bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do corporate sustainability initiatives improve corporate carbon performance? Evidence from European firms
Authors: Haque Faizul , Ntim Collins G. 
Published: April 2022

AbstractWe contribute to the business strategy and the environment literature by investigating the influence of corporate sustainability initiatives and corporate carbon performance of European listed firms. We use three‐way fixed‐effects model, and our sample comprises of 2444 firm‐year observations from 12 European countries, covering a 16‐year period (2004–2019). First, we find that corporate sustainability initiatives, a composite measure comprising of emission reduction initiatives, environmental innovations and efficient use of resources, has a positive relationship with corporate carbon performance, in terms of reduced greenhouse gas (GHG) emission intensity. Second, we find that the relationship between corporate sustainability initiatives and corporate carbon performance is stronger for firms in polluting industries. Overall, our evidence lends support for the efficiency‐oriented arguments of the neo‐institutional theory in that organisations respond to climate‐related risks by making substantive engagements in corporate sustainability initiatives, such as emission reduction initiatives, environmental innovations and efficient use of resources, which in turn facilitates organisations' effort to reduce GHG emission and improve corporate carbon performance.
Three‐dimensional printing models improve long‐term retention in medical education of pathoanatomy: A randomized controlled study
Authors: Al‐Badri Nour , Touzet‐Roumazeille Sandrine , Nuytten Alexandra , Ferri Joël , Charkaluk Marie‐Laure , Nicot Romain 
Published: April 2022

AbstractCraniosynostosis is a rare and complex pathology, and visuospatial skills are necessary for a good understanding of the condition. While the use of three‐dimensional (3D) models has improved the understanding of complex craniofacial anatomy, no study has evaluated the impact of this teaching support on long‐term retention. Our randomized controlled trial was designed to compare the long‐term retention of information with 3D‐printed models of four types of craniosynostosis versus classic 3D reconstructions displayed in two‐dimensional (2D) among undergraduate students. All students benefited from the same standardized course followed by the manipulation of the learning tool associated with the group for 15 min. Long‐term retention was assessed by the capability to properly recognize different types of craniosynostosis 3 weeks after the course. Eighty‐five students were enrolled. Previous educational achievements and baseline visuospatial skills were similar between the groups. The bivariate analysis showed the mean score in the 3D and 2D groups were 11.32 (2.89) and 8.08 (2.81), respectively (p < 0.0001). 3D‐printed models of structures with spatial complexity such as various craniosynostosis patterns improve significantly medical students' long‐term retention, indicating their educational efficacy.
Design, Synthesis, and Biological Evaluation of (+)‐Camphor‐ and (−)‐Fenchone‐Based Derivatives as Potent Orthopoxvirus Inhibitors
Authors: Sokolova Anastasiya S. , Kovaleva Kseniya S. , Kuranov Sergey O. , Bormotov Nikolay I. , Borisevich Sophia S. , Zhukovets Anastasiya A. , Yarovaya Olga I. , Serova Olga A. , Nawrozkij Maxim B. , Vernigora Andrey A. , Davidenko Andrey V. , Khamitov Eduard M. , Peshkov Roman Y. , Shishkina Larisa N. , Maksuytov Rinat A. , Salakhutdinov Nariman F. 
Published: April 2022

AbstractIn this work, a library of (+)‐camphor and (−)‐fenchone based N‐acylhydrazones, amides, and esters, including para‐substituted aromatic/hetaromatic/cyclohexane ring was synthesized, with potent orthopoxvirus inhibitors identified among them. Investigations of the structure‐activity relationship revealed the significance of the substituent at the para‐position of the aromatic ring. Also, the nature of the linker between a hydrophobic moiety and aromatic ring was clarified. Derivatives with p‐Cl, p‐Br, p‐CF3, and p‐NO2 substituted aromatic ring and derivatives with cyclohexane ring showed the highest antiviral activity against vaccinia virus, cowpox, and ectromelia virus. The hydrazone and the amide group were more favourable as a linker for antiviral activity than the ester group. Compounds 3 b and 7 e with high antiviral activity were examined using the time‐of‐addition assay and molecular docking study. The results revealed the tested compounds to inhibit the late processes of the orthopoxvirus replication cycle and the p37 viral protein to be a possible biological target.
Innovative Randomized Phase I Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID‐19 Trial of Nirmatrelvir
Authors: Singh Ravi Shankar P. , Toussi Sima S. , Hackman Frances , Chan Phylinda L. , Rao Rohit , Allen Richard , Van Eyck Lien , Pawlak Sylvester , Kadar Eugene P. , Clark Frances , Shi Haihong , Anderson Annaliesa S. , Binks Michael , Menon Sandeep , Nucci Gianluca , Bergman Arthur 
Published: April 2022

