rapid antigen tests on oropharyngeal swabs for detection of SARS-CoV-2
Authors: Ngo Nsoga Marie Thérèse , Kronig Ilona , Perez Rodriguez Francisco Javier , Sattonnet-Roche Pascale , Da Silva Diogo , Helbling Javan , Sacks Jilian A. , de Vos Margaretha , Boehm Erik , Gayet-Ageron Angèle , Berger Alice , Jacquerioz-Bausch Frédérique , Chappuis François , Kaiser Laurent , Schibler Manuel , Renzoni Adriana , Eckerle Isabella 
Published: February 2021

AbstractBackgroundAntigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients.MethodsWe conducted a prospective study in a single screening center to assess the diagnostic performance of the Panbio™ COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS.Results402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a specificity of 99.1% (95%CI: 96.9-99.9) for the Ag-RDT.For cycle threshold values ≤ 26.7 (≥ 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS.InterpretationBased on our findings, the diagnostic performance of the Panbio™ Covid-19 RDT with OPS samples meet the criteria required by the WHO for Ag-RDTs (sensitivity≥80% and specificity ≥97%).
Integrating primary care and social services for older adults with multimorbidity: A qualitative study
Authors: Dambha-Miller Hajira , Simpson Glenn , Hobson Lucy , Olaniyan Doyinsola , Hodgson Sam , Roderick Paul , Fraser Simon DS , Little Paul , Everitt Hazel , Santer Miriam 
Published: February 2021

AbstractBackgroundGrowing demand from an ageing population, chronic preventable disease and multimorbidity has resulted in complex health and social care needs requiring more integrated services. Integrating primary care with social services could more efficiently utilise resources, and improve experiences for patients, their families and carers. There is limited evidence on progress including key barriers and drivers of integration to inform large-scale national change.AimTo elicit stakeholder views on drivers and barriers of integrated primary care and social services. and highlight opportunities for successful implementation.Design and settingA qualitative interview study.MethodSemi-structured interviews with maximum variation sampling to capture stakeholder views across services and professions.ResultsThirty-seven interviews were conducted across England including GPs, nurses, social care staff, commissioners, local government, voluntary and private sectors, patients and carers. Drivers of integration included groups of like-minded individuals supported by good leadership, expanded interface roles to bridge gaps between systems and co-location of services. Barriers included structural and interdisciplinary tension between professions, organisational self-interest and challenges in record-sharing.ConclusionsDrivers and barriers to integration identified in other contexts are also present in primary care and social services. Benefits of integration are unlikely to be realised if these are not addressed in the design and execution of new initiatives. Efforts should go beyond local and professional level change to include wider systems and policy-level initiatives. This will support a more systems-wide approach to integrated care reform, which is necessary to meet the complex and growing needs of an ageing multimorbid population.
Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2
Authors: Saadat Saman , Tehrani Zahra Rikhtegaran , Logue James , Newman Michelle , Frieman Matthew B. , Harris Anthony D. , Sajadi Mohammad M. 
Published: February 2021

AbstractCoronavirus disease 2019 (COVID-19) vaccine shortages have led some experts and countries to consider untested dosing regimens. We studied antibody responses to a single dose of the Pfizer-BioNTech or Moderna vaccines in healthcare workers (HCW) with laboratory-confirmed COVID-19 infection and compared to them to antibody responses of HCW who were IgG negative to SARS-CoV-2 spike protein. HCW with prior COVID-19 showed clear secondary antibody responses to vaccination with IgG spike binding titers rapidly increasing by 7 days and peaking by days 10 and 14 post-vaccination. At all time points tested, HCW with prior COVID-19 infection showed statistically significant higher antibody titers of binding and functional antibody compared to HCW without prior COVID-19 infection (p<.0001for each of the time points tested). In times of vaccine shortage, and until correlates of protection are identified, our findings preliminarily suggest the following strategy as more evidence-based: a) a single dose of vaccine for patients already having had laboratory-confirmed COVID-19; and b) patients who have had laboratory-confirmed COVID-19 can be placed lower on the vaccination priority list.
Retinol Depletion in Severe COVID-19
Authors: Sarohan Aziz Rodan , Akelma Hakan , Araç Eşref , Aslan Özgür 
Published: February 2021

