bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the dynamics of SARS-CoV-2 immunity waning, antigenic drifting, and population serology patterns
Authors: Koopman James S. , Simon Carl P. 
Published: September 2020

AbstractReinfection with SARS-CoV-2 can result from either waning immunity, a drift in the virus that escapes previously stimulated immunity, or both. The nature of such reinfection risks will affect the choice of control tactics and vaccines. We constructed an SIR transmission model of waning and drifting that can be fitted to cross-neutralization serological data. In this model, waning occurs in individuals who have recovered from previous infections while drifting occurs during transmission to a previously infected individual. Interactions at the population level generate complex dynamics that cause drifting to occur in unanticipated but explainable ways across waning and drifting parameter sets. In particular, raising the fraction of transmissions where drifting occurs slows the rise of drifted strains to high levels and changes the equilibrium distribution of strains from ∪ shaped (extreme strains dominate) to ∩ shaped (central strains dominate). In ∪ shaped parameter regimes, endemic infection levels can rise after many years to above the original epidemic peak. The model simulates results from cross-neutralization assays given sera from previously infected individuals when multiple drifted strains are used in the assays. Fitting the model to such assay data can estimate waning and drifting parameters. Given the parameters, the model predicts infection patterns. We propose a process for using fits of our model to serological and other data called Decision Robustness and Identifiability Analysis (DRIA). This can inform decisions about vaccine options such as whether to prepare for changes in vaccine composition because the virus is changing to escape immunity.HighlightsWe construct and analyze a transmission system model that integrates immunity waning and antigenic drifting. We found no other model that integrates both.The model reveals strong joint effects of waning and drifting. For example, waning is essential for drifting. But once drifting starts, it generates its own momentum.The model generates unexpected but explainable phenomena such as: A) Given low drifting parameters, strains become increasingly different from each other, but given high drifting parameters, they merge together. B) Higher drifting rates accelerate the appearance of new strains but slow the expansion of those new strains.The model generates assay data for neutralization across drifted strains. This enables population serological analyses to estimate waning and drifting parameters.Predicting drifting through population serology analyzed by fitting models to the data has potential to better inform vaccine strain choices than the approach taken for influenza which focuses on analysis of large numbers of virus strains over time.Model elaboration using a strategy of Decision Robustness and Identifiability Analysis will inform decisions about vaccine design and use and provides insights on resistance to infection by age.
Evaluating ten commercially-available SARS-CoV-2 rapid serological tests using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) method
Authors: Dortet Laurent , Ronat Jean-Baptiste , Vauloup-Fellous Christelle , Langendorf Céline , Mendels David-Alexis , Emeraud Cécile , Oueslati Saoussen , Girlich Delphine , Chauvin Anthony , Afdjei Ali , Bernabeu Sandrine , Pape Samuel le , Kallala Rim , Rochard Alice , Verstuyft Celine , Fortineau Nicolas , Roque-Afonso Anne-Marie , Naas Thierry 
Published: September 2020

ABSTRACTNumerous SARS-CoV-2 rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially-available SARS-CoV2 rapid serological tests using the STARD methodology (Standards for Reporting of Diagnostic Accuracy Studies). 250 sera from 159 PCR-confirmed SARS-CoV-2 patients (collected from 0 to 32 days after onset of symptoms) were tested with rapid serological tests. Control sera (N=254) were retrieved from pre-COVID periods from patients with other coronavirus infections (N=11), positive rheumatoid factors (N=3), IgG/IgM hyperglobulinemia (N=9), malaria (n=5), or no documented viral infection (N=226). All samples were tested using rapid lateral flow immunoassays (LFIA) from ten manufacturers. Only four tests achieved ≥98% specificity, with other tests ranging from 75.7%-99.2%. Sensitivities varied by the day of sample collection, from 31.7%-55.4% (Days 0-9), 65.9%92.9% (Days 10-14), and 81.0%-95.2% (>14 days) after the onset of symptoms, respectively. Only three tests evaluated met French Health Authorities’ thresholds for SARS-CoV-2 serological tests (≥90% sensitivity + ≥98% specificity). Overall, the performances between tests varied greatly, with only a third meeting acceptable specificity and sensitivity thresholds. Knowing the analytical performance of these tests will allow clinicians to use them with more confidence, could help determine the general population’s immunological status, and may diagnose some patients with false-negative RT-PCR results.
Lessons from the COVID-19 pandemic: People’s experiences and satisfaction with telehealth during the COVID-19 pandemic in Australia
Authors: Isautier JMJ , Copp T , Ayre J , Cvejic E , Meyerowitz-Katz G , Batcup C , Bonner C , Dodd RH , Nickel B , Pickles K , Cornell S , Dakin T , McCaffery K 
Published: September 2020

