bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preserved recognition of Omicron Spike following COVID-19 mRNA vaccination in pregnancy
Authors: Bartsch Yannic , Atyeo Caroline , Kang Jaewon , Gray Kathryn J , Edlow Andrea G , Alter Galit 
Published: January 2022

SummaryBackgroundSARS-CoV-2 infection is associated with enhanced disease severity in pregnant women. Despite the potential of COVID-19 vaccines to reduce severe disease, vaccine uptake remained relatively low among pregnant women. Just as coordinated messaging from the CDC and leading obstetrics organizations began to increase vaccine confidence in this vulnerable group, the evolution of SARS-CoV-2 variants of concerns (VOC) including the Omicron VOC raised new concerns about vaccine efficacy, given their ability to escape vaccine-induced neutralizing antibodies. Early data point to a milder disease course following omicron VOC infection in vaccinated individuals. Thus, these data suggest that alternate vaccine induced immunity, beyond neutralization, may continue to attenuate omicron disease, such as antibody-Fc-mediated activity. However, whether vaccine induced antibodies raised in pregnancy continue to bind and leverage Fc-receptors remains unclear.MethodsVOC including Omicron receptor binding domain (RBD) or full Spike specific antibody isotype binding titers and FcγR binding were analyzed in pregnant women after the full dose regimen of either Pfizer/BioNtech BNT62b2 (n=10) or Moderna mRNA-1273 (n=10) vaccination using a multiplexing Luminex assay.FindingsComparable, albeit reduced, isotype recognition was observed to the Omicron Spike and receptor binding domain (RBD) following both vaccines. Yet, despite the near complete loss of Fc-receptor binding to the Omicron RBD, Fc-receptor binding was largely preserved to the Omicron Spike.InterpretationReduced binding titer to the Omicron RBD aligns with observed loss of neutralizing activity. Despite the loss of neutralization, preserved Omicron Spike recognition and Fc-receptor binding potentially continues to attenuate disease severity in pregnant women.FundingNIH and the Bill and Melinda Gates Foundation
Prenatal murine skeletogenesis partially recovers from absent skeletal muscle as development progresses
Authors: Sotiriou V. , Ahmed S. , Nowlan N. C. 
Published: January 2022

AbstractSkeletal muscle contractions are critical for normal growth and morphogenesis of the skeleton, but it is unclear how the detrimental effects of absent muscle on the bones and joints change over time. Joint size, shape and cavitation, and rudiment length and mineralisation were assessed in multiple rudiments at two developmental stages (Theiler Stage (TS)24 and TS27) in the splotch-delayed “muscleless limb” mouse model and littermate controls. As development progressed, the effects of absent muscle on all parameters except for cavitation become less severe. All major joints in muscleless limbs were qualitatively and quantitatively abnormal in shape at TS24, while, by TS27, most muscleless joint shapes were normal, or nearly normal. In contrast, any joints which were fused at TS24 did not cavitate by TS27. Therefore, recovery in joint shape over development occurred despite absent cavitation. Mineralisation showed the most pronounced changes between TS24 and TS27 in the muscleless limbs. At TS24, all muscleless rudiments studied had less mineralisation than the controls, while at TS27, muscleless limb rudiments had either the same or significantly more mineralisation than controls of the same age. We conclude that the effects of absent muscle on prenatal murine skeletogenesis are most pronounced in early skeletal development and reduce in severity prior to birth. Understanding how mammalian bones and joints continue to develop in an environment without muscle contractions, but with mechanical stimulation due to the movement of the mother, provides important insights into conditions affecting human babies such as developmental dysplasia of the hip and arthrogryposis.
Potential geographic distribution and ecological niche of New World dobsonflies (Megaloptera, Corydalidae): the case of the Neartic-Neotropical transition zone
Authors: Álvarez Hugo Alejandro , Rivas-Soto Miguel A. 
Published: January 2022

