bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval between doses
Authors: Tauzin Alexandra , Gong Shang Yu , Beaudoin-Bussières Guillaume , Vézina Dani , Gasser Romain , Nault Lauriane , Marchitto Lorie , Benlarbi Mehdi , Chatterjee Debashree , Nayrac Manon , Laumaea Annemarie , Prévost Jérémie , Boutin Marianne , Sannier Gérémy , Nicolas Alexandre , Bourassa Catherine , Gendron-Lepage Gabrielle , Medjahed Halima , Goyette Guillaume , Bo Yuxia , Perreault Josée , Gokool Laurie , Morrisseau Chantal , Arlotto Pascale , Bazin Renée , Dubé Mathieu , De Serres Gaston , Brousseau Nicholas , Richard Jonathan , Rovito Roberta , Côté Marceline , Tremblay Cécile , Marchetti Giulia C. , Duerr Ralf , Martel-Laferrière Valérie , Kaufmann Daniel E. , Finzi Andrés 
Published: September 2021

SUMMARYWhile the standard regimen of the BNT162b2 mRNA vaccine includes two doses administered three weeks apart, some public health authorities decided to space them, raising concerns about vaccine efficacy. Here, we analyzed longitudinal humoral responses including antibody binding, Fc-mediated effector functions and neutralizing activity against the D614G strain but also variants of concern and SARS-CoV-1 in a cohort of SARS-CoV-2 naïve and previously infected individuals, with an interval of sixteen weeks between the two doses. While the administration of a second dose to previously infected individuals did not significantly improve humoral responses, we observed a significant increase of humoral responses in naïve individuals after the 16-weeks delayed second shot, achieving similar levels as in previously infected individuals. We compared these responses to those elicited in individuals receiving a short (4-weeks) dose interval. For the naïve donors, these responses were superior to those elicited by the short dose interval.
Estimates of presumed population immunity to SARS-CoV-2 by state in the United States, August 2021
Authors: Stoner Marie C.D. , Angulo Frederick J. , Rhea Sarah , Brown Linda Morris , Atwell Jessica E. , Nguyen Jennifer L. , McLaughlin John , Swerdlow David L. , MacDonald Pia D.M. 
Published: September 2021

ABSTRACTBackgroundInformation is needed to monitor progress toward a level of population immunity to SARS-CoV-2 sufficient to disrupt viral transmission. We estimated the percentage of the United States (US) population with presumed immunity to SARS-CoV-2 due to vaccination, natural infection, or both as of August 26, 2021.MethodsPublicly available data as of August 26, 2021, from the Centers for Disease Control and Prevention (CDC) were used to calculate presumed population immunity by state. Seroprevalence data were used to estimate the percentage of the population previously infected with SARS-CoV-2, with adjustments for underreporting. Vaccination coverage data for both fully and partially vaccinated persons were used to calculate presumed immunity from vaccination. Finally, we estimated the percentage of the total population in each state with presumed immunity to SARS-CoV-2, with a sensitivity analysis to account for waning immunity, and compared these estimates to a range of population immunity thresholds.ResultsPresumed population immunity varied among states (43.1% to 70.6%), with 19 states with 60% or less of their population having been infected or vaccinated. Four states have presumed immunity greater than thresholds estimated to be sufficient to disrupt transmission of less infectious variants (67%), and none were greater than the threshold estimated for more infectious variants (78% or higher).ConclusionsThe US remains a distance below the threshold sufficient to disrupt viral transmission, with some states remarkably low. As more infectious variants emerge, it is critical that vaccination efforts intensify across all states and ages for which the vaccines are approved.SummaryAs of August 26, 2021, no state has reached a population level of immunity thought to be sufficient to disrupt transmission. (78% or higher), with some states having remarkably low presumed immunity.
Nitrogen partitioning between branched-chain amino acids and urea cycle enzymes sustains renal cancer progression
Authors: Sciacovelli Marco , Dugourd Aurelien , Jimenez Lorea Valcarcel , Yang Ming , Nikitopoulou Efterpi , Costa Ana S.H. , Tronci Laura , Caraffini Veronica , Rodrigues Paulo , Schmidt Christina , Ryan Dylan , Young Tim , Zecchini Vincent R. , Rossi Sabrina Helena , Massie Charlie , Lohoff Caroline , Barcon Maria Masid , Hatzimanikatis Vassily , Kuppe Christoph , Von Kriegsheim Alex , Kramann Rafael , Gnanapragasam Vincent , Warren Anne Y. , Stewart Grant D. , Erez Ayelet , Vanharanta Sakari , Saez-Rodriguez Julio , Frezza Christian 
Published: September 2021

SUMMARYMetabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression is poorly understood. Here, we combined multi-omics datasets of primary and metastatic clonally related clear cell renal cancer cells (ccRCC) and generated a computational tool to explore the metabolic landscape during cancer progression. We show that aVHLloss-dependent reprogramming of branched-chain amino acid catabolism is required to maintain the aspartate pool in cancer cells across all tumor stages. We also provide evidence that metastatic renal cancer cells reactivate argininosuccinate synthase (ASS1), a urea cycle enzyme suppressed in primary ccRCC, to enable invasionin vitroand metastasisin vivo. Overall, our study provides the first comprehensive elucidation of the molecular mechanisms responsible for metabolic flexibility in ccRCC, paving the way to the development of therapeutic strategies based on the specific metabolism that characterizes each tumor stage.HighlightsBranched-chain amino acids catabolism is reprogrammed in ccRCC tumorsBCAT-dependent transamination supplies nitrogen forde novobiosynthesis of amino acids including aspartate and asparagine in ccRCCAspartate produced downstream of BCAT is used specifically by metastatic cells through argininosuccinate synthase (ASS1) and argininosuccinate lyase (ASL) to generate arginine, providing a survival advantage in the presence of microenvironments with rate limiting levels of arginineASS1 is re-expressed in metastatic 786-M1A through epigenetic remodeling and it is sensitive to arginine levelsSilencing of ASS1 impairs the metastatic potentialin vitroandin vivoof ccRCC cells
Transformation of Primary Sensory Cortical Representations from Layer 4 to Layer 2
Authors: Voelcker Bettina , Peron Simon 
Published: September 2021

SUMMARYSensory input arrives from thalamus in cortical layer (L) 4, from which it flows predominantly to superficial layers, so that L4 to L2 constitutes one of the earliest cortical feedforward networks. Despite extensive study, the transformation performed by this network remains poorly understood. We use two-photon calcium imaging in L2-4 of primary vibrissal somatosensory cortex (vS1) to record neural activity as mice perform an object localization task with two whiskers. We find that touch responses sparsen but become more reliable from L4 to L2, with superficial neurons responding to a broader range of touches. Decoding of sensory features either improves from L4 to L2 or remains unchanged. Pairwise correlations increase superficially, with L2/3 containing ensembles of mostly broadly tuned neurons responding robustly to touch. Thus, from L4 to L2, cortex transitions from a dense probabilistic code to a sparse and robust ensemble-based code that improves stimulus decoding, facilitating perception.
Proximity proteome mapping reveals PD-L1-dependent pathways disrupted by anti-PD-L1 antibody specifically in EGFR-mutant lung cancer cells
Authors: Letian Anudari , Lemma Eyoel Yemanaberhan , Cavaliere Paola , Dephoure Noah , Altorki Nasser K. , McGraw Timothy E. 
Published: September 2021

