bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sputnik Light booster after Sputnik V vaccination induces robust neutralizing antibody response to B.1.1.529 (Omicron) SARS-CoV-2 variant
Authors: Dolzhikova IV , Iliukhina AA , Kovyrshina AV , Kuzina AV , Gushchin VA , Siniavin AE , Pochtovyi AA , Shidlovskaya EV , Kuznetsova NA , Megeryan MM , Dzharullaeva AS , Erokhova AS , Izhaeva FM , Grousova DM , Botikov AG , Shcheblyakov DV , Tukhvatulin AI , Zubkova OV , Logunov DY , Gintsburg AL 
Published: December 2021

AbstractCOVID-19 vaccination campaign has been launched around the world. More than 8 billion vaccines doses have been administered, according to the WHO. Published studies shows that vaccination reduces the number of COVID-19 cases and dramatically reduces COVID-19-associated hospitalizations and deaths worldwide. In turn, the emergence of SARS-CoV-2 variants of concern (VOC) with mutations in the receptor-binding domain (RBD) of S glycoprotein poses risks of diminishing the effectiveness of the vaccination campaign. In November 2021, the first information appeared about a new variant of the SARS-CoV-2 virus, which was named Omicron. The Omicron variant is of concern because it contains a large number of mutations, especially in the S glycoprotein (16 mutation in RBD), which could be associated with resistance to neutralizing antibodies (NtAB) and significantly reduce the effectiveness of COVID-19 vaccines. Neutralizing antibodies are one of the important parameters characterizing the protective properties of a vaccine. We conducted a study of neutralizing antibodies in the blood serum of people vaccinated with Sputnik V, as well as those revaccinated with Sputnik Light after Sputnik V. Results showed that a decrease in the level of neutralizing antibodies was observed against SARS-CoV-2 Omicron (B.1.1.529) variant in comparison to B.1.1.1 variant. Analysis of the sera of individuals vaccinated with Sputnik V 6-12 months ago showed that there was a decrease in the level of neutralizing antibodies by 11.76 folds. While no direct comparison with other vaccines declines has been done in this study, we note their reported decline in antibody neutralization at a much more significant level of 40-84 times. At the same time, the analysis of sera of individuals who were vaccinated with Sputnik V, and then revaccinated Sputnik Light, showed that 2-3 months after revaccination the decrease in the level of neutralizing antibodies against the Omicron variant was 7.13 folds. Despite the decrease in NtAb, we showed that all revaccinated individuals had NtAb to Omicron variant. Moreover, the NtAb level to Omicron variant in revaccinated sera are slightly higher than NtAb to B.1.1.1 in vaccinated sera.
Conformational rearrangements upon start codon recognition in human 48S translation initiation complex
Authors: Yi Sung-Hui , Petrychenko Valentyn , Schliep Jan Erik , Goyal Akanksha , Linden Andreas , Chari Ashwin , Urlaub Henning , Stark Holger , Rodnina Marina , Adio Sarah , Fischer Niels 
Published: December 2021

AbstractSelection of the translation start codon is a key step during protein synthesis in human cells. We obtained cryo-EM structures of human 48S initiation complexes and characterized the intermediates of codon recognition by kinetic methods using eIF1A as a reporter. Both approaches capture two distinct ribosome populations formed on an mRNA with a cognate AUG codon in the presence of eIF1, eIF1A, eIF2–GTP–Met-tRNAiMet, and eIF3. The ‘open’ 40S subunit conformation differs from the human 48S scanning complex and represents an intermediate preceding the codon recognition step. The ‘closed’ form is similar to reported structures of complexes from yeast and mammals formed upon codon recognition, except for the orientation of eIF1A, which is unique in our structure. Kinetic experiments show how various initiation factors mediate the population distribution of open and closed conformations until 60S subunit docking. Our results provide insights into the timing and structure of human translation initiation intermediates and suggest the differences in the mechanisms of start codon selection between mammals and yeast.
ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection
Authors: Ching Krystal L. , de Vries Maren , Gago Juan , Dancel-Manning Kristen , Sall Joseph , Rice William J. , Barnett Clea , Liang Feng-Xia , Thorpe Lorna E. , Shopsin Bo , Segal Leopoldo N. , Dittmann Meike , Torres Victor J. , Cadwell Ken 
Published: December 2021

ABSTRACTExtracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchioalveolar lavage fluid from critically ill COVID-19 patients was associated with reduced ICU and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection.
Comparative effectiveness of the BNT162b2 vs ChAdOx1 vaccine against Covid-19
Authors: xie Junqing , Feng Shuo , Li Xintong , Gea-Mallorquí Ester , Prats-Uribe Albert , Prieto-Alhambra Dani 
Published: December 2021

AbstractAlthough pivotal trials with varying populations and study methods suggest higher efficacy for mRNA than adenoviral Covid-19 vaccines, no direct evidence is available. Here, we conducted a head-to-head comparison of BNT162b2 versus ChAdOx1 against Covid-19. We analysed 235,181 UK Biobank participants aged 50 years or older and vaccinated with one or two doses of BNT162b2 or ChAdOx1. People were followed from the vaccination date until 18/10/2021. Inverse probability weighting was used to minimise confounding and the Cox models to derive hazard ratio. We found that, compared with two doses of ChAdOx1, vaccination with BNT162b2 was associated with 30% lower risks of both SARS-CoV-2 infection and related hospitalisation during the period dominated by the delta variant. Also, this comparative effectiveness was consistent across several subgroups and persisted for at least six months, suggesting no differential waning between the two vaccines. Our findings can inform evidence-based Covid-19 vaccination campaigns and booster strategies.
Temporal associations of B and T cell immunity with robust vaccine responsiveness in a 16-week interval BNT162b2 regimen
Authors: Nayrac Manon , Dubé Mathieu , Sannier Gérémy , Nicolas Alexandre , Marchitto Lorie , Tastet Olivier , Tauzin Alexandra , Brassard Nathalie , Beaudoin-Bussières Guillaume , Vézina Dani , Gong Shang Yu , Benlarbi Mehdi , Gasser Romain , Laumaea Annemarie , Bourassa Catherine , Gendron-Lepage Gabrielle , Medjahed Halima , Goyette Guillaume , Ortega-Delgado Gloria-Gabrielle , Laporte Mélanie , Niessl Julia , Gokool Laurie , Morrisseau Chantal , Arlotto Pascale , Richard Jonathan , Tremblay Cécile , Martel-Laferrière Valérie , Finzi Andrés , Kaufmann Daniel E. 
Published: December 2021

