bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timeliness of reporting of SARS-CoV-2 seroprevalence results and their utility for infectious disease surveillance
Authors: Donnici Claire , Ilincic Natasha , Cao Christian , Zhang Caseng , Deveaux Gabriel , Clifton David A. , Buckeridge David , Bobrovitz Niklas , Arora Rahul K. 
Published: February 2022

AbstractSeroprevalence studies have been used throughout the COVID-19 pandemic to monitor infection and immunity. These studies are often reported in peer-reviewed journals, but the academic writing and publishing process can delay reporting and thereby public health action. Seroprevalence estimates have been reported faster in preprints and media, but with concerns about data quality. We aimed to (i) describe the timeliness of SARS-CoV-2 serosurveillance reporting by publication venue and study characteristics and (ii) identify relationships between timeliness, data validity, and representativeness to guide recommendations for serosurveillance efforts.We included seroprevalence studies published between January 1, 2020 and December 31, 2021 from the ongoing SeroTracker living systematic review. For each study, we calculated timeliness as the time elapsed between the end of sampling and the first public report. We evaluated data validity based on serological test performance and correction for sampling error, and representativeness based on use of a representative sample frame and adequate sample coverages. We examined how timeliness varied with study characteristics, representativeness, and data validity using univariate and multivariate Cox regression.We analyzed 1,844 studies. Median time to publication was 154 days (IQR 64-255), varying by publication venue (journal articles: 212 days, preprints: 101 days, institutional reports: 18 days, and media: 12 days). Multivariate analysis confirmed the relationship between timeliness and publication venue and showed that general population studies were published faster than special population or health care worker studies; there was no relationship between timeliness and study geographic scope, geographic region, representativeness, or serological test performance.Seroprevalence studies in peer-reviewed articles and preprints are published slowly, highlighting the limitations of using the academic literature to report seroprevalence during a health crisis. More timely reporting of seroprevalence estimates can improve their usefulness for surveillance, enabling more effective responses during health emergencies.
Effect of mHealth interventions on psychological issues experienced by women diagnosed with breast cancer receiving chemotherapy: A systematic review and meta-analysis
Authors: Akingbade Oluwadamilare , Nguyen Khanh Thi , Chow Ka Ming 
Published: February 2022

AbstractBackgroundA range of psychological issues often accompany breast cancer chemotherapy. Owing to their ubiquity, mobile phones have been used to deliver supportive interventions that address these issues. However, we currently lack sufficient evidence to guide the design of such interventions.AimTo analyse and synthesise available evidence on the effectiveness of mobile-phone-based (mHealth) interventions in alleviating the psychological issues experienced by women receiving chemotherapy for breast cancer.MethodsA systematic literature search was conducted from 14 relevant databases. Revman 5.4 was used to pool the quantitative results from comparable studies for statistical meta-analysis. For clinically heterogeneous studies where statistical pooling of results was not possible, a narrative summary was used to present the findings.ResultsThe review included ten published studies which covered 1,548 patients. The meta-analysis results indicated a significant improvement in the quality of life (standardised mean difference [SMD] = 0.32, 95% confidence interval [CI] [0.07, 0.58], p = .01, I2 = 17%). No significant effects were found for anxiety (SMD = -0.01, 95% CI [-0.26, 0.25], p = 0.96, I2 = 53%) and depression (SMD = 0.02, 95% CI [-0.17, 0.20], p = .87, I2 = 0%). Individual studies suggest reduced symptom prevalence (p = .033, d =.27), symptom distress (p = .004, d = .004), symptom interference (p = .02, d = .51), supportive care needs (p < .05, d = 2.43); improved self-efficacy (p = .03, d = 0.53), self-esteem (p <.001, d = 0.87) and emotional functioning (p = .008, d = .30). The methodological quality ranged from low to moderate.ConclusionmHealth interventions might be helpful in addressing certain psychological issues experienced by this population, although the evidence is still being gathered and not yet conclusive. More rigorous trials are hereby warranted to confirm the suitable duration while addressing the methodological flaws found in previous studiesPROSPERO registration numberCRD42021224307
An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants
Authors: Du Wenjuan , Hurdiss Daniel L. , Drabek Dubravka , Mykytyn Anna Z. , Kaiser Franziska K. , González-Hernandez Mariana , Muñoz-Santos Diego , Lamers Mart M. , van Haperen Rien , Li Wentao , Drulyte Ieva , Wang Chunyan , Sola Isabel , Armando Federico , Beythien Georg , Ciurkiewicz Malgorzata , Baumgärtner Wolfgang , Guilfoyle Kate , Smits Tony , van der Lee Joline , van Kuppeveld Frank J.M. , van Amerongen Geert , Haagmans Bart L. , Enjuanes Luis , Osterhaus Albert D.M.E. , Grosveld Frank , Bosch Berend-Jan 
Published: February 2022

