bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcutaneous REGEN-COV Antibody Combination for Covid-19 Prevention
Authors: O’Brien Meagan P. , Forleo-Neto Eduardo , Musser Bret J. , Isa Flonza , Chan Kuo-Chen , Sarkar Neena , Bar Katharine J. , Barnabas Ruanne V. , Barouch Dan H. , Cohen Myron S. , Hurt Christopher B. , Burwen Dale R. , Marovich Mary A. , Hou Peijie , Heirman Ingeborg , Davis John D. , Turner Kenneth C. , Ramesh Divya , Mahmood Adnan , Hooper Andrea T. , Hamilton Jennifer D. , Kim Yunji , Purcell Lisa A. , Baum Alina , Kyratsous Christos A. , Krainson James , Perez-Perez Richard , Mohseni Rizwana , Kowal Bari , DiCioccio A. Thomas , Stahl Neil , Lipsich Leah , Braunstein Ned , Herman Gary , Yancopoulos George D. , Weinreich David M. ,   for the Covid-19 Phase 3 Prevention Trial Team
Published: June 2021

ABSTRACTBackgroundCasirivimab and imdevimab (REGEN-COV™) markedly reduces risk of hospitalization or death in high-risk individuals with Covid-19. Here we explore the possibility that subcutaneous REGEN-COV prevents SARS-CoV-2 infection and subsequent Covid-19 in individuals at high risk of contracting SARS-CoV-2 by close exposure in a household with a documented SARS-CoV-2–infected individual.MethodsIndividuals ≥12 years were enrolled within 96 hours of a household contact being diagnosed with SARS-CoV-2 and randomized 1:1 to receive 1200 mg REGEN-COV or placebo via subcutaneous injection. The primary efficacy endpoint was the proportion of participants without evidence of infection (SARS-CoV-2 RT-qPCR– negative) or prior immunity (seronegative) who subsequently developed symptomatic SARS-CoV-2 infection during a 28-day efficacy assessment period.ResultsSubcutaneous REGEN-COV significantly prevented symptomatic SARS-CoV-2 infection compared with placebo (81.4% risk reduction; 11/753 [1.5%] vs. 59/752 [7.8%], respectively; P<0.0001), with 92.6% risk reduction after the first week (2/753 [0.3%] vs. 27/752 [3.6%], respectively). REGEN-COV also prevented overall infections, either symptomatic or asymptomatic (66.4% risk reduction). Among infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV vs. placebo (1.2 vs. 3.2 weeks, respectively), and the duration of time with high viral load (>104 copies/mL) was lower (0.4 vs. 1.3 weeks, respectively). REGEN-COV was generally well tolerated.ConclusionsAdministration of subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in uninfected household contacts of infected individuals. Among individuals who became infected, REGEN-COV reduced the duration of symptomatic disease, decreased maximal viral load, and reduced the duration of detectable virus.(ClinicalTrials.gov number, NCT04452318.)
Wolbachia-mediated sterility suppressesAedes aegyptipopulations in the urban tropics
Authors:   The Project Wolbachia – Singapore Consortium, Ching Ng Lee 
Published: June 2021

AbstractIncompatible insect technique (IIT) via releases of maleWolbachia-infected mosquitoes is a promising tool for dengue control. In a three-year trial in Singaporean high-rise housing estates, we demonstrated thatWolbachia-based IIT dramatically reduces both wildtypeAedes aegyptipopulations [reductions of 92.7% (95% CI: 84.7%–95.8%) and 98.3% (97.7%–99.8%)] and dengue incidence [reductions of 71% (43%-87%) to 88% (57%-99%)] in the targeted areas. The study highlights the need to ensure adequate vertical distribution of released males in high-rise buildings, address immigration of wildtype females from neighboring areas, and prevent and mitigate stable establishment ofWolbachiain field mosquito populations. Our results demonstrate the potential ofWolbachia-based IIT (supplemented with irradiation, in Singapore’s context) for strengthening dengue control in tropical cities, where dengue burden is the greatest.One Sentence SummaryReleases of maleWolbachia-infectedAedes aegyptisuppress dengue mosquitoes and reduce dengue incidence in high-rise urban areas in Singapore.
Respiratory and C4-photosynthetic NAD-malic enzyme coexist in bundle sheath cells mitochondria and evolved via association of differentially adapted subunits
Authors: Hüdig Meike , Tronconi Marcos A. , Zubimendi Juan P. , Sage Tammy L. , Poschmann Gereon , Bickel David , Gohlke Holger , Maurino Veronica G. 
Published: June 2021