AbstractObjectivesTo determine how participants perceived telehealth consults in comparison to traditional in-person visits, and to investigate whether people believe that telehealth services would be useful beyond the pandemic.DesignA national cross-sectional community survey.ParticipantsAustralian adults aged 18 years and over (n=1369).Main outcome measuresTelehealth experiences.ResultsOf the 596 telehealth users, the majority of respondents (62%) rated their telehealth experience as “just as good” or “better” than a traditional in-person medical appointment. On average, respondents perceived that telehealth would be moderately to very useful for medical appointments after the COVID-19 pandemic is over (M=3.67 out of 5, SD=1.1). Being male (p=0.007), having a history of both depression and anxiety (p=0.037), or lower patient activation (individuals’ willingness to take on the role of managing their health/healthcare) (p=0.037) were associated with a poorer telehealth experience. Six overarching themes were identified from free-text responses of why telehealth experience was poorer than a traditional in-person medical appointment: communication is not as effective; limitations with technology; issues with obtaining prescriptions and pathology; reduced confidence in doctor; additional burden for complex care; and inability to be physically examined.ConclusionsTelehealth appointments were reported to be comparable to traditional in-person medical appointments by most of our sample. Telehealth should continue to be offered as a mode of healthcare delivery while the pandemic continues and may be worthwhile beyond the pandemic.The knownThe COVID-19 pandemic has resulted in an increase in telehealth services.The newThe majority of telehealth users (62%) perceived their experience to be just as good or better than traditional in-person medical care; and that telehealth would be at least somewhat useful beyond the pandemic.Having a history of both depression and anxiety was associated with a poorer telehealth experience and in-person visits were frequently preferred over telehealth visits for mental health appointments.The implicationTelehealth should continue to be offered while the COVID-19 pandemic continues and may be worthwhile beyond the pandemic, however, telehealth may be less effective for mental health services.
SARS-CoV-2 NSP1 C-terminal region (residues 130-180) is an intrinsically disordered region
Authors: Kumar Amit , Kumar Ankur , Kumar Prateek , Garg Neha , Giri Rajanish 
Published: September 2020

AbstractNonstructural protein 1 (NSP1) of SARS-CoV-2 plays a key role in downregulation of RIG-I pathways and interacts with 40 S ribosome. Recently, the cryo-EM structure in complex with 40S ribosome is deciphered. However, the structure of full length NSP1 without any partner has not been studies. Also, the conformation of NSP1-C terminal region in isolation is not been studied. In this study, we have investigated the conformational dynamics of NSP1C-terminal region (NSP1-CTR; amino acids 130-180) in isolation and under different solvent environments. The NSP1-CTR is found to be intrinsically disordered in aqueous solution. Further, we used alpha helix inducer, trifluoroethanol, and found induction of alpha helical conformation using CD spectroscopy. Additionally, in the presence of SDS, NSP1-CTR is showing a conformational change from disordered to ordered, possibly gaining alpha helix in part. But in presence of neutral lipid DOPC, a slight change in conformation is observed. This implies the possible role of hydrophobic interaction and electrostatic interaction on the conformational changes of NSP1. The changes in structural conformation were further studied by fluorescence-based studies, which showed significant blue shift and fluorescence quenching in the presence of SDS and TFE. Lipid vesicles also showed fluorescence-based quenching. In agreement to these result, fluorescence lifetime and fluorescence anisotropy decay suggests a change in conformational dynamics. The zeta potential studies further validated that the conformational dynamics is mostly because of hydrophobic interaction. In last, these experimental studies were complemented through Molecular Dynamics (MD) simulation which have also shown a good correlation and testify our experiments. We believe that the intrinsically disordered nature of the NSP1-CTR will have implications in disorder based binding promiscuity with its interacting proteins.
Proteomics of autophagy deficient macrophages reveals enhanced antimicrobial immunity via the oxidative stress response
Authors: Maculins Timurs , Verschueren Erik , Hinkle Trent , Chang Patrick , Chalouni Cecile , Lim Junghyun , Katakam Anand Kumar , Kunz Ryan C. , Erickson Brian K. , Huang Ting , Choi Meena , Tsai Tsung-Heng , Vitek Olga , Reichelt Mike , Rohde John , Dikic Ivan , Kirkpatrick Donald S. , Murthy Aditya 
Published: September 2020