AbstractPD-L1, a transmembrane ligand for immune checkpoint receptor PD1, has been successfully targeted to activate an anti-tumor immune response in a variety of solid tumors, including non-small cell lung cancer (NSCLC). Despite the success of targeting PD-L1, only about 20% of patients achieve a durable response. The reasons for the heterogeneity in response are not understood, although some molecular subtypes (e.g., mutant EGF receptor tumors) are generally poor responders. Although PD-L1 is best characterized as a transmembrane PD1 ligand, the emerging view is that PD-L1 has functions independent of activating PD1 signaling. It is not known whether these cell-intrinsic functions of PD-L1 are shared among non-transformed and transformed cells, if they vary among cancer molecular subtypes, or if they are impacted by anti-PD-L1 therapy. Here we use quantitative microscopy techniques and APEX2 proximity mapping to describe the behavior of PD-L1 and to identify PD-L1’s proximal proteome in human lung epithelial cells. Our data reveal growth factor control of PD-L1 recycling as a mechanism for acute and reversible regulation of PD-L1 density on the plasma membrane. In addition, we describe novel PD-L1 biology restricted to mutant EGFR cells. Anti-PD-L1 antibody treatment of mutant EGFR cells perturbs cell intrinsic PD-L1 functions, leading to reduced cell migration, increased half-life of EGFR and increased extracellular vesicle biogenesis, whereas anti-PD-L1 antibody does not induce these changes in wild type EGFR cells. These specific effects in mutant EGFR cells might contribute to the poor anti-PD-L1 response of mutant EGFR tumors.
Structural and functional characterization of Rv0792c from Mycobacterium tuberculosis: identifying small molecule inhibitors against GntR protein
Authors: Chauhan Neeraj Kumar , Anand Anjali , Sharma Arun , Dhiman Kanika , Gosain Tannu Priya , Singh Prashant , Khan Eshan , Kumar Amit , Sharma Deepak , Ashish  , Sharma Tarun Kumar , Singh Ramandeep 
Published: September 2021

ABSTRACTIn order to adapt in host tissues, microbial pathogens regulate their gene expression through an array of transcription factors. Here, we have functionally characterized Rv0792c, a GntR homolog from M. tuberculosis. In comparison to the parental strain, ΔRv0792c mutant strain of M. tuberculosis was compromised for survival upon exposure to oxidative stress, cell wall agents and infection in guinea pigs. RNA-seq analysis revealed that Rv0792c regulates the expression of genes that are involved in stress adaptation and virulence of M. tuberculosis. Solution small angle X-ray scattering (SAXS) data steered model building confirmed that the C-terminal region plays a pivotal role in dimer formation. Systematic evolution of ligands by exponential enrichment resulted in identification of ssDNA aptamers that can be used as a tool to identify small molecule inhibitors targeting Rv0792c. Using SELEX and SAXS data based modelling, we identified residues essential for the DNA binding activity of Rv0792c and I-OMe-Tyrphostin as an inhibitor of Rv0792c aptamer binding activity. Taken together, we provide a detailed shape-function characterization of GntR family of transcription factors from M. tuberculosis. To the best of our knowledge, this is the first study that has resulted in the identification of small molecule inhibitors against GntR family of transcription factors from bacterial pathogens.
A Novel Mistranslating tRNA Model in Drosophila melanogaster has Diverse, Sexually Dimorphic Effects
Authors: Isaacson Joshua R. , Berg Matthew D. , Jagiello Jessica , Villén Judit , Brandl Christopher J. , Moehring Amanda J. 
Published: September 2021

ABSTRACTTransfer RNAs (tRNAs) are the adaptor molecules required for reading of the genetic code and the accurate production of proteins. tRNA variants can lead to genome-wide mistranslation, the misincorporation of amino acids not specified by the standard genetic code into nascent proteins. While genome sequencing has identified putative mistranslating tRNA variants in human populations, little is known regarding how mistranslation affects multicellular organisms. Here, we create a Drosophila melanogaster model for mistranslation by integrating a serine tRNA variant that mistranslates serine for proline (tRNASerUGG, G26A) into the fly genome. Using mass spectrometry, we find that tRNASerUGG, G26A misincorporates serine for proline at a frequency of ∼ 0.6% per codon. We find that mistranslation extends development time and decreases the number of flies that reach adulthood. Adult flies containing tRNASerUGG, G26A present with more morphological deformities and worse climbing performance than flies expressing only wild type tRNA. Female flies with the serine tRNA variant have more deformities and experience a faster decline in climbing performance than males, suggesting sex-specific effects. This model will enable studies into the synergistic effects of mistranslating tRNA variants and disease-causing alleles.
Impact of zoonotic disease outbreaks on international wildlife trade dynamics in Ghana
Authors: Bempah Godfred , Nartey Moses A. , Dakwa Kwaku B. , Messenger Kevin 
Published: September 2021