ABSTRACTIn different lineages of Cleomaceae, NAD-malic enzyme (NAD-ME) was independently co-opted to participate in C4 photosynthesis. In the C4 Cleome species Gynandropsis gynandra and Cleome angustifolia, all NAD-ME genes (NAD-MEα, NAD-MEβ1, and NAD-MEβ2) were affected by C4 evolution and are expressed at higher levels than their orthologs in the C3 Cleome species Tarenaya hassleriana. In the latter C3 species, the NAD-ME housekeeping function is performed by two heteromers, NAD-MEα/β1 and NAD-MEα/β2, with similar biochemical properties. In both C4 species analyzed, this role is restricted the NAD-MEα/β2 heteromer. In the C4 species, NAD-MEα/β1 is exclusively present in the leaves, where it accounts for most of the enzymatic activity. GgNAD-MEα/β1 exhibits high catalytic efficiency and is differentially activated by the C4 intermediate aspartate, confirming its role as the C4-decarboxylase. During C4 evolution, GgNAD-MEβ1and CaNAD-MEβ1 lost their catalytic activity; their contribution to enzymatic activity results from a stabilizing effect on the associated α-subunit. We conclude that in bundle sheath cell mitochondria of C4 Cleome species, the functions of NAD-ME as C4 photosynthetic decarboxylase and as a tricarboxylic acid cycle-associated housekeeping enzyme coexist and are performed by isoforms that combine the same α subunit with differentially adapted β subunits.
Molnupiravir, an Oral Antiviral Treatment for COVID-19
Authors: Fischer William , Eron Joseph J. , Holman Wayne , Cohen Myron S. , Fang Lei , Szewczyk Laura J. , Sheahan Timothy P , Baric Ralph , Mollan Katie R. , Wolfe Cameron R. , Duke Elizabeth R. , Azizad Masoud M. , Borroto-Esoda Katyna , Wohl David A. , Loftis Amy James , Alabanza Paul , Lipansky Felicia , Painter Wendy P. 
Published: June 2021

AbstractBackgroundEasily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 (ClinicalTrials.govNCT04405570).MethodsEligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs.ResultsAmong 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups.ConclusionsMolnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.
Conformational and interface variability of bivalent RNF4-SIM diSUMO3 interaction
Authors: Kötter Alex , Mootz Henning D. , Heuer Andreas 
Published: June 2021

AbstractSUMO targeted ubiqutin ligases (STUbLs) like RNF4 or Arkadia/RNF111 recognize SUMO chains through multiple SUMO interacting motifs (SIMs). Typically, these are contained in disordered regions of these enzymes and also the individual SUMO domains of SUMO chains move relatively freely. It is assumed that binding the SIM region significantly restricts the conformational freedom of SUMO chains. Here, we present the results of extensive molecular dynamics simulations on the complex formed by the SIM2-SIM3 region of RNF4 and diSUMO3. Though our simulations highlight the importance of typical SIM-SUMO interfaces also in the multivalent situation, we observe that frequently other regions of the peptide than the canonical SIMs establish this interface. This variability regarding the individual interfaces leads to a conformationally highly flexible complex. Even though this is in contrast to previous models of the RNF4 SUMO chain interaction, we demonstrate that our simulations are clearly consistent with previous experimental results.
Alzheimer’s disease-associated P460L mutation in ephrin receptor type A1 (EphA1) leads to dysregulated Rho-GTPase signaling
Authors: Kim Y. , Lasso G. , Patel H. , Vardarajan B. , Santa-Maria I , Lefort R. 
Published: June 2021

ABSTRACTRecently, late onset AD (LOAD) genome-wide association studies identified EphA1, a member of receptor tyrosine kinase family (RTK) as a disease associated loci. In the follow-up study where 3 independent LOAD cohorts were performed, a P460L coding mutation in EphA1 loci showed a significant association with LOAD. However, the role of EphA1 and P460L mutant EphA1 in AD is not fully understood. We have characterized this mutation biophysically and biochemically. Our structural in silico model and in vitro biochemical analysis demonstrate that EphA1-P460L mutation makes the receptor constitutively active suggesting a gain-of-toxic function leading to chronic EphA1 signaling in the brain. Moreover, we report that the EphA1 P460L variant triggers Rho-GTPase signaling dysregulation that could potentially contribute to spine morphology abnormalities and synaptic dysfunction observed in AD pathology.
Towards more accurate preclinical glioblastoma modelling: reverse translation of clinical standard of care in a glioblastoma mouse model
Authors: Riva Matteo , Bevers Sien , Wouters Roxanne , Thirion Gitte , Vandenbrande Katja , Vankerckhoven Ann , Berckmans Yani , Verbeeck Jelle , De Keersmaecker Kim , Coosemans An 
Published: June 2021