Coronavirus disease 2019 (COVID‐19) is a continued leading cause of hospitalization and death. Safe, efficacious COVID‐19 antivirals are needed urgently. Nirmatrelvir (PF‐07321332), the first orally bioavailable, severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) Mpro inhibitor against the coronaviridae family, has demonstrated potent preclinical antiviral activity and benign safety profile. We report safety, tolerability, and pharmacokinetic data of nirmatrelvir with and without ritonavir as a pharmacokinetic enhancer, from an accelerated randomized, double‐blind, placebo‐controlled, phase I study. Two interleaving single‐ascending dose (SAD) cohorts were evaluated in a three‐period crossover. Multiple‐ascending dose (MAD) with nirmatrelvir/ritonavir twice daily (b.i.d.) dosing was evaluated over 10 days in five parallel cohorts. Safety was assessed, including in a supratherapeutic exposure cohort. Dose and dosing regimen for clinical efficacy evaluation in phase II/III clinical trials were supported by integrating modeling and simulations of SAD/MAD data with nonclinical data and a quantitative systems pharmacology model (QSP). In SAD, MAD, and supratherapeutic exposure cohorts, nirmatrelvir/ritonavir was safe and well‐tolerated. Nirmatrelvir exposure and half‐life were considerably increased by ritonavir, enabling selection of nirmatrelvir/ritonavir dose and regimen for phase II/III trials (300/100 mg b.i.d.), to achieve concentrations continuously above those required for 90% inhibition of viral replication in vitro. The QSP model suggested that a 5‐day regimen would significantly decrease viral load in SARS‐CoV‐2‐infected patients which may prevent development of severe disease, hospitalization, and death. In conclusion, an innovative and seamless trial design expedited establishment of phase I safety and pharmacokinetics of nirmatrelvir/ritonavir, enabling high confidence in phase II/III dose selection and accelerated pivotal trials’ initiation (NCT04756531).
Applying Modeling and Simulations for Rational Dose Selection of Novel Toll‐Like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need
Authors: Klopp‐Schulze Lena , Shaw Jamie V. , Dong Jennifer Q. , Khandelwal Akash , Vazquez‐Mateo Cristina , Goteti Kosalaram 
Published: April 2022

Dual toll‐like receptor (TLR) 7 and TLR8 inhibitor enpatoran is under investigation as a treatment for lupus and coronavirus disease 2019 (COVID‐19) pneumonia. Population pharmacokinetic/pharmacodynamic (PopPK/PD) model‐based simulations, using PK and PD (inhibition of ex vivo‐stimulated interleukin‐6 (IL‐6) and interferon‐α (IFN‐α) secretion) data from a phase I study of enpatoran in healthy participants, were leveraged to inform dose selection for lupus and repurposed for accelerated development in COVID‐19. A two‐compartment PK model was linked to sigmoidal maximum effect (Emax) models with proportional decrease from baseline characterizing the PD responses across the investigated single and multiple doses, up to 200 mg daily for 14 days (n = 72). Concentrations that maintain 50/60/90% inhibition (IC50/60/90) of cytokine secretion (IL‐6/IFN‐α) over 24 hours were estimated and stochastic simulations performed to assess target coverage under different dosing regimens. Simulations suggested investigating 25, 50, and 100 mg enpatoran twice daily (b.i.d.) to explore the anticipated therapeutic dose range for lupus. With 25 mg b.i.d., > 50% of subjects are expected to achieve 60% inhibition of IL‐6. With 100 mg b.i.d., most subjects are expected to maintain almost complete target coverage for 24 hours (> 80% subjects IC90,IL‐6 = 15.5 ng/mL; > 60% subjects IC90,IFN‐α = 22.1 ng/mL). For COVID‐19, 50 and 100 mg enpatoran b.i.d. were recommended; 50 mg b.i.d. provides shorter IFN‐α inhibition (median time above IC90 = 13 hours/day), which may be beneficial to avoid interference with the antiviral immune response. Utilization of PopPK/PD models initially developed for lupus enabled informed dose selection for the accelerated development of enpatoran in COVID‐19.
Restoring ornithine transcarbamylase (OTC) activity in an OTC‐deficient mouse model using LUNAR‐OTC mRNA
Authors: Yu Hailong , Brewer Edward , Shields Michael , Crowder Michael , Sacchetti Cristiano , Soontornniyomkij Benchawanna , Dou Dandan , Clemente Brenda , Sablad Marciano , Chivukula Padmanabh , Hughes Steve , Roberts Scott , Rajappan Kumar , Tannis Steve , Sekulovich Rose , Parker Suezanne , Limphong Pattraranee 
Published: April 2022