AbstractThe ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity.One sentence summaryA human monoclonal antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants
CipA mediates complement resistance of Acinetobacter baumannii by formation of a Factor I-dependent quadripartite assemblage
Authors: Ries Julia I. , Heß Marie , Nouri Noura , Wichelhaus Thomas A. , Göttig Stephan , Falcone Franco H. , Kraiczy Peter 
Published: February 2022

AbstractMultidrug-resistant Acinetobacter baumannii is known to be one of the leading pathogens that cause severe nosocomial infections. To overcome eradication by the innate immune system during infection, A. baumannii developed a number of immune evasion strategies. Previously, we identified CipA as a plasminogen-binding and complement-inhibitory protein. Here we show that CipA strongly inhibits all three complement activation pathways and interacts with key complement components C3, C3b, C4b, C5, Factor B, Factor D, and in particular Factor I. CipA also targets function of the C5 convertase as cleavage of C5 was impaired. Systematic screening of CipA variants identified two separate binding sites for C3b and a Factor I-interacting domain located at the C-terminus. Structure predictions using AlphaFold2 and binding analyses employing CipA variants lacking Factor I-binding capability confirmed that the orientation of the C-terminal domain is essential for the interaction with Factor I. Hence, our analyses point to a novel, Factor I-dependent mechanisms of complement inactivation mediated by CipA of A. baumannii. Recrutiment of Factor I by CipA initiates the assembly of a quadripartite complex following binding of either Factor H or C4b-binding protein to degrade C3b and C4b, respectively. Loss of Factor I binding in a CipA-deficient strain, or a strain producing a CipA variant lacking Factor I-binding capability, correlated with a higher susceptibility to human serum, indicating that recruitment of Factor I enables A. baumannii to resist complement-mediated killing.Significance StatementThe Gram-negative bacterium Acinetobacter baumannii causes severe nosocomial infections and has developed various immune evasion strategies to overcome complement. The mechanisms how Acinetobacter baumannii successfully circumvents complement-mediated bacteriolysis are still poorly understood. Here, we show that the plasminogen-binding and complement inhibitory protein CipA terminates all three complement activation pathways. We describe a novel mechanism by which CipA cleaves the key complement components C3b and C4b in the presence of Factor H and C4b-binding protein by formation of a novel Factor I-dependent quadripartite complex. CipA, which has recently been successfully used for vaccination approaches, might represent an attractive target for the development of novel therapeutic interventions to block disorders with excessive hyperinflammatory complement activation.
Distinct physiological responses ofCoccolithus braarudiilife cycle phases to light intensity and nutrient availability
Authors: Langer Gerald , Jie Vun Wen , Kottmeier Dorothee , Flori Serena , Sturm Daniela , de Vries Joost , Harper Glenn M. , Brownlee Colin , Wheeler Glen 
Published: February 2022

AbstractCoccolithophores feature a haplo-diplontic life cycle comprised of diploid cells producing heterococcoliths and haploid cells producing morphologically different holococcoliths. These life cycle phases of each species appear to have distinct spatial and temporal distributions in the oceans, with the heavily-calcified heterococcolithophores (HET) often more prevalent in winter and at greater depths, whilst the lightly-calcified holococcolithophores (HOL) are more abundant in summer and in shallower waters. The haplo-diplontic life cycle may therefore allow coccolithophores to expand their ecological niche, switching between life cycle phases to exploit conditions that are more favourable. However, coccolithophore life cycles remain poorly understood and fundamental information on the physiological differences between life cycle phases is required if we are to better understand the ecophysiology of coccolithophores. In this study, we have examined the physiology of HET and HOL phases of the coccolithophoreCoccolithus braarudiiin response to changes in light and nutrient availability. We found that the HOL phase was more tolerant to high light than the HET phase, which exhibited defects in calcification at high irradiances. The HET phase exhibited defects in coccolith formation under both nitrate (N) and phosphate (P) limitation, whilst no defects in calcification were detected in the HOL phase. The HOL phase grew to a higher cell density under P-limitation than N-limitation, whereas no difference was observed in the maximum cell density reached by the HET phase at these nutrient concentrations. HET cells grown under a light:dark cycle divided primarily in the dark and early part of the light phase, whereas HOL cells continued to divide throughout the 24 h period. The physiological differences may contribute to the distinct biogeographical distributions observed between life cycle phases, with the HOL phase potentially better adapted to high light, low nutrient regimes, such as those found in seasonally stratified surface waters.HighlightsCoccolithus braarudiilife cycle phases exhibit different physiological responses.The heavily-calcified heterococcolithophores (HET) life cycle phase is more sensitive to high light.The lightly-calcified holococcolithophores (HOL) life cycle phase may be better suited to growth under low phosphate availability.
Low Density Lipoprotein Receptor-Related Protein 1 (LRP1) as an auxiliary host factor for RNA viruses including SARS-CoV-2
Authors: Devignot Stephanie , Sha Tim Wai , Burkard Thomas R. , Schmerer Patrick , Hagelkruys Astrid , Mirazimi Ali , Elling Ulrich , Penninger Josef M. , Weber Friedemann 
Published: February 2022