SUMMARYSpacing of the BNT162b2 mRNA doses beyond 3 weeks raised concerns about vaccine efficacy. We longitudinally analyzed B cell, T cell and humoral responses to two BNT162b2 mRNA doses administered 16 weeks apart in 53 SARS-CoV-2 naïve and previously-infected donors. This regimen elicited robust RBD-specific B cell responses whose kinetics differed between cohorts, the second dose leading to increased magnitude in naïve participants only. While boosting did not increase magnitude of CD4+ T cell responses further compared to the first dose, unsupervised clustering analyses of single-cell features revealed phenotypic and functional shifts over time and between cohorts. Integrated analysis showed longitudinal immune component-specific associations, with early Thelper responses post-first dose correlating with B cell responses after the second dose, and memory Thelper generated between doses correlating with CD8 T cell responses after boosting. Therefore, boosting elicits a robust cellular recall response after the 16-week interval, indicating functional immune memory.
Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa
Authors: Viana Raquel , Moyo Sikhulile , Amoako Daniel G , Tegally Houriiyah , Scheepers Cathrine , Althaus Christian L , Anyaneji Ugochukwu J , Bester Phillip A , Boni Maciej F , Chand Mohammed , Choga Wonderful T , Colquhoun Rachel , Davids Michaela , Deforche Koen , Doolabh Deelan , Engelbrecht Susan , Everatt Josie , Giandhari Jennifer , Giovanetti Marta , Hardie Diana , Hill Verity , Hsiao Nei-Yuan , Iranzadeh Arash , Ismail Arshad , Joseph Charity , Joseph Rageema , Koopile Legodile , Pond Sergei L Kosakovsky , Kraemer Moritz UG , Kuate-Lere Lesego , Laguda-Akingba Oluwakemi , Lesetedi-Mafoko Onalethatha , Lessells Richard J , Lockman Shahin , Lucaci Alexander G , Maharaj Arisha , Mahlangu Boitshoko , Maponga Tongai , Mahlakwane Kamela , Makatini Zinhle , Marais Gert , Maruapula Dorcas , Masupu Kereng , Matshaba Mogomotsi , Mayaphi Simnikiwe , Mbhele Nokuzola , Mbulawa Mpaphi B , Mendes Adriano , Mlisana Koleka , Mnguni Anele , Mohale Thabo , Moir Monika , Moruisi Kgomotso , Mosepele Mosepele , Motsatsi Gerald , Motswaledi Modisa S , Mphoyakgosi Thongbotho , Msomi Nokukhanya , Mwangi Peter N , Naidoo Yeshnee , Ntuli Noxolo , Nyaga Martin , Olubayo Lucier , Pillay Sureshnee , Radibe Botshelo , Ramphal Yajna , Ramphal Upasana , San James E , Scott Lesley , Shapiro Roger , Singh Lavanya , Smith-Lawrence Pamela , Stevens Wendy , Strydom Amy , Subramoney Kathleen , Tebeila Naume , Tshiabuila Derek , Tsui Joseph , van Wyk Stephanie , Weaver Steven , Wibmer Constantinos K , Wilkinson Eduan , Wolter Nicole , Zarebski Alexander E , Zuze Boitumelo , Goedhals Dominique , Preiser Wolfgang , Treurnicht Florette , Venter Marietje , Williamson Carolyn , Pybus Oliver G , Bhiman Jinal , Glass Allison , Martin Darren P , Rambaut Andrew , Gaseitsiwe Simani , von Gottberg Anne , de Oliveira Tulio 
Published: December 2021

SummaryThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively1–3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.
Bounding the levels of transmissibility & immune evasion of the Omicron variant in South Africa
Authors: Pearson Carl A. B. , Silal Sheetal P. , Li Michael W.Z. , Dushoff Jonathan , Bolker Benjamin M. , Abbott Sam , van Schalkwyk Cari , Davies Nicholas G. , Barnard Rosanna C. , Edmunds W. John , Bingham Jeremy , Meyer-Rath Gesine , Jamieson Lise , Glass Allison , Wolter Nicole , Govender Nevashan , Stevens Wendy S. , Scott Lesley , Mlisana Koleka , Moultrie Harry , Pulliam Juliet R. C. 
Published: December 2021

AbstractA new SARS-CoV-2 variant of concern, Omicron (B.1.1.529), has been identified based on genomic sequencing and epidemiological data in South Africa. Presumptive Omicron cases in South Africa have grown extremely rapidly, despite high prior exposure and moderate vaccination coverage. The available evidence suggests that Omicron spread is at least in part due to evasion of this immune protection, though Omicron may also exhibit higher intrinsic transmissibility. Using detailed laboratory and epidemiological data from South Africa, we estimate the constraints on these two characteristics of the new variant and their relationship. Our estimates and associated uncertainties provide essential information to inform projection and scenario modeling analyses, which are crucial planning tools for governments around the world.One Sentence SummaryWe report a region of plausibility for the relative transmissibility and immune escape characteristics of the SARS-CoV-2 Omicron variant estimated by integrating laboratory and epidemiological data from South Africa.
Government messaging about COVID-19 vaccination in Canada and Australia: a Narrative Policy Framework study
Authors: Saich Freya , Martiniuk Alexandra 
Published: December 2021