AbstractDefective autophagy is associated with chronic inflammation. Loss-of-function of the core autophagy gene Atg16l1 increases risk for Crohn’s disease by enhancing innate immunity in macrophages. However, autophagy also mediates clearance of intracellular pathogens. These divergent observations prompted a re-evaluation of ATG16L1 in antimicrobial immunity. In this study, we found that loss of Atg16l1 in macrophages enhanced the killing of virulentShigella flexneri(S.flexneri), an enteric bacterium that resides within the cytosol by escaping all membrane-bound compartments. Quantitative multiplexed proteomics revealed that ATG16L1 deficiency significantly upregulated proteins involved in the glutathione-mediated antioxidant response to compensate for elevated oxidative stress, which also promotedS.flexnerikilling. Consistently, myeloid cell-specific deletion of Atg16l1 accelerated bacterial clearancein vivo. Finally, pharmacological modulation of oxidative stress by suppression of cysteine import conferred enhanced microbicidal properties to wild type macrophages. These findings demonstrate that control of oxidative stress by ATG16L1 regulates antimicrobial immunity against intracellular pathogens.Impact statementMaculinset alutilize multiplexed mass spectrometry to show that loss of the autophagy geneAtg16l1in macrophages enhances antimicrobial immunity against intracellular pathogens via the oxidative stress response.
The impact of the Covid-19 pandemic on emergency and elective hip surgeries in Norway
Authors: Magnusson Karin , Helgeland Jon , Grøsland Mari , Telle Kjetil 
Published: September 2020

AbstractObjectiveTo assess the effects of Covid-19 pandemic lockdown restrictions on the number of emergency and elective hip joint surgeries, and explore whether these procedures are more/less affected by lockdown restrictions than other hospital care.MethodsIn 1.344.355 persons aged ≥35 years in the Norwegian emergency preparedness (BEREDT C19) register, we studied the daily number of persons having 1) emergency surgeries due to hip fractures, and 2) electively planned surgeries due to hip osteoarthritis before and after Covid-19 lockdown restrictions were implemented nationally on March 13th 2020, for different age and sex groups. Incidence Rate Ratios [IRR] reflect the after-lockdown number of surgeries divided by the before-lockdown number of surgeries.ResultsAfter-lockdown elective hip surgeries were one third the number of before-lockdown (IRR ∼0.3), which is a greater drop than the drop seen in all-cause elective hospital care (IRR ∼0.6) (no age/sex differences). Men aged 35-69 had half the number of emergency hip fracture surgeries (IRR ∼0.6), whereas women aged ≥70 had the same number of emergency hip fracture surgeries after lockdown (IRR ∼1). Only women aged 35–69 and men aged ≥70 had emergency hip fracture surgery rates after lockdown comparable to what may be expected based on analyses of all-cause acute care (IRR ∼0.80)ConclusionImportant to note for future pandemics management is that lockdown restrictions may impact more on scheduled joint surgery than other scheduled hospital care. Lockdown may also impact on the number of emergency joint surgeries for men aged ≥35 but not for women aged ≥70.
Increased extravascular lung water index (EVLWI) reflects rapid inflammatory oedema and mortality in COVID-19 associated ARDS
Authors: Rasch Sebastian , Schmidle Paul , Sancak Sengül , Herner Alexander , Huberle Christina , Schulz Dominik , Mayr Ulrich , Schneider Jochen , Spinner Christoph , Geisler Fabian , Schmid Roland M. , Lahmer Tobias , Huber Wolfgang 
Published: September 2020