AbstractWildlife is under intense pressure from trade, which most likely contributes to zoonotic diseases. The study explores the impact of zoonotic disease outbreaks on the wildlife trade of Ghana. This study provides an in-depth analysis of the trends of taxa trade and factors that influence trade from 1975–2018 by combining zoonotic disease data with data from the CITES database. Trade flow showed that reptiles were the most traded group, followed by birds, mammals, and amphibians. Species of the families Pythonidae, Dendrobatidae, Cercopithecidae, and Psittacidae were the most traded. The decade mean number of trade for 1997–2007 was the highest (n = 62) followed by 2008–2018 (n = 54.4). Most exporter countries that traded with Ghana are from Africa and importers from the United States of America, Europe and Asia. Continuous trade in reptiles and birds, especially the endangered pythons and psittacus species, could lead to their extinction in the wild. The outbreak of zoonotic diseases influenced the dynamics of the wildlife trade in Ghana as traders shifted their activities among taxa over a period of time. Because those taxa were observed to harbour zoonotic diseases and constitute high health risks when traded. Mammals’ trade flow decreased with disease outbreaks over time, while reptiles increased. Early detection of zoonotic diseases and the adoption of an expanded education module on avoiding species capable of harbouring pathogens will most likely help reduce trade in wildlife.
Potential COVID-19 vaccination opportunities in primary care practices in the United States
Authors: Basu Sanjay , Weintraub Rebecca , Ganguli Ishani , Phillips Russell , Phillips Robert , Bitton Asaf 
Published: September 2021

AbstractRapid, widespread COVID-19 vaccination is critical to pandemic mitigation and recovery. To help policymakers interested in further enhancing primary care delivery of COVID-19 vaccines, it is important to estimate the absolute number of vaccination opportunities, and identify how these opportunities may fall disproportionately among different communities given the unequal way that COVID-19 falls upon communities of color, low-income, and rural communities. To quantify the potential benefits of greater primary care engagement in vaccination efforts, we estimated the number of potential vaccination opportunities (PVOs) in primary care in the remaining calendar months of year 2021, and the possible uptake if we supplied enough vaccine to primary care practices to fulfill their opportunities. To estimate how many potential vaccination opportunities (PVOs) may occur in primary care, we used three sets of data, analyzing the latest available waves of the following: (i) the National Ambulatory Medical Care Survey (NAMCS, 2016, N = 677 providers); (ii) the National Health Interview Survey (NHIS, 2018, N = 29,839 individuals in 29,839 households); and (iii) the Medical Expenditure Panel Survey (MEPS, 2018, N = 40,025 individuals in 14,500 households). Per the NAMCS data, which provide a nationally-representative sample of ambulatory care visits, primary care physicians normally provide 40.2 million primary care visits per month. The majority of the primary care utilization is absorbed by those aged 16 to 64 years old who are not otherwise priority groups (i.e., not having chronic diseases as defined by ACIP) but the second large group of visits are those with a chronic disease (27.2% of all visits). As compared to the NAMCS data providing an estimate of care from the perspective of providers, the overall sample in NHIS provides a view of primary care access and utilization from a population perspective. Per NHIS, 34% of the civilian US population saw a generalist physician in the prior calendar year, or 109.8 million people. Overall, we would estimate that over the latter half of calendar year 2021, approximately 15 million potential vaccine opportunities per month would be available through US primary care practices.
University patenting and licensing practices in the United Kingdom during the COVID-19 pandemic
Authors: Keestra Sarai , Rodgers Florence , Osborne Rhiannon , Wimmer Sabrina 
Published: September 2021