AbstractThe dobsonflies (Megaloptera, Corydalidae) are an interesting group of insects, but among the New World dobsonflies, it is not known the effect of the Neartic-Neotropical transition zone on their biogeographic distribution. Here we studied at the species level, the records on the geographic range of the dobsonflies that occurred in and near the transition zone. We presented potential geographic distributions based on ecological niche models for several species of dobsonflies. Results suggested that the geographic range of dobsonflies in the transition zone is associated to mountainous formations and that most species favor warm climates with higher precipitation rates. Climate types tend to be important for species that show narrow geographic ranges, but precipitation tends to be the most important variable to explain species dispersion. Overall, our models support the dispersion of dobsonflies from the Neotropics to North America and explain the two endemic species in Mexico as the result of the formation of the transition zone.
Factors predicting serum clozapine levels in Middle Eastern patients: an observational study
Authors: Errasoul Ahmed Hassab , Alarabi Mohammed A. 
Published: January 2022

AbstractBackgroundDespite its superiority over other drugs for psychosis, clozapine remains underused and is associated with many clinical challenges, including difficulties in predicting serum levels. We found no large or recent study that investigated the determinants of serum clozapine levels in Middle Eastern patients. We thus investigated the association between clozapine dose and serum levels and the clinical predictors of clozapine serum levels in Middle Eastern patients.MethodsThis was a cross-sectional study including 94 patients of Middle Eastern ethnicity attending the Clozapine Clinic in King Saud University Medical City in Riyadh, Saudi Arabia.ResultsThe average clozapine dose and serum level were 400 mg/daily and 705 ng/mL, respectively. Clozapine dose and serum levels were positively correlated (rs[94]=0.32,p=0.002). We generated a predictive model of serum clozapine levels which revealed that the daily dose, smoking status, use of fluvoxamine or lamotrigine, and body mass index (BMI) predicted 43.6% of the variance in serum levels (p<0.001). Using this model, we calculated that the maximum doses of clozapine to avoid levels above the optimal range (>650 ng/mL) were 300, 250, or 225 mg/day for non-smokers with a body mass index of 25, 30, or 35 kg/m2, respectively, and 475, 425, or 400 mg/day for smokers with a body mass index of 25, 30, or 35 kg/m2, respectively.ConclusionsThis is a naturalistic study of the clozapine dose-level relationship and the clinical predictors of serum clozapine levels in Middle Eastern patients. These findings do not reduce the value of individualised therapeutic drug monitoring but may assist clinicians when prescribing clozapine to Middle Eastern patients. Further psychopharmacological studies are needed on this demographic population.
Potential application of Rapid Antigen Diagnostic Tests for the detection of infectious individuals attending mass gatherings – a simulation study
Authors: McAloon Conor G. , Dahly Darren , Walsh Cathal , Wall Patrick , Smyth Breda , More Simon , Teljeur Conor 
Published: January 2022