AbstractIntroductionContrarily to clinical trials, where glioblastoma (GBM) patients are usually heavily pre-treated (surgery, radiotherapy (RT) and temozolomide (TMZ)) before receiving the experimental therapies, in preclinical GBM studies experimental treatments have mostly been administered as monotherapy or combined with a very limited part of the clinical standard of care. This discrepancy can explain the failed clinical translation of preclinically successful treatments. This study is aimed at evaluating the feasibility and survival impact of the clinical standard of care in glioma-bearing mice. Methods. Neurospheres CT-2A tumor-bearing mice were treated with fluorescence-guided tumor resection, focal RT and oral TMZ.ResultsThe implementation of postoperative intensive care treatment reduced surgical mortality by approximately 50% and increased experimental cost-effectiveness. Partial and total tumor resection significantly prolonged survival, the latter showing the strongest effect. Mice treated with surgery combined with RT or with RT and TMZ survived significantly longer than untreated controls.ConclusionsImplementing the current GBM clinical standard of care in preclinical research is feasible and it leads to results in line with those obtained in patients. Systematic preclinical evaluation of the efficacy of experimental therapies in combination with standard of care treatments could improve the translational impact of next generation GBM animal studies.
Separate physiological roles of specific and non-specific DNA binding of HU protein in Escherichia coli
Authors: Verma Subhash , Adhya Sankar 
Published: June 2021

SUMMARYConserved in bacteria, the histone-like protein HU is crucial for genome organization and expression of many genes. It binds DNA regardless of the sequence and exhibits two binding affinities in vitro, low-affinity to any B-DNA (non-specific) and high-affinity to DNA with distortions like kinks and cruciforms (structure-specific), but the physiological relevance of the two binding modes needed further investigation. We validated and defined the three conserved lysine residues, K3, K18, and K83, in Escherichia coli HU as critical amino acid residues for both non-specific and structure-specific binding and the conserved proline residue P63 additionally for only the structure-specific binding. By mutating these residues in vivo, we showed that two DNA binding modes of HU play separate physiological roles. The DNA structure-specific binding, occurring at specific sites in the E. coli genome, promotes higher-order DNA structure formation, regulating the expression of many genes, including those involved in chromosome maintenance and segregation. The non-specific binding participates in numerous associations of HU with the chromosomal DNA, dictating chromosome structure and organization. Our findings underscore the importance of DNA structure in transcription regulation and promiscuous DNA-protein interactions in a dynamic organization of a bacterial genome.
Vapor mediation as a tool to control micro-nano scale dendritic crystallization and preferential bacterial distribution in drying respiratory droplets
Authors: Hegde Omkar , Chatterjee Ritika , Rasheed Abdur , Chakravortty Dipshikha , Basu Saptarshi 
Published: June 2021

AbstractDeposits of biofluid droplets on surfaces (such as respiratory droplets formed during an expiratory event fallen on surfaces) are composed of the water-based salt-protein solution that may also contain an infection (bacterial/viral).The final patterns of the deposit formed are dictated by the composition of the fluid and flow dynamics within the droplet. This work reports the spatio-temporal, topological regulation of deposits of respiratory fluid droplets and control of motility of bacteria by tweaking flow inside droplets using non-contact vapor-mediated interactions. When evaporated on a glass surface, respiratory droplets form haphazard multiscale dendritic, cruciform-shaped precipitates—using vapor mediation as a tool to control these deposits at the level of nano-micro-millimeter scales. Wemorphologically control dendrite orientation, size and subsequently suppress cruciform-shaped crystals. The nucleation sites are controlled via preferential transfer of solutes in the droplets; thus, achieving control over crystal occurrence and growth dynamics. The active living matter like bacteria is also preferentially segregated with controlled motility without attenuation of its viability and pathogenesis. For the first time, we have experimentally presented a proof-of-concept to control the motion of live active matter like bacteria in a near non-intrusive manner. The methodology can have ramifications in biomedical applications like disease detection, controlling bacterial motility, and bacterial segregation.
Teaching BIM as a collaborative information management process through a continuous improvement assessment lens: a case study
Authors: Nikolic Dragana , Castronovo Fadi , Leicht Robert 
Published: June 2021