AbstractBackgroundStorytelling and narratives are critical components to public policy and have been central to public policy communicators throughout the COVID-19 pandemic.AimThis study applied the Narrative Policy Framework to compare and contrast the policy narratives of the Canadian and Australian Prime Ministers regarding COVID-19 vaccination.MethodsOfficial media releases, transcripts and speeches published on the websites of Prime Minister Morrison and Prime Minister Trudeau between 31 August 2020 and 10 September 2021 relating to COVID-19 vaccines were thematically analysed according to the Narrative Policy Framework.ResultsThe policy narratives of Scott Morrison and Justin Trudeau tended towards describing both governments as heroes for securing and rolling out vaccines. Trudeau tended to focus on the villain of COVID-19 while Morrison regularly described other countries as victims of COVID-19 to position Australia as superior in its decision-making. These findings also demonstrate how narratives shifted over time due to changing COVID-19 case numbers, emergence of rare complications associated with the AstraZeneca vaccine and as new information arose.ConclusionThese findings offer lessons for COVID-19 times as well as future pandemics and disease outbreaks by providing insight into how policy narratives influenced policy processes in both Australia and Canada.
Deep Learning Auto-Segmentation of Cervical Neck Skeletal Muscle for Sarcopenia Analysis Using Pre-Therapy CT in Patients with Head and Neck Cancer
Authors: Naser Mohamed A. , Wahid Kareem A. , Grossberg Aaron J. , Olson Brennan , Jain Rishab , El-Habashy Dina , Dede Cem , Salama Vivian , Abobakr Moamen , Mohamed Abdallah S.R. , He Renjie , Jaskari Joel , Sahlsten Jaakko , Kaski Kimmo , Fuller Clifton D. 
Published: December 2021

ABSTRACTBackground/PurposeSarcopenia is a prognostic factor in patients with head and neck cancer (HNC). Sarcopenia can be determined using the skeletal muscle index (SMI) calculated from cervical neck SM segmentations. However, SM segmentation requires manual input, which is time-consuming and variable. Therefore, we developed a fully-automated approach to segment cervical vertebra SM.Materials/Methods390 HNC patients with corresponding contrast-enhanced computed tomography (CT) scans were utilized (300-training, 90-testing). Ground-truth single-slice SM segmentations at the C3 vertebra were manually generated. A multi-stage deep learning pipeline was developed, where a 3D ResUNet auto-segmented the C3 section (33 mm window), the middle slice of the section was auto-selected, and a 2D ResUNet auto-segmented the auto-selected slice. Both the 3D and 2D approaches trained five sub-models (5-fold cross-validation) and combined sub-model predictions on the test set using majority vote ensembling. Model performance was primarily determined using the Dice similarity coefficient (DSC). Predicted SMI was calculated using the auto-segmentation cross-sectional area. Finally, using established SMI cutoffs, we performed a Kaplan-Meier analysis to determine associations with overall survival.ResultsMean test set DSC of the 3D and 2D models were 0.96 and 0.95, respectively. Predicted SMI had high correlation to the ground-truth SMI in males and females (r>0.96). Predicted SMI stratified patients for overall survival in males (log-rank p = 0.01) but not females (log-rank p = 0.07), consistent with ground-truth SMI.ConclusionWe developed a high-performance, multi-stage, fully-automated approach to segment cervical vertebra SM. Our study is an essential step towards fully-automated sarcopenia-related decision-making.
A two-sex model of human papillomavirus infection: Vaccination strategies and a case study
Authors: Gao Shasha , Martcheva Maia , Miao Hongyu , Rong Libin 
Published: December 2021