AbstractBackground and PurposeVitamin A is depleted during infections. Vitamin A has been used successfully in measles, RSV and AIDS patients and is an effective vaccine adjuvant. In this study, low retinol levels were found in patients with severe COVID-19. Retinoid signaling impairment in COVID-19 disrupts Type-I interferon synthesis.Material and MethodTwo groups were formed in the study. The patient group consisted of 27 (Group 1) severe COVID-19 patients hospitalized in the intensive care unit with respiratory failure, and the control group consisted of 23 (Group 2) patients without COVID-19 symptoms. Serum retinol levels were analyzed by ELIZA and HPLC in both groups.FindingsRetinol levels were found to be significantly lower in the patient group (P <0.001). There was no difference in retinol between two different age groups in the patient group (P> 0.05). There was no significant difference in retinol between men and women (P> 0.05). Comorbidity did not affect serum retinol levels (P >0.05).ConclusionSerum retinol levels were low in patients with severe COVID-19. Drugs preventing retinol excretion were not stopped in the patient group. Some patients took vitamin A externally. Despite this, retinol was low in COVID-19 patients. Retinol depletion impairs Type-I interferon synthesis by impairing retinoid signaling. Retinoid signaling may be the main pathogenetic disorder in COVID-19. This pathogenesis can serve as a guide for adjuvants, drug targets, and candidate drugs. Retinol, retinoic acid derivatives, and some CYP450 inhibitors may work on COVID-19.
piRNAs Coordinate poly(UG) Tailing to Prevent Aberrant and Permanent Gene Silencing
Authors: Shukla Aditi , Perales Roberto , Kennedy Scott 
Published: February 2021

AbstractNoncoding RNAs have emerged as mediators of transgenerational epigenetic inheritance (TEI) in a number of organisms. A robust example of RNA-directed TEI is the inheritance of gene silencing states following RNA interference (RNAi) in the metazoan C. elegans. During RNAi inheritance, gene silencing is transmitted by a self-perpetuating cascade of siRNA-directed poly(UG) tailing of mRNA fragments (pUGylation), followed by siRNA synthesis from poly(UG)-tailed mRNA templates (termed pUG RNA/siRNA cycling). Despite the self-perpetuating nature of pUG RNA/siRNA cycling, RNAi inheritance is finite, suggesting that systems likely exist to prevent permanent RNAi-triggered gene silencing. Here we show that, in the absence of Piwi-interacting RNAs (piRNAs), an animal-specific class of small noncoding RNA, RNAi-based gene silencing can become essentially permanent, lasting at near 100% penetrance for more than five years and hundreds of generations. This permanent gene silencing is mediated by perpetual activation of the pUG RNA/siRNA TEI pathway. Further, we find that piRNAs coordinate endogenous RNAi pathways to prevent germline-expressed genes, which are not normally subjected to TEI, from entering a state of permanent and irreversible epigenetic silencing also mediated by perpetual activation of pUG RNA/siRNA cycling. Together, our results show that one function of C. elegans piRNAs is to insulate germline-expressed genes from aberrant and runaway inactivation by the pUG RNA/siRNA epigenetic inheritance system.
Expected 10-anonymity of HyperLogLog sketches for federated queries of clinical data repositories
Authors: Tao Ziye , Weber Griffin M. , Yu Yun William 
Published: February 2021

AbstractMotivationThe rapid growth in of electronic medical records provide immense potential to researchers, but are often silo-ed at separate hospitals. As a result, federated networks have arisen, which allow simultaneously querying medical databases at a group of connected institutions. The most basic such query is the aggregate count—e.g. How many patients have diabetes? However, depending on the protocol used to estimate that total, there is always a trade-off in the accuracy of the estimate against the risk of leaking confidential data. Prior work has shown that it is possible to empirically control that trade-off by using the HyperLogLog (HLL) probabilistic sketch.ResultsIn this article, we prove complementary theoretical bounds on the k-anonymity privacy risk of using HLL sketches, as well as exhibit code to efficiently compute those bounds.Availabilityhttps://github.com/tzyRachel/K-anonymity-ExpectationContactywyu@math.toronto.eduSupplementary informationN/A
Probing individual-level structural atrophy in frontal glioma patients
Authors: Zhang Guobin , Huang Huawei , Zhang Xiaokang , Wang Yonggang , Li Haoyi , Duan Yunyun , Chen Hongyan , Liu Yaou , Jing Bin , Lin Song 
Published: February 2021

AbstractAlthough every glioma patient varies in tumor size, location, histological grade and molecular biomarkers, structural abnormalities are commonly conducted in a group-level, leading to the miss of individual structural atrophy. In this study, we introduced an individual-level structural abnormality detection method for glioma patients and proposed several novel abnormality indexes to depict the individual atrophy pattern. Forty-five glioma patients in frontal lobe and fifty-two age-matched healthy controls participated in the study. All patients underwent neurocognitive test and molecular examinations, including 1p/19q co-deletion, isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation. Individual structural abnormality maps for every glioma patient were calculated from the preoperative T1 images, and the individual abnormality index were further computed and explored the associations with clinical indicators. The results manifested that: 1. Every glioma patient show unique atrophy pattern; 2. Glioma patients also share consistent atrophy regions; 3. The atrophy pattern is influenced by some molecular biomarkers. Our study provides an effective way to access the individual structural abnormalities in glioma patients, and displays great potentials in individualized precision medicine for glioma patients.
Sense of Agency for Mental Actions: Insights from a Belief-Based Action-Effect Paradigm
Authors: Lopez-Sola Edmundo , Moreno-Bote Rubén , Arsiwalla Xerxes D. 
Published: February 2021