AbstractRapid Antigen Diagnostic Tests (RADTs) for the detection of SARS-CoV-2 offer advantages in that they are cheaper and faster than currently used PCR tests but have reduced sensitivity and specificity. One potential application of RADTs is to facilitate gatherings of individuals, through testing of attendees at the point of, or immediately prior to entry at a venue. Understanding the baseline risk in the tested population is of particular importance when evaluating the utility of applying diagnostic tests for screening purposes. We used incidence data to estimate the prevalence of infectious individuals in the community at a particular time point and simulated mass gatherings by sampling from a series of age cohorts. Nine different illustrative scenarios were simulated, small (n=100), medium (n=1000) and large (n=10,000) gatherings each with 3 possible age constructs: mostly younger, mostly older or a gathering with equal numbers from each age cohort. For each scenario, we estimated the prevalence of infectious attendees, then simulated the likely number of positive and negative test results, the proportion of cases detected and the corresponding positive and negative predictive values, and the cost per case identified. Our findings suggest that for each detected individual on a given day, there are likely to be 13.8 additional infectious individuals also present in the community. Prevalence of infectious individuals at events was highest with ‘mostly younger’ attendees (1.00%), followed by homogenous age gatherings (0.55%) and lowest with ‘mostly older events’ (0.26%). For small events (100 attendees) the expected number of infectious attendees was less than 1 across all age constructs of attendees. For large events (10,000 attendees) the expected number of infectious attendees ranged from 26 (95% confidence intervals 12 to 45) for mostly older events, to almost 100 (95% confidence intervals 46 to 174) infectious attendees for mostly younger attendees. Given rapid changes in SARS-CoV-2 incidence over time, we developed an RShiny app to allow users to run updated simulations for specific events.
Estimating protection afforded by prior infection in preventing reinfection: Applying the test-negative study design
Authors: Ayoub Houssein H. , Tomy Milan , Chemaitelly Hiam , Altarawneh Heba N. , Coyle Peter , Tang Patrick , Hasan Mohammad R. , Kanaani Zaina Al , Kuwari Einas Al , Butt Adeel A. , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Nasrallah Gheyath K. , Benslimane Fatiha M. , Khatib Hebah A. Al , Yassine Hadi M. , Kuwari Mohamed G. Al , Al Romaihi Hamad Eid , Abdul-Rahim Hanan F. , Al-Thani Mohamed H. , Khal Abdullatif Al , Bertollini Roberto , Abu-Raddad Laith J. 
Published: January 2022

AbstractBackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic has highlighted an urgent need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection (PES) by novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsMathematical modeling was used to demonstrate the applicability of the test-negative, case-control study design to derive PES. Modeling was also used to investigate effects of bias in PES estimation. The test-negative design was applied to national-level testing data in Qatar to estimate PES for SARS-CoV-2 infection and to validate this design.ResultsApart from the very early phase of an epidemic, the difference between the test-negative estimate for PES and the true value of PES was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of PES even when PES began to wane after prior infection. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated PES, but the underestimate was considerable only when >50% of the population was ever infected. Misclassification of latent infection, misclassification of current active infection, and scale-up of vaccination all resulted in negligible bias in estimated PES. PES against SARS-CoV-2 Alpha and Beta variants was estimated at 97.0% (95% CI: 93.6-98.6) and 85.5% (95% CI: 82.4-88.1), respectively. These estimates were validated using a cohort study design.ConclusionsThe test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection.
Integrin/TGF-β1 inhibitor GLPG-0187 blocks SARS-CoV-2 Delta and Omicron pseudovirus infection of airway epithelial cells which could attenuate disease severity
Authors: Huntington Kelsey E. , Carlsen Lindsey , So Eui-Young , Piesche Matthias , Liang Olin , El-Deiry Wafik S. 
Published: January 2022

AbstractAs COVID-19 continues to pose major risk for vulnerable populations including the elderly, immunocompromised, patients with cancer, and those with contraindications to vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins either independently or as a co-receptor with surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 to demonstrate blockade of SARS-CoV-2 pseudovirus infection of target cells. Omicron pseudovirus infected normal human small airway epithelial (HSAE) cells significantly less than D614G or Delta variant pseudovirus, and GLPG-0187 effectively blocked SARS-CoV-2 pseudovirus infection in a dose-dependent manner across multiple viral variants. GLPG-0187 inhibited Omicron and Delta pseudovirus infection of HSAE cells more significantly than other variants. Pre-treatment of HSAE cells with MEK inhibitor (MEKi) VS-6766 enhanced inhibition of pseudovirus infection by GLPG-0187. Because integrins activate TGF-β signaling, we compared plasma levels of active and total TGF-β in COVID-19+ patients. Plasma TGF-β1 levels correlated with age, race, and number of medications upon presentation with COVID-19, but not with sex. Total plasma TGF-β1 levels correlated with activated TGF-β1 levels. In our preclinical studies, Omicron infects lower airway lung cells less efficiently than other COVID-19 variants. Moreover, inhibition of integrin signaling prevents SARS-CoV-2 Delta and Omicron pseudovirus infectivity, and may mitigate COVID-19 severity through decreased TGF-β1 activation. This therapeutic strategy may be further explored through clinical testing in vulnerable and unvaccinated populations.
Target attainment of extended-interval dosing of tobramycin in patients less than five years of age with cystic fibrosis: A pharmacokinetic analysis
Authors: Downes Kevin J , Grim Austyn , Shanley Laura , Rubenstein Ronald C , Zuppa Athena F , Gastonguay Marc R. 
Published: January 2022