AbstractUniversities play a vital role in biomedical innovation during the COVID-19 pandemic, and decisions made during technology transfer may affect affordability, accessibility, and availability of health technologies downstream. We investigated the measures the top 35 UK universities receiving most Medical Research Council funding have taken in technology transfer to ensure global equitable access to health technologies. We sent Freedom Of Information (FOI) requests and analysed universities’ websites, to (i.) assess institutional strategies on the patenting and licensing of COVID-19-related health technologies, (ii.) identify all COVID-19-related health technologies licensed or patented, and (iii.) record whether universities engaged with the Open-COVID pledge, COVID-19 Technology Access Pool (C-TAP), or Association of University Technology Managers (AUTM) COVID-19 licensing guidelines. Except for the Universities of Oxford and Edinburgh, UK universities have not updated their institutional strategies during the pandemic. Nine universities licensed 22 COVID-19 health technologies. Imperial College London disclosed 10 patents relevant to COVID-19. No UK universities participate in the Open-COVID Pledge or C-TAP, but discussions are ongoing. The University of Bristol signed up to the AUTM guidelines. Despite several important COVID-19 health technologies being developed by UK universities, our findings suggest minimal engagement with measures that may promote equitable access downstream. We suggest that universities review their technology transfer policies and implement global equitable access strategies for COVID-19 health technologies. We furthermore propose that public and charitable funders can play a larger role in encouraging universities to adopt such practices, by making access and transparency clauses a mandatory condition for receiving public funds for research.
Social relationships and activities following elimination of SARS-CoV-2: a qualitative cross-sectional study
Authors: Long Nicholas J. , Appleton Nayantara Sheoran , Davies Sharyn Graham , Deckert Antje , Fehoko Edmond , Holroyd Eleanor , Martin-Anatias Nelly , Sterling Rogena , Trnka Susanna , Tunufa’i Laumua 
Published: September 2021

AbstractObjectivesTo investigate how successfully SARS-CoV-2 elimination strategies fulfil their promise of allowing a return to a ‘normal’ social life, and to identify obstacles and challenges that may inhibit the realisation of this goal.DesignQualitative cross-sectional survey.SettingNew Zealand community cohort.Participants1040 respondents entered the study (18–90 years, M = 48.18.11, SD = 15.52, 76% women). 966 completed the questions relevant to this article. Participants were recruited via online advertisement campaigns designed to maximise variation in the sample as far as practicably possible.Main outcome measuresThematic analysis of participants’ narratives.ResultsA majority of participants reported that the elimination of SARS-CoV-2 had allowed their life to go back to being ‘more or less the same’ as before the pandemic. A small number indicated the pandemic had inspired them to become more social following elimination. Nevertheless, a sizeable minority of respondents reported being less social, even many months after SARS-CoV-2 had been eliminated. This was often because of fears that the virus might be circulating undetected, or because the March-May 2020 lockdown had led to changes in relationships and personal habits that were not easily reversed. Becoming less social was associated with having an underlying health condition that heightened one’s vulnerability to COVID-19 (p = 0.00005) and older age (p = 0.007).ConclusionsElimination strategies can successfully allow the public to return to a pre-pandemic ‘normal’ – or reinvent and improve their social lives should they wish. However, such outcomes are not inevitable. Re-establishing social connections after elimination can sometimes be a challenging process, with which people may need support. Plans for providing such support should be an integral part of elimination strategies.
Cross-cultural competence and social capital dynamic process in cross-border M&A, a theoretical framework based on a multi-case study
Authors: Gu Zhouyang , Meng Fanchen 
Published: September 2021

PurposeIn the process of cross-border mergers and acquisitions (M&A), the social capital of enterprises is dynamic. In this context, cross-cultural competence plays an important role and can affect the transformation process of social capital and further influence the realisation of M&A performance. However, there is still not enough research on the process of social capital transformation and corporate cross-cultural competence. This study aims to explore the influence mechanism of social capital and the cross-cultural competence of enterprises.Design/methodology/approachIn this paper, four typical manufacturing M&A case studies were analysed and a grounded theoretical analysis process was used to explore the structure of cross-cultural competence and its impact on the dynamic process of social capital.FindingsThe results of this study imply that social capital experiences three stages of transformation in the process of M&A. There are also four dimensions of corporate cross-cultural competence, which are composed of various factors. These all affect the dynamic process of social capital through different influence mechanisms.Originality/valueAccording to the results, a mechanism model was composed to determine how corporate cross-cultural ability affects the social capital process. This is of practical significance as it can enhance the performance of M&A integration in a cross-cultural context.