AbstractA substantial body of research in the past few decades has converged on the idea that the so-called “sense of agency”, the feeling of being in control of our own actions, arises from the integration of multiple sources of information at different levels. In this study, we investigated whether a measurable sense of agency can be detected for mental actions, without the contribution of motor components. We used a fake action-effect paradigm, where participants were led to think that a motor action or a particular thought could trigger a sound. Results showed that the high-level sense of agency, measured through explicit reports, was of comparable strength for motor and mental actions. The ‘intentional binding’ effect, a phenomenon typically associated with the experience of agency, was also observed for both motor and mental actions, with the only exception of short action-effect delays. Furthermore, a consistent relationship between explicit reports of agency and intentional binding was found. Taken together, our results provide novel insights into the specific role of intentional cues in instantiating a sense of agency, even in the absence of motor signals. These results may have important implications for future brain-computer interfaces as well as for the study of pathological disruptions of agency.
AhNGE: A Database forArachis hypogaeaNodule Developmental Gene Expression
Authors: Shaheen Tarannum , Tembhare Kunal , Singh Ajeet , Raul Bikash , Ghosh Asim Kumar , Torres-Jerez Ivone , Clevenger Josh , Udvardi Michael , Scheffler Brian E. , Ozias-Akins Peggy , Bandyopadhyay Kaustav , Kumar Shailesh , Sinharoy Senjuti 
Published: February 2021

AbstractSymbiotic nitrogen fixation (SNF) inside root-nodules is a primary and sustainable source of soil nitrogen. Understanding nodule development and metabolism in crop legumes may lead to more effective SNF in agriculture. Peanut (Arachis hypogaea) is an economically important allotetraploid legume with non-canonical nodule developmental features. Recent genome sequencing of peanut has opened the possibility of making peanut a model for studying atypical nodule development. To help the community of nodule biologists, we have developed a database called AhNGE (Arachis hypogaeaNodule Developmental Gene Expression:http://nipgr.ac.in/AhNGE/index.php). AhNGE contains RNAseq data from six data points of nodule development inA. hypogagea cv. Tifrunner. This data represents a dynamic view of gene expression during peanut nodule development. Research in model legumes has generated a huge knowledgebase in the last twenty years. To streamline comparative genomics among legumes, we performed ortholog analysis among four legumes (Cicer, Glycine, Lotus, and Medicago) and one non-legume (Arabidopsis). This will facilitate the integration of existing knowledge in nodule development with theArachistranscriptome. The available data can be retrieved using a single or batch query or searching using gene ID, from above mentioned five species. The output displays the gene expression pattern in graphical as well as tabular form, along with further options to download the sequence data. The database is linked with PeanutBase, the main genomic resource of peanut. Additionally, the expression level of different splicing variants can be retrieved from the database. In summary, AhNGE serves as an important resource for the scientific community working on nodule development.
Multiplexed live visualization of cell fate dynamics in hPSCs at single-cell resolution
Authors: Kim Sungmin , Ren Edward , Casanova Paola Marco , Piddini Eugenia , Salas Rafael Carazo 
Published: February 2021

ABSTRACTLive imaging can provide powerful insights into developmental and cellular processes but availability of multiplexable reporters has been limiting. Here we describe ORACLE, a cell fate reporter class in which fluorescent proteins fused with the nucleoporin POM121 are driven by promoters of transcription factors of interest. ORACLE’s nuclear rim localisation therefore enables multiplexing with conventional nuclear reporters. We applied ORACLE to investigate the dynamics of pluripotency exit at single-cell level, using human pluripotent stem cells (hPSCs) imaged by multi-day time-lapse high-content microscopy. Using an ORACLE-OCT4 pluripotency marker we reveal that G1 phase length and OCT4 level are strongly coupled and that spatial location in a colony impacts the timing of pluripotency exit. Combining ORACLE-OCT4 and an ORACLE-SOX1 early neuronal differentiation marker, we visualize in real-time the dynamics of cell fate transition between pluripotency and early neural fate, and show that pluripotency exit and differentiation onset are likely not tightly coupled in single-cells. Thus ORACLE is a powerful tool to enable quantitative studies of spatiotemporal cell fate control.
Membrane barrels are taller, fatter, inside-out soluble barrels
Authors: Dhar Rik , Feehan Ryan , Slusky Joanna S.G. 
Published: February 2021