AbstractOrnithine transcarbamylase (OTC) catalyses the reaction from ornithine to citrulline in the urea cycle. Ornithine transcarbamylase deficiency (OTCD) results in episodes of hyperammonemia. Arcturus Therapeutics developed a lipid nanoparticle (LNP)‐encapsulated OTC‐mRNA (LUNAR‐OTC) that results in a replacement enzyme and is currently undergoing clinical trials. In this study, the efficacy of LUNAR OTC‐mRNA drug in the spfash mouse model was examined by measuring the OTC enzyme activity and protein expression in the liver and plasma of OTC‐mRNA‐treated mice. Using purified citrulline‐D4 as the substrate improved the sensitivity of the OTC activity assay and allowed us to quantify the ornithine‐D4 product from the mouse plasma samples. OTC activity in the liver showed a clear dose response: The lowest dose, 0.3 mg/kg, resulted in higher activity than that of the untreated group, and the highest dose, 3 mg/kg, resulted in completely restored OTC activity in the liver. OTC activity in plasma was also dose‐dependent. A clear positive correlation between the OTC activity in the liver and that in the plasma suggests that the plasma OTC activity assay may serve as a surrogate for measuring OTC activity in liver biopsy samples. In addition, the OTC protein expression levels correlated well with the OTC activity in liver samples, but there was no quantifiable OTC protein in the plasma samples. This finding suggests that the sensitivity of the OTC activity assay is superior to that of the protein expression assay. Overall, the results of this study suggest that the OTC activity assay described here can be used as a clinical pharmacodynamic endpoint to measure the effectiveness of OTCD treatment.
Building a spectral cytometry toolbox: Coupling fluorescent proteins and antibodies to microspheres
Authors: Monard Simon 
Published: April 2022

AbstractFluorescent proteins (FPs) have become an essential tool for biological research. Since the isolation and description of GFP, hundreds of fluorescent proteins have been discovered and created with various characteristics. The excitation of these proteins ranges from ultra‐violet (UV) up to near infra‐RED (NIR). Using conventional cytometry with each detector assigned to each fluorochrome, great care must be taken when selecting the optimal bandpass filters to minimalize the spectral overlap. In the last 8 years, several companies have released full spectrum flow cytometers which eliminates the need to change optical filters for analyzing FPs. This addressed at least part of the problem however, the laser wavelengths in commercial instruments are generally not ideal for all fluorescent proteins yet do allow the separation of at least six FPs. Another technical challenge is to have convenient single color controls. If four different FPs are being used in an experiment, single color controls will be needed to compensate or unmix the data. In the case of cultured cells this will involve having each of the FPs expressed in cell lines separately with a parental cell line expressing none. In the case of in vivo experiments, colonies of animals may need to be maintained expressing each FP along with a wildtype animal. This represents a considerable expense and inconvenience. An appealing alternative is to produce and purify FPs and covalently couple to polystyrene microspheres. Such microspheres are ready to use and can be stored at 4°C for months or even years without any deterioration in fluorescence. The same procedure can be used to couple antibodies to these particles. Here we describe this procedure which can be executed in any lab without any special equipment or skills.
Erythroid side scatter: A parameter that improves diagnostic accuracy of flow cytometry myelodysplastic syndrome scoring
Authors: Johansson Ulrika , Rolf Nina , Futhee Natasha , Stewart Andrew 
Published: April 2022