AbstractVaccination is effective in preventing human papillomavirus (HPV) infection. It still remains debatable whether males should be included in a vaccination program and unclear how to allocate the vaccine in genders to achieve the maximum benefits. In this paper, we use a two-sex model to assess HPV vaccination strategies and use the data from Guangxi Province in China as a case study. Both mathematical analysis and numerical simulations show that the basic reproduction number, an important indicator of the transmission potential of the infection, achieves its minimum when the priority of vaccination is given to the gender with a smaller recruit rate. Given a fixed amount of vaccine, splitting the vaccine evenly usually leads to a larger basic reproduction number and a higher prevalence of infection. Vaccination becomes less effective in reducing the infection once the vaccine amount exceeds the smaller recruit rate of the two genders. In the case study, we estimate the basic reproduction number is 1.0333 for HPV 16/18 in people aged 15-55. The minimal bivalent HPV vaccine needed for the disease prevalence to be below 0.05% is 24050 per year, which should be given to females. However, with this vaccination strategy it would require a very long time and a large amount of vaccine to achieve the goal. In contrast with allocating the same vaccine amount every year, we find that a variable vaccination strategy with more vaccine given in the beginning followed by less vaccine in later years can save time and total vaccine amount. The variable vaccination strategy illustrated in this study can help to better distribute the vaccine to reduce the HPV prevalence. Although this work is for HPV infection and the case study is for a province in China, the model, analysis and conclusions may be applicable to other sexually transmitted diseases in other regions or countries.
Genome-Wide Analysis of Horizontal Transfer in Non-Model Wild Species from a Natural Ecosystem Reveals New Insights into Genetic Exchange in Plants
Authors: Aubin Emilie , Llauro Christel , Garrigue Joseph , Mirouze Marie , Panaud Olivier , El Baidouri Moaine 
Published: December 2021

AbstractBackgroundHorizontal transfer (HT) refers to the exchange of genetic material between divergent species by mechanisms other than reproduction. In recent years, several studies have demonstrated HTs in eukaryotes, particularly in the context of parasitic relationships and in model species. However, very little is known about HT in natural ecosystems, especially those involving non-parasitic wild species, and the nature of the ecological relationships that promote these HTs.ResultsIn this work, we conducted a pilot study investigating HTs by sequencing the genomes of 17 wild non-model species from a natural ecosystem, the Massane forest, located in southern France. To this end, we developed a new computational pipeline called INTERCHANGE that is able to characterize HTs at the whole genome level without prior annotation and directly in the raw sequencing reads. Using this pipeline, we identified 12 HT events, half of which occurred between lianas and trees. We found that mainly low copy number LTRs retrotransposons from the Copia superfamily were transferred between these wild plant species, especially those of the Ivan and Ale lineages.ConclusionThis study revealed a possible new route for HTs between non-parasitic plants and provides new insights into the genomic characteristics of horizontally transferred DNA in plant genomes.
Human embryos arrest in a quiescent-like state characterized by metabolic and zygotic genome activation problems
Authors: Yang Yang , Shi Liyang , Fu Xiuling , Ma Gang , Yang Zhongzhou , Li Yuhao , Zhou Yibin , Yuan Lihua , Xia Ye , Zhong Xiufang , Yin Ping , Sun Li , Wuwen Zhang , Babarinde Isaac A. , Wang Yongjun , Zhao Xiaoyang , Hutchins Andrew P. , Tong Guoqing 
Published: December 2021

AbstractAround 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3-8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a quiescent-like state, marked by cell cycle arrest, the downregulation of ribosomes and histones and downregulation of MYC and p53 activity. Mechanistically, the arrested embryos can be divided into three types. Type I embryos fail to complete the maternal-zygotic transition, and type II/III embryos have erroneously low levels of glycolysis and variable levels of oxidative phosphorylation. Treatment with resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype. The mechanism of reactivation involves the upregulation of SIRT1, and activation of glycolysis and fatty acid oxidation which forces the embryos out of a quiescent state. Overall, our data reveal how human embryo arrest can be overcome by modulating metabolic pathways.