AbstractViruses with an RNA genome are often the cause of zoonotic infections. In order to identify novel pro-viral host cell factors, we screened a haploid insertion-mutagenized mouse embryonic cell library for clones that rendered them resistant to the zoonotic Rift Valley fever virus (RVFV; familyPhleboviridae, orderBunyavirales). This screen returned the Low Density Lipoprotein Receptor-Related protein 1 (LRP1, or CD91) as top hit, a 600 kDa plasma membrane protein known to be involved in a wide variety of cell activities. Inactivation of LRP1 expression in human cells reduced RVFV RNA levels already at the attachment and entry stages of infection. Moreover, the role of LRP1 in promoting RVFV infection was dependent on physiological levels of cholesterol and on endocytosis. In the highly LRP1-positive human cell line HuH-7, LRP1 also promoted the early infection stages of Sandfly fever Sicilian virus (SFSV; familyPhleboviridae, orderBunyavirales), La Crosse virus (LACV; familyPeribunyaviridae, orderBunyavirales), had a minor effect on RNA levels during the late infection stages by vesicular stomatitis virus (VSV; familyRhabdoviridae, orderMononegavirales), whereas infection by Encephalomyocarditis virus (EMCV, familyPicornaviridae) was entirely LRP1-independent. Moreover, siRNA experoments in human Calu-3 cells demonstrated that also SARS-CoV-2 infection benefitted from LRP1. Thus, we identified LRP1 as a host factor that supports infection by a spectrum of RNA viruses.
A novel fluorescent multi-domain protein construct reveals the individual steps of the unfoldase action of Hsp70
Authors: Tiwari Satyam , Fauvet Bruno , Assenza Salvatore , De los Rios Paolo , Goloubinoff Pierre 
Published: February 2022

AbstractA detailed understanding of the mechanism by which Hsp70 chaperones protect cells against protein aggregation is hampered by the detailed characterization of the aggregates, which are typically heterogeneous. To tackle this problem, we designed here a reporter chaperone substrate, MLucV, composed of a stress-labile luciferase core, flanked by stress-resistant fluorescent mTFP and Venus domains, which upon denaturation formed a discrete stable population of small aggregates. Combining Förster Resonance Energy Transfer and enzymatic activity measurements provided unprecedent details on MLucV states, including native, aggregated, unfolded and chaperone-bound conformations. Using MLucV, we probed the various steps undertaken by bacterial Hsp70 to convert stable discrete aggregates into native proteins. The mechanism first involved an ATP-fuelled disaggregation and unfolding step of the stable pre-aggregated substrate, with a consequent stretching of MLucV beyond simply-unfolded conformations, followed, upon release, by native refolding. Furthermore, the ATP-fuelled unfolding action of Hsp70 on MLucV aggregates could accumulate native MLucV species under elevated denaturing temperatures, highly adverse to the native state. These results unambiguously excluded binding and preventing aggregation from the non-equilibirum mechanism by which Hsp70 converts stable aggregates into metastable native proteins.
Benchmarking Peptide Structure Prediction with AlphaFold2
Authors: Gulsevin Alican , Meiler Jens 
Published: February 2022

AbstractAlphaFold2 (AF2) is a computational tool developed for the determination of protein structures with high accuracy. AF2 has been used for the modeling of many soluble and membrane proteins, but its performance in modeling peptide structures has not been systematically investigated so far. We benchmarked the accuracy of AF2 in predicting peptide structures between 16 – 60 amino acids using experimentally-determined peptide structures as reference. Our results show that while AF2 can predict the structures of certain peptide scaffolds with RMSD values below 3 Å, it is less successful in predicting the structures of peptides that have kinks, turns, or have extended flexible regions. Further, AF2 had several shortcomings in predicting rotamer recoveries, disulfide bonds, and the lowest RMSD structures based on pLDDT values. In summary, AF2 can be a powerful tool to determine peptide structures, but additional steps may be necessary to analyze and validate the results.
How drought affects range and variability of environmental conditions in subtropical South African estuaries
Authors: Scharler UM , Bownes SJ , Jerling H 
Published: February 2022