AbstractBackground: Flow cytometry immunophenotyping (FCM) is a benchmark test for integrated diagnosis of myelodysplastic syndromes (MDS). Our department's FCM‐MDS‐score follows international guidelines and additionally includes the maturing erythroid (mEry) side scatter (SSC)/lymphocyte SSC ratio (mErySSCr), often increased in MDS patients. A recent exploratory computational flow analysis study highlighted mErySSC as the top feature for separating MDS from non‐MDS. Thus, we sought to systematically evaluate the diagnostic accuracy of mErySSCr in conventional diagnostic FCM as used currently in‐house.Methods: Historical MDS (n = 93), chronic myelomonocytic leukemia (CMML; n = 27) and non‐neoplastic cytopenia (n = 57) cohorts were created. Differences between these cohorts and LG‐MDS entities were mapped and the mErySSCr cut‐off was refined. Prospective bone marrows (n = 213) received for marrow failure work‐up were used to determine the sensitivity and specificity of mErySSCr, both as a sole parameter and as a component of the MDS‐score.Results: Low‐grade (LG)‐MDS mErySSCr differed more prominently from controls (p = <0.0001) than high‐grade (HG)‐MDS (p = 0.024). CMML and controls had a similar mErySSCr. As sole parameter, mErySSCr specificity was 91.1% (n = 112 non‐MDS diagnoses) and sensitivity was 36% for LG‐MDS (n = 36) and 25% for new HG‐MDS diagnoses (n = 16). The specificity of the MDS‐score was similar if mErySSCr was omitted (81.3% with and 82.1% without). The MDS‐score sensitivity for new HG‐MDS diagnoses and CMML (n = 17) was 100%, and was not affected by mErySSCr. The score sensitivity for LG‐MDS however, dropped from 86.1% to 72.2% when mErySSCr was excluded.Conclusion: mErySSCr increases the diagnostic accuracy of flow‐based MDS scoring in our setting, particularly for LG‐MDS.
An energy‐efficient data management scheme for industrial IoT
Authors: Ghaderi Ali , Movahedi Zeinab 
Published: April 2022

SummaryIndustry 4.0 is the emerging trend of manufacturing technologies towards smart factories. The industrial internet of things (IIoT) plays a primordial role to achieve the objectives of Industry 4.0, by enabling the cyber‐physical production systems to communicate and cooperate with each other and with humans both internally and across the participants of the supply chain. The Publish/Subscribe is the communication model used commonly in IIoT networks, in which the data generated by sensors are cached in a central controller to be subsequently consumed by actuators. However, the traditional centralized data management is inappropriate for real applications because of its communication overhead and inability to cope with strict delay requirements of IIoT applications and energy constraints of IIoT networks. To address these issues, we propose an energy‐efficient data management scheme (EDMS), in which a set of IoT nodes are selected to cache data distributedly, so that the network energy consumption is optimized while the constraints on data access latency and nodes' cache capacity are met. In this measure, the extra IoT nodes not involved in data transmission nor in data caching are switched off to prolong the network lifetime. We model the aforementioned optimization problem as an integer linear programming (ILP) considering the realistic constraints and characteristics of IIoT networks and solve it using the CPLEX tool. Moreover, we propose a metaheuristic algorithm based on ant colony optimization to solve the aforementioned problem in a timely manner. Simulation results show that EDMS outperforms significantly alternative solutions in terms of energy consumption, data latency, and cache utilization.
Observed and modelled tidal bar sedimentology reveals preservation bias against mud in estuarine stratigraphy
Authors: Braat Lisanne , Pierik Harm Jan , van Dijk Wout M. , van de Lageweg Wietse I. , Brückner Muriel Z. M. , van der Meulen Bas , Kleinhans Maarten G. 
Published: April 2022