AbstractOBJECTIVENearly 5 % of the patients with COVID-19 develop an acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to controls and whether EVLWI has the potential to monitor disease progression.METHODSFrom the day of intubation, EVLWI, cardiac function were monitored by transpulmonary thermodilution in n=25 patients with COVID-19 and compared to a control group of 49 non-COVID-19 ARDS-patients.RESULTSEVLWI in COVID-19-patients was noticeably elevated and significantly higher than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p<0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p=0.003) suggest inflammatory oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and mortality (23.2±6.7% vs. 30.3±6.0%, p=0.025).CONCLUSIONSCompared to the control group, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 associated ARDS and could serve as parameter to monitor ARDS progression.
Socio-demographic correlate of knowledge and practice toward novel coronavirus among people living in Mosul-Iraq: A cross-sectional study
Authors: Qubais Saeed Balsam , Al-Shahrabi Rula , Bolarinwa Obasanjo Afolabi 
Published: September 2020

ABSTRACTBackgroundSince the World Health Organization (WHO) announced that the 2019 novel coronavirus (2019-nCoV) is a worldwide pandemic, as the Iraqi authorities have started responding and taking action to control the spread of the pandemic. The knowledge and practices of the public play an important role in curbing the spreading of the virus by following the health guidelines. This study aimed to assess the socio-demographic correlate of knowledge and practices of Iraqi living in Mosul-Iraq towards novel coronavirus during its rapid rise.MethodsA cross-sectional online survey of 909 participants was conducted among Mosul-Iraq between 20th June to 1st July 2020. The survey included three parts: 1) socio-demographic characteristics, 2) participants' knowledge, 3) participants' practices. T-test, ANOVA, chi-square, and binary logistic regression were used. A p-value less than 0.05 (p < 0.05) was considered statistically significant.ResultsThe results showed knowledge and practice mean score of (12.91±1.67) and (21.56± 2.92) with cumulative knowledge and practice of 86% and 76% respectively towards 2019-nCoV. Socio-demographic characteristics such as age, marital status, gender, level of education and employment were statistically related with a higher mean score of knowledge and practice towards the virus as P<0.05.ConclusionsWe concluded that the majority of the respondents demonstrate a high level of knowledge and practices towards 2019-nCoV except respondents with socio-demographic characteristics such as those who were younger, male respondents, those with lower education and those unemployed as such campaigns that will increase the knowledge and encourage adequate preventive practice towards 2019-nCoV should be targeted towards this group.
Asymmetric evolvability leads to specialization without trade-offs
Authors: Draghi Jeremy A. 
Published: September 2020

AbstractMany ideas about the evolution of specialization rely on trade-offs—an inability for one organism to express maximal performance in two or more environments. However, optimal foraging theory suggests that populations can evolve specialization on a superior resource without explicit trade-offs. Classical results in population genetics show that the process of adaptation can be biased toward further improvement in already productive environments, potentially widening the gap between superior and inferior resources. Here I synthesize these approaches with new insights on evolvability at low recombination rates, showing that emergent asymmetries in evolvability can push a population toward specialization in the absence of trade-offs. Simulations are used to demonstrate how adaptation to a more common environment interferes with adaptation to a less common but otherwise equal alternative environment. Shaped by recombination rates and other population-genetic parameters, this process results in either the retention of a generalist niche without trade-offs or entrapment at the local optimum of specialization on the common environment. These modeling results predict that transient differences in evolvability across traits during an episode of adaptation could have long-term consequences for a population’s niche.
Clostridioides difficilespore-entry into intestinal epithelial cells contributes to recurrence of the disease
Authors: Castro-Córdova Pablo , Mora-Uribe Paola , Reyes-Ramírez Rodrigo , Cofré-Araneda Glenda , Orozco-Aguilar Josué , Brito-Silva Christian , Mendoza-León María José , Kuehne Sarah A. , Minton Nigel P. , Pizarro-Guajardo Marjorie , Paredes-Sabja Daniel 
Published: September 2020