AbstractUp-and-down β-barrel topology exists in both the membrane and soluble environment. However, β-barrels are virtually the only topology that exist in the outer membrane. By comparing features of these structurally similar proteins, we can determine what features are particular to the environment rather than the fold. Here we compare structures of membrane β-barrels to soluble β-barrels and evaluate their relative size, shape, amino acid composition, hydrophobicity, and periodicity. We find that membrane β-barrels are generally larger than soluble β-barrels in with more strands per barrel and more amino acids per strand, making them wider and taller. We also find that membrane β-barrels are inside-out soluble β-barrels. The inward region of membrane β-barrels have similar hydrophobicity to the outward region of soluble β-barrels, and the outward region of membrane β-barrels has similar hydrophobicity to the inward region of the soluble β-barrels. Moreover, even though both types of β-barrel have been assumed to have strands with amino acids that alternate in direction and hydrophobicity, we find that the membrane β-barrels have more regular alternation than soluble β-barrels. These features give insight into how membrane barrels maintain their fold and function in the membrane.
Production of SARS-CoV-2 virus-like particles in insect cells
Authors: Mi Youjun , Xie Tao , Zhu Bingdong , Tan Jiying , Li Xuefeng , Luo Yanping , Li Fei , Niu HongXia , Han Jiangyuan , Lv Wei , Wang Juan 
Published: February 2021

ABSTRACTCoronavirus disease (COVID-19) causes a serious threat to human health. To production of SARS-COV-2 virus-like particles (VLPs) in insect cells for vaccine development and scientific research. The E, M and S genes were cloned into multiple cloning sites of the new triple expression plasmid with one p10 promoter, two pPH promoters and three multiple cloning sites. The plasmid was transformed into DH10 BacTMEscherichia colicompetent cells to obtain recombinant bacmid. Then the recombinant bacmid was transfected in ExpiSf9™ insect cells to generate recombinant baculovirus. After ExpiSf9™ infected with the recombinant baculovirus, the E, M, and S protein co-expressed in insect cells. Finally, SARS-CoV-2 VLPs were self-assembled in insect cells after infection. The morphology and the size of SARS-CoV-2 VLPs are similar to the native virions.
Hydrogen bonds meet self-attention: all you need for general-purpose protein structure embedding
Authors: Chen Cheng , Zha Yuguo , Zhu Daming , Ning Kang , Cui Xuefeng 
Published: February 2021

AbstractGeneral-purpose protein structure embedding can be used for many important protein biology tasks, such as protein design, drug design and binding affinity prediction. Recent researches have shown that attention-based encoder layers are more suitable to learn high-level features. Based on this key observation, we treat low-level representation learning and high-level representation learning separately, and propose a two-level general-purpose protein structure embedding neural network, called ContactLib-ATT. On the local embedding level, a simple yet meaningful hydrogen-bond representation is learned. On the global embedding level, attention-based encoder layers are employed for global representation learning. In our experiments, ContactLib-ATT achieves a SCOP superfamily classification accuracy of 82.4% (i.e., 6.7% higher than state-of-the-art method) on the SCOP40 2.07 dataset. Moreover, ContactLib-ATT is demonstrated to successfully simulate a structure-based search engine for remote homologous proteins, and our top-10 candidate list contains at least one remote homolog with a probability of 91.9%. Source codes:https://github.com/xfcui/contactlib.
A Facile and Rapid Route to Self-Digitization of Samples into a High Density Microwell Array for Digital Bioassays
Authors: Cui Xu , Hu Tianbao , Chen Qiang , Zhao Qiang , Wu Yin , Xie Tengbao , Liu Pengyong , Su Xi , Li Gang 
Published: February 2021

ABSTRACTDigital bioassays are powerful methods to detect rare analytes from complex mixtures and study the temporal processes of individual entities within biological systems. In digital bioassays, a crucial first step is the discretization of samples into a large number of identical independent partitions. Here, we developed a rapid and facile sample partitioning method for versatile digital bioassays. This method is based on a detachable self-digitization (DSD) chip which couples a reversible assembly configuration and a predegassing-based self-pumping mechanism to achieve an easy, fast and large-scale sample partitioning. The DSD chip consists of a channel layer used for loading sample and a microwell layer used for holding the sample partitions. Benefitting from its detachability, the chip avoids a lengthy oil flushing process used to remove the excess sample in loading channels and can compartmentalize a sample into more than 100,000 wells of picoliter volume with densities up to 14,000 wells/cm2in less than 30 s. We also demonstrated the utility of the proposed method by applying it to digital PCR and digital microbial assays.