ABSTRACTBackgroundExtended interval dosing (EID) of tobramycin is recommended for treatment of pulmonary exacerbations in adults and older children with cystic fibrosis (CF), but data are limited in patients less than 5 years of age.MethodsWe performed a retrospective population pharmacokinetic (PK) analysis of hospitalized children with CF <5 years of age prescribed intravenous tobramycin for a pulmonary exacerbation from March 2011 to September 2018 at our hospital. Children with normal renal function who had ≥1 tobramycin concentration available were included. Nonlinear mixed effects population PK modeling was performed using NONMEM® using data from the first 48 hours of tobramycin treatment. Monte Carlo simulations were implemented to determine the fraction of simulated patients that met published therapeutic targets with regimens of 10-15 mg/kg/day once daily dosing.ResultsFifty-eight patients received 111 tobramycin courses (range 1-9/patient). A 2-compartment model best described the data. Age, glomerular filtration rate, and vancomycin coadministration were significant covariates on tobramycin clearance. The typical values of clearance and central volume of distribution were 0.252 L/hr/kg^0.75 and 0.308 L/kg, respectively. No once daily regimens achieved all pre-specified targets simultaneously in >75% of simulated subjects. A dosage of 13 mg/kg/dose best met the predefined targets of Cmax >25 mg/L and AUC24 of 80-120 mg*h/L.ConclusionsBased on our population PK analysis and simulations, once daily dosing of tobramycin would not achieve all therapeutic goals in young patients with CF. However, extended-interval dosing regimens may attain therapeutic targets in the majority of young patients.
ClusTrast: a short readde novotranscript isoform assembler guided by clustered contigs
Authors: Westrin Karl Johan , Kretzschmar Warren W. , Emanuelsson Olof 
Published: January 2022

AbstractBackgroundTranscriptome assembly from RNA-sequencing data in species without a reliable reference genome has to be performedde novo, but studies have shown thatde novomethods often have inadequate ability to reconstruct transcript isoforms. We address this issue by constructing an assembly pipeline whose main purpose is to produce a comprehensive set of transcript isoforms.ResultsWe present thede novotranscript isoform assembler ClusTrast, which takes short read RNA-seq data as input, constructs a primary assembly, clusters a set of guiding contigs, aligns the short reads to the guiding contigs, assembles each clustered set of short reads individually, and merges the primary and clusterwise assemblies into the final assembly. We tested ClusTrast on real datasets from six eukaryotic species, and showed that Clus-Trast reconstructed more expressed known isoforms than any of the other testedde novoassemblers, at a moderate reduction in precision. For recall, ClusTrast was on top in the lower end of expression levels (<15% percentile) for all tested datasets, and over the entire range for almost all datasets. Reference transcripts were often (35–69% for the six datasets) reconstructed to at least 95% of their length by ClusTrast, and more than half of reference transcripts (58–81%) were reconstructed with contigs that exhibited polymorphism, measuring on a subset of reliably predicted contigs. ClusTrast recall increased when using a union of assembled transcripts from more than one assembly tool as primary assembly.ConclusionWe suggest that ClusTrast can be a useful tool for studying isoforms in species without a reliable reference genome, in particular when the goal is to produce a comprehensive transcriptome set with polymorphic variants.
How can suppliers increase their buyers’ CSR engagement: the role of internal and relational factors
Authors: Peng Ye , Zhang Xuan , van Donk Dirk Pieter , Wang Can 
Published: January 2022