AbstractClostridioides difficilespores produced during infection are essential for the recurrence of the disease. However, howC. difficilespores persist in the intestinal mucosa to cause recurrent infection remains unknown. Here, we show thatC. difficilespores gain entry into the intestinal mucosa via fibronectin-α5β1and vitronectin-αvβ1specific-pathways. The spore-surface exosporium BclA3 protein is essential for both spore-entry pathways into intestinal epithelial cells. Furthermore,C. difficilespores of abclA3isogenic mutant exhibited reduced entry into the intestinal mucosa and reduced recurrence of the disease in a mouse model of the disease. Inhibition ofC. difficilespore-entry led to reduced spore-entry into the intestinal epithelial barrier and recurrence ofC. difficileinfectionin vivo. These findings suggest thatC. difficilespore-entry into the intestinal barrier is a novel mechanism of spore-persistence that can contribute to infection recurrence and have implications for the rational design of therapies.
A non-canonical EZH2 function sensitizes solid tumors to genotoxic stress
Authors: Liao Yiji , Chen Chen-Hao , Shah Neel , Xiao Tengfei , Feit Avery , Yang Mei , Cai Changmeng , Gao Shuai , Xue Pengya , Liu Zhijie , Xu Han , Lee Jihoon , Li Wei , Mei Shenglin , Pierre Roodolph S. , Shu Shaokun , Fei Teng , Duarte Melissa , Zhao Jin , Bradner James E. , Polyak Kornelia , Kantoff Philip W. , Long Henry , Balk Steven P. , Liu X. Shirley , Brown Myles , Xu Kexin 
Published: September 2020

SummaryDrugs that block the activity of the methyltransferase EZH2 are in clinical development for the treatment of non-Hodgkin lymphomas harboring gain-of-function EZH2 mutations that enhance its polycomb repressive function. In contrast, in castration-resistant prostate cancer (CRPC) we have previously reported that EZH2 plays a non-canonical role as a transcriptional activator. In this setting, we now show that EZH2 inhibitors can also block the non-canonical activity of EZH2 and inhibit the growth of CRPC cells. Gene expression and epigenomic profiling of cells treated with EZH2 inhibitors demonstrated that rather than de-repressing tumor suppressor genes silenced by PRC2, EZH2 inhibitors downregulate a set of DNA repair genes that are directly regulated by EZH2. In addition, genome-wide CRISPR/Cas9-mediated loss-of-function screens in the presence of EZH2 inhibitors identified these DNA repair genes to underlie the growth-inhibitory function of these compounds. Interrogation of public data from diverse solid tumor types expressing wild-type EZH2 showed that expression of DNA damage repair genes is significantly correlated with cellular sensitivity to EZH2 inhibitors. Consistent with these findings, treatment of CRPC cells with EZH2 inhibitors dramatically enhanced their sensitivity to genotoxic stress. These studies reveal a previously unappreciated mechanism of action of EZH2 inhibitors and provide a mechanistic basis for potential new combination cancer therapies.
Unique and distinct identities and functions of leaf phloem cells revealed by single cell transcriptomics
Authors: Kim Ji-Yun , Symeonidi Efthymia , Pang Tin Yau , Denyer Tom , Weidauer Diana , Bezrutczyk Margaret , Miras Manuel , Zöllner Nora , Wudick Michael M. , Lercher Martin , Chen Li-Qing , Timmermans Marja C.P , Frommer Wolf B. 
Published: September 2020

AbstractThe leaf vasculature plays a key role in solute translocation. Veins consist of at least seven distinct cell types, with specific roles in transport, metabolism, and signaling. Little is known about the vascular cells in leaves, in particular the phloem parenchyma (PP). PP effluxes sucrose into the apoplasm as a basis for phloem loading; yet PP has only been characterized microscopically. Here, we enriched vascular cells from Arabidopsis leaves to generate a single-cell transcriptome atlas of leaf vasculature. We identified ≥19 cell clusters, encompassing epidermis, guard cells, hydathodes, mesophyll, and all vascular cell types, and used metabolic pathway analysis to define their roles. Clusters comprising PP cells were enriched for transporters, includingSWEET11andSWEET12sucrose and UmamiT amino acid efflux carriers. PP development occurs independently from APL, a transcription factor required for phloem differentiation. PP cells have a unique pattern of amino acid metabolism activity distinct from companion cells (CC), explaining differential distribution/metabolism of amino acids in veins. The kinship relation of the vascular clusters is strikingly similar to the vein morphology, except for a clear separation of CC from the other vascular cells including PP. In summary, our scRNA-seq analysis provides a wide range of information into the leaf vasculature and the role and relationship of the leaf cell types.