AbstractGlobally estuaries are under increasing pressure from human development impacts as well as the growing effects of climate change that is already, and increasingly so, causing major changes in events such as droughts. Although droughts are regular occurrences and are projected to become progressively more significant in many parts of the world, their potential impacts on estuaries requires better understanding and quantification. This study aims to quantify environmental and phytoplankton parameter changes in two contrasting subtropical estuary types in South Africa; the temporarily closed uMdloti Estuary and the predominantly open to the sea uMlalazi Estuary during a hydrological drought event and subsequent non-drought period. Drought caused lower salinities, almost exclusively freshwater, throughout the temporarily closed estuarine type uMdloti. The marine-estuarine salinity environment of the predominantly open uMlalazi during drought expanded to include lower salinities in the non-drought period. Dissolved oxygen levels were more variable during drought conditions including periods of hypoxia, but more stable at elevated levels in both estuaries during the non- drought period. Temperature measurements included higher values during drought, especially in the dry season. Chl-a concentrations were overall higher and more variable during drought in uMdloti, with periods of bloom formation as well as decay. Drought-induced conditions can span several generations for estuarine and estuarine associated organisms. The results from the study provide quantitative support for the hypothesis that extended periods of drought conditions lead to a decrease in niche availability to estuarine organisms in a range of estuary types.
In situ architecture of human kinetochore-microtubule interface visualized by cryo-electron tomography
Authors: Zhao Wei , Jensen Grant J. 
Published: February 2022

AbstractFaithful segregation of chromosomes during mitosis relies on a carefully coordinated and intricate interplay between the centromere, kinetochore, and spindle microtubules. Despite its importance, the architecture of this interface remains elusive. Here we used in situ cryo-electron tomography to visualize the native architecture of the kinetochore-microtubule interface in human U2OS cells at different stages of mitosis. We find that the centromere forms a pocket-like structure around kinetochore microtubules. Two morphologically distinct fibrillar densities form end-on and side-on connections to the plus-ends of microtubules within this centromeric pocket. Our data suggest a dynamic kinetochore-microtubule interface with multiple interactions between outer kinetochore components and spindle microtubules.
Hyperactivity of indirect pathway-projecting spiny projection neurons drives compulsive behavior
Authors: Piantadosi Sean C , Manning Elizabeth E , Chamberlain Brittany L , Hyde James , LaPalombara Zoe , Bannon Nicholas M , Pierson Jamie L , Namboodiri Vijay MK , Ahmari Susanne E 
Published: February 2022

AbstractCompulsive behaviors are a hallmark symptom of obsessive compulsive disorder (OCD). Striatal hyperactivity has been linked to compulsive behavior generation in correlative studies in humans and causal studies in rodents. However, the contribution of the two distinct striatal output populations to the generation and treatment of compulsive behavior is unknown. These populations of direct and indirect pathway-projecting spiny projection neurons (SPNs) have classically been thought to promote or suppress actions, respectively, leading to a long-held hypothesis that increased output of direct relative to indirect pathway promotes compulsive behavior. Contrary to this hypothesis, here we find that indirect pathway hyperactivity drives compulsive grooming in the Sapap3-knockout mouse model of OCD-relevant behavior. Furthermore, we show that suppression of indirect pathway activity using optogenetics or treatment with the first-line OCD pharmacotherapy fluoxetine is associated with reduced compulsive behavior. Together, these findings highlight the striatal indirect pathway as a potential new treatment target for compulsive behavior.
The empirical relationship between contractor success and project innovation
Authors: Langston Craig 
Published: February 2022

PurposeInnovation during project delivery is contested space. The aim in this research is to empirically explore the theory of this contested space and how project implementation can be optimized by the contractor to deliver better outcomes. It is hypothesized that project innovation has a proportional and measurable relationship to contractor success.Design/methodology/approachBased on a novel conceptual framework, this research applies a case study methodology to analyse 31 construction projects undertaken by a single Australian middle-tier contractor. Benefits from innovation are not often equitably shared. There are risks and rewards. The project innovation zone is defined as a combination of three key performance indicators – efficacy, efficiency and margin – merged into a single index that most likely shows evidence of “working smarter”.FindingsClient–contractor project innovation (c2pi) is demonstrated to be strongly correlated with head contractor success (HCS), yielding an r2 value of 71%. Innovative projects mostly show positive change in efficacy, efficiency and margin when comparing “planned” and “actual” outcomes. Across the cases studied, 35% demonstrated likely evidence of innovative delivery and 52% demonstrated evidence of success from the construction contractor's perspective.Originality/valueThese findings verify that, within the studied sample, the pursuit of innovation leads to projects that are likely to also have greater success for the head contractor, evidenced by the mix of five critical success factors: finishing on schedule, making profit, and having less defects, less accidents and higher quality workmanship. These outcomes arguably also apply to sub-contractors, where the head contractor assumes the role of “client”.