PurposeBuyer engagement proves important supports for suppliers' corporate social responsibility (CSR); however, little is known about whether and how buyer CSR engagement can be actively searched for by a supplier and what activities and policies of suppliers could enhance buyer CSR engagement. From the perspective of resource dependence theory, this study aims to explore how suppliers seek to achieve buyers' CSR engagement.Design/methodology/approachThe proposed model and hypotheses were tested by structural equation modeling methodology using survey data collected from 243 manufacturing and service firms in China.FindingsThe results show that instrumental CSR motives and internalization of CSR policies jointly improve buyers' dependence, which in turn increases buyers' CSR engagement. In addition, this study investigates the influence of suppliers' trust on the effect of buyers' dependence on buyers' CSR engagement and finds a negative moderating effect on the dependence–engagement relation.Practical implicationsThe findings show that suppliers can actively engage in CSR to strengthen their position and improve the buyer CSR engagement. In fact, proactive CSR policies and implementation do pay off in the long run for them.Originality/valueThis study offers a fresh perspective on the role of suppliers in improving CSR. In contrast to much of the literature that has considered buyer-initiated practices and policies, this is the first theoretical and empirical investigation into how suppliers can increase the buyer CSR engagement.
An open systems model of successful school leadership
Authors: Gurr David , Drysdale Lawrie , Goode Helen 
Published: January 2022

PurposeThrough description and consideration of 12 models developed as part of the International Successful School Principalship Project (ISSPP), a new model of successful school leadership is developed.Design/methodology/approachThe paper is necessarily descriptive in nature. For the first time, 12 ISSPP models are described together, and these descriptions are then used inductively to create a new successful school leadership model.FindingsThe open systems approach adopted depicts schools as a continuous cycle of input-transformation-output with feedback loops that inform each stage of the cycle. The inputs are the variables that lead to transformation. The transformation stage is the actions or processes that individuals, groups and organisations engage in because of the inputs, and these lead to a range of student and school outcomes. Feedback loops connect the stages, and the whole model is open to the influence of five contextual forces: economic, political, socio-cultural, technological and system, institutional and educational.Originality/valueModels are an important way to make sense of complex phenomena. A new model of successful school leadership, with an open systems approach, provides a different frame to consider the findings of the ISSPP and potentially allows the ISSPP research to inform practice and connect with other school leadership views in new ways.
How do barriers to the activities of social enterprises affect their financial situation? Evidence based on data from Poland and resource mobilization theory
Authors: Mikołajczak Paweł 
Published: January 2022

Purpose
The purpose of the research is to identify the degree of intensity of barriers to the activities of social enterprises (SEs) and to examine the significance of such barriers regarding the financial situation of SE’s in emerging economies.

Design/methodology/approach
The data relates to 200 SEs selected from a national survey of 1,300 Polish non-governmental organizations (NGOs). An analysis of barriers to SEs according to the frequency of their occurrence was conducted. An indicator of the intensity of barriers to the activities of social enterprises and an indicator on these enterprises’ overall financial condition were determined. Spearman rank correlation analysis was used to assess the relationship between the indices.

Findings
The results of the study indicate that in addition to excessive bureaucracy in public administration and the complex formalities related to the use of private and public funds, SEs have difficulties in maintaining good staff and volunteers, whereas people in key positions reference burnout, not only among their own employees but also in themselves. These have a significant impact on the financial situation of SEs.

Originality/value
This study contributes to the field of social entrepreneurship in two ways. One is at the macro level in that it provides suggestions for public authorities in emerging economies interested in maintaining SEs in good financial condition so that they can effectively fulfil their social functions. The second contribution – the micro approach – is recognizing the extent of the impact of barriers on the financial condition of SEs and also determining the intensity of such barriers with regard to the mobilization of resources by managers, especially in the field of human resources.