AbstractMud plays a pivotal role in estuarine ecology and morphology. However, field data on the lateral and vertical depositional record of mud are rare. Furthermore, numerical morphodynamic models often ignore mud due to long computational times and simplifications of mixed depositional processes. This study aims to understand the spatial distribution, formative conditions and preservation of mud deposits in the intertidal zone of bars in high‐energy sand‐dominated estuaries, and to elucidate the effects of mud on morphology, ecology and stratigraphic architecture. To meet these objectives, field data (historic bathymetry, bio‐morphological maps and sediment cores of the shoal of Walsoorden, Western Scheldt estuary, the Netherlands) were combined with complementary hydro‐morphodynamic numerical modelling (Delft3D). Based on the field observations, two types of mud deposits were distinguished: (1) mudflat deposits, which are thick (>10 cm) mud beds at the surface associated with high elevations and low accumulation rates; and (2) mud drapes, which are thin (millimetre to centimetre) buried laminae that form and preserve at a wide range of elevations and energy conditions. Model results show that deposition on mudflats occurs just after high‐tide slack water in areas shielded from high flood velocities, suggesting that mud accumulation is mostly controlled by elevation, flow velocity and flow direction. Mud accumulation increases shoal elevation, sometimes to supratidal levels. This reduces flow over the shoal, which in turn reduces chute channel formation, stabilises bar morphology and decreases local tidal prism. These effects further promote mud deposition and vegetation settling. Although observations show that mud cover at the surface is relatively high (20%–40% of the intertidal area), mud constitutes only a small percentage of the total estuary volume (ca 5%) revealing that only a small fraction is preserved in the stratigraphy. Due to this mismatch between surface and subsurface expression of mud, interpretations of estuarine stratigraphy risk underestimating the influence of mud at the surface on morphodynamics and habitats.
Climate change mitigation and improvement of water quality from the restoration of a subtropical coastal wetland
Authors: Iram Naima , Maher Damien T. , Lovelock Catherine E. , Baker Tallis , Cadier Charles , Adame Maria F. 
Published: April 2022

AbstractCoastal wetland restoration is an important activity to achieve greenhouse gas (GHG) reduction targets, improve water quality, and reach the Sustainable Development Goals. However, many uncertainties remain in connection with achieving, measuring, and reporting success from coastal wetland restoration. We measured levels of carbon (C) abatement and nitrogen (N) removal potential of restored coastal wetlands in subtropical Queensland, Australia. The site was originally a supratidal forest composed of Melaleuca spp. that was cleared and drained in the 1990s for sugarcane production. In 2010, tidal inundation was reinstated, and a mosaic of coastal vegetation (saltmarshes, mangroves, and supratidal forests) emerged. We measured soil GHG fluxes (CH4, N2O, CO2) and sequestration of organic C in the trees and soil to estimate the net C abatement associated with the reference, converted, and restored sites. To assess the influence of restoration on water quality improvement, we measured denitrification and soil N accumulation. We calculated C abatement of 18.5 Mg CO2−eq ha−1 year−1 when sugarcane land transitioned to supratidal forests, 11.0 Mg CO2−eq ha−1 year−1 when the land transitioned to mangroves, and 6.2 Mg CO2−eq ha−1 year−1 when the land transitioned to saltmarshes. The C abatement was due to tree growth, soil accumulation, and reduced N2O emissions due to the cessation of fertilization. Carbon abatement was still positive, even accounting for CH4 emissions, which increased in the wetlands due to flooding and N2O production due to enhanced levels of denitrification. Coastal wetland restoration in this subtropical setting effectively reduces CO2 emissions while providing additional cobenefits, notably water quality improvement.
Community size structure varies with predator–prey size relationships and temperature across Australian reefs
Authors: Coghlan Amy Rose , Blanchard Julia L. , Heather Freddie J. , Stuart‐Smith Rick D. , Edgar Graham J. , Audzijonyte Asta 
Published: April 2022

AbstractClimate change and fisheries exploitation are dramatically changing the abundances, species composition, and size spectra of fish communities. We explore whether variation in ‘abundance size spectra’, a widely studied ecosystem feature, is influenced by a parameter theorized to govern the shape of size‐structured ecosystems—the relationship between the sizes of predators and their prey (predator–prey mass ratios, or PPMRs). PPMR estimates are lacking for avast number of fish species, including at the scale of trophic guilds. Using measurements of 8128 prey items in gut contents of 97 reef fish species, we established predator–prey mass ratios (PPMRs) for four major trophic guilds (piscivores, invertivores, planktivores, and herbivores) using linear mixed effects models. To assess the theoretical predictions that higher community‐level PPMRs leads to shallower size spectrum slopes, we compared observations of both ecosystem metrics for ~15,000 coastal reef sites distributed around Australia. PPMRs of individual fishes were remarkably high (median ~71,000), with significant variation between different trophic guilds (~890 for piscivores; ~83,000 for planktivores), and ~8700 for whole communities. Community‐level PPMRs were positively related to size spectrum slopes, broadly consistent with theory, however, this pattern was also influenced by the latitudinal temperature gradient. Tropical reefs showed a stronger relationship between community‐level PPMRs and community size spectrum slopes than temperate reefs. The extent that these patterns apply outside Australia and consequences for community structure and dynamics are key areas for future investigation.