PurposeThis study explores a pedagogical approach to teaching students a collaborative information delivery process in the context of BIM. The objectives were to understand how students approach this complex, open-ended problem of planning their collaborative process and then identify strategies for improving their process through a plan-do-check-act cycle and reflecting on the applicability of industry standards.Design/methodology/approachThe authors present a longitudinal case study based on qualitative data from the 3 consecutive years of teaching a senior undergraduate course in a construction engineering program.FindingsThe findings offer a rich picture of how students approached this collaborative process and emphasize the complex nature of teaching BIM as information management process. The authors present instances of how students made sense of BIM standards through applied experience. The findings also demonstrate the value of an outcome-based approach whereby knowledge is gained through an iterative plan-do-check-act cycle. Here, the BEP and model deliverables served only as vehicles to test and apply a range of skills by making them more explicit.Practical implicationsThe research contributes to the literature on mechanisms that support students in planning, managing and improving collaborative information strategies in a BIM context. Specifically, the authors illustrate a tension in how to pedagogically deploy industry-oriented process planning methods to establish relevance for students in order to effectively engage in interdisciplinary teams.Originality/valueIn this paper, the authors argue that teaching students how to plan, design and enact effective BIM collaboration information delivery is firmly nested within pedagogical management and communication skills. The authors illustrate with examples how students make sense of BIM approaches by making them concrete and meaningful to their own experience.
Trust mechanisms underlying the self-efficacy-rumour use relationship
Authors: Wang Ping , Hu Yixia , Li Qiao , Yang Hanqin 
Published: June 2021

PurposeJournalism students, a special user group with the dual perspective of both social media general users and online journalists, and their trust in rumours is a valued but understudied topic in relation to preparing rational information users and professionals for rumour control. To reveal these trust mechanisms, this paper aims to identify salient psychological and behavioural factors related to journalism students’ different levels of trust.Design/methodology/approachUsing structural equation modelling to analyse the survey data of 234 journalism students, this paper tested a theoretical model that considers self-efficacy and the expressive and consumptive use of social media rumours as the antecedents and consequences of trust belief and trust action, respectively.FindingsSelf-efficacy has a positive effect on trust belief but a negative effect on trust action. Trust belief positively affects expressive use of rumours, whereas trust action negatively affects consumptive use.Practical implicationsThis study contributes to the cultivation of future online news gatekeepers.Originality/valueThis paper distinguishes journalism students’ trust mechanisms from those of general users and online journalists. The integration of dual process theories provides insights into trust-building processes related to rumours and advances the understanding of the anchoring and adjustment effects of self-efficacy on trust.
The impact of differences in internationalization processes on innovation by emerging economy firms
Authors: Samant Shantala , Thakur-Wernz Pooja , Hatfield Donald E. 
Published: June 2021

PurposeThe purpose of this paper is to study the differences in the internationalization process of firms from emerging economies and the impact of their international expansion related choices on the nature of technological innovations developed by these firms. Specifically, the authors compare two principal perspectives on internationalization – the incremental internationalization process (slow, gradually increasing commitments using greenfield investments to similar host countries) and the springboard perspective (aggressive, rapidly increasing commitments using mergers and acquisitions to advanced host countries).Design/methodology/approachBuilding on key differences between the incremental internationalization and springboard perspectives, the authors argue that differences in the speed and mode of entry, as well as the interaction between the mode of entry and location of internationalization, will lead to differences in the types of technologies (mature versus novel) developed by emerging economy firms. The authors examine the hypotheses using panel data from 1997 to 2013 on emerging economy multinationals (EMNEs) from the Indian bio-pharmaceutical industry.FindingsThe findings suggest that firms internationalizing at higher speeds and using cross-border M&As tend to have innovations in mature technologies. The interesting findings can be explained by the challenges faced by emerging economy firms in experiential learning and the assimilation of external knowledge. In addition, the authors find that internationalization to technologically advanced countries weakens the relationship between cross-border M&As and innovation in mature technologies, suggesting that direct learning from technologically advanced environments may help alleviate the assimilation challenges of cross-border M&As.Originality/valueThe authors advance literature on EMNE internationalization by comparing the impact of their choice of internationalization approaches (incremental internationalization or springboard approach) on their innovation performance. The authors contribute to literature on EMNEs that has focused on the determinants of internationalization by identifying the learning implications of internationalization. The authors contribute to the nascent stream of literature on the level of innovation and catching up by EMNEs by performing a fine-grained analysis of the nature of technology innovation.